ACE

NASA Technical Reports Server (NTRS)

Lumia, R.

1999-01-01

This document describes the progress made during the fourth year of the Center for Autonomous Control Engineering (ACE). We currently support 30 graduate students, 52 undergraduate students, 9 faculty members, and 4 staff members. Progress will be divided into two categories. The first category explores progress for ACE in general. The second describes the results of each specific project supported within ACE.

Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

PubMed Central

He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

2013-01-01

Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written informed consent was obtained prior to the investigation. 221 hypertensives (cases) and 221 normotensives (controls) were interviewed, subjected to a physical examination, and provided blood for biochemical and genetic tests. The ACE mRNA expression was analyzed by real time fluorescent quantitative Reverse Transcription PCR (FQ-RT-PCR). We performed logistic regression to assess associations of ACE I/D genotypes, ACE activity, and ACE mRNA expression levels with hypertension. Results The results of the multivariate logistic regression analysis showed that the additive model (ID, DD versus II) of the ACE genotype revealed an association with hypertension with adjusted OR of 1.43(95% CI: 1.04-1.97), and ACE ID genotype with adjusted OR of 1.72(95% CI: 1.01-2.92), DD genotype with adjusted OR of 1.94(95% CI: 1.01-3.73), respectively. In addition, our data also indicate that plasma ACE activity (adjusted OR was 1.13(95% CI: 1.08-1.18)) was significantly related to hypertension. However, the plasma ACE mRNA expressions were not different between the cases and controls. Conclusion ACE I/D polymorphism and ACE activity revealed significant influence on hypertension, while circulating ACE mRNA expression was not important factors associated with hypertension in this Chinese population. The detection of circulating ACE mRNA expression by FQ-RT-PCR might be a useful method for early screening and monitoring of EH. PMID:24098401

Notes from the field: Educating, inspiring and activating the next generation of climate leaders

NASA Astrophysics Data System (ADS)

Anderson, R.

2010-12-01

Due to the inherent lag time within the climate system, some of the greatest impacts of climate change will be felt in future decades by those who are today too young to control the course of human action (or inaction). Though today’s youth are not in the driver’s seat yet, this does not mean they are powerless to shape their own futures. To do this, students need to be empowered with an understanding of why and how climate change is happening and how it affects their lives. To prevent students from disengaging entirely in the face of such bleak picture, however, this information must be balanced with a more hopeful message of optimism about the future that they themselves can help to create. The Alliance for Climate Education (ACE) is a non-profit organization whose mission is to educate high school students about climate change and to inspire them to take action that makes a difference on this important issue. ACE educators deliver dynamic and engaging multimedia assembly presentations to high schools in 9 regions around the country. During the 2009-2010 school year, ACE educators spoke to over 400,000 high school students at over 900 high schools, educating students about current climate science in a dynamic manner that is meaningful and relevant. The presentation uses animated graphics to explain how humans are causing climate change, providing both a historical and paleoclimate perspective. Educators discuss the consequences of climate change with real-world video footage, showing both current impacts and model-based predictions for the future. The accompanying script has been thoroughly referenced with peer-reviewed articles to back up all information given. ACE’s education model illustrates for students how climate change will and does impact their lives—which can be sobering news to young people—but also imparts to students a sense of hope for the future by giving them tools to take action. ACE strives to form a crucial link between a foundation of good science and an outlet for students to make change. With ACE, high school students have started over 400 Action Teams at their schools that take on projects ranging from a DOT campaign, where students pledge to Do One Thing to help the environment, to working to put solar panels on their school. By connecting their local actions to ACE’s network, students become part of the larger youth climate movement and can see how their separate actions add up. Through regional trainings, students develop leadership skills to go beyond individual action to collective action at the community, state and national scale. This solutions-oriented approach to climate education is essential to engaging students towards becoming not only climate literate but also climate proactive. This presentation will include selections from ACE’s high school assembly presentation as well as highlights from ACE’s follow-up program for translating education into action.

Air, Climate and Energy (ACE) Centers: Supporting Air Quality and Climate Solutions

EPA Pesticide Factsheets

EPA through its Science to Achieve Results (STAR) program, is providing $30 million in funding for three university-based research centers to investigate regional differences in air pollution and the effects of global climate change.

North Atlantic Aerosol Properties for Radiative Impact Assessments. Derived from Column Closure Analyses in TARFOX and ACE-2

NASA Technical Reports Server (NTRS)

Russell, Philip A.; Bergstrom, Robert A.; Schmid, Beat; Livingston, John M.

2000-01-01

Aerosol effects on atmospheric radiative fluxes provide a forcing function that can change the climate in potentially significant ways. This aerosol radiative forcing is a major source of uncertainty in understanding the climate change of the past century and predicting future climate. To help reduce this uncertainty, the 1996 Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the 1997 Aerosol Characterization Experiment (ACE-2) measured the properties and radiative effects of aerosols over the Atlantic Ocean. Both experiments used remote and in situ measurements from aircraft and the surface, coordinated with overpasses by a variety of satellite radiometers. TARFOX focused on the urban-industrial haze plume flowing from the United States over the western Atlantic, whereas ACE-2 studied aerosols over the eastern Atlantic from both Europe and Africa. These aerosols often have a marked impact on satellite-measured radiances. However, accurate derivation of flux changes, or radiative forcing, from the satellite measured radiances or retrieved aerosol optical depths (AODs) remains a difficult challenge. Here we summarize key initial results from TARFOX and ACE-2, with a focus on closure analyses that yield aerosol microphysical models for use in improved assessments of flux changes. We show how one such model gives computed radiative flux sensitivities (dF/dAOD) that agree with values measured in TARFOX and preliminary values computed for the polluted marine boundary layer in ACE-2. A companion paper uses the model to compute aerosol-induced flux changes over the North Atlantic from AVHRR-derived AOD fields.

The Advanced Composition Explorer is placed atop its Delta II launcher at Pad 17A, CCAS

NASA Technical Reports Server (NTRS)

1997-01-01

The Advanced Composition Explorer (ACE) spacecraft is placed atop its launch vehicle at Launch Complex 17A. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 24, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA.

Air, Climate And Energy (ACE) Centers: Supporting Air Quality And Climate Solutions

EPA Pesticide Factsheets

EPA, through its Science to Achieve Results program, is funding three university-based research centers to investigate regional differences in air pollution and effects of climate change, technology, and societal choices on local air quality and health.

The Scientific Committee on Antarctic Research (SCAR) in the IPY 2007-2009

NASA Astrophysics Data System (ADS)

Kennicutt, M. C.; Wilson, T. J.; Summerhayes, C.

2005-05-01

The Scientific Committee on Antarctic Research (SCAR) initiates, develops, and coordinates international scientific research in the Antarctic region. SCAR is assuming a leadership position in the IPY primarily through its five major Scientific Research Programs; ACE, SALE, EBA, AGCS, and ICESTAR; which will be briefly described.Antarctic Climate Evolution (ACE) promotes the exchange of data and ideas between research groups focusing on the evolution of Antarctica's climate system and ice sheet. The program will: (1) quantitatively assess the climate and glacial history of Antarctica; (2) identify the processes which govern Antarctic change and feed back around the globe; (3) improve our ability to model past changes in Antarctica; and (4)document past change to predict future change in Antarctica. Subglacial Antarctic Lake Environments (SALE) promotes, facilitates, and champions cooperation and collaboration in the exploration and study of subglacial environments in Antarctica. SALE intends to understand the complex interplay of biological, geological, chemical, glaciological, and physical processes within subglacial lake environments through coordinated international research teams. Evolution and Biodiversity in the Antarctic (EBA) will use a suite of modern techniques and interdisciplinary approaches, to explore the evolutionary history of selected modern Antarctic biota, examine how modern biological diversity in the Antarctic influences the way present-day ecosystems function, and thereby predict how the biota may respond to future environmental change. Antarctica and the Global Climate System (AGCS) will investigate the nature of the atmospheric and oceanic linkages between the climate of the Antarctic and the rest of the Earth system, and the mechanisms involved therein. A combination of modern instrumented records of atmospheric and oceanic conditions, and the climate signals held within ice cores will be used to understand past and future climate variability and change in the Antarctic as a result of natural and anthropogenic forcings over the last 100,000 years. Interhemispheric Conjugacy Effects in Solar-Terrestrial and Aeronomy Research (ICESTAR) will study the interactions between and collective behavior of the many component parts of the Earth system, including the interaction between the natural environment and human society. Objectives include specification and prediction of the state of the system and assimilation and integration of data from disparate sources to understand the complex geospace environment.

A Data Services Upgrade for Advanced Composition Explorer (ACE) Data

NASA Astrophysics Data System (ADS)

Davis, A. J.; Hamell, G.

2008-12-01

Since early in 1998, NASA's Advanced Composition Explorer (ACE) spacecraft has provided continuous measurements of solar wind, interplanetary magnetic field, and energetic particle activity from L1, located approximately 0.01 AU sunward of Earth. The spacecraft has enough fuel to stay in orbit about L1 until ~2024. The ACE Science Center (ASC) provides access to ACE data, and performs level 1 and browse data processing for the science instruments. Thanks to a NASA Data Services Upgrade grant, we have recently retooled our legacy web interface to ACE data, enhancing data subsetting capabilities and improving online plotting options. We have also integrated a new application programming interface (API) and we are working to ensure that it will be compatible with emerging Virtual Observatory (VO) data services standards. The new API makes extensive use of metadata created using the Space Physics Archive Search and Extract (SPASE) data model. We describe these recent improvements to the ACE Science Center data services, and our plans for integrating these services into the VO system.

Preparing GMAT for Operational Maneuver Planning of the Advanced Composition Explorer (ACE)

NASA Technical Reports Server (NTRS)

Qureshi, Rizwan Hamid; Hughes, Steven P.

2014-01-01

The General Mission Analysis Tool (GMAT) is an open-source space mission design, analysis and trajectory optimization tool. GMAT is developed by a team of NASA, private industry, public and private contributors. GMAT is designed to model, optimize and estimate spacecraft trajectories in flight regimes ranging from low Earth orbit to lunar applications, interplanetary trajectories and other deep space missions. GMAT has also been flight qualified to support operational maneuver planning for the Advanced Composition Explorer (ACE) mission. ACE was launched in August, 1997 and is orbiting the Sun-Earth L1 libration point. The primary science objective of ACE is to study the composition of both the solar wind and the galactic cosmic rays. Operational orbit determination, maneuver operations and product generation for ACE are conducted by NASA Goddard Space Flight Center (GSFC) Flight Dynamics Facility (FDF). This paper discusses the entire engineering lifecycle and major operational certification milestones that GMAT successfully completed to obtain operational certification for the ACE mission. Operational certification milestones such as gathering of the requirements for ACE operational maneuver planning, gap analysis, test plans and procedures development, system design, pre-shadow operations, training to FDF ACE maneuver planners, shadow operations, Test Readiness Review (TRR) and finally Operational Readiness Review (ORR) are discussed. These efforts have demonstrated that GMAT is flight quality software ready to support ACE mission operations in the FDF.

Air, Climate, and Energy Strategic Research Action Plan, 2016 – 2019

EPA Pesticide Factsheets

ACE research projects are organized into 5 topics: Climate Impacts, Vulnerability, and Adaptation; Emissions and Measurements; Atmospheric and Integrated Modeling Systems; Protecting Environmental Public Health; and Sustainable Energy and Mitigation

North Atlantic Aerosol Properties and Direct Radiative Effects: Key Results from TARFOX and ACE-2

NASA Technical Reports Server (NTRS)

Russell, P. B.; Livingston, J. M.; Schmid, B.; Bergstrom, Robert A.; Hignett, P.; Hobbs, P. V.; Durkee, P. A.

2000-01-01

Aerosol effects on atmospheric radiative fluxes provide a forcing function that can change the climate In potentially significant ways. This aerosol radiative forcing is a major source of uncertainty in understanding the observed climate change of the past century and in predicting future climate. To help reduce this uncertainty, the International Global Atmospheric Chemistry Project (IGAC) has endorsed a series of multiplatform aerosol field campaigns. The Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the second Aerosol Characterization Experiment (ACE-2) were the first IGAC campaigns to address the impact of anthropogenic aerosols, Both TARFOX and ACE-2 gathered extensive data sets on aerosol properties and radiative effects, TARFOX focused on the urban-industrial haze plume flowing from the eastern United States over the western Atlantic Ocean, whereas ACE-2 studied aerosols carried over the eastern Atlantic from both European urban/industrial and African mineral sources. These aerosols often have a marked influence on the top-of-atmosphere radiances measured by satellites. Shown there are contours of aerosol optical depth derived from radiances measured by the AVHRR sensor on the NOAA-11 satellite. The contours readily show that aerosols originating in North America, Europe, and Africa impact the radiative properties of air over the North Atlantic. However, the accurate derivation of flux changes, or radiative forcing, from the satellite measured radiances or retrieved optical depths remains a difficult challenge. In this paper we summarize key initial results from TARFOX and, to a lesser extent, ACE-2, with a focus on those results that allow an improved assessment of the flux changes caused by North Atlantic aerosols at middle latitudes.

Precipitation and Hydrology Experiment Counter-Flow Spectrometer and Impactor Field Campaign Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poellot, Michael

The U.S. Department of Energy (DOE)’s Atmospheric Radiation Measurement (ARM) Climate Research Facility Aerial Facility (ARM AAF) counter-flow spectrometer and impactor (CSI) probe was flown on the University of North Dakota Cessna Citation research aircraft during the Integrated Precipitation and Hydrology Experiment (IPHEX). The field campaign took place during May and June of 2014 over North Carolina and its coastal waters as part of a National Aeronautics and Space Administration (NASA) Global Precipitation Measurement validation campaign. The CSI was added to the Citation instrument suite to support the involvement of Jay Mace through the NASA Advanced Composition Explorer (ACE) satellitemore » program and flights of the NASA ER-2 aircraft, which is a civilian version of the Air Force’s U2-S reconnaissance platform. The ACE program funded extra ER-2 flights to focus on clouds that are weakly precipitating, which are also of interest to the Atmospheric System Research program sponsored by DOE.« less

Evaluation of the Alliance for Climate Education's national high school edutainment program (Invited)

NASA Astrophysics Data System (ADS)

Lappe, M.; Flora, J.; Saphir, M.; Roser-Renouf, C.; Maibach, E.; Leiserowitz, A.

2013-12-01

The Alliance for Climate Education educates high school students on the science of climate change and inspires them to create effective solutions. Since 2009, ACE has reached over 1.6 million students nationwide with its multi media assembly presentation. In this paper, we evaluate the climate science knowledge, beliefs, attitudes, behavior and communication impact of the ACE Assembly program in a random sample of 49 schools (from population of 779) and a panel of 1,241 high school students. Pre and post assembly surveys composed of questions from the Global Warming Six Americas segmentation and intervention specific questions were administered in classrooms. We demonstrate that exposure to climate science in an engaging edutainment format changes youths' beliefs, involvement, and behavior positively and moves them to more climate science literate audience segments. The net impact of scaled and engaging programs for youth could be a population shift in climate science literacy and positive engagement in the issue of climate change. In addition, such programs can empower youth for deeper engagement in school programs, personal action, political and consumer advocacy.

Badhwar-O'Neil 2007 Galactic Cosmic Ray (GCR) Model Using Advanced Composition Explorer (ACE) Measurements for Solar Cycle 23

NASA Technical Reports Server (NTRS)

ONeill, P. M.

2007-01-01

Advanced Composition Explorer (ACE) satellite measurements of the galactic cosmic ray flux and correlation with the Climax Neutron Monitor count over Solar Cycle 23 are used to update the Badhwar O'Neill Galactic Cosmic Ray (GCR) model.

The Advanced Composition Explorer spacecraft lifts off from Pad 17A, CCAS

NASA Technical Reports Server (NTRS)

1997-01-01

A Boeing Delta II expendable launch vehicle lifts off with NASA's Advanced Composition Explorer (ACE) observatory at 10:39 a.m. EDT, on Aug. 25, 1997, from Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. Launch was scrubbed one day by Air Force range safety personnel because two commercial fishing vessels were within the Delta's launch danger area. The ACE spacecraft will study low-energy particles of solar origin and high-energy galactic particles on its one-million-mile journey. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA. Study of these energetic particles may contribute to our understanding of the formation and evolution of the solar system. ACE has a two-year minimum mission lifetime and a goal of five years of service. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology (Caltech) in Pasadena, Calif.

Blood type gene locus has no influence on ACE association with Alzheimer's disease.

PubMed

Braae, Anne; Medway, Christopher; Carrasquillo, Minerva; Younkin, Steven; Kehoe, Patrick G; Morgan, Kevin

2015-04-01

The ABO blood group locus was recently found to contribute independently and via interactions with angiotensin-converting enzyme (ACE) gene variation to plasma levels of ACE. Variation in ACE has previously been not only implicated as individually conferring susceptibility for Alzheimer's disease (AD) but also proposed to confer risk via interactions with other as yet unknown genes. More recently, larger studies have not supported ACE as a risk factor for AD, whereas the role of ACE pathway in AD has come under increased levels of scrutiny with respect to various aspects of AD pathology and possible therapies. We explored the potential combined involvement of ABO and ACE variations in the genetic susceptibility of 2067 AD cases compared with 1376 nondemented elderly. Including the effects of ABO haplotype did not provide any evidence for the genetic association of ACE with AD. Copyright © 2015 Elsevier Inc. All rights reserved.

The Delta II with ACE aboard is prepared for liftoff from Pad 17A, CCAS

NASA Technical Reports Server (NTRS)

1997-01-01

After launch tower retraction, the Boeing Delta II expendable launch vehicle carrying the Advanced Composition Explorer (ACE) undergoes final preparations for liftoff in the predawn hours of Aug. 24, 1997, at Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. ACE with its combination of nine sensors and instruments will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology.

Exploring the Social and Economic Impacts of Adult and Community Education.

ERIC Educational Resources Information Center

Birch, Elisa-Rose; Kenyon, Peter; Koshy, Paul; Wills-Johnson, Nick

The social and economic impacts of adult and community education (ACE) in Australia were examined in an exploratory study. A provider survey that was sent to approximately 1,900 ACE providers elicited 315 responses (response rate, approximately 17%), and a student survey that was sent to 4,000 ACE students generated 400 responses (response rate,…

The Aerosol/Cloud/Ecosystems Mission (ACE)

NASA Technical Reports Server (NTRS)

Schoeberl, Mark

2008-01-01

The goals and measurement strategy of the Aerosol/Cloud/Ecosystems Mission (ACE) are described. ACE will help to answer fundamental science questions associated with aerosols, clouds, air quality and global ocean ecosystems. Specifically, the goals of ACE are: 1) to quantify aerosol-cloud interactions and to assess the impact of aerosols on the hydrological cycle and 2) determine Ocean Carbon Cycling and other ocean biological processes. It is expected that ACE will: narrow the uncertainty in aerosol-cloud-precipitation interaction and quantify the role of aerosols in climate change; measure the ocean ecosystem changes and precisely quantify ocean carbon uptake; and, improve air quality forecasting by determining the height and type of aerosols being transported long distances. Overviews are provided of the aerosol-cloud community measurement strategy, aerosol and cloud observations over South Asia, and ocean biology research goals. Instruments used in the measurement strategy of the ACE mission are also highlighted, including: multi-beam lidar, multiwavelength high spectra resolution lidar, the ocean color instrument (ORCA)--a spectroradiometer for ocean remote sensing, dual frequency cloud radar and high- and low-frequency micron-wave radiometer. Future steps for the ACE mission include refining measurement requirements and carrying out additional instrument and payload studies.

Extension of the ACE solar panels is tested in SAEF-II

NASA Technical Reports Server (NTRS)

1997-01-01

Extension of the solar panels is tested on the Advanced Composition Explorer (ACE) spacecraft in KSC's Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA.

AceTree: a major update and case study in the long term maintenance of open-source scientific software.

PubMed

Katzman, Braden; Tang, Doris; Santella, Anthony; Bao, Zhirong

2018-04-04

AceTree, a software application first released in 2006, facilitates exploration, curation and editing of tracked C. elegans nuclei in 4-dimensional (4D) fluorescence microscopy datasets. Since its initial release, AceTree has been continuously used to interact with, edit and interpret C. elegans lineage data. In its 11 year lifetime, AceTree has been periodically updated to meet the technical and research demands of its community of users. This paper presents the newest iteration of AceTree which contains extensive updates, demonstrates the new applicability of AceTree in other developmental contexts, and presents its evolutionary software development paradigm as a viable model for maintaining scientific software. Large scale updates have been made to the user interface for an improved user experience. Tools have been grouped according to functionality and obsolete methods have been removed. Internal requirements have been changed that enable greater flexibility of use both in C. elegans contexts and in other model organisms. Additionally, the original 3-dimensional (3D) viewing window has been completely reimplemented. The new window provides a new suite of tools for data exploration. By responding to technical advancements and research demands, AceTree has remained a useful tool for scientific research for over a decade. The updates made to the codebase have extended AceTree's applicability beyond its initial use in C. elegans and enabled its usage with other model organisms. The evolution of AceTree demonstrates a viable model for maintaining scientific software over long periods of time.

The Advanced Composition Explorer spacecraft lifts off from Pad 17A, CCAS

NASA Technical Reports Server (NTRS)

1997-01-01

Photographers and other onlookers watch as a Boeing Delta II expendable launch vehicle lifts off with NASA's Advanced Composition Explorer (ACE) observatory at 10:39 a.m. EDT, on Aug. 25, 1997, from Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. Liftoff had been scheduled for Aug. 24, but was scrubbed one day by Air Force range safety personnel because two commercial fishing vessels were within the Delta's launch danger area. The ACE spacecraft will study low-energy particles of solar origin and high-energy galactic particles on its one-million-mile journey. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA. Study of these energetic particles may contribute to our understanding of the formation and evolution of the solar system. ACE has a two-year minimum mission lifetime and a goal of five years of service. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology (Caltech) in Pasadena, Calif.

ACE I/D Gene Polymorphism Can't Predict the Steroid Responsiveness in Asian Children with Idiopathic Nephrotic Syndrome: A Meta-Analysis

PubMed Central

Su, Li-Na; Lei, Feng-Ying; Huang, Wei-Fang; Zhao, Yan-Jun

2011-01-01

Background The results from the published studies on the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the treatment response to steroid in Asian children with idiopathic nephrotic syndrome (INS) is still conflicting. This meta-analysis was performed to evaluate the relation between ACE I/D gene polymorphism and treatment response to steroid in Asian children and to explore whether ACE D allele or DD genotype could become a predictive marker for steroid responsiveness. Methodology/Principal Findings Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2010, and eligible investigations were synthesized using meta-analysis method. Five investigations were identified for the analysis of association between ACE I/D gene polymorphism and steroid-resistant nephrotic syndrome (SRNS) risk in Asian children and seven studies were included to explore the relationship between ACE I/D gene polymorphism and steroid-sensitive nephrotic syndrome (SSNS) susceptibility. Five investigations were recruited to explore the difference of ACE I/D gene distribution between SRNS and SSNS. There was no a markedly association between D allele or DD genotype and SRNS susceptibility or SSNS risk, and the gene distribution differences of ACE between SRNS and SSNS were not statistically significant. II genotype might play a positive role against SRNS onset but not for SSNS (OR = 0.51, P = 0.02; OR = 0.95, P = 0.85; respectively), however, the result for the association of II genotype with SRNS risk was not stable. Conclusions/Significance Our results indicate that D allele or DD homozygous can't become a significant genetic molecular marker to predict the treatment response to steroid in Asian children with INS. PMID:21611163

KSC-97PC1238

NASA Image and Video Library

1997-08-13

The Advanced Composition Explorer (ACE) spacecraft is placed atop its launch vehicle at Launch Complex 17A. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 24, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

KSC-97PC1240

NASA Image and Video Library

1997-08-13

The Advanced Composition Explorer (ACE) spacecraft is placed atop its launch vehicle at Launch Complex 17A. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 24, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

The solar array is installed on ACE in SAEF-2

NASA Technical Reports Server (NTRS)

1997-01-01

Applied Physics Laboratory engineers and technicians from Johns Hopkins University assist in guiding the Advanced Composition Explorer (ACE) as it is hoisted over a platform for solar array installation in KSC's Spacecraft Assembly and Encapsulation Facility-II. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will contribute to the understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA.

The Delta II with ACE aboard is prepared for liftoff from Pad 17A, CCAS

NASA Technical Reports Server (NTRS)

1997-01-01

The Boeing Delta II expendable launch vehicle carrying the Advanced Composition Explorer (ACE) undergoes final preparations for liftoff in the predawn hours of Aug. 25, 1997, at Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. The first launch attempt on Aug. 24 was scrubbed by Air Force range safety personnel because two commercial fishing vessels were within the Delta's launch danger area. ACE with its combination of nine sensors and instruments will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology.

KSC-97PC1228

NASA Image and Video Library

1997-08-05

The Advanced Composition Explorer (ACE) spacecraft undergoes a spin test in KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

KSC-97PC1227

NASA Image and Video Library

1997-08-05

The Advanced Composition Explorer (ACE) spacecraft undergoes a spin test in KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

KSC-97PC1287

NASA Image and Video Library

1997-08-24

After launch tower retraction, the Boeing Delta II expendable launch vehicle carrying the Advanced Composition Explorer (ACE) undergoes final preparations for liftoff in the predawn hours of Aug. 24, 1997, at Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. ACE with its combination of nine sensors and instruments will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA’s Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology

Solar Anomalous and Magnetospheric Particle Explorer attitude control electronics box design and performance

NASA Technical Reports Server (NTRS)

Chamberlin, K.; Clagett, C.; Correll, T.; Gruner, T.; Quinn, T.; Shiflett, L.; Schnurr, R.; Wennersten, M.; Frederick, M.; Fox, S. M.

1993-01-01

The attitude Control Electronics (ACE) Box is the center of the Attitude Control Subsystem (ACS) for the Solar Anomalous and Magnetospheric Particle Explorer (SAMPEX) satellite. This unit is the single point interface for all of the Attitude Control Subsystem (ACS) related sensors and actuators. Commands and telemetry between the SAMPEX flight computer and the ACE Box are routed via a MIL-STD-1773 bus interface, through the use of an 80C85 processor. The ACE Box consists of the flowing electronic elements: power supply, momentum wheel driver, electromagnet driver, coarse sun sensor interface, digital sun sensor interface, magnetometer interface, and satellite computer interface. In addition, the ACE Box also contains an independent Safehold electronics package capable of keeping the satellite pitch axis pointing towards the sun. The ACE Box has dimensions of 24 x 31 x 8 cm, a mass of 4.3 kg, and an average power consumption of 10.5 W. This set of electronics was completely designed, developed, integrated, and tested by personnel at NASA GSFC. SAMPEX was launched on July 3, 1992, and the initial attitude acquisition was successfully accomplished via the analog Safehold electronics in the ACE Box. This acquisition scenario removed the excess body rates via magnetic control and precessed the satellite pitch axis to within 10 deg of the sun line. The performance of the SAMPEX ACS in general and the ACE Box in particular has been quite satisfactory.

Outcomes of a National Environmental Edutainment Program in High Schools

NASA Astrophysics Data System (ADS)

Lappe, M. D.

2012-12-01

We present results of the first longitudinal evaluation of a nation-wide environmental edutainment program. There has recently been rapid growth in curricula on the environment and climate change, yet few reach large and diverse audiences, and fewer still are evaluated. These results are from high schools participating in the Alliance for Climate Education (ACE) program. ACE is a 3 year-old program that has reached 1.2 million students with an edutainment presentation incorporating music, multi-media, animation, and documentary footage (www.acespace.org). A projected 850 schools across 23 states will see the presentation this year; 6% of schools (3 classes each) are randomly selected to be evaluated. The data described here were collected in Fall 2011 from 1,270 students in 21 schools; the full evaluation will be complete in May 2012. The sample is ethnically and socio-economically diverse — 29% are white, and 46% receive free/reduced lunches (a proxy for socio-economic status). Outcome measures included a test of climate knowledge and intentions to take (and to ask others to take) climate-related actions. The analyses examined direct effects of the ACE program on climate knowledge and intentions, as well as the moderating effects of student gender and age on learning. Before the ACE presentation, boys had significantly higher knowledge scores than girls (54% vs. 48% correct, respectively, p < .001). Afterward, boys and girls both had significantly higher knowledge scores (64% and 63% correct, respectively) and no longer differed from each other in this respect. Before the presentation, girls expressed significantly greater intentions to take climate-related actions than did boys. Afterward, intentions increased significantly in both groups, but the gap between girls and boys remained. The gap-closing pattern was somewhat different for the moderating variable of age. Before the presentation, knowledge and intentions were significantly higher among older students (11th- and 12th-graders) than among younger students (9th- and 10th-graders). Afterward, knowledge and intentions increased significantly in both groups, but the gap between them remained for knowledge and closed for intentions. These promising early results demonstrate how a single well-designed edutaiment presentation can appeal broadly to students and advance environmental education on a large scale.

KSC-97PC1230

NASA Image and Video Library

1997-08-11

Extension of the solar panels is tested on the Advanced Composition Explorer (ACE) spacecraft in KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

Exploration of the molecular interactions between angiotensin-I-converting enzyme (ACE) and the inhibitory peptides derived from hazelnut (Corylus heterophylla Fisch.).

PubMed

Liu, Chunlei; Fang, Li; Min, Weihong; Liu, Jingsheng; Li, Hongmei

2018-04-15

The mechanism of action of food-derived angiotensin-I-converting enzyme (ACE) inhibitory peptides has not been completely elucidated. In the present study, ion-exchange chromatography, gel filtration chromatography, reverse phase-high performance liquid chromatography, and liquid chromatography-electrospray ionization-tandem mass (LC-ESI-MS/MS) were employed for purifying and identifying the ACE inhibitory peptides from hazelnut. To understand the mode of action of these peptides, ACE inhibition kinetics, in vitro and in vivo bioavailability assays, active site analysis, and interaction between the inhibitory peptides and ACE were investigated. The results identified novel ACE inhibitory peptides Ala-Val-Lys-Val-Leu (AVKVL), Tyr-Leu-Val-Arg (YLVR), and Thr-Leu-Val-Gly-Arg (TLVGR) with IC 50 values of 73.06, 15.42, and 249.3 μM, respectively. All peptides inhibited the ACE activity via a non-competitive mode. The binding free energies of AVKVL, YLVR, and TLVGR for ACE were -3.46, -6.48, and -7.37 kcal/mol, respectively. The strong inhibition of ACE by YLVR may be attributed to the formation of cation-pi interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interaction of ACE genotype and salt intake on hypertension among Chinese Kazakhs: results from a population-based cross-sectional study.

PubMed

Wang, Yuyan; Zhang, Biao; Hou, Lei; Han, Wei; Xue, Fang; Wang, Yanhong; Tang, Yong; Liang, Shaohua; Wang, Weizhi; Asaiti, Kuliqian; Wang, Zixing; Hu, Yaoda; Wang, Lei; Qiu, Changchun; Zhang, Mingtao; Jiang, Jingmei

2017-05-17

To explore the effect of interaction between ACE genotype and salt intake on hypertension among Chinese Kazakhs, and to compare applications of interactions between logistic model and generalised partially linear tree-based regression (GPLTR) model. Population-based cross-sectional study. Hong Dun, North Xinjiang, China. Non-consanguineous Chinese Kazakh participants (n=916, 342 men and 574 women) aged ≥30 years. Association between ACE genotype and hypertension, association between salt intake and hypertension, and interaction of ACE genotype and salt intake on hypertension in two models. Associations between salt intake and hypertension were different in ACE genotype of II and ID+DD. Under the logistic models, main and interaction effects were not observed for men, but effects were present in opposite directions for women (main effect of ACE: OR=0.20, p=0.003; interaction effect: OR=1.07, p=0.027). Under the GPLTR model, Bayesian information criterion trees included both salt intake and ACE genotype as split variables. Individuals with a salt intake ≥19.5 g/day and ID+DD genotypes had a 3.99-fold (p=0.004) higher risk of hypertension compared with the II genotype for men, whereas salt intake <20.1 g/day and ID+DD genotypes had an OR=0.55 (p=0.014) compared with the II genotype for women. An interaction of ACE genotype and salt intake on hypertension was observed among Chinese Kazakhs but in different ways according to sex. The GPLTR model appears to be more suitable for an exploration of interactions in complex diseases. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The solar array is installed on ACE in SAEF-2

NASA Technical Reports Server (NTRS)

1997-01-01

Applied Physics Laboratory engineers and technicians from Johns Hopkins University install solar array panels on the Advanced Composition Explorer (ACE) in KSC's Spacecraft Assembly and Encapsulation Facility-II. The panel on which they are working is identical to the panel (one of four) seen in the foreground on the ACE spacecraft. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low- energy particles of solar origin and high-energy galactic particles for a better understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA.

KSC-97PC1290

NASA Image and Video Library

1997-08-25

A Boeing Delta II expendable launch vehicle lifts off with NASA’s Advanced Composition Explorer (ACE) observatory at 10:39 a.m. EDT, on Aug. 25, 1997, from Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. Launch was scrubbed one day by Air Force range safety personnel because two commercial fishing vessels were within the Delta’s launch danger area. The ACE spacecraft will study low-energy particles of solar origin and high-energy galactic particles on its one-million-mile journey. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA. Study of these energetic particles may contribute to our understanding of the formation and evolution of the solar system. ACE has a two-year minimum mission lifetime and a goal of five years of service. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology (Caltech) in Pasadena, Calif

KSC-97PC1291

NASA Image and Video Library

1997-08-25

Photographers and other onlookers watch as a Boeing Delta II expendable launch vehicle lifts off with NASA’s Advanced Composition Explorer (ACE) observatory at 10:39 a.m. EDT, on Aug. 25, 1997, from Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. Liftoff had been scheduled for Aug. 24, but was scrubbed one day by Air Force range safety personnel because two commercial fishing vessels were within the Delta’s launch danger area. The ACE spacecraft will study low-energy particles of solar origin and high-energy galactic particles on its one-million-mile journey. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA. Study of these energetic particles may contribute to our understanding of the formation and evolution of the solar system. ACE has a two-year minimum mission lifetime and a goal of five years of service. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology (Caltech) in Pasadena, Calif

KSC-97PC1292

NASA Image and Video Library

1997-08-25

A Boeing Delta II expendable launch vehicle lifts off with NASA’s Advanced Composition Explorer (ACE) observatory at 10:39 a.m. EDT, on Aug. 25, 1997, from Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. Launch was scrubbed one day by Air Force range safety personnel because two commercial fishing vessels were within the Delta’s launch danger area. The ACE spacecraft will study low-energy particles of solar origin and high-energy galactic particles on its one-million-mile journey. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA. Study of these energetic particles may contribute to our understanding of the formation and evolution of the solar system. ACE has a two-year minimum mission lifetime and a goal of five years of service. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology (Caltech) in Pasadena, Calif

KSC-97PC1293

NASA Image and Video Library

1997-08-25

A Boeing Delta II expendable launch vehicle lifts off with NASA’s Advanced Composition Explorer (ACE) observatory at 10:39 a.m. EDT, on Aug. 25, 1997, from Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. Launch was scrubbed one day by Air Force range safety personnel because two commercial fishing vessels were within the Delta’s launch danger area. The ACE spacecraft will study low-energy particles of solar origin and high-energy galactic particles on its one-million-mile journey. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA. Study of these energetic particles may contribute to our understanding of the formation and evolution of the solar system. ACE has a two-year minimum mission lifetime and a goal of five years of service. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA's Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology (Caltech) in Pasadena, Calif

[Effect of altitude chronic hypoxia on liver enzymes and its correlation with ACE/ACE2 in yak and migrated cattle].

PubMed

Liu, Feng-yun; Hu, Lin; Li, Yu-xian; Liu, Shi-ming; Tang, Yong-ping; Qi, Sheng-gui; Yang, Lei; Wu, Tian-yi

2015-05-01

To investigate the difference of liver enzyme levels and its correlation with serum ACE/ACE2 among yak and cattle on Qinghai-Tibetan plateau, and to further explore the biochemical mechanism of their liver of altitude adaptation. The serum samples of yak were collected at 3,000 m, 3,500 m, 4,000 m and 4,300 m respectively, meanwhile the serum samples of migrated cattle on plateau (2,500 m) and lowland cattle (1,300 m) were also collected. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholinesterase (CHE), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), serum lipase (LPS), angiotensin converting enzyme(ACE), angiotensin converting enzyme-2 (ACE2) in serum were measured by using fully automatic blood biochemcal analyzer. We analysed the differences of the above enzymes and its correlation with ACE/ACE2. We used one way analysis of variance (ANOVA). The levels of ALT in 4,000 m group and 4,300 m group of yak increased significantly compared with other groups, there were no statistically significant differences in AST, CHE, GGT, ACE/ACE2 levels of yaks at different altitudes. As compared to lowland cattle, the serum levels of AST and CHE were increased, the level of LPS and ACE was decreased significantly, respectively, and especially, the ratio of ACE/ACE2 of migranted cattle reduced nearly two times. The levels of LPS were significantly correlated to the ratio of ACE/ACE2 in yak (r = 0.357, P < 0.01), and a high correlation between ALP and ACE/ACE2 in lowland cattle( r = 0.418, P < 0.05), But the biggest contribution rate of the ratio of ACE/ACE2 was only 17.5% for the changes of the levels of liver enzyme. The results indicated that with the altitude increased did not significantly influence the changes of liver enzymes' activities in mountainous yaks but not in cattle. However, all above these changes weren't actually correlated to the ratio of ACE/ACE2.

KSC-97PC905

NASA Image and Video Library

1997-06-16

Prelaunch processing begins on the Advanced Composition Explorer (ACE) spacecraft in the Spacecraft Assembly and Encapsulation Facility-2 (SAEF-2). ACE will investigate the origin and evolution of solar phenomenon, the formation of the solar corona, solar flares and the acceleration of the solar wind. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory. The spacecraft is scheduled to be launched Aug. 21 aboard a two-stage Delta II 7920-8 rocket from Space Launch Complex 17, Pad A

KSC-97PC1078

NASA Image and Video Library

1997-07-22

Applied Physics Laboratory engineers and technicians from Johns Hopkins University assist in leveling and orienting the Advanced Composition Explorer (ACE) as it is seated on a platform for solar array installation in KSC’s Spacecraft Assembly and Encapsulation Facility-II. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory has six high-resolution particle detection sensors and three monitoring instruments. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nephew, E.A.; Abbatiello, L.A.; Ballou, M.L.

The basic concept of the Annual Cycle Energy System (ACES) - an integrated system for supplying space heating, hot water, and air conditioning to a building - and the theory underlying its design and operation are described. Practical procedures for designing an ACES for a single-family residence, together with recommended guidelines for the construction and installation of system components, are presented. Methods are discussed for estimating the life-cycle cost, component sizes, and annual energy consumption of the system for residential applications in different climatic regions of the US.

Activation of renin-angiotensin-aldosterone system (RAAS) in the lung of smoking-induced pulmonary arterial hypertension (PAH) rats.

PubMed

Yuan, Yi-Ming; Luo, Li; Guo, Zhen; Yang, Ming; Ye, Ren-Song; Luo, Chuan

2015-06-01

To explore the role of the renin-angiotensin-aldosterone system (RAAS) in the pathogenesis of pulmonary arterial hypertension (PAH) induced by chronic exposure to cigarette smoke. 48 healthy male SD rats were randomly divided into four groups (12/group): control group (group A); inhibitor alone group (group B); cigarette induction group (group C); cigarette induction + inhibitor group (group D). After the establishment of smoking-induced PAH rat model, the right ventricular systolic pressure (RVSP) was detected using an inserted catheter; western blotting was used to detect the protein expression of angiotensin-converting enzyme-2 (ACE2) and angiotensin-converting enzyme (ACE); expression levels of angiotensin II (AngII) in lung tissue were measured by radioimmunoassay. After six months of cigarette exposure, the RVSP of chronic cigarette induction group was significantly higher than that of the control group; expression levels of AngII and ACE increased in lung tissues, but ACE2 expression levels reduced. Compared with cigarette exposure group, after losartan treatment, RVSP, ACE and AngII obviously decreased (P<0.05), and ACE2 expression levels significantly increased. Chronic cigarette exposure may result in PAH and affect the protein expression of ACE2 and ACE in lung tissue, suggesting that ACE2 and ACE play an important role in the pathogenesis of smoking-induced PAH. © The Author(s) 2015.

KSC-97PC1141

NASA Image and Video Library

1997-07-29

The first stage of the Delta II rocket which will to be used to launch the Advanced Composition Explorer (ACE) spacecraft is erected at Launch Complex 17A at Cape Canaveral Air Station. Scheduled for launch on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun

KSC-97PC1143

NASA Image and Video Library

1997-07-29

The first stage of the Delta II rocket which will to be used to launch the Advanced Composition Explorer (ACE) spacecraft is erected at Launch Complex 17A at Cape Canaveral Air Station. Scheduled for launch on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun

KSC-97PC1142

NASA Image and Video Library

1997-07-29

The first stage of the Delta II rocket which will to be used to launch the Advanced Composition Explorer (ACE) spacecraft is erected at Launch Complex 17A at Cape Canaveral Air Station. Scheduled for launch on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun

KSC-97PC1170

NASA Image and Video Library

1997-07-31

The solid rocket motors of the Delta II rocket which will to be used to launch the Advanced Composition Explorer (ACE) spacecraft are erected at Launch Complex 17A at Cape Canaveral Air Station. Scheduled for launch on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun

KSC-97PC1175

NASA Image and Video Library

1997-08-02

The second stage of the Delta II rocket which will to be used to launch the Advanced Composition Explorer (ACE) spacecraft is erected at Launch Complex 17A at Cape Canaveral Air Station. Scheduled for launch on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun

KSC-97PC1232

NASA Image and Video Library

1997-08-13

In KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II), the Advanced Composition Explorer (ACE) spacecraft is encapsulated and placed into the transporter which will move it to Launch Complex 17A. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 24, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

KSC-97PC1234

NASA Image and Video Library

1997-08-13

In KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II), the Advanced Composition Explorer (ACE) spacecraft is encapsulated and placed into the transporter which will move it to Launch Complex 17A. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 24, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

KSC-97PC1144

NASA Image and Video Library

1997-07-29

The first stage of the Delta II rocket which will to be used to launch the Advanced Composition Explorer (ACE) spacecraft is erected at Launch Complex 17A at Cape Canaveral Air Station. Scheduled for launch on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun

Identification and in silico characterization of a novel peptide inhibitor of angiotensin converting enzyme from pigeon pea (Cajanus cajan).

PubMed

Nawaz, K A Ayub; David, Swapna Merlin; Murugesh, Easwaran; Thandeeswaran, Murugesan; Kiran, Kalarikkal Gopikrishnan; Mahendran, Ramasamy; Palaniswamy, Muthusamy; Angayarkanni, Jayaraman

2017-12-01

Plants are important sources of bioactive peptides. Among these, angiotensin converting enzyme (ACE) inhibitory peptides have a major focus on their ability to prevent hypertension. Inhibition of ACE has been established as an effective approach for the treatment of ACE associated diseases. Some synthetic ACE inhibitory drugs cause side effects and hence there is a constant interest in natural compounds as alternatives. The study was designed to identify and characterize a peptide molecule from pigeon pea which has the biological property to inhibit ACE and can be developed as a therapeutic approach towards hypertension. Seeds of pigeon pea (Cajanus cajan (L.) Millsp.) was fermented with Aspergillus niger, a proteolytic fungus isolated from spoiled milk sweet. The extract was purified by size exclusion chromatography by FPLC system. The fractions that showed ACE inhibition was subjected to LC-MS/MS for sequence identification. The stability of the peptide was analyzed by molecular dynamic simulations and the interaction sites with ACE were identified by molecular docking. The study report a novel ACE inhibitory octapeptide Val-Val-Ser-Leu-Ser-Ile-Pro-Arg with a molecular mass of 869.53 Da. The Lineweaver-Burk plot indicated that the inhibition of ACE by this peptide is in competitive mode. Also, molecular docking and simulation studies showed a strong and stable interaction of the peptide with ACE. The results clearly show the inhibitory property of the peptide against ACE and hence it can be explored as a therapeutic strategy towards hypertension and other ACE associated diseases. Copyright © 2017 Elsevier GmbH. All rights reserved.

Antihypertensive Effects, Molecular Docking Study, and Isothermal Titration Calorimetry Assay of Angiotensin I-Converting Enzyme Inhibitory Peptides from Chlorella vulgaris.

PubMed

Xie, Jingli; Chen, Xujun; Wu, Junjie; Zhang, Yanyan; Zhou, Yan; Zhang, Lujia; Tang, Ya-Jie; Wei, Dongzhi

2018-02-14

The aim of this work is to explore angiotensin I-converting enzyme (ACE) inhibitory peptides from Chlorella vulgaris (C. vulgaris) and discover the inhibitory mechanism of the peptides. After C. vulgaris proteins were gastrointestinal digested in silico, several ACE inhibitory peptides with C-terminal tryptophan were screened. Among them, two novel noncompetitive ACE inhibitors, Thr-Thr-Trp (TTW) and Val-His-Trp (VHW), exhibited the highest inhibitory activity indicated by IC 50 values 0.61 ± 0.12 and 0.91 ± 0.31 μM, respectively. Both the peptides were demonstrated stable against gastrointestinal digestion and ACE hydrolysis. The peptides were administrated to spontaneously hypertensive rats (SHRs) in the dose 5 mg/kg body weight, and VHW could decrease 50 mmHg systolic blood pressure of SHRs (p < 0.05). Molecular docking displayed that both TTW and VHW formed six hydrogen bonds with active site pockets of ACE. Besides, isothermal titration calorimetry assay discovered that VHW could form more stable complex with ACE than TTW. Therefore, VHW was an excellent ACE inhibitor.

The DSCOVR Solar Wind Mission and Future Space Weather Products

NASA Astrophysics Data System (ADS)

Cash, M. D.; Biesecker, D. A.; Reinard, A. A.

2012-12-01

The Deep Space Climate Observatory (DSCOVR) mission, scheduled for launch in mid-2014, will provide real-time solar wind thermal plasma and magnetic measurements to ensure continuous monitoring for space weather forecasting. DSCOVR will orbit L1 and will serve as a follow-on mission to NASA's Advanced Composition Explorer (ACE), which was launched in 1997. DSCOVR will have a total of six instruments, two of which will provide real-time data necessary for space weather forecasting: a Faraday cup to measure the proton and alpha components of the solar wind, and a triaxial fluxgate magnetometer to measure the magnetic field in three dimensions. Real-time data provided by DSCOVR will include Vx, Vy, Vz, n, T, Bx, By, and Bz. Such real-time L1 data is used in generating space weather applications and products that have been demonstrated to be highly accurate and provide actionable information for customers. We evaluate current space weather products driven by ACE and discuss future products under development for DSCOVR. New space weather products under consideration include: automated shock detection, more accurate L1 to Earth delay time, and prediction of rotations in solar wind Bz within magnetic clouds. Suggestions from the community on product ideas are welcome.

The solar array is installed on ACE in SAEF-2

NASA Technical Reports Server (NTRS)

1997-01-01

Applied Physics Laboratory Engineer Cliff Willey (kneeling) and Engineering Assistant Jim Hutcheson from Johns Hopkins University install solar array panels on the Advanced Composition Explorer (ACE) in KSC's Spacecraft Assembly and Encapsulation Facility-II. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles for a better understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA.

KSC-97PC1077

NASA Image and Video Library

1997-07-22

Applied Physics Laboratory engineers and technicians from Johns Hopkins University assist in guiding the Advanced Composition Explorer (ACE) as it is hoisted over a platform for solar array installation in KSC’s Spacecraft Assembly and Encapsulation Facility-II. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will contribute to the understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

Increasing brain angiotensin converting enzyme 2 activity decreases anxiety-like behavior in male mice by activating central Mas receptors

PubMed Central

Wang, Lei; de Kloet, Annette D.; Pati, Dipanwita; Hiller, Helmut; Smith, Justin A.; Pioquinto, David J.; Ludin, Jacob A.; Oh, S. Paul; Katovich, Michael J.; Frazier, Charles J.; Raizada, Mohan K.; Krause, Eric G.

2016-01-01

Over-activation of brain renin-angiotensin system (RAS) has been implicated in the etiology of anxiety disorders. Angiotensin converting enzyme (ACE2) inhibits RAS activity by converting angiotensin II, the effector peptide of RAS, to angiotensin-(1-7), which activates Mas receptors (MasR). Whether increasing brain ACE2 activity reduces anxiety by stimulating central MasR is unknown. To test the hypothesis that increasing brain ACE2 activity reduces anxiety-like behavior via central MasR stimulation, we generated male mice overexpressing ACE2 (ACE2 KI mice) and wild type littermate controls (WT). ACE2 KI mice explored the open arms of the elevated plus maze (EPM) significantly more than WT, suggesting increasing ACE2 activity is anxiolytic. Central delivery of diminazene aceturate, an ACE2 activator, to C57BL/6 mice also reduced anxiety-like behavior in the EPM, but centrally administering ACE2 KI mice A-779, a MasR antagonist, abolished their anxiolytic phenotype, suggesting that ACE2 reduces anxiety-like behavior by activating central MasR. To identify the brain circuits mediating these effects, we measured Fos, a marker of neuronal activation, subsequent to EPM exposure and found that ACE2 KI mice had decreased Fos in the bed nucleus of stria terminalis but had increased Fos in the basolateral amygdala (BLA). Within the BLA, we determined that ~62% of GABAergic neurons contained MasR mRNA and expression of MasR mRNA was upregulated by ACE2 overexpression, suggesting that ACE2 may influence GABA neurotransmission within the BLA via MasR activation. Indeed, ACE2 overexpression was associated with increased frequency of spontaneous inhibitory postsynaptic currents (indicative of presynaptic release of GABA) onto BLA pyramidal neurons and central infusion of A-779 eliminated this effect. Collectively, these results suggest that ACE2 may reduce anxiety-like behavior by activating central MasR that facilitate GABA release onto pyramidal neurons within the BLA. PMID:26767952

Adverse life events increase risk for postpartum psychiatric episodes: A population-based epidemiologic study.

PubMed

Meltzer-Brody, S; Larsen, J T; Petersen, L; Guintivano, J; Florio, A Di; Miller, W C; Sullivan, P F; Munk-Olsen, T

2018-02-01

Trauma histories may increase risk of perinatal psychiatric episodes. We designed an epidemiological population-based cohort study to explore if adverse childhood experiences (ACE) in girls increases risk of later postpartum psychiatric episodes. Using Danish registers, we identified women born in Denmark between January 1980 and December 1998 (129,439 childbirths). Exposure variables were ACE between ages 0 and 15 including: (1) family disruption, (2) parental somatic illness, (3) parental labor market exclusion, (4) parental criminality, (5) parental death, (6) placement in out-of-home care, (7) parental psychopathology excluding substance use, and (8) parental substance use disorder. Primary outcome was first occurrence of in- or outpatient contact 0-6 months postpartum at a psychiatric treatment facility with any psychiatric diagnoses, ICD-10, F00-F99 (N = 651). We conducted survival analyses using Cox proportional hazard regressions of postpartum psychiatric episodes. Approximately 52% of the sample experienced ACE, significantly increasing risk of any postpartum psychiatric diagnosis. Highest risks were observed among women who experienced out-of-home placement, hazard ratio (HR) 2.57 (95% CI: 1.90-3.48). Women experiencing two adverse life events had higher risks of postpartum psychiatric diagnosis HR: 1.88 (95% CI: 1.51-2.36), compared to those with one ACE, HR: 1.24 (95% CI: 1.03-49) and no ACE, HR: 1.00 (reference group). ACE primarily due to parental psychopathology and disability contributes to increased risk of postpartum psychiatric episodes; and greater numbers of ACE increases risk for postpartum psychiatric illness with an observed dose-response effect. Future work should explore genetic and environmental factors that increase risk and/or confer resilience. © 2017 Wiley Periodicals, Inc.

Adverse Childhood Experiences among Veterinary Medical Students: A Multi-Site Study.

PubMed

Strand, Elizabeth B; Brandt, Jennifer; Rogers, Kenita; Fonken, Laurie; Chun, Ruthanne; Conlon, Peter; Lord, Linda

This research explores Adverse Childhood Experiences (ACEs) among veterinary medical students across six academic institutions of veterinary medicine, and their relationship with depression, stress, and desire to become a veterinarian. Between April 1, 2016, and May 23, 2016, 1,118 veterinary medical students in all 4 years of the curriculum (39% response rate) completed an anonymous web-based questionnaire about ACEs, depression using the Center for Epidemiological Studies Depression scale (CESD), stress using the Perceived Stress Scale (PSS), and the age at which they wanted to become a veterinarian. Sixty-one percent (677) of respondents reported having at least one ACE. The most prevalent ACE reported was living with a household member with a mental illness (31%). Students who had experienced four or more ACEs had an approximately threefold increase in signs of clinical depression and higher than average stress when compared to students who had experienced no ACEs. The number of ACEs showed an overall graded relationship to signs of clinical depression and higher than average stress. There was no statistically significant relationship between age at which a student wanted to become a veterinarian and exposure to ACEs. Veterinary students report being exposed to ACEs before age 18 at a rate similar to that of other population-based studies. These findings do not suggest that veterinary students enter the veterinary medical education system more at risk for poor mental health due to ACEs than the general population.

Distinct EUV minimum of the solar irradiance (16-40 nm) observed by SolACES spectrometers onboard the International Space Station (ISS) in August/September 2009

NASA Astrophysics Data System (ADS)

Nikutowski, B.; Brunner, R.; Erhardt, Ch.; Knecht, St.; Schmidtke, G.

2011-09-01

In the field of terrestrial climatology the continuous monitoring of the solar irradiance with highest possible accuracy is an important goal. SolACES as a part of the ESA mission SOLAR on the ISS is measuring the short-wavelength solar EUV irradiance from 16-150 nm. This data will be made available to the scientific community to investigate the impact of the solar irradiance variability on the Earth's climate as well as the thermospheric/ionospheric interactions that are pursued in the TIGER program. Since the successful launch with the shuttle mission STS-122 on February 7th, 2008, SolACES initially recorded the low EUV irradiance during the extended solar activity minimum. Thereafter it has been observing the EUV irradiance during the increasing solar activity with enhanced intensity and changing spectral composition. SolACES consists of three grazing incidence planar grating spectrometers. In addition there are two three-signal ionisation chambers, each with exchangeable band-pass filters to determine the absolute EUV fluxes repeatedly during the mission. One important problem of space-borne instrumentation recording the solar EUV irradiance is the degradation of the spectrometer sensitivity. The two double ionisation chambers of SolACES, which could be re-filled with three different gases for each recording, allow the recalibration of the efficiencies of the three SolACES spectrometers from time to time.

KSC-97PC1080

NASA Image and Video Library

1997-07-22

Applied Physics Laboratory engineers and technicians from Johns Hopkins University install solar array panels on the Advanced Composition Explorer (ACE) in KSC’s Spacecraft Assembly and Encapsulation Facility-II. The panel on which they are working is identical to the panel (one of four) seen in the foreground on the ACE spacecraft. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles for a better understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA

Long Term Missions at the Sun-Earth Libration Point L1: ACE, SOHO, and WIND

NASA Technical Reports Server (NTRS)

Roberts, Craig E.

2011-01-01

Three heliophysics missions - the Solar Heliospheric Observatory (SOHO), the Advanced Composition Explorer (ACE), and the Global Geoscience WIND - have been orbiting the Sun-Earth interior libration point L1 continuously since 1996, 1997, and 2004, respectively. ACE and WIND (both NASA missions) and SOHO (an ESA-NASA joint mission) are all operated from the NASA Goddard Space Flight Center Flight Dynamics Facility. While ACE and SOHO have been dedicated libration point orbiters since their launches, WIND prior to 2004 flew a remarkable 10-year deep-space trajectory that featured 38 targeted lunar flybys. The L1 orbits and the mission histories of the three spacecraft are briefly reviewed, and the station-keeping techniques and orbit maneuver experience are discussed.

Early Childhood Adversity and Pregnancy Outcomes

PubMed Central

Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

2016-01-01

Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

Adverse childhood experiences (ACEs) and later-life depression: perceived social support as a potential protective factor.

PubMed

Cheong, E Von; Sinnott, Carol; Dahly, Darren; Kearney, Patricia M

2017-09-01

To investigate associations between adverse childhood experiences (ACEs) and later-life depressive symptoms; and to explore whether perceived social support (PSS) moderates these. We analysed baseline data from the Mitchelstown (Ireland) 2010-2011 cohort of 2047 men and women aged 50-69 years. Self-reported measures included ACEs (Centre for Disease Control ACE questionnaire), PSS (Oslo Social Support Scale) and depressive symptoms (CES-D). The primary exposure was self-report of at least one ACE. We also investigated the effects of ACE exposure by ACE scores and ACE subtypes abuse, neglect and household dysfunction. Associations between each of these exposures and depressive symptoms were estimated using logistic regression, adjusted for socio-demographic factors. We tested whether the estimated associations varied across levels of PSS (poor, moderate and strong). 23.7% of participants reported at least one ACE (95% CI 21.9% to 25.6%). ACE exposures (overall, subtype or ACE scores) were associated with a higher odds of depressive symptoms, but only among individuals with poor PSS. Exposure to any ACE (vs none) was associated with almost three times the odds of depressive symptoms (adjusted OR 2.85; 95% CI 1.64 to 4.95) among individuals reporting poor PSS, while among those reporting moderate and strong PSS, the adjusted ORs were 2.21 (95% CI 1.52 to 3.22) and 1.39 (95% CI 0.85 to 2.29), respectively. This pattern of results was similar when exposures were based on ACE subtype and ACE scores, though the interaction was clearly strongest among those reporting abuse. ACEs are common among older adults in Ireland and are associated with higher odds of later-life depressive symptoms, particularly among those with poor PSS. Interventions that enhance social support, or possibly perceptions of social support, may help reduce the burden of depression in older populations with ACE exposure, particularly in those reporting abuse. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

KSC-97PC1288

NASA Image and Video Library

1997-08-25

The Boeing Delta II expendable launch vehicle carrying the Advanced Composition Explorer (ACE) undergoes final preparations for liftoff in the predawn hours of Aug. 25, 1997, at Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. The first launch attempt on Aug. 24 was scrubbed by Air Force range safety personnel because two commercial fishing vessels were within the Delta’s launch danger area. ACE with its combination of nine sensors and instruments will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA’s Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology

KSC-97PC1289

NASA Image and Video Library

1997-08-25

The Boeing Delta II expendable launch vehicle carrying the Advanced Composition Explorer (ACE) undergoes final preparations for liftoff in the predawn hours of Aug. 25, 1997, at Launch Complex 17A, Cape Canaveral Air Station. This is the second Delta launch under the Boeing name and the first from Cape Canaveral. The first launch attempt on Aug. 24 was scrubbed by Air Force range safety personnel because two commercial fishing vessels were within the Delta’s launch danger area. ACE with its combination of nine sensors and instruments will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory and is managed by the Explorer Project Office at NASA’s Goddard Space Flight Center. The lead scientific institution is the California Institute of Technology

Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats.

PubMed

Yang, Cui; Liu, Xiuxia; Li, Shengnan

2010-02-01

Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin-angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1-7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1-7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway.

Screening for Adverse Childhood Experiences in a Family Medicine Setting: A Feasibility Study.

PubMed

Glowa, Patricia T; Olson, Ardis L; Johnson, Deborah J

2016-01-01

The role of adverse childhood experiences (ACEs) in predicting later adverse adult health outcomes is being widely recognized by makers of public policy. ACE questionnaires have the potential to identify in clinical practice unaddressed key social issues that can influence current health risks, morbidity, and early mortality. This study seeks to explore the feasibility of implementing the ACE screening of adults during routine family medicine office visits. At 3 rural clinical practices, the 10-question ACE screen was used before visits with 111 consecutive patients of 7 clinicians. Clinician surveys about the use of the results and the effect on the visits were completed immediately after the visits. The presence of any ACE risk and "high-risk" ACE scores (≥4) were compared with clinician survey responses. A risk of ACEs was present in 62% of patients; 22% had scores ≥4. Clinicians were more likely to have discussed ACE issues for high-risk patients (score 0-3, 36.8%; score ≥4, 83.3%; P =. 00). Clinicians also perceived that they gained new information (score 0-3, 35.6%; score ≥4, 83.3%; P = .00). Clinical care changed for a small proportion of high-risk patients, with no change in immediate referrals or plan for follow-up. In 91% of visits where a risk of ACEs was present, visit length increased by ≤5 minutes. Incorporation of ACE screening during routine care is feasible and merits further study. ACE screening offers clinicians a more complete picture of important social determinants of health. Primary care-specific interventions that incorporate treatment of early life trauma are needed. © Copyright 2016 by the American Board of Family Medicine.

Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia.

PubMed

Gadelha, A; Vendramini, A M; Yonamine, C M; Nering, M; Berberian, A; Suiama, M A; Oliveira, V; Lima-Landman, M T; Breen, G; Bressan, R A; Abílio, V; Hayashi, M A F

2015-12-08

In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=-5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=-0.247; P=0.004) and Hopkins total (r=-0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations.

Large Uncertainties in Urban-Scale Carbon Emissions

NASA Astrophysics Data System (ADS)

Gately, C. K.; Hutyra, L. R.

2017-10-01

Accurate estimates of fossil fuel carbon dioxide (FFCO2) emissions are a critical component of local, regional, and global climate agreements. Current global inventories of FFCO2 emissions do not directly quantify emissions at local scales; instead, spatial proxies like population density, nighttime lights, and power plant databases are used to downscale emissions from national totals. We have developed a high-resolution (hourly, 1 km2) bottom-up Anthropogenic Carbon Emissions System (ACES) for FFCO2, based on local activity data for the year 2011 across the northeastern U.S. We compare ACES with three widely used global inventories, finding significant differences at regional (20%) and city scales (50-250%). At a spatial resolution of 0.1°, inventories differ by over 100% for half of the grid cells in the domain, with the largest differences in urban areas and oil and gas production regions. Given recent U.S. federal policy pull backs regarding greenhouse gas emissions reductions, inventories like ACES are crucial for U.S. actions, as the impetus for climate leadership has shifted to city and state governments. The development of a robust carbon monitoring system to track carbon fluxes is critical for emissions benchmarking and verification. We show that existing downscaled inventories are not suitable for urban emissions monitoring, as they do not consider important local activity patterns. The ACES methodology is designed for easy updating, making it suitable for emissions monitoring under most city, regional, and state greenhouse gas mitigation initiatives, in particular, for the small- and medium-sized cities that lack the resources to regularly perform their own bottom-up emissions inventories.

Radiative Flux Changes by Aerosols from North America, Europe, and Africa over the Atlantic Ocean: Measurements and Calculations from TARFOX and ACE-2

NASA Technical Reports Server (NTRS)

Russell, P. B.; Hignett, P.; Livingston, J. M.; Schmid, B.; Chien, A.; Bergstrom, R.; Durkee, P. A.; Hobbs, P. V.; Bates, T. S.; Quinn, P. K.;

Characterization of Dust Properties at the Source Region During ACE-Asia

NASA Technical Reports Server (NTRS)

Tsay, Si-Chee; Lau, William (Technical Monitor)

2001-01-01

ACE (Aerosol Characterization Experiment)-Asia is designed to study the compelling variability in spatial and temporal scale of both pollution-derived and naturally-occurring aerosols, which often exist in high concentrations over eastern Asia and along the rim of the western Pacific. The phase-I of ACE-Asia was conducted from March-May 2001 in the vicinity of the Gobi desert, east coast of China, Yellow Sea, Korea, and Japan, along the pathway of Kosa (severe events that blanket East Asia with yellow desert dust, peaked in the Spring season). Asian dust typically originates in desert areas far from polluted urban regions. During transport, dust layers can interact with anthropogenic sulfate and soot aerosols from heavily polluted urban areas. Added to the complex effects of clouds and natural marine aerosols, dust particles reaching the marine environment can have drastically different properties than those from the source. Thus, understanding the unique temporal and spatial variations of Asian dust is of special importance in regional-to-global climate issues such as radiative forcing, the hydrological cycle, and primary biological productivity in the mid-Pacific Ocean. During ACE-Asia we have measured continuously aerosol optical/radiative properties, column precipitable water amount, and surface reflectivity over homogeneous areas from surface. The inclusion of flux measurements permits the determination of dust aerosol radiative flux in addition to measurements of loading and optical thickness. At the time of the Terra/MODIS overpass, these ground-based observations can provide valuable data to compare with MODIS retrievals over land. Preliminary results will be presented and discussed their implications in regional climatic effects.

A SOAP Web Services Interface to ACE Data

NASA Astrophysics Data System (ADS)

Davis, A. J.; Hamell, G. R.

2005-05-01

Since early in 1998, NASA's Advanced Composition Explorer (ACE) spacecraft has provided continuous measurements of solar wind and energetic particle activity from L1, located approximately 0.01 AU sunward of Earth. ACE data from nine instruments are being used to measure and compare the elemental and isotopic composition of the solar corona, the nearby interstellar medium, and the Galaxy, and to study particle acceleration processes that occur in a wide range of environments. The spacecraft has enough fuel to stay in orbit about L1 until at least 2020. The ACE Science Center (ASC) provides access to ACE data, and performs level 1 and browse data processing for the science instruments. Available on-line are solar wind, solar energetic particle, and galactic cosmic ray intensity and composition data, as well as solar wind and magnetic field parameters on a variety of time scales. We describe our recent efforts to provide enhanced access to ACE data via a SOAP Web Services interface. The interface utilizes the Space Physics Archive Search and Extract (SPASE) dictionary, and will be compatible with emerging virtual observatories.

The Advanced Composition Explorer Shock Database and Application to Particle Acceleration Theory

NASA Technical Reports Server (NTRS)

Parker, L. Neergaard; Zank, G. P.

2015-01-01

The theory of particle acceleration via diffusive shock acceleration (DSA) has been studied in depth by Gosling et al. (1981), van Nes et al. (1984), Mason (2000), Desai et al. (2003), Zank et al. (2006), among many others. Recently, Parker and Zank (2012, 2014) and Parker et al. (2014) using the Advanced Composition Explorer (ACE) shock database at 1 AU explored two questions: does the upstream distribution alone have enough particles to account for the accelerated downstream distribution and can the slope of the downstream accelerated spectrum be explained using DSA? As was shown in this research, diffusive shock acceleration can account for a large population of the shocks. However, Parker and Zank (2012, 2014) and Parker et al. (2014) used a subset of the larger ACE database. Recently, work has successfully been completed that allows for the entire ACE database to be considered in a larger statistical analysis. We explain DSA as it applies to single and multiple shocks and the shock criteria used in this statistical analysis. We calculate the expected injection energy via diffusive shock acceleration given upstream parameters defined from the ACE Solar Wind Electron, Proton, and Alpha Monitor (SWEPAM) data to construct the theoretical upstream distribution. We show the comparison of shock strength derived from diffusive shock acceleration theory to observations in the 50 keV to 5 MeV range from an instrument on ACE. Parameters such as shock velocity, shock obliquity, particle number, and time between shocks are considered. This study is further divided into single and multiple shock categories, with an additional emphasis on forward-forward multiple shock pairs. Finally with regard to forward-forward shock pairs, results comparing injection energies of the first shock, second shock, and second shock with previous energetic population will be given.

The Advanced Composition Explorer Shock Database and Application to Particle Acceleration Theory

NASA Technical Reports Server (NTRS)

Parker, L. Neergaard; Zank, G. P.

2015-01-01

The theory of particle acceleration via diffusive shock acceleration (DSA) has been studied in depth by Gosling et al. (1981), van Nes et al. (1984), Mason (2000), Desai et al. (2003), Zank et al. (2006), among many others. Recently, Parker and Zank (2012, 2014) and Parker et al. (2014) using the Advanced Composition Explorer (ACE) shock database at 1 AU explored two questions: does the upstream distribution alone have enough particles to account for the accelerated downstream distribution and can the slope of the downstream accelerated spectrum be explained using DSA? As was shown in this research, diffusive shock acceleration can account for a large population of the shocks. However, Parker and Zank (2012, 2014) and Parker et al. (2014) used a subset of the larger ACE database. Recently, work has successfully been completed that allows for the entire ACE database to be considered in a larger statistical analysis. We explain DSA as it applies to single and multiple shocks and the shock criteria used in this statistical analysis. We calculate the expected injection energy via diffusive shock acceleration given upstream parameters defined from the ACE Solar Wind Electron, Proton, and Alpha Monitor (SWEPAM) data to construct the theoretical upstream distribution. We show the comparison of shock strength derived from diffusive shock acceleration theory to observations in the 50 keV to 5 MeV range from an instrument on ACE. Parameters such as shock velocity, shock obliquity, particle number, and time between shocks are considered. This study is further divided into single and multiple shock categories, with an additional emphasis on forward-forward multiple shock pairs. Finally with regard to forwardforward shock pairs, results comparing injection energies of the first shock, second shock, and second shock with previous energetic population will be given.

Adverse childhood experiences and gender influence treatment seeking behaviors in obsessive-compulsive disorder.

PubMed

Benedetti, Francesco; Poletti, Sara; Radaelli, Daniele; Pozzi, Elena; Giacosa, Chiara; Smeraldi, Enrico

2014-02-01

Exposure to adverse childhood experiences (ACE) increases the risk of adult physical and mental health disorders, including obsessive-compulsive disorder (OCD), and influences adult brain structure and function. ACE could influence the use of psychotropic drugs in adulthood, and treatment seeking behaviors. We assessed the severity of ACE in a sample of 31 healthy controls and 66 patients with OCD who were consecutively referred for hospitalization and were either drug-naïve or drug-treated. In addition, we explored the possible clinical relevance of ACE with two additional analyses: (a) a discriminant function analysis with sex and ACE as factors, and (b) a logistic regression with use of medication as dependent variable and ACE as factor. Despite comparable age, years at school, age at onset of illness, duration of illness, and severity of illness (Y-BOCS), adult drug-naïve patients reported lower exposure to ACE and later contacts with mental health professionals than drug-treated. This effect was particularly evident in female patients compared to males. The interaction of gender with factors linked with the early familial environment biased access to psychiatric care and use of medication, independent of OCD-associated factors such as severity of symptoms or duration of illness. The need for medications of patients could be higher in families where OCD symptomatology is associated with ACE. © 2014.

The Addenbrooke's Cognitive Examination Revised (ACE-R) and its sub-scores: normative values in an Italian population sample.

PubMed

Siciliano, Mattia; Raimo, Simona; Tufano, Dario; Basile, Giuseppe; Grossi, Dario; Santangelo, Franco; Trojano, Luigi; Santangelo, Gabriella

2016-03-01

The Addenbrooke's Cognitive Examination Revised (ACE-R) is a rapid screening battery, including five sub-scales to explore different cognitive domains: attention/orientation, memory, fluency, language and visuospatial. ACE-R is considered useful in discriminating cognitively normal subjects from patients with mild dementia. The aim of present study was to provide normative values for ACE-R total score and sub-scale scores in a large sample of Italian healthy subjects. Five hundred twenty-six Italian healthy subjects (282 women and 246 men) of different ages (age range 20-93 years) and educational level (from primary school to university) underwent ACE-R and Montreal Cognitive Assessment (MoCA). Multiple linear regression analysis revealed that age and education significantly influenced performance on ACE-R total score and sub-scale scores. A significant effect of gender was found only in sub-scale attention/orientation. From the derived linear equation, a correction grid for raw scores was built. Inferential cut-offs score were estimated using a non-parametric technique and equivalent scores (ES) were computed. Correlation analysis showed a good significant correlation between ACE-R adjusted scores with MoCA adjusted scores (r = 0.612, p < 0.001). The present study provided normative data for the ACE-R in an Italian population useful for both clinical and research purposes.

Adverse Childhood Experiences and Alcohol Consumption in Midlife and Early Old-Age

PubMed Central

Leung, Jessica Pui Kei; Britton, Annie; Bell, Steven

2016-01-01

Aims To examine the individual and cumulative effects of adverse childhood experiences (ACEs) on alcohol consumption in midlife and early old-age, and the role of ACEs in 10-year drinking trajectories across midlife. Methods Data were from the Whitehall II study, a longitudinal British civil service-based cohort study (N = 7870, 69.5% male). Multinomial logistic regression was used to examine the individual and cumulative effects of ACEs on weekly alcohol consumption. Mixed-effect multilevel modelling was used to explore the relationship between ACEs and change in alcohol consumption longitudinally. Results Participants who were exposed to parental arguments/fights in childhood were 1.24 (95% CI 1.06, 1.45) times more likely to drink at hazardous levels in midlife (mean age 56 years) after controlling for covariates and other ACEs. For each additional exposure to an ACE, the risk of hazardous drinking versus moderate drinking was increased by 1.12 (95% CI 1.03, 1.21) after adjusting for sex, age, adult socio-economic status, ethnicity and marital status. No associations between ACEs and increased risk of hazardous drinking in early old-age (mean age 66 years) were found. In longitudinal analyses, ACEs did not significantly influence 10-year drinking trajectories across midlife. Conclusion The effect of exposure to parental arguments on hazardous drinking persists into midlife. PMID:26553290

Comparisons of Satellite Retrieval of Aerosol Properties from SeaWiFS and TOMS to the AERONET Measurements during ACE-Asia

NASA Technical Reports Server (NTRS)

Hsu, Christina N.; Tsay, Si-Chee; Herman, R.; Holben, Brent; Bhartia, P. K. (Technical Monitor)

2002-01-01

The primary goal of the ACE (Aerosol Characterization Experiment)-Asia mission is to increase our understanding of how atmospheric aerosol particles over the Asian-Pacific region affect the Earth climate system. In support of the day-to-day flight planning of ACE-Asia, we built a near real-time system to provide satellite data from the polar-orbiting instruments Earth Probe TOMS (Total Ozone Mapping Spectrometer) (in the form of absorbing aerosol index) and SeaWiFS (Sea-Viewing Wide Field-of-View Sensor) (in the form of aerosol optical thickness and Angstrom exponent). The results were available via web access. These satellite data provide a 'big picture' of aerosol distribution in the region, which is complementary to the ground based measurements. In this paper, we will briefly discuss the algorithms used to generate these data. The retrieved aerosol optical thickness and Angstrom exponent from SeaWiFS will be compared with those obtained from various AERONET (Aerosol Robotic Network) sites over the Asian-Pacific region. The TOMS aerosol index will also be compared with AERONET aerosol optical thickness over different aerosol conditions. Finally, we will discuss the climate implication of our studies using the combined satellite and AERONET observations.

Do sleep problems mediate the link between adverse childhood experiences and delinquency in preadolescent children in foster care?

PubMed

Hambrick, Erin P; Rubens, Sonia L; Brawner, Thomas W; Taussig, Heather N

2018-02-01

Adverse childhood experiences (ACEs) are associated with multiple mental and physical health problems. Yet, mechanisms by which ACEs confer risk for specific problems are largely unknown. Children in foster care typically have multiple ACEs and high rates of negative sequelae, including delinquent behaviors. Mechanisms explaining this link have not been explored in this population. Impaired sleep has been identified as a potential mechanism by which ACEs lead to delinquency in adolescents, because inadequate sleep may lead to poor executive function and cognitive control - known risk factors for delinquency. Interviews were conducted with 516 maltreated children in foster care, ages 9-11 years, and their caregivers regarding child exposure to ACEs, sleep problems, engagement in delinquent acts, symptoms of posttraumatic stress disorder, and current psychotropic medication use. ACEs data were also obtained from child welfare case records. After controlling for age, gender, race/ethnicity, placement type (residential, kin, foster), length of time in placement, posttraumatic stress symptoms, and current psychotropic medication use, sleep partially mediated the association between ACEs and delinquency. Although delinquency is likely multiply determined in this population, improving sleep may be one important strategy to reduce delinquency. © 2017 Association for Child and Adolescent Mental Health.

The Association between Adverse Childhood Experience (ACE) and School Success in Elementary School Children

ERIC Educational Resources Information Center

Blodgett, Christopher; Lanigan, Jane D.

2018-01-01

We explored the feasibility of using school personnel as reporters to examine the relationship between the level of adverse childhood experiences (ACEs) exposure in a nonclinical sample of public elementary schoolchildren and academic risk. We selected a random sample of 2,101 children from kindergarten through 6th grade classroom rosters at 10…

Disrupted Executive Function and Aggression in Individuals With a History of Adverse Childhood Experiences: An Event-Related Potential Study.

PubMed

Xue, Jiao-Mei; Lin, Ping-Zhen; Sun, Ji-Wei; Cao, Feng-Lin

2017-12-01

Here, we explored the functional and neural mechanisms underlying aggression related to adverse childhood experiences. We assessed behavioral performance and event-related potentials during a go/no-go and N-back paradigm. The participants were 15 individuals with adverse childhood experiences and high aggression (ACE + HA), 13 individuals with high aggression (HA), and 14 individuals with low aggression and no adverse childhood experiences (control group). The P2 latency (initial perceptual processing) was longer in the ACE + HA group for the go trials. The HA group had a larger N2 (response inhibition) than controls for the no-go trials. Error-related negativity (error processing) in the ACE + HA and HA groups was smaller than that of controls for false alarm go trials. Lastly, the ACE + HA group had shorter error-related negativity latencies than controls for false alarm trials. Overall, our results reveal the neural correlates of executive function in aggressive individuals with ACEs.

Adverse Childhood Experiences Related to Poor Adult Health Among Lesbian, Gay, and Bisexual Individuals

PubMed Central

Herrick, Harry; Proescholdbell, Scott

2016-01-01

Objectives. We explored the association of sexual orientation with poor adult health outcomes before and after adjustment for exposure to adverse childhood experiences (ACEs). Methods. Data were from the 2012 North Carolina, 2011 Washington, and 2011 and 2012 Wisconsin Behavioral Risk Factor Surveillance System (BRFSS) surveys regarding health risks, perceived poor health, and chronic conditions by sexual orientation and 8 categories of ACEs. There were 711 lesbian, gay, and bisexual (LGB) respondents and 29 690 heterosexual respondents. Results. LGB individuals had a higher prevalence of all ACEs than heterosexuals, with odds ratios ranging from 1.4 to 3.1. After adjustment for cumulative exposure to ACEs, sexual orientation was no longer associated with poor physical health, current smoking, and binge drinking. Associations with poor mental health, activity limitation, HIV risk behaviors, current asthma, depression, and disability remained, but were attenuated. Conclusions. The higher prevalence of ACEs among LGB individuals may account for some of their excess risk for poor adult health outcomes. PMID:26691127

Comparison of upper tropospheric carbon monoxide from MOPITT, ACE-FTS, and HIPPO-QCLS

NASA Astrophysics Data System (ADS)

Martínez-Alonso, Sara; Deeter, Merritt N.; Worden, Helen M.; Gille, John C.; Emmons, Louisa K.; Pan, Laura L.; Park, Mijeong; Manney, Gloria L.; Bernath, Peter F.; Boone, Chris D.; Walker, Kaley A.; Kolonjari, Felicia; Wofsy, Steven C.; Pittman, Jasna; Daube, Bruce C.

2014-12-01

Products from the Measurements Of Pollution In The Troposphere (MOPITT) instrument are regularly validated using in situ airborne measurements. However, few of these measurements reach into the upper troposphere, thus hindering MOPITT validation in that region. Here we evaluate upper tropospheric (~500 hPa to the tropopause) MOPITT CO profiles by comparing them to satellite Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) retrievals and to measurements from the High-performance Instrumented Airborne Platform for Environmental Research Pole to Pole Observations (HIPPO) Quantum Cascade Laser Spectrometer (QCLS). Direct comparison of colocated v5 MOPITT thermal infrared-only retrievals, v3.0 ACE-FTS retrievals, and HIPPO-QCLS measurements shows a slight positive MOPITT CO bias within its 10% accuracy requirement with respect to the other two data sets. Direct comparison of colocated ACE-FTS and HIPPO-QCLS measurements results in a small number of samples due to the large disparity in sampling pattern and density of these data sets. Thus, two additional indirect techniques for comparison of noncoincident data sets have been applied: tracer-tracer (CO-O3) correlation analysis and analysis of profiles in tropopause coordinates. These techniques suggest a negative bias of ACE-FTS with respect to HIPPO-QCLS; this could be caused by differences in resolution (horizontal, vertical) or by deficiencies in the ACE-FTS CO retrievals below ~20 km of altitude, among others. We also investigate the temporal stability of MOPITT and ACE-FTS data, which provide unique global CO records and are thus important in climate analysis. Our results indicate that the relative bias between the two data sets has remained generally stable during the 2004-2010 period.

The Transcriptome Analysis and Comparison Explorer--T-ACE: a platform-independent, graphical tool to process large RNAseq datasets of non-model organisms.

PubMed

Philipp, E E R; Kraemer, L; Mountfort, D; Schilhabel, M; Schreiber, S; Rosenstiel, P

2012-03-15

Next generation sequencing (NGS) technologies allow a rapid and cost-effective compilation of large RNA sequence datasets in model and non-model organisms. However, the storage and analysis of transcriptome information from different NGS platforms is still a significant bottleneck, leading to a delay in data dissemination and subsequent biological understanding. Especially database interfaces with transcriptome analysis modules going beyond mere read counts are missing. Here, we present the Transcriptome Analysis and Comparison Explorer (T-ACE), a tool designed for the organization and analysis of large sequence datasets, and especially suited for transcriptome projects of non-model organisms with little or no a priori sequence information. T-ACE offers a TCL-based interface, which accesses a PostgreSQL database via a php-script. Within T-ACE, information belonging to single sequences or contigs, such as annotation or read coverage, is linked to the respective sequence and immediately accessible. Sequences and assigned information can be searched via keyword- or BLAST-search. Additionally, T-ACE provides within and between transcriptome analysis modules on the level of expression, GO terms, KEGG pathways and protein domains. Results are visualized and can be easily exported for external analysis. We developed T-ACE for laboratory environments, which have only a limited amount of bioinformatics support, and for collaborative projects in which different partners work on the same dataset from different locations or platforms (Windows/Linux/MacOS). For laboratories with some experience in bioinformatics and programming, the low complexity of the database structure and open-source code provides a framework that can be customized according to the different needs of the user and transcriptome project.

Methodology to Calculate the ACE and HPQ Metrics Used in the Wave Energy Prize

DOE Office of Scientific and Technical Information (OSTI.GOV)

Driscoll, Frederick R; Weber, Jochem W; Jenne, Dale S

The U.S. Department of Energy's Wave Energy Prize Competition encouraged the development of innovative deep-water wave energy conversion technologies that at least doubled device performance above the 2014 state of the art. Because levelized cost of energy (LCOE) metrics are challenging to apply equitably to new technologies where significant uncertainty exists in design and operation, the prize technical team developed a reduced metric as proxy for LCOE, which provides an equitable comparison of low technology readiness level wave energy converter (WEC) concepts. The metric is called 'ACE' which is short for the ratio of the average climate capture width tomore » the characteristic capital expenditure. The methodology and application of the ACE metric used to evaluate the performance of the technologies that competed in the Wave Energy Prize are explained in this report.« less

Real-time Kp predictions from ACE real time solar wind

NASA Astrophysics Data System (ADS)

Detman, Thomas; Joselyn, Joann

1999-06-01

The Advanced Composition Explorer (ACE) spacecraft provides nearly continuous monitoring of solar wind plasma, magnetic fields, and energetic particles from the Sun-Earth L1 Lagrange point upstream of Earth in the solar wind. The Space Environment Center (SEC) in Boulder receives ACE telemetry from a group of international network of tracking stations. One-minute, and 1-hour averages of solar wind speed, density, temperature, and magnetic field components are posted on SEC's World Wide Web page within 3 to 5 minutes after they are measured. The ACE Real Time Solar Wind (RTSW) can be used to provide real-time warnings and short term forecasts of geomagnetic storms based on the (traditional) Kp index. Here, we use historical data to evaluate the performance of the first real-time Kp prediction algorithm to become operational.

KSC-97PC1079

NASA Image and Video Library

1997-07-22

Applied Physics Laboratory Engineer Cliff Willey (kneeling) and Engineering Assistant Jim Hutcheson from Johns Hopkins University install solar array panels on the Advanced Composition Explorer (ACE) in KSC’s Spacecraft Assembly and Encapsulation Facility-II. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles for a better understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA

Dust Aerosols at the Source Region During ACE-ASIA: A Surface/Satellite Perspective

NASA Technical Reports Server (NTRS)

Tsay, Si-Chee; Lau, William K. M. (Technical Monitor)

2001-01-01

ACE (Aerosol Characterization Experiment)-Asia is designed to study the compelling variability in spatial and temporal scale of both pollution-derived and naturally occurring aerosols, which often exist in high concentrations over eastern Asia and along the rim of the western Pacific. The phase-I of ACE-Asia was conducted from March-May 2001 in the vicinity of the Gobi desert, East Coast of China, Yellow Sea, Korea, and Japan, along the pathway of Kosa (severe events that blanket East Asia with yellow desert dust, peaked in the Spring season). Asian dust typically originates in desert areas far from polluted urban regions. During transport, dust layers can interact with anthropogenic sulfate and soot aerosols from heavily polluted urban areas. Added to the complex effects of clouds and natural marine aerosols, dust particles reaching the marine environment can have drastically different properties than those from the source. Thus, understanding the unique temporal and spatial variations of Asian dust is of special importance in regional-to-global climate issues such as radiative forcing, the hydrological cycle, and primary biological productivity in the mid-Pacific Ocean. During ACE-Asia we have measured continuously aerosol physical/optical/radiative properties, column precipitable water amount, and surface reflectivity over homogeneous areas from surface. The inclusion of flux measurements permits the determination of dust aerosol radiative flux in addition to measurements of loading and optical thickness. At the time of the Terra/MODIS, SeaWiFS, TOMS and other satellite overpasses, these ground-based observations can provide valuable data to compare with satellite retrievals over land. Preliminary results will be presented and discussed their implications in regional climatic effects.

ASK Magazine. No. 9

NASA Technical Reports Server (NTRS)

Post, Todd (Editor)

2002-01-01

Most of this issue is about ACE (Advanced Composition Explorer). We've collected stories by four members of the ACE management team: Don Margolies, the mission manager from Goddard Space Flight Center; Frandsen, science payloads manager from the Caltech Jet Propulsion Laboratory; Mary Chin, project manager in charge of spacecraft development at the Johns Hopkins Applied Physics Laboratory; and Frank Snow, operations and ground systems manager at Goddard.

KSC-97PC1127

NASA Image and Video Library

1997-07-24

Applied Physics Laboratory engineers and technicians from Johns Hopkins University test for true perpendicular solar array deployment of the Advanced Composition Explorer (ACE) in KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). The white magnetometer boom seen across the solar array panel will deploy the panel once in space. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun

KSC-97PC1128

NASA Image and Video Library

1997-07-24

An Applied Physics Laboratory engineer from Johns Hopkins University tests for true perpendicular solar array deployment of the Advanced Composition Explorer (ACE) in KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). The white magnetometer boom seen across the solar array panel will deploy the panel once in space. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The ACE observatory will be placed into an orbit almost a million miles (1.5 million kilometers) away from the Earth, about 1/100 the distance from the Earth to the Sun

KSC-97PC1013

NASA Image and Video Library

1997-07-02

Workers from the Johns Hopkins University’s Applied Physics Laboratory (APL) install the Cosmic Ray Isotope Spectrometer (CRIS) on the Advanced Composition Explorer (ACE) spacecraft in KSC’s Spacecraft Assembly and Encapsulation Facility-2 (SAEF-2). From left, are Al Sadilek, Marcos Gonzalez and Cliff Willey. CRIS is one of nine instruments on ACE, which will investigate the origin and evolution of solar phenomenon, the formation of the solar corona, solar flares and the acceleration of the solar wind. ACE was developed for NASA by the APL. The spacecraft is scheduled to be launched Aug. 21 aboard a two-stage Delta II 7920-8 rocket from Space Launch Complex 17, Pad A

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response.

PubMed

Klempin, Friederike; Mosienko, Valentina; Matthes, Susann; Villela, Daniel C; Todiras, Mihail; Penninger, Josef M; Bader, Michael; Santos, Robson A S; Alenina, Natalia

2018-04-20

Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.

KSC-97PC1126

NASA Image and Video Library

1997-07-24

Applied Physics Laboratory engineers and technicians from Johns Hopkins University test solar array deployment of the Advanced Composition Explorer (ACE) in KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). The wire hanging from the ceiling above the black solar array panel is used for "g-negation," which takes the weight off of the panel’s hinges to simulate zero gravity, mimicking deployment in space. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles. The collecting power of instruments aboard ACE is 10 to 1,000 times greater than anything previously flown to collect similar data by NASA

Modification of Epigenetic Patterns in Low Birth Weight Children: Importance of Hypomethylation of the ACE Gene Promoter

PubMed Central

Rangel, Marina; dos Santos, Jéssica Cassilla; Ortiz, Paula Helena Lima; Hirata, Mario; Jasiulionis, Miriam Galvonas; Araujo, Ronaldo C.; Ierardi, Daniela Filippini; Franco, Maria do Carmo

2014-01-01

There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels. PMID:25170764

Modification of epigenetic patterns in low birth weight children: importance of hypomethylation of the ACE gene promoter.

PubMed

Rangel, Marina; dos Santos, Jéssica Cassilla; Ortiz, Paula Helena Lima; Hirata, Mario; Jasiulionis, Miriam Galvonas; Araujo, Ronaldo C; Ierardi, Daniela Filippini; Franco, Maria do Carmo

2014-01-01

There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels.

Adverse Childhood Experiences and Health and Wellness Outcomes among Black Men Who Have Sex with Men.

PubMed

Ports, K A; Lee, R D; Raiford, J; Spikes, P; Manago, C; Wheeler, D P

2017-06-01

Black men who have sex with men (BMSM) are a population at the intersection of two minority statuses-racial minority and sexual minority. Membership in either group, compared to white or heterosexual group membership, may increase one's risk of negative childhood and adult experiences. Baseline data from an HIV intervention efficacy trial (the Black Men Evolving Study) were used to explore the prevalence of adverse childhood experiences (ACEs) among 536 BMSM and associations between ACEs and adult mental and physical health outcomes. Overall, the prevalence of ACEs was high among this sample of BMSM with almost 90% experiencing at least one ACE. Findings revealed that ACE score was significantly associated with adult mental health (AOR = 1.21, 95% CI [1.12, 1.30]), but not with adult physical health. All ACEs were significantly associated with mental health, but only physical neglect and household substance abuse were significantly associated with physical health (AOR = 1.69, 95% CI [1.02, 2.74] and AOR = 1.57, 95% CI [1.03, 2.40], respectively). The findings support the need for interventions targeting improved adult health outcomes, particularly for minority groups, to consider the impact of early adversity on health and wellness.

The NASA Decadal Survey Aerosol, Cloud, Ecosystems Mission

NASA Technical Reports Server (NTRS)

McClain, Charles R.; Bontempi, Paula; Maring, Hal

2011-01-01

In 2007, the National Academy of Sciences delivered a Decadal Survey (Earth Science and Applications from Space: National Imperatives for the Next Decade and Beyond) for NASA, NOAA, and USGS, which is a prioritization of future satellite Earth observations. The recommendations included 15 missions (13 for NASA, two for NOAA), which were prioritized into three groups or tiers. One of the second tier missions is the Aerosol, Cloud, (ocean) Ecosystems (ACE) mission, which focuses on climate forcing, cloud and aerosol properties and interactions, and ocean ecology, carbon cycle science, and fluxes. The baseline instruments recommended for ACE are a cloud radar, an aerosol/cloud lidar, an aerosol/cloud polarimeter, and an ocean radiometer. The instrumental heritage for these measurements are derived from the Cloudsat, CALIPSO, Glory, SeaWiFS and Aqua (MODIS) missions. In 2008, NASA HQ, lead by Hal Maring and Paula Bontempi, organized an interdisciplinary science working group to help formulate the ACE mission by refining the science objectives and approaches, identifying measurement (satellite and field) and mission (e.g., orbit, data processing) requirements, technology requirements, and mission costs. Originally, the disciplines included the cloud, aerosol, and ocean biogeochemistry communities. Subsequently, an ocean-aerosol interaction science working group was formed to ensure the mission addresses the broadest range of science questions possible given the baseline measurements, The ACE mission is a unique opportunity for ocean scientists to work closely with the aerosol and cloud communities. The science working groups are collaborating on science objectives and are defining joint field studies and modeling activities. The presentation will outline the present status of the ACE mission, the science questions each discipline has defined, the measurement requirements identified to date, the current ACE schedule, and future opportunities for broader community participation.

Adverse childhood experiences and sexual victimization in adulthood.

PubMed

Ports, Katie A; Ford, Derek C; Merrick, Melissa T

2016-01-01

Understanding the link between adverse childhood experiences (ACEs) and sexual victimization (SV) in adulthood may provide important information about the level of risk for adult SV and sexual re-victimization among childhood sexual abuse (CSA) survivors. In the present paper, we explore the relationship between ACEs, including CSA, and SV in adulthood. Data from the CDC-Kaiser ACE Study were used to examine the effect of experiences of early adversity on adult SV. Adult HMO members (n=7,272) undergoing a routine health exam provided detailed information about ACEs that occurred at age 18 or younger and their experiences of SV in adulthood. Analyses revealed that as ACE score increased, so did risk of experiencing SV in adulthood. Each of the ACE variables was significantly associated with adult SV, with CSA being the strongest predictor of adult SV. In addition, for those who reported CSA, there was a cumulative increase in adult SV risk with each additional ACE experienced. As such, early adversity is a risk factor for adult SV. In particular, CSA is a significant risk factor for sexual re-victimization in adulthood, and additional early adversities experienced by CSA survivors may heighten adult SV risk above and beyond the risk associated with CSA alone. Given the interconnectedness among various experiences of early adversity, adult SV prevention actions must consider how other violence-related and non-violence-related traumatic experiences may exacerbate the risk conferred by CSA on subsequent victimization. Published by Elsevier Ltd.

Airborne Polarimeter Intercomparison for the NASA Aerosols-Clouds-Ecosystems (ACE) Mission

NASA Technical Reports Server (NTRS)

Knobelspiesse, Kirk; Redemann, Jens

2014-01-01

The Aerosols-Clouds-Ecosystems (ACE) mission, recommended by the National Research Council's Decadal Survey, calls for a multi-angle, multi-spectral polarimeter devoted to observations of atmospheric aerosols and clouds. In preparation for ACE, NASA funds the deployment of airborne polarimeters, including the Airborne Multi-angle SpectroPolarimeter Imager (AirMSPI), the Passive Aerosol and Cloud Suite (PACS) and the Research Scanning Polarimeter (RSP). These instruments have been operated together on NASA's ER-2 high altitude aircraft as part of field campaigns such as the POlarimeter DEfinition EXperiment (PODEX) (California, early 2013) and Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS, California and Texas, summer 2013). Our role in these efforts has been to serve as an assessment team performing level 1 (calibrated radiance, polarization) and level 2 (retrieved geophysical parameter) instrument intercomparisons, and to promote unified and generalized calibration, uncertainty assessment and retrieval techniques. We will present our progress in this endeavor thus far and describe upcoming research in 2015.

Progress in Airborne Polarimeter Inter Comparison for the NASA Aerosols-Clouds-Ecosystems (ACE) Mission

NASA Technical Reports Server (NTRS)

Knobelspiesse, Kirk; Redemann, Jens

2014-01-01

The Aerosols-Clouds-Ecosystems (ACE) mission, recommended by the National Research Council's Decadal Survey, calls for a multi-angle, multi-spectral polarimeter devoted to observations of atmospheric aerosols and clouds. In preparation for ACE, NASA funds the deployment of airborne polarimeters, including the Airborne Multiangle SpectroPolarimeter Imager (AirMSPI), the Passive Aerosol and Cloud Suite (PACS) and the Research Scanning Polarimeter (RSP). These instruments have been operated together on NASA's ER-2 high altitude aircraft as part of field campaigns such as the POlarimeter DEfinition EXperiment (PODEX) (California, early 2013) and Studies of Emissions and Atmospheric Composition, Clouds and Climate Coupling by Regional Surveys (SEAC4RS, California and Texas, summer 2013). Our role in these efforts has been to serve as an assessment team performing level 1 (calibrated radiance, polarization) and level 2 (retrieved geophysical parameter) instrument intercomparisons, and to promote unified and generalized calibration, uncertainty assessment and retrieval techniques. We will present our progress in this endeavor thus far and describe upcoming research in 2015.

A Small Spacecraft Swarm Deployment and Stationkeeping Strategy for Sun-Earth L1 Halo Orbits

NASA Technical Reports Server (NTRS)

Conn, Tracie R.; Bookbinder, Jay

2018-01-01

Spacecraft orbits about the Sun-Earth librarian point L1 have been of interest since the 1950s. An L1 halo orbit was first achieved with the International Sun-Earth Explorer-3 (ISEE-3) mission, and similar orbits around Sun-Earth L1 were achieved in the Solar and Heliospheric Observatory (SOHO), Advanced Composition Explorer (ACE), Genesis, and Deep Space Climate Observatory (DSCOVR) missions. With recent advancements in CubeSat technology, we envision that it will soon be feasible to deploy CubeSats at L1. As opposed to these prior missions where one large satellite orbited alone, a swarm of CubeSats at L1 would enable novel science data return, providing a topology for intersatellite measurements of heliophysics phenomena both spatially and temporally, at varying spatial scales.The purpose of this iPoster is to present a flight dynamics strategy for a swarm of numerous CubeSats orbiting Sun-Earth L1. The presented method is a coupled, two-part solution. First, we present a deployment strategy for the CubeSats that is optimized to produce prescribed, time-varying intersatellite baselines for the purposes of collecting magnetometer data as well as radiometric measurements from cross-links. Second, we employ a loose control strategy that was successfully applied to SOHO and ACE for minimized stationkeeping fuel expenditure. We emphasize that the presented solution is practical within the current state-of-the-art and heritage CubeSat technology, citing capabilities of CubeSat designs that will launch on the upcoming Exploration Mission 1 (EM-1) to lunar orbits and beyond. Within this iPoster, we present animations of the simulated deployment strategy and resulting spacecraft trajectories. Mission design parameters such as total delta-v required for long-term station keeping and minimummaximummean spacecraft separation distances are also presented.

A Small Spacecraft Swarm Deployment and Stationkeeping Strategy for Sun-Earth L1 Halo Orbits

NASA Astrophysics Data System (ADS)

Renea Conn, Tracie; Bookbinder, Jay

2018-01-01

Spacecraft orbits about the Sun-Earth librarian point L1 have been of interest since the 1950s. An L1 halo orbit was first achieved with the International Sun-Earth Explorer-3 (ISEE-3) mission, and similar orbits around Sun-Earth L1 were achieved in the Solar and Heliospheric Observatory (SOHO), Advanced Composition Explorer (ACE), Genesis, and Deep Space Climate Observatory (DSCOVR) missions. With recent advancements in CubeSat technology, we envision that it will soon be feasible to deploy CubeSats at L1. As opposed to these prior missions where one large satellite orbited alone, a swarm of CubeSats at L1 would enable novel science data return, providing a topology for intersatellite measurements of heliophysics phenomena both spatially and temporally, at varying spatial scales.The purpose of this iPoster is to present a flight dynamics strategy for a swarm of numerous CubeSats orbiting Sun-Earth L1. The presented method is a coupled, two-part solution. First, we present a deployment strategy for the CubeSats that is optimized to produce prescribed, time-varying intersatellite baselines for the purposes of collecting magnetometer data as well as radiometric measurements from cross-links. Second, we employ a loose control strategy that was successfully applied to SOHO and ACE for minimized stationkeeping propellant expenditure. We emphasize that the presented solution is practical within the current state-of-the-art and heritage CubeSat technology, citing capabilities of CubeSat designs that will launch on the upcoming Exploration Mission 1 (EM-1) to lunar orbits and beyond. Within this iPoster, we present animations of the simulated deployment strategy and resulting spacecraft trajectories. Mission design parameters such as total Δv required for long-term station keeping and minimum/maximum/mean spacecraft separation distances are also presented.

Automated canopy estimator (ACE): Enhancing crop modelling and decision making in agriculture

USDA-ARS?s Scientific Manuscript database

The Caribbean agriculture sector is dominated by small holdings, which are overly reliant on rainfall and highly dependent on manual means of optimization. The sector is therefore very vulnerable to the vagaries of climate variability and change, with rainfall variations being of particular concern...

Adverse Outcome Pathways (AOPs) in Human Systems Biology: Gas-Phase Probes for Assessing In Vitro Enzyme System Perturbations

EPA Science Inventory

The Air, Climate, and Energy (ACE) and Chemical Safety for Sustainability (CSS) programs at the U.S. EnvironmentalProtection Agency (EPA) encompass broad-based research that includes assessment of the health and environmentalimpacts of anthropogenic and manufactured chemicals. On...

KSC-97PC904

NASA Image and Video Library

1997-06-16

Workers in the Spacecraft Assembly and Encapsulation Facility-2 (SAEF-2) begin prelaunch processing of the Advanced Composition Explorer (ACE) which will investigate the origin and evolution of solar phenomenon, the formation of the solar corona, solar flares and the acceleration of the solar wind. ACE was built for NASA by the Johns Hopkins Applied Physics Laboratory. The spacecraft is scheduled to be launched Aug. 21 aboard a two-stage Delta II 7920-8 rocket from Space Launch Complex 17, Pad A

New temperature and pressure retrieval algorithm for high-resolution infrared solar occultation spectroscopy: analysis and validation against ACE-FTS and COSMIC

NASA Astrophysics Data System (ADS)

Olsen, Kevin S.; Toon, Geoffrey C.; Boone, Chris D.; Strong, Kimberly

2016-03-01

Motivated by the initial selection of a high-resolution solar occultation Fourier transform spectrometer (FTS) to fly to Mars on the ExoMars Trace Gas Orbiter, we have been developing algorithms for retrieving volume mixing ratio vertical profiles of trace gases, the primary component of which is a new algorithm and software for retrieving vertical profiles of temperature and pressure from the spectra. In contrast to Earth-observing instruments, which can rely on accurate meteorological models, a priori information, and spacecraft position, Mars retrievals require a method with minimal reliance on such data. The temperature and pressure retrieval algorithms developed for this work were evaluated using Earth-observing spectra from the Atmospheric Chemistry Experiment (ACE) FTS, a solar occultation instrument in orbit since 2003, and the basis for the instrument selected for a Mars mission. ACE-FTS makes multiple measurements during an occultation, separated in altitude by 1.5-5 km, and we analyse 10 CO2 vibration-rotation bands at each altitude, each with a different usable altitude range. We describe the algorithms and present results of their application and their comparison to the ACE-FTS data products. The Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) provides vertical profiles of temperature up to 40 km with high vertical resolution. Using six satellites and GPS radio occultation, COSMIC's data product has excellent temporal and spatial coverage, allowing us to find coincident measurements with ACE with very tight criteria: less than 1.5 h and 150 km. We present an intercomparison of temperature profiles retrieved from ACE-FTS using our algorithm, that of the ACE Science Team (v3.5), and from COSMIC. When our retrievals are compared to ACE-FTS v3.5, we find mean differences between -5 and +2 K and that our retrieved profiles have no seasonal or zonal biases but do have a warm bias in the stratosphere and a cold bias in the mesosphere. When compared to COSMIC, we do not observe a warm/cool bias and mean differences are between -4 and +1 K. COSMIC comparisons are restricted to below 40 km, where our retrievals have the best agreement with ACE-FTS v3.5. When comparing ACE-FTS v3.5 to COSMIC we observe a cold bias in COSMIC of 0.5 K, and mean differences are between -0.9 and +0.6 K.

Effect of Aloe vera (Aloe barbadensis Miller) on survivability, extent of proteolysis and ACE inhibition of potential probiotic cultures in fermented milk.

PubMed

Basannavar, Santosh; Pothuraju, Ramesh; Sharma, Raj Kumar

2014-10-01

In the present investigation, the effect of Aloe vera gel powder on angiotensin-converting enzyme (ACE) inhibitory activity, extent of proteolysis during fermentation and survival of Lactobacillus casei NCDC19 during storage of fermented milk was studied. Among the different cultures screened for ACE inhibitory activity, Lactobacillus casei NCDC 19 exhibited the highest ACE inhibition (approx. 40%) as well as extent of proteolysis (0.37, Abs₃₄₀). In the presence of Aloe vera (0.5% and 1% w/v) an increase in extent of proteolysis (0.460 ± 0.047 and 0.480 ± 0.027) and percent ACE inhibitory activity (44.32 ± 2.83 and 47.52 ± 1.83) was observed in comparison to control. Aloe vera powder addition also led to an increase in viable counts (>11 log cfu mL⁻¹) of L. casei NCDC 19 in fermented milk during storage for 7 days and the counts were maintained in sufficiently higher numbers. The study suggests Aloe vera to be a good functional ingredient which can be further explored for different health attributes. © 2014 Society of Chemical Industry.

Assessing stratospheric transport in the CMAM30 simulations using ACE-FTS measurements

NASA Astrophysics Data System (ADS)

Kolonjari, Felicia; Plummer, David A.; Walker, Kaley A.; Boone, Chris D.; Elkins, James W.; Hegglin, Michaela I.; Manney, Gloria L.; Moore, Fred L.; Pendlebury, Diane; Ray, Eric A.; Rosenlof, Karen H.; Stiller, Gabriele P.

2018-05-01

Stratospheric transport in global circulation models and chemistry-climate models is an important component in simulating the recovery of the ozone layer as well as changes in the climate system. The Brewer-Dobson circulation is not well constrained by observations and further investigation is required to resolve uncertainties related to the mechanisms driving the circulation. This study has assessed the specified dynamics mode of the Canadian Middle Atmosphere Model (CMAM30) by comparing to the Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) profile measurements of CFC-11 (CCl3F), CFC-12 (CCl2F2), and N2O. In the CMAM30 specified dynamics simulation, the meteorological fields are nudged using the ERA-Interim reanalysis and a specified tracer was employed for each species, with hemispherically defined surface measurements used as the boundary condition. A comprehensive sampling technique along the line of sight of the ACE-FTS measurements has been utilized to allow for direct comparisons between the simulated and measured tracer concentrations. The model consistently overpredicts tracer concentrations of CFC-11, CFC-12, and N2O in the lower stratosphere, particularly in the northern hemispheric winter and spring seasons. The three mixing barriers investigated, including the polar vortex, the extratropical tropopause, and the tropical pipe, show that there are significant inconsistencies between the measurements and the simulations. In particular, the CMAM30 simulation underpredicts mixing efficiency in the tropical lower stratosphere during the June-July-August season.

Single Nucleotide Polymorphisms of the Angiotensin-Converting Enzyme (ACE) Gene Are Associated with Essential Hypertension and Increased ACE Enzyme Levels in Mexican Individuals

PubMed Central

Martínez-Rodríguez, Nancy; Posadas-Romero, Carlos; Villarreal-Molina, Teresa; Vallejo, Maite; Del-Valle-Mondragón, Leonardo; Ramírez-Bello, Julian; Valladares, Adan; Cruz-López, Miguel; Vargas-Alarcón, Gilberto

2013-01-01

Aim To explore the role of the ACE gene polymorphisms in the risk of essential hypertension in Mexican Mestizo individuals and evaluate the correlation between these polymorphisms and the serum ACE levels. Methods Nine ACE gene polymorphisms were genotyped by 5′ exonuclease TaqMan genotyping assays and polymerase chain reaction (PCR) in 239 hypertensive and 371 non- hypertensive Mexican individuals. Haplotypes were constructed after linkage disequilibrium analysis. ACE serum levels were determined in selected individuals according to different haplotypes. Results Under a dominant model, rs4291 rs4335, rs4344, rs4353, rs4362, and rs4363 polymorphisms were associated with an increased risk of hypertension after adjusting for age, gender, BMI, triglycerides, alcohol consumption, and smoking. Five polymorphisms (rs4335, rs4344, rs4353, rs4362 and rs4363) were in strong linkage disequilibrium and were included in four haplotypes: H1 (AAGCA), H2 (GGATG), H3 (AGATG), and H4 (AGACA). Haplotype H1 was associated with decreased risk of hypertension, while haplotype H2 was associated with an increased risk of hypertension (OR = 0.77, P = 0.023 and OR = 1.41, P = 0.004 respectively). According to the codominant model, the H2/H2 and H1/H2 haplotype combinations were significantly associated with risk of hypertension after adjusted by age, gender, BMI, triglycerides, alcohol consumption, and smoking (OR = 2.0; P = 0.002 and OR = 2.09; P = 0.011, respectively). Significant elevations in serum ACE concentrations were found in individuals with the H2 haplotype (H2/H2 and H2/H1) as compared to H1/H1 individuals (P = 0.0048). Conclusion The results suggest that single nucleotide polymorphisms and the “GGATG” haplotype of the ACE gene are associated with the development of hypertension and with increased ACE enzyme levels. PMID:23741507

Single nucleotide polymorphisms of the angiotensin-converting enzyme (ACE) gene are associated with essential hypertension and increased ACE enzyme levels in Mexican individuals.

PubMed

Martínez-Rodríguez, Nancy; Posadas-Romero, Carlos; Villarreal-Molina, Teresa; Vallejo, Maite; Del-Valle-Mondragón, Leonardo; Ramírez-Bello, Julian; Valladares, Adan; Cruz-López, Miguel; Vargas-Alarcón, Gilberto

2013-01-01

To explore the role of the ACE gene polymorphisms in the risk of essential hypertension in Mexican Mestizo individuals and evaluate the correlation between these polymorphisms and the serum ACE levels. Nine ACE gene polymorphisms were genotyped by 5' exonuclease TaqMan genotyping assays and polymerase chain reaction (PCR) in 239 hypertensive and 371 non- hypertensive Mexican individuals. Haplotypes were constructed after linkage disequilibrium analysis. ACE serum levels were determined in selected individuals according to different haplotypes. Under a dominant model, rs4291 rs4335, rs4344, rs4353, rs4362, and rs4363 polymorphisms were associated with an increased risk of hypertension after adjusting for age, gender, BMI, triglycerides, alcohol consumption, and smoking. Five polymorphisms (rs4335, rs4344, rs4353, rs4362 and rs4363) were in strong linkage disequilibrium and were included in four haplotypes: H1 (AAGCA), H2 (GGATG), H3 (AGATG), and H4 (AGACA). Haplotype H1 was associated with decreased risk of hypertension, while haplotype H2 was associated with an increased risk of hypertension (OR = 0.77, P = 0.023 and OR = 1.41, P = 0.004 respectively). According to the codominant model, the H2/H2 and H1/H2 haplotype combinations were significantly associated with risk of hypertension after adjusted by age, gender, BMI, triglycerides, alcohol consumption, and smoking (OR = 2.0; P = 0.002 and OR = 2.09; P = 0.011, respectively). Significant elevations in serum ACE concentrations were found in individuals with the H2 haplotype (H2/H2 and H2/H1) as compared to H1/H1 individuals (P = 0.0048). The results suggest that single nucleotide polymorphisms and the "GGATG" haplotype of the ACE gene are associated with the development of hypertension and with increased ACE enzyme levels.

A human GRPr-transfected Ace-1 canine prostate cancer model in mice.

PubMed

Ding, Haiming; Kothandaraman, Shankaran; Gong, Li; Williams, Michelle M; Dirksen, Wessel P; Rosol, Thomas J; Tweedle, Michael F

2016-06-01

A versatile drug screening system was developed to simplify early targeted drug discovery in mice and then translate readily from mice to a dog prostate cancer model that more fully replicates the features of human prostate cancer. We stably transfected human cDNA of the GRPr bombesin (BBN) receptor subtype to canine Ace-1 prostate cancer cells (Ace-1(huGRPr) ). Expression was examined by (125) I-Tyr(4) -BBN competition, calcium stimulation assay, and fluorescent microscopy. A dual tumor nude mouse xenograft model was developed from Ace-1(CMV) (vector transfected Ace-1) and Ace-1(huGRPr) cells. The model was used to explore the in vivo behavior of two new IRDye800-labeled GRPr binding optical imaging agents: 800-G-Abz4-t-BBN, from a GRPr agonist peptide, and 800-G-Abz4-STAT, from a GRPr antagonist peptide, by imaging the tumor mice and dissected organs. Both agents bound Ace-1(huGRPr) and PC-3, a known GRPr-expressing human prostate cancer cell line, with 4-13 nM IC50 against (125) I-Tyr(4) -BBN, but did not bind Ace-1(CMV) cells (vector transfected). Binding was blocked by bombesin. Ca(2+) activation assays demonstrated that Ace-1(huGPRr) expressed biologically active GRPr. Both Ace-1 cell lines grew in the flanks of 100% of the nude mice and formed tumors of ∼0.5 cm diameter in 1 week. In vivo imaging of the mice at 800 nm emission showed GRPr+: GRPr- tumor signal brighter by a factor of two at 24 h post IV administration of 10 nmol of the imaging agents. Blood retention (4-8% ID at 1 h) was greater by a factor >10 and cumulative urine accumulation (28-30% at 4 h) was less by a factor 2 compared to a radioactive analog of the t-BBN containing agent, (177) LuAMBA, probably due to binding to blood albumin, which we confirmed in a mouse serum assay. The dual tumor Ace-1(CMV) /Ace-1(huGRPr) model system provides a rapid test of specific to nonspecific binding of new GRPr avid agents in a model that will extend logically to the known Ace-1 orthotopic canine prostate cancer model. Prostate 76:783-795, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The experience of adverse childhood experiences and dental care in childhood.

PubMed

Crouch, Elizabeth; Radcliff, Elizabeth; Nelson, Joni; Strompolis, Melissa; Martin, Amy

2018-06-06

Routine preventive dental care is important to overall child health and well-being. However, the experience of adversity in childhood may prevent children from getting adequate preventive care. This study seeks to explore how the prevalence of adverse childhood experiences (ACEs) and the role of a protective adult may be associated with dental care utilization in childhood. Data from the 2016 South Carolina Behavioral Risk Factor Surveillance System (SC BRFSS), which interviews adults eighteen year of age and older, were used in this study. Dental care utilization in childhood was measured as the adult retrospectively reported frequency of dental care in childhood: at least once every 2 years (adequate dental care) or less often than every 2 years (inadequate dental care). ACEs were determined by asking about each of respondent's childhood exposure to eleven childhood experiences, including divorce, parental incarceration, domestic violence, drug and alcohol abuse, mental illness and emotional, physical or sexual abuse. The presence of a protective adult in childhood included respondents who had an adult who made them feel safe and protected during childhood. Descriptive and bivariate statistics explored differences in the adequacy of child dental care by ACE exposure, the presence of a protective adult and selected demographic characteristics. Multivariate regression models were used to examine the impact of counts and types of ACEs and the presence of a protective adult with inadequate childhood dental care. The unweighted study sample included 7079 respondents ageing from 18 to 79 years of age Sampling weights were used for all analyses. Among all respondents, 71.7% reported receiving adequate dental care during childhood; 28.3% responded that they received inadequate dental care. Adjusting for sociodemographic characteristics, respondents who experienced four or more ACEs had a higher likelihood of inadequate dental care than respondents who reported no ACEs (aOR 2.79; 95% CI 2.77-2.82). The odds of reporting inadequate dental care were lower among those grew up with an adult who made them feel safe and protected (aOR 0.38; 95% CI 0.37-0.39). The presence of protective factors may mitigate the effects of ACEs on paediatric dental care. This research contributes to the literature through the further identification of the role of dentists in identifying signs of abuse and neglect. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Foundations for screening adverse childhood experiences: Exploring patterns of exposure through infancy and toddlerhood.

PubMed

McKelvey, Lorraine M; Selig, James P; Whiteside-Mansell, Leanne

2017-08-01

Adverse childhood experiences (ACEs) have lifetime consequences for health and development. Identification of ACEs early in childhood provides the potential to intervene before health and development are impaired. This study examined the timing and duration of exposure to ACEs experienced by children from low-income families from ages one to three years to identify whether there were patterns of exposure when infants and toddlers were most vulnerable. We were able to confirm the early negative consequences on cognitive, health, and behavior outcomes previously reported in young children using a national, longitudinal data set of parents and children from low-income households (N=2250). Using Finite Mixture Models, five classes of exposure were identified for children, Consistently Low (63.8%), Decreasing (10.3%), High at Age 2 (11.4%), Increasing (10.4%), and Consistently High (4%). The Consistently Low and Consistently High classes had the most and least optimal development across all domains, respectively. When examining child development outcomes among children with variable exposures to adversities, we found that for cognitive, language, and physical development, the most proximal ACEs were more robust for predicting child outcomes. For socioemotional health, exposure at any time from one to three to ACEs had negative consequences. As a whole, findings from this study highlight the need to consider ACEs screening tools that are both time-sensitive and permit a lifetime report. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vapor compression heat pump system field tests at the TECH complex

NASA Astrophysics Data System (ADS)

Baxter, V. D.

1985-07-01

The Tennessee Energy Conservation In Housing (TECH) complex has been utilized since 1977 as a field test site for several novel and conventional heat pump systems for space conditioning and water heating. Systems tested include the Annual Cycle Energy System (ACES), solar assisted heat pumps (SAHP) both parallel and series, two conventional air-to-air heat pumps, an air-to-air heat pump with desuperheater water heater, and horizontal coil and multiple shallow vertical coil ground-coupled heat pumps (GCHP). A direct comparison of the measured annual performance of the test systems was not possible. However, a cursory examination revealed that the ACES had the best performance. However, its high cost makes it unlikely that it will achieve widespread use. Costs for the SAHP systems are similar to those of the ACES but their performance is not as good. Integration of water heating and space conditioning functions with a desuperheater yielded significant efficiency improvement at modest cost. The GCHP systems performed much better for heating than for cooling and may well be the most efficient alternative for residences in cold climates.

Vapor compression heat pump system field tests at the tech complex

NASA Astrophysics Data System (ADS)

Baxter, Van D.

1985-11-01

The Tennessee Energy Conservation In Housing (TECH) complex has been utilized since 1977 as a field test site for several novel and conventional heat pump systems for space conditioning and water heating. Systems tested include the Annual Cycle Energy System (ACES), solar assisted heat pumps (SAHP) both parallel and series, two conventional air-to-air heat pumps, an air-to-air heat pump with desuperheater water heater, and horizontal coil and multiple shallow vertical coil ground-coupled heat pumps (GCHP). A direct comparison of the measured annual performance of the test systems was not possible. However, a cursory examination revealed that the ACES had the best performance, however, its high cost makes it unlikely that it will achieve wide-spread use. Costs for the SAHP systems are similar to those of the ACES but their performance is not as good. Integration of water heating and space conditioning functions with a desuperheater yielded significant efficiency improvement at modest cost. The GCHP systems performed much better for heating than for cooling and may well be the most efficient alternative for residences in cold climates.

Cortical dynamics and subcortical signatures of motor-language coupling in Parkinson's disease.

PubMed

Melloni, Margherita; Sedeño, Lucas; Hesse, Eugenia; García-Cordero, Indira; Mikulan, Ezequiel; Plastino, Angelo; Marcotti, Aida; López, José David; Bustamante, Catalina; Lopera, Francisco; Pineda, David; García, Adolfo M; Manes, Facundo; Trujillo, Natalia; Ibáñez, Agustín

2015-07-08

Impairments of action language have been documented in early stage Parkinson's disease (EPD). The action-sentence compatibility effect (ACE) paradigm has revealed that EPD involves deficits to integrate action-verb processing and ongoing motor actions. Recent studies suggest that an abolished ACE in EPD reflects a cortico-subcortical disruption, and recent neurocognitive models highlight the role of the basal ganglia (BG) in motor-language coupling. Building on such breakthroughs, we report the first exploration of convergent cortical and subcortical signatures of ACE in EPD patients and matched controls. Specifically, we combined cortical recordings of the motor potential, functional connectivity measures, and structural analysis of the BG through voxel-based morphometry. Relative to controls, EPD patients exhibited an impaired ACE, a reduced motor potential, and aberrant frontotemporal connectivity. Furthermore, motor potential abnormalities during the ACE task were predicted by overall BG volume and atrophy. These results corroborate that motor-language coupling is mainly subserved by a cortico-subcortical network including the BG as a key hub. They also evince that action-verb processing may constitute a neurocognitive marker of EPD. Our findings suggest that research on the relationship between language and motor domains is crucial to develop models of motor cognition as well as diagnostic and intervention strategies.

What are the ideal properties for functional food peptides with antihypertensive effect? A computational peptidology approach.

PubMed

Zhou, Peng; Yang, Chao; Ren, Yanrong; Wang, Congcong; Tian, Feifei

2013-12-01

Peptides with antihypertensive potency have long been attractive to the medical and food communities. However, serving as food additives, rather than therapeutic agents, peptides should have a good taste. In the present study, we explore the intrinsic relationship between the angiotensin I-converting enzyme (ACE) inhibition and bitterness of short peptides in the framework of computational peptidology, attempting to find out the appropriate properties for functional food peptides with satisfactory bioactivities. As might be expected, quantitative structure-activity relationship modeling reveals a significant positive correlation between the ACE inhibition and bitterness of dipeptides, but this correlation is quite modest for tripeptides and, particularly, tetrapeptides. Moreover, quantum mechanics/molecular mechanics analysis of the structural basis and energetic profile involved in ACE-peptide complexes unravels that peptides of up to 4 amino acids long are sufficient to have efficient binding to ACE, and more additional residues do not bring with substantial enhance in their ACE-binding affinity and, thus, antihypertensive capability. All of above, it is coming together to suggest that the tripeptides and tetrapeptides could be considered as ideal candidates for seeking potential functional food additives with both high antihypertensive activity and low bitterness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aerosol Optical Properties Measured Onboard the Ronald H. Brown During ACE Asia as a Function of Aerosol Chemical Composition and Source Region

NASA Technical Reports Server (NTRS)

Quinn, P. K.; Coffman, D. J.; Bates, T. S.; Welton, E. J.; Covert, D. S.; Miller, T. L.; Johnson, J. E.; Maria, S.; Russell, L.; Arimoto, R.

2004-01-01

During the ACE Asia intensive field campaign conducted in the spring of 2001 aerosol properties were measured onboard the R/V Ronald H. Brown to study the effects of the Asian aerosol on atmospheric chemistry and climate in downwind regions. Aerosol properties measured in the marine boundary layer included chemical composition; number size distribution; and light scattering, hemispheric backscattering, and absorption coefficients. In addition, optical depth and vertical profiles of aerosol 180 deg backscatter were measured. Aerosol within the ACE Asia study region was found to be a complex mixture resulting from marine, pollution, volcanic, and dust sources. Presented here as a function of air mass source region are the mass fractions of the dominant aerosol chemical components, the fraction of the scattering measured at the surface due to each component, mass scattering efficiencies of the individual components, aerosol scattering and absorption coefficients, single scattering albedo, Angstrom exponents, optical depth, and vertical profiles of aerosol extinction. All results except aerosol optical depth and the vertical profiles of aerosol extinction are reported at a relative humidity of 55 +/- 5%. An over-determined data set was collected so that measured and calculated aerosol properties could be compared, internal consistency in the data set could be assessed, and sources of uncertainty could be identified. By taking into account non-sphericity of the dust aerosol, calculated and measured aerosol mass and scattering coefficients agreed within overall experimental uncertainties. Differences between measured and calculated aerosol absorption coefficients were not within reasonable uncertainty limits, however, and may indicate the inability of Mie theory and the assumption of internally mixed homogeneous spheres to predict absorption by the ACE Asia aerosol. Mass scattering efficiencies of non-sea salt sulfate aerosol, sea salt, submicron particulate organic matter, and dust found for the ACE Asia aerosol are comparable to values estimated for ACE 1, Aerosols99, and INDOEX. Unique to the ACE Asia aerosol was the large mass fractions of dust, the dominance of dust in controlling the aerosol optical properties, and the interaction of dust with soot aerosol.

Angiotensin-converting enzyme (ACE) inhibitory potential of standardized Mucuna pruriens seed extract.

PubMed

Chaudhary, Sushil Kumar; De, Apurba; Bhadra, Santanu; Mukherjee, Pulok K

2015-01-01

Mucuna pruriens Linn. (Fabaceae) is a tropical legume, traditionally used for controlling blood pressure. Inhibition of angiotensin-converting enzyme (ACE) is one of the successful strategies for controlling hypertension. The present study evaluated the ACE inhibition potential of the standardized extract of M. pruriens seeds. Standardization of the extract and its fractions were carried out by RP-HPLC method [methanol and 1% v/v acetic acid in water (5:95 v/v)] using levodopa as a marker. The ACE inhibition activity of the extract and fractions was evaluated at different concentrations (20, 40, 60, 80, and 100 µg/mL) using the HPLC-DAD and the UV spectrophotometric method. The liberation of hippuric acid (HA) from hippuryl-L-histidyl-L-leucine (HHL) was estimated in the spectrophotometric method and RP-HPLC assay at 228 nm. Methanol extract and aqueous fraction showed a maximum activity with IC50 values of 38.44 ± 0.90 and 57.07 ± 2.90 µg/mL (RP-HPLC), and 52.68 ± 2.02 and 67.65 ± 2.40 µg/mL (spectrophotometry), respectively. The study revealed that the aqueous extract contains the highest amount of levodopa. Eventually the methanol extract showed highest ACE inhibition activity except levodopa alone. It was further observed that the inhibition was altered with respect to the change in the content of levodopa in the extract. Thus, it can be assumed that levodopa may be responsible for the ACE inhibition activity of M. pruriens seeds. It can be concluded that M. pruriens seed is a potential ACE inhibitor can be explored further as an effective antihypertensive agent.

Is There a Cumulative Association Between Adverse Childhood Experiences and Intimate Partner Violence in Emerging Adulthood?

PubMed

Nikulina, Valentina; Gelin, Melissa; Zwilling, Amanda

2017-12-01

Adverse childhood experiences (ACEs) have been shown to cumulatively predict a range of poor physical and mental health outcomes across adulthood. The cumulative effect of ACEs on intimate partner violence (IPV) in emerging adulthood has not been previously explored. The current study examined the individual and cumulative associations between nine ACEs (emotional abuse, physical abuse, sexual abuse, emotional neglect, physical neglect, witnessing domestic violence, living with a mentally ill, substance abusing, or incarcerated household member) and IPV in a diverse sample of college students ( N = 284; M age = 20.05 years old [ SD = 2.5], 32% male, 37% Caucasian, 30% Asian, 33% other, and 27% Hispanic) from an urban, public college in the Northeast of the United States. Participants reported ACEs (measured by the Adverse Childhood Experiences Survey) and IPV perpetration and victimization (measured with the Revised Conflict Tactics Scale-2) of physical and psychological aggression in an online study that took place from 2015 to 2016. Bivariate and multivariate associations between ACEs, cumulative ACEs (assessed by the sum of adverse experiences), and IPV outcomes were assessed, while controlling for demographics and socioeconomic status. No cumulative associations were observed between ACEs and any of the IPV subscales in multivariate regressions, while witnessing domestic violence was significantly associated with perpetration and victimization of physical aggression and injury, and household member incarceration and physical abuse were associated with physical aggression perpetration. Adverse childhood events do not seem to associate cumulatively with IPV in emerging adulthood and the contributions of individual childhood experiences appear to be more relevant for IPV outcomes. Clinical and research implications are discussed.

The Impact of DNA Topology and Guide Length on Target Selection by a Cytosine-Specific Cas9.

PubMed

Tsui, Tsz Kin Martin; Hand, Travis H; Duboy, Emily C; Li, Hong

2017-06-16

Cas9 is an RNA-guided DNA cleavage enzyme being actively developed for genome editing and gene regulation. To be cleaved by Cas9, a double stranded DNA, or the protospacer, must be complementary to the guide region, typically 20-nucleotides in length, of the Cas9-bound guide RNA, and adjacent to a short Cas9-specific element called Protospacer Adjacent Motif (PAM). Understanding the correct juxtaposition of the protospacer- and PAM-interaction with Cas9 will enable development of versatile and safe Cas9-based technology. We report identification and biochemical characterization of Cas9 from Acidothermus cellulolyticus (AceCas9). AceCas9 depends on a 5'-NNNCC-3' PAM and is more efficient in cleaving negative supercoils than relaxed DNA. Kinetic as well as in vivo activity assays reveal that AceCas9 achieves optimal activity when combined with a guide RNA containing a 24-nucleotide complementarity region. The cytosine-specific, DNA topology-sensitive, and extended guide-dependent properties of AceCas9 may be explored for specific genome editing applications.

Effects of acetylate hyperforin on the processing of amyloid precursor protein.

PubMed

Chen, Xiang; Feng, Wenshang; Chen, Qing; Yang, Xiangling; Yang, Depo; Wang, Dongmei; Zhong, Ling

2009-02-20

Hyperforin (HF) is a phloroglucinol compound obtained from St. John's Wort (Hypericum perforatum). Recent studies have shown that Hyperforin can be used to improve psychopathologic symptoms of Alzheimer's disease but the mechanism is not clear. This may be partly due to the difficult in studying Hyperforin, since this chemical is unstable and is sensitive to light, oxygen, and heat. In this study, we explored the effects of acetylate hyperforin (ace-HF), a stable derivative of hyperforin, on the processing of amyloid precursor protein (APP). HEK293 cells transfected with pcDNA3.1APP695sw and SH-SY5Y cells were treated with ace-HF, followed by measuring the levels of APP and sAPPα. Twelve hours of treatment led to an increase in extracellular sAPPα, but APP mRNA and protein levels were unchanged. Further studies with α-secretase and a pan PKC inhibitor, Calphostin C, indicated that ace-HF's effect on extracellular sAPPα was closely related to PKC activities and α-secretase activities. Our findings suggest that ace-HF can modulate α-secretase-mediated APP processing via a PKC signaling pathway.

KSC-97PC1129

NASA Image and Video Library

1997-07-24

Applied Physics Laboratory engineers and technicians from Johns Hopkins University test solar array deployment of the Advanced Composition Explorer (ACE) in KSC’s Spacecraft Assembly and Encapsulation Facility-II (SAEF-II). The wire hanging from the ceiling above the black solar array panel is used for "g-negation," which takes the weight off of the panel’s hinges to simulate zero gravity, mimicking deployment in space. Scheduled for launch on a Delta II rocket from Cape Canaveral Air Station on Aug. 25, ACE will study low-energy particles of solar origin and high-energy galactic particles for a better understanding of the formation and evolution of the solar system as well as the astrophysical processes involved. The collecting power of instrumentation aboard ACE is at least 100 times more sensitive than anything previously flown to collect similar data by NASA

KSC-97DC1283

NASA Image and Video Library

1997-08-19

Workers make final checks as the second part of the bi-sector payload fairing for the Advanced Composition Explorer (ACE) is closed around the spacecraft at Launch Complex 17A, Cape Canaveral Air Station. ACE will be launched on a Boeing Delta II expendable launch vehicle. The spacecraft will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. This will be the second Delta launch under the Boeing name and the first from Cape Canaveral. Liftoff is scheduled Aug. 24

KSC-97DC1286

NASA Image and Video Library

1997-08-19

Final prelaunch preparations are made at Launch Complex 17A, Cape Canaveral Air Station, for liftoff of the Boeing Delta II expendable launch vehicle with the Advanced Composition Explorer (ACE) spacecraft, at top. The black rectangular-shaped panel in front is one of ACE’s solar arrays. ACE will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. This will be the second Delta launch under the Boeing name and the first from Cape Canaveral. Liftoff is scheduled Aug. 24

ACE-CIVA1.5 (T005 MS2): Assessing impacts from climate change and N deposition on Northeastern Forests using ForSAFE-VEG.

EPA Pesticide Factsheets

This dataset describes the simulations at two pilot sites in the northeast from 1900-2100 for several soil and plant community responses to climate and nitrogen deposition across a number of future scenarios. This dataset is associated with the following publication:Phelan, J., S. Belyazid, C. Clark , P. Jones, and J. Cajka. Assessing the Effects of Climate Change and Air Pollution on Soil Properties and Plant Diversity in Sugar Maple-Beech-Yellow Birch Hardwood Forests in the Northeastern United States: Model Simulations from 1900-2100. WATER, AIR, & SOIL POLLUTION. Springer, New York, NY, USA, 227(3): 1-30, (2016).

Development of a Robust star identification technique for use in attitude determination of the ACE spacecraft

NASA Technical Reports Server (NTRS)

Woodard, Mark; Rohrbaugh, Dave

1995-01-01

The Advanced Composition Explorer (ACE) spacecraft is designed to fly in a spin-stabilized attitude. The spacecraft will carry two attitude sensors - a digital fine Sun sensor and a charge coupled device (CCD) star tracker - to allow ground-based determination of the spacecraft attitude and spin rate. Part of the processing that must be performed on the CCD star tracker data is the star identification. Star data received from the spacecraft must be matched with star information in the SKYMAP catalog to determine exactly which stars the sensor is tracking. This information, along with the Sun vector measured by the Sun sensor, is used to determine the spacecraft attitude. Several existing star identification (star ID) systems were examined to determine whether they could be modified for use on the ACE mission. Star ID systems which exist for three-axis stabilized spacecraft tend to be complex in nature and many require fairly good knowledge of the spacecraft attitude, making their use for ACE excessive. Star ID systems used for spinners carrying traditional slit star sensors would have to be modified to model the CCD star tracker. The ACE star ID algorithm must also be robust, in that it will be able to correctly identify stars even though the attitude is not known to a high degree of accuracy, and must be very efficient to allow real-time star identification. The paper presents the star ID algorithm that was developed for ACE. Results from prototype testing are also presented to demonstrate the efficiency, accuracy, and robustness of the algorithm.

Anti-angiotensin converting enzyme (ACE) proteins from mycelia of Ganoderma lucidum (Curtis) P. Karst

PubMed Central

2013-01-01

Background Ganoderma lucidum has been purported as a potent remedy in the treatment and prevention of several ailments, including hypertension. This study aimed to explore the anti-ACE potential of protein fractions from the mycelia of G. lucidum. Methods Ganoderma lucidum mycelia were cultivated by submerged fermentation in a liquid medium containing brown sugar and spent brewer’s yeast. Intracellular proteins were fractionated from mycelia crude water extract by ammonium sulphate precipitation, and their angiotensin converting enzyme inhibitory activity was evaluated. The potential anti-ACE protein fractions were further separated by RP-HPLC and characterised using proteomics platforms. Results Preliminary result demonstrated that the mycelia crude water extract inhibited ACE at IC50 value of 1.134 ± 0.036 mg/mL. Following protein fractionation and HPLC purification, the presence of highly potential anti-ACE proteins with the IC50 values less than 200 μg/mL was detected. Characterisation of these proteins demonstrated the presence of four different antihypertensive-related proteins involved in the regulation of blood pressure through different mechanisms. Conclusions This study suggests that the mycelia of G. lucidum has high potential in lowering blood pressure level due to the presence of several antihypertensive-related proteins such as cystathionine beta synthase-like protein, DEAD/DEAH box helicase-like protein, paxillin-like protein, and alpha/beta hydrolase-like protein. PMID:24093919

Time-lag and Correlation between ACE and RBSPICE Injection Event Observations during Storm Times

NASA Astrophysics Data System (ADS)

Madanian, H.; Patterson, J. D.; Manweiler, J. W.; Soto-chavez, A. R.; Gerrard, A. J.; Lanzerotti, L. J.

2017-12-01

The Radiation Belt Storm Probes Ion Composition Experiment (RBSPICE) on the Van Allen Probes mission measures energetic charged particles [ 20 keV to 1 MeV] in the inner magnetosphere and ring current. During geomagnetic storms, injections of energetic ions into the ring current change the ion population and produce geomagnetic field depressions on Earth's surface. We analyzed the magnetic field strength and particle composition in the interplanetary medium measured by instruments on the Advanced Composition Explorer (ACE) spacecraft near the inner Lagrangian point. The Electron, Proton, and Alpha Monitor-Low Energy Magnetic Spectrometer (EPAM-LEMS) sensor on ACE measures energetic particles [ 50 keV to 5 MeV] in the interplanetary space. The SYM-H index is utilized to classify the storm events by magnitude and to select more than 60 storm events between 2013 and 2017. We cross-compared ACE observations at storm times, with the RBSPICE ion measurements at dusk to midnight magnetic local time and over the 3-6 L-shell range. We report on the relative composition of the solar particles and the relative composition of the inner magnetospheric hot plasma during storm times. The data correlation is accomplished by shifting the observation time from ACE to RBSPICE using the solar wind velocity at the time of the observation. We will discuss time lags between storm onset at the magnetopause and injection events measured for each storm.

Angiotensin-converting enzyme gene polymorphism in arrhythmogenic right ventricular dysplasia: is DD genotype helpful in predicting syncope risk?

PubMed

Ozben, Beste; Altun, Ibrahim; Sabri Hancer, Veysel; Bilge, Ahmet Kaya; Tanrikulu, Azra Meryem; Diz-Kucukkaya, Reyhan; Fak, Ali Serdar; Yilmaz, Ercument; Adalet, Kamil

2008-12-01

Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable disorder characterised by fibrofatty replacement of right ventricular myocytes and increased risk of ventricular arrhythmias and sudden cardiac death. Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects myocardial ACE levels. DD genotype favours myocardial fibrosis and is associated with malignant ventricular tachycardia. The aim of this study was to explore ACE gene polymorphism in ARVD patients. Twenty-nine patients with ARVD and 24 controls were included. All ARVD patients had documented sustained ventricular tachycardia. Thirteen patients had syncopal episodes. Six patients were resuscitated from sudden cardiac death. ACE gene polymorphism was identified by polymerase chain reaction technique. There was no significant difference in DD genotype frequency between ARVD patients and controls (44.8% vs. 45.8%, p=0.94). However, DD genotype frequency was significantly higher in ARVD patients with syncopal episodes compared to those without syncope (69.2% vs. 25.0%, p=0.017, odds ratio:6.750, 95% confidence interval: 1.318-34.565). DD genotype was detected in higher frequency also in patients with a family history of sudden cardiac death (66.7% vs. 39.1%,p=0.36). High prevalence of DD genotype in ARVD patients with syncope suggests that ACE I/D polymorphism might be useful in identifying high-risk patients for syncope.

Model Estimated GCR Particle Flux Variation - Assessment with CRIS Data

NASA Astrophysics Data System (ADS)

Saganti, Premkumar

We present model calculated particle flux as a function of time during the current solar cycle along with the comparisons from the ACE/CRIS data and the Mars/MARIE data. In our model calculations we make use of the NASA's HZETRN (High Z and Energy Transport) code along with the nuclear fragmentation cross sections that are described by the quantum multiple scattering (QMSFRG) model. The time dependant variation of the GCR environment is derived making use of the solar modulation potential, phi. For the past ten years, Advanced Composition Explorer (ACE) has been in orbit at the Sun- Earth libration point (L1). Data from the Cosmic Ray Isotope Spectrometer (CRIS) instrument onboard the ACE spacecraft has been available from 1997 through the present time. Our model calculated particle flux showed high degree of correlation during the earlier phase of the current solar cycle (2003) in the lower Z region within 15

Possible Improvements of the ACE Diversity Interchange Methodology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Etingov, Pavel V.; Zhou, Ning; Makarov, Yuri V.

2010-07-26

North American Electric Reliability Corporation (NERC) grid is operated by about 131 balancing authorities (BA). Within each BA, operators are responsible for managing the unbalance (caused by both load and wind). As wind penetration levels increase, the challenges of managing power variation increases. Working independently, balancing area with limited regulating/load following generation and high wind power penetration faces significant challenges. The benefits of BA cooperation and consolidation increase when there is a significant wind energy penetration. To explore the benefits of BA cooperation, this paper investigates ACE sharing approach. A technology called ACE diversity interchange (ADI) is already in usemore » in the western interconnection. A new methodology extending ADI is proposed in the paper. The proposed advanced ADI overcoming some limitations existing in conventional ADI. Simulations using real statistical data of CAISO and BPA have shown high performance of the proposed advanced ADI methodology.« less

A Gentle Touch

NASA Technical Reports Server (NTRS)

Frandsen, Allan

2002-01-01

One aspect of my job as Payload Manager on the Advanced Composition Explorer (ACE) mission involved keeping track of what the different science teams were working on, and offering help where it was needed. At first it seemed like many of the scientists or their technical staff were not sure how safe it was to confide in me. Everybody knew I had spent most of my career with NASA at the Jet Propulsion Laboratory (JPL). All of my staff, initially four of them, came from JPL too. Left to our own devices, would we impose onerous NASA rules that could stifle innovation in the ACE (Advanced Composition Explorer) mission instrument development labs? The challenge to my team was getting the science groups to regard us as partners, or as people who could help them rather than as what they seemed to expect--a troop of requirements enforcers.

Sensitivity of multiangle photo-polarimetry to absorbing aerosol vertical layering and properties: Quantifying measurement uncertainties for ACE requirements

NASA Astrophysics Data System (ADS)

Kalashnikova, O. V.; Garay, M. J.; Davis, A. B.; Natraj, V.; Diner, D. J.; Tanelli, S.; Martonchik, J. V.; JPl Team

2011-12-01

The impact of tropospheric aerosols on climate can vary greatly based upon relatively small variations in aerosol properties, such as composition, shape and size distributions, as well as vertical layering. Multi-angle polarimetric measurements have been advocated in recent years as an additional tool to better understand and retrieve the aerosol properties needed for improved predictions of aerosol radiative forcing on climate. The central concern of this work is the assessment of the effects of absorbing aerosol properties under measurement uncertainties achievable for future generation multi-angle, polarimetric imaging instruments under ACE mission requirements. As guidelines, the on-orbit performance of MISR for multi-angle intensity measurements and the reported polarization sensitivities of a MSPI prototype were adopted. In particular, we will focus on sensitivities to absorbing aerosol layering and observation-constrained refractive indices (resulting in various single scattering albedos (SSA)) of both spherical and non-spherical absorbing aerosol types. We conducted modeling experiments to determine how the measured Stokes vector elements are affected in UV-NIR range by the vertical distribution, mixing and layering of smoke and dust aerosols, and aerosol SSA under the assumption of a black and polarizing ocean surfaces. We use a vector successive-orders-of-scattering (SOS) and VLIDORT transfer codes that show excellent agreement. Based on our sensitivity studies we will demonstrate advantages and disadvantages of wavelength selection in UV-NIR range to access absorbing aerosol properties. Polarized UV channels do not show particular advantage for absorbing aerosol property characterization due to dominating molecular signal. Polarimetric SSA sensitivity is small, however needed to be considered in the future polarimetric retrievals under ACE-defined uncertainty.

Characterization of Dust Properties during ACE-Asia and PRIDE: A Column Satellite-Surface Perspective

NASA Technical Reports Server (NTRS)

Lau, William K. M. (Technical Monitor); Tsay, Si-Chee; Hsu, N. Christina; Herman, Jay R.; Ji, Q. Jack

2002-01-01

Many recent field experiments are designed to study the compelling variability in spatial and temporal scale of both pollution-derived and naturally occurring aerosols, which often exist in high concentration over particular pathways around the globe. For example, the ACE-Asia (Aerosol Characterization Experiment-Asia) was conducted from March-May 2001 in the vicinity of the Taklimakan and Gobi deserts, East Coast of China, Yellow Sea, Korea, and Japan, along the pathway of Kosa (severe events that blanket East Asia with yellow desert dust, peaked in the Spring season). The PRIDE (Puerto RIco Dust Experiment, July 2000) was designed to measure the properties of Saharan dust transported across the Atlantic Ocean to the Caribbean. Dust particles typically originate in desert areas far from polluted urban regions. During transport, dust layers can interact with anthropogenic sulfate and soot aerosols from heavily polluted urban areas. Added to the complex effects of clouds and natural marine aerosols, dust particles reaching the marine environment can have drastically different properties than those from the source. Thus, understanding the unique temporal and spatial variations of dust aerosols is of special importance in regional-to-global climate issues such as radiative forcing, the hydrological cycle, and primary biological productivity in the ocean. During ACE-Asia and PRIDE we had measured aerosol physical/optical/radiative properties, column precipitable water amount, and surface reflectivity over homogeneous areas from ground-based remote sensing. The inclusion of flux measurements permits the determination of aerosol radiative flux in addition to measurements of loading and optical depth. At the time of the Terra/MODIS, SeaWiFS, TOMS and other satellite overpasses, these ground-based observations can provide valuable data to compare with satellite retrievals over land. We will present the results and discuss their implications in regional climatic effects.

Characterization of Dust Properties Near Source Region During ACE-Asia: A Column Satellite-Surface Perspective

NASA Technical Reports Server (NTRS)

Tsay, S. -C.; Ji, Q.; Chu, A.; Hsu, C.; Holben, B.; Campbell, J.; Welton, E. J.; Shu, P. K.

2002-01-01

Many recent field experiments are designed to study the compelling variability in spatial and temporal scale of both pollution-derived and naturally occurring aerosols, which often exist in high concentrations over eastern/southeastern Asia and along the rim of the western Pacific. For example, the ACE-Asia was conducted from March-May 2001 in the vicinity of the Taklimakan and Gobi deserts, East Coast of China, Yellow Sea, Korea, and Japan, along the pathway of Kosa (severe events that blanket East Asia with yellow desert dust, peaked in the Spring season). Asian dust typically originates in desert areas far from polluted urban regions. During transport, dust layers can interact with anthropogenic sulfate and soot aerosols from heavily polluted urban areas. Added to the complex effects of clouds and natural marine aerosols, dust particles reaching the marine environment can have drastically different properties than those from the source. Thus, understanding the unique temporal and spatial variations of Asian aerosols is of special importance in regional-to-global climate issues such as radiative forcing, the hydrological cycle, and primary biological productivity in the mid-Pacific Ocean. During ACE-Asia we have measured continuously aerosol physical/optical/radiative properties, column precipitable water amount, and surface reflectivity over homogeneous areas from surface. The inclusion of flux measurements permits the determination of aerosol radiative flux in addition to measurements of loading and optical depth. At the time of the Terra/MODIS, SeaWiFS, TOMS and other satellite overpasses, these ground-based observations can provide valuable data to compare with satellite retrievals over land. Preliminary results will be presented and discussed their implications in regional climatic effects.

Comparison of Aerosol Single Scattering Albedos Derived By Diverse Techniques in Two North Atlantic Experiments

NASA Technical Reports Server (NTRS)

Russell, P. B.; Redemann, J.; Schmid, B.; Bergstrom, R. W.; Livingston, J. M.; McIntosh, D. M.; Hartley, S.; Hobbs, P. V.; Quinn, P. K.; Carrico, C. M.;

Technology Development for 3-D Wide Swath Imaging Supporting ACE

NASA Technical Reports Server (NTRS)

Racette, Paul; Heymsfield, Gerry; Li, Lihua; Mclinden, Matthew; Park, Richard; Cooley, Michael; Stenger, Pete; Hand, Thomas

2014-01-01

The National Academy of Sciences Decadal Survey (DS) Aerosol-Cloud-Ecosystems Mission (ACE) aims to advance our ability to observe and predict changes to the Earth's hydrological cycle and energy balance in response to climate forcing, especially those changes associated with the effects of aerosol on clouds and precipitation. ACE is focused on obtaining measurements to reduce the uncertainties in current climate models arising from the lack in understanding of aerosol-cloud interactions. As part of the mission instrument suite, a dual-frequency radar comprised of a fixed-beam 94 gigahertz (W-band) radar and a wide-swath 35 gigahertz (Ka-band) imaging radar has been recommended by the ACE Science Working Group.In our 2010 Instrument Incubator Program project, we've developed a radar architecture that addresses the challenge associated with achieving the measurement objectives through an innovative, shared aperture antenna that allows dual-frequency radar operation while achieving wide-swath (100 kilometers) imaging at Ka-band. The antenna system incorporates 2 key technologies; a) a novel dual-band reflectorreflectarray and b) a Ka-band Active Electronically Scanned Array (AESA) feed module. The dual-band antenna is comprised of a primary cylindrical reflectorreflectarray surface illuminated by a point-focus W-band feed (compatible with a quasi-optical beam waveguide feed, such as that employed on CloudSat); the Ka-band AESA line feed provides wide-swath across-track scanning. The benefits of this shared-aperture approach include significant reductions in ACE satellite payload size, weight, and cost, as compared to a two aperture approach. Four objectives were addressed in our project. The first entailed developing the tools for the analysis and design of reflectarray antennas, assessment of candidate reflectarray elements, and validation using test coupons. The second objective was to develop a full-scale aperture design utilizing the reflectarray surface and to detail specific requirements and trades for the Ka-band AESA line feed. As part of the third objective a subscale antenna, similar to the full-scale aperture design, was developed, integrated, and flown with the Cloud Radar System during the 2014 Integrated Precipitation and Hydrology Experiment. The fourth and ongoing objective entails developing a GaN MMIC (Gallium Nitride Monolithic Microwave Integrated Circuits) power amplifier for use in the Ka-band AESA. An overview of the progress made on this project and a look ahead at the 2013 IIP (Instrument Incubator Program) award selection will be presented.

KSC-97PC1236

NASA Image and Video Library

1997-08-12

The Advanced Composition Explorer (ACE) undergoes final prelaunch processing in KSC’s Spacecraft Assembly and Encapsulation Facility-2 (SAEF-2) before being transported to Pad A at Launch Complex 17, Cape Canaveral Air Station, for mating to the Delta II launch vehicle. This photo was taken during a news media opportunity. The worker at right is installing protective covering over one of the spacecraft’s solar arrays. ACE with its combination of nine sensors and instruments will investigate the origin and evolution of solar phenomenon, the formation of solar corona, solar flares and acceleration of the solar wind. Launch is targeted for Aug. 24

Effects of acetylate hyperforin on the processing of amyloid precursor protein

PubMed Central

Chen, Xiang; Feng, Wenshang; Chen, Qing; Yang, Xiangling; Yang, Depo; Wang, Dongmei; Zhong, Ling

2009-01-01

Hyperforin (HF) is a phloroglucinol compound obtained from St. John's Wort (Hypericum perforatum). Recent studies have shown that Hyperforin can be used to improve psychopathologic symptoms of Alzheimer's disease but the mechanism is not clear. This may be partly due to the difficult in studying Hyperforin, since this chemical is unstable and is sensitive to light, oxygen, and heat. In this study, we explored the effects of acetylate hyperforin (ace-HF), a stable derivative of hyperforin, on the processing of amyloid precursor protein (APP). HEK293 cells transfected with pcDNA3.1APP695sw and SH-SY5Y cells were treated with ace-HF, followed by measuring the levels of APP and sAPPα. Twelve hours of treatment led to an increase in extracellular sAPPα, but APP mRNA and protein levels were unchanged. Further studies with α-secretase and a pan PKC inhibitor, Calphostin C, indicated that ace-HF's effect on extracellular sAPPα was closely related to PKC activities and α-secretase activities. Our findings suggest that ace-HF can modulate α-secretase-mediated APP processing via a PKC signaling pathway. PMID:21383880

Changes of Gene Expressions in Spontaneously Hypertensive Rat Model After Losartan Treatment

PubMed Central

Cha, Ji Hei; Lee, Hye Ryon; Kim, Kwan Chang; Cho, Min-Sun

2012-01-01

Background and Objectives The renin angiotensin system seems to play an important role in the development of cardiac and vascular hypertrophy in hypertension. The changes in pathology, and gene expressions of the angiotensin II receptor type 1A (ATIA) and angiotensin converting enzyme (ACE) were investigated in order to explore the effects of losartan in spontaneously hypertensive rat (SHR) models. Materials and Methods Twelve week-old male Wistar rats were grouped as follows: control (C) group, hypertension (H) group, and losartan (L) group in which SHR was treated with losartan (10 mg/kg/day). Western blot and reverse transcription-polymerase chain reaction analysis regarding seven genes such as endothelin-1, ACE, ATIA, neutrophil cytosolic factor, brain natriuretic peptide, troponin I, endothelial nitric oxide synthase were performed. Results Systolic blood pressure was significantly decreased in the L group compared with the H group in weeks 3 and 5. ACE and ATIA proteins in the L group were lower than H group in week 5. Conclusion Losartan reduced blood pressure, cardiac hypertrophy and protein expressions of ACE and ATIA. Changes of protein expressions were more sensitive than changes in pathology. Further study is needed for the differing doses of losartan in SHR models. PMID:23236328

OLYMPEX Counterflow Spectrometer and Impactor Field Campaign Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poellot, Michael

The U.S. Department of Energy (DOE) Atmospheric Radiation Measurement (ARM) Climate Research Facility’s ARM Aerial Facility (AAF) Counterflow Spectrometer and Impactor (CSI) probe was flown on the University of North Dakota Cessna Citation research aircraft during the Olympic Mountain Experiment (OLYMPEX). The field campaign took place from November 12 through December 19, 2015, over the Olympic Mountains and coastal waters of Washington State as part of a National Aeronautics and Space Administration (NASA) Global Precipitation Measurement (GPM) validation campaign. The CSI was added to the Citation instrument suite to support the NASA Aerosol-Cloud Ecosystem (ACE) satellite program and flights ofmore » the NASA Lockheed Earth Resources (ER-2) aircraft. ACE funded extra ER-2 flights to focus on clouds that are weakly precipitating, which are also of interest to the DOE Atmospheric System Research (ASR) program.« less

Wave Energy Prize - 1/20th Testing - SEWEC

DOE Data Explorer

Wesley Scharmen

2016-10-07

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the SEWEC team, including the 1/20th scale test plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the Wave Energy Prize (WEP) winners. * Note: During the TG4 judging meeting, the Wave Energy Prize judges reviewed the data collected during the testing of SEWEC's device at Carderock and determined that the data were inconclusive and did not allow an ACE value to be calculated for the device. Consequently, the SEWEC device was deemed ineligible to be considered for the Wave Energy Prize.

Linking Adverse Childhood Effects and Attachment: A Theory of Etiology for Sexual Offending.

PubMed

Grady, Melissa D; Levenson, Jill S; Bolder, Tess

2016-01-25

Sexual violence continues to be a significant public health problem affecting significant portions of the population. Unfortunately, an agreed upon theory of etiology remains elusive leading to challenges in developing effective prevention and treatment interventions. Recently, there is a growing body of literature examining the role of adverse childhood experiences (ACEs) in the development of sexually violent behavior. This research has begun to explore the rates of various types of child maltreatments and family dysfunction in individuals who have been convicted of a sexual crime. These empirical inquiries have been primarily descriptive in nature and have not yet provided a cohesive theoretical model as to why the presence of ACEs might contribute to sexually abusive behavior. This article suggests that attachment theory offers an explanatory link between early adversity and sexually abusive behavior in adulthood. We first summarize important attachment theory concepts, then integrate them with research in the area of developmental psychopathology and ACEs, and finally propose a model by which attachment can be used as an explanatory theory for subsequent sexualized coping and sexually abusive behaviors. Finally, this article explores the implications for practice, policy, and research using this explanatory theory as a framework for understanding sexual violence. © The Author(s) 2016.

A mutation within the SH2 domain of slp-76 regulates the tissue distribution and cytokine production of iNKT cells in mice.

PubMed

Danzer, Claudia; Koller, Anna; Baier, Julia; Arnold, Harald; Giessler, Claudia; Opoka, Robert; Schmidt, Stephanie; Willers, Maike; Mihai, Sidonia; Parsch, Hans; Wirtz, Stefan; Daniel, Christoph; Reinhold, Annegret; Engelmann, Swen; Kliche, Stefanie; Bogdan, Christian; Hoebe, Kasper; Mattner, Jochen

2016-09-01

TCR ligation is critical for the selection, activation, and integrin expression of T lymphocytes. Here, we explored the role of the TCR adaptor protein slp-76 on iNKT-cell biology. Compared to B6 controls, slp-76(ace/ace) mice carrying a missense mutation (Thr428Ile) within the SH2-domain of slp-76 showed an increase in iNKT cells in the thymus and lymph nodes, but a decrease in iNKT cells in spleens and livers, along with reduced ADAP expression and cytokine response. A comparable reduction in iNKT cells was observed in the livers and spleens of ADAP-deficient mice. Like ADAP(-/-) iNKT cells, slp-76(ace/ace) iNKT cells were characterized by enhanced CD11b expression, correlating with an impaired induction of the TCR immediate-early gene Nur77 and a decreased adhesion to ICAM-1. Furthermore, CD11b-intrinsic effects inhibited cytokine release, concanavalin A-mediated inflammation, and iNKT-cell accumulation in the liver. Unlike B6 and ADAP(-/-) mice, the expression of the transcription factors Id3 and PLZF was reduced, whereas NP-1-expression was enhanced in slp-76(ace/ace) mice. Blockade of NP-1 decreased the recovery of iNKT cells from peripheral lymph nodes, identifying NP-1 as an iNKT-cell-specific adhesion factor. Thus, slp-76 contributes to the regulation of the tissue distribution, PLZF, and cytokine expression of iNKT cells via ADAP-dependent and -independent mechanisms. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Does angiotensin-converting enzyme-1 (ACE-1) gene polymorphism lead to chronic kidney disease among hypertensive patients?

PubMed

Sarkar, Taposh; Singh, Narinder Pal; Kar, Premashish; Husain, Syed Akhtar; Kapoor, Seema; Pollipalli, Sunil Kumar; Kumar, Anish; Garg, Neena

2016-06-01

Hypertension is one of the important contributing factors linked with both causation and development of kidney disease. It is a multifactorial, polygenic, and complex disorder due to interaction of several risk genes with environmental factors. The present study was aimed to explore genetic polymorphism in ACE-1 gene as a risk factor for CKD among hypertensive patients. Three hundred patients were enrolled in the study. Ninety were hypertensive patients with CKD taken as cases, whereas 210 hypertensive patients without CKD were taken as controls. Demographic data including age, sex, Body mass index (BMI), and other risk factors were also recorded. DNA was extracted from blood by salting out method. Genotyping of ACE gene was done by PCR technique. All the statistical analysis was done by using Epi Info and SPSS version 16 software (SPSS Inc., Chicago, IL). Mean age was higher in the control group (p < 0.05). Variables among two groups were compared out of which age, BMI, hemoglobin (Hb) was found to be statistically significant whereas other variables like systolic blood pressure, triglyceride and low-density lipoprotein were not. Blood urea and serum creatinine levels were statistically significant in the two genotypes (p < 0.05). Total and HDL cholesterol were statistically significant for DD genotype of ACE gene (OR = 1.42, 95% CI = 0.72-2.81). Similarly, the risk for CKD among hypertensive patients was also associated with D allele of ACE gene (OR = 1.25, 95% CI = 0.86-1.79). It is concluded that ACE-DD genotype may be a risk factor for the causation and development of chronic kidney failure among hypertensive patients.

Exploring Intercultural and Ethical Understanding through "Ethical Intelligence" and Drama in Asian Texts for the "Australian Curriculum: English"

ERIC Educational Resources Information Center

Jetnikoff, Anita

2013-01-01

This paper focuses on Australian texts with Asian representations, which will be discussed in terms of Ethical Intelligence (Weinstein, 2011) explored through drama. This approach aligns with the architecture of the "Australian Curriculum: English" (AC:E, v5, 2013), in particular the general capabilities of "ethical…

Adverse childhood experiences and dental health in children and adolescents.

PubMed

Bright, Melissa A; Alford, Shannon M; Hinojosa, Melanie S; Knapp, Caprice; Fernandez-Baca, Daniel E

2015-06-01

This study seeks to explore the how specific toxic stressors, specifically adverse childhood experiences (ACEs), and their frequencies may be associated with tooth condition and the presence of caries. Data from the 2011-12 National Survey for Child Health (NSCH), a nationally representative survey of child health, were used in this study. Pediatric dental health was measured using parent report of two characteristics: condition of teeth and having a toothache, decayed teeth, and/or unfilled cavities in the past 12 months. ACEs were measured by asking about a child's exposure to the divorce of a parent, parental incarceration, domestic violence, neighborhood violence, drug and alcohol abuse, mental illness, and financial hardship. Analyses were adjusted by sociodemographic characteristics, healthcare access and utilization, and comorbid chronic conditions. The presence of even one ACE in a child's life increased the likelihood of having poor dental health. Additionally, having multiple ACEs had a cumulative negative effect on the condition of their teeth and the presence of dental caries (Odds Ratios 1.61-2.55). Adjusted models show that racial and socioeconomic factors still play a significant role in dental health. In addition to the known disparities in dental caries, this study demonstrates that there is significant association between childhood psychosocial issues and dental health. Preventive dental care should be considered incorporating the screening of multiple biological stressors, including ACEs, in routine dental visits as a means of identifying and reducing dental health inequities. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Serapeo Temple in Pozzuoli, Italy--the unique gauge for the sea (world ocean) level and the Earth surface temperature for over 2100 years].

PubMed

Karnaukhov, V N; Karnaukhov, A V

2010-01-01

The changes in the sea level relative to the position of the Serapeo Temple in Pozzuoly (Italia) over a period of 2100 years are discussed in the context of the well known periods of climate cooling off (Neoglacial, Little Ace Period) and climate warming (Middle Ages Optimum, Modern climate warming). It is noted that the rate of sea level lifting relative to the position of the Serapeo Temple in the modern phase of climate warming, which began the end of the 18th Century is approximately two times higher than in the previous phase of climate warming in the period from the fifth to the mid-tenth century A.D. This indicates that not only the natural cyclic component contributes to the mechanisms of Modern Climate warming but also the anthropogenic component of approximately equivalent power, which results from the waste of CO2 caused by the burning of fossilized fuels.

The Stocker AstroScience Center at Florida International University

NASA Astrophysics Data System (ADS)

Webb, James R.

2014-01-01

The new Stocker AstroScience Center located on the MMC campus at Florida International University in Miami Florida represents a unique facility for STEM education that arose from a combination of private, State and university funding. The building, completed in the fall of 2013, contains some unique spaces designed not only to educate, but also to inspire students interested in science and space exploration. The observatory consists of a 4-story building (3 floors) with a 24” ACE automated telescope in an Ash dome, and an observing platform above surrounding buildings. Some of the unique features of the observatory include an entrance/exhibition hall with a 6-ft glass tile floor mural linking the Florida climate to space travel, a state-of-the art telescope control that looks like a starship bridge, and displays such as “Music from the universe”. The observatory will also be the focus of our extensive public outreach program that is entering its 20 year.

Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding

PubMed Central

Danilov, Sergei M.; Lünsdorf, Heinrich; Akinbi, Henry T.; Nesterovitch, Andrew B.; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V.; Piegeler, Tobias; Golukhova, Elena Z.; Schwartz, David E.; Dull, Randal O.; Minshall, Richard D.; Kost, Olga A.; Garcia, Joe G. N.

2016-01-01

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients. PMID:27734897

Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding.

PubMed

Danilov, Sergei M; Lünsdorf, Heinrich; Akinbi, Henry T; Nesterovitch, Andrew B; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V; Piegeler, Tobias; Golukhova, Elena Z; Schwartz, David E; Dull, Randal O; Minshall, Richard D; Kost, Olga A; Garcia, Joe G N

2016-10-13

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.

Advancements in the safe identification of explosives using a Raman handheld instrument (ACE-ID)

NASA Astrophysics Data System (ADS)

Arnó, Josep; Frunzi, Michael; Kittredge, Marina; Sparano, Brian

2014-05-01

Raman spectroscopy is the technology of choice to identify bulk solid and liquid phase unknown samples without the need to contact the substance. Materials can be identified through transparent and semi-translucent containers such as plastic and glass. ConOps in emergency response and military field applications require the redesign of conventional laboratory units for: field portability; shock, thermal and chemical attack resistance; easy and intuitive use in restrictive gear; reduced size, weight, and power. This article introduces a new handheld instrument (ACE-IDTM) designed to take Raman technology to the next level in terms of size, safety, speed, and analytical performance. ACE-ID is ruggedized for use in severe climates and terrains. It is lightweight and can be operated with just one hand. An intuitive software interface guides users through the entire identification process, making it easy-to-use by personnel of different skill levels including military explosive ordinance disposal technicians, civilian bomb squads and hazmat teams. Through the use of embedded advanced algorithms, the instrument is capable of providing fluorescence correction and analysis of binary mixtures. Instrument calibration is performed automatically upon startup without requiring user intervention. ACE-ID incorporates an optical rastering system that diffuses the laser energy over the sample. This important innovation significantly reduces the heat induced in dark samples and the probability of ignition of susceptible explosive materials. In this article, the explosives identification performance of the instrument will be provided in addition to a quantitative evaluation of the safety improvements derived from the reduced ignition probabilities.

ACE phenotyping in human heart.

PubMed

Tikhomirova, Victoria E; Kost, Olga A; Kryukova, Olga V; Golukhova, Elena Z; Bulaeva, Naida I; Zholbaeva, Aigerim Z; Bokeria, Leo A; Garcia, Joe G N; Danilov, Sergei M

2017-01-01

Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10-15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. "Conformational fingerprint" of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk.

A SURVEY OF MAGNETIC WAVES EXCITED BY NEWBORN INTERSTELLAR He{sup +} OBSERVED BY THE ACE SPACECRAFT AT 1 au

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, Meghan K.; Argall, Matthew R.; Joyce, Colin J., E-mail: mkl54@wildcats.unh.edu, E-mail: Matthew.Argall@unh.edu, E-mail: cjl46@wildcats.unh.edu

We report observations of low-frequency waves at 1 au by the magnetic field instrument on the Advanced Composition Explorer ( ACE /MAG) and show evidence that they arise due to newborn interstellar pickup He{sup +}. Twenty-five events are studied. They possess the generally predicted attributes: spacecraft-frame frequencies slightly greater than the He{sup +} cyclotron frequency, left-hand polarization in the spacecraft frame, and transverse fluctuations with minimum variance directions that are quasi-parallel to the mean magnetic field. Their occurrence spans the first 18 years of ACE operations, with no more than 3 such observations in any given year. Thus, the eventsmore » are relatively rare. As with past observations by the Ulysses and Voyager spacecraft, we argue that the waves are seen only when the background turbulence is sufficiently weak as to allow for the slow accumulation of wave energy over many hours.« less

ACE phenotyping in human heart

PubMed Central

Tikhomirova, Victoria E.; Kost, Olga A.; Kryukova, Olga V.; Golukhova, Elena Z.; Bulaeva, Naida I.; Zholbaeva, Aigerim Z.; Bokeria, Leo A.; Garcia, Joe G. N.

2017-01-01

Aims Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, is expressed as a type-1 membrane glycoprotein on the surface of different cells, including endothelial cells of the heart. We hypothesized that the local conformation and, therefore, the properties of heart ACE could differ from lung ACE due to different microenvironment in these organs. Methods and results We performed ACE phenotyping (ACE levels, conformation and kinetic characteristics) in the human heart and compared it with that in the lung. ACE activity in heart tissues was 10–15 lower than that in lung. Various ACE effectors, LMW endogenous ACE inhibitors and HMW ACE-binding partners, were shown to be present in both heart and lung tissues. “Conformational fingerprint” of heart ACE (i.e., the pattern of 17 mAbs binding to different epitopes on the ACE surface) significantly differed from that of lung ACE, which reflects differences in the local conformations of these ACEs, likely controlled by different ACE glycosylation in these organs. Substrate specificity and pH-optima of the heart and lung ACEs also differed. Moreover, even within heart the apparent ACE activities, the local ACE conformations, and the content of ACE inhibitors differ in atria and ventricles. Conclusions Significant differences in the local conformations and kinetic properties of heart and lung ACEs demonstrate tissue specificity of ACE and provide a structural base for the development of mAbs able to distinguish heart and lung ACEs as a potential blood test for predicting atrial fibrillation risk. PMID:28771512

An Angiotensin I-Converting Enzyme Mutation (Y465D) Causes a Dramatic Increase in Blood ACE via Accelerated ACE Shedding

PubMed Central

Gordon, Kerry; Nesterovitch, Andrew B.; Lünsdorf, Heinrich; Chen, Zhenlong; Castellon, Maricela; Popova, Isolda A.; Kalinin, Sergey; Mendonca, Emma; Petukhov, Pavel A.; Schwartz, David E.

2011-01-01

Background Angiotensin I-converting enzyme (ACE) metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D) substitution, distal to the stalk region, in the N domain of ACE. Methodology/Principal Findings HEK and CHO cells expressing mutant (Tyr465Asp) ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE - between Arg1203 and Ser1204 - was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure) and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another. Conclusions/Significance The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase). PMID:21998728

Latent Classes and Cumulative Impacts of Adverse Childhood Experiences.

PubMed

Barboza, Gia Elise

2018-05-01

Studies of adverse childhood experiences (ACEs) have gauged severity using a cumulative risk (CR) index. Few studies have focused on the nature of the context of adversity and their association with psychosocial outcomes. The objective of this study was to examine the patterning of ACEs and to explore the resultant patterns' association with HIV risk-taking, problem drinking, and depressive symptoms in adulthood. Latent class analysis (LCA) was used to identify homogeneous, mutually exclusive "classes" of 11 of the most commonly used ACEs. The LCA resulted in four high-risk profiles and one low-risk profile, which were labeled: (1) highly abusive and dysfunctional (3.3%; n = 1,983), (2) emotionally abusive alcoholic with parental conflict (6%, n = 3,303), (3) sexual abuse only (4.3%, n = 2,260), (4) emotionally abusive and alcoholic (30.3%, n = 17,460), and (5) normative, low risk (56.3%, n = 32,950). Compared to the low-risk class, each high-risk profile was differentially associated with adult psychosocial outcomes even when the conditional CR within that class was similar. The results further our understanding about the pattern of ACEs and the unique pathways to poor health. Implications for child welfare systems when dealing with individuals who have experienced multiple forms of early childhood maltreatment and/or household dysfunction are discussed.

NASA Studies Lightning Storms Using High-Flying, Uninhabited Vehicle

NASA Technical Reports Server (NTRS)

2002-01-01

A NASA team studying the causes of electrical storms and their effects on our home planet achieved a milestone on August 21, 2002, completing the study's longest-duration research flight and monitoring four thunderstorms in succession. Based at the Naval Air Station Key West, Florida, researchers with the Altus Cumulus Electrification Study (ACES) used the Altus II remotely-piloted aircraft to study thunderstorms in the Atlantic Ocean off Key West and the west of the Everglades. Data obtained through sensors mounted to the aircraft will allow researchers in ACES to gauge elements such as lightning activity and the electrical environment in and around storms. By learning more about individual storms, scientists hope to better understand the global water and energy cycle, as well as climate variability. Contained in one portion of the aircraft is a three-axis magnetic search coil, which measures the AC magnetic field; a three-axis electric field change sensor; an accelerometer; and a three-axis magnetometer, which measures the DC magnetic field. With dual goals of gathering weather data safely and testing the adaptability of the uninhabited aircraft, the ACES study is a collaboration among the Marshall Space Flight Center, the University of Alabama in Huntsville, NASA's Goddard Space Flight Center in Greenbelt, Maryland, Pernsylvania State University in University Park, and General Atomics Aeronautical Systems, Inc.

Earth Science

NASA Image and Video Library

2002-08-01

A NASA team studying the causes of electrical storms and their effects on our home planet achieved a milestone on August 21, 2002, completing the study's longest-duration research flight and monitoring four thunderstorms in succession. Based at the Naval Air Station Key West, Florida, researchers with the Altus Cumulus Electrification Study (ACES) used the Altus II remotely-piloted aircraft to study thunderstorms in the Atlantic Ocean off Key West and the west of the Everglades. Data obtained through sensors mounted to the aircraft will allow researchers in ACES to gauge elements such as lightning activity and the electrical environment in and around storms. By learning more about individual storms, scientists hope to better understand the global water and energy cycle, as well as climate variability. Contained in one portion of the aircraft is a three-axis magnetic search coil, which measures the AC magnetic field; a three-axis electric field change sensor; an accelerometer; and a three-axis magnetometer, which measures the DC magnetic field. With dual goals of gathering weather data safely and testing the adaptability of the uninhabited aircraft, the ACES study is a collaboration among the Marshall Space Flight Center, the University of Alabama in Huntsville, NASA's Goddard Space Flight Center in Greenbelt, Maryland, Pernsylvania State University in University Park, and General Atomics Aeronautical Systems, Inc.

[Study of association between adverse experiences in childhood, social support, and physical and psychological sub-health status among middle school students in 3 cities in China].

PubMed

Wan, Y H; Ma, S S; Xu, S J; Zhang, S C; Hao, J H; Tao, F B

2017-09-06

Objective: To explore the relationship between adverse experience in childhood, social support, and physical and psychological sub-health status among middle school students in 3 cities in China. Methods: 15 278 adolescents were selected as subjects from 20 junior and senior middle schools located in 3 cities of China by stratified cluster sampling method. The survey collected the demographic information, ACEs, social support and physical-psychological status. A total of 14 820 valid questionnaires were retained for analysis. We assessed ACE score (count of six categories of childhood adversity), social support (adolescent social support questionnaire), and the prevalence of two outcomes: physiological and psychological sub-health status. Logistic regression was used to analyze the relationship between adverse childhood experiences, social support, and physiological and psychological sub-health status. Results: The prevalence of physiological and psychological sub-health status were 26.4% (3 917/14 820) and 24.1%(3 572/14 820), respectively. A total of 89.4% (13 247/14 820) reported at least 1 adverse childhood experiences. The rates of physiological and psychological sub-health status were higher among girls (28.1%(2 092/7 443), 26.0%(1 932/7 443)) than boys (24.7%(1 825/7 377), 22.2%(1 640/7 377)). Among adolescents without ACEs, the rate of physiological and psychological sub-health status were 15.4%(243/1 573) and 10.4%(163/1 573), for those with 5-6 ACEs, the rate were 40.9%(636/1 556) and 43.6%(678/1 556). Among adolescents with higher social support, the rate of physiological and psychological sub-health status were 19.9%(724/3 635) and 13.0%(474/3 635) for those with lower social support, the rate of physiological and psychological sub-health status were 35.9%(1 403/3 913) and 39.0%(1 528/3 913). The rates of physiological and psychological sub-health status were higher with more ACE exposure or less social support. At each level of ACE exposure, physiological and psychological sub-health status were less in those with greater social support. For example, among adolescents reporting 5-6 ACEs, those in the lowest tertile of social support increased the risk of physiological sub-health status than those in the highest tertile (adjusted prevalence ratio (95% CI )=1.79 (1.23-2.56)); for those reporting no ACEs, the ratio was 3.04 (1.91-4.83). Among adolescents reporting 5-6 ACEs, those in the lowest tertile of social support increased the risk of psychological sub-health status than those in the highest tertile (adjusted prevalence ratio (95% CI )=3.77 (2.57-5.52)); for those reporting no ACEs, the ratio was 3.97(2.33-6.76). Conclusion: The findings suggest that ACEs should be considered as risk factors for physiological and psychological sub-health status among middle school students. Across a range of exposures to ACEs, less social support was associated with more physiological and psychological sub-health status. Identifying those with ACE exposure who also have lower social support could be used to improve the health of adolescents.

Tissue-specific expression of transgenic secreted ACE in vasculature can restore normal kidney functions, but not blood pressure, of Ace-/- mice.

PubMed

Chattopadhyay, Saurabh; Kessler, Sean P; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE.

Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

PubMed Central

Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

2014-01-01

Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

Single-domain angiotensin I converting enzyme (kininase II): characterization and properties.

PubMed

Deddish, P A; Wang, L X; Jackman, H L; Michel, B; Wang, J; Skidgel, R A; Erdös, E G

1996-12-01

Somatic angiotensin I converting enzyme (ACE; kininase II) has two active sites, in two (N and C) domains. We studied the active centers with separate N-domain ACE (N-ACE), testicular C-domain ACE (germinal ACE) and, as control, renal somatic ACE. Germinal ACE cleaved the nonapeptide bradykinin about two times faster than N-ACE in 20 mM Cl-. Bradykinin1-7 was hydrolyzed further to bradykinin1-5 by N-ACE four times faster in the absence of Cl-, but at 300 mM Cl- the C-domain hydrolyzed it twice as fast. The hematopoietic system regulatory peptide acetyl-Ser-Asp-Lys-Pro was split to two dipeptides by N-ACE, depending on the chloride concentration, 8 to 24 times faster than by germinal ACE; at 100 mM Cl-, the Kcat with N-ACE was eight times higher. One millimolar 1-fluoro-2,4-dinitrobenzene inhibited germinal ACE 96% but it inhibited N-ACE by only 31%. [3H]Ramiprilat was displaced by other unlabeled ACE inhibitors to establish their relative affinities. Captopril had the lowest IC50 (0.5 nM) with N-ACE and the highest IC50 (8.3 nM) with the germinal ACE. The IC50 values of ramiprilat and quinaprilat were about the same with both active sites. The association and dissociation constants of [3H]ramiprilat indicated faster association with and faster dissociation from N-ACE than from germinal ACE. After exposure to alkali or moderate heat, somatic ACE was cleaved by plasmin and kallikrein, releasing N-ACE and apparently inactivating the C-domain. These studies affirm the differences in the activity, stability and inhibition of the two active sites of ACE.

Water Vapor Permeability of the Advanced Crew Escape Suit

NASA Technical Reports Server (NTRS)

Bue, Grant; Kuznetz, Larry; Gillis, David; Jones, Jeffery; Daniel, Brian; Gernhardt, Michael; Hamilton, Douglas

2009-01-01

Crew Exploration Vehicle (CEV) crewmembers are expected to return to earth wearing a suit similar to the current Advanced Crew Escape Suit (ACES). To ensure optimum cognitive performance, suited crewmembers must maintain their core body temperature within acceptable limits. There are currently several options for thermal maintenance in the post-landing phase. These include the current baseline, which uses an ammonia boiler, purge flow using oxygen in the suit, accessing sea water for liquid cooling garment (LCG) cooling and/or relying on the evaporative cooling capacity of the suit. These options vary significantly in mass, power, engineering and safety factors, with relying on the evaporative cooling capacity of the suit being the least difficult to implement. Data from previous studies indicates that the evaporative cooling capacity of the ACES was much higher than previously expected, but subsequent tests were performed for longer duration and higher metabolic rates to better define the water vapor permeability of the ACES. In these tests five subjects completed a series of tests performing low to moderate level exercise in order to control for a target metabolic rate while wearing the ACES in an environmentally controlled thermal chamber. Four different metabolic profiles at a constant temperature of 95 F and relative humidity of 50% were evaluated. These tests showed subjects were able to reject about twice as much heat in the permeable ACES as they were in an impermeable suit that had less thermal insulation. All of the heat rejection differential is attributed to the increased evaporation capability through the Gortex bladder of the suit.

Association of ACE gene A2350G and I/D polymorphisms with essential hypertension in the northernmost province of China.

PubMed

Sun, Feifei; He, Ning; Zhang, Keyong; Wu, Nan; Zhao, Jingbo; Qiu, Changchun

2018-01-01

Angiotensin converting enzyme (ACE) gene, as a strong candidate gene for essential hypertension(EH), has been extensively studied. In this study, we carried out a population-based case-control study to explore whether ACE gene I/D and A2350G polymorphisms could consider to be risk factors for EH. A total of 2040 subjeces were recruited from Chinese Han in this study, out of which 1010 were cases and 1030 were normotensive individuals. ACE gene A2350G and I/D polymorphisms were amplified by polymerase chain reaction (PCR) and A2350G polymorphism was detected after restriction enzyme digestion with BstuI. Besides, we choosed 10% samples randomly sequencing to verify the accuracy of results. Genotype and allele frequencies distribution of I/D and A2350G in EH and control groups were significantly different. After grouped by sex or age, there were still statistical significances for two polymorphisms. In dominant and recessive model of A2350G, we found significant differences between two groups, respectively. For ACE I/D polymorphism, we observed that the existence of dramatical difference in dominant model between two groups, while in recessive model, marginally significant difference was found. Among the four haplotypes composed by ACE gene A2350G and I/D, haplotype G-D reached the statistical significance in two groups, and exhibited to be a risk factor for the development of EH, whose P < 0.001 and OR 95%CI = 1.639(1.435-1.872), while the other haplotypes were the protective factors and decreased the susceptibility to EH(P < 0.05). ACE gene A2350G and I/D polymorphisms were associated with increasing the risk of suffering from EH in the northernmost province of China individuals, with D allele and G allele individuals had a higher risk of EH(OR = 1.443, 95%CI = 1.273-1.636 and OR = 1.481, 95%CI = 1.303-1.684).

Polymorphism of angiotensin-converting enzyme gene in sarcoidosis.

PubMed

Arbustini, E; Grasso, M; Leo, G; Tinelli, C; Fasani, R; Diegoli, M; Banchieri, N; Cipriani, A; Gorrini, M; Semenzato, G; Luisetti, M

1996-02-01

Sarcoidosis is the disease in which increased levels of serum Angiotensin-converting enzyme (sACE) are most often detected. It has recently been shown that the deletion (D) or the insertion (I) of a 250bp-DNA fragment in the ACE gene accounts for three main ACE genotypes (i.e., II, ID, and DD) and for 47% of total phenotypic variance in sACE level. The aim of our work was to investigate whether or not patients with sarcoidosis have an increased incidence of those ACE genotypes coding for highest sACE levels and to investigate whether or not sACE level in sarcoidosis is related to ACE genotypes. We studied 61 unrelated patients with sarcoidosis (test group) and 80 unrelated healthy control subjects (control group). The ACE I and D alleles were detected with polymerase chain reaction on genomic DNA. In the control group we found an ACE genotype distribution that agreed with the Hardy-Weinberg proportion. The ACE genotype distribution was not significantly different in the test group. There was no correlation between ACE genotype and roentgenologic stage of sarcoidosis. Plotting the sACE level in the control group against ACE genotype, we found a trend of increasing mean sACE value according to the order II < ID < DD. The same trend for ACE genotype was found in the test group, in which it also paralleled the trend of sACE values plotted against roentgenologic stage, according to the order Stage I < Stage II < Stage III. We conclude that in sarcoidosis the ACE genotype distribution is not altered. The trends for increasing sACE values in sarcoidosis according to both ACE genotype and roentgenologic stage would suggest that both mechanisms play a role in determining sACE level.

Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1–FoxM1 complex

PubMed Central

Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

2016-01-01

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy. PMID:27601681

Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1-FoxM1 complex.

PubMed

Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

2016-09-20

Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy.

Apoptosis of Hepatocellular Carcinoma Cells Induced by Nanoencapsulated Polysaccharides Extracted from Antrodia Camphorata

PubMed Central

Chang, Ke Liang B.; Kong, Zwe-Ling

2015-01-01

Antrodia camphorata is a well-known medicinal mushroom in Taiwan and has been studied for decades, especially with focus on anti-cancer activity. Polysaccharides are the major bioactive compounds reported with anti-cancer activity, but the debates on how they target cells still remain. Research addressing the encapsulation of polysaccharides from A. camphorata extract (ACE) to enhance anti-cancer activity is rare. In this study, ACE polysaccharides were nano-encapsulated in chitosan-silica and silica (expressed as ACE/CS and ACE/S, respectively) to evaluate the apoptosis effect on a hepatoma cell line (Hep G2). The results showed that ACE polysaccharides, ACE/CS and ACE/S all could damage the Hep G2 cell membrane and cause cell death, especially in the ACE/CS group. In apoptosis assays, DNA fragmentation and sub-G1 phase populations were increased, and the mitochondrial membrane potential decreased significantly after treatments. ACE/CS and ACE/S could also increase reactive oxygen species (ROS) generation, induce Fas/APO-1 (apoptosis antigen 1) expression and elevate the proteolytic activities of caspase-3, caspase-8 and caspase-9 in Hep G2 cells. Unsurprisingly, ACE/CS induced a similar apoptosis mechanism at a lower dosage (ACE polysaccharides = 13.2 μg/mL) than those of ACE/S (ACE polysaccharides = 21.2 μg/mL) and ACE polysaccharides (25 μg/mL). Therefore, the encapsulation of ACE polysaccharides by chitosan-silica nanoparticles may provide a viable approach for enhancing anti-tumor efficacy in liver cancer cells. PMID:26327534

Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy.

PubMed

Eriguchi, Masahiro; Lin, Mercury; Yamashita, Michifumi; Zhao, Tuantuan V; Khan, Zakir; Bernstein, Ellen A; Gurley, Susan B; Gonzalez-Villalobos, Romer A; Bernstein, Kenneth E; Giani, Jorge F

2018-04-01

Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.

ACE Phenotyping as a Guide Toward Personalized Therapy With ACE Inhibitors.

PubMed

Danilov, Sergei M; Tovsky, Stan I; Schwartz, David E; Dull, Randal O

2017-07-01

Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype"-for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mg enalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment with hydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient's blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. Due to the fact that "20% of patients do not respond to ACEI by blood pressure drop," the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.

Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session.

PubMed

Yang, Chung-Wei; Lu, Li-Che; Chang, Chia-Chu; Cho, Ching-Chang; Hsieh, Wen-Yeh; Tsai, Chin-Hung; Lin, Yi-Chang; Lin, Chih-Sheng

2017-11-01

The renin-angiotensin system (RAS) has significant influences on heart and renal disease progression. Angiotensin converting enzyme (ACE) and angiotensin converting enzyme II (ACE2) are major peptidases of RAS components and play counteracting functions through angiotensin II (Ang II)/ATIR and angiotensin-(1-7) (Ang-(1-7))/Mas axis, respectively. There were 360 uremic patients on regular hemodialysis (HD) treatment (inclusive of 119 HD patients with cardiovascular diseases (CVD) and 241 HD patients without CVD and 50 healthy subjects were enrolled in this study. Plasma ACE, ACE2, Ang II and Ang-(1-7) levels of the HD patients were determined. We compared pre-HD levels of plasma ACE, ACE2, Ang II and Ang-(1-7) in the HD patients with and without CVD to those of the controls. The HD patients, particularly those with CVD, showed a significant increase in the levels of ACE and Ang II, whereas ACE2 and Ang-(1-7) levels were lower than those in the healthy controls. Therefore, imbalanced ACE/ACE2 was observed in the HD patients with CVD. In the course of a single HD session, the plasma ACE, ACE/ACE2 and Ang II levels in the HD patients with CVD were increased from pre-HD to post-HD. On the contrary, ACE2 levels were decreased after the HD session. These changes were not detected in the HD patients without CVD. Pathogenically imbalanced circulating ACE/ACE2 was detected in the HD patients, particularly those with CVD. HD session could increase ACE/Ang II/AT1R axis and decrease ACE2/Ang-(1-7)/Mas axis activity in the circulation of HD patients with CVD.

Relationship of angiotensin I-converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy.

PubMed

Zou, Honghong; Wu, Guoqing; Lv, Jinlei; Xu, Gaosi

2017-06-01

To determine whether ACE 2 I/D and BDKRB2 3 +9/-9 polymorphism causatively affect diabetic nephropathy progression RESULTS: STZ-induced metabolic disorder, as well as inflammatory responses, was significantly aggravated in ACE II-B2R 4 +9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp diabetic mice but not ACE II-B2R-9bp, indicating the genetic susceptibility of ACE DD or B2R+9bp to diabetic nephropathy. Furthermore, ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp rather than ACE II-B2R-9bp, worsened renal performance and enhanced pathological alterations induced by STZ. Markedly elevated monocyte chemoattractant protein-1(MCP-1), podocin, osteopontin (OPN), transforming growth factor-β1 (TGF-β1), and reduced nephrin, podocin were also detected both in diabetic mice and podocytes under hyperglycemic conditions in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp, versus ACE II-B2R-9bp. In addition, high glucose-induced mitochondrial oxidative stress and cell apoptosis were observably increased in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp but not ACE II-B2R-9bp. We provide first evidence indicating the causation between ACE DD or B2R+9bp genotype and the increased risk for diabetic nephropathy, broadening our horizon about the role of genetic modulators in this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Sex dimorphism in ANGII-mediated crosstalk between ACE2 and ACE in diabetic nephropathy.

PubMed

Clotet-Freixas, Sergi; Soler, Maria Jose; Palau, Vanesa; Anguiano, Lidia; Gimeno, Javier; Konvalinka, Ana; Pascual, Julio; Riera, Marta

2018-06-08

Angiotensin-converting enzyme (ACE) and ACE2 play a critical role in the renin-angiotensin system (RAS) by altering angiotensin II (ANGII) levels, thus governing its deleterious effects. Both enzymes are altered by sex and diabetes, and play an important role in the development of diabetic nephropathy (DN). Importantly, previous evidence in diabetic and ACE2-deficient (ACE2KO) males suggest a sex-dependent crosstalk between renal ACE and ACE2. In the present work, we aimed to study the sex-specific susceptibility to diabetes and direct infusion of ANGII in kidney disease progression, with a special focus on its link to ACE2 and ACE. In our mouse model, ANGII promoted hypertension, albuminuria, reduced glomerular filtration, and glomerular histological alterations. ANGII adverse effects were accentuated by diabetes and ACE2 deficiency, in a sex-dependent fashion: ACE2 deficiency accentuated ANGII-induced hypertension, albuminuria, and glomerular hypertrophy in diabetic females, whereas in diabetic males exacerbated ANGII-mediated glomerular hypertrophy, mesangial expansion, and podocyte loss. At the molecular level, ANGII downregulated renal ACE gene and enzymatic activity levels, as well as renin gene expression in ACE2KO mice. Interestingly, male sex and diabetes accentuated this effect. Here we show sex dimorphism in the severity of diabetes- and ANGII-related renal lesions, and demonstrate that ACE2- and ACE-related compensatory mechanisms are sex-specific. Supporting our previous findings, the modulation and ANGII-mediated crosstalk between ACE2 and ACE in DN progression was more evident in males. This work increases the understanding of the sex-specific role of ACE2 and ACE in DN, reinforcing the necessity of more personalized treatments targeting RAS.

Regulation of the aceI multidrug efflux pump gene in Acinetobacter baumannii.

PubMed

Liu, Qi; Hassan, Karl A; Ashwood, Heather E; Gamage, Hasinika K A H; Li, Liping; Mabbutt, Bridget C; Paulsen, Ian T

2018-06-01

To investigate the function of AceR, a putative transcriptional regulator of the chlorhexidine efflux pump gene aceI in Acinetobacter baumannii. Chlorhexidine susceptibility and chlorhexidine induction of aceI gene expression were determined by MIC and quantitative real-time PCR, respectively, in A. baumannii WT and ΔaceR mutant strains. Recombinant AceR was prepared as both a full-length protein and as a truncated protein, AceR (86-299), i.e. AceRt, which has the DNA-binding domain deleted. The binding interaction of the purified AceR protein and its putative operator region was investigated by electrophoretic mobility shift assays and DNase I footprinting assays. The binding of AceRt with its putative ligand chlorhexidine was examined using surface plasmon resonance and tryptophan fluorescence quenching assays. MIC determination assays indicated that the ΔaceI and ΔaceR mutant strains both showed lower resistance to chlorhexidine than the parental strain. Chlorhexidine-induced expression of aceI was abolished in a ΔaceR background. Electrophoretic mobility shift assays and DNase I footprinting assays demonstrated chlorhexidine-stimulated binding of AceR with two sites upstream of the putative aceI promoter. Surface plasmon resonance and tryptophan fluorescence quenching assays suggested that the purified ligand-binding domain of the AceR protein was able to bind with chlorhexidine with high affinity. This study provides strong evidence that AceR is an activator of aceI gene expression when challenged with chlorhexidine. This study is the first characterization, to our knowledge, of a regulator controlling expression of a PACE family multidrug efflux pump.

Discovery of Anti-Hypertensive Oligopeptides from Adlay Based on In Silico Proteolysis and Virtual Screening

PubMed Central

Qiao, Liansheng; Li, Bin; Chen, Yankun; Li, Lingling; Chen, Xi; Wang, Lingzhi; Lu, Fang; Luo, Ganggang; Li, Gongyu; Zhang, Yanling

2016-01-01

Adlay (Coix larchryma-jobi L.) was the commonly used Traditional Chinese Medicine (TCM) with high content of seed storage protein. The hydrolyzed bioactive oligopeptides of adlay have been proven to be anti-hypertensive effective components. However, the structures and anti-hypertensive mechanism of bioactive oligopeptides from adlay were not clear. To discover the definite anti-hypertensive oligopeptides from adlay, in silico proteolysis and virtual screening were implemented to obtain potential oligopeptides, which were further identified by biochemistry assay and molecular dynamics simulation. In this paper, ten sequences of adlay prolamins were collected and in silico hydrolyzed to construct the oligopeptide library with 134 oligopeptides. This library was reverse screened by anti-hypertensive pharmacophore database, which was constructed by our research team and contained ten anti-hypertensive targets. Angiotensin-I converting enzyme (ACE) was identified as the main potential target for the anti-hypertensive activity of adlay oligopeptides. Three crystal structures of ACE were utilized for docking studies and 19 oligopeptides were finally identified with potential ACE inhibitory activity. According to mapping features and evaluation indexes of pharmacophore and docking, three oligopeptides were selected for biochemistry assay. An oligopeptide sequence, NPATY (IC50 = 61.88 ± 2.77 µM), was identified as the ACE inhibitor by reverse-phase high performance liquid chromatography (RP-HPLC) assay. Molecular dynamics simulation of NPATY was further utilized to analyze interactive bonds and key residues. ALA354 was identified as a key residue of ACE inhibitors. Hydrophobic effect of VAL518 and electrostatic effects of HIS383, HIS387, HIS513 and Zn2+ were also regarded as playing a key role in inhibiting ACE activities. This study provides a research strategy to explore the pharmacological mechanism of Traditional Chinese Medicine (TCM) proteins based on in silico proteolysis and virtual screening, which could be beneficial to reveal the pharmacological action of TCM proteins and provide new lead compounds for peptides-based drug design. PMID:27983650

Inter-Agency Consultative Group for Space Science (IACG): Handbook of Missions and Payloads

NASA Technical Reports Server (NTRS)

1994-01-01

The ACE spacecraft design is based on the Charge Composition Explorer (CCE) built by Johns Hopkins University (JHU) and the Applied Physics Lab (APL) for the AMPTE program. ACE is designed as a spinning spacecraft with its spin axis aligned to the Earth-Sun axis. The ACE launch weight will be approx. 633 kg, including 105 kg of scientific instruments and 184 kg of propellant. Using a Delta-class expendable launch vehicle, ACE will be launched into an L1 libration point (240 R(sub e)) orbit. Telemetry will be 6.7 kbps average, using tape recorder storage with daily readout to DSN. The experiment power requirement is approximately 76 W nominal and 96 W peak. The prime objective of the ACE mission is: (1) to determine accurate elemental and isotropic abundances including solar matter, local interstellar matter and local galactic matter; (2) to study the origin of elements and evolutionary processing in galactic nucleosynthesis, galactic evolution, origin and evolution of the solar system; (3) to study coronal formation and solar-wind acceleration processes; and (4) to study particle acceleration and transport, including coronal shock acceleration, stochastic flare acceleration, interplanetary shock acceleration, and interstellar acceleration and propagation. To accomplish this objective, ACE will perform comprehensive and coordinated determinations of the elemental and isotopic composition of energetic nuclei accelerated on the Sun, in interplanetary space, and from galactic sources. These observations will span five decades in energy, from solar wind to galactic cosmic ray energies, and will cover the element range from H-1 to Zr-40. Comparison of these samples of matter will be used to study the origin and subsequent evolution of both solar system and galactic material by isolating the effects of fundamental processes that include nucleosynthesis, charged and neutral particle separation, bulk plasma acceleration, and the acceleration of suprathermal and high-energy particles.

Tissue Specificity of Human Angiotensin I-Converting Enzyme

PubMed Central

Kryukova, Olga V.; Tikhomirova, Victoria E.; Golukhova, Elena Z.; Evdokimov, Valery V.; Kalantarov, Gavreel F.; Trakht, Ilya N.; Schwartz, David E.; Dull, Randal O.; Gusakov, Alexander V.; Uporov, Igor V.; Kost, Olga A.; Danilov, Sergei M.

2015-01-01

Background Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood. Methods/Principal Findings We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests. Conclusions Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs. PMID:26600189

Gender difference of serum angiotensin-converting enzyme (ACE) activity in DD genotype of ACE insertion/deletion polymorphism in elderly Chinese.

PubMed

Zhang, Ya-Feng; Cheng, Qiong; Tang, Nelson L S; Chu, Tanya T W; Tomlinson, Brian; Liu, Fan; Kwok, Timothy C Y

2014-12-01

In this study we investigated the gender difference of serum angiotensin-converting enzyme (ACE) activity in a population of Hong Kong-dwelling elderly Chinese. A total of 1767 (843 male, 924 female) Hong Kong-dwelling elderly Chinese were recruited. ACE I/D genotypes were identified by polymerase chain reaction amplification and serum ACE activity was determined using a commercially available kinetic kit. ACE I/D genotype distribution was compared by chi-square test, the correlation between ACE I/D polymorphism and serum ACE activity was analysed by ANOVA test and gender difference of serum ACE activity of different genotypes was compared by independent sample t-test. No statistically significant difference of genotype distribution between male and female subjects was found. Serum ACE activity was significantly correlated with ACE genotype. Overall, there was no gender difference of serum ACE activity; however, when sub-grouping the subjects by ACE I/D genotype, male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. No significant gender difference of genotype distribution was found in elderly Chinese. Serum ACE activity was significantly correlated with ACE I/D polymorphism in elderly Chinese. Male subjects with DD genotype had higher serum ACE activity than female subjects with DD genotype. © The Author(s) 2013.

ACE as a Mechanosensor to Shear Stress Influences the Control of Its Own Regulation via Phosphorylation of Cytoplasmic Ser1270

PubMed Central

Barauna, Valerio Garrone; Campos, Luciene Cristina Gastalho; Miyakawa, Ayumi Aurea; Krieger, Jose Eduardo

2011-01-01

Objectives We tested whether angiotensin converting enzyme (ACE) and phosphorylation of Ser1270 are involved in shear-stress (SS)-induced downregulation of the enzyme. Methods and Results Western blotting analysis showed that SS (18 h, 15 dyn/cm2) decreases ACE expression and phosphorylation as well as p-JNK inhibition in human primary endothelial cells (EC). CHO cells expressing wild-type ACE (wt-ACE) also displayed SS-induced decrease in ACE and p-JNK. Moreover, SS decreased ACE promoter activity in wt-ACE, but had no effect in wild type CHO or CHO expressing ACE without either the extra- or the intracellular domains, and decreased less in CHO expressing a mutated ACE at Ser1270 compared to wt-ACE (13 vs. 40%, respectively). The JNK inhibitor (SP600125, 18 h), in absence of SS, also decreased ACE promoter activity in wt-ACE. Finally, SS-induced inhibition of ACE expression and phosphorylation in EC was counteracted by simultaneous exposure to an ACE inhibitor. Conclusions ACE displays a key role on its own downregulation in response to SS. This response requires both the extra- and the intracellular domains and ACE Ser1270, consistent with the idea that the extracellular domain behaves as a mechanosensor while the cytoplasmic domain elicits the downstream intracellular signaling by phosphorylation on Ser1270. PMID:21901117

ACE-Asia Aerosol Optical Depth and Water Vapor Measured by Airborne Sunphotometers and Related to Other Measurements and Calculations

NASA Technical Reports Server (NTRS)

Livingston, John M.; Russell, P. B.; Schmid, B.; Redemann, J.; Eilers, J. A.; Ramirez, S. A.; Kahn, R.; Hegg, D.; Pilewskie, P.; Anderson, T.;

Validation of the MIPAS CO2 volume mixing ratio in the mesosphere and lower thermosphere and comparison with WACCM simulations

NASA Astrophysics Data System (ADS)

López-Puertas, Manuel; Funke, B.; Jurado-Navarro, Á. A.; García-Comas, M.; Gardini, A.; Boone, C. D.; Rezac, L.; Garcia, R. R.

2017-08-01

We present the validation of Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) CO2 daytime concentration in the mesosphere and lower thermosphere by comparing with Atmospheric Chemistry Experiment (ACE) Fourier transform spectrometer and Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) data. MIPAS shows a very good agreement with ACE below 100 km with differences of ˜5%. Above 100 km, MIPAS CO2 is generally lower than ACE with differences growing from ˜5% at 100 km to 20-40% near 110-120 km. Part of this disagreement can be explained by the lack of a nonlocal thermodynamic equilibrium correction in ACE. MIPAS also agrees very well (˜5%) with SABER below 100 km. At 90-105 km, MIPAS is generally smaller than SABER by 10-30% in the polar summers. At 100-120 km, MIPAS and SABER CO2 agree within ˜10% during equinox but, for solstice, MIPAS is larger by 10-25%, except near the polar summer. Whole Atmosphere Community Climate Model (WACCM) CO2 shows the major MIPAS features. At 75-100 km, the agreement is very good (˜5%), with maximum differences of ˜10%. At 95-115 km MIPAS CO2 is larger than WACCM by 20-30% in the winter hemisphere but smaller (20-40%) in the summer. Above 95-100 km WACCM generally overestimates MIPAS CO2 by about 20-80% except in the polar summer where underestimates it by 20-40%. MIPAS CO2 favors a large eddy diffusion below 100 km and suggests that the meridional circulation of the lower thermosphere is stronger than in WACCM. The three instruments and WACCM show a clear increase of CO2 with time, more markedly at 90-100 km.

The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity.

PubMed

Woodman, Zenda L; Schwager, Sylva L U; Redelinghuys, Pierre; Carmona, Adriana K; Ehlers, Mario R W; Sturrock, Edward D

2005-08-01

sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the k(cat) for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates.

The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity

PubMed Central

Woodman, Zenda L.; Schwager, Sylva L. U.; Redelinghuys, Pierre; Carmona, Adriana K.; Ehlers, Mario R. W.; Sturrock, Edward D.

2005-01-01

sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the kcat for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates. PMID:15813703

Conformational Changes of Blood ACE in Chronic Uremia

PubMed Central

Petrov, Maxim N.; Shilo, Valery Y.; Tarasov, Alexandr V.; Schwartz, David E.; Garcia, Joe G. N.; Kost, Olga A.; Danilov, Sergei M.

2012-01-01

Background The pattern of binding of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) comprise a conformational ACE fingerprint and is a sensitive marker of subtle protein conformational changes. Hypothesis Toxic substances in the blood of patients with uremia due to End Stage Renal Disease (ESRD) can induce local conformational changes in the ACE protein globule and alter the efficacy of ACE inhibitors. Methodology/Principal Findings The recognition of ACE by 16 mAbs to the epitopes on the N and C domains of ACE was estimated using an immune-capture enzymatic plate precipitation assay. The precipitation pattern of blood ACE by a set of mAbs was substantially influenced by the presence of ACE inhibitors with the most dramatic local conformational change noted in the N-domain region recognized by mAb 1G12. The “short” ACE inhibitor enalaprilat (tripeptide analog) and “long” inhibitor teprotide (nonapeptide) produced strikingly different mAb 1G12 binding with enalaprilat strongly increasing mAb 1G12 binding and teprotide decreasing binding. Reduction in S-S bonds via glutathione and dithiothreitol treatment increased 1G12 binding to blood ACE in a manner comparable to enalaprilat. Some patients with uremia due to ESRD exhibited significantly increased mAb 1G12 binding to blood ACE and increased ACE activity towards angiotensin I accompanied by reduced ACE inhibition by inhibitory mAbs and ACE inhibitors. Conclusions/Significance The estimation of relative mAb 1G12 binding to blood ACE detects a subpopulation of ESRD patients with conformationally changed ACE, which activity is less suppressible by ACE inhibitors. This parameter may potentially serve as a biomarker for those patients who may need higher concentrations of ACE inhibitors upon anti-hypertensive therapy. PMID:23166630

Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE

PubMed Central

Rella, Monika; Elliot, Joann L; Revett, Timothy J; Lanfear, Jerry; Phelan, Anne; Jackson, Richard M; Turner, Anthony J; Hooper, Nigel M

2007-01-01

Background Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals. Results Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reverse-transcription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified. Conclusion In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene. PMID:17597519

Observational Simulation of Icing in Extreme Weather Conditions

NASA Astrophysics Data System (ADS)

Gultepe, Ismail; Heymsfield, Andrew; Agelin-Chaab, Martin; Komar, John; Elfstrom, Garry; Baumgardner, Darrel

2017-04-01

Observations and prediction of icing in extreme weather conditions are important for aviation, transportation, and shipping applications, and icing adversely affects the economy. Icing environments can be studied either in the outdoor atmosphere or in the laboratory. There have been several aircraft based in-situ studies related to weather conditions affecting aviation operations, transportation, and marine shipping that includes icing, wind, and turbulence. However, studying severe weather conditions from aircraft observations are limited due to safety and sampling issues, instrumental uncertainties, and even the possibility of aircraft producing its own physical and dynamical effects. Remote sensing based techniques (e.g. retrieval techniques) for studying severe weather conditions represent usually a volume that cannot characterize the important scales and also represents indirect observations. Therefore, laboratory simulations of atmospheric processes can help us better understand the interactions among microphysical and dynamical processes. The Climatic Wind Tunnel (CWT) in ACE at the University of Ontario Institute of Technology (UOIT) has a large semi-open jet test chamber with flow area 7-13 m2 that can precisely control temperatures down to -40°C, and up to 250 km hr-1 wind speeds, for heavy or dry snow conditions with low visibility, similar to ones observed in the Arctic and cold climate regions, or at high altitude aeronautical conditions. In this study, the ACE CWT employed a spray nozzle array suspended in its settling chamber and fed by pressurized water, creating various particle sizes from a few microns up to mm size range. This array, together with cold temperature and high wind speed, enabled simulation of severe weather conditions, including icing, visibility, strong wind and turbulence, ice fog and frost, freezing fog, heavy snow and blizzard conditions. In this study, the test results will be summarized, and their application to aircraft icing will be provided in detail. Overall, based on these results, scientific challenges related to icing environments will be emphasized for Arctic and cold environments in future projects in the ACE CWT.

Comparison of Aerosol Single Scattering Albedos Derived by Diverse Techniques In Two North Atlantic Experiments

NASA Technical Reports Server (NTRS)

Russell, P. B.; Redemann, J.; Schmid, B.; Bergstrom, R. W.; Livingston, J. M.; McIntosh, D. M.; Ramirez, S. A.; Hartley, S.; Hobbs, P. V.; Quinn, P. K.

2002-01-01

Aerosol single scattering albedo omega (the ratio of scattering to extinction) is important in determining aerosol climatic effects, in explaining relationships between calculated and measured radiative fluxes, and in retrieving aerosol optical depths from satellite radiances. Recently, two experiments in the North Atlantic region, the Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the Second Aerosol Characterization Experiment (ACE-2), determined aerosol omega by a variety of techniques. The techniques included fitting of calculated to measured radiative fluxes; retrievals of omega from skylight radiances; best fits of complex refractive index to profiles of backscatter extinction, and size distribution; and in situ measurements of scattering and absorption at the surface and aloft. Both TARFOX and ACE-2 found a fairly wide range of values for omega at midvisable wavelengths approx. 550 nm, with omega(sub midvis) greater than or equal to 0.85 and less than or equal to 0.99 for the marine aerosol impacted by continental pollution. Frequency distributions of omega could usually be approximated by lognormals in omega(sub max) - omega, with some occurrence of bimodality, suggesting the influence of different aerosol sources or processing. In both TARFOX and ACE-2, closure tests between measured and calculated radiative fluxes yielded best-fit values of omega(sub midvis) 0.90 +/- 0.04 for the polluted boundary layer. Although these results have the virtue of describing the column aerosol unperturbed by sampling, they are subject to questions about representativeness and other uncertainties (e.g., thermal offsets, unknown gas absorption) The other techniques gave larger values for omega(sub midvis) for the polluted boundary layer, with a typical result of omega(sub midvis) = 0.95 +/- 0.04. Current uncertainties in omega are large in terms of climate effects More tests are needed of the consistency among different methods and of humidification effects on omega.

Hydronephrosis alters cardiac ACE2 and Mas receptor expression in mice.

PubMed

Zhang, Yanling; Ma, Lulu; Wu, Junyan; Chen, Tingting

2015-06-01

Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. However, whether alterations of angiotensin-converting enzyme (ACE), ACE2 and Mas receptor in the heart are observed in hydronephrosis is unknown. Thus, we assessed these components in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor. Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. The levels of cardiac ACE, ACE2 and Mas receptor were measured after treatment of losartan or enalapril. Hydronephrosis led to an increase of ACE level and a decrease of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (p < 0.01). Enalapril increased ACE2 levels (p < 0.01), but did not affect Mas receptor in the heart. Plasma renin activity (PRA) and Ang II decreased in hydronephrotic mice, but significantly increased after treatment with losartan or enalapril. Hydronephrosis increased cardiac ACE and suppressed ACE2 and Mas receptor levels. AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals. © The Author(s) 2015.

Osthole protects lipopolysaccharide-induced acute lung injury in mice by preventing down-regulation of angiotensin-converting enzyme 2.

PubMed

Shi, Yun; Zhang, Bo; Chen, Xiang-Jun; Xu, Dun-Quan; Wang, Yan-Xia; Dong, Hai-Ying; Ma, Shi-Rong; Sun, Ri-He; Hui, Yan-Ping; Li, Zhi-Chao

2013-03-12

The renin-angiotensin-aldosterone system (RAAS) plays an important role in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Angiotensin converting enzyme 2 (ACE2) plays a protective role in acute lung injury. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to have anti-inflammatory effect, but the effect of osthole on the ALI is largely unknown. The aim of this study is to explore whether and by what mechanisms osthole protects lipopolysaccharide(LPS)-induced acute lung injury. Herein, we found that osthole had a beneficial effect on LPS-induced ALI in mice. As revealed by survival study, pretreatment with high doses of osthole reduced the mortality of mice from ALI. Osthole pretreatment significantly improved LPS-induced lung pathological changes, reduced lung wet/dry weight ratios and total protein in BALF. Osthole also inhibited the release of inflammatory mediators TNF-α and IL-6. Meanwhile, osthole markedly prevented the loss of ACE2 and Ang1-7 in lung tissue of ALI mice. ACE2 inhibitor blocked the protective effect of osthole in NR 8383 cell lines. Taken together, our study showed that osthole improved survival rate and attenuated LPS-induced ALI and ACE2 may play a role in it. Copyright © 2013 Elsevier B.V. All rights reserved.

Multi-spacecraft observations of recurrent {sup 3}He-rich solar energetic particles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bučík, R.; Innes, D. E.; Mall, U.

2014-05-01

We study the origin of {sup 3}He-rich solar energetic particles (<1 MeV nucleon{sup –1}) that are observed consecutively on STEREO-B, Advanced Composition Explorer (ACE), and STEREO-A spacecraft when they are separated in heliolongitude by more than 90°. The {sup 3}He-rich period on STEREO-B and STEREO-A commences on 2011 July 1 and 2011 July 16, respectively. The ACE {sup 3}He-rich period consists of two sub-events starting on 2011 July 7 and 2011 July 9. We associate the STEREO-B July 1 and ACE July 7 {sup 3}He-rich events with the same sizeable active region (AR) producing X-ray flares accompanied by prompt electronmore » events, when it was near the west solar limb as seen from the respective spacecraft. The ACE July 9 and STEREO-A July 16 events were dispersionless with enormous {sup 3}He enrichment, lacking solar energetic electrons and occurring in corotating interaction regions. We associate these events with a small, recently emerged AR near the border of a low-latitude coronal hole that produced numerous jet-like emissions temporally correlated with type III radio bursts. For the first time we present observations of (1) solar regions with long-lasting conditions for {sup 3}He acceleration and (2) solar energetic {sup 3}He that is temporarily confined/re-accelerated in interplanetary space.« less

Enzyme Hydrolysates from Stichopus horrens as a New Source for Angiotensin-Converting Enzyme Inhibitory Peptides

PubMed Central

Forghani, Bita; Ebrahimpour, Afshin; Bakar, Jamilah; Abdul Hamid, Azizah; Hassan, Zaiton; Saari, Nazamid

2012-01-01

Stichopus horrens flesh was explored as a potential source for generating peptides with angiotensin-converting enzyme (ACE) inhibitory capacity using 6 proteases, namely alcalase, flavourzyme, trypsin, papain, bromelain, and protamex. Degree of hydrolysis (DH) and peptide profiling (SDS-PAGE) of Stichopus horrens hydrolysates (SHHs) was also assessed. Alcalase hydrolysate showed the highest DH value (39.8%) followed by flavourzyme hydrolysate (32.7%). Overall, alcalase hydrolysate exhibited the highest ACE inhibitory activity (IC50 value of 0.41 mg/mL) followed by flavourzyme hydrolysate (IC50 value of 2.24 mg/mL), trypsin hydrolysate (IC50 value of 2.28 mg/mL), papain hydrolysate (IC50 value of 2.48 mg/mL), bromelain hydrolysate (IC50 value of 4.21 mg/mL), and protamex hydrolysate (IC50 value of 6.38 mg/mL). The SDS-PAGE results showed that alcalase hydrolysate represented a unique pattern compared to others, which yielded potent ACE inhibitory peptides with molecular weight distribution lower than 20 kDa. The evaluation of the relationship between DH and IC50 values of alcalase and flavourzyme hydrolysates revealed that the trend between those parameters was related to the type of the protease used. We concluded that the tested SHHs would be used as a potential source of functional ACE inhibitory peptides for physiological benefits. PMID:22927875

Enzyme Hydrolysates from Stichopus horrens as a New Source for Angiotensin-Converting Enzyme Inhibitory Peptides.

PubMed

Forghani, Bita; Ebrahimpour, Afshin; Bakar, Jamilah; Abdul Hamid, Azizah; Hassan, Zaiton; Saari, Nazamid

2012-01-01

Stichopus horrens flesh was explored as a potential source for generating peptides with angiotensin-converting enzyme (ACE) inhibitory capacity using 6 proteases, namely alcalase, flavourzyme, trypsin, papain, bromelain, and protamex. Degree of hydrolysis (DH) and peptide profiling (SDS-PAGE) of Stichopus horrens hydrolysates (SHHs) was also assessed. Alcalase hydrolysate showed the highest DH value (39.8%) followed by flavourzyme hydrolysate (32.7%). Overall, alcalase hydrolysate exhibited the highest ACE inhibitory activity (IC(50) value of 0.41 mg/mL) followed by flavourzyme hydrolysate (IC(50) value of 2.24 mg/mL), trypsin hydrolysate (IC(50) value of 2.28 mg/mL), papain hydrolysate (IC(50) value of 2.48 mg/mL), bromelain hydrolysate (IC(50) value of 4.21 mg/mL), and protamex hydrolysate (IC(50) value of 6.38 mg/mL). The SDS-PAGE results showed that alcalase hydrolysate represented a unique pattern compared to others, which yielded potent ACE inhibitory peptides with molecular weight distribution lower than 20 kDa. The evaluation of the relationship between DH and IC(50) values of alcalase and flavourzyme hydrolysates revealed that the trend between those parameters was related to the type of the protease used. We concluded that the tested SHHs would be used as a potential source of functional ACE inhibitory peptides for physiological benefits.

N-domain angiotensin-I converting enzyme is expressed in immortalized mesangial, proximal tubule and collecting duct cells.

PubMed

Mei Wang, Pamella Huey; Andrade, Maria Claudina; Quinto, Beata Marie Redublo; Di Marco, Giovana; Mortara, Renato Arruda; Vio, Carlos P; Casarini, Dulce Elena

2015-01-01

Somatic ACE (sACE) is found in glomerulus, proximal tubule and excreted in urine. We hypothesized that N-domain ACE can also be found at these sites. ACE profile was analyzed in mesangial (IMC), proximal (LLC-PK1), distal tubule (MDCK) and collecting duct (IMCD) cells. Cell lysate and culture medium were submitted to gel filtration chromatography, which separated two peaks with ACE activity from cells and medium, except from distal tubule. The first had a high molecular weight and the second, a lower one (65 kDa; N-domain ACE). We focused on N-domain ACE purification and characterization from LLC-PK1. Total LLC-PK1 N-domain ACE purification was achieved by ion-exchange chromatography, which presented only one peak with ACE activity, denominated ACE(int2A). ACE(int2A) activity was influenced by pH, NaCl and temperature. The purified enzyme was inhibited by Captopril and hydrolyzed AngI, Ang1-7 and AcSDKP. Its ability to hydrolyze AcSDKP characterized it as an N-domain ACE. ACE(int2A) also presented high amino acid sequence homology with the N-terminal part of sACE from mouse, rat, human and rabbit. The presence of secreted and intracellular N-domain ACE and sACE in IMC, LLC-PK1 and IMCD cells confirmed our studies along the nephron. We identified, purified and characterized N-domain ACE from LLC-PK1. Copyright © 2014 Elsevier B.V. All rights reserved.

The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice.

PubMed

Bian, Xiaoming; Chi, Liang; Gao, Bei; Tu, Pengcheng; Ru, Hongyu; Lu, Kun

2017-01-01

Artificial sweeteners have been widely used in the modern diet, and their observed effects on human health have been inconsistent, with both beneficial and adverse outcomes reported. Obesity and type 2 diabetes have dramatically increased in the U.S. and other countries over the last two decades. Numerous studies have indicated an important role of the gut microbiome in body weight control and glucose metabolism and regulation. Interestingly, the artificial sweetener saccharin could alter gut microbiota and induce glucose intolerance, raising questions about the contribution of artificial sweeteners to the global epidemic of obesity and diabetes. Acesulfame-potassium (Ace-K), a FDA-approved artificial sweetener, is commonly used, but its toxicity data reported to date are considered inadequate. In particular, the functional impact of Ace-K on the gut microbiome is largely unknown. In this study, we explored the effects of Ace-K on the gut microbiome and the changes in fecal metabolic profiles using 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. We found that Ace-K consumption perturbed the gut microbiome of CD-1 mice after a 4-week treatment. The observed body weight gain, shifts in the gut bacterial community composition, enrichment of functional bacterial genes related to energy metabolism, and fecal metabolomic changes were highly gender-specific, with differential effects observed for males and females. In particular, ace-K increased body weight gain of male but not female mice. Collectively, our results may provide a novel understanding of the interaction between artificial sweeteners and the gut microbiome, as well as the potential role of this interaction in the development of obesity and the associated chronic inflammation.

The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice

PubMed Central

Bian, Xiaoming; Chi, Liang; Gao, Bei; Tu, Pengcheng; Ru, Hongyu

2017-01-01

Artificial sweeteners have been widely used in the modern diet, and their observed effects on human health have been inconsistent, with both beneficial and adverse outcomes reported. Obesity and type 2 diabetes have dramatically increased in the U.S. and other countries over the last two decades. Numerous studies have indicated an important role of the gut microbiome in body weight control and glucose metabolism and regulation. Interestingly, the artificial sweetener saccharin could alter gut microbiota and induce glucose intolerance, raising questions about the contribution of artificial sweeteners to the global epidemic of obesity and diabetes. Acesulfame-potassium (Ace-K), a FDA-approved artificial sweetener, is commonly used, but its toxicity data reported to date are considered inadequate. In particular, the functional impact of Ace-K on the gut microbiome is largely unknown. In this study, we explored the effects of Ace-K on the gut microbiome and the changes in fecal metabolic profiles using 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS) metabolomics. We found that Ace-K consumption perturbed the gut microbiome of CD-1 mice after a 4-week treatment. The observed body weight gain, shifts in the gut bacterial community composition, enrichment of functional bacterial genes related to energy metabolism, and fecal metabolomic changes were highly gender-specific, with differential effects observed for males and females. In particular, ace-K increased body weight gain of male but not female mice. Collectively, our results may provide a novel understanding of the interaction between artificial sweeteners and the gut microbiome, as well as the potential role of this interaction in the development of obesity and the associated chronic inflammation. PMID:28594855

Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

PubMed Central

Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

2016-01-01

There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham-operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre-treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang-(1–7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang-(1–7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre-treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA. PMID:27633002

ACE phenotyping in Gaucher disease.

PubMed

Danilov, Sergei M; Tikhomirova, Victoria E; Metzger, Roman; Naperova, Irina A; Bukina, Tatiana M; Goker-Alpan, Ozlem; Tayebi, Nahid; Gayfullin, Nurshat M; Schwartz, David E; Samokhodskaya, Larisa M; Kost, Olga A; Sidransky, Ellen

2018-04-01

Gaucher disease is characterized by the activation of splenic and hepatic macrophages, accompanied by dramatically increased levels of angiotensin-converting enzyme (ACE). To evaluate the source of the elevated blood ACE, we performed complete ACE phenotyping using blood, spleen and liver samples from patients with Gaucher disease and controls. ACE phenotyping included 1) immunohistochemical staining for ACE; 2) measuring ACE activity with two substrates (HHL and ZPHL); 3) calculating the ratio of the rates of substrate hydrolysis (ZPHL/HHL ratio); 4) assessing the conformational fingerprint of ACE by evaluating the pattern of binding of monoclonal antibodies to 16 different ACE epitopes. We show that in patients with Gaucher disease, the dramatically increased levels of ACE originate from activated splenic and/or hepatic macrophages (Gaucher cells), and that both its conformational fingerprint and kinetic characteristics (ZPHL/HHL ratio) differ from controls and from patients with sarcoid granulomas. Furthermore, normal spleen was found to produce high levels of endogenous ACE inhibitors and a novel, tightly-bound 10-30 kDa ACE effector which is deficient in Gaucher spleen. The conformation of ACE is tissue-specific. In Gaucher disease, ACE produced by activated splenic macrophages differs from that in hepatic macrophages, as well as from macrophages and dendritic cells in sarcoid granulomas. The observed differences are likely due to altered ACE glycosylation or sialylation in these diseased organs. The conformational differences in ACE may serve as a specific biomarker for Gaucher disease. Copyright © 2018 Elsevier Inc. All rights reserved.

AceTree: a tool for visual analysis of Caenorhabditis elegans embryogenesis

PubMed Central

Boyle, Thomas J; Bao, Zhirong; Murray, John I; Araya, Carlos L; Waterston, Robert H

2006-01-01

Background The invariant lineage of the nematode Caenorhabditis elegans has potential as a powerful tool for the description of mutant phenotypes and gene expression patterns. We previously described procedures for the imaging and automatic extraction of the cell lineage from C. elegans embryos. That method uses time-lapse confocal imaging of a strain expressing histone-GFP fusions and a software package, StarryNite, processes the thousands of images and produces output files that describe the location and lineage relationship of each nucleus at each time point. Results We have developed a companion software package, AceTree, which links the images and the annotations using tree representations of the lineage. This facilitates curation and editing of the lineage. AceTree also contains powerful visualization and interpretive tools, such as space filling models and tree-based expression patterning, that can be used to extract biological significance from the data. Conclusion By pairing a fast lineaging program written in C with a user interface program written in Java we have produced a powerful software suite for exploring embryonic development. PMID:16740163

AceTree: a tool for visual analysis of Caenorhabditis elegans embryogenesis.

PubMed

Boyle, Thomas J; Bao, Zhirong; Murray, John I; Araya, Carlos L; Waterston, Robert H

2006-06-01

The invariant lineage of the nematode Caenorhabditis elegans has potential as a powerful tool for the description of mutant phenotypes and gene expression patterns. We previously described procedures for the imaging and automatic extraction of the cell lineage from C. elegans embryos. That method uses time-lapse confocal imaging of a strain expressing histone-GFP fusions and a software package, StarryNite, processes the thousands of images and produces output files that describe the location and lineage relationship of each nucleus at each time point. We have developed a companion software package, AceTree, which links the images and the annotations using tree representations of the lineage. This facilitates curation and editing of the lineage. AceTree also contains powerful visualization and interpretive tools, such as space filling models and tree-based expression patterning, that can be used to extract biological significance from the data. By pairing a fast lineaging program written in C with a user interface program written in Java we have produced a powerful software suite for exploring embryonic development.

The Processing of Airspace Concept Evaluations Using FASTE-CNS as a Pre- or Post-Simulation CNS Analysis Tool

NASA Technical Reports Server (NTRS)

Mainger, Steve

2004-01-01

As NASA speculates on and explores the future of aviation, the technological and physical aspects of our environment increasing become hurdles that must be overcome for success. Research into methods for overcoming some of these selected hurdles have been purposed by several NASA research partners as concepts. The task of establishing a common evaluation environment was placed on NASA's Virtual Airspace Simulation Technologies (VAST) project (sub-project of VAMS), and they responded with the development of the Airspace Concept Evaluation System (ACES). As one examines the ACES environment from a communication, navigation or surveillance (CNS) perspective, the simulation parameters are built with assumed perfection in the transactions associated with CNS. To truly evaluate these concepts in a realistic sense, the contributions/effects of CNS must be part of the ACES. NASA Glenn Research Center (GRC) has supported the Virtual Airspace Modeling and Simulation (VAMS) project through the continued development of CNS models and analysis capabilities which supports the ACES environment. NASA GRC initiated the development a communications traffic loading analysis tool, called the Future Aeronautical Sub-network Traffic Emulator for Communications, Navigation and Surveillance (FASTE-CNS), as part of this support. This tool allows for forecasting of communications load with the understanding that, there is no single, common source for loading models used to evaluate the existing and planned communications channels; and that, consensus and accuracy in the traffic load models is a very important input to the decisions being made on the acceptability of communication techniques used to fulfill the aeronautical requirements. Leveraging off the existing capabilities of the FASTE-CNS tool, GRC has called for FASTE-CNS to have the functionality to pre- and post-process the simulation runs of ACES to report on instances when traffic density, frequency congestion or aircraft spacing/distance violations have occurred. The integration of these functions require that the CNS models used to characterize these avionic system be of higher fidelity and better consistency then is present in FASTE-CNS system. This presentation will explore the capabilities of FASTE-CNS with renewed emphasis on the enhancements being added to perform these processing functions; the fidelity and reliability of CNS models necessary to make the enhancements work; and the benchmarking of FASTE-CNS results to improve confidence for the results of the new processing capabilities.

Breaching Around Corners: Engineer Operations in Urban Environments

DTIC Science & Technology

2003-09-01

determine what combinations of resources are available to accomplish the mission. The combat engineer vehicle (CEV) no longer provides rubble removal under ... armor . It is questionable whether the M9 armored combat earthmover (ACE) has the mass and traction to push rubble. Therefore, we need to explore

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

PubMed Central

Roca-Ho, Heleia; Riera, Marta; Palau, Vanesa; Pascual, Julio; Soler, Maria Jose

2017-01-01

Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS. PMID:28273875

The relationship between angiotensin-converting enzyme (ACE) insertion (I) / deletion (D) polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese.

PubMed

Zhang, Ya-Feng; Wang, Hong; Cheng, Qiong; Qin, Ling; Tang, Nelson Ls; Leung, Ping-Chong; Kwok, Timothy Cy

2017-01-01

In this study, we set out to investigate the relationship between angiotensin-converting enzyme ( ACE) I/D polymorphism, serum ACE activity and bone mineral density (BMD) in older Chinese. A standardized, structured, face-to-face interview was performed to collect demographic information. BMD was measured using dual-energy X-ray absorptiometry (DXA). I/D genotypes of ACE were determined by polymerase chain reaction (PCR) amplification. Serum ACE activity was determined photometrically by a commercially available kinetic kit. Multiple linear regression analysis was used to examine the relationship between ACE I/D polymorphism, serum ACE activity and BMD. A total of 1567 males and 1760 females were selected for analyzing the relationship between ACE I/D polymorphism and BMD. There was no significant difference in spine BMD, total hip BMD and femur neck BMD among different ACE I/D genotypes both in males and females. A total of 1699 males and 1739 females were selected for analyzing the relationship between serum ACE activity and BMD. There was also no significant difference in spine BMD, total hip BMD and femur neck BMD among different serum ACE activity groups both in males and females. There was no relationship between ACE I/D polymorphism, serum ACE activity and BMD in older Chinese.

Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse.

PubMed

Roca-Ho, Heleia; Riera, Marta; Palau, Vanesa; Pascual, Julio; Soler, Maria Jose

2017-03-05

Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.

Biomarkers in Lake Van sediments reveal dry conditions in eastern Anatolia during 110.000-10.000 years B.P.

NASA Astrophysics Data System (ADS)

Randlett, Marie-Eve; Bechtel, Achim; van der Meer, Marcel T. J.; Peterse, Francien; Litt, Thomas; Pickarski, Nadine; Kwiecien, Ola; Stockhecke, Mona; Wehrli, Bernhard; Schubert, Carsten J.

2017-02-01

Lipid biomarkers were analyzed in Lake Van sediments covering the last 600 ka, with a focus on the period between 110 and 10 ka, when a broad maximum in pore water salinity as a relict from the past suggests dry conditions. The occurrence and distribution of biomarkers indicative for terrestrial plants (long-chain n-alkane C29), haptophyte algae (methyl alkenones C37) and halophilic archaea (archaeol) all point toward a dry climate in Lake Van region during this time interval. The hydrogen isotopic composition of C29 n-alkanes (δDC29) and C37 alkenones (δDC37) is enriched between MIS 4 and MIS 2, which is interpreted as a decrease in the regional ratio of precipitation to evaporation. Similarly, the low abundance of the acyclic glycerol dialkyl glycerol tetraether GDGT-0 relative to archaeol, quantified by the Archaeol and Caldarchaeol Ecometric (ACE) is assumed to reflect the presence of halophilic euryarchaeota adapted to high salinity water. The climate around Lake Van appears in phase with the Yammouneh basin 800 km southwest and Lake Urmia 250 km southeast of Lake Van over the last two glacial periods. The results highlight the potential of combining ACE, δDC29, and δDC37 for reconstructing salinity changes and regional precipitation to evaporation ratio from lake sediments.

Angiotensin-converting enzyme activity in Cavalier King Charles Spaniels with an ACE gene polymorphism and myxomatous mitral valve disease.

PubMed

Meurs, Kathryn M; Olsen, Lisbeth H; Reimann, Maria J; Keene, Bruce W; Atkins, Clarke E; Adin, Darcy; Aona, Brent; Condit, Julia; DeFrancesco, Teresa; Reina-Doreste, Yamir; Stern, Joshua A; Tou, Sandra; Ward, Jessica; Woodruff, Kathleen

2018-02-01

Myxomatous mitral valve disease (MMVD) is the most common heart disease in the dog. It is particularly common in the Cavalier King Charles Spaniel (CKCS) breed and affected dogs are frequently managed with angiotensin-converting enzyme inhibitors (ACE-I). We have previously identified a canine ACE gene polymorphism associated with a decrease in angiotensin-converting enzyme (ACE) activity. The aim of this study was to evaluate for the prevalence of the ACE polymorphism in CKCS with mitral valve disease and to determine whether the presence of the polymorphism is associated with alterations in ACE activity at different stages of cardiac disease. Seventy-three dogs with a diagnosis of mitral valve disease were evaluated and a blood sample was drawn for ACE polymorphism genotyping and ACE activity measurement. Forty-three dogs were homozygous for the ACE polymorphism; five were heterozygous and 25 were homozygous wild type. The mean age and the median severity of disease were not different for dogs with the polymorphism and dogs with the wild-type sequence. The median baseline ACE activity was significantly lower for the ACE polymorphism (27.0 U/l) than the wild-type sequence dogs (31.0 U/l) (P=0.02). Dogs with more severe disease and the ACE polymorphism had significantly lower levels of ACE activity than dogs with the wild-type sequence (P=0.03). The CKCS appears to have a high prevalence of the ACE variant. Dogs with the ACE variant had lower levels of ACE activity even in more advanced mitral valve disease than dogs without the variant. The clinical significance of this finding and its impact on the need for ACE-I in dogs with the polymorphism and heart disease deserves further study.

Estradiol, acting through ERα, induces endothelial non-classic renin-angiotensin system increasing angiotensin 1-7 production.

PubMed

Mompeón, Ana; Lázaro-Franco, Macarena; Bueno-Betí, Carlos; Pérez-Cremades, Daniel; Vidal-Gómez, Xavier; Monsalve, Elena; Gironacci, Mariela M; Hermenegildo, Carlos; Novella, Susana

2016-02-15

Intracellular renin-angiotensin system (RAS) can operate independently of the circulating RAS. Estrogens provide protective effects by modulating the RAS. Our aim was to investigate the effect of estradiol (E2) on angiotensin converting enzymes (ACE) 1 and ACE2 expression and activities in human endothelial cells (HUVEC), and the role of estrogen receptors (ER). The results confirmed the presence of active intracellular RAS in HUVEC. Physiological concentrations of E2 induced a concentration-dependent increase of ACE1 and ACE2 mRNA expression and ACE1, but not ACE2, protein levels. ACE1 and ACE2 enzymatic activities were also induced with E2. These effects were mediated through ERα activation, since ER antagonists ICI 182780 and MPP completely abolished the effect of E2. Moreover, the ERα agonist PPT mirrored the E2 effects on ACE1 and ACE2 protein expression and activity. Exposure of endothelial cells to E2 significantly increased Ang-(1-7) production. In conclusion, E2 increases Ang-(1-7) production, through ERα, involving increased ACE1 and ACE2 mRNA expression and activity and ACE1 protein levels. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

America's Children and the Environment

MedlinePlus

... Labs and Research Centers America's Children and the Environment (ACE) Contact Us Share ACE presents key information ... of updates to ACE . America's Children and the Environment (ACE) America's Children and the Environment (ACE) is ...

Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitor-Based Treatment on Cardiovascular Outcomes in Hypertensive Blacks versus Whites

PubMed Central

Ogedegbe, Gbenga; Shah, Nirav R.; Phillips, Christopher; Goldfeld, Keith; Roy, Jason; Guo, Yu; Gyamfi, Joyce; Torgersen, Christopher; Capponi, Louis; Bangalore, Sripal

2015-01-01

BACKGROUND Clinical trial evidence suggests poorer outcomes in blacks compared to whites when treated with angiotensin-converting enzyme (ACE) inhibitor-based regimen, but this has not been evaluated in clinical practice. OBJECTIVES We evaluated the comparative effectiveness of an ACE inhibitor-based regimen on a composite outcome of all-cause mortality, stroke, and acute myocardial infarction (AMI) in hypertensive blacks compared to whites. METHODS We conducted a retrospective cohort study of 434,646 patients in a municipal health care system. Four exposure groups (Black-ACE, Black-NoACE, White-ACE, White-NoACE) were created based on race and treatment exposure (ACE or NoACE). Risk of the composite outcome and its components was compared across treatment groups and race using weighted Cox proportional hazard models. RESULTS Our analysis included 59,316 new users of ACE inhibitors, 47% of whom were black. Baseline characteristics were comparable for all groups after inverse probability weighting adjustment. For the composite outcome, the race treatment interaction was significant (p = 0.04); ACE use in blacks was associated with poorer cardiovascular outcomes (ACE vs. NoACE: 8.69% vs. 7.74%; p = 0.05) but not in whites (6.40% vs. 6.74%; p = 0.37). Similarly, the Black-ACE group had higher rates of AMI (0.46% vs. 0.26%; p = 0.04), stroke (2.43% vs. 1.93%; p = 0.05) and chronic heart failure (3.75% vs. 2.25%; p < 0.0001) than the Black-NoACE group. However, the Black-ACE group was no more likely to develop adverse effects than the White-ACE group. CONCLUSIONS ACE inhibitor-based therapy was associated with poorer cardiovascular outcomes in hypertensive blacks but not in whites. These findings confirm clinical trial evidence that hypertensive blacks have poorer outcomes than whites when treated with an ACE inhibitor-based regimen. PMID:26361152

Mental Health Among Help-Seeking Urban Women: The Relationships Between Adverse Childhood Experiences, Sexual Abuse, and Suicidality.

PubMed

Hamdullahpur, Kevin; Jacobs, Kahá Wi J; Gill, Kathryn J

2018-03-01

Adverse childhood experiences (ACEs) and adult mental health were explored in a sample of urban Aboriginal ( n = 83) and non-Aboriginal ( n = 89) women. Childhood sexual abuse (CSA) was associated with negative home environments, teenage pregnancy, lifetime suicide attempts, and treatment seeking. Aboriginal women with CSA witnessed higher levels of physical/sexual abuse of family members. The severity of current psychological distress was associated with a history of childhood neglect. The results indicate that CSA rarely occurs in isolation, and that multiple ACEs are strongly associated with suicide attempts and treatment seeking in adulthood. Future studies should focus on the role of CSA in suicidality, as well as familial, community, and cultural protective factors.

ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy.

PubMed

Rahimi, Zohreh

2012-10-01

Angiotensin converting enzyme (ACE) gene encodes ACE, a key component of renin angiotensin system (RAS), plays an important role in blood pressure homeostasis by generating the vasoconstrictor peptide angiotensin II. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.

What's Educational Leadership without an African-Centered Perspective? Explorations and Extrapolations

ERIC Educational Resources Information Center

Hopson, Rodney K. M.; Hotep, Uhuru; Schneider, Dana L.; Turenne, Ithamar Grace

2010-01-01

This article provides an overview of current issues confronting educational leaders dedicated to the fundamentals, curriculum, pedagogy, and practices of African-centered education (ACE) and its evolving nature in the 21st century. By considering and situating African-centered leadership in the discussion of educational leadership generally, and…

Investigation into the Mechanism of Homo- and Heterodimerization of Angiotensin-Converting Enzyme.

PubMed

Abrie, J Albert; Moolman, Wessel J A; Cozier, Gyles E; Schwager, Sylva L; Acharya, K Ravi; Sturrock, Edward D

2018-04-01

Angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin system (RAS), which is primarily responsible for blood pressure homeostasis. Studies have shown that ACE inhibitors yield cardiovascular benefits that cannot be entirely attributed to the inhibition of ACE catalytic activity. It is possible that these benefits are due to interactions between ACE and RAS receptors that mediate the protective arm of the RAS, such as angiotensin II receptor type 2 (AT 2 R) and the receptor MAS. Therefore, in this study, we investigated the molecular interactions of ACE, including ACE homodimerization and heterodimerization with AT 2 R and MAS, respectively. Molecular interactions were assessed by fluorescence resonance energy transfer and bimolecular fluorescence complementation in human embryonic kidney 293 cells and Chinese hamster ovary-K1 cells transfected with vectors encoding fluorophore-tagged proteins. The specificity of dimerization was verified by competition experiments using untagged proteins. These techniques were used to study several potential requirements for the germinal isoform of angiotensin-converting enzyme expressed in the testes (tACE) dimerization as well as the effect of ACE inhibitors on both somatic isoforms of angiotensin-converting enzyme expressed in the testes (sACE) and tACE dimerization. We demonstrated constitutive homodimerization of sACE and of both of its domains separately, as well as heterodimerization of both sACE and tACE with AT 2 R, but not MAS. In addition, we investigated both soluble sACE and the sACE N domain using size-exclusion chromatography-coupled small-angle X-ray scattering and we observed dimers in solution for both forms of the enzyme. Our results suggest that ACE homo- and heterodimerization does occur under physiologic conditions. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Profiles of childhood adversities in pathological gamblers - A latent class analysis.

PubMed

Lotzin, Annett; Ulas, Mehmet; Buth, Sven; Milin, Sascha; Kalke, Jens; Schäfer, Ingo

2018-06-01

Despite of high rates of adverse childhood experiences (ACEs) in pathological gamblers, researchers have rarely studied which types of ACEs often co-occur and how these profiles of ACEs are related to current psychopathology. We aimed to identify profiles of ACEs in pathological gamblers and examined how these profiles were related to gambling-related characteristics and current general psychopathology. In 329 current or lifetime pathological gamblers, diagnosed with the Composite Diagnostic Interview for DSM-IV, 10 types of ACEs were measured using the Adverse Childhood Experiences Questionnaire. Global psychopathology was assessed using the Symptom Checklist SCL-27. ACE profiles were identified using latent class analysis. Differences between ACE profiles in gambling-related characteristics and global psychopathology were analyzed using MANOVA. We found that four out of five gamblers (n=257, 78.1%) reported at least one ACE. Four distinct ACE profiles were identified: 'Low ACE', 'High ACE', 'Physical and emotional abuse', and 'Neglect'. The number of the fulfilled pathological gambling criteria and the severity of current global psychopathology differed between the ACE profiles: Gamblers with a 'High ACE' profile fulfilled more pathological gambling criteria and showed a more severe current psychopathology than gamblers of the 'Low ACE' profile. Gamblers with a 'Physical and emotional abuse' or an 'Emotion neglect' profile showed an intermediate severity of psychopathology. Our findings indicate that four different ACE profiles can be distinguished in pathological gamblers that differed in their gambling-related characteristics and current psychopathology. Systematic assessment of profiles of ACEs in pathological gamblers may inform about the severity of current global psychopathology that might be important to be addressed in addition to gambling-specific treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gestational Protein Restriction Increases Angiotensin II Production in Rat Lung1

PubMed Central

Gao, Haijun; Yallampalli, Uma; Yallampalli, Chandra

2013-01-01

ABSTRACT Gestational protein restriction (PR) alters the renin-angiotensin system in uterine arteries and placentas and elevates plasma levels of angiotensin II in pregnant rats. To date, how PR increases maternal plasma levels of angiotensin II remains unknown. In this study, we hypothesize that the expression and/or the activity of angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE) in lungs, but not kidneys and blood, largely contribute to elevated plasma angiotensin II levels in pregnant rats subject to gestational PR. Time-scheduled pregnant Sprague-Dawley rats were fed a normal or low-protein diet from Day 3 of pregnancy until euthanized at Day 19 or 22. Expressions of Ace and Ace2 (angiotens in I converting enzyme [peptidyl-dipeptidase A] 2) in lungs and kidneys from pregnant rats by quantitative real-time PCR and Western blotting, and the activities of these proteins in lungs, kidneys, and plasma, were measured. The mRNA levels of Ace and Ace2 in lungs were elevated by PR at both Days 19 and 22 of pregnancy. The abundance of ACE protein in lungs was increased, but ACE2 protein was decreased, by PR. The activities of ACE, but not ACE2, in lungs were increased by PR. PR did not change expressions of Ace and Ace2, the activities of both ACE and ACE2 in kidneys, and the abundance and activity of plasma ACE. These findings suggest that maternal lungs contribute to the elevated plasma levels of angiotensin II by increasing both the expression and the activity of ACE in response to gestational PR. PMID:23365412

A Novel Angiotensin I-Converting Enzyme Mutation (S333W) Impairs N-Domain Enzymatic Cleavage of the Anti-Fibrotic Peptide, AcSDKP

PubMed Central

Danilov, Sergei M.; Wade, Michael S.; Schwager, Sylva L.; Douglas, Ross G.; Nesterovitch, Andrew B.; Popova, Isolda A.; Hogarth, Kyle D.; Bhardwaj, Nakul; Schwartz, David E.; Sturrock, Edward D.; Garcia, Joe G. N.

2014-01-01

Background Angiotensin I-converting enzyme (ACE) has two functional N- and C-domain active centers that display differences in the metabolism of biologically-active peptides including the hemoregulatory tetrapeptide, Ac-SDKP, hydrolysed preferentially by the N domain active center. Elevated Ac-SDKP concentrations are associated with reduced tissue fibrosis. Results We identified a patient of African descent exhibiting unusual blood ACE kinetics with reduced relative hydrolysis of two synthetic ACE substrates (ZPHL/HHL ratio) suggestive of the ACE N domain center inactivation. Inhibition of blood ACE activity by anti-catalytic mAbs and ACE inhibitors and conformational fingerprint of blood ACE suggested overall conformational changes in the ACE molecule and sequencing identified Ser333Trp substitution in the N domain of ACE. In silico analysis demonstrated S333W localized in the S1 pocket of the active site of the N domain with the bulky Trp adversely affecting binding of ACE substrates due to steric hindrance. Expression of mutant ACE (S333W) in CHO cells confirmed altered kinetic properties of mutant ACE and conformational changes in the N domain. Further, the S333W mutant displayed decreased ability (5-fold) to cleave the physiological substrate AcSDKP compared to wild-type ACE. Conclusions and Significance A novel Ser333Trp ACE mutation results in dramatic changes in ACE kinetic properties and lowered clearance of Ac-SDKP. Individuals with this mutation (likely with significantly increased levels of the hemoregulatory tetrapeptide in blood and tissues), may confer protection against fibrosis. PMID:24505347

Up-Regulation of Angiotensin-Converting Enzyme (ACE) Enhances Cell Proliferation and Predicts Poor Prognosis in Laryngeal Cancer.

PubMed

Han, Chao-Dong; Ge, Wen-Sheng

2016-11-01

BACKGROUND The angiotensin-converting enzyme (ACE, CD143) gene plays a crucial role in the pathology of many cancers. Previous studies mostly focused on the gene polymorphism, but the other functions of ACE have rarely been reported. The purpose of this study was to investigate the expression of ACE and its biological function, as well as its prognostic value, in laryngeal cancer. MATERIAL AND METHODS The expression of ACE was detected by quantitative real-time polymerase chain reaction (qRT-PCR) analysis in 106 patients with laryngeal cancer and 85 healthy people. Then the cell proliferation was estimated after the cell lines Hep-2 were transfected with pGL3-ACE and empty vector, respectively. In addition, the relationship between ACE expression and clinicopathologic characteristics was analyzed. Finally, Kaplan-Meier analysis was used to evaluate the overall survival of patients with different ACE expression, while Cox regression analysis was conducted to reveal the prognostic value of ACE in laryngeal cancer. RESULTS Our results demonstrate that ACE is over-expressed in laryngeal cancer and thus promotes cell proliferation. The up-regulation of ACE was significantly influenced by tumor stage and lymph node metastasis. Patients with high ACE expression had a shorter overall survival compared with those with low ACE expression according to Kaplan-Meier analysis. The ACE gene was also found to be an important factor in the prognosis of laryngeal cancer. CONCLUSIONS Our study shows that the ACE gene was up-regulated, which promoted the cell proliferation, and it could be an independent prognostic marker in laryngeal cancer.

Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita.

PubMed

Cui, Ruqiang; Zhang, Lei; Chen, Yuyan; Huang, Wenkun; Fan, Chengming; Wu, Qingsong; Peng, Deliang; da Silva, Washington; Sun, Xiaotang

2017-05-01

The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant. Copyright © 2017. Published by Elsevier Inc.

Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity

PubMed Central

Giani, Jorge F.; Eriguchi, Masahiro; Bernstein, Ellen A.; Katsumata, Makoto; Shen, Xiao Z.; Li, Liang; McDonough, Alicia A.; Fuchs, Sebastien; Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.

2017-01-01

Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension. PMID:27988209

Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease.

PubMed

Wang, Wang; Patel, Vaibhav B; Parajuli, Nirmal; Fan, Dong; Basu, Ratnadeep; Wang, Zuocheng; Ramprasath, Tharmarajan; Kassiri, Zamaneh; Penninger, Josef M; Oudit, Gavin Y

2014-08-01

Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby negatively regulating the renin-angiotensin system. However, heart disease in humans and in animal models is associated with only a partial loss of ACE2. ACE2 is an X-linked gene; and as such, we tested the clinical relevance of a partial loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote) mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and worsening systolic and diastolic dysfunction. These changes were associated with increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene expression. In response to Ang II infusion, there was increased NADPH oxidase activity and myocardial fibrosis resulting in the worsening of Ang II-induced diastolic dysfunction with a preserved systolic function. Ang II-mediated cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-) hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2 and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response with increased vascular fibrosis and stiffness. Vascular superoxide and nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with increased vascular oxidative stress. These changes occurred with increased renal fibrosis and superoxide production. Partial heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease secondary to pressure overload and Ang II infusion. Heart disease in humans with idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure overload-induced heart disease. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial loss of ACE2 is sufficient to enhance the susceptibility to heart disease.

Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.

PubMed

Sun, Xiaoou; Wiesner, Burkhard; Lorenz, Dorothea; Papsdorf, Gisela; Pankow, Kristin; Wang, Po; Dietrich, Nils; Siems, Wolf-Eberhard; Maul, Björn

2008-12-01

Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.

N-Domain Isoform of Angiotensin I Converting Enzyme as a Marker of Hypertension: Populational Study

PubMed Central

Maluf-Meiken, Leila C. V.; Fernandes, Fernanda B.; Aragão, Danielle S.; Ronchi, Fernanda A.; Andrade, Maria C. C.; Franco, Maria C.; Febba, Andreia C. S.; Plavnik, Frida L.; Krieger, José E.; Mill, Jose G.; Sesso, Ricardo C. C.; Casarini, Dulce E.

2012-01-01

The aim of this paper was to investigate the presence of the urinary 90 kDa N-domain ACE in a cohort of the population from Vitoria, Brazil, to verify its association with essential hypertension since this isoform could be a possible genetic marker of hypertension. Anthropometric, clinical, and laboratory parameters of the individuals were evaluated (n = 1150) and the blood pressure (BP) was measured. The study population was divided according to ACE isoforms in urine as follows: ACE 65/90/190, presence of three ACE isoforms (n = 795), ACE 90+ (65/90) (n = 186), and ACE 90− (65/190) (n = 169) based on the presence (+) or absence (−) of the 90 kDa ACE isoform. The anthropometric parameters, lipid profile, serum levels of uric acid, glucose, and the systolic and diastolic BP were significantly greater in the ACE 90+ compared with the ACE 90− and ACE 65/90/190 individuals. We found that 98% of individuals from the ACE 90+ group and 38% from the ACE 65/90/190 group had hypertension, compared to only 1% hypertensive individuals in the ACE 90− group. There is a high presence of the 90 kDa N-domain ACE isoform (85%) in the studied population. The percentile of normotensive subjects with three isoforms was 62%. Our findings could contribute to the development of new efficient strategy to prevent and treat hypertension to avoid the development of cardiovascular disease. PMID:22666552

Angiotensin-I-converting enzyme and its relatives

PubMed Central

Riordan, James F

2003-01-01

Angiotensin-I-converting enzyme (ACE) is a monomeric, membrane-bound, zinc- and chloride-dependent peptidyl dipeptidase that catalyzes the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a carboxy-terminal dipeptide. ACE has long been known to be a key part of the renin angiotensin system that regulates blood pressure, and ACE inhibitors are important for the treatment of hypertension. There are two forms of the enzyme in humans, the ubiquitous somatic ACE and the sperm-specific germinal ACE, both encoded by the same gene through transcription from alternative promoters. Somatic ACE has two tandem active sites with distinct catalytic properties, whereas germinal ACE, the function of which is largely unknown, has just a single active site. Recently, an ACE homolog, ACE2, has been identified in humans that differs from ACE in being a carboxypeptidase that preferentially removes carboxy-terminal hydrophobic or basic amino acids; it appears to be important in cardiac function. ACE homologs (also known as members of the M2 gluzincin family) have been found in a wide variety of species, even in those that neither have a cardiovascular system nor synthesize angiotensin. X-ray structures of a truncated, deglycosylated form of germinal ACE and a related enzyme from Drosophila have been reported, and these show that the active site is deep within a central cavity. Structure-based drug design targeting the individual active sites of somatic ACE may lead to a new generation of ACE inhibitors, with fewer side-effects than currently available inhibitors. PMID:12914653

How the Timing of Climate Change Policy Affects Infrastructure Turnover in the Electricity Sector: Engineering, Economic and Policy Considerations

NASA Astrophysics Data System (ADS)

Izard, Catherine Finlay

The electricity sector is responsible for producing 35% of US greenhouse gas (GHG) emissions. Estimates suggest that ideally, the electricity sector would be responsible for approximately 85% of emissions abatement associated with climate polices such as America's Clean Energy and Security Act (ACES). This is equivalent to ˜50% cumulative emissions reductions below projected cumulative business-as-usual (BAU) emissions. Achieving these levels of emissions reductions will require dramatic changes in the US electricity generating infrastructure: almost all of the fossil-generation fleet will need to be replaced with low-carbon sources and society is likely to have to maintain a high build rate of new capacity for decades. Unfortunately, the inertia in the electricity sector means that there may be physical constraints to the rate at which new electricity generating capacity can be built. Because the build rate of new electricity generating capacity may be limited, the timing of regulation is critical---the longer the U.S. waits to start reducing GHG emissions, the faster the turnover in the electricity sector must occur in order to meet the same target. There is a real, and thus far unexplored, possibility that the U.S. could delay climate change policy implementation for long enough that it becomes infeasible to attain the necessary rate of turnover in the electricity sector. This dissertation investigates the relationship between climate policy timing and infrastructure turnover in the electricity sector. The goal of the dissertation is to answer the question: How long can we wait before constraints on infrastructure turnover in the electricity sector make achieving our climate goals impossible? Using the Infrastructure Flow Assessment Model, which was developed in this work, this dissertation shows that delaying climate change policy increases average retirements rates by 200-400%, increases average construction rates by 25-85% and increases maximum construction rates by 50-300%. It also shows that delaying climate policy has little effect on the age of retired plants or the stranded costs associated with premature retirement. In order for the electricity sector to reduce emissions to a level required by ACES while limiting construction rates to within achievable levels, it is necessary to start immediately. Delaying the process of decarbonization means that more abatement will be necessary from other sectors or geoengineering. By not starting emissions abatement early, therefore, the US forfeits its most accessible abatement potential and increases the challenge of climate change mitigation unnecessarily.

Wave Energy Prize - 1/20th Testing - AquaHarmonics

DOE Data Explorer

Scharmen, Wesley

2016-09-02

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the AquaHarmonics team, including the 1/20th scale test plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the Wave Energy Prize (WEP) winners.

Wave Energy Prize - 1/20th Testing - Waveswing America

DOE Data Explorer

Scharmen, Wesley

2016-08-19

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the Waveswing America team, including the 1/20th scale test plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the Wave Energy Prize (WEP) winners.

Wave Energy Prize - 1/20th Testing - M3 Wave

DOE Data Explorer

Wesley Scharmen

2016-08-12

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the M3 Wave team, including the 1/20th scale test plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the Wave Energy Prize (WEP) winners.

Wave Energy Prize - 1/20th Testing - Sea Potential

DOE Data Explorer

Scharmen, Wesley

2016-09-23

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the Sea Potential team, including the 1/20th scale test plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the Wave Energy Prize (WEP) winners.

Wave Energy Prize - 1/20th Testing - Oscilla Power

DOE Data Explorer

Scharmen, Wesley

2016-09-16

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the Oscilla Power team, including the 1/20th Test Plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the WEPrize winners.

Wave Energy Prize - 1/20th Testing - RTI Wave Power

DOE Data Explorer

Scharmen, Wesley

2016-09-30

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the RTI Wave Power team, including the 1/20th Test Plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the Wave Energy Prize (WEP) winners.

Wave Energy Prize - 1/20th Testing - Harvest Wave Energy

DOE Data Explorer

Wesley Scharmen

2016-08-26

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the Harvest Wave Energy team, including the 1/20th scale test plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the Wave Energy Prize (WEP) winners.

Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation.

PubMed

Rivière, Guillaume; Lienhard, Daniel; Andrieu, Thomas; Vieau, Didier; Frey, Brigitte M; Frey, Felix J

2011-04-01

Somatic angiotensin-converting enzyme (sACE) is crucial in cardiovascular homeostasis and displays a tissue-specific profile. Epigenetic patterns modulate genes expression and their alterations were implied in pathologies including hypertension. However, the influence of DNA methylation and chromatin condensation state on the expression of sACE is unknown. We examined whether such epigenetic mechanisms could participate in the control of sACE expression in vitro and in vivo. We identified two CpG islands in the human ace-1 gene 3 kb proximal promoter region. Their methylation abolished the luciferase activity of ace-1 promoter/reporter constructs transfected into human liver (HepG2), colon (HT29), microvascular endothelial (HMEC-1) and lung (SUT) cell lines (p < 0.001). Bisulphite sequencing revealed a cell-type specific basal methylation pattern of the ace-1 gene -1,466/+25 region. As assessed by RT-qPCR, inhibition of DNA methylation by 5-aza-2'-deoxycytidine and/or of histone deacetylation by trichostatin A highly stimulated sACE mRNA expression cell-type specifically (p < 0.001 vs. vehicle treated cells). In the rat, in vivo 5-aza-cytidine injections demethylated the ace-1 promoter and increased sACE mRNA expression in the lungs and liver (p = 0.05), but not in the kidney. In conclusion, the expression level of somatic ACE is modulated by CpG-methylation and histone deacetylases inhibition. The basal methylation pattern of the promoter of the ace-1 gene is cell-type specific and correlates to sACE transcription. DNMT inhibition is associated with altered methylation of the ace-1 promoter and a cell-type and tissue-specific increase of sACE mRNA levels. This study indicates a strong influence of epigenetic mechanisms on sACE expression.

ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone.

PubMed

Gadelha, Ary; Yonamine, Camila M; Ota, Vanessa K; Oliveira, Vitor; Sato, João Ricardo; Belangero, Sintia I; Bressan, Rodrigo A; Hayashi, Mirian A F

2015-05-01

Angiotensin-I converting enzyme (ACE) is a key component of the renin-angiotensin system (RAS). Although the several contradictory data, ACE has been associated with schizophrenia (SCZ) pathophysiology. Here the ACE activity of SCZ patients and healthy controls (HCs), and its possible correlations with the ACE polymorphism genotype and symptomatic dimensions, was investigated. ACE activity of 86 SCZ patients and 100 HCs paired by age, gender and educational level was measured, using the FRET peptide substrate and the specific inhibitor lisinopril. The ACE insertion/deletion (I/D) genotypes were assessed by the restriction fragment length polymorphism (RFLP) technique. Significantly higher ACE activity was observed in SCZ patients compared to HCs (t=-5.09; p<0.001). The area under the receiver operating characteristic (ROC) curve was 0.701. Mean ACE activity levels were higher for the D-allele carriers (F=5.570; p=0.005), but no significant difference was found among SCZ patients and HCs for genotypes frequencies (Chi-squared=2.08; df=2; p=0.35). Interestingly, we found that the difference between the measured ACE activity for each SCZ patient and the expected average mean value for each respective genotype group (for control subjects) was a better predictor of SCZ than the ACE dichotomized values (high/low) or ACE I/D. Our results suggest that higher levels of ACE activity are associated with SCZ with stronger impact when the genetic background of each individual is considered. This may explain the heterogeneity of the results on ACE previously reported. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina: A randomized placebo-controlled trial

PubMed Central

Suhrs, Elena; Raft, Kristoffer Flintholm; Høst, Nis; Prescott, Eva

2018-01-01

Objective Studies have suggested a beneficial effect of angiotensin-converting enzyme (ACE) inhibition. To explore whether the ACE inhibitor ramipril has a direct effect on the microvasculature beyond the blood pressure (BP) lowering effect, we investigated whether ramipril improved coronary microvascular function in normotensive women with coronary microvascular dysfunction (CMD). Methods We included 63 normotensive women with angina, no epicardial stenosis>50% and CMD defined as a coronary flow velocity reserve (CFVR)<2.2 assessed by adenosine stress-echocardiography in a randomized double-blinded, superiority trial with 1:1 allocation to placebo or ramipril (maximum dose 10 mg depending on blood pressure) for 24±6 weeks. Primary outcome was CFVR. Secondary outcomes were left ventricular systolic and diastolic function and symptoms evaluated by Seattle Angina Questionnaire (clinicaltrials.gov, NCT02525081). Results Follow-up was available on 55 patients. BP remained unchanged during treatment in both groups. CFVR improved in both the ramipril (p = 0.004) and placebo group (p = 0.026) with no difference between groups (p = 0.63). Symptoms improved in both groups with no significant between-group differences. No changes were detected in parameters of systolic and diastolic function. No serious adverse reactions were reported. Conclusions In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction. PMID:29883497

The NOAA Real-Time Solar-Wind (RTSW) System using ACE Data

NASA Astrophysics Data System (ADS)

Zwickl, R. D.; Doggett, K. A.; Sahm, S.; Barrett, W. P.; Grubb, R. N.; Detman, T. R.; Raben, V. J.; Smith, C. W.; Riley, P.; Gold, R. E.; Mewaldt, R. A.; Maruyama, T.

1998-07-01

The Advanced Composition Explorer (ACE) RTSW system is continuously monitoring the solar wind and produces warnings of impending major geomagnetic activity, up to one hour in advance. Warnings and alerts issued by NOAA allow those with systems sensitive to such activity to take preventative action. The RTSW system gathers solar wind and energetic particle data at high time resolution from four ACE instruments (MAG, SWEPAM, EPAM, and SIS), packs the data into a low-rate bit stream, and broadcasts the data continuously. NASA sends real-time data to NOAA each day when downloading science data. With a combination of dedicated ground stations (CRL in Japan and RAL in Great Britain), and time on existing ground tracking networks (NASA's DSN and the USAF's AFSCN), the RTSW system can receive data 24 hours per day throughout the year. The raw data are immediately sent from the ground station to the Space Environment Center in Boulder, Colorado, processed, and then delivered to its Space Weather Operations center where they are used in daily operations; the data are also delivered to the CRL Regional Warning Center at Hiraiso, Japan, to the USAF 55th Space Weather Squadron, and placed on the World Wide Web. The data are downloaded, processed and dispersed within 5 min from the time they leave ACE. The RTSW system also uses the low-energy energetic particles to warn of approaching interplanetary shocks, and to help monitor the flux of high-energy particles that can produce radiation damage in satellite systems.

Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

PubMed Central

Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

2015-01-01

Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1–7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1–7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation. PMID:26569234

Relationship between adverse early experiences, stressors, psychosocial resources and wellbeing.

PubMed

Mc Elroy, Sharon; Hevey, David

2014-01-01

The study examined a diathesis stress model of the relationship between adverse child experiences (ACEs), stressors and psychosocial resources to explore their relationship with wellbeing. A cross sectional study was conducted across two mental health and addiction treatment centers. 176 individuals were interviewed using a demographics form, SCID-DSM-IV(First, Spitzer, Gibbon, &Williams, 2002), Child Trauma Questionnaire (Bernstein & Fink, 1998), NEO-Five Factor Inventory (Costa & McCrae, 1992), Trait Emotional Intelligence Questionnaire (Petrides, 2009), The Coping, Inventory for Stressful Situations (CISS) (Endler & Parker, 1990), Recent Life Events Questionnaire (Department of Health, 1985) and perceived social support from family, friends and religion. Multiple, regressions and correlations were used to analyze the data. All early experiences, except physical, abuse and death of a parent in childhood, were significantly correlated with increased number of, stressors and lower wellbeing scores. This is possibly because of sample specific issues. Number of stressors partially mediated the relationship between ACEs and wellbeing. Increased number of ACEs was related to higher neuroticism and emotion-focused coping and lower conscientiousness, agreeableness, trait emotional intelligence and task coping scores. These resources were significantly related to increased stressors and lower wellbeing. Distraction and emotion coping significantly moderated the relationship between number of stressors and wellbeing. These findings support the diathesis stress model and indicate that there are significant relationships between ACEs, psychosocial, resources, stressors and wellbeing. Recommendations to improve wellbeing are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dependence of the Interplanetary Magnetic Field on Heliocentric Distance between 0.3 and 1.7 AU from MESSENGER, ACE and MAVEN data

NASA Astrophysics Data System (ADS)

Hanneson, C.; Johnson, C.; Al Asad, M.

2017-12-01

Magnetometer data from the MErcury Surface, Space ENvironment, GEochemistry and Ranging (MESSENGER), Advanced Composition Explorer (ACE) and Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft were used to characterize the variation of the interplanetary magnetic field (IMF) with heliocentric distance from 0.3 to 1.7 AU. MESSENGER and ACE data form a set of simultaneous observations that spans eight years, from March 2007 until April 2015, with ACE observations continuing until the present. MAVEN data have been collected since November 2014. Furthermore, for the period 2008-2015, MESSENGER and ACE observations were taken over the same range of heliocentric distances: 0.31-0.47 AU and 0.94-1.00 AU respectively. The IMF varies with the solar sunspot cycle, and so data taken simultaneously at different heliocentric distances allow solar-cycle effects to be decoupled from the radial evolution of the IMF. The data were averaged temporally by taking 1-hour means, and median values were then computed in 0.01-AU bins. For the time interval spanned by all observations, the median value of the magnitude of the IMF decreases steadily from 30.1 nT at 0.3 AU to 4.3 nT at 1.0 AU and 2.5 nT at 1.6 AU. The magnitude of the IMF was found to decay with heliocentric distance according to an inverse power law with an exponent equal to the adiabatic index for an ideal monatomic gas, 5/3, within 95% confidence limits. The magnitude of the radial component decays with distance as an inverse square law within 95% confidence limits. We also consider temporal variations of the heliocentric-dependence of the IMF over the current solar cycle by computing power law fits to the simultaneous MESSENGER and ACE observations using a moving window. Our study complements the recent study of Gruesbeck et al. (2017) that used Juno data to consider the variation in IMF properties over the heliocentric distance range 1 to 6 AU.

Short- and long-term effects of the modified swedish version of the Active Communication Education (ACE) program for adults with hearing loss.

PubMed

Oberg, Marie; Bohn, Therese; Larsson, Ulrika

2014-10-01

In Sweden, there is a lack of evidence-based rehabilitation programs for hearing loss. The Active Communication Education program (ACE) has successfully been used in Australia and was translated and evaluated in a Swedish pilot study. The pilot study included 23 participants (age 87 yr). No statistically significant effects were found, but the qualitative assessments indicated that this population found the program to be beneficial. The participants requested more focus on the psychosocial consequences of hearing loss, and the modules in the original ACE program were modified. The aim of this study was to explore the effects of a modified Swedish version of the ACE program in a population aged 39-82 yr old. Design was a between-group and within-group intervention study. The participants were recruited from the hearing health clinic in Linköping during 2010 and 2012. A total of 73 participants agreed to undergo the ACE, and 67 (92%) completed three or more sessions. The ACE program consists of five weekly 2 hr group sessions with 6 to 10 participants per group. The outcomes were measured before initiation of the program, 3 wk after program completion, and 6 mo after program completion and included communication strategy use, activity and participation, health-related quality of life, and anxiety and depression. In addition, outcomes were measured after program completion using the International Outcome Inventory-Alternative Interventions, a modified version of the Client Oriented Scale of Improvement, and qualitative feedback was obtained about the response to the program and actions taken as a result of participation. The treatment effects were examined using repeated-measures analyses of variance. Statistically significant effects were found for communication strategy use, activity and participation, and psychosocial well-being. Statistically significant effects were found for gender and degree of hearing loss, indicating that women and those with mild hearing loss significantly improved communication strategies. It is suggested that the program be implemented as part of regular audiological rehabilitation and offered in an early stage of rehabilitation. American Academy of Audiology.

Somatic ACE regulates self-renewal of mouse spermatogonial stem cells via the MAPK signaling pathway.

PubMed

Gao, Tingting; Zhao, Xin; Liu, Chenchen; Shao, Binbin; Zhang, Xi; Li, Kai; Cai, Jinyang; Wang, Su; Huang, Xiaoyan

2018-05-24

Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in regulation of the renin-angiotensin system. Here, we used RT-PCR and Western blot analysis to confirm that somatic ACE (sACE) but not testicular ACE (tACE) is highly expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs. Treating cultured SSCs with the ACE competitive inhibitor captopril was found to inhibit sACE activity, and significantly reduced the proliferation rate of SSCs. Microarray analysis identified 651 genes with significant differential expression. KEGG pathway analysis showed that these differentially expressed genes are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway and cell cycle. sACE was found to play an important role in SSC self-renewal via the regulation of MAPK-dependent cell proliferation.

Angiotensin converting enzyme immobilized on magnetic beads as a tool for ligand fishing.

PubMed

de Almeida, Fernando G; Vanzolini, Kenia L; Cass, Quezia B

2017-01-05

Angiotensin converting enzyme (ACE) presents an important role in blood pressure regulation, since that converts angiotensin I to the vasoconstrictor angiotensin II. Some commercially available ACE inhibitors are captopril, lisinopril and enalapril; due to their side effects, naturally occurring inhibitors have been prospected. In order to endorse this research field we have developed a new tool for ACE ligand screening. To this end, ACE was extracted from bovine lung, purified and chemically immobilized in modified ferrite magnetic beads (ACE-MBs). The ACE-MBs have shown a Michaelian kinetic behavior towards hippuryl-histidyl-leucine. Moreover, as proof of concept, the ACE-MBs was inhibited by lisinopril with a half maximal inhibitory concentration (IC 50 ) of 10nM. At the fishing assay, ACE-MBs were able not only to fish out the reference inhibitor, but also one peptide from a pool of tryptic digested BSA. In conclusion, ACE-MBs emerge as new straightforward tool for ACE kinetics determination, inhibition and binder screening. Copyright © 2016 Elsevier B.V. All rights reserved.

Serine proteases as candidates for proteolytic processing of angiotensin-I converting enzyme.

PubMed

Aragão, Danielle S; de Andrade, Maria Claudina C; Ebihara, Fabiana; Watanabe, Ingrid K M; Magalhães, Dayane C B P; Juliano, Maria Aparecida; Hirata, Izaura Yoshico; Casarini, Dulce Elena

2015-01-01

Somatic angiotensin-I converting enzyme (sACE) is a broadly distributed peptidase which plays a role in blood pressure and electrolyte homeostasis by the conversion of angiotensin I into angiotensin II. N-domain isoforms (nACE) with 65 and 90 kDa have been described in body fluids, tissues and mesangial cells (MC), and a 90 kDa nACE has been described only in spontaneously hypertensive rats. The aim of this study was to investigate the existence of proteolytic enzymes that may act in the hydrolysis of sACE generating nACEs in MC. After the confirmation of the presence of ACE sheddases in Immortalized MC (IMC), we purified and characterized these enzymes using fluorogenic substrates specifically designed for ACE sheddases. Purified enzyme identified as a serine protease by N-terminal sequence was able to generate nACE. In the present study, we described for the first time the presence of ACE sheddases in IMC, identified as serine proteases able to hydrolyze sACE in vitro. Further investigations are necessary to elucidate the mechanisms responsible for the expression and regulation of ACE sheddases in MC and their roles in the generation of nACEs, especially the 90 kDa form possibly related to hypertension. Copyright © 2014 Elsevier B.V. All rights reserved.

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

PubMed Central

Ong, Frank S.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Giani, Jorge F.; Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sebastien

2013-01-01

Angiotensin-converting enzyme (ACE) is a zinc-dependent peptidase responsible for converting angiotensin I into the vasoconstrictor angiotensin II. However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. The defining feature of ACE is that it is composed of two homologous and independently catalytic domains, the result of an ancient gene duplication, and ACE-like genes are widely distributed in nature. The two ACE catalytic domains contribute to the wide substrate diversity of ACE and, by extension, the physiologic impact of the enzyme. Several studies suggest that the two catalytic domains have different biologic functions. Recently, the X-ray crystal structure of ACE has elucidated some of the structural differences between the two ACE domains. This is important now that ACE domain-specific inhibitors have been synthesized and characterized. Once widely available, these reagents will undoubtedly be powerful tools for probing the physiologic actions of each ACE domain. In turn, this knowledge should allow clinicians to envision new therapies for diseases not currently treated with ACE inhibitors. PMID:23257181

Unpacking the impact of adverse childhood experiences on adult mental health.

PubMed

Merrick, Melissa T; Ports, Katie A; Ford, Derek C; Afifi, Tracie O; Gershoff, Elizabeth T; Grogan-Kaylor, Andrew

2017-07-01

Exposure to childhood adversity has an impact on adult mental health, increasing the risk for depression and suicide. Associations between Adverse Childhood Experiences (ACEs) and several adult mental and behavioral health outcomes are well documented in the literature, establishing the need for prevention. The current study analyzes the relationship between an expanded ACE score that includes being spanked as a child and adult mental health outcomes by examining each ACE separately to determine the contribution of each ACE. Data were drawn from Wave II of the CDC-Kaiser ACE Study, consisting of 7465 adult members of Kaiser Permanente in southern California. Dichotomous variables corresponding to each of the 11 ACE categories were created, with ACE score ranging from 0 to 11 corresponding to the total number of ACEs experienced. Multiple logistic regression modeling was used to examine the relationship between ACEs and adult mental health outcomes adjusting for sociodemographic covariates. Results indicated a graded dose-response relationship between the expanded ACE score and the likelihood of moderate to heavy drinking, drug use, depressed affect, and suicide attempts in adulthood. In the adjusted models, being spanked as a child was significantly associated with all self-reported mental health outcomes. Over 80% of the sample reported exposure to at least one ACE, signifying the potential to capture experiences not previously considered by traditional ACE indices. The findings highlight the importance of examining both cumulative ACE scores and individual ACEs on adult health outcomes to better understand key risk and protective factors for future prevention efforts. Copyright © 2017. Published by Elsevier Ltd.

Acetylcholinesterase genes within the Diptera: takeover and loss in true flies

PubMed Central

Huchard, Elise; Martinez, Michel; Alout, Haoues; Douzery, Emmanuel J.P; Lutfalla, Georges; Berthomieu, Arnaud; Berticat, Claire; Raymond, Michel; Weill, Mylène

2006-01-01

It has recently been reported that the synaptic acetylcholinesterase (AChE) in mosquitoes is encoded by the ace-1 gene, distinct and divergent from the ace-2 gene, which performs this function in Drosophila. This is an unprecedented situation within the Diptera order because both ace genes derive from an old duplication and are present in most insects and arthropods. Nevertheless, Drosophila possesses only the ace-2 gene. Thus, a secondary loss occurred during the evolution of Diptera, implying a vital function switch from one gene (ace-1) to the other (ace-2). We sampled 78 species, representing 50 families (27% of the Dipteran families) spread over all major subdivisions of the Diptera, and looked for ace-1 and ace-2 by systematic PCR screening to determine which taxonomic groups within the Diptera have this gene change. We show that this loss probably extends to all true flies (or Cyclorrhapha), a large monophyletic group of the Diptera. We also show that ace-2 plays a non-detectable role in the synaptic AChE in a lower Diptera species, suggesting that it has non-synaptic functions. A relative molecular evolution rate test showed that the intensity of purifying selection on ace-2 sequences is constant across the Diptera, irrespective of the presence or absence of ace-1, confirming the evolutionary importance of non-synaptic functions for this gene. We discuss the evolutionary scenarios for the takeover of ace-2 and the loss of ace-1, taking into account our limited knowledge of non-synaptic functions of ace genes and some specific adaptations of true flies. PMID:17002944

Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development.

PubMed

Heisenberg, C P; Brennan, C; Wilson, S W

1999-05-01

During the development of the zebrafish nervous system both noi, a zebrafish pax2 homolog, and ace, a zebrafish fgf8 homolog, are required for development of the midbrain and cerebellum. Here we describe a dominant mutation, aussicht (aus), in which the expression of noi and ace is upregulated. In aus mutant embryos, ace is upregulated at many sites in the embryo, while noi expression is only upregulated in regions of the forebrain and midbrain which also express ace. Subsequent to the alterations in noi and ace expression, aus mutants exhibit defects in the differentiation of the forebrain, midbrain and eyes. Within the forebrain, the formation of the anterior and postoptic commissures is delayed and the expression of markers within the pretectal area is reduced. Within the midbrain, En and wnt1 expression is expanded. In heterozygous aus embryos, there is ectopic outgrowth of neural retina in the temporal half of the eyes, whereas in putative homozygous aus embryos, the ventral retina is reduced and the pigmented retinal epithelium is expanded towards the midline. The observation that aus mutant embryos exhibit widespread upregulation of ace raised the possibility that aus might represent an allele of the ace gene itself. However, by crossing carriers for both aus and ace, we were able to generate homozygous ace mutant embryos that also exhibited the aus phenotype. This indicated that aus is not tightly linked to ace and is unlikely to be a mutation directly affecting the ace locus. However, increased Ace activity may underly many aspects of the aus phenotype and we show that the upregulation of noi in the forebrain of aus mutants is partially dependent upon functional Ace activity. Conversely, increased ace expression in the forebrain of aus mutants is not dependent upon functional Noi activity. We conclude that aus represents a mutation involving a locus normally required for the regulation of ace expression during embryogenesis.

Association of Urinary N-Domain Angiotensin I-Converting Enzyme with Plasma Inflammatory Markers and Endothelial Function

PubMed Central

Fernandes, Fernanda B; Plavnik, Frida L; Teixeira, Andressa MS; Christofalo, Dejaldo MJ; Ajzen, Sergio A; Higa, Elisa MS; Ronchi, Fernanda A; Sesso, Ricardo CC; Casarini, Dulce E

2008-01-01

The aim of this study was to investigate the association between urinary 90 kDa N-domain Angiotensin I-converting enzyme (ACE) form with C-reactive protein (CRP) and homocysteine plasma levels (Hcy), urinary nitric oxide (NOu), and endothelial function (EF) in normotensive subjects. Forty healthy subjects were evaluated through brachial Doppler US to test the response to reactive hyperemia and a panel of blood tests to determine CRP and Hcy levels, NOu, and urinary ACE. They were divided into groups according to the presence (ACE90+) or absence (ACE90–) of the 90 kDa ACE, the presence (FH+) or absence (FH–) of family history of hypertension, and the presence or absence of these two variables FH+/ACE90+ and FH–/ACE90–. We found an impaired endothelial dilatation in subjects who presented the 90 kDa N-domain ACE as follows: 11.4% ± 5.3% in ACE90+ compared with 17.6% ± 7.1% in ACE90– group and 12.4% ± 5.6% in FH+/ACE90+ compared with 17.7% ± 6.2% in FH–/ACE90– group, P < 0.05. Hcy and CRP levels were statistically significantly lower in FH+/ACE90+ than in FH–/ACE90– group, as follows: 10.0 ± 2.3 μM compared with 12.7 ± 1.5 μM, and 1.3 ± 1.8 mg/L compared with 3.6 ± 2.0 mg/L, respectively. A correlation between flow-mediated dilatation (FMD) and CRP, Hcy, and NOu levels was not found. Our study suggests a reduction in the basal NO production confirmed by NOu analysis in subjects with the 90 kDa N-domain ACE isoform alone or associated with a family history of hypertension. Our data suggest that the presence of the 90 kDa N-domain ACE itself may have a negative impact on flow-mediated dilatation stimulated by reactive hyperemia. PMID:18475311

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) III: Endogenous Inhibition of Angiotensin Converting Enzyme (ACE) Provides Protection against Cardiovascular Diseases

PubMed Central

Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Édes, István; Papp, Zoltán; Tóth, Attila

2014-01-01

ACE inhibitor drugs decrease mortality by up to one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors. Here we investigated the clinical significance of this potential endogenous ACE inhibition. ACE concentration and activity was measured in patient's serum samples (n = 151). ACE concentration was found to be in a wide range (47–288 ng/mL). ACE activity decreased with the increasing concentration of the serum albumin (HSA): ACE activity was 56±1 U/L in the presence of 2.4±0.3 mg/mL HSA, compared to 39±1 U/L in the presence of 12±1 mg/mL HSA (values are mean±SEM). Effects of the differences in ACE concentration were suppressed in human sera: patients with ACE DD genotype exhibited a 64% higher serum ACE concentration (range, 74–288 ng/mL, median, 155.2 ng/mL, n = 52) compared to patients with II genotype (range, 47–194 ng/mL, median, 94.5 ng/mL, n = 28) while the difference in ACE activities was only 32% (range, 27.3–59.8 U/L, median, 43.11 U/L, and range 15.6–55.4 U/L, median, 32.74 U/L, respectively) in the presence of 12±1 mg/mL HSA. No correlations were found between serum ACE concentration (or genotype) and cardiovascular diseases, in accordance with the proposed suppressed physiological ACE activities by HSA (concentration in the sera of these patients: 48.5±0.5 mg/mL) or other endogenous inhibitors. Main implications are that (1) physiological ACE activity can be stabilized at a low level by endogenous ACE inhibitors, such as HSA; (2) angiotensin II elimination may have a significant role in angiotensin II related pathologies. PMID:24690767

Angiotensin I-converting enzyme Gln1069Arg mutation impairs trafficking to the cell surface resulting in selective denaturation of the C-domain.

PubMed

Danilov, Sergei M; Kalinin, Sergey; Chen, Zhenlong; Vinokour, Elena I; Nesterovitch, Andrew B; Schwartz, David E; Gribouval, Olivier; Gubler, Marie-Claire; Minshall, Richard D

2010-05-03

Angiotensin-converting enzyme (ACE; Kininase II; CD143) hydrolyzes small peptides such as angiotensin I, bradykinin, substance P, LH-RH and several others and thus plays a key role in blood pressure regulation and vascular remodeling. Complete absence of ACE in humans leads to renal tubular dysgenesis (RTD), a severe disorder of renal tubule development characterized by persistent fetal anuria and perinatal death. Patient with RTD in Lisbon, Portugal, maintained by peritoneal dialysis since birth, was found to have a homozygous substitution of Arg for Glu at position 1069 in the C-terminal domain of ACE (Q1069R) resulting in absence of plasma ACE activity; both parents and a brother who are heterozygous carriers of this mutation had exactly half-normal plasma ACE activity compared to healthy individuals. We hypothesized that the Q1069R substitution impaired ACE trafficking to the cell surface and led to accumulation of catalytically inactive ACE in the cell cytoplasm. CHO cells expressing wild-type (WT) vs. Q1069R-ACE demonstrated the mutant accumulates intracellularly and also that it is significantly degraded by intracellular proteases. Q1069R-ACE retained catalytic and immunological characteristics of WT-ACE N domain whereas it had 10-20% of the nativity of the WT-ACE C domain. A combination of chemical (sodium butyrate) or pharmacological (ACE inhibitor) chaperones with proteasome inhibitors (MG 132 or bortezomib) significantly restored trafficking of Q1069R-ACE to the cell surface and increased ACE activity in the cell culture media 4-fold. Homozygous Q1069R substitution results in an ACE trafficking and processing defect which can be rescued, at least in cell culture, by a combination of chaperones and proteasome inhibitors. Further studies are required to determine whether similar treatment of individuals with this ACE mutation would provide therapeutic benefits such as concentration of primary urine.

Presence of angiotensin converting enzyme isoforms in larval lepidoptera (Spodoptera littoralis).

PubMed

Lemeire, E; Van Camp, J; Smagghe, G

2007-01-01

In this research the presence of angiotensin converting enzyme (ACE) in larvae of the lepidopteran Spodoptera littoralis was evaluated. Making use of the substrate Abz-FRK-(Dnp)P-OH and the specific inhibitor captopril at 10 microM, ACE activity was determined in a fluorescence assay for intact larvae, hemolymph, head, midgut and dorsal tissue. In dorsal tissue and hemolymph, ACE activity was highest. These data are consistent with a possible role for ACE in contractions of the dorsal vessel and metabolism of circulating peptide hormones in the hemolymph. After the presence of ACE was confirmed, a sequential procedure of anion exchange and size exclusion chromatography was applied to purify ACE from whole wandering larvae (last stage). With this procedure, three different ACE pools were collected that cleaved the fluorogenic substrate Abz-FRK-(Dnp)P-OH. Activity could be inhibited by a final concentration of 2.5 microM captopril. In addition, two out of three samples eluted at different salt concentration and thus ACE 1, 2 and 3 represent at least two different ACE isoforms. These data reveal that ACE is present in S. littoralis and that at least two out of three isolated ACE forms are truly isoforms.

ACE insertion/deletion polymorphism and submaximal exercise hemodynamics in postmenopausal women.

PubMed

Hagberg, James M; McCole, Steve D; Brown, Michael D; Ferrell, Robert E; Wilund, Kenneth R; Huberty, Andrea; Douglass, Larry W; Moore, Geoffrey E

2002-03-01

We sought to determine whether the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism is associated with submaximal exercise cardiovascular hemodynamics. Postmenopausal healthy women (20 sedentary, 20 physically active, 22 endurance athletes) had cardiac output (acetylene rebreathing) measured during 40, 60, and 80% VO(2 max) exercise. The interaction of ACE genotype and habitual physical activity (PA) level was significantly associated with submaximal exercise systolic blood pressure, with only sedentary women exhibiting differences among genotypes. No significant effects of ACE genotype or its interaction with PA levels was observed for submaximal exercise diastolic blood pressure. ACE genotype was significantly associated with submaximal exercise heart rate (HR) with ACE II having approximately 10 beats/min higher HR than ACE ID/DD genotype women. ACE genotype did not interact significantly with habitual PA level to associate with submaximal exercise HR. ACE genotype was not independently, but was interactively with habitual PA levels, associated with differences in submaximal exercise cardiac output and stroke volume. For cardiac output, ACE II genotype women athletes had ~25% greater cardiac output than ACE DD genotype women athletes, whereas for stroke volume genotype-dependent differences were observed in both the physically active and athletic women. ACE genotype was not significantly associated, either independently or interactively with habitual PA levels, with submaximal exercise total peripheral resistance or arteriovenous O(2) difference. Thus the common ACE locus polymorphic variation is associated with many submaximal exercise cardiovascular hemodynamic responses.

How long will I have my ACE? The natural history of the antegrade continence enema stoma in idiopathic constipation.

PubMed

Khoo, A Kate; Askouni, Evita; Basson, Sonia; Ng, Jessica; Cleeve, Stewart

2017-11-01

We aim to determine the natural history of the ACE in idiopathic constipation and factors predictive of closure. A retrospective case-note review of all patients undergo ACE formation for idiopathic constipation Jan 2003-Mar 2016. Kaplan-Meier analysis was used to determine ACE survival and Cox's proportional hazard models to examine potential predictors of closure. 29/84 (35%) ACEs were closed: 21/84 due to success and 8/84 due to failure. Median age of closure was 15.5 years (3.5-23.6). Median ACE survival was 77.0 months (95% CI 58.0-96.0). An ACE survival curve was derived from which we estimate that 5-year post-ACE, one-third of patients can expect to have had their ACE closed. Younger age at ACE was predictive of earlier closure (p = 0.023) and closure for success (p < 0.001). Neither patient sex (p = 0.546) nor presence of psychological comorbidities (p = 0.769) predicted likelihood of closure. Incontinence 6-week post-ACE was also associated with increased likelihood of closure (p = 0.042). The ACE survival curve estimates the proportion of patients with idiopathic constipation who can expect closure (either due to success or failure) at certain timepoints. This may be useful for patient counseling. Younger age at ACE was associated with earlier closure (for success).

Crystal structures of sampatrilat and sampatrilat-Asp in complex with human ACE - a molecular basis for domain selectivity.

PubMed

Cozier, Gyles E; Schwager, Sylva L; Sharma, Rajni K; Chibale, Kelly; Sturrock, Edward D; Acharya, K Ravi

2018-04-01

Angiotensin-1-converting enzyme (ACE) is a zinc metallopeptidase that consists of two homologous catalytic domains (known as nACE and cACE) with different substrate specificities. Based on kinetic studies it was previously reported that sampatrilat, a tight-binding inhibitor of ACE, K i = 13.8 nm and 171.9 nm for cACE and nACE respectively [Sharma et al., Journal of Chemical Information and Modeling (2016), 56, 2486-2494], was 12.4-fold more selective for cACE. In addition, samAsp, in which an aspartate group replaces the sampatrilat lysine, was found to be a nonspecific and lower micromolar affinity inhibitor. Here, we report a detailed three-dimensional structural analysis of sampatrilat and samAsp binding to ACE using high-resolution crystal structures elucidated by X-ray crystallography, which provides a molecular basis for differences in inhibitor affinity and selectivity for nACE and cACE. The structures show that the specificity of sampatrilat can be explained by increased hydrophobic interactions and a H-bond from Glu403 of cACE with the lysine side chain of sampatrilat that are not observed in nACE. In addition, the structures clearly show a significantly greater number of hydrophilic and hydrophobic interactions with sampatrilat compared to samAsp in both cACE and nACE consistent with the difference in affinities. Our findings provide new experimental insights into ligand binding at the active site pockets that are important for the design of highly specific domain selective inhibitors of ACE. The atomic coordinates and structure factors for N- and C-domains of ACE bound to sampatrilat and sampatrilat-Asp complexes (6F9V, 6F9R, 6F9T and 6F9U respectively) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/). © 2018 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

[Conformational Fingerprinting Using Monoclonal Antibodies
(on the Example of Angiotensin I-Converting Enzyme-ACE)].

PubMed

Danilov, S M

2017-01-01

During the past 30 years my laboratory has generated 40+ monoclonal antibodies (mAbs) directed to structural and conformational epitopes on human ACE as well as ACE from rats, mice and other species. These mAbs were successfully used for detection and quantification of ACE by ELISA, Western blotting, flow cytometry and immunohistochemistry. In all these applications mainly single mAbs were used. We hypothesized that we can obtain a completely new kind of information about ACE structure and function if we use the whole set of mAbs directed to different epitopes on the ACE molecule. When we finished epitope mapping of all mAbs to ACE (and especially, those recognizing conformational epitopes), we realized that we had obtained a new tool to study ACE. First, we demonstrated that binding of some mAbs is very sensitive to local conformational changes on the ACE surface-due to local denaturation, inactivation, ACE inhibitor or mAbs binding or due to diseases. Second, we were able to detect, localize and characterize several human ACE mutations. And, finally, we established a new concept - conformational fingerprinting of ACE using mAbs that in turn allowed us to obtain evidence for tissue specificity of ACE, which has promising scientific and diagnostic perspectives. The initial goal for the generation of mAbs to ACE 30 years ago was obtaining mAbs to organ-specific endothelial cells, which could be used for organ-specific drug delivery. Our systematic work on characterization of mAbs to numerous epitopes on ACE during these years has lead not only to the generation of the most effective mAbs for specific drug/gene delivery into the lung capillaries, but also to the establishment of the concept of conformational fingerprinting of ACE, which in turn gives a theoretical base for the generation of mAbs, specific for ACE from different organs. We believe that this concept could be applicable for any glycoprotein against which there is a set of mAbs to different epitopes.

Lest we forget: comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health.

PubMed

Reuben, Aaron; Moffitt, Terrie E; Caspi, Avshalom; Belsky, Daniel W; Harrington, Honalee; Schroeder, Felix; Hogan, Sean; Ramrakha, Sandhya; Poulton, Richie; Danese, Andrea

2016-10-01

Adverse childhood experiences (ACEs; e.g. abuse, neglect, and parental loss) have been associated with increased risk for later-life disease and dysfunction using adults' retrospective self-reports of ACEs. Research should test whether associations between ACEs and health outcomes are the same for prospective and retrospective ACE measures. We estimated agreement between ACEs prospectively recorded throughout childhood (by Study staff at Study member ages 3, 5, 7, 9, 11, 13, and 15) and retrospectively recalled in adulthood (by Study members when they reached age 38), in the population-representative Dunedin cohort (N = 1,037). We related both retrospective and prospective ACE measures to physical, mental, cognitive, and social health at midlife measured through both objective (e.g. biomarkers and neuropsychological tests) and subjective (e.g. self-reported) means. Dunedin and U.S. Centers for Disease Control ACE distributions were similar. Retrospective and prospective measures of adversity showed moderate agreement (r = .47, p < .001; weighted Kappa = .31, 95% CI: .27-.35). Both associated with all midlife outcomes. As compared to prospective ACEs, retrospective ACEs showed stronger associations with life outcomes that were subjectively assessed, and weaker associations with life outcomes that were objectively assessed. Recalled ACEs and poor subjective outcomes were correlated regardless of whether prospectively recorded ACEs were evident. Individuals who recalled more ACEs than had been prospectively recorded were more neurotic than average, and individuals who recalled fewer ACEs than recorded were more agreeable. Prospective ACE records confirm associations between childhood adversity and negative life outcomes found previously using retrospective ACE reports. However, more agreeable and neurotic dispositions may, respectively, bias retrospective ACE measures toward underestimating the impact of adversity on objectively measured life outcomes and overestimating the impact of adversity on self-reported outcomes. Associations between personality factors and the propensity to recall adversity were extremely modest and warrant further investigation. Risk predictions based on retrospective ACE reports should utilize objective outcome measures. Where objective outcome measurements are difficult to obtain, correction factors may be warranted. © 2016 Association for Child and Adolescent Mental Health.

Lest we forget: Comparing retrospective and prospective assessments of adverse childhood experiences in the prediction of adult health

PubMed Central

Reuben, Aaron; Moffitt, Terrie E.; Caspi, Avshalom; Belsky, Daniel W.; Harrington, Honalee; Schroeder, Felix; Hogan, Sean; Ramrakha, Sandhya; Poulton, Richie; Danese, Andrea

2017-01-01

Background Adverse childhood experiences (ACEs; e.g., abuse, neglect, parental loss, etc.) have been associated with increased risk for later-life disease and dysfunction using adults’ retrospective self-reports of ACEs. Research should test whether associations between ACEs and health outcomes are the same for prospective and retrospective ACE measures. Methods We estimated agreement between ACEs prospectively-recorded throughout childhood (by Study staff at Study member ages 3, 5, 7, 9, 11, 13, and 15) and retrospectively-recalled in adulthood (by Study members when they reached age 38), in the population-representative Dunedin cohort (N=1,037). We related both retrospective and prospective ACE measures to physical, mental, cognitive, and social health at midlife measured through both objective (e.g., biomarkers and neuropsychological tests) and subjective (e.g., self-reported) means. Results Dunedin and CDC ACE distributions were similar. Retrospective and prospective measures of adversity showed moderate agreement (r=.47, p<.001; weighted Kappa = .31, 95% CI: .27–.35). Both associated with all midlife outcomes. As compared to prospective ACEs, retrospective ACEs showed stronger associations with life outcomes that were subjectively assessed, and weaker associations with life outcomes that were objectively assessed. Recalled ACEs and poor subjective outcomes were correlated regardless of whether prospectively-recorded ACEs were evident. Individuals who recalled more ACEs than had been prospectively recorded were more neurotic than average, and individuals who recalled fewer ACEs than recorded were more agreeable. Conclusions Prospective ACE records confirm associations between childhood adversity and negative life outcomes found previously using retrospective ACE reports. However, more agreeable and neurotic dispositions may respectively bias retrospective ACE measures toward underestimating the impact of adversity on objectively-measured life outcomes and overestimating the impact of adversity on self-reported outcomes. Associations between personality factors and the propensity to recall adversity were extremely modest and warrant further investigation. Risk predictions based on retrospective ACE reports should utilize objective outcome measures. Where objective outcome measurements are difficult to obtain, correction factors may be warranted. PMID:27647050

Adverse Childhood Experiences and Health in Adulthood in a Rural Population-Based Sample

PubMed Central

Iniguez, Kristen C.; Stankowski, Rachel V.

2016-01-01

Background Adverse childhood experiences (ACEs), including emotional abuse, substance abuse in the household, separation or divorce, physical abuse, violence between adults, mental illness in the household, sexual abuse, or incarceration of a household member, have the potential to profoundly impact health and well-being in adulthood. To assess whether previously reported relationships between ACEs and health outcomes withstand validation, we conducted a community-based ACE study with the unique capacity to link self-reported ACEs and other survey results to validated health data in an electronic medical record (EMR). Methods Information regarding ACEs and health outcomes was captured from 2013–2014 via a telephone survey of residents of the predominantly rural northern and central regions of Wisconsin and electronic abstraction of EMR data. ACE score was calculated by counting each exposure as one point. We examined the relationship between ACE score, type, and self-reported and validated health outcomes. Results A total of 800 participants completed the telephone survey. Overall, 62% reported at least one ACE and 15% reported experiencing four or more. All self-reported measures of poor health were associated with increased ACE score. EMR data were positively correlated with ACE score for increased body mass index and diagnoses of depression, anxiety, and asthma. In contrast, diagnoses of hypertension, hypercholesterolemia, myocardial infarction, and skin and other cancers were inversely related to ACE score. Emotional abuse was the most common ACE reported followed by substance abuse in the household. ACEs tended to cluster so that people who reported at least one ACE were likely to have experienced multiple ACEs. There was no clear correlation between abuse type (e.g., direct abuse vs. household dysfunction) and health outcomes. Conclusions In the first community-based study to link self-reported ACEs to comprehensive health measures documented in the medical record, we observed previously reported associations between childhood adversity and poor outcomes in adulthood, but also noted an inverse relationship between ACE score and certain medical diagnoses. Potential explanations for this finding warrant further investigation. PMID:27503793

ACE/SWICS OBSERVATIONS OF HEAVY ION DROPOUTS WITHIN THE SOLAR WIND

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weberg, Micah J.; Zurbuchen, Thomas H.; Lepri, Susan T., E-mail: mjweberg@umich.edu, E-mail: thomasz@umich.edu, E-mail: slepri@umich.edu

2012-11-20

We present the first in situ observations of heavy ion dropouts within the slow solar wind, observed for select elements ranging from helium to iron. For iron, these dropouts manifest themselves as depletions of the Fe/H ratio by factors up to {approx}25. The events often exhibit mass-dependent fractionation and are contained in slow, unsteady wind found within a few days from known stream interfaces. We propose that such dropouts are evidence of gravitational settling within large coronal loops, which later undergo interchange reconnection and become source regions of slow, unsteady wind. Previously, spectroscopic studies by Raymond et al. in 1997more » (and later Feldman et al. in 1999) have yielded strong evidence for gravitational settling within these loops. However, their expected in situ signature plasma with heavy elements fractionated by mass was not observed prior to this study. Using data from the SWICS instrument on board the Advanced Composition Explorer (ACE), we investigate the composition of the solar wind within these dropouts and explore long term trends over most of a solar cycle.« less

Obtaining Reliable Predictions of Terrestrial Energy Coupling From Real-Time Solar Wind Measurements

NASA Technical Reports Server (NTRS)

Weimer, Daniel R.

2002-01-01

Measurements of the interplanetary magnetic field (IMF) from the ACE (Advanced Composition Explorer), Wind, IMP-8 (Interplanetary Monitoring Platform), and Geotail spacecraft have revealed that the IMF variations are contained in phase planes that are tilted with respect to the propagation direction, resulting in continuously variable changes in propagation times between spacecraft, and therefore, to the Earth. Techniques for using 'minimum variance analysis' have been developed in order to be able to measure the phase front tilt angles, and better predict the actual propagation times from the L1 orbit to the Earth, using only the real-time IMF measurements from one spacecraft. The use of empirical models with the IMF measurements at L1 from ACE (or future satellites) for predicting 'space weather' effects has also been demonstrated.

jsc2018m000297_Investigation_Seeks_to_Create_Self-Assembling_Materials-MP4

NASA Image and Video Library

2018-05-14

Investigation Seeks to Create Self-Assembling Materials------ As we travel farther into space, clever solutions to problems like engine part malfunctions and other possible mishaps will be a vital part of the planning process. 3D printing, or additive manufacturing, is an emerging technology that may be used to custom-create mission-critical parts. An integral piece of this process is understanding how particle shape, size distribution and packing behavior affect the manufacturing process. The Advanced Colloids Experiment-Temperature-7 investigation (ACE-T-7) aboard the International Space Station explores the feasibility of creating self-assembling microscopic particles for use in the manufacturing of materials during spaceflight. Read more about ACE-T-& here: https://www.nasa.gov/feature/investigation-seeks-to-create-self-assembling-materials

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) I: Endogenous Angiotensin Converting Enzyme (ACE) Inhibition

PubMed Central

Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Édes, István; Papp, Zoltán; Tóth, Attila

2014-01-01

Angiotensin-converting enzyme (ACE) inhibitors represent the fifth most often prescribed drugs. ACE inhibitors decrease 5-year mortality by approximately one-fifth in cardiovascular patients. Surprisingly, there are reports dating back to 1979 suggesting the existence of endogenous ACE inhibitors, which endogenous inhibitory effects are much less characterized than that for the clinically administered ACE inhibitors. Here we aimed to investigate this endogenous ACE inhibition in human sera. It was hypothesized that ACE activity is masked by an endogenous inhibitor, which dissociates from the ACE when its concentration decreases upon dilution. ACE activity was measured by FAPGG hydrolysis first. The specific (dilution corrected) enzyme activities significantly increased by dilution of human serum samples (23.2±0.7 U/L at 4-fold dilution, 51.4±0.3 U/L at 32-fold dilution, n = 3, p = 0.001), suggesting the presence of an endogenous inhibitor. In accordance, specific enzyme activities did not changed by dilution when purified renal ACE was used, where no endogenous inhibitor was present (655±145 U/L, 605±42 U/L, n = 3, p = 0.715, respectively). FAPGG conversion strongly correlated with angiotensin I conversion suggesting that this feature is not related to the artificial substrate. Serum samples were ultra-filtered to separate ACE (MW: 180 kDa) and the hypothesized inhibitor. Filtering through 50 kDa filters was without effect, while filtering through 100 kDa filters eliminated the inhibiting factor (ACE activity after <100 kDa filtering: 56.4±2.4 U/L, n = 4, control: 26.4±0.7 U/L, n = 4, p<0.001). Lineweaver-Burk plot indicated non-competitive inhibition of ACE by this endogenous factor. The endogenous inhibitor had higher potency on the C-terminal active site than N-terminal active site of ACE. Finally, this endogenous ACE inhibition was also present in mouse, donkey, goat, bovine sera besides men (increasing of specific ACE activity from 4-fold to 32-fold dilution: 2.8-fold, 1.7-fold, 1.5-fold, 1.8-fold, 2.6-fold, respectively). We report here the existence of an evolutionary conserved mechanism suppressing circulating ACE activity, in vivo, similarly to ACE inhibitory drugs. PMID:24691160

New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human

PubMed Central

Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Fülöp, Gábor Á.; Csató, Viktória; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Szentkirályi, István Elek; Maros, Tamás Miklós; Szerafin, Tamás; Édes, István; Papp, Zoltán; Tóth, Attila

2014-01-01

About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7±0.7 and 9.5±1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14±1.34 mN, without HSA: 13.54±2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73±2.17 mN, without HSA: 19.22±3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo. PMID:24691203

Associations Between Adverse Childhood Experiences and ADHD Diagnosis and Severity.

PubMed

Brown, Nicole M; Brown, Suzette N; Briggs, Rahil D; Germán, Miguelina; Belamarich, Peter F; Oyeku, Suzette O

Although identifying adverse childhood experiences (ACEs) among children with behavioral disorders is an important step in providing targeted therapy and support, little is known about the burden of ACEs among children with attention deficit-hyperactivity disorder (ADHD). We described the prevalence of ACEs in children with and without ADHD, and examined associations between ACE type, ACE score, and ADHD diagnosis and severity. Using the 2011 to 2012 National Survey of Children's Health, we identified children aged 4 to 17 years whose parents indicated presence and severity of ADHD, and their child's exposure to 9 ACEs. Multivariate logistic regression was used to estimate associations between ACEs, ACE score, and parent-reported ADHD and ADHD severity, adjusted for sociodemographic characteristics. In our sample (N = 76,227, representing 58,029,495 children), children with ADHD had a higher prevalence of each ACE compared with children without ADHD. Children who experienced socioeconomic hardship (adjusted odds ratio [aOR], 1.39; 95% confidence interval [CI], 1.21-1.59), divorce (aOR, 1.34; 95% CI, 1.16-1.55), familial mental illness (aOR, 1.55; 95% CI, 1.26-1.90), neighborhood violence (aOR, 1.47; 95% CI, 1.23-1.75), and incarceration (aOR, 1.39; 95% CI, 1.12-1.72) were more likely to have ADHD. A graded relationship was observed between ACE score and ADHD. Children with ACE scores of 2, 3, and ≥4 were significantly more likely to have moderate to severe ADHD. Children with ADHD have higher ACE exposure compared with children without ADHD. There was a significant association between ACE score, ADHD, and moderate to severe ADHD. Efforts to improve ADHD assessment and management should consider routinely evaluating for ACEs. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

The ACE2 gene: its potential as a functional candidate for cardiovascular disease.

PubMed

Burrell, Louise M; Harrap, Stephen B; Velkoska, Elena; Patel, Sheila K

2013-01-01

The RAS (renin-angiotensin system) plays an important role in the pathophysiology of CVD (cardiovascular disease), and RAS blockade is an important therapeutic strategy in the management of CVD. A new counterbalancing arm of the RAS is now known to exist in which ACE (angiotensin-converting enzyme) 2 degrades Ang (angiotensin) II, the main effector of the classic RAS, and generates Ang-(1-7). Altered ACE2 expression is associated with cardiac and vascular disease in experimental models of CVD, and ACE2 is increased in failing human hearts and atherosclerotic vessels. In man, circulating ACE2 activity increases with coronary heart disease, as well as heart failure, and a large proportion of the variation in plasma ACE2 levels has been attributed to hereditary factors. The ACE2 gene maps to chromosome Xp22 and this paper reviews the evidence associating ACE2 gene variation with CVD and considers clues to potential functional ACE2 variants that may alter gene expression or transcriptional activity. Studies to date have investigated ACE2 gene associations in hypertension, left ventricular hypertrophy and coronary artery disease, but the results have been inconsistent. The discrepancies may reflect the sample size of the studies, the gender or ethnicity of subjects, the cardiovascular phenotype or the ACE2 SNP investigated. The frequent observation of apparent sex-dependence might be of special importance, if confirmed. As yet, there are no studies to concurrently assess ACE2 gene polymorphisms and circulating ACE2 activity. Large-scale carefully conducted clinical studies are urgently needed to clarify more precisely the potential role of ACE2 in the CVD continuum.

Gonadectomy prevents the increase in blood pressure and glomerular injury in angiotensin-converting enzyme 2 knockout diabetic male mice. Effects on renin-angiotensin system.

PubMed

Clotet, Sergi; Soler, María José; Rebull, Marta; Gimeno, Javier; Gurley, Susan B; Pascual, Julio; Riera, Marta

2016-09-01

Angiotensin-converting enzyme 2 (ACE2) deletion worsens kidney injury, and its amplification ameliorates diabetic nephropathy. Male sex increases the incidence, prevalence, and progression of chronic kidney disease in our environment. Here, we studied the effect of ACE2 deficiency and gonadectomy (GDX) on diabetic nephropathy and its relationship with fibrosis, protein kinase B (Akt) activation, and the expression of several components of the renin-angiotensin system (RAS).Mice were injected with streptozotocin to induce diabetes and followed for 19 weeks. Physiological and renal parameters were studied in wild-type and ACE2 knockout (ACE2KO) male mice with and without GDX. Diabetic ACE2KO showed increased blood pressure (BP), glomerular injury, and renal fibrosis compared with diabetic wild-type. Gonadectomized diabetic ACE2KO presented a decrease in BP. In the absence of ACE2, GDX attenuated albuminuria and renal lesions, such as mesangial matrix expansion and podocyte loss. Both, α-smooth muscle actin accumulation and collagen deposition were significantly decreased in renal cortex of gonadectomized diabetic ACE2KO but not diabetic wild-type mice. GDX also reduced circulating ACE activity in ACE2KO mice. Loss of ACE2 modified the effect of GDX on cortical gene expression of RAS in diabetic mice. Akt phosphorylation in renal cortex was increased by diabetes and loss of ACE2 and decreased by GDX in control and diabetic ACE2KO but not in wild-type mice. Our results suggest that GDX may exert a protective effect within the kidney under pathological conditions of diabetes and ACE2 deficiency. This renoprotection may be ascribed to different mechanisms such as decrease in BP, modulation of RAS, and downregulation of Akt-related pathways.

Angiotensin I-converting enzyme insertion/deletion polymorphism and adrenergic response to exercise in hypertensive patients.

PubMed

Jalil, Jorge E; Córdova, Samuel; Ocaranza, Marí a; Schumacher, Erwin; Braun, Sandra; Chamorro, Gastón; Fardella, Carlos; Lavandero, Sergio

2002-08-01

The insertion/deletion ACE polymorphism (ACE I/D) regulates different levels of circulating and tissue ACE activities, which may induce diverse adrenergic responses to physiological stimuli. The aim of this study was to evaluate the influence of the ACE I/D polymorphism on the adrenergic response to isotonic exercise in middle-aged hypertensive patients. Submaximal exercise (on a treadmill, using the Naughton protocol at 75% of maximal heart rate) was performed in 34 patients homozygous for the ACE I/D polymorphism (ACE II and ACE DD) with untreated essential hypertension (II = 19, DD = 15). Plasma venous adrenaline and noradrenaline were measured at rest and at submaximal exercise. Plasma ACE activity was significantly higher in the hypertensive patients carrying the ACE DD genotype compared with the ACE II group. Left atrium size, as well as LV dimensions, mass, and function, were similar in both groups. Total exercise time, baseline and 75% maximal heart rate (MHR) and blood pressure were similar in both groups. Baseline plasma adrenaline and noradrenaline levels were similar in both groups and increased significantly (p<0.05) by ca. 300% at submaximal exercise without differences between groups. The presence of the D allele on the ACE gene in middle-aged hypertensive patients determines higher circulating ACE activity but not increased sympathetic activity in response to submaximal exercise.

Ancylostoma ceylanicum Excretory-Secretory Protein 2 Adopts a Netrin-Like Fold and Defines a Novel Family of Nematode Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

K Kucera; L Harrison; M Cappello

2011-12-31

Hookworms are human parasites that have devastating effects on global health, particularly in underdeveloped countries. Ancylostoma ceylanicum infects humans and animals, making it a useful model organism to study disease pathogenesis. A. ceylanicum excretory-secretory protein 2 (AceES-2), a highly immunoreactive molecule secreted by adult worms at the site of intestinal attachment, is partially protective when administered as a mucosal vaccine against hookworm anemia. The crystal structure of AceES-2 determined at 1.75 {angstrom} resolution shows that it adopts a netrin-like fold similar to that found in tissue inhibitors of matrix metalloproteases (TIMPs) and in complement factors C3 and C5. However, recombinantmore » AceES-2 does not significantly inhibit the 10 most abundant human matrix metalloproteases or complement-mediated cell lysis. The presence of a highly acidic surface on AceES-2 suggests that it may function as a cytokine decoy receptor. Several small nematode proteins that have been annotated as TIMPs or netrin-domain-containing proteins display sequence homology in structurally important regions of AceES-2's netrin-likefold. Together, our results suggest that AceES-2 defines a novel family of nematode netrin-like proteins, which may function to modulate the host immune response to hookworm and other parasites.« less

Long Term Missions at the Sun-Earth Libration Point L1: ACE, SOHO, and WIND

NASA Technical Reports Server (NTRS)

Roberts, Craig E.

2011-01-01

Three heliophysics missions -- the Advanced Composition Explorer (ACE), Solar Heliospheric Observatory (SOHO), and the Global Geoscience WIND -- have been orbiting the Sun-Earth interior libration point L1 continuously since 1997, 1996, and 2004, respectively. ACE and WIND (both NASA missions) and SOHO (an ESA-NASA joint mission) are all operated from the NASA Goddard Space Flight Center (GSFC). While ACE and SOHO have been dedicated libration point orbiters since their launches, WIND has had also a remarkable 10-year career flying a deep-space, multiple lunar-flyby trajectory prior to 2004. That era featured 36 targeted lunar flybys with excursions to both L1 and L2 before its final insertion in L1 orbit. A figure depicts the orbits of the three spacecraft, showing projections of the orbits onto the orthographic planes of a solar rotating ecliptic frame of reference. The SOHO orbit is a quasi-periodic halo orbit, where the frequencies of the in-plane and out-of-plane motions are practically equal. Such an orbit is seen to repeat itself with a period of approximately 178 days. For ACE and WIND, the frequencies of the in-plane and out-of-plane motions are unequal, giving rise to the characteristic Lissajous motion. ACE's orbit is of moderately small amplitude, whereas WIND's orbit is a large-amplitude Lissajous of dimensions close to those of the SOHO halo orbit. As motion about the collinear points is inherently unstable, stationkeeping maneuvers are necessary to prevent orbital decay and eventual escape from the L1 region. Though the three spacecraft are dissimilar (SOHO is a 3-axis stabilized Sun pointer, WIND is a spin-stabilized ecliptic pole pointer, and ACE is also spin-stabilized with its spin axis maintained between 4 and 20 degrees of the Sun), the stationkeeping technique for the three is fundamentally the same. The technique consists of correcting the energy of the orbit via a delta-V directed parallel or anti-parallel to the Spacecraft-to-Sun line. SOHO achieves this using thrusters oriented in line with the solar direction. WIND achieves the delta-V via pulsing radial thrusters when aligned with the Sun. ACE uses axial thrusters to apply delta-V with a component that is 94% or more aligned with the ACE-Sun line. Sunward thrust adds energy to the orbit preventing decay back toward Earth. Thrust directed anti-Sunward takes energy out of the L1 orbit, thereby preventing escape from the Earth-Moon system into independent heliocentric orbit. Libration point orbit stationkeeping delta-V costs grow exponentially with time elapsed from the last maneuver performed. The doubling time constant is approximately 16 days. For the sake of fuel conservation, and for limiting the absolute magnitude of propulsion performance errors, stationkeeping maneuvers should be performed before the delta-V grows too large; for our purposes 'too large' is considered to be greater than 0.5 m/sec. In practice, the typical interval between burns for this trio is about three months, and the typical delta-V is much smaller than 0.5 m/sec. Typical annual stationkeeping costs have been around 1.0 m/sec for ACE and WIND, and much less than that for SOHO. All three spacecraft have ample fuel remaining; barring contingencies all three could, in principle, be maintained at L1 for decades to come. This paper will review the L1 orbits and the mission history of ACE, WIND, and SOHO, and describe the stationkeeping techniques and orbit maneuver experience. The Lissajous phase control that was practiced for ACE during the period from 1999 to 2001 will also be briefly discussed. The final section will consider the future of these ongoing missions.

Modified ACES Portable Life Support Integration, Design, and Testing for Exploration Missions

NASA Technical Reports Server (NTRS)

Kelly, Cody

2014-01-01

NASA's next generation of exploration missions provide a unique challenge to designers of EVA life support equipment, especially in a fiscally-constrained environment. In order to take the next steps of manned space exploration, NASA is currently evaluating the use of the Modified ACES (MACES) suit in conjunction with the Advanced Portable Life Support System (PLSS) currently under development. This paper will detail the analysis and integration of the PLSS thermal and ventilation subsystems into the MACES pressure garment, design of prototype hardware, and hardware-in-the-loop testing during the spring 2014 timeframe. Prototype hardware was designed with a minimal impact philosophy in order to mitigate design constraints becoming levied on either the advanced PLSS or MACES subsystems. Among challenges faced by engineers were incorporation of life support thermal water systems into the pressure garment cavity, operational concept definition between vehicle/portable life support system hardware, and structural attachment mechanisms while still enabling maximum EVA efficiency from a crew member's perspective. Analysis was completed in late summer 2013 to 'bound' hardware development, with iterative analysis cycles throughout the hardware development process. The design effort will cumulate in the first ever manned integration of NASA's advanced PLSS system with a pressure garment originally intended primarily for use in a contingency survival scenario.

High-Throughput and Rapid Screening of Novel ACE Inhibitory Peptides from Sericin Source and Inhibition Mechanism by Using in Silico and in Vitro Prescriptions.

PubMed

Sun, Huaju; Chang, Qing; Liu, Long; Chai, Kungang; Lin, Guangyan; Huo, Qingling; Zhao, Zhenxia; Zhao, Zhongxing

2017-11-22

Several novel peptides with high ACE-I inhibitory activity were successfully screened from sericin hydrolysate (SH) by coupling in silico and in vitro approaches for the first time. Most screening processes for ACE-I inhibitory peptides were achieved through high-throughput in silico simulation followed by in vitro verification. QSAR model based predicted results indicated that the ACE-I inhibitory activity of these SH peptides and six chosen peptides exhibited moderate high ACE-I inhibitory activities (log IC 50 values: 1.63-2.34). Moreover, two tripeptides among the chosen six peptides were selected for ACE-I inhibition mechanism analysis which based on Lineweaver-Burk plots indicated that they behave as competitive ACE-I inhibitors. The C-terminal residues of short-chain peptides that contain more H-bond acceptor groups could easily form hydrogen bonds with ACE-I and have higher ACE-I inhibitory activity. Overall, sericin protein as a strong ACE-I inhibition source could be deemed a promising agent for antihypertension applications.

Unraveling the Pivotal Role of Bradykinin in ACE Inhibitor Activity.

PubMed

Taddei, Stefano; Bortolotto, L

2016-10-01

Historically, the first described effect of an angiotensin converting enzyme (ACE) inhibitor was an increased activity of bradykinin, one of the substrates of ACE. However, in the subsequent years, molecular models describing the mechanism of action of ACE inhibitors in decreasing blood pressure and cardiovascular risk have focused mostly on the renin-angiotensin system. Nonetheless, over the last 20 years, the importance of bradykinin in regulating vasodilation, natriuresis, oxidative stress, fibrinolysis, inflammation, and apoptosis has become clearer. The affinity of ACE appears to be higher for bradykinin than for angiotensin I, thereby suggesting that ACE inhibitors may be more effective inhibitors of bradykinin degradation than of angiotensin II production. Data describing the effect of ACE inhibition on bradykinin signaling support the hypothesis that the most cardioprotective benefits attributed to ACE inhibition may be due to increased bradykinin signaling rather than to decreased angiotensin II signaling, especially when high dosages of ACE inhibitors are considered. In particular, modulation of bradykinin in the endothelium appears to be a major target of ACE inhibition. These new mechanistic concepts may lead to further development of strategies enhancing the bradykinin signaling.

Methods to Assess Adverse Childhood Experiences of Children and Families: Toward Approaches to Promote Child Well-being in Policy and Practice.

PubMed

Bethell, Christina D; Carle, Adam; Hudziak, James; Gombojav, Narangerel; Powers, Kathleen; Wade, Roy; Braveman, Paula

Advances in human development sciences point to tremendous possibilities to promote healthy child development and well-being across life by proactively supporting safe, stable and nurturing family relationships (SSNRs), teaching resilience, and intervening early to promote healing the trauma and stress associated with disruptions in SSNRs. Assessing potential disruptions in SSNRs, such as adverse childhood experiences (ACEs), can contribute to assessing risk for trauma and chronic and toxic stress. Asking about ACEs can help with efforts to prevent and attenuate negative impacts on child development and both child and family well-being. Many methods to assess ACEs exist but have not been compared. The National Survey of Children's Health (NSCH) now measures ACEs for children, but requires further assessment and validation. We identified and compared methods to assess ACEs among children and families, evaluated the acceptability and validity of the new NSCH-ACEs measure, and identified implications for assessing ACEs in research and practice. Of 14 ACEs assessment methods identified, 5 have been used in clinical settings (vs public health assessment or research) and all but 1 require self or parent report (3 allow child report). Across methods, 6 to 20 constructs are assessed, 4 of which are common to all: parental incarceration, domestic violence, household mental illness/suicide, household alcohol or substance abuse. Common additional content includes assessing exposure to neighborhood violence, bullying, discrimination, or parental death. All methods use a numeric, cumulative risk scoring methodology. The NSCH-ACEs measure was acceptable to respondents as evidenced by few missing values and no reduction in response rate attributable to asking about children's ACEs. The 9 ACEs assessed in the NSCH co-occur, with most children with 1 ACE having additional ACEs. This measure showed efficiency and confirmatory factor analysis as well as latent class analysis supported a cumulative risk scoring method. Formative as well as reflective measurement models further support cumulative risk scoring and provide evidence of predictive validity of the NSCH-ACEs. Common effects of ACEs across household income groups confirm information distinct from economic status is provided and suggest use of population-wide versus high-risk approaches to assessing ACEs. Although important variations exist, available ACEs measurement methods are similar and show consistent associations with poorer health outcomes in absence of protective factors and resilience. All methods reviewed appear to coincide with broader goals to facilitate health education, promote health and, where needed, to mitigate the trauma, chronic stress, and behavioral and emotional sequelae that can arise with exposure to ACEs. Assessing ACEs appears acceptable to individuals and families when conducted in population-based and clinical research contexts. Although research to date and neurobiological findings compel early identification and health education about ACEs in clinical settings, further research to guide use in pediatric practice is required, especially as it relates to distinguishing ACEs assessment from identifying current family psychosocial risks and child abuse. The reflective as well as formative psychometric analyses conducted in this study confirm use of cumulative risk scoring for the NSCH-ACEs measure. Even if children have not been exposed to ACEs, assessing ACEs has value as an educational tool for engaging and educating families and children about the importance of SSNRs and how to recognize and manage stress and learn resilience. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

ACE2-EPC-EXs protect ageing ECs against hypoxia/reoxygenation-induced injury through the miR-18a/Nox2/ROS pathway.

PubMed

Zhang, Cheng; Wang, Jinju; Ma, Xiaotang; Wang, Wenjun; Zhao, Bin; Chen, Yanfang; Chen, Can; Bihl, Ji C

2018-03-01

Oxidative stress is one of the mechanisms of ageing-associated vascular dysfunction. Angiotensin-converting enzyme 2 (ACE2) and microRNA (miR)-18a have shown to be down-regulated in ageing cells. Our previous study has shown that ACE2-primed endothelial progenitor cells (ACE2-EPCs) have protective effects on endothelial cells (ECs), which might be due to their released exosomes (EXs). Here, we aimed to investigate whether ACE2-EPC-EXs could attenuate hypoxia/reoxygenation (H/R)-induced injury in ageing ECs through their carried miR-18a. Young and angiotensin II-induced ageing ECs were subjected to H/R and co-cultured with vehicle (medium), EPC-EXs, ACE2-EPCs-EXs, ACE2-EPCs-EXs + DX600 or ACE2-EPCs-EXs with miR-18a deficiency (ACE2-EPCs-EXs anti-miR-18a ). Results showed (1) ageing ECs displayed increased senescence, apoptosis and ROS production, but decreased ACE2 and miR-18a expressions and tube formation ability; (2) under H/R condition, ageing ECs showed higher rate of apoptosis, ROS overproduction and nitric oxide reduction, up-regulation of Nox2, down-regulation of ACE2, miR-18a and eNOS, and compromised tube formation ability; (3) compared with EPC-EXs, ACE2-EPC-EXs had better efficiencies on protecting ECs from H/R-induced changes; (4) The protective effects were less seen in ACE2-EPCs-EXs + DX600 and ACE2-EPCs-EXs anti-miR-18a groups. These data suggest that ACE-EPCs-EXs have better protective effects on H/R injury in ageing ECs which could be through their carried miR-18a and subsequently down-regulating the Nox2/ROS pathway. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Angiotensin converting enzyme over expression in myelocytes enhances the immune response

PubMed Central

Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.; Giani, Jorge F.; Shah, Kandarp; Bernstein, Ellen; Janjulia, Tea; Koronyo, Yosef; Shi, Peng D.; Koronyo-Hamaoui, Maya; Fuchs, Sebastien; Shen, Xiao Z.

2015-01-01

Angiotensin converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis and several aspects of the immune response. ACE 10/10 mice over express ACE in monocytic cells; macrophages from ACE 10/10 mice demonstrate increased polarization towards a proinflammatory phenotype. As a result, ACE 10/10 mice have a highly effective immune response following challenge with either melanoma, bacterial infection or Alzheimer’s disease. The ACE 10/10 mice suggest that enhanced monocytic function greatly contributes to the ability of the immune response to defend against a wide variety of antigenic and non-antigenic challenges. PMID:24633750

Just Out of Reach: On the Reliability of the Action-Sentence Compatibility Effect

PubMed Central

Papesh, Megan H.

2015-01-01

The action-sentence compatibility effect (ACE; Glenberg & Kaschak, 2002), a hallmark finding in Embodied Cognition, implicates the motor system in language comprehension. In the ACE, people process sentences implying movement toward or away from themselves, responding with actions toward or away from their bodies. These processes interact, implying a linkage between linguistic and motor systems. From a theoretical perspective, the ACE has been extremely influential, being widely-cited evidence in favor of embodied cognition. The present study began as an attempt to extend the ACE in a new direction, but eventually became a series of attempts to simply replicate the effect. Across eight experiments, I tested whether the ACE extends to a novel mouse-tracking method and/or is susceptible to higher-order cognitive influences. In three experiments, attempts were made to “disembody” the ACE by presenting participants' names on the computer screen (as in Markman & Brendl, 2005). In each experiment, the ACE could not be disembodied, because the ACE did not occur. In further experiments, the ACE was not observed in reading times, regardless of response mode (mouse movements versus button-presses) or stimuli, including those from the original research. Similarly, no ACE was observed in physical movement times. Bayes Factor analyses of the current experiments, and the previous ACE literature, suggest that the evidence for the ACE is generally weak: Many studies considered as positive evidence actually support the null hypothesis, and very few published results offer strong evidence for the ACE. Implications for the embodiment hypothesis are discussed. PMID:26595844

Angiotensin Converting Enzyme Regulates Cell Proliferation and Migration

PubMed Central

Carvalho, Clarissa Coelho; Florentino, Rodrigo Machado; França, Andressa; Matias, Eveline; Guimarães, Paola Bianchi; Batista, Carolina; Freire, Valder; Carmona, Adriana Karaoglanovic; Pesquero, João Bosco; de Paula, Ana Maria; Foureaux, Giselle; Leite, Maria de Fatima

2016-01-01

Background The angiotensin-I converting enzyme (ACE) plays a central role in the renin-angiotensin system, acting by converting the hormone angiotensin-I to the active peptide angiotensin-II (Ang-II). More recently, ACE was shown to act as a receptor for Ang-II, and its expression level was demonstrated to be higher in melanoma cells compared to their normal counterparts. However, the function that ACE plays as an Ang-II receptor in melanoma cells has not been defined yet. Aim Therefore, our aim was to examine the role of ACE in tumor cell proliferation and migration. Results We found that upon binding to ACE, Ang-II internalizes with a faster onset compared to the binding of Ang-II to its classical AT1 receptor. We also found that the complex Ang-II/ACE translocates to the nucleus, through a clathrin-mediated process, triggering a transient nuclear Ca2+ signal. In silico studies revealed a possible interaction site between ACE and phospholipase C (PLC), and experimental results in CHO cells, demonstrated that the β3 isoform of PLC is the one involved in the Ca2+ signals induced by Ang-II/ACE interaction. Further studies in melanoma cells (TM-5) showed that Ang-II induced cell proliferation through ACE activation, an event that could be inhibited either by ACE inhibitor (Lisinopril) or by the silencing of ACE. In addition, we found that stimulation of ACE by Ang-II caused the melanoma cells to migrate, at least in part due to decreased vinculin expression, a focal adhesion structural protein. Conclusion ACE activation regulates melanoma cell proliferation and migration. PMID:27992423

The Pharmacogenetic Footprint of ACE Inhibition: A Population-Based Metabolomics Study.

PubMed

Altmaier, Elisabeth; Menni, Cristina; Heier, Margit; Meisinger, Christa; Thorand, Barbara; Quell, Jan; Kobl, Michael; Römisch-Margl, Werner; Valdes, Ana M; Mangino, Massimo; Waldenberger, Melanie; Strauch, Konstantin; Illig, Thomas; Adamski, Jerzy; Spector, Tim; Gieger, Christian; Suhre, Karsten; Kastenmüller, Gabi

2016-01-01

Angiotensin-I-converting enzyme (ACE) inhibitors are an important class of antihypertensives whose action on the human organism is still not fully understood. Although it is known that ACE especially cleaves COOH-terminal dipeptides from active polypeptides, the whole range of substrates and products is still unknown. When analyzing the action of ACE inhibitors, effects of genetic variation on metabolism need to be considered since genetic variance in the ACE gene locus was found to be associated with ACE-concentration in blood as well as with changes in the metabolic profiles of a general population. To investigate the interactions between genetic variance at the ACE-locus and the influence of ACE-therapy on the metabolic status we analyzed 517 metabolites in 1,361 participants from the KORA F4 study. We replicated our results in 1,964 individuals from TwinsUK. We observed differences in the concentration of five dipeptides and three ratios of di- and oligopeptides between ACE inhibitor users and non-users that were genotype dependent. Such changes in the concentration affected major homozygotes, and to a lesser extent heterozygotes, while minor homozygotes showed no or only small changes in the metabolite status. Two of these resulting dipeptides, namely aspartylphenylalanine and phenylalanylserine, showed significant associations with blood pressure which qualifies them-and perhaps also the other dipeptides-as readouts of ACE-activity. Since so far ACE activity measurement is substrate specific due to the usage of only one oligopeptide, taking several dipeptides as potential products of ACE into account may provide a broader picture of the ACE activity.

Brain ACE2 shedding contributes to the development of neurogenic hypertension

PubMed Central

Chhabra, Kavaljit H.; Lazartigues, Eric

2015-01-01

Rationale Over-activity of the brain Renin Angiotensin System (RAS) is a major contributor to neurogenic hypertension. While over-expression of Angiotensin-Converting Enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming Angiotensin (Ang)-II into Ang-(1-7), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension. Objective We hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension. Methods and Results To test this hypothesis, we used the DOCA-salt model of neurogenic hypertension in non-transgenic (NT) and syn-hACE2 mice over-expressing ACE2 in neurons. DOCA-salt treatment in NT mice led to significant increases in blood pressure, hypothalamic Ang-II levels, inflammation, impaired baroreflex sensitivity, autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, while these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled a rise in ACE2 activity in the cerebrospinal fluid of NT mice following DOCA-salt treatment and was accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function. Conclusions Our data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension. PMID:24014829

Scaling Climate Change Communication for Behavior Change

NASA Astrophysics Data System (ADS)

Rodriguez, V. C.; Lappé, M.; Flora, J. A.; Ardoin, N. M.; Robinson, T. N.

2014-12-01

Ultimately, effective climate change communication results in a change in behavior, whether the change is individual, household or collective actions within communities. We describe two efforts to promote climate-friendly behavior via climate communication and behavior change theory. Importantly these efforts are designed to scale climate communication principles focused on behavior change rather than soley emphasizing climate knowledge or attitudes. Both cases are embedded in rigorous evaluations (randomized controlled trial and quasi-experimental) of primary and secondary outcomes as well as supplementary analyses that have implications for program refinement and program scaling. In the first case, the Girl Scouts "Girls Learning Environment and Energy" (GLEE) trial is scaling the program via a Massive Open Online Course (MOOC) for Troop Leaders to teach the effective home electricity and food and transportation energy reduction programs. The second case, the Alliance for Climate Education (ACE) Assembly Program, is advancing the already-scaled assembly program by using communication principles to further engage youth and their families and communities (school and local communities) in individual and collective actions. Scaling of each program uses online learning platforms, social media and "behavior practice" videos, mastery practice exercises, virtual feedback and virtual social engagement to advance climate-friendly behavior change. All of these communication practices aim to simulate and advance in-person train-the-trainers technologies.As part of this presentation we outline scaling principles derived from these two climate change communication and behavior change programs.

A qualitative evaluation of the 2005-2011 National Academic Centers of Excellence in Youth Violence Prevention Program.

PubMed

Holland, Kristin M; Vivolo-Kantor, Alana M; Dela Cruz, Jason; Massetti, Greta M; Mahendra, Reshma

2015-12-01

The Centers for Disease Control and Prevention's Division of Violence Prevention (DVP) funded eight National Academic Centers of Excellence (ACEs) in Youth Violence Prevention from 2005 to 2010 and two Urban Partnership Academic Centers of Excellence (UPACEs) in Youth Violence Prevention from 2006 to 2011. The ACEs and UPACEs constitute DVP's 2005-2011 ACE Program. ACE Program goals include partnering with communities to promote youth violence (YV) prevention and fostering connections between research and community practice. This article describes a qualitative evaluation of the 2005-2011 ACE Program using an innovative approach for collecting and analyzing data from multiple large research centers via a web-based Information System (ACE-IS). The ACE-IS was established as an efficient mechanism to collect and document ACE research and programmatic activities. Performance indicators for the ACE Program were established in an ACE Program logic model. Data on performance indicators were collected through the ACE-IS biannually. Data assessed Centers' ability to develop, implement, and evaluate YV prevention activities. Performance indicator data demonstrate substantial progress on Centers' research in YV risk and protective factors, community partnerships, and other accomplishments. Findings provide important lessons learned, illustrate progress made by the Centers, and point to new directions for YV prevention research and programmatic efforts. Published by Elsevier Ltd.

Adverse childhood experiences (ACE) and adult attachment interview (AAI) in a non-clinical population.

PubMed

Thomson, Paula; Jaque, S Victoria

2017-08-01

Adverse childhood experiences (ACE) tend to be interrelated rather than independently occurring. There is a graded effect associated with ACE exposure and pathology, with an increase when ACE exposure is four or more. This study examined a sample of active individuals (n=129) to determine distribution patterns and relationships between ACEs, attachment classification, unresolved mourning (U), and disclosure difficulty. The results of this study demonstrated a strong relationship between increased ACEs and greater unresolved mourning. Specifically, the group differences for individuals who experienced no ACE (n=42, 33%), those with 1-3 ACEs (n=48, 37.8%), and those with ≥4 ACEs (n=37, 29.1%) revealed a pattern in which increased group ACE exposure was associated with greater lack of resolution for past trauma/loss experiences, more adult traumatic events, and more difficulty disclosing past trauma. Despite ≥4 ACEs, 51.4% of highly exposed individuals were classified as secure in the Adult Attachment Interview. Resilience in this group may be related to a combination of attachment security, college education, and engagement in meaningful activities. Likewise, adversity may actually encourage the cultivation of more social support, goal efficacy, and planning behaviors; factors that augment resilience to adversity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparative Study of Three Methods for Affinity Measurements: Capillary Electrophoresis Coupled with UV Detection and Mass Spectrometry, and Direct Infusion Mass Spectrometry

NASA Astrophysics Data System (ADS)

Mironov, Gleb G.; Logie, Jennifer; Okhonin, Victor; Renaud, Justin B.; Mayer, Paul M.; Berezovski, Maxim V.

2012-07-01

We present affinity capillary electrophoresis and mass spectrometry (ACE-MS) as a comprehensive separation technique for label-free solution-based affinity analysis. The application of ACE-MS for measuring affinity constants between eight small molecule drugs [ibuprofen, s-flurbiprofen, diclofenac, phenylbutazone, naproxen, folic acid, resveratrol, and 4,4'-(propane-1,3-diyl) dibenzoic acid] and β-cyclodextrin is described. We couple on-line ACE with MS to combine the separation and kinetic capability of ACE together with the molecular weight and structural elucidation of MS in one system. To understand the full potential of ACE-MS, we compare it with two other methods: Direct infusion mass spectrometry (DIMS) and ACE with UV detection (ACE-UV). After the evaluation, DIMS provides less reliable equilibrium dissociation constants than separation-based ACE-UV and ACE-MS, and cannot be used solely for the study of noncovalent interactions. ACE-MS determines apparent dissociation constants for all reacting small molecules in a mixture, even in cases when drugs overlap with each other during separation. The ability of ACE-MS to interact, separate, and rapidly scan through m/z can facilitate the simultaneous affinity analysis of multiple interacting pairs, potentially leading to the high-throughput screening of drug candidates.

ACE Inhibitor and ARB utilization and expenditures in the Medicaid fee-for-service program from 1991 to 2008.

PubMed

Bian, Boyang; Kelton, Christina M L; Guo, Jeff J; Wigle, Patricia R

2010-01-01

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely prescribed for the treatment of hypertension and heart failure, as well as for kidney disease prevention in patients with diabetes mellitus and the management of patients after myocardial infarction. To (a) describe ACE inhibitor and ARB utilization and spending in the Medicaid fee-for-service program from 1991 through 2008, and (b) estimate the potential cost savings for the collective Medicaid programs from a higher ratio of generic ACE inhibitor utilization. A retrospective, descriptive analysis was performed using the National Summary Files from the Medicaid State Drug Utilization Data, which are composed of pharmacy claims that are subject to federally mandated rebates from pharmaceutical manufacturers. For the years 1991-2008, quarterly claim counts and expenditures were calculated by summing data for individual ACE inhibitors and ARBs. Quarterly per-claim expenditure as a proxy for drug price was computed for all brand and generic drugs. Market shares were calculated based on the number of pharmacy claims and Medicaid expenditures. In the Medicaid fee-for-service program, ACE inhibitors accounted for 100% of the claims in the combined market for ACE inhibitors and ARBs in 1991, 80.6% in 2000, and 64.7% in 2008. The Medicaid expenditure per ACE inhibitor claim dropped from $37.24 in 1991 to $24.03 in 2008 when generics accounted for 92.5% of ACE inhibitor claims; after adjusting for inflation for the period from 1991 to 2008, the real price drop was 59.2%. Brand ACE inhibitors accounted for only 7.5% of the claims in 2008 for all ACE inhibitors but 32.1% of spending; excluding the effects of manufacturer rebates, Medicaid spending would have been reduced by $28.7 million (9%) in 2008 if all ACE inhibitor claims were generic. The average price per ACE inhibitor claim in 2008 was $24.03 ($17.64 per generic claim vs. $103.45 per brand claim) versus $81.98 per ARB claim. If the ACE inhibitor ratio had been 75% in 2008 rather than 64.7%, the Medicaid program would have saved approximately 13% or about $41.8 million, again excluding the effects of manufacturer rebates. If the ACE inhibitor ratio had been 90% in 2008, the cost savings for the combined Medicaid fee-forservice programs would have been about 33% or about $102.3 million. The total cost savings opportunity with 100% generic ACE inhibitor utilization in 2008 and an ACE inhibitor ratio of 75% was $75.1 million (24%) or $142.3M (46%) with a 90% ACE inhibitor ratio. Factors that affect Medicaid spending by contributing to increased utilization of ACE inhibitors and ARBs, such as the rising prevalence of hypertension, heart disease, and diabetes, can be offset by reduction in the average price attained through a higher proportion of ACE inhibitors and a higher percentage of generic versus brand ACE inhibitors.

Airborne Sunphotometry of Aerosol Optical Depth and Columnar Water Vapor During ACE-Asia

NASA Technical Reports Server (NTRS)

Redemann, Jens; Schmid, B.; Russell, P. B.; Livingston, J. M.; Eilers, J. A.; Ramirez, S. A.; Kahn, R.; Hipskind, R. Stephen (Technical Monitor)

2001-01-01

During the Intensive Field Campaign (IFC) of the Aerosol Characterization Experiment - Asia (ACE-Asia), March-May 2001, the 6-channel NASA Ames Airborne Tracking Sunphotometer (AATS-6) operated during 15 of the 19 research flights aboard the NCAR C- 130, while its 14-channel counterpart (AATS- 14) was flown successfully on all 18 research flights of a Twin Otter aircraft operated by the Center for Interdisciplinary Remotely Piloted Aircraft Studies (CIRPAS), Monterey, CA. ACE-Asia was the fourth in a series of aerosol characterization experiments and focused on aerosol outflow from the Asian continent to the Pacific basin. Each ACE was designed to integrate suborbital and satellite measurements and models so as to reduce the uncertainty in calculations of the climate forcing due to aerosols. The Ames Airborne Tracking Sunphotometers measured solar beam transmission at 6 (380-1021 nm, AATS-6) and 14 wavelengths (353-1558 nm, AATS-14) respectively, yielding aerosol optical depth (AOD) spectra and column water vapor (CWV). Vertical differentiation in profiles yielded aerosol extinction and water vapor concentration. The wavelength dependence of AOD and extinction indicates that supermicron dust was often a major component of the aerosol. Frequently this dust-containing aerosol extended to high altitudes. For example, in data flights analyzed to date 34 +/- 13% of full-column AOD(525 nm) was above 3 km. In contrast, only 10 +/- 4% of CWV was above 3 km. In this paper, we will show first sunphotometer-derived results regarding the spatial variation of AOD and CWV, as well as the vertical distribution of aerosol extinction and water vapor concentration. Preliminary comparison studies between our AOD/aerosol extinction data and results from: (1) extinction products derived using in situ measurements and (2) AOD retrievals using the Multi-angle Imaging Spectro-Radiometer (MISR) aboard the TERRA satellite will also be presented.

An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito.

PubMed

Assogba, Benoît S; Djogbénou, Luc S; Milesi, Pascal; Berthomieu, Arnaud; Perez, Julie; Ayala, Diego; Chandre, Fabrice; Makoutodé, Michel; Labbé, Pierrick; Weill, Mylène

2015-10-05

Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1(R) allele), is already present. Furthermore, a duplicated allele (ace-1(D)) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1(D) confers less resistance than ace-1(R), the high fitness cost associated with ace-1(R) is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management.

An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito

PubMed Central

Assogba, Benoît S.; Djogbénou, Luc S.; Milesi, Pascal; Berthomieu, Arnaud; Perez, Julie; Ayala, Diego; Chandre, Fabrice; Makoutodé, Michel; Labbé, Pierrick; Weill, Mylène

2015-01-01

Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1R allele), is already present. Furthermore, a duplicated allele (ace-1D) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1D confers less resistance than ace-1R, the high fitness cost associated with ace-1R is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management. PMID:26434951

ACE blood test

MedlinePlus

... to help diagnose and monitor a disorder called sarcoidosis . People with sarcoidosis may have their ACE level tested regularly to ... normal ACE level may be a sign of sarcoidosis. ACE levels may rise or fall as sarcoidosis ...

Affinity capillary electrophoresis for studying interactions in life sciences.

PubMed

Olabi, Mais; Stein, Matthias; Wätzig, Hermann

2018-05-10

Affinity capillary electrophoresis (ACE) analyzes noncovalent interactions between ligands and analytes based on changes in their electrophoretic mobility. This technique has been widely used to investigate various biomolecules, mainly proteins, polysaccharides and hormones. ACE is becoming a technique of choice to validate high throughput screening results, since it is very predictively working in realistic and relevant media, e.g. in body fluids. It is highly recommended to incorporate ACE as a powerful analytical tool to properly prepare animal testing and preclinical studies. The interacting molecules can be found free in solution or can be immobilized to a solid support. Thus, ACE is classified in two modes, free solution ACE and immobilized ACE. Every ACE mode has advantages and disadvantages. Each can be used for a variety of applications. This review covers literature of scopus and SciFinder data base in the period from 2016 until beginning 2018, including the keywords "affinity capillary electrophoresis", "immunoaffinity capillary electrophoresis", "immunoassay capillary electrophoresis" and "immunosorbent capillary electrophoresis". More than 200 articles have been found and 112 have been selected and thoroughly discussed. During this period, the data processing and the underlying calculations in mobility shift ACE (ms ACE), frontal analysis ACE (FA ACE) and plug-plug kinetic capillary electrophoresis (ppKCE) as mostly applied free solution techniques have substantially improved. The range of applications in diverse free solution and immobilized ACE techniques has been considerably broadened. Copyright © 2018. Published by Elsevier Inc.

Patterns of adverse childhood experiences and substance use among young adults: A latent class analysis.

PubMed

Shin, Sunny H; McDonald, Shelby Elaine; Conley, David

2018-03-01

Adverse childhood experiences (ACEs) have been strongly linked with subsequent substance use. The aim of this study was to investigate how different patterns of ACEs influence substance use in young adulthood. Using a community sample of young individuals (N=336; ages 18-25), we performed latent class analyses (LCA) to identify homogenous groups of young people with similar patterns of ACEs. Exposure to ACEs incorporates 13 childhood adversities including childhood maltreatment, household dysfunction, and community violence. Multiple linear and logistic regression models were used in an effort to examine the associations between ACEs classes and four young adult outcomes such as alcohol-related problems, current tobacco use, drug dependence symptoms, and psychological distress. LCA identified four heterogeneous classes of young people distinguished by different patterns of ACEs exposure: Low ACEs (56%), Household Dysfunction/Community Violence (14%), Emotional ACEs (14%), and High/Multiple ACEs (16%). Multiple regression analyses found that compared to those in the Low ACEs class, young adults in the High/Multiple ACEs class reported more alcohol-related problems, current tobacco use, and psychological symptoms, controlling for sociodemographic characteristics and common risk factors for substance use such as peer substance use. Our findings confirm that for many young people, ACEs occur as multiple rather than single experiences. The results of this research suggest that exposure to poly-victimization during childhood is particularly related to substance use during young adulthood. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maternal adverse childhood experiences and antepartum risks: the moderating role of social support.

PubMed

Racine, Nicole; Madigan, Sheri; Plamondon, Andre; Hetherington, Erin; McDonald, Sheila; Tough, Suzanne

2018-03-28

The aims of the current study were to examine the association between maternal adverse childhood experiences (ACEs) and antepartum health risks, and to investigate whether social support moderated this association. It was hypothesized that ACEs would be associated with antepartum health risks; however, social support in the prenatal period would buffer mothers from the deleterious consequences of ACEs. Data from 1994 women (mean age = 31 years) and their infants were collected from a longitudinal cohort recruited in health care offices in Alberta, Canada. Pregnant women completed questionnaires related to ACEs prior to the age of 18 and prenatal social support, and a health care professional assessed the mother's antepartum health risk. ACEs included physical, emotional, and sexual abuse, exposure to domestic violence, as well as exposure to household dysfunction such as parental substance use, mental illness, or incarceration. Regression analyses demonstrated a positive association between ACEs and antepartum health risks. However, a significant interaction between maternal ACEs and social support was also observed. Specifically, women exposed to high ACEs and low social support in pregnancy had high antepartum health risks. However, among mothers who had high ACEs but also high levels of social support, there was no association between ACEs and antepartum health risk. A history of ACEs can place mothers at risk of antepartum health complications. However, a resiliency effect was observed: women with a history of ACEs were buffered from experiencing antepartum health risks if they reported high levels of social support in pregnancy.

Real-time Upstream Monitoring System: Using ACE Data to Predict the Arrival of Interplanetary Shocks

NASA Astrophysics Data System (ADS)

Donegan, M. M.; Wagstaff, K. L.; Ho, G. C.; Vandegriff, J.

2003-12-01

We have developed an algorithm to predict Earth arrival times for interplanetary (IP) shock events originating at the Sun. Our predictions are generated from real-time data collected by the Electron, Proton, and Alpha Monitor (EPAM) instrument on NASA's Advanced Composition Explorer (ACE) spacecraft. The high intensities of energetic ions that occur prior to and during an IP shock pose a radiation hazard to astronauts as well as to electronics in Earth orbit. The potential to predict such events is based on characteristic signatures in the Energetic Storm Particle (ESP) event ion intensities which are often associated with IP shocks. We have previously reported on the development and implementation of an algorithm to forecast the arrival of ESP events. Historical ion data from ACE/EPAM was used to train an artificial neural network which uses the signature of an approaching event to predict the time remaining until the shock arrives. Tests on the trained network have been encouraging, with an average error of 9.4 hours for predictions made 24 hours in advance, and an reduced average error of 4.9 hours when the shock is 12 hours away. The prediction engine has been integrated into a web-based system that uses real-time ACE/EPAM data provided by the NOAA Space Environment Center (http://sd-www.jhuapl.edu/UPOS/RISP/ index.html.) This system continually processes the latest ACE data, reports whether or not there is an impending shock, and predicts the time remaining until the shock arrival. Our predictions are updated every five minutes and provide significant lead-time, thereby supplying critical information that can be used by mission planners, satellite operations controllers, and scientists. We have continued to refine the prediction capabilities of this system; in addition to forecasting arrival times for shocks, we now provide confidence estimates for those predictions.

Mechanism of antihypertensive effect of Mucuna pruriens L. seed extract and its isolated compounds.

PubMed

Khan, Mohammad Yaseen; Kumar, Vimal

2017-06-21

Background In the search of safe and effective lead molecules from natural sources, Mucuna pruriens (MP) L. (Fabaceae) seeds were utilized for exploring the antihypertensive potential. Traditionally, it is used as diuretic and hypotensive. Methods Bioassay-guided fractions were utilized for the isolation of active compounds by column chromatography. IC50 value, enzyme kinetics and inhibition mechanism were determined. In vivo time and dose-dependent hypotensive study followed by changes in mean arterial pressure (MAP) induced by angiotensin I (3 nmol/kg), angiotensin II (3 nmol/kg), and bradykinin (10 nmol/kg) in anesthetized rats was done. Plasma and tissue angiotensin I-converting enzyme (ACE) activities were also determined. Results Phytochemical analysis by spectroscopic techniques revealed the presence of known compounds like genistein, ursolic acid and L-DOPA from the ethyl acetate and water fraction, respectively. In vitro study revealed MP ethyl acetate (MPEA) fraction and genistein as the most active fraction (IC50 156.45 µg/mL) and compound (IC50 253.81 µM), respectively. Lineweaver-Burk plots revealed a non-competitive mode of inhibition. ACE protein precipitation was the suggested mechanism for inhibition. The extract showed a time- and dose-dependent decrease in MAP. Genistein was able to dose-dependently reduce the MAP, up to 53±1.5 mmHg (40 mg/kg, i.v.). As compared to control, it showed a dose-dependent decrease in plasma ACE activity of 40.61 % and 54.76 % at 10 mg/kg and 20 mg/kg, respectively. It also decreased the ACE activity in the aorta (107.67nM/ml min at 10 mg, p<0.001; 95.33nM/ml min at 20 mg p<0.001). Captopril was used as a standard for various in vitro and in vivo assays. Conclusions The study revealed the antihypertensive potential of MP seed compounds via ACE inhibition.

Space Weather Drivers in the ACE Era

NASA Astrophysics Data System (ADS)

Vogt, M.; Puhl-Quinn, P.; Jordanova, V. K.; Smith, C. W.; Cohen, C. M.

2004-12-01

The Advanced Composition Explorer (ACE) spacecraft was launched Aug.~25, 1997 [Stone et al., 1998]. Beginning shortly after launch and continuing to the present day ACE has provided real-time data telemetry of solar wind conditions upstream of the Earth. The real-time data includes solar wind speed and density, magnetic field direction and magnitude, and a range of energetic particle intensities [Zwickl et al., 1999]. The real-time data product is provided within 5 minutes of observation and many partners from both industry and science use these data for a variety of purposes. The most common purpose of practical industrial application involves mitigation of lost services arising from magnetospheric storm activity. Many space weather efforts are directed at providing improved predictions of magnetospheric response that can be applied to real-time data in the hope of better predicting the vulnerability and required action of industry to approaching disturbances. It therefore seems prudent that following 6 years of activity including one solar maximum period we should evaluate the nature and strength of the largest disturbances observed with the hope of better assessing the industrial response. Simply put: ``Did ACE observe disturbances that were as large as those seen previously during the space age?'' If not, it may be the case that industry must evaluate its response to the real-time warnings and not become complacent by the simple act of survival. We compare the most intense space weather events of the ACE era with those recorded on the Omnitape data set spanning 40+ years of spacecraft measurements in the near-Earth environment. We compare both magnetospheric response parameters and solar wind drivers. In addition, we compare the large energetic particle events over the same time frame. Stone, E.~C., et al., Space Science Rev., 86(1-4), 357-408, 1998. Zwickl, R.~D., et al., Space Science Rev., 86(1-4), 633-648, 1998.

Angiotensin-converting enzyme activity and cognitive impairment during hypoglycaemia in healthy humans.

PubMed

Pedersen-Bjergaard, Ulrik; Thomsen, Carsten E; Høgenhaven, Hans; Smed, Annelise; Kjaer, Troels W; Holst, Jens J; Dela, Flemming; Hilsted, Linda; Frandsen, Erik; Pramming, Stig; Thorsteinsson, Birger

2008-03-01

In type 1 diabetes increased risk of severe hypoglycaemia is associated with high angiotensin-converting enzyme (ACE) activity. We tested in healthy humans the hypothesis that this association is explained by the reduced ability of subjects with high ACE activity to maintain normal cognitive function during hypoglycaemia. Sixteen healthy volunteers selected by either particularly high or low serum ACE activity were subjected to hypoglycaemia (plasma glucose 2.7 mmol/L). Cognitive function was assessed by choice reaction tests. Despite a similar hypoglycaemic stimulus in the two groups, only the group with high ACE activity showed significant deterioration in cognitive performance during hypoglycaemia. In the high ACE group mean reaction time (MRT) in the most complex choice reaction task was prolonged and error rate (ER) was increased in contrast to the low ACE group. The total hypoglycaemic symptom response was greater in the high ACE group than in the low ACE group (p=0.031). There were no differences in responses of counterregulatory hormones or in concentrations of substrates between the groups. Healthy humans with high ACE activity are more susceptible to cognitive dysfunction and report higher symptom scores during mild hypoglycaemia than subjects with low ACE activity.

Fine-Mapping Angiotensin-Converting Enzyme Gene: Separate QTLs Identified for Hypertension and for ACE Activity

PubMed Central

Chung, Chia-Min; Wang, Ruey-Yun; Fann, Cathy S. J.; Chen, Jaw-Wen; Jong, Yuh-Shiun; Jou, Yuh-Shan; Yang, Hsin-Chou; Kang, Chih-Sen; Chen, Chien-Chung; Chang, Huan-Cheng; Pan, Wen-Harn

2013-01-01

Angiotensin-converting enzyme (ACE) has been implicated in multiple biological system, particularly cardiovascular diseases. However, findings associating ACE insertion/deletion polymorphism with hypertension or other related traits are inconsistent. Therefore, in a two-stage approach, we aimed to fine-map ACE in order to narrow-down the function-specific locations. We genotyped 31 single nucleotide polymorphisms (SNPs) of ACE from 1168 individuals from 305 young-onset (age ≤40) hypertension pedigrees, and found four linkage disequilibrium (LD) blocks. A tag-SNP, rs1800764 on LD block 2, upstream of and near the ACE promoter, was significantly associated with young-onset hypertension (p = 0.04). Tag-SNPs on all LD blocks were significantly associated with ACE activity (p-value: 10–16 to <10–33). The two regions most associated with ACE activity were found between exon13 and intron18 and between intron 20 and 3′UTR, as revealed by measured haplotype analysis. These two major QTLs of ACE activity and the moderate effect variant upstream of ACE promoter for young-onset hypertension were replicated by another independent association study with 842 subjects. PMID:23469169

Association of Angiotensin-Converting Enzyme ACE Gene Polymorphism with ACE Activity and Susceptibility to Vitiligo in Egyptian Population.

PubMed

Badran, Dahlia I; Nada, Hesham; Hassan, Ranya

2015-05-01

The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with vitiligo in the Indians and Koreans, but not in those of English or Turkish background. We investigated the ACE (I/D) polymorphism in vitiligo patients for the first time in Egypt and compared serum ACE levels between vitiligo patients and controls. The present study was carried out in 100 vitiligo patients (40 males and 60 females) and in 100 healthy controls of an Egyptian population using the polymerase chain reaction genotyping method. The ACE genotype and allele frequency was significantly different between vitiligo patients and controls. Our results revealed a significant increase in the frequency of the ACE I allele (p=0.002; odds ratio: 1.99; 95% confidence intervals: 1.207-3.284) with an overrepresentation of I/D genotype in the vitiligo patient group. Furthermore, there was a significant difference between the segmental, nonsegmental, and focal vitiligo in ACE gene genotype distribution. Serum ACE levels were significantly increased in vitiligo patients compared to controls (p=0.034). This study suggests that, for the first time, ACE gene polymorphism confers susceptibility to vitiligo in the Egyptian population.

A novel acetylcholinesterase gene in mosquitoes codes for the insecticide target and is non-homologous to the ace gene in Drosophila.

PubMed Central

Weill, Mylène; Fort, Philippe; Berthomieu, Arnaud; Dubois, Marie Pierre; Pasteur, Nicole; Raymond, Michel

2002-01-01

Acetylcholinesterase (AChE) is the target of two major insecticide families, organophosphates (OPs) and carbamates. AChE insensitivity is a frequent resistance mechanism in insects and responsible mutations in the ace gene were identified in two Diptera, Drosophila melanogaster and Musca domestica. However, for other insects, the ace gene cloned by homology with Drosophila does not code for the insensitive AChE in resistant individuals, indicating the existence of a second ace locus. We identified two AChE loci in the genome of Anopheles gambiae, one (ace-1) being a new locus and the other (ace-2) being homologous to the gene previously described in Drosophila. The gene ace-1 has no obvious homologue in the Drosophila genome and was found in 15 mosquito species investigated. In An. gambiae, ace-1 and ace-2 display 53% similarity at the amino acid level and an overall phylogeny indicates that they probably diverged before the differentiation of insects. Thus, both genes are likely to be present in the majority of insects and the absence of ace-1 in Drosophila is probably due to a secondary loss. In one mosquito (Culex pipiens), ace-1 was found to be tightly linked with insecticide resistance and probably encodes the AChE OP target. These results have important implications for the design of new insecticides, as the target AChE is thus encoded by distinct genes in different insect groups, even within the Diptera: ace-2 in at least the Drosophilidae and Muscidae and ace-1 in at least the Culicidae. Evolutionary scenarios leading to such a peculiar situation are discussed. PMID:12396499

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

PubMed Central

Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

2016-01-01

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration. PMID:28066203

A Novel Splice-Site Mutation in Angiotensin I-Converting Enzyme (ACE) Gene, c.3691+1G>A (IVS25+1G>A), Causes a Dramatic Increase in Circulating ACE through Deletion of the Transmembrane Anchor

PubMed Central

Persu, Alexandre; Lambert, Michel; Deinum, Jaap; Cossu, Marta; de Visscher, Nathalie; Irenge, Leonid; Ambroise, Jerôme; Minon, Jean-Marc; Nesterovitch, Andrew B.; Churbanov, Alexander; Popova, Isolda A.; Danilov, Sergei M.; Danser, A. H. Jan; Gala, Jean-Luc

2013-01-01

Background Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. Methods and Results Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. Conclusions We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences. PMID:23560051

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment.

PubMed

Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

2016-01-01

Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients ( p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) ( p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score ( p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups ( p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

Functional characterisation of a cyst nematode acetylcholinesterase gene using Caenorhabditis elegans as a heterologous system.

PubMed

Costa, Joana C; Lilley, Catherine J; Atkinson, Howard J; Urwin, Peter E

2009-06-01

Migration of plant-parasitic nematode infective larval stages through soil and invasion of roots requires perception and integration of sensory cues culminating in particular responses that lead to root penetration and parasite establishment. Components of the chemoreceptive neuronal circuitry involved in these responses are targets for control measures aimed at preventing infection. Here we report, to our knowledge, the first isolation of cyst nematode ace-2 genes encoding acetylcholinesterase (AChE). The ace-2 genes from Globodera pallida (Gp-ace-2) and Heterodera glycines (Hg-ace-2) show homology to ace-2 of Caenorhabditis elegans (Ce-ace-2). Gp-ace-2 is expressed most highly in the infective J2 stage with lowest expression in the early parasitic stages. Expression and functional analysis of the Globodera gene were carried out using the free-living nematode C. elegans in order to overcome the refractory nature of the obligate parasite G. pallida to many biological studies. Caenorhabditis elegans transformed with a GFP reporter construct under the control of the Gp-ace-2 promoter exhibited specific and restricted GFP expression in neuronal cells in the head ganglia. Gp-ACE-2 protein can functionally complement its C. elegans homologue. A chimeric construct containing the Ce-ace-2 promoter region and the Gp-ace-2 coding region and 3' untranslated region was able to restore a normal phenotype to the uncoordinated C. elegans double mutant ace-1;ace-2. This study demonstrates conservation of AChE function and expression between free-living and plant-parasitic nematode species, and highlights the utility of C. elegans as a heterologous system to study neuronal aspects of plant-parasitic nematode biology.

Rural–urban differences in exposure to adverse childhood experiences among South Carolina adults.

PubMed

Radcliff, Elizabeth; Crouch, Elizabeth; Strompolis, Melissa

2018-02-01

Adverse childhood experiences (ACEs) are traumatic events that occur in a child's life between birth and 18 years. Exposure to one or more ACE has been linked to participation in risky health behaviors and the experience of chronic health conditions in adulthood. The risk for poor outcomes increases as the number of ACEs experienced increases. This research investigates rural-urban differences in exposure to ACEs using a sample from a representative southern US state, South Carolina. Using data from the 2014-2015 South Carolina Behavioral Risk Factor Surveillance System (BRFSS) and residential rurality based on UICs, ACE exposure among South Carolina adults was tabulated by urban versus rural residence and selected other demographic characteristics. Using standard descriptive statistics, frequencies and proportions were calculated for each categorical variable. Multivariable regression modeling was used to examine the impact of residential rurality and selected sociodemographic characteristics on overall and specific types of ACE exposure. All analyses used survey sampling weights that accounted for the BRFSS sampling strategy. The analytic sample of 18 176 respondents comprised 15.9% rural residents. Top reported ACEs for both rural and urban residents were the same: parental divorce/separation, emotional abuse, and household substance use. Compared to urban residents, a higher proportion of rural respondents reported experiencing no ACEs (41.4% vs 38.3%, p<0.01). The prevalence of four or more ACEs in rural respondents was 15.0%; in comparison, 17.6% of urban respondents had four or more ACEs (p<0.01). In logistic regression predicting exposure to four or more ACEs and adjusting for sex, age, race/ethnicity, education, and income, rural respondents were less likely than urban respondents to report four or more ACEs (adjusted odds ratio 0.75, 95% confidence interval 0.74-0.75). Despite reporting less ACE exposure than urban counterparts, almost 60% of rural residents reported at least one ACE and 15% reported experiencing four or more ACEs. In contrast to urban residents, rural residents may experience more social connections within their families and communities, which may influence ACE exposure; however, care coordination, social support services, and access to health care are limited in rural areas. Thus, families in rural areas may be less equipped to mitigate and manage the effects of ACEs. Findings from this study thus suggest that interventions to prevent ACE exposure are just as needed in rural southern communities as they are in urban southern communities. Topics important for future research could include an examination of ACEs in rural communities in terms of individuals' health outcomes and their access to health care, as well as the role of protective factors. Programs and policies that assist in ACE prevention in rural areas are important to reducing these multigenerational threats to health and wellbeing.

Adverse Childhood Experiences, Support, and the Perception of Ability to Work in Adults with Disability.

PubMed

Schüssler-Fiorenza Rose, Sophia Miryam; Eslinger, Jessica G; Zimmerman, Lindsey; Scaccia, Jamie; Lai, Betty S; Lewis, Catrin; Alisic, Eva

2016-01-01

To examine the impact of adverse childhood experiences (ACEs) and support on self-reported work inability of adults reporting disability. Adults (ages 18-64) who participated in the Behavioral Risk Factor Surveillance System in 2009 or 2010 and who reported having a disability (n = 13,009). The study used a retrospective cohort design with work inability as the main outcome. ACE categories included abuse (sexual, physical, emotional) and family dysfunction (domestic violence, incarceration, mental illness, substance abuse, divorce). Support included functional (perceived emotional/social support) and structural (living with another adult) support. Logistic regression was used to adjust for potential confounders (age, sex and race) and to evaluate whether there was an independent effect of ACEs on work inability after adding other important predictors (support, education, health) to the model. ACEs were highly prevalent with almost 75% of the sample reporting at least one ACE category and over 25% having a high ACE burden (4 or more categories). ACEs were strongly associated with functional support. Participants experiencing a high ACE burden had a higher adjusted odds ratio (OR) [95% confidence interval] of 1.9 [1.5-2.4] of work inability (reference: zero ACEs). Good functional support (adjusted OR 0.52 [0.42-0.63]) and structural support (adjusted OR 0.48 [0.41-0.56]) were protective against work inability. After adding education and health to the model, ACEs no longer appeared to have an independent effect. Structural support remained highly protective, but functional support only appeared to be protective in those with good physical health. ACEs are highly prevalent in working-age US adults with a disability, particularly young adults. ACEs are associated with decreased support, lower educational attainment and worse adult health. Health care providers are encouraged to screen for ACEs. Addressing the effects of ACEs on health and support, in addition to education and retraining, may increase ability to work in those with a disability.

Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial

PubMed Central

Bhatnagar, Vibha; O’Connor, Daniel T.; Schork, Nicholas J.; Salem, Rany M.; Nievergelt, Caroline M.; Rana, Brinda K.; Smith, Douglas W.; Bakris, George L.; Middleton, John P.; Norris, Keith C.; Wright, Jackson T.; Cheek, Deanna; Hiremath, Leena; Contreras, Gabriel; Appel, Lawrence J.; Lipkowitz, Michael S.

2009-01-01

Objective It has yet to be determined whether genotyping at the angiotensin-converting enzyme (ACE) locus is predictive of blood pressure response to an ACE inhibitor. Methods Participants from the African American Study of Kidney Disease and Hypertension trial randomized to the ACE inhibitor ramipril (n = 347) were genotyped at three polymorphisms on ACE, just downstream from the ACE insertion/deletion polymorphism (Ins/Del): G12269A, C17888T, and G20037A. Time to reach target mean arterial pressure (≤ 107 mmHg) was analyzed by genotype and ACE haplotype using Kaplan–Meier survival curves and Cox proportional hazard models. Results Individuals with a homozygous genotype at G12269A responded significantly faster than those with a heterozygous genotype; the adjusted (average number of medications and baseline mean arterial pressure) hazard ratio (homozygous compared to heterozygous genotype) was 1.86 (95% confidence limits 1.32–3.23; P < 0.001 for G12269A genotype). The adjusted hazard ratio for participants with homozygous ACE haplotypes compared to those heterozygous ACE haplotypes was 1.40 (1.13–1.75; P = 0.003 for haplotype). The ACE genotype effects were specific for ACE inhibition (i.e., not seen among those randomized to a calcium channel blocker), and were independent of population stratification. Conclusions African-Americans with a homozygous genotype at G12269A or homozygous ACE haplotypes responded to ramipril significantly faster than those with a heterozygous genotype or heterozygous haplotypes, suggesting that heterosis may be an important determinant of responsiveness to an ACE inhibitor. These associations may be a result of biological activity of this polymorphism, or of linkage disequilibrium with nearby variants such as the ACE Ins/Del, perhaps in the regulation of ACE splicing. PMID:17885551

Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease.

PubMed

Tekatas, Demet D; Bahcecioglu, Ibrahim H; Ispiroglu, Murat; Sahin, Abdurrahman; Ilhan, Necip; Yalniz, Mehmet; Demirel, Ulvi

2016-01-01

In this study, we aimed to investigate the histological and clinical effect of angiotensin-converting enzyme (ACE) and ACE gene polymorphism in nonalcoholic fatty liver disease (NAFLD) and their roles in the progression of the disease. Liver function tests, body mass index, waist circumference, lipid parameters, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), homeostasis model assessment-IR (HOMA-IR), ACE, and ACE gene polymorphism were evaluated in the NAFLD group and control group. The study group was evaluated by dividing the group into four subgroups by ACE gene polymorphism (D/D homozygous, I/I homozygous, D/I heterozygous, I/D heterozygous). Liver biopsies were evaluated according to Brunt Classification. A total of 31 patients who were diagnosed with NAFLD and 40 healthy individuals were included in the study. The ACE level was found to be 11.69 ± 1.99 in the NAFLD group and 11.52 ± 1.72 in the control group (p = 0.70). There was a negative correlation between ACE levels and HOMA-IR levels (p = 0.008, r= -0.512). Biochemical parameters were not different among ACE gene polimorphism subgroups, except FBG (between D/D, I/D and D/I, I/D; p = 0.02). When the ACE levels were compared in terms of grade and stage, no significant difference was found (for stage and grade p = 0.68). The ACE gene polymorphism subgroups did not differ by histopathologic findings; grade and stage (for grade p = 0.42, for stage p = 0.92). In this study, we could not find a correlation of ACE and ACE gene polymorphism with metabolic risk factors and the disease severity in NAFLD. Tekatas DD, Bahcecioglu IH, Ispiroglu M, Sahin A, Ilhan N, Yalniz M, Demirel U. Role of Renin-Angiotensin-converting Enzyme Level and ACE Gene Polymorphism in Patients with Nonalcoholic Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2016;6(2):137-142.

ACE ID genotype and the muscle strength and size response to unilateral resistance training.

PubMed

Pescatello, Linda S; Kostek, Matthew A; Gordish-Dressman, Heather; Thompson, Paul D; Seip, Richard L; Price, Thomas B; Angelopoulos, Theodore J; Clarkson, Priscilla M; Gordon, Paul M; Moyna, Niall M; Visich, Paul S; Zoeller, Robert F; Devaney, Joseph M; Hoffman, Eric P

2006-06-01

To examine associations among the angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and the response to a 12-wk (2 d.wk) unilateral, upper-arm resistance training (RT) program in the trained (T, nondominant) and untrained (UT, dominant) arms. Subjects were 631 (mean+/-SEM, 24.2+/-0.2 yr) white (80%) men (42%) and women (58%). The ACE ID genotype was in Hardy-Weinberg equilibrium with frequencies of 23.1, 46.1, and 30.8% for ACE II, ID, and DD, respectively (chi=1.688, P=0.430). Maximum voluntary contraction (MVC) and one-repetition maximum (1RM) assessed peak elbow flexor muscle strength. Magnetic resonance imaging measured biceps muscle cross-sectional area (CSA). Multiple variable and repeated-measures ANCOVA tested whether muscle strength and size differed at baseline and pre- to post-RT among T and UT and ACE ID genotype. Baseline muscle strength and size were greater in UT than T (P<0.001) and did not differ among ACE ID genotype in either arm (P >or= 0.05). In T, MVC increases were greater for ACE II/ID (22%) than DD (17%) (P<0.05), whereas 1RM (51%) and CSA (19%) gains were not different among ACE ID genotype pre- to post-RT (P >or= 0.05). In UT, MVC increased among ACE II/ID (7%) (P<0.001) but was similar among ACE DD (2%) pre- to post-RT (P >or= 0.05). In UT, 1RM (11%) and CSA (2%) increases were greater for ACE DD/ID than ACE II (1RM, 7%; CSA, -0.1%) (P<0.05). ACE ID genotype explained approximately 1% of the MVC response to RT in T and approximately 2% of MVC, 2% of 1RM, and 4% of CSA response in UT (P<0.05). ACE ID genotype is associated with the contralateral effects of unilateral RT, perhaps more so than with the muscle strength and size adaptations that result from RT.

A qualitative evaluation of the 2005–2011 National Academic Centers of Excellence in Youth Violence Prevention Program☆

PubMed Central

Holland, Kristin M.; Vivolo-Kantor, Alana M.; Cruz, Jason Dela; Massetti, Greta M.; Mahendra, Reshma

2018-01-01

The Centers for Disease Control and Prevention’s Division of Violence Prevention (DVP) funded eight National Academic Centers of Excellence (ACEs) in Youth Violence Prevention from 2005 to 2010 and two Urban Partnership Academic Centers of Excellence (UPACEs) in Youth Violence Prevention from 2006 to 2011. The ACEs and UPACEs constitute DVP’s 2005–2011 ACE Program. ACE Program goals include partnering with communities to promote youth violence (YV) prevention and fostering connections between research and community practice. This article describes a qualitative evaluation of the 2005–2011 ACE Program using an innovative approach for collecting and analyzing data from multiple large research centers via a web-based Information System (ACE-IS). The ACE-IS was established as an efficient mechanism to collect and document ACE research and programmatic activities. Performance indicators for the ACE Program were established in an ACE Program logic model. Data on performance indicators were collected through the ACE-IS biannually. Data assessed Centers’ ability to develop, implement, and evaluate YV prevention activities. Performance indicator data demonstrate substantial progress on Centers’ research in YV risk and protective factors, community partnerships, and other accomplishments. Findings provide important lessons learned, illustrate progress made by the Centers, and point to new directions for YV prevention research and programmatic efforts. PMID:26319174

Operational warning of interplanetary shock arrivals using energetic particle data from ACE: Real-time Upstream Monitoring System

NASA Astrophysics Data System (ADS)

Donegan, M.; Vandegriff, J.; Ho, G. C.; Julia, S. J.

2004-12-01

We report on an operational system which provides advance warning and predictions of arrival times at Earth of interplanetary (IP) shocks that originate at the Sun. The data stream used in our prediction algorithm is real-time and comes from the Electron, Proton, and Alpha Monitor (EPAM) instrument on NASA's Advanced Composition Explorer (ACE) spacecraft. Since locally accelerated energetic storm particle (ESP) events accompany most IP shocks, their arrival can be predicted using ESP event signatures. We have previously reported on the development and implementation of an algorithm which recognizes the upstream particle signature of approaching IP shocks and provides estimated countdown predictions. A web-based system (see (http://sd-www.jhuapl.edu/UPOS/RISP/index.html) combines this prediction capability with real-time ACE/EPAM data provided by the NOAA Space Environment Center. The most recent ACE data is continually processed and predictions of shock arrival time are updated every five minutes when an event is impending. An operational display is provided to indicate advisories and countdowns for the event. Running the algorithm on a test set of historical events, we obtain a median error of about 10 hours for predictions made 24-36 hours before actual shock arrival and about 6 hours when the shock is 6-12 hours away. This system can provide critical information to mission planners, satellite operations controllers, and scientists by providing significant lead-time for approaching events. Recently, we have made improvements to the triggering mechanism as well as re-training the neural network, and here we report prediction results from the latest system.

Exploring the relationship between adverse childhood experiences and oral health-related quality of life.

PubMed

Kabani, Faizan; Lykens, Kristine; Tak, Hyo Jung

2018-05-12

Evidence indicates that adverse childhood experiences (ACEs) have destructive impacts on quality of life, health outcomes, and health-care expenditures. Studies further demonstrate a dose-response relationship between the number of ACEs and risk for experiencing chronic illness, such as oral diseases later in life. Research is scarce on the prioritization of contextualized public health interventions addressing this important threat. Cross-sectional data from 2011 to 2012 National Survey of Children's Health (NSCH) provided a nationally representative sample of children in the United States, ages 1-17 for dentate status (n = 61,530). The dependent variables identified untreated oral health-care needs and preventive dental utilization. The key independent variables included exposure to parental death, parental divorce, parental incarceration, mental health illnesses, domestic violence, neighborhood violence, and racial discrimination. Exogenous variables included age, sex, race/ethnicity, number of children in household, socioeconomic status proxies, health insurance status, and special health needs. The data, when adjusted for complex survey design, proportionately represent children in the United States. Unadjusted and adjusted logistic regressions revealed varying magnitudes of significance across diverse racial and ethnic profiles. Exposures to parental divorce and parental death particularly exhibited critical magnitudes of influence, compared to all other ACEs. In keeping with the Pareto Principle, exposure to certain ACEs, namely parental divorce and parental death, potentially introduces more profound social and health-related consequences later in life. Therefore, contextualized interventions should prioritize public health efforts to address households burdened with exposure to parental divorce and/or parental death. © 2018 American Association of Public Health Dentistry.

Assessing the Temporal Relationship between Race and Ecstasy Use among High School Seniors.

ERIC Educational Resources Information Center

Yacoubian, George S., Jr.

2002-01-01

Analyzes data from 10,088 high school seniors surveyed through the Monitoring the Future study between 1996 and 1999. Chi-square statistics are used to explore the temporal relationship between ace and the use of ecstasy during this time frame. Statistically significant relationship between race and ecstasy use are discerned. (Contains 46…

Awarding College Credit for MOOCSs: The Role of the American Council on Education

ERIC Educational Resources Information Center

Stone, Jason

2016-01-01

Emerging alongside the open educational resources movement of the past decade, Massive Open Online Courses (MOOCs) have been widely heralded as advancing cause of providing increased access to higher education. The article explores the implications of the recommendation by the American Council on Education (ACE) to offer college credit for a…

Use of the SAT in Advisement and Placement: What the Research Tells Us

ERIC Educational Resources Information Center

Shaw, Emily J.

2009-01-01

Presented at the College Board Western Regional Office (WRO) Forum in San Diego in February 2009. This presentation explores SAT test validity and how it can be used to inform both advisement and placement at the national or institution level. Institutional validity can be measured using the Admitted Class Evaluation Service (ACES) which schools…

Reporting of the translation and cultural adaptation procedures of the Addenbrooke's Cognitive Examination version III (ACE-III) and its predecessors: a systematic review.

PubMed

Mirza, Nadine; Panagioti, Maria; Waheed, Muhammad Wali; Waheed, Waquas

2017-09-13

The ACE-III, a gold standard for screening cognitive impairment, is restricted by language and culture, with no uniform set of guidelines for its adaptation. To develop guidelines a compilation of all the adaptation procedures undertaken by adapters of the ACE-III and its predecessors is needed. We searched EMBASE, Medline and PsychINFO and screened publications from a previous review. We included publications on adapted versions of the ACE-III and its predecessors, extracting translation and cultural adaptation procedures and assessing their quality. We deemed 32 papers suitable for analysis. 7 translation steps were identified and we determined which items of the ACE-III are culturally dependent. This review lists all adaptations of the ACE, ACE-R and ACE-III, rates the reporting of their adaptation procedures and summarises adaptation procedures into steps that can be undertaken by adapters.

Adverse childhood events and current depressive symptoms among women in Hawaii: 2010 BRFSS, Hawaii.

PubMed

Remigio-Baker, Rosemay A; Hayes, Donald K; Reyes-Salvail, Florentina

2014-12-01

Research on the association between adverse childhood events (ACEs) and depression among women in Hawaii is scarce. ACEs have been linked to unfavorable health behaviors such as smoking and binge drinking which are more prevalent in the state compared to the US overall. The concomitant presence of ACEs with smoking or binge drinking may explain the excess depression prevalence in Hawaii compared to the national average. Using data of women residing in the state (2010 Hawaii Behavioral Risk Factor Surveillance System Survey), we examined the association between ACEs count or type (household dysfunction and physical, verbal and sexual abuse) and current depressive symptoms (CDS), in addition to modification by current smoking status (smoked >100 cigarettes in a lifetime and currently smoke) and binge drinking (consumed ≥4 alcoholic beverage within the past month and in ≥1 occasion(s)). Evaluation of ACEs before age 18 consisted of 11 indicators. Eight indicators of the Patient Health Questionnaire (PHQ-8) were used to assess CDS. All analyses utilized logistic regression taking into account sampling design. The odds ratio of having CDS between those with versus without ACEs increased per increasing number of ACEs (1 ACE: OR = 2.11, CI = 1.16-3.81; 2 ACEs: OR = 2.90, CI = 1.51-5.58; 3 or 4 ACEs: OR = 3.94, CI = 2.13-7.32; 5+ ACEs: OR = 4.04, CI = 2.26-7.22). Household dysfunction (OR = 2.10, CI = 1.37-3.23), physical abuse (OR = 1.67, CI = 1.08-2.59), verbal abuse (OR = 3.21, CI = 2.03-5.09) and sexual abuse (OR = 1.68, CI = 1.04-2.71) were all positively associated with CDS. Verbal abuse had the strongest magnitude of association. Neither current smoking status nor binge drinking modified the relationship between ACEs count (or type) and CDS. In conclusion, the presence of ACEs among women in Hawaii was indicative of CDS in adulthood, notably verbal abuse. Further, a dose response existed between the number of ACEs and the odds for CDS. The concomitant exposure to ACEs and current smoking status or binge drinking did not elevate odds for CDS.

Adverse Childhood Experiences (ACEs) questionnaire and Adult Attachment Interview (AAI): implications for parent child relationships.

PubMed

Murphy, Anne; Steele, Miriam; Dube, Shanta Rishi; Bate, Jordan; Bonuck, Karen; Meissner, Paul; Goldman, Hannah; Steele, Howard

2014-02-01

Although Adverse Childhood Experiences (ACEs) are linked to increased health problems and risk behaviors in adulthood, there are no studies on the association between ACEs and adults' states of mind regarding their early childhood attachments, loss, and trauma experiences. To validate the ACEs questions, we analyzed the association between ACEs and emotional support indicators and Adult Attachment Interview (AAI) classifications in terms of unresolved mourning regarding past loss or trauma and discordant states of mind in cannot classify (U/CC) interviews. Seventy-five urban women (41 clinical and 34 community) completed a questionnaire on ACEs, which included 10 categories of abuse, neglect, and household dysfunction, in addition to emotional support. Internal psychological processes or states of mind concerning attachment were assessed using the AAI. ACE responses were internally consistent (Cronbach's α=.88). In the clinical sample, 84% reported≥4 ACEs compared to 27% among the community sample. AAIs judged U/CC occurred in 76% of the clinical sample compared to 9% in the community sample. When ACEs were≥4, 65% of AAIs were classified U/CC. Absence of emotional support in the ACEs questionnaire was associated with 72% of AAIs being classified U/CC. As the number of ACEs and the lack of emotional support increases so too does the probability of AAIs being classified as U/CC. Findings provide rationale for including ACEs questions in pediatric screening protocols to identify and offer treatment reducing the intergenerational transmission of risk associated with problematic parenting. Copyright © 2013 Elsevier Ltd. All rights reserved.

DNA Methylation Analysis of the Angiotensin Converting Enzyme (ACE) Gene in Major Depression

PubMed Central

Zill, Peter; Baghai, Thomas C.; Schüle, Cornelius; Born, Christoph; Früstück, Clemens; Büttner, Andreas; Eisenmenger, Wolfgang; Varallo-Bedarida, Gabriella; Rupprecht, Rainer; Möller, Hans-Jürgen; Bondy, Brigitta

2012-01-01

Background The angiotensin converting enzyme (ACE) has been repeatedly discussed as susceptibility factor for major depression (MD) and the bi-directional relation between MD and cardiovascular disorders (CVD). In this context, functional polymorphisms of the ACE gene have been linked to depression, to antidepressant treatment response, to ACE serum concentrations, as well as to hypertension, myocardial infarction and CVD risk markers. The mostly investigated ACE Ins/Del polymorphism accounts for ∼40%–50% of the ACE serum concentration variance, the remaining half is probably determined by other genetic, environmental or epigenetic factors, but these are poorly understood. Materials and Methods The main aim of the present study was the analysis of the DNA methylation pattern in the regulatory region of the ACE gene in peripheral leukocytes of 81 MD patients and 81 healthy controls. Results We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) and a significant inverse correlation between the ACE serum concentration and ACE promoter methylation frequency in the total sample (p = 0.02). Furthermore, a significant inverse correlation between the concentrations of the inflammatory CVD risk markers ICAM-1, E-selectin and P-selectin and the degree of ACE promoter methylation in MD patients could be demonstrated (p = 0.01 - 0.04). Conclusion The results of the present study suggest that aberrations in ACE promoter DNA methylation may be an underlying cause of MD and probably a common pathogenic factor for the bi-directional relationship between MD and cardiovascular disorders. PMID:22808171

Estimations of natural variability between satellite measurements of trace species concentrations

NASA Astrophysics Data System (ADS)

Sheese, P.; Walker, K. A.; Boone, C. D.; Degenstein, D. A.; Kolonjari, F.; Plummer, D. A.; von Clarmann, T.

2017-12-01

In order to validate satellite measurements of atmospheric states, it is necessary to understand the range of random and systematic errors inherent in the measurements. On occasions where the measurements do not agree within those errors, a common "go-to" explanation is that the unexplained difference can be chalked up to "natural variability". However, the expected natural variability is often left ambiguous and rarely quantified. This study will look to quantify the expected natural variability of both O3 and NO2 between two satellite instruments: ACE-FTS (Atmospheric Chemistry Experiment - Fourier Transform Spectrometer) and OSIRIS (Optical Spectrograph and Infrared Imaging System). By sampling the CMAM30 (30-year specified dynamics simulation of the Canadian Middle Atmosphere Model) climate chemistry model throughout the upper troposphere and stratosphere at times and geolocations of coincident ACE-FTS and OSIRIS measurements at varying coincidence criteria, height-dependent expected values of O3 and NO2 variability will be estimated and reported on. The results could also be used to better optimize the coincidence criteria used in satellite measurement validation studies.

Boundary Layer Thermodynamics and Cloud Microphysics for a Mixed Stratocumulus and Cumulus Cloud Field Observed during ACE-ENA

NASA Astrophysics Data System (ADS)

Jensen, M. P.; Miller, M. A.; Wang, J.

2017-12-01

The first Intensive Observation Period of the DOE Aerosol and Cloud Experiments in the Eastern North Atlantic (ACE-ENA) took place from 21 June through 20 July 2017 involving the deployment of the ARM Gulfstream-159 (G-1) aircraft with a suite of in situ cloud and aerosol instrumentation in the vicinity of the ARM Climate Research Facility Eastern North Atlantic (ENA) site on Graciosa Island, Azores. Here we present preliminary analysis of the thermodynamic characteristics of the marine boundary layer and the variability of cloud properties for a mixed cloud field including both stratiform cloud layers and deeper cumulus elements. Analysis combines in situ atmospheric state observations from the G-1 with radiosonde profiles and surface meteorology from the ENA site in order to characterize the thermodynamic structure of the marine boundary layer including the coupling state and stability. Cloud/drizzle droplet size distributions measured in situ are combined with remote sensing observations from a scanning cloud radar, and vertically pointing cloud radar and lidar provide quantification of the macrophysical and microphysical properties of the mixed cloud field.

The two-component system GrvRS (EtaRS) regulates ace expression in Enterococcus faecalis OG1RF.

PubMed

Roh, Jung Hyeob; Singh, Kavindra V; La Rosa, Sabina Leanti; Cohen, Ana Luisa V; Murray, Barbara E

2015-01-01

Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46 °C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

High altitude smoke in the NASA GISS GCM

NASA Technical Reports Server (NTRS)

Field, Robert; Luo, M.; Fromm, M.; Voulgarakis, A.; Mangeon, S.; Worden, J.

2015-01-01

High altitude smoke-plumes from large, explosive fires were discovered in the late 1990sThey can now be observed with unprecedented detail from space-borne instruments with high vertical resolution in the UTLS such as CALIOP, MLS and ACE. These events inject large quantities of pollutants into a relatively clean and dry environment They serve as unique natural experiments with which to understand, using chemical transport and composition-climate models, the chemical and radiative impacts of long-lived biomass burning emissions. We are currently studying the Black Saturday bushfires in Australia during February 2009

Wave Energy Prize - 1/20th Testing - CalWave Power Technologies

DOE Data Explorer

Scharmen, Wesley

2016-09-09

Data from the 1/20th scale testing data completed on the Wave Energy Prize for the CalWave Power Technologies team, including the 1/20th scale test plan, raw test data, video, photos, and data analysis results. The top level objective of the 1/20th scale device testing is to obtain the necessary measurements required for determining Average Climate Capture Width per Characteristic Capital Expenditure (ACE) and the Hydrodynamic Performance Quality (HPQ), key metrics for determining the Wave Energy Prize (WEP) winners.

Predictions and Tests of the "Late Noachian Icy Highlands" Climate Model: Can Evidence for Fluvial/Lacustrine Systems Be Reconciled?

NASA Astrophysics Data System (ADS)

Head, J. W., III

2016-12-01

Improved 3D global simulations (GCMs) of the early martian climate have found that for atmospheric pressures greater than a fraction of a bar, atmospheric-surface thermal coupling occurs and the adiabatic cooling effect (ACE) causes temperatures in the southern uplands to fall significantly below the global average. Long-term climate evolution simulations indicate that in these circumstances, water ice is transported to the highlands from low-lying regions for a wide range of obliquities. Conditions are too cold (MAT 225 K) to permit the presence of long-term surface liquid water, including streams, lakes and oceans. The LNIH equilibrium state predicts: 1) a global permafrost layer, 2) a horizontally stratified hydrological cycle/system, 3) thick ice deposits in the southern uplands, 4) an extended water ice cap on the southern pole, and 5) no rainfall, streams lakes or oceans. The majority of these predictions are in direct conflict with the observed fluvial/lacustrine geologic record. Can non-equilibrium conditions in a LNIH scenario explain these conflicts by transient heating and melting of the LNIH? As steps in the comprehensive testing of this "Late Noachian Icy Highlands" (LNIH) model we explore the predictions for geologic settings and processes in both equilibrium and non-equilibrium climate states. We assess the following sources of disequilibrium: 1) Top-down heating and melting: a) impact cratering, b) extrusive/explosive volcanism, and c) short-term emission of greenhouse gases. 2) Bottom up heating and melting: a) enhanced regional-global geothermal gradients, and b) thick ice accumulation to cause/sustain basal melting, wet-based glaciation and runoff. We assess these disequilibrium mechanisms in terms of: 1) the altitude dependence of melting, 2) melting duration, 3) volumes of meltwater produced, 4) predicted locations of meltwater production, and 6) comparison to the distribution of fluvial/lacustrine features. We find that the Late Noachian Icy Highlands climate model cannot be reconciled with observations unless punctuated non-equilibrium conditions occur. We show that the best candidates for LNIH disequilibrium conditions involve top-down heating and melting conditions chronologically summing in duration to more than tens of thousands to millions of years.

Pharmacologic modulation of ACE2 expression.

PubMed

Soler, María José; Barrios, Clara; Oliva, Raymond; Batlle, Daniel

2008-10-01

Angiotensin-converting enzyme 2 (ACE2) is an enzymatically active homologue of angiotensin-converting enzyme that degrades angiotensin I, angiotensin II, and other peptides. Recent studies have shown that under pathologic conditions, ACE2 expression in the kidney is altered. In this review, we briefly summarize recent studies dealing with pharmacologic interventions that modulate ACE2 expression. ACE2 amplification may have a potential therapeutic role for kidney disease and hypertension.

A Discussion of Aerodynamic Control Effectors (ACEs) for Unmanned Air Vehicles (UAVs)

NASA Technical Reports Server (NTRS)

Wood, Richard M.

2002-01-01

A Reynolds number based, unmanned air vehicle classification structure has been developed which identifies four classes of unmanned air vehicle concepts. The four unmanned air vehicle (UAV) classes are; Micro UAV, Meso UAV, Macro UAV, and Mega UAV. In a similar fashion a labeling scheme for aerodynamic control effectors (ACE) was developed and eleven types of ACE concepts were identified. These eleven types of ACEs were laid out in a five (5) layer scheme. The final section of the paper correlated the various ACE concepts to the four UAV classes and ACE recommendations are offered for future design activities.

A Low-Protein Diet Enhances Angiotensin II Production in the Lung of Pregnant Rats but Not Nonpregnant Rats

PubMed Central

Gao, Haijun; Tanchico, Daren Tubianosa; Yallampalli, Uma; Yallampalli, Chandrasekhar

2016-01-01

Pulmonary angiotensin II production is enhanced in pregnant rats fed a low-protein (LP) diet. Here we assessed if LP diet induces elevations in angiotensin II production in nonpregnant rats and whether Ace expression and ACE activity in lungs are increased. Nonpregnant rats were fed a normal (CT) or LP diet for 8, 12, or 17 days and timed pregnant rats fed for 17 days from Day 3 of pregnancy. Plasma angiotensin II, expressions of Ace and Ace2, and activities of these proteins in lungs, kidneys, and plasma were measured. These parameters were compared among nonpregnant rats or between nonpregnant and pregnant rats fed different diets. Major findings are as follows: (1) plasma angiotensin II levels were slightly higher in the LP than CT group on Days 8 and 12 in nonpregnant rats; (2) expression of Ace and Ace2 and abundance and activities of ACE and ACE2 in lungs, kidneys, and plasma of nonpregnant rats were unchanged by LP diet except for minor changes; (3) the abundance and activities of ACE in lungs of pregnant rats fed LP diet were greater than nonpregnant rats, while those of ACE2 were decreased. These results indicate that LP diet-induced increase in pulmonary angiotensin II production depends on pregnancy. PMID:27195150

Associations between ACE-Inhibitors, Angiotensin Receptor Blockers, and Lean Body Mass in Community Dwelling Older Women.

PubMed

Bea, Jennifer W; Wassertheil-Smoller, Sylvia; Wertheim, Betsy C; Klimentidis, Yann; Chen, Zhao; Zaslavsky, Oleg; Manini, Todd M; Womack, Catherine R; Kroenke, Candyce H; LaCroix, Andrea Z; Thomson, Cynthia A

2018-01-01

Studies suggest that ACE-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) may preserve skeletal muscle with aging. We evaluated longitudinal differences in lean body mass (LBM) among women diagnosed with hypertension and classified as ACE-I/ARB users and nonusers among Women's Health Initiative participants that received dual energy X-ray absorptiometry scans to estimate body composition ( n =10,635) at baseline and at years 3 and 6 of follow-up. Of those, 2642 were treated for hypertension at baseline. Multivariate linear regression models, adjusted for relevant demographics, behaviors, and medications, assessed ACE-I/ARB use/nonuse and LBM associations at baseline, as well as change in LBM over 3 and 6 years. Although BMI did not differ by ACE-I/ARB use, LBM (%) was significantly higher in ACE-I/ARB users versus nonusers at baseline (52.2% versus 51.3%, resp., p =0.001). There was no association between ACE-I/ARB usage and change in LBM over time. Reasons for higher LBM with ACE-I/ARB use cross sectionally, but not longitundinally, are unclear and may reflect a threshold effect of these medications on LBM that is attenuated over time. Nevertheless, ACE-I/ARB use does not appear to negatively impact LBM in the long term.

Adverse Childhood Experiences and Disordered Gambling: Assessing the Mediating Role of Emotion Dysregulation.

PubMed

Poole, Julia C; Kim, Hyoun S; Dobson, Keith S; Hodgins, David C

2017-12-01

Adverse childhood experiences (ACEs), such as sexual and physical abuse, have been established as risk factors for the development of disordered gambling. The underlying mechanism by which ACEs influence disordered gambling, however, remains unknown. The aims of the present research were to comprehensively investigate ten types of childhood adversity and their relationships to disordered gambling in adulthood, and to test whether emotion dysregulation mediated the relationship between ACEs and disordered gambling. A sample of community gamblers (N = 414) completed self-report measures of ACEs, emotion dysregulation, and gambling severity. Results revealed a significant association between all but one type (physical abuse) of ACEs and disordered gambling. Further, the results highlighted the cumulative impact of ACEs on gambling. Specifically, individuals who experienced three or more types of ACEs were more than three times as likely to report disordered gambling as compared to individuals with no history of childhood adversity. Importantly, as hypothesized, emotion dysregulation mediated the relationship between ACEs and disordered gambling. Findings from this research describe the association between ACEs and gambling and indicate a causal link between childhood adversity and disordered gambling. Results suggest that treatment initiatives may do well to address both ACEs and emotion dysregulation in the treatment of problem gambling.

RNA interference targeting the ACE gene reduced blood pressure and improved myocardial remodelling in SHRs.

PubMed

He, Junhua; Bian, Yunfei; Gao, Fen; Li, Maolian; Qiu, Ling; Wu, Weidong; Zhou, Hua; Liu, Gaizhen; Xiao, Chuanshi

2009-02-01

The purpose of the present study was to investigate the effects on blood pressure and myocardial hypertrophy in SHRs (spontaneously hypertensive rats) of RNAi (RNA interference) targeting ACE (angiotensin-converting enzyme). SHRs were treated with normal saline as vehicle controls, with Ad5-EGFP as vector controls, and with recombinant adenoviral vectors Ad5-EGFP-ACE-shRNA, carrying shRNA (small hairpin RNA) for ACE as ACE-RNAi. WKY (Wistar-Kyoto) rats were used as normotensive controls treated with normal saline. The systolic blood pressure of the caudal artery was recorded. Serum levels of ACE and AngII (angiotensin II) were determined using ELISA. ACE mRNA and protein levels were determined in aorta, myocardium, kidney and lung. On day 32 of the experiment, the heart was pathologically examined. The ratios of heart weight/body weight and left ventricular weight/body weight were calculated. The serum concentration of ACE was lower in ACE-RNAi rats (16.37+/-3.90 ng/ml) compared with vehicle controls and vector controls (48.26+/-1.50 ng/ml and 46.67+/-2.82 ng/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (14.88+/-3.15 ng/ml; P>0.05). The serum concentration of AngII was also significantly lower in ACE-RNAi rats (18.24+/-3.69 pg/ml) compared with vehicle controls and vector controls (46.21+/-5.06 pg/ml and 44.93+/-4.12 pg/ml respectively; both P<0.05), but comparable between ACE-RNAi rats and WKY rats (16.06+/-3.11 pg/ml; P>0.05). The expression of ACE mRNA and ACE protein were significantly reduced in the myocardium, aorta, kidney and lung in ACE-RNAi rats compared with that in vehicle controls and in vector controls (all P<0.05). ACE-RNAi treatment resulted in a reduction in systolic blood pressure by 22+/-3 mmHg and the ACE-RNAi-induced reduction lasted for more than 14 days. In contrast, blood pressure was continuously increased in the vehicle controls as well as in the vector controls. The ratios of heart weight/body weight and left ventricular weight/body weight were significantly lower in ACE-RNAi rats (3.12+/-0.23 mg/g and 2.24+/-0.19 mg/g) compared with the vehicle controls (4.29+/-0.24 mg/g and 3.21+/-0.13 mg/g; P<0.05) and the vector controls (4.43+/-0.19 mg/g and 3.13+/-0.12 mg/g; P<0.05). The conclusion of the present study is that ACE-silencing had significant antihypertensive effects and reversed hypertensive-induced cardiac hypertrophy in SHRs, and therefore RNAi might be a new strategy in controlling hypertension.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daud, A.I.; Bumpus, F.M.; Husain, A.

Ovarian angiotensin I (Ang I)-converting enzyme (ACE), estimated by the specific binding of the ACE inhibitor (125I)iodo-MK-351A, is localized on multiple ovarian structures, including follicular granulosa cells, corpora lutea, terminal epithelium, and ovarian blood vessels, but total ovarian ACE does not display a cyclic pattern of variation during the rat estrous cycle. We have previously shown that ACE is localized on the granulosa cell layer of a subpopulation of rat ovarian follicles. Our present study shows that ovarian granulosa cells contain high affinity (binding site affinity (Kd), approximately 90 pM) and low capacity (binding site density (Bmax), approximately 12 fmol/2.5more » X 10(5) cells) (125I)iodo-MK-351A-binding sites and convert (125I)iodo-Ang I to (125I)iodo-Ang II (greater than 85% of this conversion was inhibited by the ACE inhibitor captopril). Throughout the rat estrous cycle, 94-100% of developing follicles and 89-96% of atretic follicles contained high levels of ACE; however, ACE was either not observed or its levels were very low in preovulatory follicles. These findings indicate the presence of high levels of biologically active ACE on the surface of granulosa cells and suggest a potential role for follicular ACE in early stages of follicular maturation and atresia. Although ACE is known to process a variety of peptides found within the ovary, and these peptides may have opposing effects on follicular maturation, we attempted to define the cumulative effect of ACE inhibition on follicular maturation.« less

ACE genotype, phenotype and all-cause mortality in different cohorts of patients with type 1 diabetes.

PubMed

Færch, Louise H; Sejling, Anne-Sophie; Lajer, Maria; Tarnow, Lise; Thorsteinsson, Birger; Pedersen-Bjergaard, Ulrik

2015-06-01

Carrying the D-allele of the angiotensin-converting enzyme (ACE) I/D polymorphism and high ACE activity are prognostic factors in diabetic nephropathy, which predicts mortality in type 1 diabetes. We studied the association between the ACE D-allele and ACE phenotype and long-term all-cause mortality in three single-institution outpatient cohorts. Genotype-based analyses were performed in 269 patients from Hillerød Hospital (HIH) (follow-up: 12 years) and in 439 patients with diabetic nephropathy and 437 patients with persistent normoalbuminuria from the Steno Diabetes Center (SDC) (follow-up: 9.5 years). Patients not on renin-angiotensin system (RAS)-blocking treatment were included in analyses of serum ACE activity (HIH: n = 208) and plasma ACE concentration (SDC: n=269). In the HIH cohort, carrying a D-allele was associated with excess mortality (hazard ratio (HR) = 4.0 (95% confidence interval (CI) 1.0-16)), but not in the SDC cohorts. At HIH, serum ACE activity was associated with excess mortality (HR=1.04 (95% CI 1.0-1.1 per unit increase)), but in the SDC cohort plasma ACE concentration was not. In unselected patients with type 1 diabetes, carrying the ACE D-allele and high spontaneous serum ACE activity were associated with 12-year excess mortality. These findings could not be reproduced in two other cohorts with persistent normoalbuminuria or diabetic nephropathy. © The Author(s) 2013.

Genetic Deletion of ACE2 Induces Vascular Dysfunction in C57BL/6 Mice: Role of Nitric Oxide Imbalance and Oxidative Stress.

PubMed

Rabelo, Luiza A; Todiras, Mihail; Nunes-Souza, Valéria; Qadri, Fatimunnisa; Szijártó, István András; Gollasch, Maik; Penninger, Josef M; Bader, Michael; Santos, Robson A; Alenina, Natalia

2016-01-01

Accumulating evidence indicates that angiotensin-converting enzyme 2 (ACE2) plays a critical role in cardiovascular homeostasis, and its altered expression is associated with major cardiac and vascular disorders. The aim of this study was to evaluate the regulation of vascular function and assess the vascular redox balance in ACE2-deficient (ACE2-/y) animals. Experiments were performed in 20-22 week-old C57BL/6 and ACE2-/y male mice. Evaluation of endothelium-dependent and -independent relaxation revealed an impairment of in vitro and in vivo vascular function in ACE2-/y mice. Drastic reduction in eNOS expression at both protein and mRNA levels, and a decrease in •NO concentrations were observed in aortas of ACE2-/y mice in comparison to controls. Consistently, these mice presented a lower plasma and urine nitrite concentration, confirming reduced •NO availability in ACE2-deficient animals. Lipid peroxidation was significantly increased and superoxide dismutase activity was decreased in aorta homogenates of ACE2-/y mice, indicating impaired antioxidant capacity. Taken together, our data indicate, that ACE2 regulates vascular function by modulating nitric oxide release and oxidative stress. In conclusion, we elucidate mechanisms by which ACE2 is involved in the maintenance of vascular homeostasis. Furthermore, these findings provide insights into the role of the renin-angiotensin system in both vascular and systemic redox balance.

77 FR 48527 - National Customs Automation Program (NCAP) Test Concerning Automated Commercial Environment (ACE...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Program (NCAP) Test Concerning Automated Commercial Environment (ACE) Simplified Entry: Modification of... Automated Commercial Environment (ACE). The test's participant selection criteria are modified to reflect... (NCAP) test concerning Automated Commercial Environment (ACE) Simplified Entry functionality (Simplified...

ACE2 alterations in kidney disease.

PubMed

Soler, María José; Wysocki, Jan; Batlle, Daniel

2013-11-01

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1-7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance.

ACE2 alterations in kidney disease

PubMed Central

Soler, María José; Wysocki, Jan; Batlle, Daniel

2013-01-01

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1–7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance. PMID:23956234

Chronic School Absenteeism and the Role of Adverse Childhood Experiences.

PubMed

Stempel, Hilary; Cox-Martin, Matthew; Bronsert, Michael; Dickinson, L Miriam; Allison, Mandy A

To examine the association between chronic school absenteeism and adverse childhood experiences (ACEs) among school-age children. We conducted a secondary analysis of data from the 2011-2012 National Survey of Children's Health including children 6 to 17 years old. The primary outcome variable was chronic school absenteeism (≥15 days absent in the past year). We examined the association between chronic school absenteeism and ACEs by logistic regression with weighting for individual ACEs, summed ACE score, and latent class analysis of ACEs. Among the 58,765 school-age children in the study sample, 2416 (4.1%) experienced chronic school absenteeism. Witnessing or experiencing neighborhood violence was the only individual ACE significantly associated with chronic absenteeism (adjusted odds ratio [aOR] 1.55, 95% confidence interval [CI] 1.20-2.01). Having 1 or more ACE was significantly associated with chronic absenteeism: 1 ACE (aOR 1.35, 95% CI 1.02-1.79), 2 to 3 ACEs (aOR 1.81, 95% CI 1.39-2.36), and ≥4 ACEs (aOR 1.79, 95% CI 1.32-2.43). Three of the latent classes were also associated with chronic absenteeism, and children in these classes had a high probability of endorsing neighborhood violence, family substance use, or having multiple ACEs. ACE exposure was associated with chronic school absenteeism in school-age children. To improve school attendance, along with future graduation rates and long-term health, these findings highlight the need for an interdisciplinary approach to address child adversity that involves pediatricians, mental health providers, schools, and public health partners. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Poster - 07: Investigations of the Advanced Collapsed-cone Engine for HDR Brachytherapy Scalp Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cawston-Grant, Brie; Morrison, Hali; Sloboda, Ron

Purpose: To present an investigation of the Advanced Collapsed-cone Engine (ACE) in Oncentraê Brachy (OcB) v4.5 using a tissue equivalent phantom modeling scalp brachytherapy (BT) treatments. Methods: A slab phantom modeling the skin, skull, brain and mold was used. A dose of 400cGy was prescribed to just above the skull layer using TG-43 and was delivered using an HDR afterloader. Measurements were made using Gafchromic™ EBT3 film at four depths within the phantom. The TG-43 planned and film measured doses were compared to the standard (sACE) and high (hACE) accuracy ACE options in OcB between the surface and below themore » skull. Results: The average difference between the TG-43 calculated and film measured doses was −11.25±3.38% when there was no air gap between the mold and skin; sACE and hACE doses were on average lower than TG-43 calculated doses by 3.41±0.03% and 2.45±0.03%, respectively. With a 3mm air gap between the mold and skin, the difference between the TG-43 calculated and measured doses was −8.28±5.76%; sACE and hACE calculations yielded average doses 1.87±0.03% and 1.78±0.04% greater than TG-43, respectively. Conclusions: TG-43, sACE, and hACE were found to overestimate doses below the skull layer compared to film. With a 3mm air gap between the mold and skin, sACE and hACE more accurately predicted the film dose to the skin surface than TG-43. More clinical variations and their implications are currently being investigated.« less

Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Kailang; Peng, Guiqing; Wilken, Matthew

The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional,more » and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals.« less

Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome Coronavirus*

PubMed Central

Wu, Kailang; Peng, Guiqing; Wilken, Matthew; Geraghty, Robert J.; Li, Fang

2012-01-01

The severe acute respiratory syndrome coronavirus (SARS-CoV) from palm civets has twice evolved the capacity to infect humans by gaining binding affinity for human receptor angiotensin-converting enzyme 2 (ACE2). Numerous mutations have been identified in the receptor-binding domain (RBD) of different SARS-CoV strains isolated from humans or civets. Why these mutations were naturally selected or how SARS-CoV evolved to adapt to different host receptors has been poorly understood, presenting evolutionary and epidemic conundrums. In this study, we investigated the impact of these mutations on receptor recognition, an important determinant of SARS-CoV infection and pathogenesis. Using a combination of biochemical, functional, and crystallographic approaches, we elucidated the molecular and structural mechanisms of each of these naturally selected RBD mutations. These mutations either strengthen favorable interactions or reduce unfavorable interactions with two virus-binding hot spots on ACE2, and by doing so, they enhance viral interactions with either human (hACE2) or civet (cACE2) ACE2. Therefore, these mutations were viral adaptations to either hACE2 or cACE2. To corroborate the above analysis, we designed and characterized two optimized RBDs. The human-optimized RBD contains all of the hACE2-adapted residues (Phe-442, Phe-472, Asn-479, Asp-480, and Thr-487) and possesses exceptionally high affinity for hACE2 but relative low affinity for cACE2. The civet-optimized RBD contains all of the cACE2-adapted residues (Tyr-442, Pro-472, Arg-479, Gly-480, and Thr-487) and possesses exceptionally high affinity for cACE2 and also substantial affinity for hACE2. These results not only illustrate the detailed mechanisms of host receptor adaptation by SARS-CoV but also provide a molecular and structural basis for tracking future SARS-CoV evolution in animals. PMID:22291007

Sexual Identity, Adverse Childhood Experiences, and Suicidal Behaviors.

PubMed

Clements-Nolle, Kristen; Lensch, Taylor; Baxa, Amberlee; Gay, Christopher; Larson, Sandra; Yang, Wei

2018-02-01

The objective of this study was to examine the influence of sexual identity and adverse childhood experiences (ACEs) on suicidal behaviors in a population-based sample of high school students. A two-stage cluster random sampling design was used to recruit 5,108 students from 97 high schools. A total of 4,955 students (97%) provided information that allowed for classification of sexual identity into three groups: (1) lesbian, gay, or bisexual (LGB) (10%); (2) not sure (4.6%); and (3) heterosexual (85.4%). Five measures of childhood abuse and household dysfunction were summed, and the ACE score was categorized as 0, 1, 2, and 3-5 ACEs. Weighted logistic regression was used to assess the influence of sexual identity, ACEs, and their interaction on suicide ideation and attempts in the past 12 months. Compared with heterosexual students, those who were LGB and were not sure had higher odds of suicide ideation and attempts. There was also a graded relationship between cumulative ACE exposure and suicidal behaviors. Although sexual identity/ACE interaction was not observed, LGB/not sure students who experienced a high number of ACEs were disproportionately affected. Compared with heterosexual students with 0 ACE, LGB/not sure students with 0 ACE (adjusted odds ratio [AOR] = 3.32, 95% confidence interval [CI] = 1.96-5.61), 1 ACE (AOR = 6.58, 95% CI = 4.05-10.71), 2 ACEs (AOR 13.50, 95% CI = 8.45-21.58), and 3-5 ACEs (AOR = 14.04, 95% CI = 8.72, 22.62) had higher odds of suicide ideation. A similar pattern was observed for suicide attempts. LGB and students not sure of their sexual identity with greater exposure to ACEs have disproportionately high levels of suicide ideation and attempts. Trauma-informed interventions for these populations are warranted. Copyright © 2017 The Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Activation of angiotensin-converting enzyme 2 (ACE2) attenuates allergic airway inflammation in rat asthma model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhawale, Vaibhav Shrirang; Amara, Venkateswara Rao

Angiotensin-I converting enzyme (ACE) is positively correlated to asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and is highly expressed in lungs. ACE2, the counteracting enzyme of ACE, was proven to be protective in pulmonary, cardiovascular diseases. In the present study we checked the effect of ACE2 activation in animal model of asthma. Asthma was induced in male wistar rats by sensitization and challenge with ovalbumin and then treated with ACE2 activator, diminazene aceturate (DIZE) for 2 weeks. 48 h after last allergen challenge, animals were anesthetized, blood, BALF, femoral bone marrow lavage were collected for leucocytemore » count; trachea for measuring airway responsiveness to carbachol; lungs and heart were isolated for histological studies and western blotting. In our animal model, the characteristic features of asthma such as altered airway responsiveness to carbachol, eosinophilia and neutrophilia were observed. Western blotting revealed the increased pulmonary expression of ACE1, IL-1β, IL-4, NF-κB, BCL2, p-AKT, p-p38 and decreased expression of ACE2 and IκB. DIZE treatment prevented these alterations. Intraalveolar interstitial thickening, inflammatory cell infiltration, interstitial fibrosis, oxidative stress and right ventricular hypertrophy in asthma control animals were also reversed by DIZE treatment. Activation of ACE2 by DIZE conferred protection against asthma as evident from biochemical, functional, histological and molecular parameters. To the best of our knowledge, we report for the first time that activation of ACE2 by DIZE prevents asthma progression by altering AKT, p38, NF-κB and other inflammatory markers. - Highlights: • Diminazene aceturate (DIZE), an ACE2 activator prevents ovalbumin-induced asthma. • DIZE acted by upregulating ACE2, downregulating ACE1, MAPKs, markers of inflammation, apoptosis. • DIZE reduced airway inflammation, fibrosis, right ventricular hypertrophy and restored airway responsiveness.« less

Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

NASA Astrophysics Data System (ADS)

Kong, Zwe-Ling; Chang, Jenq-Sheng; Chang, Ke Liang B.

2013-09-01

Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

[Angiotensin converting enzyme: the antigenic properties of the domain, role in Alzheimer's disease and tumor progression].

PubMed

Kugaevskaya, E V; Timoshenko, O S; Solovyeva, N I

2015-01-01

Angiotensin converting enzyme (ACE, EC 3.4.15.1) was discovered and characterized in the Laboratory of biochemistry and chemical pathology of proteins under the direction of academician V.N. Orekhovich, where its physiological function, associated with a key role in the regulation of the renin-angiotensin (RAS) and the kallikrein-kinin systems that control blood flow in the body and homeostasis was first deciphered. We carried out a search for structural differences between the two highly homologous domains (N- and C-domains) of somatic ACE (sACE); it was based on a comparative analysis of antigenic determinants (or B-epitopes) of both domains. The revealed epitopes were classified with variable and conserved regions and functionally important sites of the molecule ACE. Essential difference was demonstrated between locations of the epitopes in the N- and C-domains. These data indicate the existence of structural differences between the domains of sACE. We studied the role of the domains of ACE in the metabolism of human amyloid beta peptide (Ab) - the main component of senile plaques, found in the brains of patients with Alzheimer's disease (AD). Our results demonstrated that only N-domain ACE cleaved the Ab between residues R5-H6, while, the C-domain of ACE failed to hydrolyze this region. In addition, the effect of post-translational modifications of Ab on its hydrolysis by the ACE was investigated. We show that isomerization of residue D7, a common non-enzymatic age-related modification found in AD-associated species, does not reduce the affinity of the peptide to the N-domain of ACE, and conversely, it increases. According to our data, the role of ACE in the metabolism of Ab becomes more significant in the development of AD. RAS is involved in malignant transformation and tumor progression. RAS components, including ACE and angiotensin II receptors type 1 (AT1R) are expressed in various human tumors. We found a significant increase in the level of ACE activity in the tumor tissue of squamous cell carcinoma of the cervix. In our viewpoint, the increase in ACE activity may be a marker of poor clinical prognosis.

Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villard, E.; Soubrier, F.; Tiret, L.

1996-06-01

Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage disequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms couldmore » be divided into two groups: five polymorphisms in the 5{prime} region and three in the coding sequence and the 3{prime} UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5{prime} group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT){sub 2/3} polymorphism. The second QTL would have a frequency of {approximately}.20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. 30 refs., 1 fig., 6 tabs.« less

The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism

PubMed Central

Vaughan, David; Brogioli, Michael; Maier, Thomas; White, Andy; Waldron, Sarah; Rittweger, Jörn; Toigo, Marco; Wettstein, Jessica; Laczko, Endre; Flück, Martin

2016-01-01

Objective A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle. Methods Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc. Results Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon. Conclusion The observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working skeletal muscle. ACE-DD genotypes thereby transit into a pre-diabetic state with exhaustive exercise, which relates to a lowered muscle capillarisation, and deregulation of mitochondria-associated metabolism. PMID:26982073

Identification and the molecular mechanism of a novel myosin-derived ACE inhibitory peptide.

PubMed

Yu, Zhipeng; Wu, Sijia; Zhao, Wenzhu; Ding, Long; Shiuan, David; Chen, Feng; Li, Jianrong; Liu, Jingbo

2018-01-24

The objective of this work was to identify a novel ACE inhibitory peptide from myosin using a number of in silico methods. Myosin was evaluated as a substrate for use in the generation of ACE inhibitory peptides using BIOPEP and ExPASy PeptideCutter. Then the ACE inhibitory activity prediction of peptides in silico was evaluated using the program peptide ranker, following the database search of known and unknown peptides using the program BIOPEP. In addition, the interaction mechanisms of the peptide and ACE were evaluated by DS. All of the tripeptides were predicted to be nontoxic. Results suggested that the tripeptide NCW exerted potent ACE inhibitory activity with an IC 50 value of 35.5 μM. Furthermore, the results suggested that the peptide NCW comes into contact with Zn 701, Tyr 523, His 383, Glu 384, Glu 411, and His 387. The potential molecular mechanism of the NCW/ACE interaction was investigated. Results confirmed that the higher inhibitory potency of NCW might be attributed to the formation of more hydrogen bonds with the ACE's active site. Therefore, the in silico method is effective to predict and identify novel ACE inhibitory peptides from protein hydrolysates.

Activation pattern of ACE2/Ang-(1-7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice.

PubMed

Tyrankiewicz, Urszula; Olkowicz, Mariola; Skórka, Tomasz; Jablonska, Magdalena; Orzylowska, Anna; Bar, Anna; Gonet, Michal; Berkowicz, Piotr; Jasinski, Krzysztof; Zoladz, Jerzy A; Smolenski, Ryszard T; Chlopicki, Stefan

2018-01-01

Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8-10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1-7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1-10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1-7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1-7) pathway, whereas the end-stage HF was associated with downregulation of ACE2/angiotensin-(1-7) and upregulation of the ACE/Ang II pathway. ACE/ACE-2 balance seems to determine the decompensation of HF in this model.

ACES--Today and Tomorrow.

ERIC Educational Resources Information Center

Hackney, Harold

1991-01-01

Presents text of Presidential Address delivered March 24, 1991, at the Association for Counselor Education and Supervision (ACES) luncheon, part of the American Association for Counseling and Development Convention held in Reno, Nevada. Comments on past, present, and future of ACES, particularly on future challenges and role of ACES. (ABL)

Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease.

PubMed

Anguiano, Lidia; Riera, Marta; Pascual, Julio; Valdivielso, José Manuel; Barrios, Clara; Betriu, Angels; Mojal, Sergi; Fernández, Elvira; Soler, María José

2015-07-01

Patients with cardiovascular (CV) disease have an increased circulating angiotensin-converting enzyme 2 (ACE2) activity, but there is little information about changes in ACE2 in chronic kidney disease (CKD) patients without history of CV disease. We examined circulating ACE2 activity in CKD patients at stages 3-5 (CKD3-5) and in dialysis (CKD5D) without any history of CV disease. Circulating ACE2 activity was measured in human ethylenediamine-tetraacetic acid (EDTA)-plasma samples from the NEFRONA study (n = 2572): control group (CONT) (n = 568), CKD3-5 (n = 1458) and CKD5D (n = 546). Different clinical and analytical variables such as gender; age; history of diabetes mellitus (DM), dyslipidemia and hypertension; glycaemic, renal, lipid and anaemia profiles; vitamin D analogues treatment and antihypertensive treatments (angiotensin-converting enzyme inhibitor and angiotensin receptor blockade) were analysed. Circulating ACE2 and ACE activities were measured using modified fluorimetric assay for EDTA-plasma samples, where zinc chloride was added to recover enzymatic activity. In CKD3-5 and CKD5D, significant decrease in circulating ACE2 activity was observed when compared with CONT, but no differences were found between CKD3-5 and CKD5 when performing paired case-control studies. By multivariate linear regression analysis, male gender and advanced age were identified as independent predictors of ACE2 activity in all groups. Diabetes was identified as independent predictor of ACE2 activity in CKD3-5. Significant increase in the activity of circulating ACE was found in CKD3-5 and CKD5D when compared with CONT and in CKD5D when compared with CKD3-5. By multiple regression analysis, female gender and younger age were identified as independent predictors of ACE activity in CONT and CKD3-5. Diabetes was also identified as an independent predictor of ACE activity in CKD3-5 patients. Circulating ACE2 and ACE activities can be measured in human EDTA-plasma samples with zinc added to recover enzymatic activity. In a CKD population without previous history of CV disease, ACE2 activity from human EDTA-plasma samples directly correlated with the classical CV risk factors namely older age, diabetes and male gender. Our data suggest that circulating ACE2 is altered in CKD patients at risk for CV event. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Impact of angiotensin-converting enzyme gene polymorphism on neurohormonal responses to high- versus low-dose enalapril in advanced heart failure.

PubMed

Tang, W H Wilson; Vagelos, Randall H; Yee, Yin-Gail; Fowler, Michael B

2004-11-01

The impact of angiotensin-converting enzyme (ACE) gene polymorphism on neurohormonal dose response to ACE inhibitor therapy is unclear. ACE Insertion (I) or Deletion (D) genotype was determined in 74 patients with chronic heart failure who were randomly assigned to receive either high-dose or low-dose enalapril over a period of 6 months. Monthly pre-enalapril and post-enalapril neurohormone levels (serum ACE activity (sACE), plasma angiotensin II (A-II), plasma renin activity (PRA), and serum aldosterone (ALDO) were compared between genotype subgroups and between patients who received high- or low-dose enalapril within each genotype subgroup. At baseline, predose/postdose sACE and postdose PRA were significantly higher in the DD genotype. At 6-month follow-up, postdose sACE was reduced in a dose-dependent fashion in all three genotypes (P < .05). However, predose and postdose ALDO and A-II levels did not differ between each genotype subgroup at baseline or by enalapril dose within each genotype subgroup. ALDO escape and A-II reactivation were not affected by ACE genotype or enalapril dosage. Predose sACE were consistently higher in the DD genotype when compared with ID or II subgroups. Despite a dose-dependent suppression of sACE, there were no observed statistically significant differences in ALDO and A-II suppression or escape with escalating doses of enalapril within each subgroup.

CD36/Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice

PubMed Central

Qadri, Fatimunnisa; Penninger, Josef M.; Santos, Robson Augusto S.; Bader, Michael

2016-01-01

Background and Aims. Angiotensin converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system. Since angiotensin peptides have been shown to be involved in hepatic steatosis, we aimed to evaluate the hepatic lipid profile in ACE2-deficient (ACE2−/y) mice. Methods. Male C57BL/6 and ACE2−/y mice were analyzed at the age of 3 and 6 months for alterations in the lipid profiles of plasma, faeces, and liver and for hepatic steatosis. Results. ACE2−/y mice showed lower body weight and white adipose tissue at all ages investigated. Moreover, these mice had lower levels of cholesterol, triglycerides, and nonesterified fatty acids in plasma. Strikingly, ACE2−/y mice showed high deposition of lipids in the liver. Expression of CD36, a protein involved in the uptake of triglycerides in liver, was increased in ACE2−/y mice. Concurrently, these mice exhibited an increase in hepatic oxidative stress, evidenced by increased lipid peroxidation and expression of uncoupling protein 2, and downregulation of sirtuin 1. ACE2−/y mice also showed impairments in glucose metabolism and insulin signaling in the liver. Conclusions. Deletion of ACE2 causes CD36/sirtuin 1 axis impairment and thereby interferes with lipid homeostasis, leading to lipodystrophy and steatosis. PMID:28101297

Emerging Biodegradation of the Previously Persistent Artificial Sweetener Acesulfame in Biological Wastewater Treatment.

PubMed

Kahl, Stefanie; Kleinsteuber, Sabine; Nivala, Jaime; van Afferden, Manfred; Reemtsma, Thorsten

2018-03-06

The persistence of acesulfame (ACE) in wastewater treatment (and subsequently the aquatic environment) has led to its use as a marker substance for wastewater input into surface water and groundwater. However, ACE degradation of >85% during summer and autumn was observed in nine German wastewater treatment plants (WWTPs). Annual removal performance was more stable in larger plants, enhanced by low biological oxygen demand and impeded by water temperatures below 10 °C. Literature data suggest that the potential to degrade ACE emerged in WWTPs around the year 2010. This development is ongoing, as illustrated by ACE content in the German rivers Elbe and Mulde: Between 2013 and 2016 the ACE mass load decreased by 70-80%. In enrichment cultures with ACE as sole carbon source the carbonaceous fraction of ACE was removed completely, indicating catabolic biotransformation and the inorganic compound sulfamic acid formed in quantitative amounts. Sequencing of bacterial 16S rRNA genes suggests that several species are involved in ACE degradation, with proteobacterial species affiliated to Phyllobacteriaceae, Methylophilaceae, Bradyrhizobiaceae, and Pseudomonas becoming specifically enriched. ACE appears to be the first micropollutant for which the evolution of a catabolic pathway in WWTPs has been witnessed. It can yet only be speculated whether the emergence of ACE removal in WWTPs in different regions of the world is due to independent evolution or to global spreading of genes or adapted microorganisms.

ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.

PubMed

Zhang, Yue Hui; Hao, Qing Qing; Wang, Xiao Yu; Chen, Xu; Wang, Nan; Zhu, Li; Li, Shu Ying; Yu, Qing Tao; Dong, Bo

2015-06-01

Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway. © The Author(s) 2014.

Clinical and biochemical presentation of sarcoidosis with high and normal serum angiotensin-converting enzyme.

PubMed

Sejdic, A; Graudal, N; Baslund, B

2018-06-22

The presentation of sarcoidosis can involve symptoms from all organs and the diagnosis is therefore often difficult. A raised serum level of serum angiotensin-converting enzyme (sACE) can be detected in 41-58% of patients. However, whether the sACE level per se reflects the severity of the sarcoid inflammation at the onset of the disease is not well described. The purpose of this study was to investigate the clinical and laboratory significance of high versus normal sACE levels in sarcoidosis. Journal data were retrospectively extracted from 101 patients from our clinic. Clinical and biochemical data were compared between patients with high sACE levels (> 115 U/L) on at least one occasion and normal sACE levels (< 115 U/L). In total, 48% (n = 48) of the patients had high ACE and 52% (n = 53) had normal ACE. The most common extrapulmonary manifestation for both groups was arthritis, followed by skin and eye involvement, but none of these differed between the two groups. Serum ionized calcium was significantly higher in the high sACE group, with a correlation coefficient of 0.112 (p = 0.460). Our study demonstrates that serum ionized calcium is significantly higher in the high sACE group but there was no statistical correlation to sACE. No other clinical or biochemical differences were observed.

[Angiotensin converting enzyme 2 and its emerging role in the regulation of the renin angiotensin system].

PubMed

Soler, María José; Lloveras, Josep; Batlle, Daniel

2008-07-12

The renin-angiotensin system (RAS) plays a key role in the regulation of cardiovascular and renal function. Thus, RAS blockade with an angiotensin-converting enzyme (ACE) and/or angiotensin receptor blocker decreases blood pressure, cardiovascular events, and delays the progression of kidney disease. The discovery of ACE2, a homologue of ACE, capable of degrading angiotensin II to angiotensin 1-7, may offer new insights into the RAS. In this review we discuss the possible protective role of ACE2 in different organs, namely heart, lungs and kidneys. The role of this enzyme is inferred from recent studies performed using genetically manipulated mice that lack the ACE2 gene and also mice treated with pharmacological ACE2 inhibitors. These results suggest that ACE2 might be a new therapeutic target within the RAS.

Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents?

PubMed

Wang, Pei; Fedoruk, Matthew N; Rupert, Jim L

2008-01-01

In the decade since the angiotensin-converting enzyme (ACE) gene was first proposed to be a 'human gene for physical performance', there have been numerous studies examining the effects of ACE genotype on physical performance phenotypes such as aerobic capacity, muscle function, trainability, and athletic status. While the results are variable and sometimes inconsistent, and corroborating phenotypic data limited, carriers of the ACE 'insertion' allele (the presence of an alu repeat element in intron 16 of the gene) have been reported to have higher maximum oxygen uptake (VO2max), greater response to training, and increased muscle efficiency when compared with individuals carrying the 'deletion' allele (absence of the alu repeat). Furthermore, the insertion allele has been reported to be over-represented in elite athletes from a variety of populations representing a number of endurance sports. The mechanism by which the ACE insertion genotype could potentiate physical performance is unknown. The presence of the ACE insertion allele has been associated with lower ACE activity (ACEplasma) in number of studies, suggesting that individuals with an innate tendency to have lower ACE levels respond better to training and are at an advantage in endurance sporting events. This could be due to lower levels of angiotensin II (the vasoconstrictor converted to active form by ACE), higher levels of bradykinin (a vasodilator degraded by ACE) or some combination of the two phenotypes. Observations that individuals carrying the ACE insertion allele (and presumably lower ACEplasma) have an enhanced response to training or are over-represented amongst elite athletes raises the intriguing question: would individuals with artificially lowered ACEplasma have similar training or performance potential? As there are a number of drugs (i.e. ACE inhibitors and angiotensin II type 1 receptor antagonists [angiotensin receptor blockers--ARBs]) that have the ability to either reduce ACEplasma activity or block the action of angiotensin II, the question is relevant to the study of ergogenic agents and to the efforts to rid sports of 'doping'. This article discusses the possibility that ACE inhibitors and ARBs, by virtue of their effects on ACE or angiotensin II function, respectively, have performance-enhancing capabilities; it also reviews the data on the effects of these medications on VO2max, muscle composition and endurance capacity in patient and non-patient populations. We conclude that, while the direct evidence supporting the hypothesis that ACE-related medications are potential doping agents is not compelling, there are insufficient data on young, athletic populations to exclude the possibility, and there is ample, albeit indirect, support from genetic studies to suggest that they should be. Unfortunately, given the history of drug experimentation in athletes and the rapid appropriation of therapeutic agents into the doping arsenal, this indirect evidence, coupled with the availability of ACE-inhibiting and ACE-receptor blocking medications may be sufficiently tempting to unscrupulous competitors looking for a shortcut to the finish line.

En Route to Transformation. On Change: An Occasional Paper Series of the ACE Project on Leadership and Institutional Transformation.

ERIC Educational Resources Information Center

Eckel, Peter; Hill, Barbara; Green, Madeleine

This paper explores transformation and change in American higher education. It begins by examining the debate over the type of change needed in higher education from the radical change suggested by some as necessary for survival to concepts of continual improvement urged by others. A definition of transformational change is offered which…

Adverse childhood experiences and association with health, mental health, and risky behavior in the kingdom of Saudi Arabia.

PubMed

Almuneef, Maha; Hollinshead, Dana; Saleheen, Hassan; AlMadani, Sereen; Derkash, Bridget; AlBuhairan, Fadia; Al-Eissa, Majid; Fluke, John

2016-10-01

The aim of this study is to determine if ACEs impact the health and risk behavior burden among Kingdom of Saudi Arabia (KSA) adults. In 2013, a cross-sectional study was conducted across KSA to identify the retrospective prevalence of ACEs and their association with high risk behaviors and chronic diseases. Surveys from 10,156 adults in all 13 Saudi regions were obtained using an Arabic version of the WHO ACE-IQ (KSA ACE-IQ). Compared to respondents reporting no ACEs, even just one ACE contributed significantly to the odds of experiencing diabetes mellitus (OR=1.3), depression (OR=1.32), or anxiety (OR=1.79) outcomes. Two ACEs were necessary for statistically significant, higher odds to emerge for hypertension (OR=1.46), mental illness (OR=1.93), smoking (OR=1.17), alcohol use (OR=1.75), and drug use (OR=1.45). Respondents who reported four or more ACEs had greater odds of coronary heart disease (OR=1.94), and obesity (OR=2.25). Compared to those reporting no ACEs, respondents reporting four or more ACEs had over four times the odds of Alcohol or Drug Use, Mental Illness, Depression, and/or Anxiety outcomes and more than twice the odds of diabetes, hypertension, obesity, and/or smoking outcomes. Findings from this analysis underscore the potential benefit of providing focused preventative approaches to mitigating ACEs in KSA in relation to both the specific and cumulative burden of health and risky behavior outcomes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adverse childhood experiences and blood pressure trajectories from childhood to young adulthood: the Georgia stress and Heart study.

PubMed

Su, Shaoyong; Wang, Xiaoling; Pollock, Jennifer S; Treiber, Frank A; Xu, Xiaojing; Snieder, Harold; McCall, W Vaughn; Stefanek, Michael; Harshfield, Gregory A

2015-05-12

The purposes of this study were to assess the long-term effect of adverse childhood experiences (ACEs) on blood pressure (BP) trajectories from childhood to young adulthood and to examine whether this relation is explained by childhood socioeconomic status (SES) or risk behaviors that are associated with ACEs. Systolic and diastolic BPs were measured up to 16 times (13 times on average) over a 23-year period in 213 African Americans and 181 European Americans 5 to 38 years of age. Retrospective data on traumatic experiences before 18 years of age were collected, including abuse, neglect, and household dysfunction. Individual growth curve modeling within a multilevel framework was used to examine the relation between exposure to ACEs and BP development. No main effect of ACEs on average BP levels was found. However, a significant interaction of ACE score with age(3) was observed (systolic BP, P=0.033; diastolic BP, P=0.017). Subjects who experienced multiple traumatic events during childhood showed a faster rise in BP levels after 30 years of age than those without ACEs. As expected, a graded association of ACEs with childhood socioeconomic status and negative health behaviors was observed (P<0.001). The ACE-systolic BP relation was not explained by these factors, whereas the ACE-diastolic BP relation was partially mediated by illicit drug use. In this novel longitudinal study, we observed that participants who were exposed to multiple ACEs displayed a greater increase in BP levels in young adulthood compared with their counterparts without ACEs. © 2015 American Heart Association, Inc.

Effects of Small Molecule Calcium-Activated Chloride Channel Inhibitors on Structure and Function of Accessory Cholera Enterotoxin (Ace) of Vibrio cholerae

PubMed Central

Chatterjee, Tanaya; Sheikh, Irshad Ali; Chakravarty, Devlina; Chakrabarti, Pinak; Sarkar, Paramita; Saha, Tultul; Chakrabarti, Manoj K.; Hoque, Kazi Mirajul

2015-01-01

Cholera pathogenesis occurs due to synergistic pro-secretory effects of several toxins, such as cholera toxin (CTX) and Accessory cholera enterotoxin (Ace) secreted by Vibrio cholerae strains. Ace activates chloride channels stimulating chloride/bicarbonate transport that augments fluid secretion resulting in diarrhea. These channels have been targeted for drug development. However, lesser attention has been paid to the interaction of chloride channel modulators with bacterial toxins. Here we report the modulation of the structure/function of recombinant Ace by small molecule calcium-activated chloride channel (CaCC) inhibitors, namely CaCCinh-A01, digallic acid (DGA) and tannic acid. Biophysical studies indicate that the unfolding (induced by urea) free energy increases upon binding CaCCinh-A01 and DGA, compared to native Ace, whereas binding of tannic acid destabilizes the protein. Far-UV CD experiments revealed that the α-helical content of Ace-CaCCinh-A01 and Ace-DGA complexes increased relative to Ace. In contrast, binding to tannic acid had the opposite effect, indicating the loss of protein secondary structure. The modulation of Ace structure induced by CaCC inhibitors was also analyzed using docking and molecular dynamics (MD) simulation. Functional studies, performed using mouse ileal loops and Ussing chamber experiments, corroborate biophysical data, all pointing to the fact that tannic acid destabilizes Ace, inhibiting its function, whereas DGA stabilizes the toxin with enhanced fluid accumulation in mouse ileal loop. The efficacy of tannic acid in mouse model suggests that the targeted modulation of Ace structure may be of therapeutic benefit for gastrointestinal disorders. PMID:26540279

Our ACE in the HOLE: Justifying the Use of Angiotensin-converting Enzyme Inhibitors as Adjuvants to Standard Chemotherapy.

PubMed

Radin, Daniel P; Krebs, Austin; Maqsudlu, Arman; Patel, Parth

2018-01-01

Angiotensin-I-converting enzyme (ACE) inhibitors have been very effective in treating cardiac hypertension since their clinical inception over four decades ago. Since then, it has been established that angiotensin II, the product of ACE, has oncogenic and pro-proliferative qualities, which begs the question as to whether ACE inhibitors may have oncolytic characteristics. In fact, scattered reports suggest that ACE inhibitors are oncolytic and oncopreventive, but the available literature has yet to be thoroughly examined. In the present review, we examine the available literature and determine that ACE inhibitors would have great utility in the prevention and treatment of cancer. At the same time, they would augment the efficacy of chemo- and radiotherapy as well as mitigating damage to healthy tissue by standard chemotherapeutic regimens. We review some of the mounting clinical evidence and show that ACE inhibitors have oncolytic activity in multiple types of cancer and discuss the ability of ACE inhibitors to prevent cardiotoxicity of multiple chemotherapies. Our analysis demonstrates that the actions of ACE inhibitors converge on vascular endolthelial growth factor to reduce its levels in tumors and prevent construction of blood vessels to masses, leaving them nutrient-depleted and subsequently hindering their growth. Given that ACE inhibitors are approved by the Federal Drug Administration and the therapeutic dose for hypertension treatment also slows the growth of multiple cancers types, ACE inhibitors are in a perfect position to be repurposed as oncolytic agents, that would widely increase their utility in the clinic. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Adverse Childhood Experiences and Blood Pressure Trajectories from Childhood to Young Adulthood: The Georgia Stress and Heart Study

PubMed Central

Su, Shaoyong; Wang, Xiaoling; Pollock, Jennifer S.; Treiber, Frank A.; Xu, Xiaojing; Snieder, Harold; McCall, W. Vaughn; Stefanek, Michael; Harshfield, Gregory A.

2015-01-01

Background The purpose of this study was to assess the long-term effect of adverse childhood experiences (ACEs) on blood pressure (BP) trajectories from childhood to young adulthood and to examine whether this relation is explained by childhood socioeconomic status (SES) and/or risk behaviors that are associated with ACEs. Methods and Results Systolic and diastolic blood pressure (SBP and DBP) were measured up to 16 times (13 times on average) over a 23-year period in 213 African Americans (AAs) and 181 European Americans (EAs) aged 5 to 38 years. Retrospective data on traumatic experiences prior to age 18 were collected, including abuse, neglect and household dysfunction. Individual growth curve modeling within a multilevel framework was used to examine the relation between exposure to ACEs and BP development. No main effect of ACEs on average BP levels was found. However, a significant interaction of ACE score with age3 was observed (SBP: p=0.033; DBP: p=0.017). Subjects who experienced multiple traumatic events during childhood showed a faster rise of BP levels after age of 30 years than those without ACEs. As expected, a graded association of ACEs with childhood SES and negative health behaviors was observed (p<0.001). The ACE-SBP relation was not explained by these factors, while the ACE-DBP relation was partially mediated by illicit drug use. Conclusions In this novel longitudinal study, we observed that participants who were exposed to multiple ACEs displayed a greater increase of BP levels in young adulthood compared to their counterparts without ACEs. PMID:25858196

Adverse childhood experiences, gender, and HIV risk behaviors: Results from a population-based sample.

PubMed

Fang, Lin; Chuang, Deng-Min; Lee, Yookyong

2016-12-01

Recent HIV research suggested assessing adverse childhood experiences (ACEs) as contributing factors of HIV risk behaviors. However, studies often focused on a single type of adverse experience and very few utilized population-based data. This population study examined the associations between ACE (individual and cumulative ACE score) and HIV risk behaviors. We analyzed the 2012 Behavioral Risk Factor Surveillance Survey (BRFSS) from 5 states. The sample consisted of 39,434 adults. Eight types of ACEs that included different types of child abuse and household dysfunctions before the age of 18 were measured. A cumulative score of ACEs was also computed. Logistic regression estimated of the association between ACEs and HIV risk behaviors using odds ratio (OR) with 95% confidence intervals (CIs) for males and females separately. We found that ACEs were positively associated with HIV risk behaviors overall, but the associations differed between males and females in a few instances. While the cumulative ACE score was associated with HIV risk behaviors in a stepwise manner, the pattern varied by gender. For males, the odds of HIV risk increased at a significant level as long as they experienced one ACE, whereas for females, the odds did not increase until they experienced three or more ACEs. Future research should further investigate the gender-specific associations between ACEs and HIV risk behaviors. As childhood adversities are prevalent among general population, and such experiences are associated with increased risk behaviors for HIV transmission, service providers can benefit from the principles of trauma-informed practice.

Do Pediatricians Ask About Adverse Childhood Experiences in Pediatric Primary Care?

PubMed

Kerker, Bonnie D; Storfer-Isser, Amy; Szilagyi, Moira; Stein, Ruth E K; Garner, Andrew S; O'Connor, Karen G; Hoagwood, Kimberly E; Horwitz, Sarah M

2016-03-01

The stress associated with adverse childhood experiences (ACEs) has immediate and long-lasting effects. The objectives of this study were to examine 1) how often pediatricians ask patients' families about ACEs, 2) how familiar pediatricians are with the original ACE study, and 3) physician/practice characteristics, physicians' mental health training, and physicians' attitudes/beliefs that are associated with asking about ACEs. Data were collected from 302 nontrainee pediatricians exclusively practicing general pediatrics who completed the 2013 American Academy of Pediatrics Periodic Survey. Pediatricians indicated whether they usually, sometimes, or never inquired about or screened for 7 ACEs. Sample weights were used to reduce nonresponse bias. Weighted descriptive and logistic regression analyses were conducted. Only 4% of pediatricians usually asked about all 7 ACEs; 32% did not usually ask about any. Less than 11% of pediatricians reported being very or somewhat familiar with the ACE study. Pediatricians who screened/inquired about ACEs usually asked about maternal depression (46%) and parental separation/divorce (42%). Multivariable analyses showed that pediatricians had more than twice the odds of usually asking about ACEs if they disagreed that they have little effect on influencing positive parenting skills, disagreed that screening for social emotional risk factors within the family is beyond the scope of pediatricians, or were very interested in receiving further education on managing/treating mental health problems in children and adolescents. Few pediatricians ask about all ACEs. Pediatric training that emphasizes the importance of social/emotional risk factors may increase the identification of ACEs in pediatric primary care. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Optimal attitude maneuver execution for the Advanced Composition Explorer (ACE) mission

NASA Technical Reports Server (NTRS)

Woodard, Mark A.; Baker, David

1995-01-01

The Advanced Composition Explorer (ACE) spacecraft will require frequent attitude reorientations in order to maintain the spacecraft high gain antenna (HGA) within 3 deg of earth-pointing. These attitude maneuvers will be accomplished by employing a series of ground-commanded thruster pulses, computed by ground operations personnel, to achieve the desired change in the spacecraft angular momentum vector. With each maneuver, attitude nutation will be excited. Large nutation angles are undesirable from a science standpoint. It is important that the thruster firings be phased properly in order to minimize the nutation angle at the end of the maneuver so that science collection time is maximized. The analysis presented derives a simple approximation for the nutation contribution resulting from a series of short thruster burns. Analytic equations are derived which give the induced nutation angle as a function of the number of small thruster burns used to execute the attitude maneuver and the phasing of the burns. The results show that by properly subdividing the attitude burns, the induced nutation can be kept low. The analytic equations are also verified through attitude dynamics simulation and simulation results are presented. Finally, techniques for quantifying the post-maneuver nutation are discussed.

The Acceleration of Thermal Protons and Minor Ions at a Quasi-Parallel Interplanetary Shock

NASA Astrophysics Data System (ADS)

Giacalone, J.; Lario, D.; Lepri, S. T.

2017-12-01

We compare the results from self-consistent hybrid simulations (kinetic ions, massless fluid electrons) and spacecraft observations of a strong, quasi-parallel interplanetary shock that crossed the Advanced Composition Explorer (ACE) on DOY 94, 2001. In our simulations, the un-shocked plasma-frame ion distributions are Maxwellian. Our simulations include protons and minor ions (alphas, 3He++, and C5+). The interplanetary shock crossed both the ACE and the Wind spacecraft, and was associated with significant increases in the flux of > 50 keV/nuc ions. Our simulation uses parameters (ion densities, magnetic field strength, Mach number, etc.) consistent with those observed. Acceleration of the ions by the shock, in a manner similar to that expected from diffusive shock acceleration theory, leads to a high-energy tail in the distribution of the post-shock plasma for all ions we considered. The simulated distributions are directly compared to those observed by ACE/SWICS, EPAM, and ULEIS, and Wind/STICS and 3DP, covering the energy range from below the thermal peak to the suprathermal tail. We conclude from our study that the solar wind is the most significant source of the high-energy ions for this event. Our results have important implications for the physics of the so-called `injection problem', which will be discussed.

Adverse Childhood Experiences and Arrest Patterns in a Sample of Sexual Offenders.

PubMed

Levenson, Jill S; Socia, Kelly M

2016-06-01

Developmental psychopathology theories suggest that childhood adversity can contribute to antisocial conduct and delinquent activities. The purpose of this study was to explore the influence of adverse childhood experiences (ACE) on arrest patterns in a sample of sexual offenders (N = 740). Higher ACE scores were associated with a variety of arrest outcomes, indicating that the accumulation of early trauma increased the likelihood of versatility and persistence of criminal behavior. Rapists of adults had higher ACE scores, lower levels of specialization, and higher levels of persistence than sex offenders with minor victims only. Child sexual abuse, emotional neglect, and domestic violence in the childhood home were significant predictors of a higher number of sex crime arrests. For measures of nonsexual arrests and criminal versatility, it was the household dysfunction factors-substance abuse, unmarried parents, and incarceration of a family member-that were predictive, suggesting that family dysfunction and a chaotic home environment contributed significantly to increased risk of general criminal behavior. Sex offenders inspire little sympathy in our society but may be among those most in need of trauma-informed models of treatment that recognize the influence of early adversity on maladaptive schema and self-regulation deficits related to criminal behavior. © The Author(s) 2015.

Effect of Delta Tabs on Free Jets from Complex Nozzles

NASA Technical Reports Server (NTRS)

Zaman, K. B. M. Q.

2001-01-01

Effects of 'delta-tabs' on the mixing and noise characteristics of two model-scale nozzles have been investigated experimentally. The two models are (1) an eight-lobed nozzle simulating the primary flow of a mixer-ejector configuration considered for the HSCT program, (2) an axisymmetric nozzle with a centerbody simulating the 'ACE' configuration also considered for the HSCT program. Details of the flow-field for model (1) are explored, while primarily the noise-field is explored for model (2). Effects of different tab configurations are documented.

FIRE III ACE

Atmospheric Science Data Center

2013-01-23

FIRE III ACE Data Sets The First International Satellite Cloud ... Regional Experiment (FIRE) - Arctic Cloud Experiment (ACE) was conducted April through July of 1998. It was held in conjunction with ... Heat Budget of the Arctic Ocean (SHEBA) Experiment. The FIRE-ACE focused on all aspects of Arctic cloud systems. The main facility was ...

Correlates of current and heavy smoking among U.S. soldiers returning from combat.

PubMed

Lopez, Alexa A; Toblin, Robin L; Riviere, Lyndon A; Lee, James D; Adler, Amy B

2018-06-01

Smoking rates are higher in U.S. soldiers than civilians, with combat-experienced soldiers particularly at risk for heavy smoking (≥20 cigarettes/day). While heavy smoking is correlated with mental health symptoms in civilian samples, the extent to which these symptoms, background variables, and unit climate (self-reported assessments of cohesion, organizational support, and leadership) are linked to smoking in at-risk soldiers remains unclear. The present study examines a range of correlates of smoking-related behavior. Cross-sectional, anonymous surveys were collected from 3,380 soldiers following a deployment in 2008-2009. Measures included demographics, combat exposures, unit climate (e.g., unit cohesion, perceived organizational support, leadership), short sleep duration, and behavioral health variables (e.g., posttraumatic stress disorder, depression, anxiety, alcohol misuse, aggression, adverse childhood experiences [ACEs]). Logistic regression modeled the effects of these variables on two outcome variables: daily smoking and heavy smoking. In the current sample, nearly half (47%) of soldiers reported smoking daily, with 35% of all smokers reporting heavy smoking (17% of the entire sample). Daily smoking was associated with demographic (age, gender, education, rank), behavioral health (ACE, alcohol misuse, sleep duration, aggression), and unit characteristics (unit cohesion); only increased combat exposures and aggression were specifically associated with heavy smoking. Interventions focused on the postdeployment period could incorporate messages about alternatives to smoking as a coping strategy while unit interventions or individual counseling addressing aggression could also address smoking as a negative coping strategy. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Solar radiation variability over La Réunion island and associated larger-scale dynamics

NASA Astrophysics Data System (ADS)

Mialhe, Pauline; Morel, Béatrice; Pohl, Benjamin; Bessafi, Miloud; Chabriat, Jean-Pierre

2017-04-01

This study aims to examine the solar radiation variability over La Réunion island and its relationship with large-scale circulation. The Satellite Application Facility on Climate Monitoring (CM SAF) produces a Shortwave Incoming Solar radiation (SIS) data record called Solar surfAce RAdiation Heliosat - East (SARAH-E). A comparison to in situ observations from Météo-France measurements networks quantifies the skill of SARAH-E grids which we use as dataset. First step of the work, irradiance mean cycles are calculated to describe the diurnal-seasonal SIS behaviour over La Réunion island. By analogy with the climate anomalies, instantaneous deviations are computed after removal of the mean states. Finally, we associate these anomalies with larger-scale atmospheric dynamics into the South West Indian Ocean by applying multivariate clustering analyses (Hierarchical Ascending Classification, k-means).

Economic evaluation of the Annual Cycle Energy System (ACES). Volume 1: Executive summary

NASA Astrophysics Data System (ADS)

1980-05-01

Three different classes of building are investigated, namely: single family residence; multifamily residence; and commercial office building. For each building type in each geographic location, the economic evaluation of the annual cycle energy system (ACES) is based on a comparison of the present worth of the ACES to the present worth of a number of conventional systems. The results of this analysis indicate that the economic viability of the ACES is very sensitive to the assumed value of the property tax, maintenance cost, and fuel escalation rates, while it is relatively insensitive to the assumed values of other parameters. Fortunately, any conceivable change in the fuel escalation rates would tend to increase the viability of the ACES concept. An increase in the assumed value of the maintenance cost or property tax would tend to make the ACES concept less viable; a decrease in either would tend to make the ACES concept more viable.

ACE Over Expression in Myelomonocytic Cells: Effect on a Mouse Model of Alzheimer's Disease

PubMed Central

Koronyo-Hamaoui, Maya; Shah, Kandarp; Koronyo, Yosef; Bernstein, Ellen; Giani, Jorge F.; Janjulia, Tea; Black, Keith L.; Shi, Peng D.; Gonzalez-Villalobos, Romer A.; Fuchs, Sebastien; Shen, Xiao Z.; Bernstein, Kenneth E.

2014-01-01

While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice over express ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer's disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD. PMID:24792094

Identification of an ACE-Inhibitory Peptide from Walnut Protein and Its Evaluation of the Inhibitory Mechanism.

PubMed

Wang, Cong; Tu, Maolin; Wu, Di; Chen, Hui; Chen, Cheng; Wang, Zhenyu; Jiang, Lianzhou

2018-04-11

In the present study, a novel angiotensin I-converting enzyme inhibitory (ACE inhibitory) peptide, EPNGLLLPQY, derived from walnut seed storage protein, fragment residues 80-89, was identified by ultra-high performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) from walnut protein hydrolysate. The IC 50 value of the peptide was 233.178 μM, which was determined by the high performance liquid chromatography method by measuring the amount of hippuric acid (HA) generated from the ACE decomposition substrate (hippuryl-l-histidyl-l-leucine (HHL) to assess the ACE activity. Enzyme inhibitory kinetics of the peptide against ACE were also conducted, by which the inhibitory mechanism of ACE-inhibitory peptide was confirmed. Moreover, molecular docking was simulated by Discovery Studio 2017 R2 software to provide the potential mechanisms underlying the ACE-inhibitory activity of EPNGLLLPQY.

Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Plants

PubMed Central

Daskaya-Dikmen, Ceren; Yucetepe, Aysun; Karbancioglu-Guler, Funda; Daskaya, Hayrettin; Ozcelik, Beraat

2017-01-01

Hypertension is an important factor in cardiovascular diseases. Angiotensin-I-converting enzyme (ACE) inhibitors like synthetic drugs are widely used to control hypertension. ACE-inhibitory peptides from food origins could be a good alternative to synthetic drugs. A number of plant-based peptides have been investigated for their potential ACE inhibitor activities by using in vitro and in vivo assays. These plant-based peptides can be obtained by solvent extraction, enzymatic hydrolysis with or without novel food processing methods, and fermentation. ACE-inhibitory activities of peptides can be affected by their structural characteristics such as chain length, composition and sequence. ACE-inhibitory peptides should have gastrointestinal stability and reach the cardiovascular system to show their bioactivity. This paper reviews the current literature on plant-derived ACE-inhibitory peptides including their sources, production and structure, as well as their activity by in vitro and in vivo studies and their bioavailability. PMID:28333109

Trauma-Sensitive Schools: An Evidence-Based Approach

ERIC Educational Resources Information Center

Plumb, Jacqui L.; Bush, Kelly A.; Kersevich, Sonia E.

2016-01-01

Adverse childhood experiences (ACEs) are a common and pervasive problem. There is a positive correlation between ACEs and difficulties across the lifespan. Unlike healthy forms of stress, ACEs have a detrimental impact on the developing brain. There are three types of trauma: acute, chronic, and complex. Most ACEs are considered complex trauma,…

Adverse childhood experiences, family functioning and adolescent health and emotional well-being.

PubMed

Balistreri, K S; Alvira-Hammond, M

2016-03-01

Adverse childhood experiences (ACEs) have been consistently linked in a strong and graded fashion to a host of health problems in later adulthood but few studies have examined the more proximate effect of ACEs on health and emotional well-being in adolescence. Nationally representative cross-sectional study. Using logistic regression on the 2011/12 National Survey of Children's Health, we examined the cumulative effect of total ACE score on the health and emotional well-being of US adolescents aged 12 to 17 years. We investigated the moderating effect of family functioning on the impact of ACE on adolescent health and emotional well-being. Adolescents with higher ACE scores had worse reported physical and emotional well-being than adolescents with fewer ACEs net of key demographic and socio-economic characteristics. Family functioning moderated the negative impact of cumulative ACE on adolescent health and emotional well-being. Adolescent well-being has enduring consequences; identifying children with ACE exposure who also have lower-functioning family could also help identify those families at particular risk. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

ACE2 activation by xanthenone prevents leptin-induced increases in blood pressure and proteinuria during pregnancy in Sprague-Dawley rats.

PubMed

Ibrahim, Hisham Saleh; Froemming, Gabrielle Ruth Anisah; Omar, Effat; Singh, Harbindar Jeet

2014-11-01

This study investigates the effect of ACE2 activation on leptin-induced changes in systolic blood pressure (SBP), proteinuria, endothelial activation and ACE2 expression during pregnancy in Sprague-Dawley rats. Pregnant rats were given subcutaneous injection of either saline, or leptin, or leptin plus xanthenone (ACE2 activator), or xanthenone (XTN) alone. SBP, serum ACE, ACE2, endothelin-1, E-selectin and ICAM-1 levels were estimated; also their gene expressions were determined in the kidney and aorta respectively. Compared to control, SBP was higher in the leptin-only treated group (P<0.001) and lower in rats treated with xanthenone alone (P<0.01). Proteinuria, markers of endothelial activation were significantly higher than controls in leptin-only treated rats (P<0.05). ACE2 activity and expression were lower in leptin-only treated rats when compared to controls (P<0.05). It seems, leptin administration during pregnancy significantly increases SBP, proteinuria, endothelial activation, but decreases ACE2 level and expression. These effects are prevented by concurrent administration of xanthenone. Copyright © 2014 Elsevier Inc. All rights reserved.

Does acute care for the elderly (ACE) unit decrease the incidence of falls?

PubMed

Abdalla, Ahmed; Adhaduk, Mehul; Haddad, Raad A; Alnimer, Yanal; Ríos-Bedoya, Carlos F; Bachuwa, Ghassan

2017-11-11

To determine whether acute care for the elderly (ACE) units decrease the incidence of patient falls compared to general medical and surgical (GMS) units, a non-concurrent prospective study included individuals aged 65 and older admitted to ACE or GMS units over a 2-year span was done. There were 7069 admissions corresponded to 28,401 patient-days. A total of 149 falls were reported for an overall incidence rate (IR) of 5.2 falls per 1000 patient-days, 95% CI, 4.4/1000-6.1/1000 patient-days. The falls IR ratio for patients in ACE unit compared to those in non-ACE units after adjusting for age, sex, prescribed psychotropics and hypnotics, and Morse Fall Score was 0.27/1000 patient-days; 95% CI, 0.13-0.54; p < 0.001. So, an estimated 73% reduction in patient falls between ACE unit and non-ACE units. Hospitals may consider investing in ACE units to decrease the risk of falls and the associated medical and financial costs. Copyright © 2017 Elsevier Inc. All rights reserved.

Bioavailability of angiotensin I-converting enzyme (ACE) inhibitory peptides derived from Virgibacillus halodenitrificans SK1-3-7 proteinases hydrolyzed tilapia muscle proteins.

PubMed

Toopcham, Tidarat; Mes, Jurriaan J; Wichers, Harry J; Roytrakul, Sittiruk; Yongsawatdigul, Jirawat

2017-04-01

The angiotensin I-converting enzyme (ACE) inhibitory activity of protein hydrolysates from tilapia muscle fractions, namely mince (M), washed mince (WM), and sarcoplasmic protein (SP), were investigated. Each fraction was hydrolyzed by Virgibacillus halodenitrificans SK1-3-7 proteinases for up to 24h. After 8h of hydrolysis, the M hydrolysate (48% degree of hydrolysis (DH)) showed the highest ACE inhibitory activity, with an IC 50 value of 0.54mg/ml, while the SP hydrolysate exhibited the lowest DH and ACE inhibition. In vitro gastrointestinal digestion reduced the ACE inhibitory activity of the M hydrolysate but enhanced its transport across Caco-2 cell monolayers. The transported peptides were found to contain 3-4 amino acid residues showing strong ACE inhibition. The novel ACE inhibitory peptide with the highest inhibition was found to be MCS, with an IC 50 value of 0.29μM. Therefore, tilapia mince hydrolyzed by V. halodenitrificans proteinases contained ACE inhibitory peptides that are potentially bioavailable. Copyright © 2016 Elsevier Ltd. All rights reserved.

ADVERSE CHILDHOOD EXPERIENCES, FAMILY FUNCTIONING AND ADOLESCENT HEALTH AND EMOTIONAL WELL-BEING

PubMed Central

Balistreri, Kelly Stamper; Alvira-Hammond, Marta

2015-01-01

Objectives Adverse childhood experiences (ACE) have been consistently linked in a strong and graded fashion to a host of health problems in later adulthood but few studies have examined the more proximate effect of ACE on health and emotional well-being in adolescence. Study Design Nationally representative cross-sectional study. Methods Using logistic regression on the 2011/12 National Survey of Children’s Health, we examined the cumulative effect of total ACE score on the health and emotional well-being of US adolescents ages 12 through 17. We investigated the moderating effect of family functioning on the impact of ACE on adolescent health and emotional well-being. Results Adolescents with higher ACE scores had worse reported physical and emotional well-being than adolescents with fewer ACEs net of key demographic and socioeconomic characteristics. Family functioning moderated the negative impact of cumulative ACE on adolescent health and emotional well-being. Conclusions Adolescent well-being has enduring consequences; identifying children with ACE exposure who also have lower-functioning family could also help identify those families at particular risk. PMID:26718424

Adverse Childhood Experiences (ACEs), Stress and Mental Health in College Students.

PubMed

Karatekin, Canan

2018-02-01

The goal of this short-term longitudinal study was to examine whether adverse childhood experiences (ACEs) could be used to identify college students at risk for mental health problems and whether current level of stress mediates the relationship between ACEs and mental health. Data on ACEs and mental health (depression, anxiety and suicidality) were collected at the beginning of the semester, and data on current stressors and mental health were collected toward the end of the semester (n = 239). Findings indicated that ACEs predicted worsening of mental health over the course of a semester and suggested current number of stressors as a mediator of the relationship between ACEs and mental health. Results suggest that screening for ACEs might be useful to identify students at high risk for deterioration in mental health. Results further suggest that stress-related interventions would be beneficial for students with high levels of ACEs and point to the need for more research and strategies to increase help-seeking in college students. Copyright © 2017 John Wiley & Sons, Ltd.

The role of glycosylation and domain interactions in the thermal stability of human angiotensin-converting enzyme.

PubMed

O'Neill, Hester G; Redelinghuys, Pierre; Schwager, Sylva L U; Sturrock, Edward D

2008-09-01

The N and C domains of somatic angiotensin-converting enzyme (sACE) differ in terms of their substrate specificity, inhibitor profiling, chloride dependency and thermal stability. The C domain is thermally less stable than sACE or the N domain. Since both domains are heavily glycosylated, the effect of glycosylation on their thermal stability was investigated by assessing their catalytic and physicochemical properties. Testis ACE (tACE) expressed in mammalian cells, mammalian cells in the presence of a glucosidase inhibitor and insect cells yielded proteins with altered catalytic and physicochemical properties, indicating that the more complex glycans confer greater thermal stabilization. Furthermore, a decrease in tACE and N-domain N-glycans using site-directed mutagenesis decreased their thermal stability, suggesting that certain N-glycans have an important effect on the protein's thermodynamic properties. Evaluation of the thermal stability of sACE domain swopover and domain duplication mutants, together with sACE expressed in insect cells, showed that the C domain contained in sACE is less dependent on glycosylation for thermal stabilization than a single C domain, indicating that stabilizing interactions between the two domains contribute to the thermal stability of sACE and are decreased in a C-domain-duplicating mutant.

Small-angle neutron scattering study of specific interaction and coordination structure formed by mono-acetyl-substituted dibenzo-20-crown-6-ether and cesium ions

DOE PAGES

Motokawa, Ryuhei; Kobayashi, Tohru; Endo, Hitoshi; ...

2015-10-26

This study uses small-angle neutron scattering (SANS) to elucidate the coordination structure of the complex of mono-acetyl-substituted dibenzo-20-crown-6-ether (ace-DB20C6) with cesium ions (Cs +). SANS profiles obtained for the complex of ace-DB20C6 and Cs + (ace-DB20C6/Cs) in deuterated dimethyl sulfoxide indicated that Cs + coordination resulted in a more compact structure than the free ace-DB20C6. The data were fitted well with SANS profiles calculated using Debye function for scattering on an absolute scattering intensity scale. For this theoretical calculation of the scattering profiles, the coordination structure proposed based on density functional theory calculation was used. Furthermore, we conclude that themore » SANS analysis experimentally supports the proposed coordination structure of ace-DB20C6/Cs and suggests the following: (1) the complex of ace-DB20C6 and Cs + is formed with an ace-DB20C6/Cs molar ratio of 1/1 and (2) the two benzene rings of ace-DB20C6 fold around Cs + above the center of the crown ether ring of ace-DB20C6.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Strittmatter, S.M.

(/sup 3/H)Captopril binds to angiotensin converting enzyme (ACE) in rat tissue homogenates. The pharmacology, regional distribution and copurification of (/sup 3/H)captopril binding with enzymatic activity demonstrate the selectivity of (/sup 3/H)captopril labeling of ACE. (/sup 3/H)Captopril binding to purified ACE reveals differences in cationic dependence and anionic regulation between substrate catalysis and inhibitor recognition. (/sup 3/H)Captopril association with ACE is entropically driven. The selectivity of (/sup 3/H)captopril binding permits autoradiographic localization of the ACE in the brain, male reproductive system, pituitary gland and adrenal gland. In the brain, ACE is visualized in a striatonigral neuronal pathway which develops between 1more » and 7 d after birth. In the male reproductive system, (/sup 3/H)captopril associated silver grains are found over spermatid heads and in the lumen of seminiferous tubules in stages I-VIII and XII-XIV. In the pituitary gland, ACE is localized to the posterior lobe and patches of the anterior lobe. The adrenal medulla contains moderate ACE levels while low levels are found in the adrenal cortex. Adrenal medullary ACE is increased after hypophysectomy and after reserpine treatment. The general of ligand binding techniques for the study of enzymes is demonstrated by the specific labeling of another enzyme, enkephaline convertase, in crude tissue homogenates by the inhibitor (/sup 3/H)GEMSA.« less

Small-angle neutron scattering study of specific interaction and coordination structure formed by mono-acetyl-substituted dibenzo-20-crown-6-ether and cesium ions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Motokawa, Ryuhei; Kobayashi, Tohru; Endo, Hitoshi

This study uses small-angle neutron scattering (SANS) to elucidate the coordination structure of the complex of mono-acetyl-substituted dibenzo-20-crown-6-ether (ace-DB20C6) with cesium ions (Cs +). SANS profiles obtained for the complex of ace-DB20C6 and Cs + (ace-DB20C6/Cs) in deuterated dimethyl sulfoxide indicated that Cs + coordination resulted in a more compact structure than the free ace-DB20C6. The data were fitted well with SANS profiles calculated using Debye function for scattering on an absolute scattering intensity scale. For this theoretical calculation of the scattering profiles, the coordination structure proposed based on density functional theory calculation was used. Furthermore, we conclude that themore » SANS analysis experimentally supports the proposed coordination structure of ace-DB20C6/Cs and suggests the following: (1) the complex of ace-DB20C6 and Cs + is formed with an ace-DB20C6/Cs molar ratio of 1/1 and (2) the two benzene rings of ace-DB20C6 fold around Cs + above the center of the crown ether ring of ace-DB20C6.« less

The Atmospheric Chemistry Experiment (ACE): Status and Latest Results

NASA Astrophysics Data System (ADS)

Bernath, P. F.; Boone, C. D.; McElroy, C. T.

2017-12-01

ACE (also known as SCISAT) is making a comprehensive set of simultaneous measurements of numerous trace gases, thin clouds, aerosols and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74°) orbit gives ACE coverage of tropical, mid-latitudes and polar regions. The primary instrument is a high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating in the 750-4400 cm-1 region, which provides the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. A second instrument, a dual spectrophotometer called MAESTRO, extends the wavelength coverage to the 400-1000 nm spectral region. Aerosols and clouds are being monitored through the extinction of solar radiation using two filtered imagers and by MAESTRO as well as by their infrared spectra. After 14 years in orbit, the ACE is still operating well. A short overview of the ACE mission will be presented (see http://www.ace.uwaterloo.ca for more information). The current version (v. 3.5/3.6) of ACE-FTS processing includes more than 30 molecules and twenty isotopologues; v.3.5/3.6 is now available in near-real time. This talk will focus on recent ACE results and the new version 4.0 of ACE-FTS processing.

Angiotensin-converting enzyme in Spodoptera littoralis: molecular characterization, expression and activity profile during development.

PubMed

Lemeire, Els; Vanholme, Bartel; Van Leeuwen, Thomas; Van Camp, John; Smagghe, Guy

2008-02-01

The characterization of the full-length angiotensin-converting enzyme (ACE) cDNA sequence of the lepidopteran Spodoptera littoralis is reported in this study. The predicted open reading frame encodes a 647 amino acids long protein (SlACE) and shows 63.6% identity with the Bombyx mori ACE sequence. A 3D-model, consisting of 26 alpha-helices and three beta-sheets, was predicted for the sequence. SlACE expression was studied in the embryonic, larval and pupal stages of S. littoralis and in different tissues of the last larval stage by reverse-transcribed PCR. This revealed that the gene is expressed throughout the life cycle and especially in brain, gut and fat body tissue of the last stage. These results are in agreement with a role of ACE in the metabolism of neuropeptides and gut hormones. In addition, ACE activity has been studied in more detail during development, making use of a fluorescent assay. High ACE peptidase activity coincides with every transition state, from embryo to larva, from larva to larva and from larva to pupa. A peak value in activity occurs during the early pupal stage. These results indicate the importance of SlACE during metamorphosis and reveal the high correlation of ACE activity with the insect's development, which is regulated by growth and developmental hormones.

Comparative Validation of Realtime Solar Wind Forecasting Using the UCSD Heliospheric Tomography Model

NASA Technical Reports Server (NTRS)

MacNeice, Peter; Taktakishvili, Alexandra; Jackson, Bernard; Clover, John; Bisi, Mario; Odstrcil, Dusan

2011-01-01

The University of California, San Diego 3D Heliospheric Tomography Model reconstructs the evolution of heliospheric structures, and can make forecasts of solar wind density and velocity up to 72 hours in the future. The latest model version, installed and running in realtime at the Community Coordinated Modeling Center(CCMC), analyzes scintillations of meter wavelength radio point sources recorded by the Solar-Terrestrial Environment Laboratory(STELab) together with realtime measurements of solar wind speed and density recorded by the Advanced Composition Explorer(ACE) Solar Wind Electron Proton Alpha Monitor(SWEPAM).The solution is reconstructed using tomographic techniques and a simple kinematic wind model. Since installation, the CCMC has been recording the model forecasts and comparing them with ACE measurements, and with forecasts made using other heliospheric models hosted by the CCMC. We report the preliminary results of this validation work and comparison with alternative models.

Comparative study of predicted and experimentally detected interplanetary shocks

NASA Astrophysics Data System (ADS)

Kartalev, M. D.; Grigorov, K. G.; Smith, Z.; Dryer, M.; Fry, C. D.; Sun, Wei; Deehr, C. S.

2002-03-01

We compare the real time space weather prediction shock arrival times at 1 AU made by the USAF/NOAA Shock Time of Arrival (STOA) and Interplanetary Shock Propagation Model (ISPM) models, and the Exploration Physics International/University of Alaska Hakamada-Akasofu-Fry Solar Wind Model (HAF-v2) to a real time analysis analysis of plasma and field ACE data. The comparison is made using an algorithm that was developed on the basis of wavelet data analysis and MHD identification procedure. The shock parameters are estimated for selected "candidate events". An appropriate automatically performing Web-based interface periodically utilizes solar wind observations made by the ACE at L1. Near real time results as well an archive of the registered interesting events are available on a specially developed web site. A number of events are considered. These studies are essential for the validation of real time space weather forecasts made from solar data.

The drive for Aircraft Energy Efficiency

NASA Technical Reports Server (NTRS)

James, R. L., Jr.; Maddalon, D. V.

1984-01-01

NASA's Aircraft Energy Efficiency (ACEE) program, which began in 1976, has mounted a development effort in four major transport aircraft technology fields: laminar flow systems, advanced aerodynamics, flight controls, and composite structures. ACEE has explored two basic methods for achieving drag-reducing boundary layer laminarization: the use of suction through the wing structure (via slots or perforations) to remove boundary layer turbulence, and the encouragement of natural laminar flow maintenance through refined design practices. Wind tunnel tests have been conducted for wide bodied aircraft equipped with high aspect ratio supercritical wings and winglets. Maneuver load control and pitch-active stability augmentation control systems reduce fuel consumption by reducing the drag associated with high aircraft stability margins. Composite structures yield lighter airframes that in turn call for smaller wing and empennage areas, reducing induced drag for a given payload. In combination, all four areas of development are expected to yield a fuel consumption reduction of 40 percent.

EFFECT OF COHERENT STRUCTURES ON ENERGETIC PARTICLE INTENSITY IN THE SOLAR WIND AT 1 AU

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tessein, Jeffrey A.; Matthaeus, William H.; Wan, Minping

2015-10-10

We present results from an analysis of Advanced Composition Explorer (ACE) observations of energetic particles in the 0.047–4.78 MeV range associated with shocks and discontinuities in the solar wind. Previous work found a strong correlation between coherent structures and energetic particles measured by ACE/EPAM. Coherent structures are identified using the Partial Variance of Increments (PVI) method, which is essentially a normalized vector increment. The correlation was based on a superposed epoch analysis using over 12 years of data. Here, we examine many individual high-PVI events to better understand this association emphasizing intervals selected from data with shock neighborhoods removed. Wemore » find that in many cases the local maximum in PVI is in a region of rising or falling energetic particle intensity, which suggests that magnetic discontinuities may act as barriers inhibiting the motion of energetic particles across them.« less

Comparative Diagnostic Accuracy of the ACE-III, MIS, MMSE, MoCA, and RUDAS for Screening of Alzheimer Disease.

PubMed

Matías-Guiu, Jordi A; Valles-Salgado, María; Rognoni, Teresa; Hamre-Gil, Frank; Moreno-Ramos, Teresa; Matías-Guiu, Jorge

2017-01-01

Our aim was to evaluate and compare the diagnostic properties of 5 screening tests for the diagnosis of mild Alzheimer disease (AD). We conducted a prospective and cross-sectional study of 92 patients with mild AD and of 68 healthy controls from our Department of Neurology. The diagnostic properties of the following tests were compared: Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination III (ACE-III), Memory Impairment Screen (MIS), Montreal Cognitive Assessment (MoCA), and Rowland Universal Dementia Assessment Scale (RUDAS). All tests yielded high diagnostic accuracy, with the ACE-III achieving the best diagnostic properties. The area under the curve was 0.897 for the ACE-III, 0.889 for the RUDAS, 0.874 for the MMSE, 0.866 for the MIS, and 0.856 for the MoCA. The Mini-ACE score from the ACE-III showed the highest diagnostic capacity (area under the curve 0.939). Memory scores of the ACE-III and of the RUDAS showed a better diagnostic accuracy than those of the MMSE and of the MoCA. All tests, especially the ACE-III, conveyed a higher diagnostic accuracy in patients with full primary education than in the less educated group. Implementing normative data improved the diagnostic accuracy of the ACE-III but not that of the other tests. The ACE-III achieved the highest diagnostic accuracy. This better discrimination was more evident in the more educated group. © 2017 S. Karger AG, Basel.

Evaluation of ACE gene I/D polymorphism in Iranian elite athletes.

PubMed

Shahmoradi, Somayeh; Ahmadalipour, Ali; Salehi, Mansoor

2014-01-01

Angiotensin converting enzyme (ACE) is an important gene, which is associated with the successful physical activity. The ACE gene has a major polymorphism (I/D) in intron 16 that determines its plasma and tissue levels. In this study, we aimed to determine whether there is an association between this polymorphism and sports performance in our studied population including elite athletes of different sports disciplines. We investigated allele frequency and genotype distribution of the ACE gene in 156 Iranian elite athletes compared to 163 healthy individuals. We also investigated this allele frequency between elite athletes in three functional groups of endurance, power, and mixed sports performances. DNA was extracted from peripheral blood, and polymerase chain reaction (PCR) method was performed on intron 16 of the ACE gene. The ACE genotype was determined for each subject. Statistical analysis was performed by SPSS 15, and results were analyzed by Chi-Square test. There was a significant difference in genotype distribution and allele frequency of the ACE gene in athletes and control group (P = 0.05, P = 0.03, respectively). There was also a significant difference in allele frequency of the ACE gene in 3 groups of athletes with different sports disciplines (P = 0.045). Proportion of the ACE gene D allele was greater in elite endurance athletes (37 high-distance cyclists) than two other groups. Findings of the present study demonstrated that there is an association between the ACE gene I/D polymorphism and sports performance in Iranian elite athletes.

Income Inequality and the Differential Effect of Adverse Childhood Experiences in US Children.

PubMed

Halfon, Neal; Larson, Kandyce; Son, John; Lu, Michael; Bethell, Christina

Adverse childhood experiences (ACEs) can affect health and development across the life course. Despite a general understanding that adversity is associated with lower income, we know less about how ACEs manifest at different income levels and how these income-related patterns affect children's health and development. Data from the 2011 to 2012 National Survey of Children's Health were used to examine the prevalence of 9 ACEs in US children, across 4 levels of household income, and in relationship to 5 parent-reported measures of child health. Bivariate analyses and multivariable logistic regression models were used to examine the associations between number of ACEs and children's health outcomes on the basis of the 4 income groups. When partitioned according to income strata, the proportion of children who experienced ACEs showed a steep income gradient, particularly for children who experienced ≥4 ACEs. The linear gradient across income groups was less pronounced for each specific ACE, with several ACEs (experience of divorce, drug and alcohol exposure, parental mental illness) showing high reported prevalence in all but the highest income group. Multivariate analysis showed a consistent income-related gradient for each of the health outcomes. However, higher income was not necessarily found to be a protective factor against ACEs. ACEs are distributed across the income ladder and not just concentrated below the poverty level. This suggests that a more comprehensive policy strategy that includes targeted as well as universal interventions is warranted. Copyright © 2016 Academic Pediatric Association. All rights reserved.

Coupling corticotropin-releasing-hormone and angiotensin converting enzyme 2 dampens stress responsiveness in male mice.

PubMed

Wang, Lei A; de Kloet, Annette D; Smeltzer, Michael D; Cahill, Karlena M; Hiller, Helmut; Bruce, Erin B; Pioquinto, David J; Ludin, Jacob A; Katovich, Michael J; Raizada, Mohan K; Krause, Eric G

2018-05-01

This study used mice to evaluate whether coupling expression of corticotropin-releasing hormone (CRH) and angiotensin converting enzyme 2 (ACE2) creates central interactions that blunt endocrine and behavioral responses to psychogenic stress. Central administration of diminazene aceturate, an ACE2 activator, had no effect on restraint-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis; however, mice that ubiquitously overexpress ACE2 had reduced plasma corticosterone (CORT) and pituitary expression of POMC mRNA. The Cre-LoxP system was used to restrict ACE2 overexpression to CRH synthesizing cells and probe whether HPA axis suppression was the result of central ACE2 and CRH interactions. Within the paraventricular nucleus of the hypothalamus (PVN), mice with ACE2 overexpression directed to CRH had a ≈2.5 fold increase in ACE2 mRNA, which co-localized with CRH mRNA. Relative to controls, mice overexpressing ACE2 in CRH cells had a decreased CORT response to restraint as well as decreased CRH mRNA in the PVN and CEA and POMC mRNA in the pituitary. Administration of ACTH similarly increased plasma CORT, indicating that the blunted HPA axis activation that accompanies ACE2 overexpression in CRH cells is centrally mediated. Anxiety-like behavior was assessed to determine whether the decreased HPA axis activation was predictive of anxiolysis. Mice with ACE2 overexpression directed to CRH cells displayed decreased anxiety-like behavior in the elevated plus maze and open field when compared to that of controls. Collectively, these results suggest that exogenous ACE2 suppresses CRH synthesis, which alters the central processing of psychogenic stress, thereby blunting HPA axis activation and attenuating anxiety-like behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

High-resolution crystal structures of Drosophila melanogaster angiotensin-converting enzyme in complex with novel inhibitors and antihypertensive drugs.

PubMed

Akif, Mohd; Georgiadis, Dimitris; Mahajan, Aman; Dive, Vincent; Sturrock, Edward D; Isaac, R Elwyn; Acharya, K Ravi

2010-07-16

Angiotensin I-converting enzyme (ACE), one of the central components of the renin-angiotensin system, is a key therapeutic target for the treatment of hypertension and cardiovascular disorders. Human somatic ACE (sACE) has two homologous domains (N and C). The N- and C-domain catalytic sites have different activities toward various substrates. Moreover, some of the undesirable side effects of the currently available and widely used ACE inhibitors may arise from their targeting both domains leading to defects in other pathways. In addition, structural studies have shown that although both these domains have much in common at the inhibitor binding site, there are significant differences and these are greater at the peptide binding sites than regions distal to the active site. As a model system, we have used an ACE homologue from Drosophila melanogaster (AnCE, a single domain protein with ACE activity) to study ACE inhibitor binding. In an extensive study, we present high-resolution structures for native AnCE and in complex with six known antihypertensive drugs, a novel C-domain sACE specific inhibitor, lisW-S, and two sACE domain-specific phosphinic peptidyl inhibitors, RXPA380 and RXP407 (i.e., nine structures). These structures show detailed binding features of the inhibitors and highlight subtle changes in the orientation of side chains at different binding pockets in the active site in comparison with the active site of N- and C-domains of sACE. This study provides information about the structure-activity relationships that could be utilized for designing new inhibitors with improved domain selectivity for sACE. 2010 Elsevier Ltd. All rights reserved.

Expression of Magnaporthe grisea Avirulence Gene ACE1 Is Connected to the Initiation of Appressorium-Mediated Penetration▿

PubMed Central

Fudal, Isabelle; Collemare, Jérôme; Böhnert, Heidi U.; Melayah, Delphine; Lebrun, Marc-Henri

2007-01-01

Magnaporthe grisea is responsible for a devastating fungal disease of rice called blast. Current control of this disease relies on resistant rice cultivars that recognize M. grisea signals corresponding to specific secreted proteins encoded by avirulence genes. The M. grisea ACE1 avirulence gene differs from others, since it controls the biosynthesis of a secondary metabolite likely recognized by rice cultivars carrying the Pi33 resistance gene. Using a transcriptional fusion between ACE1 promoter and eGFP, we showed that ACE1 is only expressed in appressoria during fungal penetration into rice and barley leaves, onion skin, and cellophane membranes. ACE1 is almost not expressed in appressoria differentiated on Teflon and Mylar artificial membranes. ACE1 expression is not induced by cellophane and plant cell wall components, demonstrating that it does not require typical host plant compounds. Cyclic AMP (cAMP) signaling mutants ΔcpkA and Δmac1 sum1-99 and tetraspanin mutant Δpls1::hph differentiate melanized appressoria with normal turgor but are unable to penetrate host plant leaves. ACE1 is normally expressed in these mutants, suggesting that it does not require cAMP signaling or a successful penetration event. ACE1 is not expressed in appressoria of the buf1::hph mutant defective for melanin biosynthesis and appressorial turgor. The addition of hyperosmotic solutes to buf1::hph appressoria restores appressorial development and ACE1 expression. Treatments of young wild-type appressoria with actin and tubulin inhibitors reduce both fungal penetration and ACE1 expression. These experiments suggest that ACE1 appressorium-specific expression does not depend on host plant signals but is connected to the onset of appressorium-mediated penetration. PMID:17142568

Isolation, Purification and Molecular Mechanism of a Peanut Protein-Derived ACE-Inhibitory Peptide

PubMed Central

Shi, Aimin; Liu, Hongzhi; Liu, Li; Hu, Hui; Wang, Qiang; Adhikari, Benu

2014-01-01

Although a number of bioactive peptides are capable of angiotensin I-converting enzyme (ACE) inhibitory effects, little is known regarding the mechanism of peanut peptides using molecular simulation. The aim of this study was to obtain ACE inhibiting peptide from peanut protein and provide insight on the molecular mechanism of its ACE inhibiting action. Peanut peptides having ACE inhibitory activity were isolated through enzymatic hydrolysis and ultrafiltration. Further chromatographic fractionation was conducted to isolate a more potent peanut peptide and its antihypertensive activity was analyzed through in vitro ACE inhibitory tests and in vivo animal experiments. MALDI-TOF/TOF-MS was used to identify its amino acid sequence. Mechanism of ACE inhibition of P8 was analyzed using molecular docking and molecular dynamics simulation. A peanut peptide (P8) having Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence was obtained which had the highest ACE inhibiting activity of 85.77% (half maximal inhibitory concentration (IC50): 0.0052 mg/ml). This peanut peptide is a competitive inhibitor and show significant short term (12 h) and long term (28 days) antihypertensive activity. Dynamic tests illustrated that P8 can be successfully docked into the active pocket of ACE and can be combined with several amino acid residues. Hydrogen bond, electrostatic bond and Pi-bond were found to be the three main interaction contributing to the structural stability of ACE-peptide complex. In addition, zinc atom could form metal-carboxylic coordination bond with Tyr, Met residues of P8, resulting into its high ACE inhibiting activity. Our finding indicated that the peanut peptide (P8) having a Lys-Leu-Tyr-Met-Arg-Pro amino acid sequence can be a promising candidate for functional foods and prescription drug aimed at control of hypertension. PMID:25347076

Angiotensin Converting Enzyme Inhibitors and the Reduced Risk of Alzheimer’s Disease in the Absence of Apolipoprotein E4 Allele

PubMed Central

Qiu, Wei Qiao; Mwamburi, Mkaya; Besser, Lilah M.; Zhu, Haihao; Li, Huajie; Wallack, Max; Phillips, Leslie; Qiao, Liyan; Budson, Andrew E.; Stern, Robert; Kowall, Neil

2014-01-01

Our cross-sectional study showed that the interaction between apolipoprotein E4 (ApoE4) and angiotensin converting enzyme (ACE) inhibitors was associated with Alzheimer’s disease (AD). The aim of this longitudinal study was to differentiate whether ACE inhibitors accelerate or reduce the risk of AD in the context of ApoE alleles. Using the longitudinal data from the National Alzheimer’s Coordinating Center (NACC) with ApoE genotyping and documentation of ACE inhibitors use, we found that in the absence of ApoE4, subjects who had been taking central ACE inhibitor use (χ2 test: 21% versus 27%, p = 0.0002) or peripheral ACE inhibitor use (χ2 test: 13% versus 27%, p < 0.0001) had lower incidence of AD compared with those who had not been taking an ACE inhibitor. In contrast, in the presence of ApoE4, there was no such association between ACE inhibitor use and the risk of AD. After adjusting for the confounders, central ACE inhibitor use (OR = 0.68, 95% CI = 0.55, 0.83, p = 0.0002) or peripheral ACE inhibitor use (OR = 0.33, 95% CI = 0.33, 0.68, p < 0.0001) still remained inversely associated with a risk of developing AD in ApoE4 non-carriers. In conclusion, ACE inhibitors, especially peripherally acting ones, were associated with a reduced risk of AD in the absence of ApoE4, but had no such effect in those carrying the ApoE4 allele. A double-blind clinical trial should be considered to determine the effect of ACE inhibitors on prevention of AD in the context of ApoE genotype. PMID:23948883

An investigation of the concomitant use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs and diuretics.

PubMed

Bucsa, C; Moga, D C; Farcas, A; Mogosan, C; Dumitrascu, D L

2015-08-01

To determine in retrospective data the prevalence at hospital discharge of co-prescribing angiotensin-converting enzyme inhibitors (ACE-I) and non-steroidal anti-inflammatory drugs (NSAIDs) and ACE-I/NSAIDs and diuretics and to identify factors associated with the co-prescription. Secondary, we evaluated the extent of serum creatinine and potassium monitoring in patients treated with ACE-I and these associations and determined the prevalence of values above the upper normal limit (UNL) in monitored patients. Hospitalized patients with ACE-I in their therapy at discharge were included in 3 groups as follows: ACE-I, DT (double therapy with ACE-I and NSAIDs) and TT (triple therapy with ACE-I, NSAIDs and diuretics) groups. We evaluated differences on demographic characteristics, co-morbidities, medications, laboratory monitoring and quantified the patients with serum creatinine and potassium levels above the UNL using descriptive statistics. Logistic regression analysis with backward elimination was performed to identify significant predictors of combination therapy. Of 9960 admitted patients, 1214 were prescribed ACE-I, 40 were prescribed ACE-I/NSAIDs and 22 were prescribed ACE-I/NSAIDs/diuretics (3.13% and 1.72%, respectively, of the patients prescribed with ACE-I). Serum creatinine and potassium were monitored for the great majority of patients from all groups. The highest percentage of hyperkalemia was found in the DT group (10% of the patients) and of serum creatinine above UNL in the TT group (45.45%). The logistic regression final model showed that younger patients and monitoring for potassium were significantly associated with combination therapy. The prevalence of patients receiving DT/TT was relatively low and their monitoring during hospitalization was high. Factors associated with the combinations were younger patients and patients not tested for serum potassium.

ACE-FTS ozone, water vapour, nitrous oxide, nitric acid, and carbon monoxide profile comparisons with MIPAS and MLS

NASA Astrophysics Data System (ADS)

Sheese, Patrick E.; Walker, Kaley A.; Boone, Chris D.; Bernath, Peter F.; Froidevaux, Lucien; Funke, Bernd; Raspollini, Piera; von Clarmann, Thomas

2017-01-01

The atmospheric limb sounders, ACE-FTS on the SCISAT satellite, MIPAS on ESA's Envisat satellite, and MLS on NASA's Aura satellite, take measurements used to retrieve atmospheric profiles of O3, N2O, H2O, HNO3, and CO. Each was taking measurements between February 2004 and April 2012 (ACE-FTS and MLS are currently operational), providing hundreds of profile coincidences in the Northern and Southern hemispheres, and during local morning and evening. Focusing on determining diurnal and hemispheric biases in the ACE-FTS data, this study compares ACE-FTS version 3.5 profiles that are collocated with MIPAS and MLS, and analyzes the differences between instrument retrievals for Northern and Southern hemispheres and for local morning and evening data. For O3, ACE-FTS is typically within ±5% of mid-stratospheric MIPAS and MLS data and exhibits a positive bias of 10 to 20% in the upper stratosphere - lower mesosphere. For H2O, ACE-FTS exhibits an average bias of -5% between 20 and 60 km. For N2O, ACE-FTS agrees with MIPAS and MLS within -20 to +10% up to 45 km and 35 km, respectively. For HNO3, ACE-FTS typically agrees within ±10% below 30 km, and exhibits a positive bias of 10 to 20% above 30 km. With respect to MIPAS CO, ACE-FTS exhibits an average -11% bias between 28 and 50 km, and at higher altitudes a positive bias on the order of 10% (>100%) in the winter (summer). With respect to winter MLS CO, ACE-FTS is typically within ±10% between 25 and 40 km, and has an average bias of -11% above 40 km.

Adverse Childhood Experiences and School-Based Victimization and Perpetration.

PubMed

Forster, Myriam; Gower, Amy L; McMorris, Barbara J; Borowsky, Iris W

2017-01-01

Retrospective studies using adult self-report data have demonstrated that adverse childhood experiences (ACEs) increase risk of violence perpetration and victimization. However, research examining the associations between adolescent reports of ACE and school violence involvement is sparse. The present study examines the relationship between adolescent reported ACE and multiple types of on-campus violence (bringing a weapon to campus, being threatened with a weapon, bullying, fighting, vandalism) for boys and girls as well as the risk of membership in victim, perpetrator, and victim-perpetrator groups. The analytic sample was comprised of ninth graders who participated in the 2013 Minnesota Student Survey ( n ~ 37,000). Multinomial logistic regression models calculated the risk of membership for victim only, perpetrator only, and victim-perpetrator subgroups, relative to no violence involvement, for students with ACE as compared with those with no ACE. Separate logistic regression models assessed the association between cumulative ACE and school-based violence, adjusting for age, ethnicity, family structure, poverty status, internalizing symptoms, and school district size. Nearly 30% of students were exposed to at least one ACE. Students with ACE represent 19% of no violence, 38% of victim only, 40% of perpetrator only, and 63% of victim-perpetrator groups. There was a strong, graded relationship between ACE and the probability of school-based victimization: physical bullying for boys but not girls, being threatened with a weapon, and theft or property destruction ( ps < .001) and perpetration: bullying and bringing a weapon to campus ( ps < .001), with boys especially vulnerable to the negative effects of cumulative ACE. We recommend that schools systematically screen for ACE, particularly among younger adolescents involved in victimization and perpetration, and develop the infrastructure to increase access to trauma-informed intervention services. Future research priorities and implications are discussed.

Increased frequency of angiotensin-converting enzyme DD genotype in patients with type 2 diabetes in Taiwan.

PubMed

Hsieh, M C; Lin, S R; Hsieh, T J; Hsu, C H; Chen, H C; Shin, S J; Tsai, J H

2000-07-01

Diabetes is one of the major causes of end-stage renal failure in the Taiwanese population. Previous studies have shown that angiotensin-converting enzyme (ACE) inhibitor can improve glucose utilization and suppress hepatic glucose production and the renin-angiotensin system may play an important role in the initiation and progression of diabetic nephropathy. Thus, ACE gene polymorphism may be associated with type 2 diabetes and diabetic nephropathy. To investigate the distribution of ACE-I/D genotype in type 2 diabetes and diabetic nephropathy, we examined 336 patients with type 2 diabetes (157 without nephropathy and 179 with nephropathy) and 263 age-matched normal controls. The diagnosis of nephropathy was made when daily protein loss exceeded 500 mg. ACE gene polymorphism was analysed by use of polymerase chain reaction. Our study revealed that the frequency of the D allele of the ACE gene was 29.3% in normal controls. The frequency of ACE DD genotype was significantly higher in type 2 diabetics compared with normal controls (18.2 vs 9.1%, P<0.01). The frequency of ACE DD genotype in patients with diabetic nephropathy was significantly higher than in patients without nephropathy (22.3 vs 13.4%, P<0.05). To determine whether ACE gene polymorphism was associated with the severity of diabetic nephropathy, we divided patients with diabetic nephropathy into dialysis and non-dialysis groups. The frequency of ACE DD genotype in the dialysis group was significantly higher than in non-dialysis group (28.7 vs 15.3%, P<0.05). Our results indicate that the frequency of ACE DD genotype is markedly higher in patients with type 2 diabetes, and the ACE DD genotype is significantly associated with diabetic nephropathy.

High frequency of DD polymorphism of the angiotensin-converting enzyme gene in Turkish asthmatic patients.

PubMed

Urhan, Meral; Degirmenci, Irfan; Harmanci, Emel; Gunes, Hasan V; Metintas, Muzaffer; Basaran, Ayse

2004-01-01

The aim of this study is to detect the incidence of the angiotensin-converting enzyme (ACE) gene polymorphism in Turkish asthmatic patients and to examine whether there is an association between the disease and ACE gene polymorphism. In our study, the genomic DNA of 100 asthmatic patients and 88 healthy subjects was analyzed Genomic DNA was isolated from peripheral blood by using standard methods. The intron 16 of the ACE gene was amplified by the polymerase chain reaction (PCR) method using primers ACE and ACEX to examine the presence and absence of a 287-base pair (bp) DNA fragment that showed I/D polymorphism genotypes. PCR products were separated by agarose gel electrophoresis and were visualized by a charge-coupled device camera. Serum ACE activities were measured using an ACE kit. The results were evaluated statistically using the chi-square test and one-way analysis of variance. Although the population of patients with asthma was characterized by a higher frequency (30%) of the DD genotype of ACE, they were characterized by lower frequency (48%) of the ID genotype of ACE (DD, 16%, and ID, 64%, in healthy control subjects). The frequency of the I and D alleles of the ACE gene was not significantly different between asthmatic patients (0.46/0.54) and healthy controls (0.52/ 0.48). In addition, in both asthmatic patients and controls, there was a significant decrease of the levels of ACE activity in individuals that have II genotypes when compared with individuals that have DD genotypes. ACE activities were increased significantly in all asthmatic patients (67.20 +/- 1.95 IU/L) compared with all healthy controls (60.90 +/- 2.12 IU/L).

Association of Angiotensin-Converting Enzyme (ACE) Gene Polymorphism with Inflammation and Cellular Cytotoxicity in Vitiligo Patients.

PubMed

Rashed, Laila; Abdel Hay, Rania; Mahmoud, Rania; Hasan, Nermeen; Zahra, Amr; Fayez, Salwa

2015-01-01

Vitiligo is a disorder with profound heterogeneity in its aetio-pathophysiology. Angiotensin converting enzyme (ACE) plays an important role in the physiology of the vasculature, blood pressure and inflammation. An insertion/deletion (I/D) polymorphism of the ACE gene was reported be associated with the development of vitiligo. Our aim was to evaluate the ACE I/D polymorphism in vitiligo patients and controls. Our second aim was to find a possible association between ACE gene polymorphism and inflammatory mediators (as interleukin (IL)-6) and/or cellular cytotoxicity induced by serum nitrite (as a breakdown product of the cytotoxic nitric oxide) in vitiligo patients. This case-control study included 74 vitiligo patients and 75 apparently healthy controls. The distribution of ACE gene I/D genotype was investigated using PCR. Serum ACE, IL-6 and nitrite were measured by colorimetric method, ELISA and Griess assay respectively. The ACE allele frequency was significantly different between vitiligo patients and healthy controls (P = 0.026). However there was no significant difference between the ACE genotyping frequency in both groups (P = 0.115). There were statistically significant higher VIDA score (P = 0.007), and serum IL-6 (P < 0.001) in patients with the DD genotype when compared to other genotypes. Serum nitrite in patients with the DD genotype was significantly higher (P = 0.007) when compared to patients with II genotype. Serum levels of ACE, IL-6 and nitrite in vitiligo patients were statistically significantly higher than those in controls. As a conclusion, ACE gene polymorphism might grant susceptibility to develop vitiligo. Serum IL-6 and nitrite levels might have an important role in the pathogenesis of vitiligo. Targeting these two factors might have an implication in the treatment of some resistant cases.

Production of the angiotensin I converting enzyme inhibitory peptides and isolation of four novel peptides from jellyfish (Rhopilema esculentum) protein hydrolysate.

PubMed

Liu, Xin; Zhang, Miansong; Shi, Yaping; Qiao, Ruojin; Tang, Wei; Sun, Zhenliang

2016-07-01

Angiotensin I converting enzyme (ACE) plays an important role in regulating blood pressure in the human body. ACE inhibitory peptides derived from food proteins could exert antihypertensive effects without side effects. Jellyfish (Rhopilema esculentum) is an important fishery resource suitable for production of ACE inhibitory peptides. The objective of this study was to optimize the hydrolysis conditions for production of protein hydrolysate from R. esculentum (RPH) with ACE inhibitory activity, and to isolate and identify the ACE inhibitory peptides from RPH. Rhopilema esculentum protein was hydrolyzed with Compound proteinase AQ to produce protein hydrolysate with ACE inhibitory activity, and the hydrolysis conditions were optimized using response surface methodology. The optimum parameters for producing peptides with the highest ACE inhibitory activity were as follows: hydrolysis time 3.90 h, hydrolysis temperature 58 °C, enzyme:substrate ratio 2.8% and pH 7.60. Under these conditions, the ACE inhibitory rate reached 32.21%. In addition, four novel ACE inhibitory peptides were isolated, and their amino acids sequences were identified as Val-Gly-Pro-Tyr, Phe-Thr-Tyr-Val-Pro-Gly, Phe-Thr-Tyr-Val-Pro-Gly-Ala and Phe-Gln-Ala-Val-Trp-Ala-Gly, respectively. The IC50 value of the purified peptides for ACE inhibitory activity was 8.40, 23.42, 21.15 and 19.11 µmol L(-1) . These results indicate that the protein hydrolysate prepared from R. esculentum might be a commercial competitive source of ACE inhibitory ingredients to be used in functional foods. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Adverse childhood experiences and frequent insufficient sleep in 5 U.S. States, 2009: a retrospective cohort study.

PubMed

Chapman, Daniel P; Liu, Yong; Presley-Cantrell, Letitia R; Edwards, Valerie J; Wheaton, Anne G; Perry, Geraldine S; Croft, Janet B

2013-01-03

Although adverse childhood experiences (ACEs) have previously been demonstrated to be adversely associated with a variety of health outcomes in adulthood, their specific association with sleep among adults has not been examined. To better address this issue, this study examines the relationship between eight self-reported ACEs and frequent insufficient sleep among community-dwelling adults residing in 5 U.S. states in 2009. To assess whether ACEs were associated with frequent insufficient sleep (respondent did not get sufficient rest or sleep ≥ 14 days in past 30 days) in adulthood, we analyzed ACE data collected in the 2009 Behavioral Risk Factor Surveillance System, a random-digit-dialed telephone survey in Arkansas, Louisiana, New Mexico, Tennessee, and Washington. ACEs included physical abuse, sexual abuse, verbal abuse, household mental illness, incarcerated household members, household substance abuse, parental separation/divorce, and witnessing domestic violence before age 18. Smoking status and frequent mental distress (FMD) (≥ 14 days in past 30 days when self-perceived mental health was not good) were assessed as potential mediators in multivariate logistic regression analyses of frequent insufficient sleep by ACEs adjusted for race/ethnicity, gender, education, and body mass index. Overall, 28.8% of 25,810 respondents reported frequent insufficient sleep, 18.8% were current smokers, 10.8% reported frequent mental distress, 59.5% percent reported ≥ 1 ACE, and 8.7% reported ≥ 5 ACEs. Each ACE was associated with frequent insufficient sleep in multivariate analyses. Odds of frequent insufficient sleep were 2.5 (95% CI, 2.1-3.1) times higher in persons with ≥ 5 ACEs compared to those with no ACEs. Most relationships were modestly attenuated by smoking and FMD, but remained significant. Childhood exposures to eight indicators of child maltreatment and household dysfunction were significantly associated with frequent insufficient sleep during adulthood in this population. ACEs could be potential indicators promoting further investigation of sleep insufficiency, along with consideration of FMD and smoking.

Angiotensin converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy

PubMed Central

Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M.; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

2016-01-01

Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II(1-8) that could also be effective involves fostering its degradation. Angiotensin converting enzyme 2 (ACE2) is a monocarboxypeptidase than cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity and glomerular size, were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic nephropathy. PMID:27927599

Angiotensin-converting enzyme 2 amplification limited to the circulation does not protect mice from development of diabetic nephropathy.

PubMed

Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel

2017-06-01

Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II (1-8) that could also be effective involves fostering its degradation. Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity, and glomerular size were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic nephropathy. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Angiotensin converting enzyme genotype and chronic allograft nephropathy in protocol biopsies.

PubMed

Hueso, Miguel; Alía, Pedro; Moreso, Francesc; Beltrán-Sastre, Violeta; Riera, Luis; González, Carlota; Navarro, Miguel Angel; Grinyó, Josep Maria; Navarro, Estanis; Serón, Daniel

2004-08-01

Genotype DD of the angiotensin-converting enzyme (ACE) is not associated with an increased incidence of native renal diseases, although it could modulate progression to renal failure in patients who already display chronic lesions. Because its role in renal allograft degeneration is not well characterized, whether ACE genotype was associated with the prevalence of chronic allograft nephropathy (CAN) was studied, in a group of protocol biopsies from 180 patients, or with the incidence of CAN in 152 patients with at least two sequential biopsies. As a control group, ACE genotype was also studied in 41 donors and 72 healthy subjects. For analyzing the influence of ACE genotype in graft survival, patients were grouped into six categories (II-normal biopsy, ID-normal, DD-normal, II-CAN, ID-CAN and DD-CAN). Finally, relative renal ACE mRNA levels were measured in 67 cases by real-time PCR using the delta threshold cycle method. ACE-DD genotype was more frequent in patients who received a transplant than in control subjects (43.3% versus 30.1%, P = 0.026), but prevalence (DD = 42.7% versus non-DD = 42.2%) or incidence (DD = 24.6% versus non-DD = 29.9%) of CAN was not different regarding recipient ACE genotype. Furthermore, patients with the ACE-DD genotype and CAN had the poorest graft survival (II-normal = 100%, ID-normal = 91%, DD-normal = 84%, II-CAN = 100%, ID-CAN = 66%, and DD-CAN = 36%; P = 0.034) and higher ACE mRNA levels than non-DD and CAN (DD = -3.36 +/- 2.35 versus non-DD = -5.65 +/- 1.72-fold in ACE copies; P = 0.012). It is concluded that ACE-DD genotype is not associated with an increased prevalence or incidence of CAN but is actually associated with higher ACE mRNA levels and poorer graft survival in patients who already display CAN.

Circulating angiotensin-converting enzyme 2 activity in kidney transplantation: a longitudinal pilot study.

PubMed

Soler, María José; Riera, Marta; Crespo, Marta; Mir, Marisa; Márquez, Eva; Pascual, María José; Puig, Josep M; Pascual, Julio

2012-01-01

Angiotensin-converting enzyme 2 (ACE2) is the only known active homologue of ACE, and degrades angiotensin (Ang) II and Ang I to Ang(1-7) and Ang(1-9), respectively. The role of ACE2 in kidney transplant (KT) is unknown. Our objective was to investigate circulating ACE2 activity in KT patients, and the relationship between serum ACE2 activity and age, gender, graft function and cardiovascular risk markers in KT patients. 113 KT patients with stable graft function were included in this cross-sectional study. Circulating ACE2 activity was assessed using a fluorescent assay. Circulating ACE2 activity was detectable in KT patients and was increased in KT with ischemic heart disease as compared to KT without ischemic heart disease (105.9 ± 8.7 vs. 97.1 ± 7.05 relative fluorescence units (RFU)/µl/h, p < 0.05). ACE2 activity was increased in male KT as compared to females (105.2 ± 9.1 vs. 84.7 ± 6.9 RFU/µl/h, p = 0.05). ACE2 activity correlated positively with serum creatinine (r = 0.27), serum urea (r = 0.29), age (r = 0.24), aspartate transaminase (r = 0.39), alanine transaminase (r = 0.48), γ-glutamyl transferase (γ-GT) (r = 0.52), age (r = 0.24), and glycosylated hemoglobin (r = 0.19) (p < 0.05). By multiple regression analysis, age, serum creatinine, and serum γ-GT were independent predictors of serum ACE2 activity (r = 0.66, p < 0.001). Circulating ACE2 activity is measurable in KT patients and directly correlates with age, renal allograft and liver function parameters. These findings suggest that measurement of serum ACE2 may be used as a non-invasive marker to understand the role of the renin-angiotensin system in KT patients. Copyright © 2012 S. Karger AG, Basel.

A Single Nucleotide Polymorphism Uncovers a Novel Function for the Transcription Factor Ace2 during Candida albicans Hyphal Development

PubMed Central

Orellana-Muñoz, Sara; Gutiérrez-Escribano, Pilar; Arnáiz-Pita, Yolanda; Dueñas-Santero, Encarnación; Suárez, M. Belén; Bougnoux, Marie-Elisabeth; del Rey, Francisco; Sherlock, Gavin; d’Enfert, Christophe; Correa-Bordes, Jaime; de Aldana, Carlos R. Vázquez

2015-01-01

Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages. PMID:25875512

21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Angiotensin converting enzyme (A.C.E.) test system... Test Systems § 862.1090 Angiotensin converting enzyme (A.C.E.) test system. (a) Identification. An angiotensin converting enzyme (A.C.E.) test system is a device intended to measure the activity of angiotensin...

End of Life Disposal for Three Libration Point Missions through Manipulation of the Jacobi Constant and Zero Velocity Curves

NASA Technical Reports Server (NTRS)

Petersen, Jeremy; Brown, Jonathan

2015-01-01

Flight Dynamics Facility (FDF) located at NASA Goddard Space Flight Center (GSFC) provides the flight dynamics expertise for three Sun-Earth Moon L1 missions. Advanced Composition Explorer (ACE) launched August 1997 Solar and Heliospheric Observatory (SOHO) launched December 1995 Global Geospace Science WIND satellite launched November 1994 entered Lagrange point orbit in 2004.

ACE2 Therapy Using Adeno-associated Viral Vector Inhibits Liver Fibrosis in Mice

PubMed Central

Mak, Kai Y; Chin, Ruth; Cunningham, Sharon C; Habib, Miriam R; Torresi, Joseph; Sharland, Alexandra F; Alexander, Ian E; Angus, Peter W; Herath, Chandana B

2015-01-01

Angiotensin converting enzyme 2 (ACE2) which breaks down profibrotic peptide angiotensin II to antifibrotic peptide angiotensin-(1–7) is a potential therapeutic target in liver fibrosis. We therefore investigated the long-term therapeutic effect of recombinant ACE2 using a liver-specific adeno-associated viral genome 2 serotype 8 vector (rAAV2/8-ACE2) with a liver-specific promoter in three murine models of chronic liver disease, including carbon tetrachloride-induced toxic injury, bile duct ligation-induced cholestatic injury, and methionine- and choline-deficient diet-induced steatotic injury. A single injection of rAAV2/8-ACE2 was administered after liver disease has established. Hepatic fibrosis, gene and protein expression, and the mechanisms that rAAV2/8-ACE2 therapy associated reduction in liver fibrosis were analyzed. Compared with control group, rAAV2/8-ACE2 therapy produced rapid and sustained upregulation of hepatic ACE2, resulting in a profound reduction in fibrosis and profibrotic markers in all diseased models. These changes were accompanied by reduction in hepatic angiotensin II levels with concomitant increases in hepatic angiotensin-(1–7) levels, resulting in significant reductions of NADPH oxidase assembly, oxidative stress and ERK1/2 and p38 phosphorylation. Moreover, rAAV2/8-ACE2 therapy normalized increased intrahepatic vascular tone in fibrotic livers. We conclude that rAAV2/8-ACE2 is an effective liver-targeted, long-term therapy for liver fibrosis and its complications without producing unwanted systemic effects. PMID:25997428

Murine recombinant angiotensin-converting enzyme 2 attenuates kidney injury in experimental Alport syndrome.

PubMed

Bae, Eun Hui; Fang, Fei; Williams, Vanessa R; Konvalinka, Ana; Zhou, Xiaohua; Patel, Vaibhav B; Song, Xuewen; John, Rohan; Oudit, Gavin Y; Pei, York; Scholey, James W

2017-06-01

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase in the renin-angiotensin system that catalyzes the breakdown of angiotensin II to angiotensin 1-7. We have reported that ACE2 expression in the kidney is reduced in experimental Alport syndrome but the impact of this finding on disease progression has not been studied. Accordingly, we evaluated effects of murine recombinant ACE2 treatment in Col4a3 knockout mice, a model of Alport syndrome characterized by proteinuria and progressive renal injury. Murine recombinant ACE2 (0.5 mg/kg/day) was administered from four to seven weeks of age via osmotic mini-pump. Pathological changes were attenuated by murine recombinant ACE2 treatment which ameliorated kidney fibrosis as shown by decreased expression of COL1α1 mRNA, less accumulation of extracellular matrix proteins, and inhibition of transforming growth factor-β signaling. Further, increases in proinflammatory cytokine expression, macrophage infiltration, inflammatory signaling pathway activation, and heme oxygenase-1 levels in Col4a3 knockout mice were also reduced by murine recombinant ACE2 treatment. Lastly, murine recombinant ACE2 influenced the turnover of renal ACE2, as it suppressed the expression of tumor necrosis factor-α converting enzyme, a negative regulator of ACE2. Thus, treatment with exogenous ACE2 alters angiotensin peptide metabolism in the kidneys of Col4a3 knockout mice and attenuates the progression of Alport syndrome nephropathy. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ryan, J.W.; Anderson, D.R.

Eye tissues contain kininase activities, including an angiotensin converting enzyme (ACE)-like activity. The authors have begun further to characterize the ACE-like activity and to examine for another reputed kininase, carboxypeptidase N (CPN). Homogenates of tissues of 6 cat eyes and paired plasmas were assayed for ACE using 3 acyl-tripeptide substrates, /sup 3/H-benzoylated F-A-P, F-G-P and A-G-P (respectively, BFAP, BFGP and BAGP). CPN was assayed using /sup 3/H-benzoyl-A-R. All eye tissues and fluids contained ACE- and CPN-like activities. The ACE activity was clearly owing to ACE: relative values of Kc/Km for BFAP, BFGP and BAGP were those for pure ACE (2.213,more » 1.751 and 1.0); reactivities with inhibitors were as expected (Ki for captopril, MK 422 and RAC-X-65: 2.7, 0.62 and 0.31 nM). EDTA inhibited both ACE and CPN (I/sub 50/'s: 43 and 47 ..mu..M). CPN activity was inhibited by 2-mercaptomethyl-3-guanidinoethylthiopropionate (Ki 2.4 nM). However, distributions of the two enzymes differed markedly. Virtually all tissues contained ACE at specific activities higher than that of plasma. Specific activities appeared to be a function of tissue vascularity (for choroid, ciliary body, iris, retina and plasma: 7.31, 2.57, 1.98, 1.53 and 0.21 pmol/mg protein). Only iris contained more CPN that did plasma (23.0 v. 7.21 pmol/mg protein). The tissue distribution of ACE is that expected for an endothelial-associated enzyme. Plasma may be the major source of CPN in eye tissues other than iris.« less

On Becoming Trauma-Informed: Role of the Adverse Childhood Experiences Survey in Tertiary Child and Adolescent Mental Health Services and the Association with Standard Measures of Impairment and Severity.

PubMed

Rahman, Abdul; Perri, Andrea; Deegan, Avril; Kuntz, Jennifer; Cawthorpe, David

2018-01-01

There is a movement toward trauma-informed, trauma-focused psychiatric treatment. To examine Adverse Childhood Experiences (ACE) survey items by sex and by total scores by sex vs clinical measures of impairment to examine the clinical utility of the ACE survey as an index of trauma in a child and adolescent mental health care setting. Descriptive, polychoric factor analysis and regression analyses were employed to analyze cross-sectional ACE surveys (N = 2833) and registration-linked data using past admissions (N = 10,400) collected from November 2016 to March 2017 related to clinical data (28 independent variables), taking into account multicollinearity. Distinct ACE items emerged for males, females, and those with self-identified sex and for ACE total scores in regression analysis. In hierarchical regression analysis, the final models consisting of standard clinical measures and demographic and system variables (eg, repeated admissions) were associated with substantial ACE total score variance for females (44%) and males (38%). Inadequate sample size foreclosed on developing a reduced multivariable model for the self-identified sex group. The ACE scores relate to independent clinical measures and system and demographic variables. There are implications for clinical practice. For example, a child presenting with anxiety and a high ACE score likely requires treatment that is different from a child presenting with anxiety and an ACE score of zero. The ACE survey score is an important index of presenting clinical status that guides patient care planning and intervention in the progress toward a trauma-focused system of care.

ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity.

PubMed

Patel, Vaibhav B; Mori, Jun; McLean, Brent A; Basu, Ratnadeep; Das, Subhash K; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M; Grant, Maria B; Lopaschuk, Gary D; Oudit, Gavin Y

2016-01-01

Obesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

MSCs with ACE II gene affect apoptosis pathway of acute lung injury induced by bleomycin.

PubMed

Zhang, Xiaomiao; Gao, Fengying; Li, Qian; Dong, Zhixia; Sun, Bo; Hou, Lili; Li, Zhuozhe; Liu, Zhenwei

2015-02-01

The aim of this study was to evaluate the effect and related mechanisms of Mesenchymal stem cells (MSCs) and Angiotensin converting enzyme II (ACE II) on acute lung injury (ALI). MSCs were separated from umbilical cord cells, and the changes of phenotype before and after ACE II silence were observed using Flow Cytometer. ALI model was induced by 10 mg/mL bleomycin in 60 Balb/c mice, and the rest 8 mice were regarded as the baseline group. The mice were randomly divided into four groups (n = 15): control, ACE II, stem, and stem + ACE II. The apoptotic index (AI) was calculated using TUNEL, and the detection of protein and mRNA of Bax, Bak and p53, Bcl-2, Grp78, CHOP and Caspase 12 were used by western-blot and RT-PCR, respectively. The umbilical cord cells differentiated into stable MSCs about 14 days, and ACE II transfection reached a peak at the 5th day after transfection. ACE II silence did not affect the phenotype of MSCs. All the proteins and mRNAs expression except Bcl-2 in the stem and stem + ACE II were significantly lower than those in control from 8 h (p < 0.05, p < 0.01), while Bcl-2 exhibited an opposite trend. Stem + ACE II performed a better effect than single stem in most indexes, including AI (p < 0.05, p < 0.01). The co-administration of MSCs and ACE II can significantly suppress apoptosis in ALI mice, and may be an effective clinical treatment for ALI.

In vitro autoradiographic localization of angiotensin-converting enzyme in sarcoid lymph nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allen, R.K.; Chai, S.Y.; Dunbar, M.S.

1986-09-01

Angiotensin-converting enzyme (ACE) was localized in sarcoid lymph nodes by an in vitro autoradiographic technique using a synthetic ACE inhibitor of high affinity, /sup 125/I-labelled 351A. The lymph nodes were from seven patients with active sarcoidosis who underwent mediastinoscopy and from six control subjects who had nodes resected at either mediastinoscopy or laparotomy. Angiotensin-converting enzyme was localized in the epithelioid cells of sarcoid granulomata in markedly increased amounts compared with control nodes, where it was restricted to vessels and some histiocytes. In sarcoid lymph nodes, there was little ACE present in lymphocytes or fibrous tissue. Sarcoid nodes with considerable fibrosismore » had much less intense ACE activity than the nonfibrotic nodes. The specific activity of ACE measured by an enzymatic assay in both the control and sarcoid lymph nodes closely reflected the ACE activity demonstrated by autoradiography. Sarcoid lymph nodes with fibrosis had an ACE specific activity of half that of nonfibrotic nodes (p less than 0.05). There was a 15-fold increase in specific ACE activity in sarcoid nodes (p less than 0.05) compared to normal. Serum ACE was significantly higher in those sarcoid patients whose lymph nodes were not fibrosed compared with those with fibrosis (p less than 0.01). This technique offers many advantages over the use of polyclonal antibodies. The 351A is a highly specific ACE inhibitor, chemically defined and in limitless supply. This method enables the quantitation of results, and autoradiographs may be stored indefinitely for later comparison.« less

Absence of cell surface expression of human ACE leads to perinatal death

PubMed Central

Michaud, Annie; Acharya, K. Ravi; Masuyer, Geoffrey; Quenech'du, Nicole; Gribouval, Olivier; Morinière, Vincent; Gubler, Marie-Claire; Corvol, Pierre

2014-01-01

Renal tubular dysgenesis (RTD) is a recessive autosomal disease characterized most often by perinatal death. It is due to the inactivation of any of the major genes of the renin-angiotensin system (RAS), one of which is the angiotensin I-converting enzyme (ACE). ACE is present as a tissue-bound enzyme and circulates in plasma after its solubilization. In this report, we present the effect of different ACE mutations associated with RTD on ACE intracellular trafficking, secretion and enzymatic activity. One truncated mutant, R762X, responsible for neonatal death was found to be an enzymatically active, secreted form, not inserted in the plasma membrane. In contrast, another mutant, R1180P, was compatible with life after transient neonatal renal insufficiency. This mutant was located at the plasma membrane and rapidly secreted. These results highlight the importance of tissue-bound ACE versus circulating ACE and show that the total absence of cell surface expression of ACE is incompatible with life. In addition, two missense mutants (W594R and R828H) and two truncated mutants (Q1136X and G1145AX) were also studied. These mutants were neither inserted in the plasma membrane nor secreted. Finally, the structural implications of these ACE mutations were examined by molecular modelling, which suggested some important structural alterations such as disruption of intra-molecular non-covalent interactions (e.g. salt bridges). PMID:24163131

Validity of the T-ACE in pregnancy in predicting child outcome and risk drinking.

PubMed

Chiodo, Lisa M; Sokol, Robert J; Delaney-Black, Virginia; Janisse, James; Hannigan, John H

2010-01-01

Preventing fetal alcohol spectrum disorders (FASDs) requires detection of in-pregnancy maternal risk drinking. The widely used T-ACE screen has been applied in various ways, although the impact of those different uses on effectiveness is uncertain. We examined relations among different T-ACE scoring criteria, maternal drinking, and child outcome. Self-reported across-pregnancy maternal drinking was assessed in 75 African-American women. The different T-ACE criteria used varied the level of drinking that defined tolerance (two or three drinks) and the total T-ACE score cut-points (two or three). Receiver operator curves and regression analysis assessed the significance of relations. Increasing the total T-ACE score cut-point to 3 almost doubled specificity in detecting risk drinking whereas maintaining adequate sensitivity, equivalent to that in the original report, and identified substantially more neurobehavioral deficits in children. Redefining tolerance at three drinks did not improve T-ACE effectiveness in predicting outcomes. This study is among the first to show the ability of an in-pregnancy T-ACE assessment to predict child neurodevelopmental outcome. In addition, increasing the total T-ACE score criterion (from 2 to 3) improved identification of non-drinking mothers and unaffected children with little loss in detection of drinkers and affected children. Efficient in-pregnancy screens for risk drinking afford greater opportunities for intervention that could prevent/limit FASDs. Published by Elsevier Inc.

Angiotensin-converting enzyme inhibitor (enalapril maleate) accelerates recovery of mouse skin from UVB-induced wrinkles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuura-Hachiya, Yuko; Arai, Koji Y.; Ozeki, Rieko

Highlights: •Angiotensin converting enzyme (ACE) increases in UVB-irradiated skin. •Administration of an ACE inhibitor improved UVB-induced skin wrinkle. •ACE inhibitor improved UVB-induced epidermal hypertrophy. •ACE inhibitor improved transepidermal water loss in the UVB-irradiated skin. -- Abstract: Angiotensin-converting enzyme (ACE) activity and angiotensin II signaling regulate cell proliferation, differentiation, and tissue remodeling, as well as blood pressure, while in skin, angiotensin II signaling is involved in wound healing, inflammation, and pathological scar formation. Therefore, we hypothesized that angiotensin II is also involved in photoaging of skin. In this study, we examined the effect of enalapril maleate, an ACE inhibitor, on recoverymore » of wrinkled skin of hairless mice exposed to long-term UVB irradiation. Immunohistochemical observation revealed that expression of ACE, angiotensin II, and angiotensin II type 1 (AT1) and type 2 (AT2) receptors in the skin was increased after UVB irradiation (3 times/week at increasing intensities for 8 weeks). Administration of enalapril maleate (5 times/week for 6 weeks, starting 1 week after 10-week irradiation) accelerated recovery from UVB-induced wrinkles, epidermal hyperplasia and epidermal barrier dysfunction, as compared with the vehicle control. Our results indicate that ACE and angiotensin II activity are involved in skin photoaging, and suggest that ACE inhibitor such as enalapril maleate may have potential for improvement of photoaged skin.« less

Effect of protease inhibitors on angiotensin-converting enzyme activity in human T-lymphocytes.

PubMed

Petrov, V; Fagard, R; Lijnen, P

2000-05-01

The purpose of these investigations was to determine whether the aminopeptidase B and leucine aminopeptidase inhibitor bestatin, the chymase inhibitor chymostatin, the calpain inhibitor E-64, and the neutral serine protease inhibitor leupeptin affect the angiotensin converting enzyme (ACE) activity in T-lymphocytes. ACE activity in homogenates of T-lymphocytes or in intact T-lymphocytes in suspension was measured by determining fluorimetrically histidyl-leucine, formed from the conversion of hippuryl-histidyl-leucine, coupled with ophtaldialdehyde. The effect of various concentrations (10(-9) to 10(-3) mol/L) of the angiotensin-converting enzyme inhibitors lisinopril and captopril and of the various protease inhibitors on ACE activity was studied. Lisinopril and captopril reduced the ACE activity in homogenates of T-lymphocytes in a concentration-dependent manner. Lisinopril exhibited a more pronounced inhibition of ACE in T-lymphocytes than did captopril. Chymostatin and E-64 had no effect on the ACE activity in T-lymphocytes, whereas leupeptin inhibited its activity in a dose-dependent fashion. Bestatin, on the contrary, increased the ACE activity in homogenates of T-lymphocytes as well as in intact T-lymphocytes in proportion to the concentration. Our data showed that the ACE activity in T-lymphocytes was stimulated by bestatin and inhibited by leupeptin, whereas chymostatin and E-64 did not affect the ACE activity in T-lymphocytes.

Scientific Discovery through Advanced Computing (SciDAC-3) Partnership Project Annual Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoffman, Forest M.; Bochev, Pavel B.; Cameron-Smith, Philip J..

The Applying Computationally Efficient Schemes for BioGeochemical Cycles ACES4BGC Project is advancing the predictive capabilities of Earth System Models (ESMs) by reducing two of the largest sources of uncertainty, aerosols and biospheric feedbacks, with a highly efficient computational approach. In particular, this project is implementing and optimizing new computationally efficient tracer advection algorithms for large numbers of tracer species; adding important biogeochemical interactions between the atmosphere, land, and ocean models; and applying uncertainty quanti cation (UQ) techniques to constrain process parameters and evaluate uncertainties in feedbacks between biogeochemical cycles and the climate system.

ACE [Adult and Community Education] into the 21st Century: A Vision.

ERIC Educational Resources Information Center

Adult, Community, and Further Education Board, Melbourne (Australia).

This document outlines a vision for adult and community education (ACE) in Victoria for the next 3 years and provides a broad map of how to reach that vision. A description of the context is followed by the ACE vision statement: ACE delivers accessible, quality, and timely learning in autonomous, community settings as a valued and essential…

Vibrio cholerae ACE stimulates Ca(2+)-dependent Cl(-)/HCO(3)(-) secretion in T84 cells in vitro.

PubMed

Trucksis, M; Conn, T L; Wasserman, S S; Sears, C L

2000-09-01

ACE, accessory cholera enterotoxin, the third enterotoxin in Vibrio cholerae, has been reported to increase short-circuit current (I(sc)) in rabbit ileum and to cause fluid secretion in ligated rabbit ileal loops. We studied the ACE-induced change in I(sc) and potential difference (PD) in T84 monolayers mounted in modified Ussing chambers, an in vitro model of a Cl(-) secretory cell. ACE added to the apical surface alone stimulated a rapid increase in I(sc) and PD that was concentration dependent and immediately reversed when the toxin was removed. Ion replacement studies established that the current was dependent on Cl(-) and HCO(3)(-). ACE acted synergistically with the Ca(2+)-dependent acetylcholine analog, carbachol, to stimulate secretion in T84 monolayers. In contrast, the secretory response to cAMP or cGMP agonists was not enhanced by ACE. The ACE-stimulated secretion was dependent on extracellular and intracellular Ca(2+) but was not associated with an increase in intracellular cyclic nucleotides. We conclude that the mechanism of secretion by ACE involves Ca(2+) as a second messenger and that this toxin stimulates a novel Ca(2+)-dependent synergy.

ACE Gene I/D Polymorphism and Obesity in 1,574 Patients with Type 2 Diabetes Mellitus.

PubMed

Pan, Yan-Hong; Wang, Min; Huang, Yan-Mei; Wang, Ying-Hui; Chen, Yin-Ling; Geng, Li-Jun; Zhang, Xiao-Xi; Zhao, Hai-Lu

2016-01-01

Association between ACE gene I/D polymorphism and the risk of overweight/obesity remains controversial. We investigated the possible relationship between ACE gene I/D polymorphism and obesity in Chinese type 2 diabetes mellitus (T2DM) patients. In this study, obesity was defined as a body mass index (BMI) value ≥ 25 kg/m 2 and subjects were classified into 4 groups (lean, normal, overweight, and obese). PCR (polymerase chain reaction) was used to detect the ACE gene I/D polymorphism in T2DM patients. Metabolic measurements including blood glucose, lipid profile, and blood pressure were obtained. Frequencies of the ACE genotypes (DD, ID, and II) were not significant among the 4 groups of BMI-defined patients ( P = 0.679) while ACE II carriers showed higher systolic blood pressure (SBP) and pulse pressure (PP) (all P < 0.050). Hyperglycemia, hypertension, and dyslipidemia in these T2DM patients were found to be significantly associated with BMI. In conclusion, the relationship of ACE gene I/D polymorphism with obesity is insignificant in Chinese patients with T2DM. SBP and PP might be higher in the ACE II carriers than in the DD and ID carriers.

Production of angiotensin I converting enzyme inhibitory (ACE-I) peptides during milk fermentation and their role in reducing hypertension.

PubMed

Rai, Amit Kumar; Sanjukta, Samurailatpam; Jeyaram, Kumaraswamy

2017-09-02

Fermented milk is a potential source of various biologically active peptides with specific health benefits. Angiotensin converting enzyme inhibitory (ACE-I) peptides are one of the most studied bioactive peptides produced during milk fermentation. The presence of these peptides is reported in various fermented milk products such as, yoghurt, cheese, sour milk, etc., which are also available as commercial products. Many of the ACE-I peptides formed during milk fermentation are resistant to gastrointestinal digestion and inhibit angiotensin converting enzyme (ACE) in the rennin angiotension system (RAS). There are various factors, which affect the formation ACE-I peptides and their ability to reach the target tissue in active form, which includes type of starters (lactic acid bacteria (LAB), yeast, etc.), substrate composition (casein type, whey protein, etc.), composition of ACE-I peptide, pre and post-fermentation treatments, and its stability during gastrointestinal digestion. The antihypertensive effect of fermented milk products has also been proved by various in vitro and in vivo (animal and human trials) experiments. This paper reviews the literature on fermented milk products as a source of ACE-I peptides and various factors affecting the production and activity of ACE-I peptides.

Focus on increased serum angiotensin-converting enzyme level: From granulomatous diseases to genetic mutations.

PubMed

Lopez-Sublet, Marilucy; di Lanzacco, Lorenzo Caratti; Jan Danser, A H; Lambert, Michel; Elourimi, Ghassan; Persu, Alexandre

2018-06-18

Angiotensin I-converting enzyme (ACE) is a well-known zinc-metallopeptidase that converts angiotensin I to the potent vasoconstrictor angiotensin II and degrades bradykinin, a powerful vasodilator, and as such plays a key role in the regulation of vascular tone and cardiac function. Increased circulating ACE (cACE) activity has been reported in multiple diseases, including but not limited to granulomatous disorders. Since 2001, genetic mutations leading to cACE elevation have also been described. This review takes advantage of the identification of a novel ACE mutation (25-IVS25 + 1G > A) in two Belgian pedigrees to summarize current knowledge about the differential diagnosis of cACE elevation, based on literature review and the experience of our centre. Furthermore, we propose a practical approach for the evaluation and management of patients with elevated cACE and discuss in which cases search for genetic mutations should be considered. Copyright © 2018. Published by Elsevier Inc.

Occurrence and fate of ACE-inhibitor peptides in cheeses and in their digestates following in vitro static gastrointestinal digestion.

PubMed

Stuknytė, Milda; Cattaneo, Stefano; Masotti, Fabio; De Noni, Ivano

2015-02-01

The occurrence of the casein-derived angiotensin converting enzyme-inhibitor (ACE-I) peptides VPP, IPP, RYLGY, RYLG, AYFYPEL, AYFYPE, LHLPLP and HLPLP were investigated in 12 different cheese samples by Ultra Performance Liquid Chromatography/High-Resolution Mass Spectrometry. The total amount of ACE-I peptides was in the range 0.87-331mgkg(-1). VPP and IPP largely prevailed in almost all cheeses. Following in vitro static gastrointestinal digestion of Cheddar, Gorgonzola, Maasdam and Grana Padano cheeses, type and amount of ACE-I peptides changed, and only VPP, IPP, HLPLP and LHLPLP were detected in the intestinal digestates. The results evidenced that the degree of proteolysis itself cannot be regarded as a promoting or hindering factor for ACE-I peptide release during cheese digestion. Moreover, the data indicated that the ACE-I potential of cheeses cannot be inferred based on the type and amount of ACE-I peptides present in undigested samples. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessment of the rs4340 ACE gene polymorphism in acute coronary syndrome in a Western Mexican population.

PubMed

Valdez-Haro, A; Valle, Y; Valdes-Alvarado, E; Casillas-Muñoz, F; Muñoz-Valle, J F; Reynoso-Villalpando, G L; Flores-Salinas, H E; Padilla-Gutiérrez, J R

2017-09-27

Acute coronary syndrome (ACS) is considered one of the main causes of death worldwide. Contradictory findings concerning the impact of the angiotensin-converting enzyme (ACE) gene on cardiovascular diseases have been reported. Previous conclusions point out that the variability in results depends on ethnicity and genetic polymorphisms to determine the association of rs4340 polymorphisms of the ACE gene and ACE circulating levels in ACS. Genotyping of rs4340 polymorphisms was performed in a total of 600 individuals from Western Mexico divided into two groups: the ACS and the control group (CG). The polymorphisms were identified by polymerase chain reaction. Serum ACE concentration was determined by enzyme-linked immunosorbent assay. D/D carriers had higher ACE levels than I/I carriers (3.6 vs 2.8 ng/mL, P < 0.0021) in the CG. The D/D genotype of the rs4340 polymorphism is associated with higher ACE concentration levels; however, the polymorphism was not associated with ACS.

Separation and Characterization of Angiotensin I Converting Enzyme (ACE) Inhibitory Peptides from Saurida elongata Proteins Hydrolysate by IMAC-Ni2.

PubMed

Sun, Lixia; Wu, Shanguang; Zhou, Liqin; Wang, Feng; Lan, Xiongdiao; Sun, Jianhua; Tong, Zhangfa; Liao, Dankui

2017-02-15

Lizard fish protein hydrolysates (LFPH) were prepared from Lizard fish ( Saurida elongata ) proteins possessing powerful angiotensin I converting enzyme (ACE) inhibitory activity and the fraction (LFPH-I) with high ACE inhibitory activity was obtained through ultrafiltration. The active Fraction (F2) was isolated from LFPH-I using immobilized metal affinity chromatography (IMAC - Ni 2+ ). Analysis of amino acid levels revealed that F2 eluted from IMAC was enriched in Met, His, Tyr, Pro, Ile, and Leu compared to the crude peptide LFPH-I. F2 with the high ACE inhibitory activity (IC 50 of 0.116 mg·mL -1 ) was further separated by a reverse-phase column to yield a novel ACE inhibitory peptide with IC 50 value of 52 μM. The ACE inhibitory peptide was identified as Arg-Tyr-Arg-Pro, RYRP. The present study demonstrated that IMAC may be a useful tool for the separation of ACE inhibitory peptides from protein hydrolysate.

ACE I/D and MMP-7 A-181G variants and the risk of end stage renal disease.

PubMed

Rahimi, Zohreh; Abdi, Hamed; Tanhapoor, Maryam; Rahimi, Ziba; Vaisi-Raygani, Asad; Nomani, Hamid

2017-03-01

The variants of angiotensin converting enzyme ( ACE ) and matrix metalloproteinases (MMPs) genes might be involved in the pathogenesis of end stage renal disease (ESRD) and hypertension. We studied the ACE insertion/deletion (I/D) and MMP-7 A-181G variants in 99 unrelated ESRD patients and 117 individuals without renal complications from Western Iran with Kurdish ethnic background. The frequency of ACE I/D variants was not significantly different between ESRD patients and controls. However, the presence of ACE D allele increased the risk of hypertension in ESRD patients by 2.14-fold (P=0.036). The MMP-7 -181 AG genotype increased the risk of ESRD by 2.04 times (P=0.026). The present study indicated the absence of an association between the ACE I/D polymorphism with the risk of ESRD. However, the ACE D allele increased the risk of hypertension in ESRD patients. Also, the present study suggests a role for MMP-7 AG genotype in the pathogenesis of ESRD.

Identification of ACE-inhibitory peptides from Phaseolus vulgaris after in vitro gastrointestinal digestion.

PubMed

Tagliazucchi, Davide; Martini, Serena; Bellesia, Andrea; Conte, Angela

2015-01-01

The objective of this study was to identify the angiotensin I-converting enzyme (ACE)-inhibitory peptides released from thermally treated Phaseolus vulgaris (pinto) whole beans after in vitro gastrointestinal digestion. The degree of hydrolysis increased during digestion reaching a value of 50% at the end of the pancreatic digestion. The <3 kDa fraction of the postpancreatic sample showed high ACE-inhibitory activity (IC50 = 105.6 ± 2.1 μg of peptides/mL). Peptides responsible for the ACE-inhibitory activity were isolated by reverse-phase high-performance liquid chromatography (HPLC). Three fractions, showing the highest inhibitory activity, were selected for tandem mass spectrometry (MS/MS) experiments. Eleven of the identified sequences have previously been described as ACE-inhibitors. Most of the identified bioactive peptides have a hydrophobic amino acid, (iso)leucine or phenylalanine, or proline at the C-terminal position, which is crucial for their ACE-inhibitory activity. The sequence of some peptides allowed us to anticipate the presence of ACE-inhibitory activity.

The effects analysis of two neonicotinoid insecticides on in vitro maturation of porcine oocytes using hanging drop monoculture method.

PubMed

Ishikawa, Sadamasa; Hiraga, Kou; Hiradate, Yuuki; Tanemura, Kentaro

2015-06-01

Acetamiprid (ACE) and imidacroprid (IMI) are known neonicotinoid insecticides with strong affinities for the insect-selective nicotinic acetylcholine receptor. These provide insect control by hyperstimulating insect nerves and are used for agricultural pest management. However, it has also been reported that ACE and IMI affect mammalian reproductive function. We determined the effects of ACE and IMI on the in vitro maturation of porcine oocytes. Significant decreases in nuclear maturation rates were observed in the ACE or IMI-exposed groups. Also, in matured oocytes from the ACE or IMI-exposed groups, irregular chromosomes were observed. Our results suggest that ACE and IMI exposure was detrimental to porcine oocytes and the extent of the effects depends on the concentration of exposure.

Adverse childhood experiences, posttraumatic stress disorder symptoms, and emotional intelligence in partner aggression.

PubMed

Swopes, Rachael M; Simonet, Daniel V; Jaffe, Anna E; Tett, Robert P; Davis, Joanne L

2013-01-01

Intimate partner violence (IPV) has been linked to childhood abuse, posttraumatic stress disorder (PTSD), and low emotional intelligence (EI). Relationships among adverse childhood experiences (ACE), PTSD symptoms, and partner aggression (i.e., generalized tendency to aggress toward one's partner) were assessed in 108 male IPV offenders. It was hypothesized that ACE is positively correlated with partner aggression, PTSD mediates the ACE-aggression relationship, and the ACE-PTSD-aggression mediation varies by selected EI facets. Results indicate that ACE has an indirect effect on partner aggression via PTSD and PTSD mediates the ACE-aggression link when emotional self-regulation is low and when intuition (vs. reason) is high. Trauma-exposed IPV offenders may benefit from comprehensive treatments focusing on PTSD symptoms, emotional control, and reasoning skills to reduce aggression.

Synthesis and evaluation of novel triazoles and mannich bases functionalized 1,4-dihydropyridine as angiotensin converting enzyme (ACE) inhibitors.

PubMed

Kumbhare, Ravindra M; Kosurkar, Umesh B; Bagul, Pankaj K; Kanwal, Abhinav; Appalanaidu, K; Dadmal, Tulshiram L; Banerjee, Sanjay Kumar

2014-11-01

A series of novel diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate embedded triazole and mannich bases were synthesized, and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. Screening of above synthesized compounds for ACE inhibition showed that triazoles functionalized compounds have better ACE inhibitory activity compared to that of mannich bases analogues. Among all triazoles we found 6 h, 6 i and 6 j to have good ACE inhibition activity with IC50 values 0.713 μM, 0.409 μM and 0.653 μM, respectively. Among mannich bases series compounds, only 7c resulted as most active ACE inhibitor with IC50 value of 0.928 μM. Copyright © 2014. Published by Elsevier Ltd.

Assessment of Aerosol Distributions from GEOS-5 Using the CALIPSO Feature Mask

NASA Technical Reports Server (NTRS)

Welton, Ellsworth

2010-01-01

A-train sensors such as MODIS, MISR, and CALIPSO are used to determine aerosol properties, and in the process a means of estimating aerosol type (e.g. smoke vs. dust). Correct classification of aerosol type is important for climate assessment, air quality applications, and for comparisons and analysis with aerosol transport models. The Aerosols-Clouds-Ecosystems (ACE) satellite mission proposed in the NRC Decadal Survey describes a next generation aerosol and cloud suite similar to the current A-train, including a lidar. The future ACE lidar must be able to determine aerosol type effectively in conjunction with modeling activities to achieve ACE objectives. Here we examine the current capabilities of CALIPSO and the NASA Goddard Earth Observing System general circulation model and data assimilation system (GEOS-5), to place future ACE needs in context. The CALIPSO level 2 feature mask includes vertical profiles of aerosol layers classified by type. GEOS-5 provides global 3D aerosol mass for sulfate, sea salt, dust, and black and organic carbon. A GEOS aerosol scene classification algorithm has been developed to provide estimates of aerosol mixtures and extinction profiles along the CALIPSO orbit track. In previous work, initial comparisons between GEOS-5 derived aerosol mixtures and CALIPSO derived aerosol types were presented for July 2007. In general, the results showed that model and lidar derived aerosol types did not agree well in the boundary layer. Agreement was poor over Europe, where CALIPSO indicated the presence of dust and pollution mixtures yet GEOS-5 was dominated by pollution with little dust. Over the ocean in the tropics, the model appeared to contain less sea salt than detected by CALIPSO, yet at high latitudes the situation was reserved. Agreement between CALIPSO and GEOS-5, aerosol types improved above the boundary layer, primarily in dust and smoke dominated regions. At higher altitudes (> 5 km), the model contained aerosol layers not detected by CALIPSO. Here we present new results for a full year study using the new Version 3 CALIPSO data and most recent GEOS-5 model results.

Rediscovering ACE: Novel insights into the many roles of the angiotensin-converting enzyme

PubMed Central

Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Bernstein, Ellen A.; Janjulia, Tea; Taylor, Brian; Giani, Jorge F.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Shi, Peng D.; Fuchs, Sebastien; Bernstein, Kenneth E.

2013-01-01

Angiotensin converting enzyme (ACE) is best known for the catalytic conversion of angiotensin I to angiotensin II. However, the use of gene-targeting techniques has led to mouse models highlighting many other biochemical properties and actions of this enzyme. This review discusses recent studies examining the functional significance of ACE tissue-specific expression and the presence in ACE of two independent catalytic sites with distinct substrates and biological effects. It is these features which explain why ACE makes important contributions to many different physiological processes including renal development, blood pressure control, inflammation and immunity. PMID:23686164

Correlation of the National Board of Medical Examiners Emergency Medicine Advanced Clinical Examination Given in July to Intern American Board of Emergency Medicine in-training Examination Scores: A Predictor of Performance?

PubMed

Hiller, Katherine; Franzen, Doug; Heitz, Corey; Emery, Matthew; Poznanski, Stacy

2015-11-01

There is great variation in the knowledge base of Emergency Medicine (EM) interns in July. The first objective knowledge assessment during residency does not occur until eight months later, in February, when the American Board of EM (ABEM) administers the in-training examination (ITE). In 2013, the National Board of Medical Examiners (NBME) released the EM Advanced Clinical Examination (EM-ACE), an assessment intended for fourth-year medical students. Administration of the EM-ACE to interns at the start of residency may provide an earlier opportunity to assess the new EM residents' knowledge base. The primary objective of this study was to determine the correlation of the NBME EM-ACE, given early in residency, with the EM ITE. Secondary objectives included determination of the correlation of the United States Medical Licensing Examination (USMLE) Step 1 or 2 scores with early intern EM-ACE and ITE scores and the effect, if any, of clinical EM experience on examination correlation. This was a multi-institutional, observational study. Entering EM interns at six residencies took the EM-ACE in July 2013 and the ABEM ITE in February 2014. We collected scores for the EM-ACE and ITE, age, gender, weeks of clinical EM experience in residency prior to the ITE, and USMLE Step 1 and 2 scores. Pearson's correlation and linear regression were performed. Sixty-two interns took the EM-ACE and the ITE. The Pearson's correlation coefficient between the ITE and the EM-ACE was 0.62. R-squared was 0.5 (adjusted 0.4). The coefficient of determination was 0.41 (95% CI [0.3-0.8]). For every increase of one in the scaled EM-ACE score, we observed a 0.4% increase in the EM in-training score. In a linear regression model using all available variables (EM-ACE, gender, age, clinical exposure to EM, and USMLE Step 1 and Step 2 scores), only the EM-ACE score was significantly associated with the ITE (p<0.05). We observed significant colinearity among the EM-ACE, ITE and USMLE scores. Gender, age and number of weeks of EM prior to the ITE had no effect on the relationship between EM-ACE and the ITE. Given early during intern year, the EM-ACE score showed positive correlation with ITE. Clinical EM experience prior to the in-training exam did not affect the correlation.

Correlation of the National Board of Medical Examiners Emergency Medicine Advanced Clinical Examination Given in July to Intern American Board of Emergency Medicine in-training Examination Scores: A Predictor of Performance?

PubMed Central

Hiller, Katherine; Franzen, Doug; Heitz, Corey; Emery, Matthew; Poznanski, Stacy

2015-01-01

Introduction There is great variation in the knowledge base of Emergency Medicine (EM) interns in July. The first objective knowledge assessment during residency does not occur until eight months later, in February, when the American Board of EM (ABEM) administers the in-training examination (ITE). In 2013, the National Board of Medical Examiners (NBME) released the EM Advanced Clinical Examination (EM-ACE), an assessment intended for fourth-year medical students. Administration of the EM-ACE to interns at the start of residency may provide an earlier opportunity to assess the new EM residents’ knowledge base. The primary objective of this study was to determine the correlation of the NBME EM-ACE, given early in residency, with the EM ITE. Secondary objectives included determination of the correlation of the United States Medical Licensing Examination (USMLE) Step 1 or 2 scores with early intern EM-ACE and ITE scores and the effect, if any, of clinical EM experience on examination correlation. Methods This was a multi-institutional, observational study. Entering EM interns at six residencies took the EM-ACE in July 2013 and the ABEM ITE in February 2014. We collected scores for the EM-ACE and ITE, age, gender, weeks of clinical EM experience in residency prior to the ITE, and USMLE Step 1 and 2 scores. Pearson’s correlation and linear regression were performed. Results Sixty-two interns took the EM-ACE and the ITE. The Pearson’s correlation coefficient between the ITE and the EM-ACE was 0.62. R-squared was 0.5 (adjusted 0.4). The coefficient of determination was 0.41 (95% CI [0.3–0.8]). For every increase of one in the scaled EM-ACE score, we observed a 0.4% increase in the EM in-training score. In a linear regression model using all available variables (EM-ACE, gender, age, clinical exposure to EM, and USMLE Step 1 and Step 2 scores), only the EM-ACE score was significantly associated with the ITE (p<0.05). We observed significant colinearity among the EM-ACE, ITE and USMLE scores. Gender, age and number of weeks of EM prior to the ITE had no effect on the relationship between EM-ACE and the ITE. Conclusion Given early during intern year, the EM-ACE score showed positive correlation with ITE. Clinical EM experience prior to the in-training exam did not affect the correlation. PMID:26594299

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity

PubMed Central

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; da Mota, Glória de Fátima Alves; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

Introduction: Previous studies have linked angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. Materials and methods: A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O2 consumption (VO2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two-way repeated-measures ANOVA were used. Results: In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N-domain activity is dependent on the DD genotype. Conclusions: AET differentially affects the ACE C- and N-domain activities, and the N-domain activity is dependent on ACE polymorphism. PMID:29629833

Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies.

PubMed

Skidgel, Randal A; Erdös, Ervin G

2004-03-01

Our investigations started when synthetic bradykinin became available and we could characterize two enzymes that cleaved it: kininase I or plasma carboxypeptidase N and kininase II, a peptidyl dipeptide hydrolase that we later found to be identical with the angiotensin I converting enzyme (ACE). When we noticed that ACE can cleave peptides without a free C-terminal carboxyl group (e.g., with a C-terminal nitrobenzylamine), we investigated inactivation of substance P, which has a C-terminal Met(11)-NH(2). The studies were extended to the hydrolysis of the neuropeptide, neurotensin and to compare hydrolysis of the same peptides by neprilysin (neutral endopeptidase 24.11, CD10, NEP). Our publication in 1984 dealt with ACE and NEP purified to homogeneity from human kidney. NEP cleaved substance P (SP) at Gln(6)-Phe(7), Phe(7)[see text]-Phe(8), and Gly(9)-Leu(10) and neurotensin (NT) at Pro(10)-Tyr(11) and Tyr(11)-Ile(12). Purified ACE also rapidly inactivated SP as measured in bioassay. HPLC analysis showed that ACE cleaved SP at Phe(8)-Gly(9) and Gly(9)-Leu(10) to release C-terminal tri- and dipeptide (ratio = 4:1). The hydrolysis was Cl(-) dependent and inhibited by captopril. ACE released only dipeptide from SP free acid. ACE hydrolyzed NT at Tyr(11)-Ile(12) to release Ile(12)-Leu(13). Then peptide substrates were used to inhibit ACE hydrolyzing Fa-Phe-Gly-Gly and NEP cleaving Leu(5)-enkephalin. The K(i) values in microM were as follows: for ACE, bradykinin = 0.4, angiotensin I = 4, SP = 25, SP free acid = 2, NT = 14, and Met(5)-enkephalin = 450, and for NEP, bradykinin = 162, angiotensin I = 36, SP = 190, NT = 39, Met(5)-enkephalin = 22. These studies showed that ACE and NEP, two enzymes widely distributed in the body, are involved in the metabolism of SP and NT. Below we briefly survey how NEP and ACE in two decades have gained the reputation as very important factors in health and disease. This is due to the discovery of more endogenous substrates of the enzymes and to the very broad and beneficial therapeutic applications of ACE inhibitors.

Aerobic exercise training differentially affects ACE C- and N-domain activities in humans: Interactions with ACE I/D polymorphism and association with vascular reactivity.

PubMed

Alves, Cléber Rene; Fernandes, Tiago; Lemos, José Ribeiro; Magalhães, Flávio de Castro; Trombetta, Ivani Credidio; Alves, Guilherme Barreto; Mota, Glória de Fátima Alves da; Dias, Rodrigo Gonçalves; Pereira, Alexandre Costa; Krieger, José Eduardo; Negrão, Carlos Eduardo; Oliveira, Edilamar Menezes

2018-01-01

Previous studies have linked angiotensin-converting enzyme ( ACE) insertion (I)/deletion (D) polymorphism (II, ID and DD) to physical performance. Moreover, ACE has two catalytic domains: NH2 (N) and COOH (C) with distinct functions, and their activity has been found to be modulated by ACE polymorphism. The aim of the present study is to investigate the effects of the interaction between aerobic exercise training (AET) and ACE I/D polymorphism on ACE N- and C-domain activities and vascular reactivity in humans. A total of 315 pre-selected healthy males were genotyped for II, ID and DD genotypes. Fifty completed the full AET (II, n = 12; ID, n = 25; and DD, n = 13), performed in three 90-minute sessions weekly, in the four-month exercise protocol. Pre- and post-training resting heart rate (HR), peak O 2 consumption (VO 2 peak), mean blood pressure (MBP), forearm vascular conduction (FVC), total circulating ACE and C- and N-domain activities were assessed. One-way ANOVA and two -way repeated-measures ANOVA were used. In pre-training, all variables were similar among the three genotypes. In post-training, a similar increase in FVC (35%) was observed in the three genotypes. AET increased VO 2 peak similarly in II, ID and DD (49±2 vs. 57±1; 48±1 vs. 56±3; and 48±5 vs. 58±2 ml/kg/min, respectively). Moreover, there were no changes in HR and MBP. The DD genotype was also associated with greater ACE and C-domain activities at pre- and post-training when compared to II. AET decreased similarly the total ACE and C-domain activities in all genotypes, while increasing the N-domain activity in the II and DD genotypes. However, interestingly, the measurements of N-domain activity after training indicate a greater activity than the other genotypes. These results suggest that the vasodilation in response to AET may be associated with the decrease in total ACE and C-domain activities, regardless of genotype, and that the increase in N-domain activity is dependent on the DD genotype. AET differentially affects the ACE C- and N-domain activities, and the N-domain activity is dependent on ACE polymorphism.

The effect of structural motifs on the ectodomain shedding of human angiotensin-converting enzyme.

PubMed

Conrad, Nailah; Schwager, Sylva L U; Carmona, Adriana K; Sturrock, Edward D

2016-12-02

Somatic angiotensin converting enzyme (sACE) is comprised of two homologous domains (N and C domains), whereas the smaller germinal isoform (tACE) is identical to the C domain. Both isozymes share an identical stalk, transmembrane and cytoplasmic domain, and undergo ectodomain shedding by an as yet unknown protease. Here we present evidence for the role of regions distal and proximal to the cleavage site in human ACE shedding. First, because of intrinsic differences between the N and C domains, discrete secondary structures (α-helix 7 and 8) on the surface of tACE were replaced with their N domain counterparts. Surprisingly, neither α-helix 7 nor α-helix 8 proved to be an absolute requirement for shedding. In the proximal ectodomain of tACE residues H 610 -L 614 were mutated to alanines and this resulted in a decrease in ACE shedding. An N-terminal extension of this mutation caused a reduction in cellular ACE activity. More importantly, it affected the processing of the protein to the membrane, resulting in expression of an underglycosylated form of ACE. When E 608 -H 614 was mutated to the homologous region of the N domain, processing was normal and shedding only moderately decreased suggesting that this region is more crucial for the processing of ACE than it is for regulating shedding. Finally, to determine whether glycosylation of the asparagine proximal to the Pro1199-Leu polymorphism in sACE affected shedding, the equivalent P 623 L mutation in tACE was investigated. The P 623 L tACE mutant showed an increase in shedding and MALDI MS analysis of a tryptic digest indicated that N 620 WT was glycosylated. The absence of an N-linked glycan at N 620 , resulted in an even greater increase in shedding. Thus, the conformational flexibility that the leucine confers to the stalk, is increased by the lack of glycosylation reducing access of the sheddase to the cleavage site. Copyright © 2016 Elsevier Inc. All rights reserved.

The Relationship of Adverse Childhood Events to Smoking, Overweight, Obesity and Binge Drinking Among Women in Hawaii.

PubMed

Remigio-Baker, Rosemay A; Hayes, Donald K; Reyes-Salvail, Florentina

2017-02-01

To evaluate how the associations of adverse childhood events (ACEs) with smoking, overweight, obesity and binge drinking differ by race/ethnicity among women, including a large, understudied cohort of Asians and Native Hawaiians/Pacific Islanders (NHOPIs). The number and type (household dysfunction, and physical, verbal and sexual abuse) of ACEs were examined in relation to adulthood smoking, overweight, obesity and binge drinking among 3354 women in Hawaii using the 2010 Behavioral Risk Factor Surveillance System data using Poisson regression with robust error variance. We additionally investigated for interaction by race/ethnicity. Covariates included age, race/ethnicity, education, emotional support, healthcare coverage, and the other health outcomes. Overall, 54.9 % reported at least 1 ACE. The prevalence of smoking (PR = 1.40 (1 ACE) to PR = 2.55 [5+ ACEs]), overweight (PR = 1.22 [1 ACE] to PR = 1.31 [5+ ACEs]) and obesity (PR = 1.00 [1 ACE] to PR = 1.85 [5+ ACEs]) increased with increasing ACE count. Smoking was associated with household dysfunction (PR = 1.67, CI = 1.26-2.22), and physical (PR = 2.04, CI = 1.50-2.78) and verbal (PR = 1.62, CI = 1.25-2.10) abuse. Obesity was also significantly related to household dysfunction (PR = 1.22, CI = 1.01-1.48), and physical (PR = 1.36, CI = 1.10-1.70), verbal (PR = 1.35, CI = 1.11-1.64) and sexual (PR = 1.53, CI = 1.25-1.88) abuse. Among Asians, sexual abuse was associated with a lower prevalence of binge drinking (PR = 0.26, CI = 0.07-0.93), which was significantly different from the null association among Whites (interaction p = 0.02). Preventing/addressing ACEs may help optimize childhood health, and reduce the likelihood of smoking/obesity among women including Asians/NHOPIs. Further studies are warranted to evaluate the sexual abuse-binge drinking association among Asians, which may support the need for culturally-tailored programs to address ACEs.

Beneficial role of D allele in controlling ACE levels: a study among Brahmins of north India.

PubMed

Kumari, Shobha; Sharma, Nidhi; Thakur, Sunil; Mondal, Prakash R; Saraswathy, Kallur N

2016-06-01

India being a country with vast diversity is expected to have different dietary and life style patterns which in turn may lead to population-specific environmental risk factors. Further, the interaction of these risk factors with the genetic makeup of population makes it either susceptible or resistant to cardiovascular disease. One such candidate gene is angiotensin converting enzyme (ACE) for various cardiovascular mechanisms. ACE is the key enzyme of the renin angiotensin aldosterone system pathway which maintains homeostasis blood pressure in the body and any variation in the levels is reported to be associated with various complex diseases. The DD genotype is found to increase ACE levels, which is associated with cardiovascular diseases and decrease in ACE levels are associated with kidney diseases. The aim of this study was to understand the distribution of ACE I/D polymorphism and ACE levels among Brahmins of National Capital Region (NCR) north India, with respect to age and sex ratio distribution. In this study, 136 subjects of which 50 males and 86 females, who were unrelated up to first cousin, aged 25 to70 years were studied. ACE gene was found to be polymorphic with high frequency of heterozygote (ID) followed by II and DD genotypes. The studied population was found to be in Hardy-Weinberg equilibrium with respect to ACE I/D polymorphism (P = 0.55). I allele frequency was found to be higher (0.560) than the D allele (0.44). The median level of ACE was found to be 65.96 ng/mL (48.12-86.24) which is towards lower side of the normal range. ACE levels were found to be increased among individual having either of the homozygotes that is II or DD and higher frequency of heterozygote (ID) is indicative of advantage in the population by maintaining lower ACE levels. The limitation of the present study is low sample size, however, the merit is that the subjects belonged to a Mendalian population with a common gene pool.

The Relationship of Adverse Childhood Events To Smoking, Overweight, Obesity and Binge Drinking Among Women In Hawaii

PubMed Central

Remigio-Baker, Rosemay A.; Hayes, Donald K.; Reyes-Salvail, Florentina

2016-01-01

OBJECTIVES To evaluate how the associations of adverse childhood events (ACEs) with smoking, overweight, obesity and binge drinking differ by race/ethnicity among women, including a large, understudied cohort of Asians and Native Hawaiians/Pacific Islanders (NHOPIs). METHODS The number and type (household dysfunction, and physical, verbal and sexual abuse) of ACEs were examined in relation to adulthood smoking, overweight, obesity and binge drinking among 3,354 women in Hawaii using the 2010 Behavioral Risk Factor Surveillance System data using Poisson regression. We additionally investigated for interaction by race/ethnicity. Covariates included age, race/ethnicity, education, emotional support, healthcare coverage, and the other health outcomes. RESULTS Overall, 54.9% reported at least 1 ACE. The prevalence of smoking (Prevalence Ratio [PR]=1.40 [1 ACE] to PR=2.55 [5+ ACEs]), overweight (PR=1.22 [1 ACE] to PR=1.31 [5+ ACEs]) and obesity (PR=1.00 [1 ACE] to PR=1.85 [5+ ACEs]) increased with increasing ACE count. Smoking was associated with household dysfunction (PR=1.67, CI=1.26–2.22), and physical (PR=2.04, CI=1.50–2.78) and verbal (PR=1.62, CI=1.25–2.10) abuse. Obesity was also significantly related to household dysfunction (PR=1.22, CI=1.01–1.48), and physical (PR=1.36, CI=1.10–1.70), verbal (PR=1.35, CI=1.11–1.64) and sexual (PR=1.53, CI=1.25–1.88) abuse. Among Asians, sexual abuse was associated with a lower prevalence of binge drinking (PR=0.26, CI=0.07, 0.93), which was significantly different from the null association among Whites (interaction p=0.02). CONCLUSION Preventing/addressing ACEs may help optimize childhood health, and reduce the likelihood of smoking/obesity among women including Asians/NHOPIs. Further studies are warranted to evaluate the sexual abuse-binge drinking association among Asians, which may support the need for culturally-tailored programs to address ACEs. PMID:27449778

Near-Real-Time Detection and Monitoring of Dust Events by Satellite (SeaWIFS, MODIS, and TOMS)

NASA Technical Reports Server (NTRS)

Hsu, N. Christina; Tsay, Si-Chee; Herman, Jay R.; Kaufman, Yoram

2002-01-01

Over the last few years satellites have given us increasingly detailed information on the size, location, and duration of dust events around the world. These data not only provide valuable feedback to the modelling community as to the fidelity of their aerosol models but are also finding increasing use in near real-time applications. In particular, the ability to locate and track the development of aerosol dust clouds on a near real-time basis is being used by scientists and government to provide warning of air pollution episodes over major urban area. This ability has also become a crucial component of recent coordinated campaigns to study the characteristics of tropospheric aerosols such as dust and their effect on climate. One such recent campaign was ACE-Asia, which was designed to obtain the comprehensive set of ground, aircraft, and satellite data necessary to provide a detailed understanding of atmospheric aerosol particles over the Asian-Pacific region. As part of ACE-Asia, we developed a near real-time data processing and access system to provide satellite data from the polar-orbiting instruments Earth Probe TOMS (in the form of absorbing aerosol index) and SeaWiFS (in the form of aerosol optical thickness, AOT, and Angstrom exponent). The results were available via web access. The location and movement information provided by these data were used both in support of the day-to-day flight planning of ACE-Asia and as input into aerosol transport models. While near real-time SeaWiFS data processing can be performed using either the normal global data product or data obtained via direct broadcast to receiving stations close to the area of interest, near real-time MODIS processing of data to provide aerosol retrievals is currently only available using its direct broadcast capability. In this paper, we will briefly discuss the algorithms used to generate these data. The retrieved aerosol optical thickness and Angstrom exponent from SeaWiFS will be compared with those obtained from various AERONET sites over the Asian-Pacific region. The TOMS aerosol index will also be compared with AERONET aerosol optical thickness over different aerosol conditions, and comparisons between the MODIS and SeaWiFS data will also be presented. Finally, we will discuss the climate implication of our studies using the combined satellite and AERONET observations.

Angiotensin-Converting Enzyme Inhibition as an Adjunct to Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease

PubMed Central

Curtis, Katrina J.; Meyrick, Victoria M.; Mehta, Bhavin; Haji, Gulam S.; Li, Kawah; Montgomery, Hugh; Man, William D.-C.; Polkey, Michael I.

2016-01-01

Rationale: Epidemiological studies in older individuals have found an association between the use of angiotensin-converting enzyme (ACE) inhibition (ACE-I) therapy and preserved locomotor muscle mass, strength, and walking speed. ACE-I therapy might therefore have a role in the context of pulmonary rehabilitation (PR). Objectives: To investigate the hypothesis that enalapril, an ACE inhibitor, would augment the improvement in exercise capacity seen during PR. Methods: We performed a double-blind, placebo-controlled, parallel-group randomized controlled trial. Patients with chronic obstructive pulmonary disease, who had at least moderate airflow obstruction and were taking part in PR, were randomized to either 10 weeks of therapy with an ACE inhibitor (10 mg enalapril) or placebo. Measurements and Main Results: The primary outcome measurement was the change in peak power (assessed using cycle ergometry) from baseline. Eighty patients were enrolled, 78 were randomized (age 67 ± 8 years; FEV1 48 ± 21% predicted), and 65 completed the trial (34 on placebo, 31 on the ACE inhibitor). The ACE inhibitor–treated group demonstrated a significant reduction in systolic blood pressure (Δ, −16 mm Hg; 95% confidence interval [CI], −22 to −11) and serum ACE activity (Δ, −18 IU/L; 95% CI, −23 to −12) versus placebo (between-group differences, P < 0.0001). Peak power increased significantly more in the placebo group (placebo Δ, +9 W; 95% CI, 5 to 13 vs. ACE-I Δ, +1 W; 95% CI, −2 to 4; between-group difference, 8 W; 95% CI, 3 to 13; P = 0.001). There was no significant between-group difference in quadriceps strength or health-related quality of life. Conclusions: Use of the ACE inhibitor enalapril, together with a program of PR, in patients without an established indication for ACE-I, reduced the peak work rate response to exercise training in patients with chronic obstructive pulmonary disease. PMID:27248440

Anoctamin 6 Contributes to Cl− Secretion in Accessory Cholera Enterotoxin (Ace)-stimulated Diarrhea

PubMed Central

Aoun, Joydeep; Hayashi, Mikio; Sheikh, Irshad Ali; Sarkar, Paramita; Saha, Tultul; Ghosh, Priyanka; Bhowmick, Rajsekhar; Ghosh, Dipanjan; Chatterjee, Tanaya; Chakrabarti, Pinak; Chakrabarti, Manoj K.; Hoque, Kazi Mirajul

2016-01-01

Accessory cholera enterotoxin (Ace) of Vibrio cholerae has been shown to contribute to diarrhea. However, the signaling mechanism and specific type of Cl− channel activated by Ace are still unknown. We have shown here that the recombinant Ace protein induced ICl of apical plasma membrane, which was inhibited by classical CaCC blockers. Surprisingly, an Ace-elicited rise of current was neither affected by ANO1 (TMEM16A)-specific inhibitor T16A(inh)-AO1(TAO1) nor by the cystic fibrosis transmembrane conductance regulator (CFTR) blocker, CFTR inh-172. Ace stimulated whole-cell current in Caco-2 cells. However, the apical ICl was attenuated by knockdown of ANO6 (TMEM16F). This impaired phenotype was restored by re-expression of ANO6 in Caco-2 cells. Whole-cell patch clamp recordings of ANO currents in HEK293 cells transiently expressing mouse ANO1-mCherry or ANO6-GFP confirmed that Ace induced Cl− secretion. Application of Ace produced ANO6 but not the ANO1 currents. Ace was not able to induce a [Ca2+]i rise in Caco-2 cells, but cellular abundance of phosphatidylinositol 4,5-bisphosphate (PIP2) increased. Identification of the PIP2-binding motif at the N-terminal sequence among human and mouse ANO6 variants along with binding of PIP2 directly to ANO6 in HEK293 cells indicate likely PIP2 regulation of ANO6. The biophysical and pharmacological properties of Ace stimulated Cl− current along with intestinal fluid accumulation, and binding of PIP2 to the proximal KR motif of channel proteins, whose mutagenesis correlates with altered binding of PIP2, is comparable with ANO6 stimulation. We conclude that ANO6 is predominantly expressed in intestinal epithelia, where it contributes secretory diarrhea by Ace stimulation in a calcium-independent mechanism of RhoA-ROCK-PIP2 signaling. PMID:27799301

DNA methylation and genetic variation of the angiotensin converting enzyme (ACE) in depression.

PubMed

Lam, Dilys; Ancelin, Marie-Laure; Ritchie, Karen; Saffery, Richard; Ryan, Joanne

2018-02-01

Depression is one of the most prevalent psychiatric disorders, and in older persons is associated with high levels of comorbidity and under-treatment. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) stress axis is consistently observed in the older population as well as depressed patients, with the angiotensin converting enzyme (ACE) a key regulator of the stress response. Epigenetic regulation of ACE may play an important role in HPA axis (dys)regulation. To investigate ACE promoter methylation as a biomarker of late-life depression, and its association with genetic variation and cortisol secretion. The longitudinal general population ESPRIT study is aimed at investigating psychiatric disorders in older persons (n=1863, average age=73). Depression was assessed using the Mini International Neuropsychiatric Interview according to DSM-IV criteria and the Centre for Epidemiologic Studies Depression Scale (CES-D). Genotype information for seven polymorphisms across the ACE gene was also available. Blood and saliva samples collected at baseline and used to extract DNA and measure cortisol, respectively. Sequenom MassARRAY was used to measure promoter DNA methylation of the ACE gene (n=552). There was no evidence of an association between ACE promoter methylation and depression. However, there was evidence that ACE genetic variants influenced methylation, and modified the association between depression and methylation (Δ at various sites; -2.05% to 1.74%; p=0.019 to 0.039). Multivariate analyses were adjusted for participants' lifestyle, health and medical history. Independent of depression status, ACE methylation was inversely correlated with cortisol levels (r=-0.336, p=0.042). This study provides evidence that associations between ACE methylation and depression are genotype-dependent, suggesting that the development of reliable depression biomarkers may need to consider methylation levels in combination with underlying genetic variation. ACE methylation may also be a suitable biomarker of cortisol and/or HPA axis activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adverse Childhood Experiences and ADHD Diagnosis at Age 9 Years in a National Urban Sample.

PubMed

Jimenez, Manuel E; Wade, Roy; Schwartz-Soicher, Ofira; Lin, Yong; Reichman, Nancy E

To examine associations between adverse childhood experiences (ACEs) and attention-deficit/hyperactivity disorder (ADHD) at age 9 years using longitudinal data and assess the extent to which ACEs during middle childhood are independently associated with ADHD at age 9 years. We conducted a secondary analysis of data from the Fragile Families urban birth cohort 5- and 9-year interviews. The sample was limited to children for whom mothers were the primary caregiver and mother-reported information on 8 ACEs and ADHD were available at age 5 and 9 years. We examined associations between ACEs and parent-reported ADHD at age 9 years using logistic regression and controlling for potential confounders. We included 1572 children; 48% were African American, 11% had parent-reported ADHD at age 9 years, 41% and 42% experienced ≥1 ACE by age 5 years and between the ages of 5 and 9 years, respectively. ACEs before age 5 years were associated with ADHD at age 9 years. One, 2, and ≥3 ACEs between age 5 and 9 years were associated with ADHD at age 9 years even after controlling for ACEs before age 5 years and ADHD at age 5 years (adjusted odds ratio [AOR], 1.9; 95% confidence interval [CI], 1.2-3; AOR, 2.1; 95% CI, 1.2-3.8; and AOR, 2.2; 95% CI, 1.1-4.3). In this study of urban children, ACEs occurring before age 5 years as well as between the ages of 5 and 9 years were associated with ADHD at age 9 years. Even after controlling for early childhood ACEs and ADHD at age 5 years, the association between ADHD and ACEs in middle childhood remained significant, highlighting the importance of screening and intervention throughout childhood. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling.

PubMed

Walters, Tomos E; Kalman, Jonathan M; Patel, Sheila K; Mearns, Megan; Velkoska, Elena; Burrell, Louise M

2017-08-01

Angiotensin converting enzyme 2 (ACE2) is an integral membrane protein whose main action is to degrade angiotensin II. Plasma ACE2 activity is increased in various cardiovascular diseases. We aimed to determine the relationship between plasma ACE2 activity and human atrial fibrillation (AF), and in particular its relationship to left atrial (LA) structural remodelling. One hundred and three participants from a tertiary arrhythmia centre, including 58 with paroxysmal AF (PAF), 20 with persistent AF (PersAF), and 25 controls, underwent clinical evaluation, echocardiographic analysis, and measurement of plasma ACE2 activity. A subgroup of 20 participants underwent invasive LA electroanatomic mapping. Plasma ACE2 activity levels were increased in AF [control 13.3 (9.5-22.3) pmol/min/mL; PAF 16.9 (9.7-27.3) pmol/min/mL; PersAF 22.8 (13.7-33.4) pmol/min/mL, P = 0.006]. Elevated plasma ACE2 was associated with older age, male gender, hypertension and vascular disease, elevated left ventricular (LV) mass, impaired LV diastolic function and advanced atrial disease (P < 0.05 for all). Independent predictors of elevated plasma ACE2 activity were AF (P = 0.04) and vascular disease (P < 0.01). There was a significant relationship between elevated ACE2 activity and low mean LA bipolar voltage (adjusted R2 = 0.22, P = 0.03), a high proportion of complex fractionated electrograms (R2 = 0.32, P = 0.009) and a long LA activation time (R2 = 0.20, P = 0.04). Plasma ACE2 activity is elevated in human AF. Both AF and vascular disease predict elevated plasma ACE2 activity, and elevated plasma ACE2 is significantly associated with more advanced LA structural remodelling. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study.

PubMed

Shafaei, Armaghan; Sultan Khan, Md Shamsuddin; F A Aisha, Abdalrahim; Abdul Majid, Amin Malik Shah; Hamdan, Mohammad Razak; Mordi, Mohd Nizam; Ismail, Zhari

2016-11-09

This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure-activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX : BioSolveIT's LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC 50 value (45.77 ± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC 50 15.35 ± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.

Somatic isoform of angiotensin I-converting enzyme in the pathology of testicular germ cell tumors.

PubMed

Franke, F E; Pauls, K; Kerkman, L; Steger, K; Klonisch, T; Metzger, R; Alhenc-Gelas, F; Burkhardt, E; Bergmann, M; Danilov, S M

2000-12-01

Retained fetal expression of angiotensin I-converting enzyme (ACE, CD143) has recently been shown in intratubular germ cell neoplasms (IGCN) and invasive germ cell tumors (GCT), suggesting the somatic isoform (sACE) as a characteristic component of neoplastic germ cells. We analyzed the distribution of sACE in 159 testicular GCT, including 87 IGCN. sACE protein was determined by immunohistochemistry (MAb CG2) on routinely formalin-fixed and paraffin-embedded tissue sections, supplemented by mRNA expression analysis using in situ hybridization. These data were compared with those obtained by germ cell/placental alkaline phosphatases (PIAP; MAbs PL8-F6 and 8A9) employing an uniform score system for the evaluation of immunoreactivity (IRS; possible values from 0 to 12). Expression of sACE and PIAP was found in all 87 analyzed IGCN (IRS > 4, median IRS of 12). Heterogeneous staining patterns were not related to the type of adjacent GCT but correlated with low expression in adjacent seminomas (P =.032 for sACE; P =.005 for PIAP). Both sACE and PIAP often showed a decreased and more heterogeneous but still moderate expression in 91 classic seminomas (median IRS of 8) and were completely absent in tumor cells of spermatocytic seminomas. Despite all similarities, we found sACE and PIAP differently regulated during GCT progression. This was documented by a well-preserved expression of either sACE or PIAP or both in all classic seminomas, low PIAP immunoreactivity in metastasis of seminomas, and completely diverging expression patterns in nonseminomatous GCT. Our findings underline the close molecular relationship between IGCN and seminoma, and suggest sACE as an appropriate marker for seminomatous differentiated tumors. HUM PATHOL 31:1466-1476. Copyright 2000 by W.B. Saunders Company

On Becoming Trauma-Informed: Role of the Adverse Childhood Experiences Survey in Tertiary Child and Adolescent Mental Health Services and the Association with Standard Measures of Impairment and Severity

PubMed Central

Rahman, Abdul; Perri, Andrea; Deegan, Avril; Kuntz, Jennifer; Cawthorpe, David

2018-01-01

Context There is a movement toward trauma-informed, trauma-focused psychiatric treatment. Objective To examine Adverse Childhood Experiences (ACE) survey items by sex and by total scores by sex vs clinical measures of impairment to examine the clinical utility of the ACE survey as an index of trauma in a child and adolescent mental health care setting. Design Descriptive, polychoric factor analysis and regression analyses were employed to analyze cross-sectional ACE surveys (N = 2833) and registration-linked data using past admissions (N = 10,400) collected from November 2016 to March 2017 related to clinical data (28 independent variables), taking into account multicollinearity. Results Distinct ACE items emerged for males, females, and those with self-identified sex and for ACE total scores in regression analysis. In hierarchical regression analysis, the final models consisting of standard clinical measures and demographic and system variables (eg, repeated admissions) were associated with substantial ACE total score variance for females (44%) and males (38%). Inadequate sample size foreclosed on developing a reduced multivariable model for the self-identified sex group. Conclusion The ACE scores relate to independent clinical measures and system and demographic variables. There are implications for clinical practice. For example, a child presenting with anxiety and a high ACE score likely requires treatment that is different from a child presenting with anxiety and an ACE score of zero. The ACE survey score is an important index of presenting clinical status that guides patient care planning and intervention in the progress toward a trauma-focused system of care. PMID:29401055

Angiotensin-converting enzyme 2 is subject to post-transcriptional regulation by miR-421.

PubMed

Lambert, Daniel W; Lambert, Louise A; Clarke, Nicola E; Hooper, Nigel M; Porter, Karen E; Turner, Anthony J

2014-08-01

ACE2 (angiotensin converting enzyme 2) plays a critical role in the local tissue RAS (renin-angiotensin system) by hydrolysing the potent hypertensive and mitogenic peptide AngII (angiotensin II). Changes in the levels of ACE2 have been observed in a number of pathologies, including cardiovascular disease, but little is known of the mechanisms regulating its expression. In the present study, therefore, the potential role of miRNAs in the regulation of ACE2 expression in primary human cardiac myofibroblasts was examined. Putative miRNA-binding sites were identified in the 3'-UTR of the ACE2 transcript using online prediction algorithms. Two of these, miR-200b and miR-421, were selected for further analysis. A reporter system using the 3'-UTR of ACE2 fused to the coding region of firefly luciferase was used to determine the functionality of the identified binding sites in vitro. This identified miR-421, but not miR-200b, as a potential regulator of ACE2. The ability of miR-421, an miRNA implicated in the development of thrombosis, to down-regulate ACE2 expression was subsequently confirmed by Western blot analysis of both primary cardiac myofibroblasts and transformed cells transfected with a synthetic miR-421 precursor. Real-time PCR analysis of miR-421 revealed widespread expression in human tissues. miR-421 levels in cardiac myofibroblasts showed significant inter-patient variability, in keeping with the variability of ACE2 expression we have observed previously. In conclusion, the present study is the first to demonstrate that ACE2 may be subject to post-transcriptional regulation and reveals a novel potential therapeutic target, miR-421, which could be exploited to modulate ACE2 expression in disease.

Disability and Exposure to High Levels of Adverse Childhood Experiences: Effect on Health and Risk Behavior.

PubMed

Austin, Anna; Herrick, Harry; Proescholdbell, Scott; Simmons, Jacqueline

2016-01-01

Health disparities among persons with disabilities have been previously documented. However, there is little research specific to adverse childhood experiences (ACEs) in this population and how ACE exposure affects health outcomes in adulthood. Data from the 2012 North Carolina Behavioral Risk Factor Surveillance System (BRFSS) survey were analyzed to compare the prevalence of ACEs between adults with and without disabilities and high ACE exposure (3-8 ACEs). Adjusted risk ratios of health risks and perceived poor health by disability status were calculated using predicted marginals. A higher percentage of persons with disabilities (36.5%) than those without disabilities (19.6%) reported high ACE exposure. Among those with high ACE exposure, persons with disabilities were more likely to report several ACE categories, particularly childhood sexual abuse. In adjusted analyses, persons with disabilities had an increased risk of smoking (relative risk [RR] = 1.29; 95% CI, 1.10-1.51), poor physical health (RR = 4.34; 95% CI, 3.08-6.11), poor mental health (RR = 4.69; 95% CI, 3.19-6.87), and doctor-diagnosed depression (RR = 2.16; 95% CI, 1.82-2.56) compared to persons without disabilities. The definition of disability derived from the BRFSS survey does not allow for those with disabilities to be categorized according to physical disabilities versus mental or emotional disabilities. In addition, we were unable to determine the timing of ACE exposure in relation to disability onset. A better understanding of the life course associations between ACEs and disability and the impact of exposure to multiple types of childhood adversity on disability and health is needed to inform research and services specific to this vulnerable population. ©2016 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

Correlation of the NBME advanced clinical examination in EM and the national EM M4 exams.

PubMed

Hiller, Katherine; Miller, Emily S; Lawson, Luan; Wald, David; Beeson, Michael; Heitz, Corey; Morrissey, Thomas; House, Joseph; Poznanski, Stacey

2015-01-01

Since 2011 two online, validated exams for fourth-year emergency medicine (EM) students have been available (National EM M4 Exams). In 2013 the National Board of Medical Examiners offered the Advanced Clinical Examination in Emergency Medicine (EM-ACE). All of these exams are now in widespread use; however, there are no data on how they correlate. This study evaluated the correlation between the EM-ACE exam and the National EM M4 Exams. From May 2013 to April 2014 the EM-ACE and one version of the EM M4 exam were administered sequentially to fourth-year EM students at five U.S. medical schools. Data collected included institution, gross and scaled scores and version of the EM M4 exam. We performed Pearson's correlation and random effects linear regression. 305 students took the EM-ACE and versions 1 (V1) or 2 (V2) of the EM M4 exams (281 and 24, respectively) [corrected].The mean percent correct for the exams were as follows: EM-ACE 74.9 (SD-9.82), V1 83.0 (SD-6.39), V2 78.5 (SD-7.70) [corrected]. Pearson's correlation coefficient for the V1/EM-ACE was 0.53 (0.43 scaled) and for the V2/EM-ACE was 0.58 (0.41 scaled) [corrected]. The coefficient of determination for V1/ EM-ACE was 0.73 and for V2/EM-ACE 0.71 (0.65 and .49 for scaled scores) [ERRATUM]. The R-squared values were 0.28 and 0.30 (0.18 and 0.13 scaled), respectively [corrected]. There was significant cluster effect by institution. There was moderate positive correlation of student scores on the EM-ACE exam and the National EM M4 Exams.

Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular System.

PubMed

Wang, Wang; McKinnie, Shaun M K; Farhan, Maikel; Paul, Manish; McDonald, Tyler; McLean, Brent; Llorens-Cortes, Catherine; Hazra, Saugata; Murray, Allan G; Vederas, John C; Oudit, Gavin Y

2016-08-01

Apelin peptides mediate beneficial effects on the cardiovascular system and are being targeted as potential new drugs. However, apelin peptides have extremely short biological half-lives, and improved understanding of apelin peptide metabolism may lead to the discovery of biologically stable analogues with therapeutic potential. We examined the ability of angiotensin-converting enzyme 2 (ACE2) to cleave and inactivate pyr-apelin 13 and apelin 17, the dominant apelin peptides. Computer-assisted modeling shows a conserved binding of pyr-apelin 13 and apelin 17 to the ACE2 catalytic site. In ACE2 knockout mice, hypotensive action of pyr-apelin 13 and apelin 17 was potentiated, with a corresponding greater elevation in plasma apelin levels. Similarly, pharmacological inhibition of ACE2 potentiated the vasodepressor action of apelin peptides. Biochemical analysis confirmed that recombinant human ACE2 can cleave pyr-apelin 13 and apelin 17 efficiently, and apelin peptides are degraded slower in ACE2-deficient plasma. The biological relevance of ACE2-mediated proteolytic processing of apelin peptides was further supported by the reduced potency of pyr-apelin 12 and apelin 16 on the activation of signaling pathways and nitric oxide production from endothelial cells. Importantly, although pyr-apelin 13 and apelin 17 rescued contractile function in a myocardial ischemia-reperfusion model, ACE2 cleavage products, pyr-apelin 12 and 16, were devoid of these cardioprotective effects. We designed and synthesized active apelin analogues that were resistant to ACE2-mediated degradation, thereby confirming that stable apelin analogues can be designed as potential drugs. We conclude that ACE2 represents a major negative regulator of apelin action in the vasculature and heart. © 2016 American Heart Association, Inc.

Ventilation-induced increases in EGFR ligand mRNA are not altered by intra-amniotic LPS or ureaplasma in preterm lambs.

PubMed

Hillman, Noah H; Gisslen, Tate; Polglase, Graeme R; Kallapur, Suhas G; Jobe, Alan H

2014-01-01

Chorioamnionitis and mechanical ventilation are associated with bronchopulmonary dysplasia (BPD) in preterm infants. Mechanical ventilation at birth activates both inflammatory and acute phase responses. These responses can be partially modulated by previous exposure to intra-amniotic (IA) LPS or Ureaplasma parvum (UP). Epidermal growth factor receptor (EGFR) ligands participate in lung development, and angiotensin converting enzyme (ACE) 1 and ACE2 contribute to lung inflammation. We asked whether brief mechanical ventilation at birth altered EGFR and ACE pathways and if antenatal exposure to IA LPS or UP could modulate these effects. Ewes were exposed to IA injections of UP, LPS or saline multiple days prior to preterm delivery at 85% gestation. Lambs were either immediately euthanized or mechanically ventilated for 2 to 3 hr. IA UP and LPS cause modest changes in the EGFR ligands amphiregulin (AREG), epiregulin (EREG), heparin binding epidermal growth factor (HB-EGF), and betacellulin (BTC) mRNA expression. Mechanical ventilation greatly increased mRNA expression of AREG, EREG, and HB-EGF, with no additional increases resulting from IA LPS or UP. With ventilation AREG and EREG mRNA localized to cells in terminal airspace. EGFR mRNA also increased with mechanical ventilation. IA UP and LPS decreased ACE1 mRNA and increased ACE2 mRNA, resulting in a 4 fold change in the ACE1/ACE2 ratio. Mechanical ventilation with large tidal volumes increased both ACE1 and ACE2 expression. The alterations seen in ACE with IA exposures and EGFR pathways with mechanical ventilation may contribute to the development of BPD in preterm infants.

ACE2-Independent Action Of Presumed ACE2 Activators: Studies In Vivo, Ex Vivo and In Vitro

PubMed Central

Haber, Philipp K.; Ye, Minghao; Wysocki, Jan; Maier, Christoph; Haque, Syed K.; Batlle, Daniel

2014-01-01

Angiotensin converting enzyme 2, (ACE2), is a key enzyme in the metabolism of angiotensin II. 1-[[2-(dimetilamino)ethyl]amino]-4-(hidroximetil)-7-[[(4-metilfenil)sulfonil]oxi]-9H-xantona-9 (XNT)and Diminazene (DIZE)have been reported to exert various organ-protective effects that have been attributed to activation of ACE2. To test the effect of these compounds we studied Ang II degradation in vivo and in vitro as well as their effect on ACE2 activity in vivo and in vitro. In a model of Ang II induced acute hypertension, blood pressure recovery was markedly enhanced by XNT (slope with XNT -3.26±0.2 vs.-1.6±0.2 mmHg/min without XNT, p<0.01). After Ang II infusion, neither plasma nor kidney ACE2 activity was affected by XNT. Plasma Ang II and Ang (1-7) levels also were not significantly affected by XNT. The blood pressure lowering effect of XNT seen in WT animals was also observed in ACE2 KO mice (slope with XNT -3.09±0.30 mmHg/min vs. -1.28±0.22 mmHg/min without XNT, p<0.001). These findings show that the blood pressure lowering effect of XNT in Ang II induced hypertension cannot be due to activation of ACE2. In vitro and ex vivo experiments in both mice and rat kidney confirmed a lack of enhancement of ACE2 enzymatic activity by XNT and DIZE. Moreover, Ang II degradation in vitro and ex vivo was unaffected by XNT and DIZE. We conclude that the biologic effects of these compounds are ACE2 independent and should not be attributed to activation of this enzyme. PMID:24446061

Brain ACE2 overexpression reduces DOCA-salt hypertension independently of endoplasmic reticulum stress

PubMed Central

de Queiroz, Thyago Moreira; Sriramula, Srinivas; Feng, Yumei; Johnson, Tanya; Mungrue, Imran N.; Lazartigues, Eric

2014-01-01

Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension. SL and nontransgenic (NT) mice underwent DOCA-salt or sham treatment while infected with an adenoassociated virus (AAV) encoding Cre recombinase (AAV-Cre) or a control virus (AAV-green fluorescent protein) to the SFO or PVN. DOCA-salt-induced hypertension was reduced in SL mice, with hACE2 overexpression in the brain. This reduction was only partially blunted by knockdown of hACE2 in the SFO or PVN, suggesting that both regions are involved but not essential for ACE2 regulation of blood pressure (BP). DOCA-salt treatment did not increase the protein levels of ER stress and autophagy markers in NT mice, despite a significant increase in BP. In addition, these markers were not affected by hACE2 overexpression in the brain, despite a significant reduction of hypertension in SL mice. To further assess the role of ER stress in neurogenic hypertension, NT mice were infused intracerebroventricularlly with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, during DOCA-salt treatment. However, TUDCA infusion failed to blunt the development of hypertension in NT mice. Our data suggest that brain ER stress does not contribute to DOCA-salt hypertension and that ACE2 blunts neurogenic hypertension independently of ER stress. PMID:25519733

Enhancement of bradykinin and resensitization of its B2 receptor.

PubMed

Marcic, B; Deddish, P A; Jackman, H L; Erdös, E G

1999-03-01

We studied the enhancement of the effects of bradykinin B2 receptor agonists by agents that react with active centers of angiotensin-converting enzyme (ACE) independent of enzymatic inactivation. The potentiation and the desensitization and resensitization of B2 receptor were assessed by measuring [3H]arachidonic acid release and [Ca2+]i mobilization in Chinese hamster ovary cells transfected to express human ACE and B2 receptor, or in endothelial cells with constitutively expressed ACE and receptor. Administration of bradykinin or its ACE-resistant analogue desensitized the receptor, but it was resensitized (arachidonic acid release or [Ca2+]i mobilization) by agents such as enalaprilat (1 micromol/L). Enalaprilat was inactive in the absence of ACE expression. La3+ (100 micromol/L) inhibited the apparent resensitization, probably by blocking the entry of extracellular calcium. Enalaprilat resensitized the receptor via ACE to release arachidonic acid by bradykinin at a lower concentration (5 nmol/L) than required to mobilize [Ca2+]i (1 micromol/L). Monoclonal antibodies inhibiting the ACE N-domain active center and polyclonal antiserum potentiated bradykinin. The snake venom peptide BPP5a and metabolites of angiotensin and bradykinin (angiotensin-[1-9], angiotensin-[1-7], bradykinin-[1-8]; 1 micromol/L) enhanced arachidonic acid release by bradykinin. Angiotensin-(1-9) and -(1-7) also resensitized the receptor. Enalaprilat potentiated the bradykinin effect in cells expressing a mutant ACE with a single N-domain active site. Agents that reacted with a single active site, on the N-domain or on the C-domain, potentiated bradykinin not by blocking its inactivation but by inducing crosstalk between ACE and the receptor. Enalaprilat enhanced signaling via ACE by Galphai in lower concentration than by Galphaq-coupled receptor.

Optimized angiotensin-converting enzyme activity assay for the accurate diagnosis of sarcoidosis.

PubMed

Csongrádi, Alexandra; Enyedi, Attila; Takács, István; Végh, Tamás; Mányiné, Ivetta S; Pólik, Zsófia; Altorjay, István Tibor; Balla, József; Balla, György; Édes, István; Kappelmayer, János; Tóth, Attila; Papp, Zoltán; Fagyas, Miklós

2018-06-27

Serum angiotensin-converting enzyme (ACE) activity determination can aid the early diagnosis of sarcoidosis. We aimed to optimize a fluorescent kinetic assay for ACE activity by screening the confounding effects of endogenous ACE inhibitors and interfering factors. Genotype-dependent and genotype-independent reference values of ACE activity were established, and their diagnostic accuracies were validated in a clinical study. Internally quenched fluorescent substrate, Abz-FRK(Dnp)P-OH was used for ACE-activity measurements. A total of 201 healthy individuals and 59 presumably sarcoidotic patients were enrolled into this study. ACE activity and insertion/deletion (I/D) genotype of the ACE gene were determined. Here we report that serum samples should be diluted at least 35-fold to eliminate the endogenous inhibitor effect of albumin. No significant interferences were detected: up to a triglyceride concentration of 16 mM, a hemoglobin concentration of 0.71 g/L and a bilirubin concentration of 150 μM. Genotype-dependent reference intervals were considered as 3.76-11.25 U/L, 5.22-11.59 U/L, 7.19-14.84 U/L for II, ID and DD genotypes, respectively. I/D genotype-independent reference interval was established as 4.85-13.79 U/L. An ACE activity value was considered positive for sarcoidosis when it exceeded the upper limit of the reference interval. The optimized assay with genotype-dependent reference ranges resulted in 42.5% sensitivity, 100% specificity, 100% positive predictive value and 32.4% negative predictive value in the clinical study, whereas the genotype-independent reference range proved to have inferior diagnostic efficiency. An optimized fluorescent kinetic assay of serum ACE activity combined with ACE I/D genotype determination is an alternative to invasive biopsy for confirming the diagnosis of sarcoidosis in a significant percentage of patients.

Identification of prolyl carboxypeptidase as an alternative enzyme for processing of renal angiotensin II using mass spectrometry

PubMed Central

Grobe, Nadja; Weir, Nathan M.; Leiva, Orly; Ong, Frank S.; Bernstein, Kenneth E.; Schmaier, Alvin H.; Morris, Mariana

2013-01-01

Angiotensin-converting enzyme 2 (ACE2) catalyzes conversion of ANG II to ANG-(1–7). The present study uses newly established proteomic approaches and genetic mouse models to examine the contribution of alternative renal peptidases to ACE2-independent formation of ANG-(1–7). In situ and in vitro mass spectrometric characterization showed that substrate concentration and pH control renal ANG II processing. At pH ≥6, ANG-(1–7) formation was significantly reduced in ACE2 knockout (KO) mice. However, at pH <6, formation of ANG-(1–7) in ACE2 KO mice was similar to that in wild-type (WT) mice, suggesting alternative peptidases for renal ANG II processing. Furthermore, the dual prolyl carboxypeptidase (PCP)-prolyl endopeptidase (PEP) inhibitor Z-prolyl-prolinal reduced ANG-(1–7) formation in ACE2 KO mice, while the ACE2 inhibitor MLN-4760 had no effect. Unlike the ACE2 KO mice, ANG-(1–7) formation from ANG II in PEP KO mice was not different from that in WT mice at any tested pH. However, at pH 5, this reaction was significantly reduced in kidneys and urine of PCP-depleted mice. In conclusion, results suggest that ACE2 metabolizes ANG II in the kidney at neutral and basic pH, while PCP catalyzes the same reaction at acidic pH. This is the first report demonstrating that renal ANG-(1–7) formation from ANG II is independent of ACE2. Elucidation of ACE2-independent ANG-(1–7) production pathways may have clinically important implications in patients with metabolic and renal disease. PMID:23392115

Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells

PubMed Central

Grobe, Nadja; Di Fulvio, Mauricio; Kashkari, Nada; Chodavarapu, Harshita; Somineni, Hari K.; Singh, Richa

2015-01-01

The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal functions. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to 1) demonstrate the presence of an endogenous and functional RAS in COS7, and 2) investigate the role of a disintegrin and metalloproteinase-17 (ADAM17) in the ectodomain shedding of angiotensin converting enzyme-2 (ACE2). Reverse transcription coupled to gene-specific polymerase chain reaction demonstrated expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and renin at the transcript levels in total RNA cell extracts. Western blot and immunohistochemistry identified ACE (60 kDa), ACE2 (75 kDa), AT1R (43 kDa), renin (41 kDa), and ADAM17 (130 kDa) in COS7. At the functional level, a sensitive and selective mass spectrometric approach detected endogenous renin, ACE, and ACE2 activities. ANG-(1–7) formation (m/z 899) from the natural substrate ANG II (m/z 1,046) was detected in lysates and media. COS7 cells stably expressing shRNA constructs directed against endogenous ADAM17 showed reduced ACE2 shedding into the media. This is the first study demonstrating endogenous expression of the RAS and ADAM17 in the widely used COS7 cell line and its utility to study ectodomain shedding of ACE2 mediated by ADAM17 in vitro. The transfectable nature of this cell line makes it an attractive cell model for studying the molecular, functional, and pharmacological properties of the renal RAS. PMID:25740155

Teacher perspectives and the psychosocial climate of the classroom in a traditional BSN program.

PubMed

Rowbotham, Melodie A

2010-01-01

Developing and implementing a positive psychosocial environment should be one of the main responsibilities of educators. As educators influence the climate, learning is enhanced or hindered. Therefore educators need to understand their own teaching perspectives and how they in turn influence the classroom. Data were collected from nurse educators and BSN nursing students. The relationship between faculty teaching perspectives and the students' perceptions of the learning environment was examined. The data collection tool used to measure the educators' perspective was the Instructional Perspective Inventory (IPI), and to measure the students' perspective was the Adult Classroom Environment Scale (ACES). A MANCOVA was used to determine the relationship and significant differences between educators' and students' perspectives. The results indicated that the teachers in the high group of teacher responsiveness had students who reported greater teacher support, time on task, focus, organization, clarity of subject content, involvement, and satisfaction.

Aerosol Sources, Absorption, and Intercontinental Transport: Synergies among Models, Remote Sensing, and Atmospheric Measurements

NASA Technical Reports Server (NTRS)

Chin, Mian; Ginoux, Paul; Dubovik, Oleg; Holben, Brent; Kaufman, Yoram; chu, Allen; Anderson, Tad; Quinn, Patricia

2003-01-01

Aerosol climate forcing is one of the largest uncertainties in assessing the anthropogenic impact on the global climate system. This uncertainty arises from the poorly quantified aerosol sources, especially black carbon emissions, our limited knowledge of aerosol mixing state and optical properties, and the consequences of intercontinental transport of aerosols and their precursors. Here we use a global model GOCART to simulate atmospheric aerosols, including sulfate, black carbon, organic carbon, dust, and sea salt, from anthropogenic, biomass burning, and natural sources. We compare the model calculated aerosol extinction and absorption with those quantities from the ground-based sun photometer measurements from AERONET at several different wavelengths and the field observations from ACE-Asia, and model calculated total aerosol optical depth and fine mode fractions with the MODIS satellite retrieval. We will also estimate the intercontinental transport of pollution and dust aerosols from their source regions to other areas in different seasons.

Aerosol Sources, Absorption, and Intercontinental Transport: Synergies Among Models, Remote Sensing, and Atmospheric Measurements

NASA Technical Reports Server (NTRS)

Chin, Mian; Chu, Allen; Levy, Robert; Remer, Lorraine; Kaufman, Yoram; Dubovik, Oleg; Holben, Brent; Eck, Tom; Anderson, Tad; Quinn, Patricia

2004-01-01

Aerosol climate forcing is one of the largest uncertainties in assessing the anthropogenic impact on the global climate system. This uncertainty arises from the poorly quantified aerosol sources, especially black carbon emissions, our limited knowledge of aerosol mixing state and optical properties, and the consequences of intercontinental transport of aerosols and their precursors. Here we use a global model GOCART to simulate atmospheric aerosols, including sulfate, black carbon, organic carbon, dust, and sea salt, from anthropogenic, .biomass burning, and natural sources. We compare the model calculated aerosol extinction and absorption with those quantities from the ground-based sun photometer measurements from AERON" at several different wavelengths and the field observations from ACE-Asia, and model calculated total aerosol optical depth and fine mode fractions with the MODIS satellite retrieval. We will also estimate the intercontinental transport of pollution and dust aerosols from their source regions to other areas in different seasons.