Retraumatization Mediates the Effect of Adverse Childhood Experiences on Clinical Training-Related Secondary Traumatic Stress Symptoms.

PubMed

Butler, Lisa D; Maguin, Eugene; Carello, Janice

2018-01-01

Previous research (Butler, Carello, & Maguin, 2016) has found that exposure to trauma-related material in graduate clinical coursework and field training can put students at risk for reactivations of feelings/memories from negative past experiences (retraumatization) and for secondary traumatic stress (STS) symptoms. The present report sought to examine the role, if any, of adverse childhood experiences (ACEs) in these outcomes. Using the Butler et al. (2016) sample, we examined: (1) rates of ACEs in 195 graduate social work students, (2) whether the total number of ACEs was associated with training-related retraumatization (TRT) and/or STS symptoms, and (3) if TRT mediated the relationship between ACEs and STS symptoms. The results indicate that more than three quarters of the sample had experienced one or more ACEs before age 18 and almost one third endorsed 4 or more. The most commonly reported ACEs were household mental illness, parental separation/divorce, household alcohol/substance abuse, and emotional abuse or neglect by a parent or household member. Higher ACE scores were associated with increased likelihood of TRT experiences and STS symptoms during training. A mediation analysis confirmed that TRT mediated the effect of ACE scores on STS symptoms; this finding also provides support for the role of proximal emotional reactions in mediating the effects of distal adverse experiences on the development of trauma symptoms. In summary, despite the evident resilience of this graduate student sample, those with ACE histories were at heightened risk for training-related distress. These results underscore the need for a trauma-informed approach to clinical training.

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

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.

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.

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.

Airborne Sunphotometer, Airborne in-situ, Space-borne, and Ground-Based Measurements of Troposoheric Aerosol in Ace-2

NASA Technical Reports Server (NTRS)

Schmid, Beat; Collins, D.; Gasso, S.; Ostrom, E.; Powell, D.; Welton, E.; Durkee, P.; Livingstron, J.; Russell, P.; Flagan, R.;

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.

Advanced Collaborative Emissions Study (ACES)

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

Greenbaum, Daniel; Costantini, Maria; Van Erp, Annemoon

2013-12-31

The objective of the Advanced Collaborative Emissions Study (ACES) was to determine before widespread commercial deployment whether or not the new, energy-efficient, heavy duty diesel engines (2007 and 2010 EPA Emissions Standards Compliant) may generate anticipated toxic emissions that could adversely affect the environment and human health. ACES was planned to take place in three phases. In Phase 1, extensive emissions characterization of four production-intent prototype engine and control systems designed to meet 2007 standards for nitrogen oxides (NOx) and particulate matter (PM) was conducted at an existing emissions characterization facility: Southwest Research Institute (SwRI). One of the tested enginesmore » was selected (at random, after careful comparison of results) for health testing in Phase 3. In Phase 2, extensive emission characterization of three production-intent prototype engine and control systems meeting the 2010 standards (including more advanced NOx controls to meet the more stringent 2010 NOx standards) was conducted at the same test facility. In Phase 3, one engine/aftertreatment system selected from Phase 1 was further characterized during health effects studies (at an existing inhalation toxicology laboratory: Lovelace Respiratory Research Institute, [LRRI]) to form the basis of the ACES safety assessment. The Department of Energy (DOE) award provided funding for emissions characterization in Phases 1 and 2 as well as exposure characterization in Phase 3. The main health analyses in Phase 3 were funded separately and are not reported here.« less

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.

Transport of Aerosols from Asia and Their Radiative Effects Over the Western Pacific: A 3-D Model Study for ACE-Asia Experiment During Spring 2001

NASA Technical Reports Server (NTRS)

Chin, Mian; Ginoux, Paul; Flatau, Piotr; Anderson, Tad; Masonis, Sarah; Russell, Phil; Schmid, Beat; Livingston, John; Redemann, Jens; Kahn, Ralph;

Adverse childhood experiences and risk of type 2 diabetes: A systematic review and meta-analysis.

PubMed

Huang, Hao; Yan, Peipei; Shan, Zhilei; Chen, Sijing; Li, Moying; Luo, Cheng; Gao, Hui; Hao, Liping; Liu, Liegang

2015-11-01

It is evident that adverse childhood experiences (ACEs) can influence health status of adult life, but few large-scale studies have assessed the relation of ACEs with type 2 diabetes. This meta-analysis aimed to summarize existing evidence on the link between ACEs and type 2 diabetes in adults. We searched all published studies from PubMed and EMBASE before Aug 2015 using keywords like adverse childhood experiences and diabetes, and scanned references of relevant original articles. We included studies that reported risk estimates for diabetes by ACEs and matched our inclusion criteria. We examined the overall relationship between ACEs and diabetes, and stratified the analyses by type of childhood adversities, study design and outcome measures, respectively. Seven articles fulfilled the inclusion criteria for this Meta-analysis, comprising 4 cohort and 3 cross-section studies. A total of 87,251 participants and 5879 incident cases of type 2 diabetes were reported in these studies. The exposure of ACEs was positively associated with the risk of diabetes with a combined odds ratio of 1.32 (95% confidence interval 1.16 to 1.51) in the total participants. The influence of neglect was most prominent (pooled odds ratio 1.92, 95% confidence interval 1.43 to 2.57) while the effect of physical abuse was least strong (pooled odds ratio 1.30, 95% confidence interval 1.19 to 1.42). The pooled odds ratio associated with sexual abuse was 1.39 with the 95% confidence intervals from 1.28 to 1.52. The results support a significant association of adverse childhood experiences with an elevated risk of type 2 diabetes in adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Examining the association between adverse childhood experiences and smoking-exacerbated illnesses.

PubMed

Crouch, E; Radcliff, E; Strompolis, M; Wilson, A

2018-04-01

Adults who smoke increase their likelihood of death from smoking-exacerbated illnesses. The presence of illnesses exacerbated by smoking can be a powerful incentive to quit smoking. However, having a smoking-exacerbated illness does not stop all patients from smoking. Understanding that smoking may be a coping mechanism for stress, this study examined the association between the experiences of adverse events in childhood with continued smoking in adulthood among individuals and a smoking-exacerbated illness. This retrospective observational study used 2014-2015 data from the South Carolina Behavioral Risk Factor Surveillance System survey. We used multivariable logistic regression to examine the impact of adverse childhood experience (ACE) exposure on current smoking status. A total of 6321 respondents reported having a smoking-exacerbated illness. The most frequently reported categories of smoking-exacerbated illnesses were current asthma (63.9%), previous asthma (13.0%), and diabetes (12.3%). Overall, 62.4% of respondents had at least one ACE, with 20.3% of respondents having four or more ACEs. Respondents with one to three ACEs (adjusted odds ratio [aOR] 1.38; 95% confidence interval [CI] 1.37-1.40) and four or more ACEs (aOR 2.89; CI 2.86-2.92) were both significantly more likely to smoke than respondents with no ACEs, even in the presence of illnesses exacerbated by smoking. Results suggest that ACE exposure may influence risky health behaviors in adulthood, such as continued smoking even in the presence of illnesses that are exacerbated by smoking. Given that smoking has been found to be a coping mechanism for adversity, anti-smoking efforts might benefit from designing interventions and treatment plans that address ACE exposure. Copyright © 2018 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

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.

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.

Increased Dietary Salt Changes Baroreceptor Sensitivity and Intrarenal Renin-Angiotensin System in Goldblatt Hypertension.

PubMed

Shimoura, Caroline G; Lincevicius, Gisele S; Nishi, Erika E; Girardi, Adriana C C; Simon, Karin A; Bergamaschi, Cassia T; Campos, Ruy R

2017-01-01

Renovascular hypertension (2-kidney 1-clip model (2K1C)) is characterized by renin-angiotensin system (RAS) activation. Increased Angiotensin II (AngII) leads to sympathoexcitation, oxidative stress, and alterations in sodium and water balance. The aim of this study was to evaluate whether a discrete increase in sodium chloride intake in 2K1C rats leads to changes in cardiovascular and autonomic function, oxidative stress, and renin angiotensin aldosterone system. After 4 weeks of induction of hypertension, rats were fed a normal sodium diet (0.4% NaCl) or a high-sodium diet (2% NaCl) for 2 consecutive weeks. Experiments were carried out for 6 weeks after clipping. Mean arterial pressure (MAP), renal sympathetic nerve activity (rSNA), arterial baroreflex control of rSNA, and heart rate (HR) were assessed. Thiobarbituric acid reactive substances and glutathione were measured as indicators of systemic oxidative stress. Angiostensin-converting enzyme (ACE), ACE2, and angiotensinogen were evaluated in clipped and unclipped kidneys as also urinary angiotensinogen and plasma renin activity. Angiotensinogen, plasma renin activity (PRA) and angiotensin-converting enzyme (ACE) and ACE2 in clipped and unclipped kidneys were evaluated. High-sodium diet did not change systemic oxidative stress, and basal values of MAP, HR, or rSNA; however, increased renal (-0.7±0.2 vs. -1.5±0.1 spikes/s/mm Hg) and cardiac (-0.9±0.14 vs. -1.5±0.14 bpm/mm Hg) baroreceptor reflex sensitivity in 2K1C rats. Although there was no alteration in PRA, a high-salt diet significantly decreased urinary angiotensinogen, ACE, and ACE2 expressions in the clipped and unclipped kidneys. Increased arterial baroreceptor control associated with a suppression of the intrarenal RAS in the 2K1C rats on high-salt diet provide a salt-resistant effect on hypertension and sympathoexcitation in renovascular hypertensive rats. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

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

Strittmatter, S.M.; Snyder, S.H.

We demonstrate that (3H)captopril selectively labels angiotensin converting enzyme (EC 3.14.15.1) (ACE) and employ this technique to probe enzyme-inhibitor interactions. (3H)Captopril binding sites copurify with ACE activity from rat lung or rat brain. At each stage of the purification the Vmax/Bmax ratio, or kcat is 17,000 min-1 with hippuryl-L-histidyl-L-leucine as substrate. The specificity of (3H)captopril binding is apparent in the similar pharmacologic profile of inhibition in crude and pure enzyme preparations. Furthermore, binding sites and enzyme activity comigrate in gel filtration and sucrose gradient sedimentation experiments. Equilibrium analysis of (3H)captopril binding to purified ACE reveals a Bmax of 6 nmol/mgmore » of protein (KD = 2 nM), demonstrating the presence of one inhibitor binding site per polypeptide chain. The kinetics of (3H)captopril binding are characterized by monophasic association and dissociation rate constants of 0.026 nM-1 min-1 and 0.034 min-1, respectively. The affinity of ACE for both (3H) captopril and enalaprilat is greater at 37 degrees than at 0 degree, demonstrating that these interactions are entropically driven, perhaps by an isomerization of the enzyme molecule. The ionic requirements for (3H)captopril binding and substrate catalysis differ. Chloride and bromide ion, but not fluoride, are about 100-fold more potent stimulators of binding than catalysis. When the active site Zn2+ ion is replaced by Co2+, catalysis was stimulated 2-fold, whereas binding activity was decreased by 70%.« less

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 ...

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).

Using the Light Microscopy Module (LMM) on the International Space Station (ISS), The Advanced Colloids Experiment (ACE) and MacroMolecular Biophysics (MMB)

NASA Technical Reports Server (NTRS)

Meyer, William; Foster, William M.; Motil, Brian J.; Sicker, Ronald; Abbott-Hearn, Amber; Chao, David; Chiaramonte, Fran; Atherton, Arthur; Beltram, Alexander; Bodzioney, Christopher M.;

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

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

Neighborhood Collective Efficacy Moderates the Association between Maternal Adverse Childhood Experiences and Marital Conflict.

PubMed

Madigan, Sheri; Wade, Mark; Plamondon, André; Jenkins, Jennifer M

2016-06-01

In a socio-demographically diverse sample of 501 caregivers participating in a longitudinal birth cohort study during the childbearing years, we examined whether neighborhood collective efficacy moderated the association between maternal adverse childhood experience (ACEs) and marital conflict. Maternal ACEs were assessed via retrospective reports. Neighborhood collective efficacy was measured via maternal and paternal reports at 2 months, and maternal reports of marital conflict were collected at infant age 2 and 18 months. Multiple linear regression analyses revealed that maternal ACEs were associated with increased marital conflict. Neighborhood collective efficacy moderated the association between early maternal ACEs and marital conflict, such that mothers experiencing ACEs had lower levels of marital conflict when exposed to high levels of neighborhood collective efficacy. Results suggest that extra-familial sources of social support and control, such as feelings of security, trust, order, and connectedness with others, may buffer the effects of early adversity on marital discord. © Society for Community Research and Action 2016.

[Molecular cloning and characterization of an acetylcholinesterase gene Dd-ace-2 from sweet potato stem nematode Ditylenchus destructor].

PubMed

Ding, Zhong; Peng, Deliang; Huang, Wenkun; He, Wenting; Gao, Bida

2008-02-01

A cDNA, named Dd-ace-2, encoding an acetylcholinesterase (AChE, EC3.1.1.7), was isolated from sweet-potato-stem nematode, Ditylenchus destructor. The nucleotide and amino acid sequences among different nematode species were compared and analyzed with DNAMAN5.0, MEGA3.0 softwares. The results showed that the complete nucleotide sequence of Dd-ace-2 gene of Ditylenchus destructor contains 2425 base pairs from which deduced 734 amino acids (GenBank accession No. EF583058). The homology rates of amino acid sequences of Dd-ace-2 gene between Ditylenchus destructor and Meloidogyne incognita, Caenorhabditis elegans, Dictyocaulus viviparous were 48.0%, 42.7%, 42.1% respectively. The mature acetylcholinesterase sequences of Ditylenchus destructor may encode by the first 701 residues of deduced 734 amino acids.The conserved motifs involved in the catalytic triad, the choline binding site and 10 aromatic residues lining the catalytic gorge were present in the Dd-ace-2 deduced protein. Phylogenetic analysis based on AChEs of other nematodes and species showed that the deduced AChE formed the same cluster with ACE-2s.

Adverse Experiences in Early Childhood and Kindergarten Outcomes.

PubMed

Jimenez, Manuel E; Wade, Roy; Lin, Yong; Morrow, Lesley M; Reichman, Nancy E

2016-02-01

To examine associations between adverse childhood experiences (ACEs) in early childhood and teacher-reported academic and behavioral problems in kindergarten. We conducted a secondary analysis of data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort. Subjects with primary caregiver-reported information on ACE exposures ascertained at 5 years and teacher-reported outcomes at the end of the child's kindergarten year were included. Outcomes included teacher ratings of academic skills, emergent literacy skills, and behavior. We included 8 ACE exposures on the basis of the original Centers for Disease Control and Prevention Kaiser study and created an ACE score by summing individual adversities. We examined the associations between teacher-reported academic and behavioral outcomes and ACE scores by using logistic regression. In the study sample, 1007 children were included. Fifty-five percent had experienced 1 ACE and 12% had experienced ≥ 3. Adjusting for potential confounders, experiencing ≥ 3 ACEs was associated with below-average language and literacy skills (adjusted odds ratio [AORs]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and math skills (AOR: 1.8, 95% CI: 1.1-2.9), poor emergent literacy skills, attention problems (AOR: 3.5, 95% CI: 1.8-6.5), social problems (AOR: 2.7, 95% CI: 1.4-5.0), and aggression (AOR: 2.3, 95% CI: 1.2-4.6). In this study of urban children, experiencing ACEs in early childhood was associated with below-average, teacher-reported academic and literacy skills and behavior problems in kindergarten. These findings underscore the importance of integrated approaches that promote optimal development among vulnerable children. Copyright © 2016 by the American Academy of Pediatrics.

Adverse childhood experiences, dispositional mindfulness, and adult health.

PubMed

Whitaker, Robert C; Dearth-Wesley, Tracy; Gooze, Rachel A; Becker, Brandon D; Gallagher, Kathleen C; McEwen, Bruce S

2014-10-01

To determine whether greater dispositional mindfulness is associated with better adult health across a range of exposures to adverse childhood experiences (ACEs). In 2012, a web-based survey of 2160 Pennsylvania Head Start staff was conducted. We assessed ACE score (count of eight categories of childhood adversity), dispositional mindfulness (Cognitive and Affective Mindfulness Scale-Revised), and the prevalence of three outcomes: multiple health conditions (≥ 3 of 7 conditions), poor health behavior (≥ 2 of 5 behaviors), and poor health-related quality of life (HRQOL) (≥ 2 of 5 indicators). Respondents were 97% females, and 23% reported ≥ 3 ACEs. The prevalences of multiple health conditions, poor health behavior, and poor HRQOL were 29%, 21%, and 13%, respectively. At each level of ACE exposure, health outcomes were better in those with greater mindfulness. For example, among persons reporting ≥ 3 ACEs, those in the highest quartile of mindfulness had a prevalence of multiple health conditions two-thirds that of those in the lowest quartile (adjusted prevalence ratio (95% confidence interval)=0.66 (0.51, 0.86)); for those reporting no ACEs, the ratio was 0.62 (0.41, 0.94). Across a range of exposures to ACEs, greater dispositional mindfulness was associated with fewer health conditions, better health behavior, and better HRQOL. Copyright © 2014 Elsevier Inc. All rights reserved.

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

Sex-specific relationships between adverse childhood experiences and chronic obstructive pulmonary disease in five states.

PubMed

Cunningham, Timothy J; Ford, Earl S; Croft, Janet B; Merrick, Melissa T; Rolle, Italia V; Giles, Wayne H

2014-01-01

Adverse childhood experiences (ACEs) before age 18 have been repeatedly associated with several chronic diseases in adulthood such as depression, heart disease, cancer, diabetes, and stroke. We examined sex-specific relationships between individual ACEs and the number of ACEs with chronic obstructive pulmonary disease (COPD) in the general population. Data from 26,546 women and 19,015 men aged ≥18 years in five states of the 2011 Behavioral Risk Factor Surveillance System were analyzed. We used log-linear regression to estimate prevalence ratios (PRs) and their corresponding 95% confidence intervals (CIs) for the relationship of eight ACEs with COPD after adjustment for age group, race/ethnicity, marital status, educational attainment, employment, asthma history, health insurance coverage, and smoking status. Some 63.8% of women and 62.2% of men reported ≥1 ACE. COPD was reported by 4.9% of women and 4.0% of men. In women, but not in men, there was a higher likelihood of COPD associated with verbal abuse (PR =1.30, 95% CI: 1.05, 1.61), sexual abuse (PR =1.69, 95% CI: 1.36, 2.10), living with a substance abusing household member (PR =1.49, 95% CI: 1.23, 1.81), witnessing domestic violence (PR =1.40, 95% CI: 1.14, 1.72), and parental separation/divorce (PR =1.47, 95% CI: 1.21, 1.80) during childhood compared to those with no individual ACEs. Reporting ≥5 ACEs (PR =2.08, 95% CI: 1.55, 2.80) compared to none was associated with a higher likelihood of COPD among women only. ACEs are related to COPD, especially among women. These findings underscore the need for further research that examines sex-specific differences and the possible mechanisms linking ACEs and COPD. This work adds to a growing body of research suggesting that ACEs may contribute to health problems later in life and suggesting a need for program and policy solutions.

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.

Childhood Trauma and Adult Risk Factors and Disease in Hispanics/Latinos in the US: Results From the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary Study.

PubMed

Llabre, Maria M; Schneiderman, Neil; Gallo, Linda C; Arguelles, William; Daviglus, Martha L; Gonzalez, Franklyn; Isasi, Carmen R; Perreira, Krista M; Penedo, Frank J

Adverse childhood experiences (ACEs) are implicated in diseases of adulthood. We report the prevalence of ACEs in Hispanics/Latinos in the US and their association with major risk factors and diseases in adulthood. Data from the Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were used. The Sociocultural Ancillary Study of the Hispanic Community Health Study/Study of Latinos is an epidemiological study conducted in four urban communities in the US: Bronx, Chicago, Miami, and San Diego. The analytic sample comprised 5117 participants, ages 18 to 74 at baseline. Linear and logistic models, adjusted for sociodemographic factors, were used to examine associations of ACEs and risk factors (depressive symptoms, obesity, smoking, and alcohol use) and chronic disease (coronary heart disease, stroke, diabetes, asthma, chronic obstructive pulmonary disease, and cancer); the latter were also adjusted for risk factors. Most participants (77.2%) experienced at least one ACE, and 28.7% experienced four or more. Adverse childhood experiences were common among all ancestry groups, with variability among them. Prevalence of four or more ACEs was higher among women than men (31.2% and 25.8%, respectively). Adverse childhood experiences were associated with depressive symptoms, body mass index, smoking, alcohol use, cancer, coronary heart disease, and chronic obstructive pulmonary disease, but not asthma, diabetes, or stroke. Associations were not moderated by social support. Adverse childhood experiences are prevalent among US Hispanics/Latinos and are involved in disease in adulthood. The apparent higher prevalence of ACEs in US Hispanics/Latinos did not correspond with stronger associations with disease. Further studies are needed to identify factors that may moderate the associations of ACE with adult disease.

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.

Wiseman in with ACE sample

NASA Image and Video Library

2014-05-30

ISS040-E-006569 (2 June 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, performs an Advanced Colloids Experiment (ACE) sample 40-minute mixing activity in the Destiny laboratory of the International Space Station.

Wiseman in with ACE sample

NASA Image and Video Library

2014-05-30

ISS040-E-006567 (2 June 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, performs an Advanced Colloids Experiment (ACE) sample 40-minute mixing activity in the Destiny laboratory of the International Space Station.

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.

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.

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.

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

Adverse childhood experiences of referred children exposed to intimate partner violence: consequences for their wellbeing.

PubMed

Lamers-Winkelman, Francien; Willemen, Agnes M; Visser, Margreet

2012-02-01

This study investigated the relationships among Adverse Childhood Experiences (ACEs) in a high risk clinical sample of Dutch children whose mothers were abused by an intimate partner, and the severity of behavioral and emotional problems and trauma symptoms. The study population comprised 208 children (M=7.81 years, SD=2.39, range 2-12) who were referred to mental health and welfare institutions after reported Intimate Partner Violence (IPV). At intake, caregivers, children, and teachers completed questionnaires on Adverse Childhood Experiences, behavior and emotional problems, and trauma symptoms. The results showed that child witnesses of IPV were also exposed to other adverse experiences, such as abuse, household dysfunction and neglect. The mean number of ACEs was 5.08 (range 2-9). Twenty percent of the children in this sample experienced seven ACEs or more. The number of ACEs children were exposed to was unrelated to the level of emotional and behavioral problems, except for trauma related symptoms reported by parents. This study shows that children who witnessed Intimate Partner Violence were also exposed to other adverse experiences. The results of this study may imply that in this high-risk clinical sample of children exposed to IPV, additional adverse experiences have a limited relationship to psychological outcomes. A thorough assessment and inclusion of all Adverse Childhood Experiences is necessary for a comprehensive treatment program. Copyright © 2012 Elsevier Ltd. All rights reserved.

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.

Preparation and characterization of novel bioactive peptides responsible for angiotensin I-converting enzyme inhibition from wheat germ.

PubMed

Matsui, T; Li, C H; Osajima, Y

1999-07-01

Reported is the preparation of wheat germ (WG) hydrolyzate with potent angiotensin I-converting enzyme (ACE) inhibitory activity, and the characterization of peptides responsible for ACE inhibition. Successful hydrolyzate with the most potent ACE inhibitory activity was obtained by 0.5 wt.%-8 h Bacillus licheniformis alkaline protease hydrolysis after 3.0 wt.%-3 h alpha-amylase treatment of defatted WG (IC50; 0.37 mg protein ml(-1)). The activity of WG hydrolyzate was markedly increased by ODS and subsequent AG50W purifications (IC50; 0.018 mg protein ml(-1)). As a result of isolations by high performance liquid chromatographies, 16 peptides with the IC50 value of less than 20 microM, composed of 2-7 amino acid residues were identified from the WG hydrolyzate. Judging from the high content (260 mg in 100 g of AG50W fraction) and powerful ACE inhibitory activity (IC50; 0.48 microM), Ile-Val-Tyr was identified as a main contributor to the ACE inhibition of the hydrolyzate.

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.

The Case for Including Adverse Childhood Experiences in Child Maltreatment Education: A Path Analysis.

PubMed

Bachmann, Michael; Bachmann, Brittany A

2018-03-16

The lifelong, negative consequences of exposure to adverse childhood experiences (ACEs) for individuals and their families are well established. To demonstrate the importance of including ACE information in child maltreatment education curricula using path analysis. Survey data examined the impact of child maltreatment education programs and knowledge about ACEs on medical practitioners' reporting habits and ability to detect maltreatment. A path diagram distinguished between the direct impact of education programs on outcome measures and the indirect effect that is mediated through knowledge of ACEs. Medical practitioners' ability to detect child maltreatment and their number of referrals to Child Protective Services (CPS). The optimized path diagram (χ 2 SB(3) = 3.9, p = 0.27; RMSEA-SB = 0.017; R 2 = 0.21, where SB is Satorra-Bentler coefficient and RMSEA is root-mean-square error of approximation) revealed the mediating variable "knowledge about ACEs" as the strongest structural effect (SB-β = 0.34) on the number of CPS referrals. It was almost twice as high as the second strongest effect of formal education programs (SB-β = 0.19). For workplace training programs, the total effect when including knowledge of ACEs was almost double as strong as the direct effect alone. Even when previous child maltreatment education was controlled for, practitioners familiar with the consequences of ACEs were significantly more likely to recognize and to report abuse to CPS. This study documented the importance of specialized training programs on ACEs, and the essential role ACE knowledge plays in the effectiveness of provider education programs.

Adverse Childhood Experiences and Adult Well-Being in a Low-income, Urban Cohort.

PubMed

Giovanelli, Alison; Reynolds, Arthur J; Mondi, Christina F; Ou, Suh-Ruu

2016-04-01

This study tests the association between adverse childhood experiences (ACEs) and multidimensional well-being in early adulthood for a low-income, urban cohort, and whether a preschool preventive intervention moderates this association. Follow-up data were analyzed for 1202 low-income, minority participants in the Chicago Longitudinal Study, a prospective investigation of the impact of early experiences on life-course well-being. Born between 1979 and 1980 in high-poverty neighborhoods, individuals retrospectively reported ACEs from birth to adolescence, except in cases of child abuse and neglect. Nearly two-thirds of the study sample experienced ≥1 ACEs by age 18. After controlling for demographic factors and early intervention status, individuals reporting ACEs were significantly more likely to exhibit poor outcomes than those with no ACEs. Those with ≥4 ACEs had significantly reduced likelihood of high school graduation (odds ratio [OR] = 0.37; P < .001), increased risk for depression (OR = 3.9; P < .001), health compromising behaviors (OR = 4.5; P < .001), juvenile arrest (OR = 3.1; P < .001), and felony charges (OR = 2.8; P < .001). They were also less likely to hold skilled jobs (OR = 0.50; P = .001) and to go further in school even for adversity measured by age 5. ACEs consistently predicted a diverse set of adult outcomes in a high-risk, economically disadvantaged sample. Effective and widely available preventive interventions are needed to counteract the long-term consequences of ACEs. Copyright © 2016 by the American Academy of Pediatrics.

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 association between adverse childhood experiences (ACEs) and suicide attempts in a population-based study.

PubMed

Fuller-Thomson, E; Baird, S L; Dhrodia, R; Brennenstuhl, S

2016-09-01

To further our understanding of the relationship between Adverse Childhood Experiences (ACEs) and suicidal behaviour, this study investigates the association between three types of ACEs and lifetime suicide attempts, while considering potential gender-specific and mediating effects. Data were obtained from the 2012 Canadian Community Health Survey-Mental Health (CCHS-MH), a cross-sectional, population-based survey comprised of respondents aged 18 or older who provided self-reported data on past experiences of suicide attempts, as well as childhood sexual abuse (CSA), childhood physical abuse (CPA) and parental domestic violence (PDV) (n = 22 559). After testing for ACE by gender interactions, we estimated the odds of lifetime suicide attempts for each ACE and then investigated whether depression, anxiety, substance abuse and chronic pain acted as mediators of the relationship. The odds of suicide attempts are significantly higher among those with a history of CPA (OR = 3.29; 99.9% CI 2.33-4.64), CSA (OR = 4.42; 99.9% CI 3.14-6.23) or PDV (OR = 2.52; 99.9% CI 1.69-3.76), when ACEs are mutually adjusted. There is little evidence that gender acts as a moderator; however, depression, anxiety, substance abuse and chronic pain appear to partially mediate the associations. Depression alone accounts for about a quarter of the associations with CSA and CPA. Mental health factors and chronic pain appear only to partially mediate relationships between ACEs and lifetime suicide attempts. Future research should look at other pathways with the goal of developing multi-level interventions. © 2016 John Wiley & Sons Ltd.

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

FIRE III ACE Info

Atmospheric Science Data Center

2014-03-18

... 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 ...

Guava leaves polyphenolics-rich extract inhibits vital enzymes implicated in gout and hypertension in vitro.

PubMed

Irondi, Emmanuel Anyachukwu; Agboola, Samson Olalekan; Oboh, Ganiyu; Boligon, Aline Augusti; Athayde, Margareth Linde; Shode, Francis O

2016-01-01

Elevated uric acid level, an index of gout resulting from the over-activity of xanthine oxidase (XO), increases the risk of developing hypertension. However, research has shown that plant-derived inhibitors of XO and angiotensin 1-converting enzyme (ACE), two enzymes implicated in gout and hypertension, respectively, can prevent or ameliorate both diseases, without noticeable side effects. Hence, this study characterized the polyphenolics composition of guava leaves extract and evaluated its inhibitory effect on XO and ACE in vitro. The polyphenolics (flavonoids and phenolic acids) were characterized using high-performance liquid chromatography (HPLC) coupled with diode array detection (DAD). The XO, ACE, and Fe(2+)-induced lipid peroxidation inhibitory activities, and free radicals (2,2-diphenylpicrylhydrazyl [DPPH]* and 2,2´-azino-bis-3-ethylbenzthiazoline-6-sulphonic [ABTS]*(+)) scavenging activities of the extract were determined using spectrophotometric methods. Flavonoids were present in the extract in the order of quercetin > kaempferol > catechin > quercitrin > rutin > luteolin > epicatechin; while phenolic acids were in the order of caffeic acid > chlorogenic acid > gallic acids. The extract effectively inhibited XO, ACE and Fe(2+)-induced lipid peroxidation in a dose-dependent manner; having half-maximal inhibitory concentrations (IC50) of 38.24 ± 2.32 μg/mL, 21.06 ± 2.04 μg/mL and 27.52 ± 1.72 μg/mL against XO, ACE and Fe(2+)-induced lipid peroxidation, respectively. The extract also strongly scavenged DPPH* and ABTS*(+). Guava leaves extract could serve as functional food for managing gout and hypertension and attenuating the oxidative stress associated with both diseases.

Swanson in Node 2 with ACE samples

NASA Image and Video Library

2014-07-14

ISS040-E-060673 (14 July 2014) --- NASA astronaut Steve Swanson, Expedition 40 commander, works with test samples for the Advanced Colloids Experiment (ACE) at a work station in the Harmony node of the International Space Station.

A Global Aerosol Model Forecast for the ACE-Asia Field Experiment

NASA Technical Reports Server (NTRS)

Chin, Mian; Ginoux, Paul; Lucchesi, Robert; Huebert, Barry; Weber, Rodney; Anderson, Tad; Masonis, Sarah; Blomquist, Byron; Bandy, Alan; Thornton, Donald

2003-01-01

We present the results of aerosol forecast during the Aerosol Characterization Experiment (ACE-Asia) field experiment in spring 2001, using the Georgia Tech/Goddard Global Ozone Chemistry Aerosol Radiation and Transport (GOCART) model and the meteorological forecast fields from the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The aerosol model forecast provides direct information on aerosol optical thickness and concentrations, enabling effective flight planning, while feedbacks from measurements constantly evaluate the model, making successful model improvements. We verify the model forecast skill by comparing model predicted total aerosol extinction, dust, sulfate, and SO2 concentrations with those quantities measured by the C-130 aircraft during the ACE-Asia intensive operation period. The GEOS DAS meteorological forecast system shows excellent skills in predicting winds, relative humidity, and temperature for the ACE-Asia experiment area as well as for each individual flight, with skill scores usually above 0.7. The model is also skillful in forecast of pollution aerosols, with most scores above 0.5. The model correctly predicted the dust outbreak events and their trans-Pacific transport, but it constantly missed the high dust concentrations observed in the boundary layer. We attribute this missing dust source to the desertification regions in the Inner Mongolia Province in China, which have developed in recent years but were not included in the model during forecasting. After incorporating the desertification sources, the model is able to reproduce the observed high dust concentrations at low altitudes over the Yellow Sea. Two key elements for a successful aerosol model forecast are correct source locations that determine where the emissions take place, and realistic forecast winds and convection that determine where the aerosols are transported. We demonstrate that our global model can not only account for the large-scale intercontinental transport, but also produce the small-scale spatial and temporal variations that are adequate for aircraft measurements planning.

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.

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.

Adverse childhood experiences of low-income urban youth.

PubMed

Wade, Roy; Shea, Judy A; Rubin, David; Wood, Joanne

2014-07-01

Current assessments of adverse childhood experiences (ACEs) may not adequately encompass the breadth of adversity to which low-income urban children are exposed. The purpose of this study was to identify and characterize the range of adverse childhood experiences faced by young adults who grew up in a low-income urban area. Focus groups were conducted with young adults who grew up in low-income Philadelphia neighborhoods. Using the nominal group technique, participants generated a list of adverse childhood experiences and then identified the 5 most stressful experiences on the group list. The most stressful experiences identified by participants were grouped into a ranked list of domains and subdomains. Participants identified a range of experiences, grouped into 10 domains: family relationships, community stressors, personal victimization, economic hardship, peer relationships, discrimination, school, health, child welfare/juvenile justice, and media/technology. Included in these domains were many but not all of the experiences from the initial ACEs studies; parental divorce/separation and mental illness were absent. Additional experiences not included in the initial ACEs but endorsed by our participants included single-parent homes; exposure to violence, adult themes, and criminal behavior; personal victimization; bullying; economic hardship; and discrimination. Gathering youth perspectives on childhood adversity broadens our understanding of the experience of stress and trauma in childhood. Future work is needed to determine the significance of this broader set of adverse experiences in predisposing children to poor health outcomes as adults. Copyright © 2014 by the American Academy of Pediatrics.

Adverse childhood experiences are associated with irritable bowel syndrome and gastrointestinal symptom severity.

PubMed

Park, S H; Videlock, E J; Shih, W; Presson, A P; Mayer, E A; Chang, L

2016-08-01

Early adverse life events (EALs) are associated with irritable bowel syndrome (IBS). Exposure to EALs as assessed by the Adverse Childhood Experiences (ACE) questionnaire is associated with greater disease prevalence, but ACE has not been studied in gastrointestinal disorders. Study aims were to: (i) Estimate the prevalence of EALs in the IBS patients using the ACE questionnaire; (ii) Determine correlations between ACE and Early Trauma Inventory Self Report-Short Form (ETI-SR) scores to confirm its validity in IBS; and (iii) Correlate ACE scores with IBS symptom severity. A total of 148 IBS (73% women, mean age = 31 years) and 154 HCs (59% women, mean age = 30 years) completed the ACE and ETI-SR between June 2010 and April 2015. These surveys measured EALs before age 18 in the domains of physical, sexual, and emotional abuse, and general trauma. IBS and abdominal pain severity was measured by a 20-point scale (0 = none, 20 = worst symptoms). The ACE score increased the odds of having IBS (odds ratio [OR] = 2.05, 95% confidence interval [CI]: 1.21-3.48, p = 0.008). Household mental illness (p < 0.001), emotional abuse (p = 0.004), and incarcerated household member (p = 0.019) were significant predictors of IBS. Adverse childhood experiences and ETI-SR scores were strongly correlated (r = 0.59, p < 0.001). ACE, but not ETI-SR, modestly correlated with IBS severity (r = 0.17, p = 0.036) and abdominal pain (r = 0.20, p = 0.015). The ACE questionnaire is a useful instrument to measure EALs in IBS based on its use in large studies, its ability to measure prevalence across different EAL domains, and its correlation with symptom severity. © 2016 John Wiley & Sons Ltd.

[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.

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…

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.

The Case for Including Adverse Childhood Experiences in Child Maltreatment Education: A Path Analysis

PubMed Central

Bachmann, Michael; Bachmann, Brittany A

2018-01-01

Context The lifelong, negative consequences of exposure to adverse childhood experiences (ACEs) for individuals and their families are well established. Objective To demonstrate the importance of including ACE information in child maltreatment education curricula using path analysis. Design Survey data examined the impact of child maltreatment education programs and knowledge about ACEs on medical practitioners’ reporting habits and ability to detect maltreatment. A path diagram distinguished between the direct impact of education programs on outcome measures and the indirect effect that is mediated through knowledge of ACEs. Main Outcome Measures Medical practitioners’ ability to detect child maltreatment and their number of referrals to Child Protective Services (CPS). Results The optimized path diagram (χ2SB(3) = 3.9, p = 0.27; RMSEA-SB = 0.017; R2 = 0.21, where SB is Satorra-Bentler coefficient and RMSEA is root-mean-square error of approximation) revealed the mediating variable “knowledge about ACEs” as the strongest structural effect (SB-β = 0.34) on the number of CPS referrals. It was almost twice as high as the second strongest effect of formal education programs (SB-β = 0.19). For workplace training programs, the total effect when including knowledge of ACEs was almost double as strong as the direct effect alone. Even when previous child maltreatment education was controlled for, practitioners familiar with the consequences of ACEs were significantly more likely to recognize and to report abuse to CPS. Conclusion This study documented the importance of specialized training programs on ACEs, and the essential role ACE knowledge plays in the effectiveness of provider education programs. PMID:29616910

Relationship of quadriceps muscle power and optimal shortening velocity with angiotensin-converting enzyme activity in older women.

PubMed

Kostka, Joanna; Sikora, Joanna; Kostka, Tomasz

2017-01-01

The goal of this study was to assess whether angiotensin-converting enzyme (ACE) activity is related to muscle function (strength, power and velocity), as well as to assess if ACE inhibitors (ACEIs) and other angiotensin system blocking medications (ASBMs) influence muscle performance in elderly women. Ninety-five community-dwelling elderly women took part in this study. Anthropometric data, blood ACE activity analysis, maximum power (P max ) and optimal shortening velocity (υ opt ) of the knee extensor muscles, handgrip strength, physical activity (PA) and functional performance were measured. Women taking ACEI were on average almost 2 years older than the women who did not take ACEI. They took more medicines and were also characterized by significantly lower level of ACE, but they did not differ in terms of PA level, results of functional performance and parameters characterizing muscle functions. No correlations of ACE activity with P max and handgrip strength, as well as with PA or functional performance were found. Higher ACE activity was connected with lower υ opt for women who did not take any ASBMs (rho =-0.37; p =0.01). Serum ACE activity was not associated with muscle strength, power and functional performance in both ASBM users and nonusers, but was associated with optimal shortening velocity of quadriceps muscles in older women. Further prospective studies are needed to assess if ACEIs or other ASBMs may slow down the decline in muscle function and performance.

ACE H2 Hardware Configuration and Mix Part 1

NASA Image and Video Library

2016-01-04

ISS046e005678 (01/04/2016) ---- ESA (European Space Agency) astronaut Tim Peake works on the Advanced Colloids Experiment 2 (ACE H2) Hardware Configuration and Mix Part 1. Peake sent out a Twitter message with this image: Stirring samples using a bar magnet to turn a tiny metal rod - preparing for today's @ISS_Research. #Principia".

Analysis of shipboard aerosol optical thickness measurements from multiple sunphotometers aboard the R/V Ronald H. Brown during the Aerosol Characterization Experiment - Asia

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

Miller, Mark A.; Knobelspiesse, Kirk; Frouin, Robert

2005-06-20

Marine sunphotometer measurements collected aboard the R/V Ronald H. Brown during the Aerosol Characterization Experiment - Asia (ACE-Asia) are used to evaluate the ability of complementary instrumentation to obtain the best possible estimates of aerosol optical thickness and Angstrom exponent from ships at sea. A wide range of aerosol conditions, including clean maritime conditions and highly polluted coastal environments, were encountered during the ACE-Asia cruise. The results of this study suggest that shipboard hand-held sunphotometers and fast-rotating shadow-band radiometers (FRSRs) yield similar measurements and uncertainties if proper measurement protocols are used and if the instruments are properly calibrated. The automatedmore » FRSR has significantly better temporal resolution (2 min) than the hand-held sunphotometers when standard measurement protocols are used, so it more faithfully represents the variability of the local aerosol structure in polluted regions. Conversely, results suggest that the hand-held sunphotometers may perform better in clean, maritime air masses for unknown reasons. Results also show that the statistical distribution of the Angstrom exponent measurements is different when the distributions from hand-held sunphotometers are compared with those from the FRSR and that the differences may arise from a combination of factors.« less

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.

Genome duplication and mutations in ACE2 cause multicellular, fast-sedimenting phenotypes in evolved Saccharomyces cerevisiae

PubMed Central

Oud, Bart; Guadalupe-Medina, Victor; Nijkamp, Jurgen F.; de Ridder, Dick; Pronk, Jack T.; van Maris, Antonius J. A.; Daran, Jean-Marc

2013-01-01

Laboratory evolution of the yeast Saccharomyces cerevisiae in bioreactor batch cultures yielded variants that grow as multicellular, fast-sedimenting clusters. Knowledge of the molecular basis of this phenomenon may contribute to the understanding of natural evolution of multicellularity and to manipulating cell sedimentation in laboratory and industrial applications of S. cerevisiae. Multicellular, fast-sedimenting lineages obtained from a haploid S. cerevisiae strain in two independent evolution experiments were analyzed by whole genome resequencing. The two evolved cell lines showed different frameshift mutations in a stretch of eight adenosines in ACE2, which encodes a transcriptional regulator involved in cell cycle control and mother-daughter cell separation. Introduction of the two ace2 mutant alleles into the haploid parental strain led to slow-sedimenting cell clusters that consisted of just a few cells, thus representing only a partial reconstruction of the evolved phenotype. In addition to single-nucleotide mutations, a whole-genome duplication event had occurred in both evolved multicellular strains. Construction of a diploid reference strain with two mutant ace2 alleles led to complete reconstruction of the multicellular-fast sedimenting phenotype. This study shows that whole-genome duplication and a frameshift mutation in ACE2 are sufficient to generate a fast-sedimenting, multicellular phenotype in S. cerevisiae. The nature of the ace2 mutations and their occurrence in two independent evolution experiments encompassing fewer than 500 generations of selective growth suggest that switching between unicellular and multicellular phenotypes may be relevant for competitiveness of S. cerevisiae in natural environments. PMID:24145419

Guava leaves polyphenolics-rich extract inhibits vital enzymes implicated in gout and hypertension in vitro

PubMed Central

Irondi, Emmanuel Anyachukwu; Agboola, Samson Olalekan; Oboh, Ganiyu; Boligon, Aline Augusti; Athayde, Margareth Linde; Shode, Francis O.

2016-01-01

Background/Aim: Elevated uric acid level, an index of gout resulting from the over-activity of xanthine oxidase (XO), increases the risk of developing hypertension. However, research has shown that plant-derived inhibitors of XO and angiotensin 1-converting enzyme (ACE), two enzymes implicated in gout and hypertension, respectively, can prevent or ameliorate both diseases, without noticeable side effects. Hence, this study characterized the polyphenolics composition of guava leaves extract and evaluated its inhibitory effect on XO and ACE in vitro. Materials and Methods: The polyphenolics (flavonoids and phenolic acids) were characterized using high-performance liquid chromatography (HPLC) coupled with diode array detection (DAD). The XO, ACE, and Fe2+-induced lipid peroxidation inhibitory activities, and free radicals (2,2-diphenylpicrylhydrazyl [DPPH]* and 2,2´-azino-bis-3-ethylbenzthiazoline-6-sulphonic [ABTS]*+) scavenging activities of the extract were determined using spectrophotometric methods. Results: Flavonoids were present in the extract in the order of quercetin > kaempferol > catechin > quercitrin > rutin > luteolin > epicatechin; while phenolic acids were in the order of caffeic acid > chlorogenic acid > gallic acids. The extract effectively inhibited XO, ACE and Fe2+-induced lipid peroxidation in a dose-dependent manner; having half-maximal inhibitory concentrations (IC50) of 38.24 ± 2.32 μg/mL, 21.06 ± 2.04 μg/mL and 27.52 ± 1.72 μg/mL against XO, ACE and Fe2+-induced lipid peroxidation, respectively. The extract also strongly scavenged DPPH* and ABTS*+. Conclusion: Guava leaves extract could serve as functional food for managing gout and hypertension and attenuating the oxidative stress associated with both diseases. PMID:27104032

Aerosols, Chemistry, and Radiative Forcing: A 3-D Model Analysis of Satellite and ACE-Asia data (ACMAP)

NASA Technical Reports Server (NTRS)

Chin, Mian; Ginoux, Paul; Torres, Omar; Zhao, Xue-Peng

2005-01-01

We propose a research project to incorporate a global 3-D model and satellite data into the multi-national Aerosol Characterization Experiment-Asia (ACE-Asia) mission. Our objectives are (1) to understand the physical, chemical, and optical properties of aerosols and the processes that control those properties over the Asian-Pacific region, (2) to investigate the interaction between aerosols and tropospheric chemistry, and (3) to determine the aerosol radiative forcing over the Asia-Pacific region. We will use the Georgia TecWGoddard Global Ozone Chemistry Aerosol Radiation and Transport (GOCART) model to link satellite observations and the ACE-Asia measurements. First, we will use the GOCART model to simulate aerosols and related species, and evaluate the model with satellite and in-situ observations. Second, the model generated aerosol vertical profiles and compositions will be used to validate the satellite products; and the satellite data will be used for during- and post- mission analysis. Third, we will use the model to analyze and interpret both satellite and ACE- Asia field campaign data and investigate the aerosol-chemistry interactions. Finally, we will calculate aerosol radiative forcing over the Asian-Pacific region, and assess the influence of Asian pollution in the global atmosphere. We propose a research project to incorporate a global 3-D model and satellite data into

Carbon Dioxide (CO2) Retrievals from Atmospheric Chemistry Experiment (ACE) Solar Occultation Measurements

NASA Technical Reports Server (NTRS)

Rinsland, Curtis P.; Chiou, Linda; Boone, Chris; Bernath, Peter

2010-01-01

The Atmospheric Chemistry Experiment ACE satellite (SCISAT-1) was launched into an inclined orbit on 12 August 2003 and is now recording high signal-to-noise 0.02 per centimeter resolution solar absorption spectra covering 750-4400 per centimeter (2.3-13 micrometers). A procedure has been developed for retrieving average dry air CO2 mole fractions (X(sub CO2)) in the altitude range 7-10 kilometers from the SCISAT-1 spectra. Using the N2 continuum absorption in a window region near 2500 per centimeter, altitude shifts are applied to the tangent heights retrieved in version 2.2 SCISAT-1 processing, while cloudy or aerosol-impacted measurements are eliminated. Monthly-mean XCO2 covering 60 S to 60 N latitude for February 2004 to March 2008 has been analyzed with consistent trends inferred in both hemispheres. The ACE XCO2 time series have been compared with previously-reported surface network measurements, predictions based on upper tropospheric aircraft measurements, and space-based measurements. The retrieved X(sub CO2) from the ACE-FTS spectra are higher on average by a factor of 1.07 plus or minus 0.025 in the northern hemisphere and by a factor of 1.09 plus or minus 0.019 on average in the southern hemisphere compared to surface station measurements covering the same time span. The ACE derived trend is approximately 0.2% per year higher than measured at surface stations during the same observation period.

Adverse experiences in infancy and toddlerhood: Relations to adaptive behavior and academic status in middle childhood.

PubMed

McKelvey, Lorraine M; Edge, Nicola Conners; Mesman, Glenn R; Whiteside-Mansell, Leanne; Bradley, Robert H

2018-06-13

Findings from the Adverse Childhood Experiences (ACE) study articulated the negative effects of childhood trauma on long-term well-being. The purpose of the current study is to examine the associations between ACEs experienced in infancy and toddlerhood and adaptive behavior and academic status in middle childhood. We used data collected from a sample of low-income families during the impacts study of Early Head Start (EHS). Data were collected by trained interviewers demonstrating at least 85% reliability with protocols. Data come from 1469 socio-demographically diverse mothers and children collected at or near ages 1, 2, 3, and 11. At ages 1, 2, and 3, an EHS-ACEs index was created based on interview and observation items. The EHS-ACEs indices were averaged to represent exposure across infancy and toddlerhood. At age 11, parents were asked about school outcomes and completed the Child Behavior Checklist. Across development, children were exposed to zero (19%), one (31%), two (27%), and three or more ACEs (23%). Logistic regression analyses, controlling for EHS program assignment, and parent, school, and child characteristics, showed ACEs were significantly associated with parental report of the child: having an individualized educational program since starting school and in the current school year, having been retained a grade in school, and problems with externalizing and internalizing behavior, as well as attention. Findings suggest that ACEs influence children's behavioral and academic outcomes early in development. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

Ford poses at the FIR/LMM/ACE in the U.S. Laboratory

NASA Image and Video Library

2013-02-21

ISS034-E-056144 (21 Feb. 2013) --- Inside the U.S. Laboratory (Destiny) aboard the Earth-orbiting International Space Statio, NASA astronaut Kevin Ford, Expedition 34 commander, is seen with the Fluids Integration Rack (FIR)/Light Microscopy Module (LMM)/Advanced Colloids Experiment (ACE). ACE samples, which produce microscopic images of materials containing small colloidal particles, are scheduled for arrival on SpaceX-2 in the first week of March.

Developing a Stand Alone Sun Photometer for Ships and Buoys

NASA Technical Reports Server (NTRS)

Porter, John N.

1997-01-01

During November and December 1995 the first Aerosol Characterization Experiment (ACE 1) was carried to characterize the aerosol physical and optical properties in the clean marine atmosphere near Tasmania in the South Pacific. As part of this effort, and with funding from this proposal, we installed a sun photometer on the R/V Discoverer and a spectro-photometer on the NOAA C-130 aircraft.

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.

Inhibition of angiotensin convertin enzyme (ACE) activity by the anthocyanins delphinidin- and cyanidin-3-O-sambubiosides from Hibiscus sabdariffa.

PubMed

Ojeda, Deyanira; Jiménez-Ferrer, Enrique; Zamilpa, Alejandro; Herrera-Arellano, Armando; Tortoriello, Jaime; Alvarez, Laura

2010-01-08

The beverages of Hibiscus sabdariffa calyces are widely used in Mexico as diuretic, for treating gastrointestinal disorders, liver diseases, fever, hypercholesterolemia and hypertension. Different works have demonstrated that Hibiscus sabdariffa extracts reduce blood pressure in humans, and recently, we demonstrated that this effect is due to angiotensin converting enzyme (ACE) inhibitor activity. The aim of the current study was to isolate and characterizer the constituents responsible of the ACE activity of the aqueous extract of Hibiscus sabdariffa. Bioassay-guided fractionation of the aqueous extract of dried calyces of Hibiscus sabdariffa using preparative reversed-phase HPLC, and the in vitro ACE Inhibition assay, as biological monitor model, were used for the isolation. The isolated compounds were characterized by spectroscopic methods. The anthocyanins delphinidin-3-O-sambubioside (1) and cyanidin-3-O-sambubioside (2) were isolated by bioassay-guided purification. These compounds showed IC(50) values (84.5 and 68.4 microg/mL, respectively), which are similar to those obtained by related flavonoid glycosides. Kinetic determinations suggested that these compounds inhibit the enzyme activity by competing with the substrate for the active site. The competitive ACE inhibitor activity of the anthocyanins 1 and 2 is reported for the first time. This activity is in good agreement with the folk medicinal use of Hibiscus sabdariffa calyces as antihypertensive. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Do adverse childhood experiences predict adult interpersonal difficulties? The role of emotion dysregulation.

PubMed

Poole, Julia C; Dobson, Keith S; Pusch, Dennis

2018-06-01

Adverse childhood experiences (ACEs) are risk factors for interpersonal difficulties in adulthood, however the mechanism that underlies this association is unknown. The current study investigated the association of a wide range of ACEs with interpersonal difficulties in adulthood, and tested whether emotion dysregulation mediated the relationship between ACEs and interpersonal difficulties. Patients over the age of 18 were recruited from primary care clinics (N = 4006). Participants completed self-report questionnaires that assessed ACEs, emotion dysregulation, and interpersonal difficulties. Results indicated that, after controlling for a range of demographic variables, each type of ACE significantly predicted increased interpersonal difficulties and that cumulative ACEs predicted increased interpersonal difficulties, F(8, 3137) = 39.68, p < .001, R 2  = 0.09. Further, emotion dysregulation mediated the association between ACEs and interpersonal difficulties, B = 0.79, SE = 0.09, 95% CI [0.64, 0.97]. These findings emphasize the role of childhood adversity on interpersonal functioning in adulthood, and highlight emotion dysregulation as a mechanism by which this association occurs. Results have the potential to inform preventative and treatment efforts to improve adaptive outcomes among individuals with a history of childhood adversity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of whether the ACE gene I/D polymorphism constitutes a risk factor for chronic obstructive pulmonary disease in the Turkish population.

PubMed

Ayada, C; Toru, U; Genç, O; Yerlikaya, A; Sahin, S; Turgut, S; Turgut, G

2014-12-12

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction that occurs as a result of the normal inflammatory process to protect against harmful irritants and chemicals. Another physiological regulatory process, the renin angiotensin system (RAS), plays an important role in the pathology of many diseases. Angiotensin converting enzyme (ACE) is a key enzyme of RAS. We investigated the frequency of the ACE gene I/D polymorphism in patients with COPD in Turkey. This study was performed on 47 unrelated patients with COPD and 64 healthy subjects. DNA samples were isolated from peripheral blood, and ACE DNA was amplified by polymerase chain reaction. The frequencies of ACE genotypes were 27.7, 55.3, and 17% for DD, ID, and II in the COPD group, respectively, and 43.8, 43.8, and 12.4% in the control group. There was no statistically significant difference between groups (X(2) = 3.078; df = 2; P = 0.220). The distributions of ACE gene D alleles were 38.2% (N = 52) in the COPD group and 61.8% (N = 84) in the control group; and those of I alleles were 48.8% (N = 42) in the COPD group and 51.2% (N = 44) in the control group. There was no statistically significant difference between groups for allele frequency (X(2) = 2.419; df = 2; P = 0.120). We believe these results can be useful for large-scale population genetic research considering the frequency of the ACE gene variation in COPD patients in the Turkish population.

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.

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.

Porcine pulmonary angiotensin I-converting enzyme--biochemical characterization and spatial arrangement of the N- and C-domains by three-dimensional electron microscopic reconstruction.

PubMed

Chen, Hui-Ling; Lünsdorf, Heinrich; Hecht, Hans-Jürgen; Tsai, Hsin

2010-08-01

The somatic angiotensin I-converting enzyme (sACE; peptidyl-dipeptidase A; EC 3.4.15.1) was isolated from pig lung and purified to homogeneity. The purified enzyme has a molecular mass of about 180 kDa. Upon proteolytic cleavage, two approximately 90 kDa fragments were obtained and identified by amino-terminal sequence analysis as the N- and C-domains of sACE. Both purified domains were shown to be catalytically active. A 2.3 nm resolution model of sACE was obtained by three-dimensional electron microscopic reconstruction of negatively stained sACE particles, based on atomic X-ray data fitting. Our model shows for the first time the relative orientation of the sACE catalytically active domains and their spatial distance. (c) 2010 Elsevier Ltd. All rights reserved.

Adverse childhood experiences and consumption of alcohol, tobacco and illicit drugs among adolescents of a Brazilian birth cohort.

PubMed

Gonçalves, Helen; Soares, Ana Luiza Gonçalves; Santos, Ana Paula Gomes Dos; Ribeiro, Camila Garcez; Bierhals, Isabel Oliveira; Vieira, Luna Strieder; Hellwig, Natália Limões; Wehrmeister, Fernando C; Menezes, Ana M B

2016-11-03

The objective of this study was to investigate the association between adverse childhood experiences (ACEs) and the use of alcohol, tobacco and illicit drugs among adolescents from a Brazilian cohort. The occurrence of five ACEs, the use of alcohol and tobacco and trying illicit drugs were investigated in the 1993 Pelotas birth cohort at the age of 15 (n = 4,230). A score was created for the ACEs and their association with the use of substances was evaluated. Around 25% of adolescents consumed alcohol, 6% smoked and 2.1% reported having used drugs at least once in their lives. The ACEs were associated with the use of alcohol, tobacco and illicit drugs. A dose-response relation between the number of ACEs and the substance use was found, particularly with regard to illicit drugs. The occurrence of ACEs was positively associated with the use of alcohol, tobacco and illicit drugs among adolescents and the risk may be different for men and women. These results point to the fact that strategies for preventing the use of substances should include interventions both among adolescents and within the family environment.

ANG II is required for optimal overload-induced skeletal muscle hypertrophy

NASA Technical Reports Server (NTRS)

Gordon, S. E.; Davis, B. S.; Carlson, C. J.; Booth, F. W.

2001-01-01

ANG II mediates the hypertrophic response of overloaded cardiac muscle, likely via the ANG II type 1 (AT(1)) receptor. To examine the potential role of ANG II in overload-induced skeletal muscle hypertrophy, plantaris and/or soleus muscle overload was produced in female Sprague-Dawley rats (225-250 g) by the bilateral surgical ablation of either the synergistic gastrocnemius muscle (experiment 1) or both the gastrocnemius and plantaris muscles (experiment 2). In experiment 1 (n = 10/group), inhibiting endogenous ANG II production by oral administration of an angiotensin-converting enzyme (ACE) inhibitor during a 28-day overloading protocol attenuated plantaris and soleus muscle hypertrophy by 57 and 96%, respectively (as measured by total muscle protein content). ACE inhibition had no effect on nonoverloaded (sham-operated) muscles. With the use of new animals (experiment 2; n = 8/group), locally perfusing overloaded soleus muscles with exogenous ANG II (via osmotic pump) rescued the lost hypertrophic response in ACE-inhibited animals by 71%. Furthermore, orally administering an AT(1) receptor antagonist instead of an ACE inhibitor produced a 48% attenuation of overload-induced hypertrophy that could not be rescued by ANG II perfusion. Thus ANG II may be necessary for optimal overload-induced skeletal muscle hypertrophy, acting at least in part via an AT(1) receptor-dependent pathway.

Association of Adverse Childhood Experiences with Life Course Health and Development.

PubMed

Austin, Anna

2018-01-01

Several studies demonstrate an association between adverse childhood experiences (ACEs) and poor outcomes over the life course. Data from the 2012 North Carolina Behavioral Risk Factor Surveillance System show that ACEs are common among North Carolina residents, ACEs co-occur, and cumulative ACE exposure is associated with poor health outcomes. ©2018 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.

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.

Adverse Childhood Experiences (ACEs) and Alcohol Abuse among South Carolina Adults.

PubMed

Crouch, Elizabeth; Radcliff, Elizabeth; Strompolis, Melissa; Wilson, Abygail

2018-06-07

Adverse childhood experiences (ACEs) have been associated with negative adult health outcomes, including alcohol misuse. The impact of ACEs on alcohol use may vary by gender, with ACEs impacting women more than men in coping with adulthood stressors. The objective of this study is to examine the gender-specific relationships between ACEs and self-reported binge drinking and heavy drinking in adulthood among South Carolina residents. This study analyzed a sample of 8492 respondents who completed the 2014 or 2015 South Carolina Behavioral Risk Factor Surveillance System (BRFSS) survey. Logistic regression was used to examine the impact of types and the number of ACEs on binge drinking and heaving drinking in adulthood. Thirty-seven percent of men and 22.8% of women survey respondents reported binge drinking and 12.2% of men and 4.1% of women reported heavy drinking. Almost all categories of ACE were associated with increased odds of reporting binge and heavy drinking; household mental illness had the greatest odds for men (aOR 1.31, 95% CI 1.30-1.33) and emotional abuse had the greatest odds for women (aOR 1.42, 95% CI 1.40-1.43). Men and women with four or more ACEs had greater odds of reporting binge and heavy drinking compared to their counterparts. Conclusions/Importance: Given the potential for negative outcomes associated with alcohol misuse and transmission of risky alcohol-related behaviors from parent to child, strategies that utilize a multigenerational approach could have a large impact on population health.

Cumulative childhood stress and autoimmune diseases in adults.

PubMed

Dube, Shanta R; Fairweather, DeLisa; Pearson, William S; Felitti, Vincent J; Anda, Robert F; Croft, Janet B

2009-02-01

To examine whether childhood traumatic stress increased the risk of developing autoimmune diseases as an adult. Retrospective cohort study of 15,357 adult health maintenance organization members enrolled in the Adverse Childhood Experiences (ACEs) Study from 1995 to 1997 in San Diego, California, and eligible for follow-up through 2005. ACEs included childhood physical, emotional, or sexual abuse; witnessing domestic violence; growing up with household substance abuse, mental illness, parental divorce, and/or an incarcerated household member. The total number of ACEs (ACE Score range = 0-8) was used as a measure of cumulative childhood stress. The outcome was hospitalizations for any of 21 selected autoimmune diseases and 4 immunopathology groupings: T- helper 1 (Th1) (e.g., idiopathic myocarditis); T-helper 2 (Th2) (e.g., myasthenia gravis); Th2 rheumatic (e.g., rheumatoid arthritis); and mixed Th1/Th2 (e.g., autoimmune hemolytic anemia). Sixty-four percent reported at least one ACE. The event rate (per 10,000 person-years) for a first hospitalization with any autoimmune disease was 31.4 in women and 34.4 in men. First hospitalizations for any autoimmune disease increased with increasing number of ACEs (p < .05). Compared with persons with no ACEs, persons with >or=2 ACEs were at a 70% increased risk for hospitalizations with Th1, 80% increased risk for Th2, and 100% increased risk for rheumatic diseases (p < .05). Childhood traumatic stress increased the likelihood of hospitalization with a diagnosed autoimmune disease decades into adulthood. These findings are consistent with recent biological studies on the impact of early life stress on subsequent inflammatory responses.

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.

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.

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.

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.

Adverse Childhood Experiences and Childhood Autobiographical Memory Disturbance

ERIC Educational Resources Information Center

Brown, David W.; Anda, Robert F.; Edwards, Valerie J.; Felitti, Vincent J.; Dube, Shanta R.; Giles, Wayne H.

2007-01-01

Objective: To examine relationships between childhood autobiographical memory disturbance (CAMD) and adverse childhood experiences (ACEs) which are defined as common forms of child maltreatment and related traumatic stressors. Methods: We use the ACE score (an integer count of eight different categories of ACEs) as a measure of cumulative exposure…

Light Microsopy Module, International Space Station Premier Automated Microscope

NASA Technical Reports Server (NTRS)

Meyer, William V.; Sicker, Ronald J.; Chiaramonte, Francis P.; Brown, Daniel F.; O'Toole, Martin A.; Foster, William M.; Motil, Brian J.; Abbot-Hearn, Amber Ashley; Atherton, Arthur Johnson; Beltram, Alexander;

Effect of SQ29,852, a new angiotensin converting enzyme (ACE) inhibitor with a phosphonic acid group, on the activity of angiotensin converting enzyme from human kidney.

PubMed

Hiwada, K; Inoue, Y; Kokubu, T

1990-01-01

1. An in vitro experiment was carried out to compare the inhibitory effect of SQ29,852 on human renal angiotensin converting enzyme (ACE) with those of captopril, enalapril and enalaprilat. 2. SQ29,852 strongly inhibited human renal ACE; its IC50 value was 1.5 x 10(-8) M. In terms of the IC50, SQ29,852's efficacy was about 1/10 of that of captopril and 1/28 of that of enalaprilat, but it was about 14 times more potent than enalapril. 3. SQ29,852 showed no inhibitory effects on cathepsin D, urinary kallikrein, renal renin, pepsin, trypsin and chymotrypsin. Its ACE-specificity was higher than that of captopril. 4. ACE inhibition by SQ29,852 was shown to be competitive, as revealed by Lineweaver-Burk plots. The affinity of SQ29,852 to ACE was shown to be high by a Ki value of 1.2 x 10(-8) M.

Acoustic containerless experiment system: A non-contact surface tension measurement

NASA Technical Reports Server (NTRS)

Elleman, D. D.; Wang, T. G.; Barmatz, M.

1988-01-01

The Acoustic Containerless Experiment System (ACES) was flown on STS 41-B in February 1984 and was scheduled to be reflown in 1986. The primary experiment that was to be conducted with the ACES module was the containerless melting and processing of a fluoride glass sample. A second experiment that was to be conducted was the verification of a non-contact surface tension measurement technique using the molten glass sample. The ACES module consisted of a three-axis acoustic positioning module that was inside an electric furnace capable of heating the system above the melting temperature of the sample. The acoustic module is able to hold the sample with acoustic forces in the center of the chamber and, in addition, has the capability of applying a modulating force on the sample along one axis of the chamber so that the molten sample or liquid drop could be driven into one of its normal oscillation modes. The acoustic module could also be adjusted so that it could place a torque on the molten drop and cause the drop to rotate. In the ACES, a modulating frequency was applied to the drop and swept through a range of frequencies that would include the n = 2 mode. A maximum amplitude of the drop oscillation would indicate when resonance was reached and from that data the surface tension could be calculated. For large viscosity samples, a second technique for measuring surface tension was developed. The results of the ACES experiment and some of the problems encountered during the actual flight of the experiment will be discussed.

Assessing the interrelatedness of multiple types of adverse childhood experiences and odds for poor health in South Carolina adults.

PubMed

Crouch, Elizabeth; Strompolis, Melissa; Bennett, Kevin J; Morse, Melanie; Radcliff, Elizabeth

2017-03-01

Adverse childhood experiences (ACEs) have been linked to negative health outcomes in adulthood, but little research has been done on the effect of ACEs on the health and well-being of adults in South Carolina (SC). This study analyzed a sample of 9744 respondents who participated in the 2014 South Carolina Behavioral Risk Factor Surveillance System (BRFSS) to examine the relationship among childhood experiences of physical, sexual, and emotional abuse, as well as witnessing household violence, on mental and physical health outcomes in adulthood among SC residents. Twenty-two percent of survey respondents reported poor general health (22.1%), and a smaller proportion reported high frequent mental distress in the past month (13.1%). Each category of childhood experiences was associated with an increase in the risk of poor general health. Individuals reporting three or more types of experiences were more likely to report poor health (aOR 2.89; 95% CI 2.86-2.92) than adults without such experiences. Respondents reporting three or more types of childhood adverse experiences were more likely to report frequent mental distress (aOR 3.29; 95% CI 3.26-3.33) compared to adults who did not report three or more types of adversity. Findings from the SC BRFSS highlight a connection between ACEs and negative health outcomes later in life. Given that results of this study also demonstrated that increased exposure to ACEs was associated with greater odds of negative health in adulthood, preventing adverse events such as experiencing abuse or witnessing domestic violence in childhood will have significant effects on later adult health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does continuous trusted adult support in childhood impart life-course resilience against adverse childhood experiences - a retrospective study on adult health-harming behaviours and mental well-being.

PubMed

Bellis, Mark A; Hardcastle, Katie; Ford, Kat; Hughes, Karen; Ashton, Kathryn; Quigg, Zara; Butler, Nadia

2017-03-23

Adverse childhood experiences (ACEs) including child abuse and household problems (e.g. domestic violence) increase risks of poor health and mental well-being in adulthood. Factors such as having access to a trusted adult as a child may impart resilience against developing such negative outcomes. How much childhood adversity is mitigated by such resilience is poorly quantified. Here we test if access to a trusted adult in childhood is associated with reduced impacts of ACEs on adoption of health-harming behaviours and lower mental well-being in adults. Cross-sectional, face-to-face household surveys (aged 18-69 years, February-September 2015) examining ACEs suffered, always available adult (AAA) support from someone you trust in childhood and current diet, smoking, alcohol consumption and mental well-being were undertaken in four UK regions. Sampling used stratified random probability methods (n = 7,047). Analyses used chi squared, binary and multinomial logistic regression. Adult prevalence of poor diet, daily smoking and heavier alcohol consumption increased with ACE count and decreased with AAA support in childhood. Prevalence of having any two such behaviours increased from 1.8% (0 ACEs, AAA support, most affluent quintile of residence) to 21.5% (≥4 ACEs, lacking AAA support, most deprived quintile). However, the increase was reduced to 7.1% with AAA support (≥4 ACEs, most deprived quintile). Lower mental well-being was 3.27 (95% CIs, 2.16-4.96) times more likely with ≥4 ACEs and AAA support from someone you trust in childhood (vs. 0 ACE, with AAA support) increasing to 8.32 (95% CIs, 6.53-10.61) times more likely with ≥4 ACEs but without AAA support in childhood. Multiple health-harming behaviours combined with lower mental well-being rose dramatically with ACE count and lack of AAA support in childhood (adjusted odds ratio 32.01, 95% CIs 18.31-55.98, ≥4 ACEs, without AAA support vs. 0 ACEs, with AAA support). Adverse childhood experiences negatively impact mental and physical health across the life-course. Such impacts may be substantively mitigated by always having support from an adult you trust in childhood. Developing resilience in children as well as reducing childhood adversity are critical if low mental well-being, health-harming behaviours and their combined contribution to non-communicable disease are to be reduced.

Promoting Resilience: Breaking the Intergenerational Cycle of Adverse Childhood Experiences.

PubMed

Woods-Jaeger, Briana A; Cho, Bridget; Sexton, Chris C; Slagel, Lauren; Goggin, Kathy

2018-02-01

Adverse childhood experiences (ACEs), including trauma exposure, parent mental health problems, and family dysfunction, put children at risk for disrupted brain development and increased risk for later health problems and mortality. These negative effects may be prevented by resilience promoting environments that include protective caregiving relationships. We sought to understand (1) parents' experiences of ACEs, (2) the perceived impact on parenting, (3) protective factors that buffer ACEs potential negative impact, and (4) supports and services that can reduce the number and severity of ACEs and promote resilience among children exposed to early adversity. We conducted in-depth qualitative interviews with 11 low-income, urban parents of young children who had experienced ACEs. Interviews were analyzed for emergent themes and shared with parents from the community to ensure relevance and proper interpretation. Themes from these interviews describe the potential intergenerational cycle of ACEs and key factors that can break that cycle, including parent aspirations to make children's lives better and parent nurturance and support. Parents' suggestions for intervention are also presented. Our findings illuminate protective factors and family strengths that are important to build upon when developing and implementing interventions to promote resilience among parents and children exposed to early adversity. This study benefits from highly ecologically valid data obtained from low-socioeconomic status, racial/ethnic minority parents through one-on-one in-depth interviews and interpreted with the aid of community stakeholders through a community-based participatory research approach.

DD genotype of angiotensin-converting enzyme in type 2 diabetes mellitus with renal disease in Mexican Mestizos.

PubMed

Palomo-Piñón, Silvia; Gutiérrez-Rodríguez, Margarita E; Díaz-Flores, Margarita; Sánchez-Barrera, Reyna; Valladares-Salgado, Adán; Utrera-Barillas, Dolores; Durán-Reyes, Genoveva; Galván-Duarte, Rosa E; Trinidad-Ramos, Pedro; Cruz, Miguel

2009-04-01

The DD genotype of angiotensin-converting enzyme (ACE) has been suggested as a major contributor of diabetic nephropathy in several populations. The purpose of the present study was to determine whether micro/macroalbuminuria is associated with ACE insertion/deletion (I/D) polymorphism in Mexican Mestizos with type 2 diabetes mellitus. A total of 435 patients with type 2 diabetes mellitus, of whom 233 had albuminuria, were characterized for the ACE I/D polymorphism by the polymerase chain reaction method. Clinical and biochemical characteristics and frequencies according to DD, ID and II genotypes in patients with and without albuminuria showed no significant differences. However, only females with micro/macroalbuminuria showed higher frequency of a DD genotype than those without albuminuria (27.9%, 21.2% and 10.5%, respectively; P

Ground-Based Lidar Measurements of Aerosols During ACE-2 Instrument Description, Results, and Comparisons with Other Ground-Based and Airborne Measurements

NASA Technical Reports Server (NTRS)

Welton, Ellsworth J.; Voss, Kenneth J.; Gordon, Howard R.; Maring, Hal; Smirnov, Alexander; Holben, Brent; Schmid, Beat; Livingston, John M.; Russell, Philip B.; Durkee, Philip A.;

Ground-Based Lidar Measurements of Aerosols During ACE-2: Instrument Description, Results, and Comparisons with Other Ground-Based and Airborne Measurements

NASA Technical Reports Server (NTRS)

Welton, Ellsworth J.; Voss, Kenneth J.; Gordon, Howard R.; Maring, Hal; Smirnov, Alexander; Holben, Brent; Schmid, Beat; Livingston, John M.; Russell, Philip B.; Durkee, Philip A.

2000-01-01

A micro-pulse lidar system (MPL) was used to measure the vertical and horizontal distribution of aerosols during the Aerosol Characterization Experiment 2 (ACE-2) in June and July of 1997. The MPL measurements were made at the Izana observatory (IZO), a weather station located on a mountain ridge (28 deg 18 min N, 16 deg 30 min W, 2367 m asl) near the center of the island of Tenerife, Canary Islands. The MPL was used to acquire aerosol backscatter, extinction, and optical depth profiles for normal background periods and periods influenced by Saharan dust from North Africa. System tests and calibration procedures are discussed, and an analysis of aerosol optical profiles acquired during ACE-2 is presented. MPL data taken during normal IZO conditions (no dust) showed that upslope aerosols appeared during the day and dissipated at night and that the layers were mostly confined to altitudes a few hundred meters above IZO. MPL data taken during a Saharan dust episode on 17 July showed that peak aerosol extinction values were an order of magnitude greater than molecular scattering over IZO, and that the dust layers extended to 5 km asl. The value of the dust backscatter-extinction ratio was determined to be 0.027 +/- 0.007 sr(exp -1). Comparisons of the MPL data with data from other collocated instruments showed good agreement during the dust episode.

Effect of fed-batch vs. continuous mode of operation on microbial fuel cell performance treating biorefinery wastewater

DOE PAGES

Pannell, Tyler C.; Goud, R. Kannaiah; Schell, Daniel J.; ...

2016-05-01

Bioelectrochemical systems have been shown to treat low-value biorefinery streams while recovering energy, however, low current densities and anode conversion efficiencies (ACE) limit their application. A bioanode was developed via enrichment of electroactive biofilm under fed-batch and continuous feeding conditions using corn stover-derived waste stream. The continuously-fed MFC exhibited a current density of 5.8±0.06 A/m 2 and an ACE of 39%±4. The fed-batch MFC achieved a similar current density and an ACE of 19.2%, however, its performance dropped after 36 days of operation to 1.1 A/m 2 and 0.5%, respectively. In comparison, the ACE of the continuously-fed MFC remained stablemore » achieving an ACE of 30% ± 3 after 48 days of operation. An MFC treating a biorefinery stream post fuel separation achieved a current density of 10.7±0.1 A/m 2 and an ACE of 57% ± 9 at an organic loading of 12.5 g COD/L-day. Characterization of the microbial communities indicate higher abundance of Firmicutes and Proteobacteria and lower abundance of Bacteriodetes and a higher level of Geobacter spp. (1.4% vs. 0.2%) in continuously-fed MFC vs. fed-batch MFC. Finally, the results demonstrate that limiting substrate to the equivalent maximum current that the anode can generate, maintains MFC performance over a long term for high strength wastewaters, such as those generated in the biorefinery.« less

Effect of fed-batch vs. continuous mode of operation on microbial fuel cell performance treating biorefinery wastewater

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

Pannell, Tyler C.; Goud, R. Kannaiah; Schell, Daniel J.

Bioelectrochemical systems have been shown to treat low-value biorefinery streams while recovering energy, however, low current densities and anode conversion efficiencies (ACE) limit their application. A bioanode was developed via enrichment of electroactive biofilm under fed-batch and continuous feeding conditions using corn stover-derived waste stream. The continuously-fed MFC exhibited a current density of 5.8±0.06 A/m 2 and an ACE of 39%±4. The fed-batch MFC achieved a similar current density and an ACE of 19.2%, however, its performance dropped after 36 days of operation to 1.1 A/m 2 and 0.5%, respectively. In comparison, the ACE of the continuously-fed MFC remained stablemore » achieving an ACE of 30% ± 3 after 48 days of operation. An MFC treating a biorefinery stream post fuel separation achieved a current density of 10.7±0.1 A/m 2 and an ACE of 57% ± 9 at an organic loading of 12.5 g COD/L-day. Characterization of the microbial communities indicate higher abundance of Firmicutes and Proteobacteria and lower abundance of Bacteriodetes and a higher level of Geobacter spp. (1.4% vs. 0.2%) in continuously-fed MFC vs. fed-batch MFC. Finally, the results demonstrate that limiting substrate to the equivalent maximum current that the anode can generate, maintains MFC performance over a long term for high strength wastewaters, such as those generated in the biorefinery.« less

[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.

Tailoring health-related messages for young adults with adverse childhood experiences (ACEs).

PubMed

Karatekin, Canan; Ahluwalia, Rohini; Desir, Michelle

2018-06-01

The goal was to identify factors that might affect likelihood of seeking health-related interventions for young adults with adverse childhood experiences (ACEs). We tested whether ACEs were associated with (1) regulatory focus (tendency toward promoting good outcomes versus preventing bad outcomes), and (2) patient activation (the intention to take active charge of one's health). We further tested whether promotion and prevention and patient activation were associated with each other and with health. Students at a public university (N = 321) completed online questionnaires assessing ACEs, regulatory focus, patient activation, and health. Greater childhood adversity showed small but significant associations with being a less activated patient and being less focused on promoting good outcomes. In contrast, greater childhood adversity had a much stronger association with focusing on preventing negative outcomes. Students with a more significant mental health history were more likely to have been exposed to childhood adversity, to be less activated patients, and to focus more on prevention. Results suggest that using a prevention focus may be effective in health messages aimed to reach individuals with high levels of ACEs. Furthermore, individuals with high levels of ACEs may benefit from interventions aimed at increasing patient activation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Child and Adolescent Suicide Attempts, Suicidal Behavior, and Adverse Childhood Experiences in South Africa: A Prospective Study.

PubMed

Cluver, Lucie; Orkin, Mark; Boyes, Mark E; Sherr, Lorraine

2015-07-01

This is the first known prospective study of child suicidal behavior in sub-Saharan Africa. Aims were to determine whether (1) cumulative exposure to adverse childhood experiences (ACEs) predicts later suicidality and (2) heightened risks are mediated by mental health disorder and drug/alcohol misuse. Longitudinal repeated interviews were conducted 1 year apart (97% retention) with 3,515 adolescents aged 10-18 years in South Africa (56% female; <2.5% refusal). Random selection of census enumeration areas from urban/rural sites within two provinces and door-to-door sampling included all homes with a resident adolescent. Measures included past-month suicide attempts, planning, and ideation, mental health disorders, drug/alcohol use, and ACE, for example, parental death by AIDS or homicide, abuse, and exposure to community violence. Analyses included multivariate logistic regression and multiple mediation tests. Past-month suicidality rates were 3.2% of adolescents attempting, 5.8% planning, and 7.2% reporting ideation. After controlling for baseline suicidality and sociodemographics, a strong, graded relationship was shown between cumulative ACE and all suicide behaviors 1 year later. Baseline mental health, but not drug/alcohol misuse, mediated relationships between ACE and subsequent suicidality. Suicide attempts rose from 1.9% among adolescents with no ACE to 6.3% among adolescents with >5 ACEs (cumulative odds ratio [OR], 2.46; confidence interval [CI], 1.00-6.05); for suicide planning, from 2.4% to 12.5% (cumulative OR, 4.40; CI, 2.08-9.29); and for suicide ideation, from 4.2% to 15.6% (cumulative OR, 2.99; CI, 1.68-5.53). Preventing and mitigating childhood adversities have the potential to reduce suicidality. Among adolescents already exposed to adversities, effective mental health services may buffer against future suicidality. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. 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.

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

Screening for Adverse Childhood Experiences (ACEs) in an Integrated Pediatric Care Model

ERIC Educational Resources Information Center

Purewal, Sukhdip K.; Bucci, Monica; Wang, Lisa Gutiérrez; Koita, Kadiatou; Marques, Sara Silvério; Oh, Debora; Harris, Nadine Burke

2016-01-01

Adverse childhood experiences (ACEs) are stressful or traumatic events that place children at risk of negative health, mental health, and behavioral outcomes. The Center for Youth Wellness (CYW), working in partnership with the Bayview Child Health Center (BCHC), pioneered ACE screening for children and adolescents. This article describes the…

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.

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.

Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities.

PubMed

Yoshiji, Hitoshi; Kuriyama, Shigeki; Noguchi, Ryuichi; Yoshii, Junichi; Ikenaka, Yasuhide; Yanase, Koji; Namisaki, Tadashi; Kitade, Mitsuteru; Yamazaki, Masaharu; Akahane, Takemi; Asada, Kiyoshi; Tsujimoto, Tatsuhito; Uemura, Masahito; Fukui, Hiroshi

2006-01-01

Recent studies have revealed that angiogenesis plays a pivotal role in carcinogenesis and tumor growth. We previously reported that the clinically used vitamin K(2) (VK) and angiotensin-converting enzyme inhibitor (ACE-I) exerted potent anti-angiogenic activities. The aim of our current study was to examine the combination effect of VK and ACE-I on hepatocarcinogenesis induced by diethyl-nitrosamine, and orthotopic hepatocellular carcinoma (HCC) growth in rats. When used individually, both VK and ACE-I at clinically comparable low doses exerted significant inhibitory effects on tumor development in the liver. A combination treatment of VK and ACE-I showed a more potent suppressive effect against hepatocarcinogenesis. Neovascularization increased during hepatocarcinogenesis, and VK and ACE-I significantly attenuated angiogenesis in the tumor. In orthotopic HCC transplantation, VK and ACE-I also showed marked suppressive effects against HCC development similar to those against hepatocarcinogenesis. In both experiments, the suppressive effects of VK and ACE-I against angiogenesis were similar in magnitude to their inhibitory effects against hepatocarcinogenesis and orthotopic HCC development. In the orthotopic model, VK and ACE-I treatment resulted in a marked increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. Since both VK and ACE-I are widely used in clinical practice without serious side effects, this combination therapy may be an effective new therapeutic strategy against hepatocarcinogenesis and HCC growth in the future.

Adverse Childhood Experiences and Prescribed Psychotropic Medications in Adults

PubMed Central

Anda, Robert F.; Brown, David W.; Felitti, Vincent J.; Bremner, J. Douglas; Dube, Shanta R.; Giles, Wayne H.

2011-01-01

Background Prescription drugs are one of the fastest growing healthcare costs in the United States. However, the long-term influence of child abuse and related traumatic stressors on prescriptions for psychotropic medications in adults has not been described. This study assessed the relationship of eight adverse childhood experiences (ACEs) to rates of prescriptions for psychotropic medications throughout adulthood. These ACEs included: abuse (emotional, physical, or sexual), witnessing domestic violence, growing up with substance abusing, mentally ill, or criminal household members, and parental separation/ divorce. Methods Data about ACEs were collected between 1995 and 1997 from adult health maintenance organization patients; prescription data were available from 1997 to 2004. The number of ACEs (ACE Score: maximum 8) was used as a measure of cumulative traumatic stress during childhood. The relationship of the score to rates of prescribed psychotropic drugs was prospectively assessed among 15,033 adult patients eligible for the follow-up phase of the study (mean follow-up: 6.1 years). Data were analyzed in 2006. Multivariate models were adjusted for age, race, gender, and education. Results Prescription rates increased yearly during the follow-up and in a graded fashion as the ACE Score increased (p for trend <0.001). After adjusting compared with persons with an ACE Score of 0, persons with a score of equal to or more than 5 had a nearly threefold increase in rates of psychotropic prescriptions. Graded relationships were observed between the score and prescription rates for antidepressant, anxiolytic, antipsychotic, and mood-stabilizing/bipolar medications; rates for persons with a score of equal to or more than 5 for these classes of drugs increased 3-, 2-, 10-, and 17-fold, respectively. Conclusions The strong relationship of the ACE Score to increased utilization of psychotropic medications underscores the contribution of childhood experience to the burden of adult mental illness. Moreover, the huge economic costs associated with the use of psychotropic medications provide additional incentive to address the high prevalence and consequences of childhood traumatic stressors. PMID:17478264

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.

The ACEII recombinant Trichoderma reesei QM9414 strains with enhanced xylanase production and its applications in production of xylitol from tree barks.

PubMed

Xiong, Lili; Kameshwar, Ayyappa Kumar Sista; Chen, Xi; Guo, Zhiyun; Mao, Canquan; Chen, Sanfeng; Qin, Wensheng

2016-12-28

ACEII transcription factor plays a significant role in regulating the expression of cellulase and hemicellulase encoding genes. Apart from ACEII, transcription factors such as XYR1, CRE1, HAP2/3/5 complex and ACEI function in a coordinated pattern for regulating the gene expression of cellulases and hemicellulases. Studies have demonstrated that ACEII gene deletion results in decreased total cellulase and xylanase activities with reduced transcript levels of lignocellulolytic enzymes. In this study, we have successfully transformed the ACEII transcription factor encoding gene in Trichoderma reesei to significantly improve its degrading abilities. Transformation experiments on parental strain T. reesei QM9414 has resulted in five genetically engineered strains T/Ace2-2, T/Ace2-5, T/Ace2-8, T/Ace5-4 and T/Ace10-1. Among which, T/Ace2-2 has exhibited significant increase in enzyme activity by twofolds, when compared to parental strain. The T/Ace2-2 was cultured on growth substrates containing 2% bark supplemented with (a) sugar free + MA medium (b) glucose + MA medium and (c) xylose + MA medium. The bark degradation efficiency of genetically modified T/Ace2-2 strain was assessed by analyzing the xylitol production yield using HPAEC. By 6th day, about 10.52 g/l of xylitol was produced through enzymatic conversion of bark (2% bark + MA + xylose) by the T/Ace2-2 strain and by 7th day the conversion rate was found to be 0.21 g/g. Obtained results confirmed that bark growth medium supplemented with D-xylose has profoundly increased the conversion rate of bark by T/Ace2-2 strain when compared to sugar free and glucose supplemented growth media. Results obtained from scanning electron microscopy has endorsed our current results. Bark samples inoculated with T/Ace2-2 strain has showed large number of degraded cells with clearly visible cavities and fractures, by exposing the microfibrillar interwoven complex. We propose a cost effective and ecofriendly method for the degradation of lignocellulosic biomass such as bark to produce xylitol by using genetically modified T. reesei. Efficient conversion rate and production yield obtained in our current study provides a great scope for the xylitol industries, as our method bypasses the pretreatment of bark achieving clean and low-cost xylitol production.

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.

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.

North Atlantic Aerosol Single Scattering Albedos: TARFOX and ACE-2 Results and Their Relation to Radiative Effects Derived from Satellite Optical Depths

NASA Technical Reports Server (NTRS)

Russell, P. B.; Bergstrom, R. W.; Schmid, B.; Livingston, J. M.; Redemann, J.; Quinn, P. K.; Carrico, C. M.; Rood, M. J.

2000-01-01

Bergstrom and Russell estimated direct solar radiative flux changes caused by atmospheric aerosols over the mid-latitude North Atlantic Ocean under cloud-free and cloudy conditions. They excluded African dust aerosols, primarily by restricting calculations to latitudes 25-60 N. As inputs they used midvisible aerosol optical depth (AOD) maps derived from AVHRR satellite measurements and aerosol intensive properties determined primarily in the 1996 IGAC Troposheric Aerosol Radiative Forcing Observational Experiment (TARFOX). Those aerosol intensive properties, which included optical depth wavelength dependence and spectra of single scattering albedo (SSA) and scattering asymmetry parameter, were also checked against initial properties from the 1997 North Atlantic Aerosol Characterization Experiment (ACE 2). Bergstrom and Russell investigated the sensitivity of their derived flux changes to assumed input parameters, including midvisible AOD, SSA, and scattering asymmetry parameter. Although the sensitivity of net flux change at the tropopause to SSA was moderate over the ocean (e.g., a SSA uncertainty of 0.07 produced a flux-change uncertainty of 21%), the sensitivity over common land surfaces can be much larger. Also, flux changes within and below the aerosol layer, which affect atmospheric stability, heating rates, and cloud formation and persistence, are quite sensitive to aerosol SSA. Therefore, this paper focuses on the question: "What have we learned from TARFOX and ACE 2 regarding aerosol single scattering albedo?" Three techniques were used in TARFOX to determine midvisible SSA. One of these derived SSA as a best-fit parameter in comparing radiative flux changes measured by airborne pyranometer to those computed from aerosol properties. Another technique combined airborne measurements of aerosol scattering and absorption by nephelometer and absorption photometer. A third technique obtained SSA from best-fit complex refractive indices derived by comparing vertical profiles of lidar backscatter, sunphotometer extinction, and relative size distribution. In ACE 2 midvisible SSA was determined both as a best-fit parameter in comparing measured and calculated flux changes at the surface and by combining nephelometer and absorption photometer measurements. The nephelometer/absorption-photometer results were obtained on the ACE 2 ship (10 m asl), at the Sagres, Portugal site at 50 m asl, and also on the Pelican aircraft. This paper presents and compares the TARFOX and ACE 2 SSA results from the above techniques for different situations (e.g., marine vs continental flows, "clean" vs polluted conditions). It also discusses the strengths and limitations of the techniques, including whether they describe the aerosol in its ambient state or as perturbed by sampling processes; whether they describe the aerosol at the surface, as a function of altitude, or integrated over a column; the ease of acquiring representative data sets; results obtained in tests of consistency with radiative flux changes, and the likelihood of various artifacts and errors.

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.

Mothers' Adverse Childhood Experiences and Negative Parenting Behaviors: Connecting Mothers' Difficult Pasts to Present Parenting Behavior via Reflective Functioning

ERIC Educational Resources Information Center

Kolomeyer, Ellen; Renk, Kimberly; Cunningham, Annelise; Lowell, Amanda; Khan, Maria

2016-01-01

Previous studies have supported a connection between adverse childhood experiences (ACEs) and negative outcomes in adulthood. Fewer studies have examined the connection between ACEs and parenting behaviors, however. The study described in this article examined the relationships among ACEs, reflective functioning, and negative parenting behaviors…

Renal Effects and Underlying Molecular Mechanisms of Long-Term Salt Content Diets in Spontaneously Hypertensive Rats

PubMed Central

Berger, Rebeca Caldeira Machado; Vassallo, Paula Frizera; Crajoinas, Renato de Oliveira; Oliveira, Marilene Luzia; Martins, Flávia Letícia; Nogueira, Breno Valentim; Motta-Santos, Daisy; Araújo, Isabella Binotti; Forechi, Ludimila; Girardi, Adriana Castello Costa; Santos, Robson Augusto Souza; Mill, José Geraldo

2015-01-01

Several evidences have shown that salt excess is an important determinant of cardiovascular and renal derangement in hypertension. The present study aimed to investigate the renal effects of chronic high or low salt intake in the context of hypertension and to elucidate the molecular mechanisms underlying such effects. To this end, newly weaned male SHR were fed with diets only differing in NaCl content: normal salt (NS: 0.3%), low salt (LS: 0.03%), and high salt diet (HS: 3%) until 7 months of age. Analysis of renal function, morphology, and evaluation of the expression of the main molecular components involved in the renal handling of albumin, including podocyte slit-diaphragm proteins and proximal tubule endocytic receptors were performed. The relationship between diets and the balance of the renal angiotensin-converting enzyme (ACE) and ACE2 enzymes was also examined. HS produced glomerular hypertrophy and decreased ACE2 and nephrin expressions, loss of morphological integrity of the podocyte processes, and increased proteinuria, characterized by loss of albumin and high molecular weight proteins. Conversely, severe hypertension was attenuated and renal dysfunction was prevented by LS since proteinuria was much lower than in the NS SHRs. This was associated with a decrease in kidney ACE/ACE2 protein and activity ratio and increased cubilin renal expression. Taken together, these results suggest that LS attenuates hypertension progression in SHRs and preserves renal function. The mechanisms partially explaining these findings include modulation of the intrarenal ACE/ACE2 balance and the increased cubilin expression. Importantly, HS worsens hypertensive kidney injury and decreases the expression nephrin, a key component of the slit diaphragm. PMID:26495970

Interprofessional Education on Adverse Childhood Experiences for Associate Degree Nursing Students.

PubMed

Olsen, Jeanette M; Warring, Sarah L

2018-02-01

The health impact of adverse childhood experiences (ACEs) is significant. Nurses need knowledge and must work in multidisciplinary teams to address this problem. This study examined the effects of an interprofessional education (IPE) activity with nonhealth care students on associate degree nursing (ADN) students' ACEs knowledge and perspectives on IPE. The mixed-methods approach used a quasi-experimental pretest-posttest design with an intervention and control group and thematic analysis of focus group data. Readiness for Interprofessional Learning scale mean scores indicated positive baseline IPE perspectives. Scores changed minimally for most measures in both the intervention and control groups on posttest. However, four major relevant themes related to ACEs knowledge and two related to interprofessional learning were identified. IPE with nonhealth care students is an effective way to teach ADN students about ACEs and infuse interprofessional learning in a nonuniversity setting. However, outcomes are best captured with qualitative data. [J Nurs Educ. 2018;57(2):101-105.]. Copyright 2018, SLACK Incorporated.

Clear-Sky Closure Studies of Lower Tropospheric Aerosol and Water Vapor During ACE-2 Using Airborne Sunphotometer, Airborne In-Situ, Space-Borne, and Ground-Based Measurements

NASA Technical Reports Server (NTRS)

Schmid, Beat; Livingston, John M.; Russell, Philip B.; Durkee, Philip A.; Jonsson, Haflidi H.; Collins, Donald R.; Flagan, Richard C.; Seinfeld, John H.; Gasso, Santiago; Hegg, Dean A.;

Distinct contributions of adverse childhood experiences and resilience resources: a cohort analysis of adult physical and mental health.

PubMed

Logan-Greene, Patricia; Green, Sara; Nurius, Paula S; Longhi, Dario

2014-01-01

Although evidence is rapidly amassing as to the damaging potential of early life adversities on physical and mental health, as yet few investigations provide comparative snapshots of these patterns across adulthood. This population-based study addresses this gap, examining the relationship of adverse childhood experiences (ACEs) to physical and mental health within a representative sample (n = 19,333) of adults, comparing the prevalence and explanatory strength of ACEs among four birth cohorts spanning ages 18-79. This assessment accounts for demographic and socioeconomic factors, as well as both direct and moderating effects of resilience resources (social/emotional support, life satisfaction, and sleep quality). Findings demonstrate (1) increasing trends of reported ACEs across younger cohorts, including time period shifts such as more prevalent family incarceration, substance abuse, and divorce, (2) significant bivariate as well as independent associations of ACEs with poor health within every cohort, controlling for multiple covariates (increasing trends in older age for physical health), and (3) robust patterns wherein resilience resources moderated ACEs, indicating buffering pathways that sustained into old age. Theoretical and practice implications for health professionals are discussed.

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.

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.

Adverse childhood experiences and suicide attempts among those with mental and substance use disorders.

PubMed

Choi, Namkee G; DiNitto, Diana M; Marti, C Nathan; Segal, Steven P

2017-07-01

Using the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions data, we examined the associations of ten types of adverse childhood experiences (ACEs) with (1) lifetime suicide attempts and (2) number and age of attempts among U.S. adults aged 18+. In a case-control design, suicide attempters (5.14% of the full sample) were matched with never attempters (matched sample N=3912) on nine mental and substance use disorders. ACE rates were higher among attempters (3.30 [SE=0.07]) than their matched controls (2.19 [SE=0.06]). Results from multivariable logistic regression analyses showed that sexual abuse and parental/other family member's mental illness were associated with increased odds of having attempted suicide among both genders, and emotional neglect was also a factor for men. Population attributable risk fractions for sexual abuse were 25.75% for women and 8.56% for men. Sexual abuse and a higher number of ACEs were also related to repeated suicide attempts. A higher number of ACEs was associated with a younger first attempt age. Gay/bisexual orientation in men and the lack of college education in both genders were significant covariates. In conclusion, this study underscores that ACEs are significantly associated with lifetime suicide attempts even when mental and substance use disorders are controlled. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

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.

Adverse childhood experiences and the cardiovascular health of children: a cross-sectional study

PubMed Central

2013-01-01

Background Adverse childhood experiences (ACEs), such as abuse, household dysfunction, and neglect, have been shown to increase adults’ risk of developing chronic conditions and risk factors for chronic conditions, including cardiovascular disease (CVD). Much less work has investigated the effect of ACEs on children’s physical health status that may lead to adult chronic health conditions. Therefore, the present study examined the relationship between ACEs and early childhood risk factors for adult cardiovascular disease. Methods 1 234 grade six to eight students participated in school-based data collection, which included resting measures of blood pressure (BP), heart rate (HR), body mass index (BMI) and waist circumference (WC). Parents of these children completed an inventory of ACEs taken from the Childhood Trust Events Survey. Linear regression models were used to assess the relationship between experiencing more than 4 ACEs experienced, systolic BP, HR, BMI and WC. In additional analysis, ACEs were assessed ordinally in their relationship with systolic BP, HR, and BMI as well as clinical obesity and hypertension status. Results After adjustment for family education, income, age, sex, physical activity, and parental history of hypertension, and WC for HR models, four or more ACEs had a significant effect on HR (b = 1.8 bpm, 95% CI (0.1-3.6)) BMI (b =1.1 kg/m2, 95% CI (0.5-1.8)), and WC (b = 3.6 cm, 95% CI (1.8-5.3)). A dose–response relationship between ACE accumulation and both BMI and WC was also found to be significant. Furthermore, accumulation of 4 or more ACEs was significantly associated with clinical obesity (95th percentile), after controlling for the aforementioned covariates. Conclusions In a community sample of grade six to eight children, accumulation of 4 or more ACEs significantly increased BMI, WC and resting HR. Therefore, risk factors related to reported associations between ACEs and cardiovascular outcomes among adults are identifiable in childhood suggesting earlier interventions to reduce CVD risk are required. PMID:24344611

The Relationship Between Adverse Childhood Experiences and Recidivism in a Sample of Juvenile Offenders in Community-Based Treatment.

PubMed

Wolff, Kevin T; Baglivio, Michael T; Piquero, Alex R

2017-08-01

Adverse childhood experiences (ACEs) have been identified as a key risk factor for a range of negative life outcomes, including delinquency. Much less is known about how exposure to negative experiences relates to continued offending among juvenile offenders. In this study, we examine the effect of ACEs on recidivism in a large sample of previously referred youth from the State of Florida who were followed for 1 year after participation in community-based treatment. Results from a series of Cox hazard models suggest that ACEs increase the risk of subsequent arrest, with a higher prevalence of ACEs leading to a shorter time to recidivism. The relationship between ACEs and recidivism held quite well in demographic-specific analyses. Implications for empirical research on the long-term effects of traumatic childhood events and juvenile justice policy are discussed.

Adverse Childhood Experiences among a Community of Resilient Centenarians and Seniors: Implications for a Chronic Disease Prevention Framework.

PubMed

Spencer-Hwang, Rhonda; Torres, Xochitl; Valladares, Johanny; Pasco-Rubio, Marco; Dougherty, Molly; Kim, Wonha

2018-03-11

Research has linked adverse childhood experiences (ACEs) with chronic disease in adults and diminished life span. Adverse biological embedding of ACEs potentially occurs through inflammatory mechanisms; inflammatory marker alterations are identified as candidate biomarkers for mediating health consequences. Lifestyle practices of residents of California's Loma Linda Blue Zone, one of five worldwide longevity hotspots, may provide insight into inflammation remediation and chronic disease prevention. Little research has been done on centenarians' early-life experiences or on ACEs in a longevity community. To interview centenarians and seniors in this region regarding their childhood experiences to inform chronic disease prevention frameworks. Qualitative study of Loma Linda Blue Zone community members. Childhood exposures and practices were assessed using focus groups and semistructured key informant interviews, with open-ended questions on general hardships and ACEs and supplemented with lifestyle and resiliency factor questions. Data were audiorecorded and transcribed. Integrative grounded theory methods guided coding and theming. Exposure to ACEs and practice of resiliency factors. Participants (7 centenarians and 29 seniors) reported exposure to multiple ACEs (domains: Economic deprivation, family dysfunction, and community violence). Community members reported practicing resiliency factors, each with anti-inflammatory properties suggesting mitigation of ACE-related toxic stress. This is one of the first studies of its kind to identify a community of resilient members despite their tremendous burden of ACEs. Embedding the identified resiliency factors into chronic disease prevention frameworks has potential for mitigating systemic inflammation, alleviating chronic disease burden, and promoting a culture of health.

Adverse Childhood Experiences among a Community of Resilient Centenarians and Seniors: Implications for a Chronic Disease Prevention Framework

PubMed Central

Spencer-Hwang, Rhonda; Torres, Xochitl; Valladares, Johanny; Pasco-Rubio, Marco; Dougherty, Molly; Kim, Wonha

2018-01-01

Context Research has linked adverse childhood experiences (ACEs) with chronic disease in adults and diminished life span. Adverse biological embedding of ACEs potentially occurs through inflammatory mechanisms; inflammatory marker alterations are identified as candidate biomarkers for mediating health consequences. Lifestyle practices of residents of California’s Loma Linda Blue Zone, one of five worldwide longevity hotspots, may provide insight into inflammation remediation and chronic disease prevention. Little research has been done on centenarians’ early-life experiences or on ACEs in a longevity community. Objective To interview centenarians and seniors in this region regarding their childhood experiences to inform chronic disease prevention frameworks. Design Qualitative study of Loma Linda Blue Zone community members. Childhood exposures and practices were assessed using focus groups and semistructured key informant interviews, with open-ended questions on general hardships and ACEs and supplemented with lifestyle and resiliency factor questions. Data were audiorecorded and transcribed. Integrative grounded theory methods guided coding and theming. Main Outcome Measures Exposure to ACEs and practice of resiliency factors. Results Participants (7 centenarians and 29 seniors) reported exposure to multiple ACEs (domains: Economic deprivation, family dysfunction, and community violence). Community members reported practicing resiliency factors, each with anti-inflammatory properties suggesting mitigation of ACE-related toxic stress. Conclusion This is one of the first studies of its kind to identify a community of resilient members despite their tremendous burden of ACEs. Embedding the identified resiliency factors into chronic disease prevention frameworks has potential for mitigating systemic inflammation, alleviating chronic disease burden, and promoting a culture of health. PMID:29702049

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.

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

Characterization of angiotensin-converting enzyme inhibitory activity of fermented milk produced by Lactobacillus helveticus.

PubMed

Chen, Yongfu; Li, Changkun; Xue, Jiangang; Kwok, Lai-yu; Yang, Jie; Zhang, Heping; Menghe, Bilige

2015-08-01

Hypertension affects up to 30% of the adult population in most countries. It is a known risk factor for cardiovascular diseases, including coronary heart disease, peripheral artery disease, and stroke. Owing to the increased health awareness of consumers, the application of angiotensin-converting enzyme (ACE)-inhibitory peptides produced by Lactobacillushelveticus to prevent or control high blood pressure has drawn wide attention. A total of 59 L. helveticus strains were isolated from traditional fermented dairy products and the ACE-inhibitory activity of the fermented milks produced with the isolated microorganisms was assayed. The ACE-inhibitory activity of 38 L. helveticus strains was more than 50%, and 3 strains (IMAU80872, IMAU80852, and IMAU80851) expressing the highest ACE-inhibitory activity were selected for further studies. Particularly, the gastrointestinal protease tolerance and thermostability of the ACE-inhibitory activity in the fermented milks were assessed. Based on these 2 criteria, IMAU80872 was found to be superior over the other 2 strains. Furthermore, IMAU80872 exhibited a high in vitro ACE-inhibitory activity at the following fermentation conditions: fermentation temperature at 40°C, inoculation concentration of 1×10(6) cfu/mL, and fermentation for 18h. Finally, by using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis, we observed changes of the metabolome along the milk fermentation process of IMAU80872. Furthermore, 6 peptides were identified, which might have ACE-inhibitory activity. In conclusion, we identified a novel ACE-inhibitory L. helveticus strain suitable for the production of fermented milk or other functional dairy products. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The Relationship of Exposure to Childhood Sexual Abuse to Other Forms of Abuse, Neglect, and Household Dysfunction during Childhood.

ERIC Educational Resources Information Center

Dong, Maxia; Anda, Robert F.; Dube, Shanta R.; Giles, Wayne H.; Felitti, Vincent J.

2003-01-01

This retrospective cohort study assessed the relationship of childhood sexual abuse (CSA) to other categories of adverse childhood experiences (ACEs), such as childhood abuse, neglect, and parental separation/divorce. Adults reporting CSA experienced a 1.6- to 3.4-fold greater likelihood of experience each category of ACE. The ACE score was also…

Solvent effect on the self-assembly of salt solvates of an antihypertensive drug azilsartan and 2-methylimidazole

NASA Astrophysics Data System (ADS)

Zhang, Xian-Rui; Zhang, Lei

2017-06-01

Three salt solvates of azilsartan (AZ) with 2-methylimidazole (2MI) (namely AZ-2MI-H2O, AZ-2MI-ACE and AZ-2MI-THF) and one azilsartan solvate (AZ-DIO, ACE = acetone, THF = tetrahydrofuran, and DIO = 1,4-dioxane) were manufactured by solvent-controlled self-assembly in aqueous-organic solutions. The experimental result of AZ-DIO shows that AZ is high affinity to DIO molecule, which has a unique ability to prevent salt formation between AZ and 2MI. Thermal studies of three salt solvates exhibit poor thermodynamic stability in environmental conditions. Solubility experiments show that AZ-2MI-ACE and AZ-2MI-THF are unstable and convert to AZ-2MI-H2O in aqueous solution, and that AZ-2MI-H2O exhibits increased solubility and retention stability in an aqueous medium compared with the commercial AZ-A crystalline form.

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.

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.

Molecular characterization and transcriptional regulation of the renin-angiotensin system genes in Senegalese sole (Solea senegalensis Kaup, 1858): differential gene regulation by salinity.

PubMed

Armesto, Paula; Cousin, Xavier; Salas-Leiton, Emilio; Asensio, Esther; Manchado, Manuel; Infante, Carlos

2015-06-01

In this work, the complete cDNA sequence encoding angiotensinogen (agt) in the euryhaline flatfish Senegalese sole was obtained. Additionally, putative coding sequences belonging to other renin-angiotensin system (RAS) genes including renin (ren), angiotensin-converting enzyme (ace), angiotensin-converting enzyme 2 (ace2), as well as angiotensin II receptor type I (agtr1) and type II (agtr2), were also identified. In juvenile tissues, agt transcripts were mainly detected in liver, ren in kidney, ace and ace2 in intestine, agtr1 in kidney and brain, and agtr2 in liver and kidney. Expression analysis of the six RAS genes after a salinity shift revealed a clear increase of agt mRNA abundance in liver just after transferring soles to high salinity water (60 ppt) with a peak at 48 h. Moreover, gene expression analysis in gills showed transcriptional regulation of ace and agtr1 at 48 h and agtr2 at 96 h after transferring soles to 60 ppt. Incubation of larvae before mouth opening (until 3 days post hatch; dph) at low salinity (10 ppt) resulted in a coordinated transcriptional up-regulation of RAS genes. Nevertheless, no differences in mRNA abundance between salinities were observed when larvae were cultivated to low salinity after mouth opening. Whole-mount in situ hybridization (WISH) signal for agt and ace in 3 dph larvae incubated at 10 ppt and 35 ppt confirmed that the former gene was mainly expressed in liver whereas the later gene was mainly located in pharynx and posterior gut, without pronounced differences in intensity between salinities. Possible physiological significance of all these results is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Polymorphism of the ACE gene and the risk of obstructive sleep apnoea.

PubMed

Chmielewska, Izabela; Mlak, Radosław; Krawczyk, Paweł; Czukiewska, Ewa; Milanowski, Janusz

2013-01-01

Obstructive sleep apnoea/hypopnea syndrome (OSA) is characterized by obstruction of the upper airway during sleep, resulting in repetitive breathing pauses accompanied by oxygen desaturation and arousal from sleep. Among the candidate genes affecting the risk of OSA, genes whose polymorphisms influence the development of diseases with similar pathogenesis such as OSA could be listed: APOE, genes for leptin and leptin receptor, TNFA1, ADRB2 and ACE (gene for angiotensin-converting enzyme). Until now there has been a confirmed relationship between ACE gene polymorphism and cardiovascular diseases, but its effect on the incidence of OSA is debatable. The aim of this study was to investigate the effect of ACE gene insertion/deletion (I/D) polymorphism on the risk of OSA. Fifty-five patients with confirmed diagnose of OSA and qualified to CPAP therapy entered the study. The control group included 50 subjects who did not complain of any sleep related symptoms. Diagnose of OSA was set on the basis of full overnight polysomnography together with Epworth Sleepiness Scale according to American Academy of Sleep Medicine guidelines. DNA was isolated from peripheral blood leukocytes with Qiagen DNA mini Kit. ACE gene polymorphism was determined in genomic DNA using allele specific polymerase chain reaction. Different sizes of PCR products were observed on agarose gel electrophoresis. There were non-significant differences in the frequency of ACE genotypes. However, allele D had significantly lower prevalence in the study group than in the control group. (χ(2) = 4.25 p = 0.04). Moreover, I allele carriers had a threefold greater risk of developing OSA (HR = 2.748, 95% CI = 1.029-7.340, p < 0.05). Analysis of ACE gene polymorphism might be useful to determine the risk of developing OSA in clinically predisposed patients.

Antioxidant and anti-inflammatory properties of an aqueous cyanophyta extract derived from Arthrospira platensis: contribution to bioactivities by the non-phycocyanin aqueous fraction.

PubMed

Jensen, Gitte S; Attridge, Victoria L; Beaman, Joni L; Guthrie, Jesse; Ehmann, Axel; Benson, Kathleen F

2015-05-01

The goal for this work was to characterize basic biological properties of a novel Arthrospira platensis-based aqueous cyanophyta extract (ACE), enriched in the known anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor phycocyanin (PC), but also containing a high level of non-PC bioactive compounds. Antioxidant properties were tested in parallel in the Folin-Ciocalteu assay (chemical antioxidant capacity) and in the cellular antioxidant protection (CAP-e) bioassay, where both the PC and the non-PC fractions contributed to the antioxidant capacity and CAP of ACE. In contrast to the COX-2 inhibition seen in the presence of PC, the inhibition of enzymatic activity of the inflammatory mediator Lipoxygenase was associated specifically with the non-PC fraction of ACE. Inhibition of formation of reactive oxygen species (ROS) was evaluated using polymorphonuclear cells from healthy human donors. The inhibition of ROS formation was seen for both the PC and non-PC fractions, with ACE showing the most robust effect. The effects of PC, non-PC, and ACE on clotting and clot lysing was tested using a modified Euglobulin fibrinolytic assay in vitro. In the presence of PC, non-PC, and ACE, the time for clot formation and lysis was not affected; however, the clots were significantly more robust. This effect was statistically significant (p<.05) at doses between 125-500 μg/mL, and returned to baseline at lower doses. Both PC and the non-PC fraction contributed to the antioxidant properties and anti-inflammatory effects, without a negative impact on blood clotting in vitro. This suggests a potential benefit for the consumable ACE extract in assisting the reduction of inflammatory conditions.

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.

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.

Shortwave Radiative Fluxes, Solar-Beam Transmissions, and Aerosol Properties: TARFOX and ACE-2 Find More Absorption from Flux Radiometry than from Other Measurements

NASA Technical Reports Server (NTRS)

Russell, Philip B.; Redemann, J.; Schmid, B.; Livingston, J. M.; Bergstrom, R. W.; Ramirez, S. A.; Hipskind, R. Stephen (Technical Monitor)

2001-01-01

The Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the Second Aerosol Characterization Experiment (ACE-2) made simultaneous measurements of shortwave radiative fluxes, solar-beam transmissions, and the aerosols affecting those fluxes and transmissions. Besides the measured fluxes and transmissions, other obtained properties include aerosol scattering and absorption measured in situ at the surface and aloft; aerosol single scattering albedo retrieved from skylight radiances; and aerosol complex refractive index derived by combining profiles of backscatter, extinction, and size distribution. These measurements of North Atlantic boundary layer aerosols impacted by anthropogenic pollution revealed the following characteristic results: (1) Better agreement among different types of remote measurements of aerosols (e.g., optical depth, extinction, and backscattering from sunphotometers, satellites, and lidars) than between remote and in situ measurements; 2) More extinction derived from transmission measurements than from in situ measurements; (3) Larger aerosol absorption inferred from flux radiometry than from other measurements. When the measured relationships between downwelling flux and optical depth (or beam transmission) are used to derive best-fit single scattering albedos for the polluted boundary layer aerosol, both TARFOX and ACE-2 yield midvisible values of 0.90 +/- 0.04. The other techniques give larger single scattering albedos (i.e. less absorption) for the polluted boundary layer, with a typical result of 0.95 +/- 0.04. Although the flux-based results have the virtue of describing the column aerosol unperturbed by sampling, they are subject to questions about representativeness and other uncertainties (e.g., unknown gas absorption). Current uncertainties in aerosol single scattering albedo are large in terms of climate effects. They also have an important influence on aerosol optical depths retrieved from satellite radiances. More tests are needed of the consistency among different methods and of the effects of changing humidity on aerosol.

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.

DD Genotype of ACE I/D Polymorphism Might Confer Protection against Dental Caries in Polish Children.

PubMed

Olszowski, Tomasz; Adler, Grażyna; Janiszewska-Olszowska, Joanna; Safranow, Krzysztof; Chlubek, Dariusz

2015-01-01

The aim of the study was to examine the frequencies of the genotypes and alleles of ACE insertion/deletion (I/D) polymorphism and their association with dental caries in a sample of Polish children. The study subjects were 120 children with dental caries experience (cases) and 41 caries-free individuals (controls). The genotyping was performed using polymerase chain reaction. The genotype distributions of ACE I/D polymorphism were not statistically different between carious and control children. However, we found a borderline overrepresentation of the II + ID genotypes versus the DD genotype in the carious compared to the control group (69.2% and 51.2%, respectively, p = 0.057). Logistic regression analysis adjusted for age and sex revealed that I allele carriage was a significant predictor of dental caries susceptibility (OR = 2.14, 95% CI = 1.02-4.49, p = 0.041). In conclusion, the DD genotype of ACE I/D polymorphism might be protective against dental caries in Polish children. © 2015 S. Karger AG, Basel.

Relationships between adverse childhood experiences and adult mental well-being: results from an English national household survey.

PubMed

Hughes, Karen; Lowey, Helen; Quigg, Zara; Bellis, Mark A

2016-03-03

Individuals' childhood experiences can strongly influence their future health and well-being. Adverse childhood experiences (ACEs) such as abuse and dysfunctional home environments show strong cumulative relationships with physical and mental illness yet less is known about their effects on mental well-being in the general population. A nationally representative household survey of English adults (n = 3,885) measuring current mental well-being (Short Edinburgh-Warwick Mental Well-being Scale SWEMWBS) and life satisfaction and retrospective exposure to nine ACEs. Almost half of participants (46.4 %) had suffered at least one ACE and 8.3 % had suffered four or more. Adjusted odds ratios (AORs) for low life satisfaction and low mental well-being increased with the number of ACEs. AORs for low ratings of all individual SWEMWBS components also increased with ACE count, particularly never or rarely feeling close to others. Of individual ACEs, growing up in a household affected by mental illness and suffering sexual abuse had the most relationships with markers of mental well-being. Childhood adversity has a strong cumulative relationship with adult mental well-being. Comprehensive mental health strategies should incorporate interventions to prevent ACEs and moderate their impacts from the very earliest stages of life.

Empirical and bioinformatic characterization of buffalo (Bubalus bubalis) colostrum whey peptides & their angiotensin I-converting enzyme inhibition.

PubMed

Ashok, N R; Aparna, H S

2017-08-01

Whey based peptides are well known for their nutritional and multifunctional properties. In this context, whey proteins from buffalo colostrum & milk were digested by in vitro simulation digestion and analyzed by nano-LC-MS/MS. Functional protein association networks, gene annotations and localization of identified proteins were carried out. An ACE inhibitory peptide sorted from the library was custom synthesized and an in vitro ACE assay was performed. The study led to the identification of 74 small peptides which were clustered into 5 gene functional groups and majority of them were secretory proteins. Among the identified peptides, majority of them were found identical to angiotensin I-converting enzyme (ACE) inhibitors, antioxidant, antimicrobial, immunomodulatory and opioidal peptides. An octapeptide (m/z - 902.51, IQKVAGTW) synthesized was found to inhibit ACE with an IC 50 of 300±2µM. The present investigation thus establishes newer vista for food derived peptides having ACE inhibitory potential for nutraceutical or therapeutic applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Acquisition and Analysis of NASA Ames Sunphotometer Measurements during SAGE III Validation Campaigns and other Tropospheric and Stratospheric Research Missions

NASA Technical Reports Server (NTRS)

Livingston, John M.

2004-01-01

NASA Cooperative Agreement NCC2-1251 provided funding from April 2001 through December 2003 for Mr. John Livingston of SRI International to collaborate with NASA Ames Research Center scientists and engineers in the acquisition and analysis of airborne sunphotometer measurements during various atmospheric field studies. Mr. Livingston participated in instrument calibrations at Mauna Loa Observatory, pre-mission hardware and software preparations, acquisition and analysis of sunphotometer measurements during the missions, and post-mission analysis of data and reporting of scientific findings. The atmospheric field missions included the spring 2001 Intensive of the Asian Pacific Regional Aerosol Characterization Experiment (ACE-Asia), the Asian Dust Above Monterey-2003 (ADAM-2003) experiment, and the winter 2003 Second SAGE III Ozone Loss and Validation Experiment (SOLVE II).

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

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.

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.

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-1 experiment

NASA Image and Video Library

2013-06-24

In the International Space Stations Destiny laboratory,NASA astronaut Karen Nyberg,Expedition 36 flight engineer,speaks into a microphone while conducting a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

Contemplating Synergistic Algorithms for the NASA ACE Mission

NASA Technical Reports Server (NTRS)

Mace, Gerald G.; Starr, David O.; Marchand, Roger; Ackerman, Steven A.; Platnick, Steven E.; Fridlind, Ann; Cooper, Steven; Vane, Deborah G.; Stephens, Graeme L.

2013-01-01

ACE is a proposed Tier 2 NASA Decadal Survey mission that will focus on clouds, aerosols, and precipitation as well as ocean ecosystems. The primary objective of the clouds component of this mission is to advance our ability to predict changes to the Earth's hydrological cycle and energy balance in response to climate forcings by generating observational constraints on future science questions, especially those associated with the effects of aerosol on clouds and precipitation. ACE will continue and extend the measurement heritage that began with the A-Train and that will continue through Earthcare. ACE planning efforts have identified several data streams that can contribute significantly to characterizing the properties of clouds and precipitation and the physical processes that force these properties. These include dual frequency Doppler radar, high spectral resolution lidar, polarimetric visible imagers, passive microwave and submillimeter wave radiometry. While all these data streams are technologically feasible, their total cost is substantial and likely prohibitive. It is, therefore, necessary to critically evaluate their contributions to the ACE science goals. We have begun developing algorithms to explore this trade space. Specifically, we will describe our early exploratory algorithms that take as input the set of potential ACE-like data streams and evaluate critically to what extent each data stream influences the error in a specific cloud quantity retrieval.

Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial.

PubMed

Campbell, Craig; McMillan, Hugh J; Mah, Jean K; Tarnopolsky, Mark; Selby, Kathryn; McClure, Ty; Wilson, Dawn M; Sherman, Matthew L; Escolar, Diana; Attie, Kenneth M

2017-04-01

ACE-031 is a fusion protein of activin receptor type IIB and IgG1-Fc, which binds myostatin and related ligands. It aims to disrupt the inhibitory effect on muscle development and provide potential therapy for myopathies like Duchenne muscular dystrophy (DMD). ACE-031 was administered subcutaneously every 2-4 weeks to DMD boys in a randomized, double-blind, placebo-controlled, ascending-dose trial. The primary objective was safety evaluation. Secondary objectives included characterization of pharmacokinetics and pharmacodynamics. ACE-031 was not associated with serious or severe adverse events. The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. A trend for maintenance of the 6-minute walk test (6MWT) distance in the ACE-031 groups compared with a decline in the placebo group (not statistically significant) was noted, as was a trend for increased lean body mass and bone mineral density (BMD) and reduced fat mass. ACE-031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT. Non-muscle-related adverse events contributed to the decision to discontinue the study. Myostatin inhibition is a promising therapeutic approach for DMD. Muscle Nerve 55: 458-464, 2017. © 2016 Wiley Periodicals, Inc.

Genomic and physiological characterization of a laboratory-isolated Acinetobacter schindleri ACE strain that quickly and efficiently catabolizes acetate.

PubMed

Sigala, Juan-Carlos; Suárez, Brisa Paola; Lara, Alvaro R; Borgne, Sylvie Le; Bustos, Patricia; Santamaría, Rosa Isela; González, Víctor; Martinez, Alfredo

2017-07-01

An Acinetobacter strain, designated ACE, was isolated in the laboratory. Phylogenetic tests and average nucleotide identity value comparisons suggested that ACE belongs to the species Acinetobacterschindleri. We report for the first time the complete genome sequence of an A. schindleri strain, which consists of a single circular chromosome of 3 001 209 bp with an overall DNA G+C content of 42.9 mol% and six plasmids that account for 266 844 bp of extrachromosomal material. The presence or absence of genes related to carbon catabolism and antibiotic resistance were in agreement with the phenotypic characterization of ACE. This strain grew faster and with a higher biomass yield on acetate than the reference strain Acinetobacter baylyi ADP1. However, ACE did not use aromatic compounds and was unable to grow on common carbon sources, such as glucose, xylose, glycerol or citrate. The gluconeogenic and the catechol pathways are complete in ACE, but compounds that are converted to protocatechuate did not sustain growth since some genes of this pathway are missing. Likewise, this strain could not grow on glucose because it lacks the genes of the Entner-Doudoroff pathway. Minimal inhibitory concentration data showed that ACE was susceptible to most of the antimicrobial agents recommended for the clinical treatment of Acinetobacter spp. Some genes related to a possible human-microbe interaction were found in the ACE genome. ACE is likely to have a low pathogenic risk, as is the case with other A. schindleri strains. These results provide a valuable reference for broadening the knowledge of the biology of Acinetobacter.

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

Adverse childhood experiences: Evidence for screening beyond preventive visits.

PubMed

Duke, Naomi N; Borowsky, Iris W

2018-07-01

Primary efforts to screen for adverse childhood experiences (ACE/ACEs) are often focused on the well child/adolescent visit. The purpose of this study was to examine relationships between ACEs and youth likelihood of receiving preventive care. Data are from 126,868 students in the 8th, 9th, and 11th grades who participated in the 2016 Minnesota Student Survey, an anonymous, self-report questionnaire examining youth behaviors, experiences, and perceptions. Logistic regression models were used to determine if 10 types of ACEs, including abuse, household dysfunction, and food and housing insecurity were associated with receipt of recommended preventive medical and dental care after adjustment for demographic covariates and self-reported health. ACEs scores were entered into regression models to test for cumulative impact of adversities on preventive care outcomes. More than one third (38.5%) of youth identified at least one ACE, most commonly having a parent or guardian who had ever been in jail or prison. Each type of ACE was significantly associated with reduced odds of receiving preventive care in the last year. Associations with food insecurity were of greatest magnitude, associated with 0.32 [CI: 0.64-0.72] to 0.54 [CI: 0.44-0.49] decreased odds of receiving care. Each one point increase in the total ACE score was associated with 0.07 [CI: 0.92-0.94] to 0.15 [CI: 0.84-0.86] decreased odds of having had a preventive care visit in the last year. Findings add to the growing literature documenting significant relationships between ACEs and health, in this case, youth missing opportunities to receive recommended surveillance and anticipatory guidance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Human Trafficking of Minors and Childhood Adversity in Florida.

PubMed

Reid, Joan A; Baglivio, Michael T; Piquero, Alex R; Greenwald, Mark A; Epps, Nathan

2017-02-01

To examine the link between human trafficking of minors and childhood adversity. We compared the prevalence of adverse childhood experiences (ACEs) and cumulative childhood adversity (ACE score) among a sample of 913 juvenile justice-involved boys and girls in Florida for whom the Florida child abuse hotline accepted human trafficking abuse reports between 2009 and 2015 with those of a matched sample. ACE composite scores were higher and 6 ACEs indicative of child maltreatment were more prevalent among youths who had human trafficking abuse reports. Sexual abuse was the strongest predictor of human trafficking: the odds of human trafficking was 2.52 times greater for girls who experienced sexual abuse, and there was a 8.21 times greater risk for boys who had histories of sexual abuse. Maltreated youths are more susceptible to exploitation in human trafficking. Sexual abuse in connection with high ACE scores may serve as a key predictor of exploitation in human trafficking for both boys and girls.

Association of adverse childhood experiences with lifetime mental and substance use disorders among men and women aged 50+ years.

PubMed

Choi, Namkee G; DiNitto, Diana M; Marti, C Nathan; Choi, Bryan Y

2017-03-01

Given growing numbers of older adults with mental and substance use disorders (MSUDs), this study examined the association between ten types of adverse childhood experiences (ACEs) and lifetime MSUDs among those aged 50+. Data (N = 14,738 for the 50+ age group) came from the 2012 to 2013 National Epidemiologic Survey on Alcohol and Related Conditions. Using multivariable binary logistic regression analyses, we examined relationships between ten ACEs and six lifetime MSUDs (major depressive disorder (MDD) and anxiety, post-traumatic stress, alcohol use, drug use, and nicotine use disorders). Gender differences were examined using tests of interaction effects and gender-separate logistic regression models. Of the sample, 53.2% of women and 50.0% of men reported at least one ACE. For both genders, parental/other adult's substance abuse was the most prevalent (22.6%), followed by physical abuse, and emotional neglect. Child abuse and neglect and parental/other adult's mental illness and substance abuse had small but consistently significant associations with MSUDs (e.g., odds ratio = 1.28, 95% CI = 1.12-1.46 for parental/other adult's substance misuse and MDD). Although the relationship between total number of ACEs and MSUDs was cumulative for both men and women, the associations of physical abuse, sexual abuse, emotional neglect, and parental separation/divorce with MSUDs were stronger among men. This study underscores the significant yet modest association between ACEs and lifetime MSUDs in late life. More research is needed to investigate why ACEs seem to have greater effects on older men and to discern the sources of gender differences in ACEs' effects.

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.

[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.

The Metabolic Response of Skeletal Muscle to Endurance Exercise Is Modified by the ACE-I/D Gene Polymorphism and Training State.

PubMed

Valdivieso, Paola; Vaughan, David; Laczko, Endre; Brogioli, Michael; Waldron, Sarah; Rittweger, Jörn; Flück, Martin

2017-01-01

The insertion/deletion polymorphism in the gene for the regulator of vascular tone, angiotensin-converting enzyme (ACE), is the prototype of a genetic influence on physical fitness and this involves an influence on capillary supply lines and dependent aerobic metabolism in skeletal muscle. The respective interaction of ACE-I/D genotype and training status on local metabolic and angiogenic reactions in exercised muscle is not known. Toward this end we characterized the metabolomic and angiogenic response in knee extensor muscle, m. vastus lateralis , in 18 untrained and 34 endurance-trained (physically active, [Formula: see text]O2max > 50 mL min -1 kg -1 ) white British men to an exhaustive bout of one-legged cycling exercise. We hypothesized that training status and ACE-I/D genotype affect supply-related muscle characteristics of exercise performance in correspondence to ACE expression and angiotensin 2 levels. ACE-I/D genotype and training status developed an interaction effect on the cross-sectional area (CSA) of m. vastus lateralis and mean CSA of slow type fibers, which correlated with peak power output ( r ≥ 0.44). Genotype × training interactions in muscle also resolved for exercise-induced alterations of 22 metabolites, 8 lipids, glycogen concentration ( p = 0.016), ACE transcript levels ( p = 0.037), and by trend for the pro-angiogenic factor tenascin-C post exercise ( p = 0.064). Capillary density ( p = 0.001), capillary-to-fiber ratio ( p = 0.010), systolic blood pressure ( p = 0.014), and exercise-induced alterations in the pro-angiogenic protein VEGF ( p = 0.043) depended on the ACE-I/D genotype alone. Our observations indicate that variability in aerobic performance in the studied subjects was in part reflected by an ACE-I/D-genotype-modulated metabolic phenotype of a major locomotor muscle. Repeated endurance exercise appeared to override this genetic influence in skeletal muscle by altering the ACE-related metabolic response and molecular aspects of the angiogenic response to endurance exercise.

The Metabolic Response of Skeletal Muscle to Endurance Exercise Is Modified by the ACE-I/D Gene Polymorphism and Training State

PubMed Central

Valdivieso, Paola; Vaughan, David; Laczko, Endre; Brogioli, Michael; Waldron, Sarah; Rittweger, Jörn; Flück, Martin

2017-01-01

The insertion/deletion polymorphism in the gene for the regulator of vascular tone, angiotensin-converting enzyme (ACE), is the prototype of a genetic influence on physical fitness and this involves an influence on capillary supply lines and dependent aerobic metabolism in skeletal muscle. The respective interaction of ACE-I/D genotype and training status on local metabolic and angiogenic reactions in exercised muscle is not known. Toward this end we characterized the metabolomic and angiogenic response in knee extensor muscle, m. vastus lateralis, in 18 untrained and 34 endurance-trained (physically active, V˙O2max > 50 mL min−1 kg−1) white British men to an exhaustive bout of one-legged cycling exercise. We hypothesized that training status and ACE-I/D genotype affect supply-related muscle characteristics of exercise performance in correspondence to ACE expression and angiotensin 2 levels. ACE-I/D genotype and training status developed an interaction effect on the cross-sectional area (CSA) of m. vastus lateralis and mean CSA of slow type fibers, which correlated with peak power output (r ≥ 0.44). Genotype × training interactions in muscle also resolved for exercise-induced alterations of 22 metabolites, 8 lipids, glycogen concentration (p = 0.016), ACE transcript levels (p = 0.037), and by trend for the pro-angiogenic factor tenascin-C post exercise (p = 0.064). Capillary density (p = 0.001), capillary-to-fiber ratio (p = 0.010), systolic blood pressure (p = 0.014), and exercise-induced alterations in the pro-angiogenic protein VEGF (p = 0.043) depended on the ACE-I/D genotype alone. Our observations indicate that variability in aerobic performance in the studied subjects was in part reflected by an ACE-I/D-genotype-modulated metabolic phenotype of a major locomotor muscle. Repeated endurance exercise appeared to override this genetic influence in skeletal muscle by altering the ACE-related metabolic response and molecular aspects of the angiogenic response to endurance exercise. PMID:29311951

Adverse Childhood Experiences, the Medical Home, and Child Well-Being.

PubMed

Balistreri, Kelly Stamper

2015-11-01

To examine the relationship between adverse childhood experiences (ACE), access to a medical home and a global measure of well-being among children ages 6-17 using the 2011-2012 National Survey of Children's Health. Multivariate linear regressions assessed the associations between each adverse experience and an index of child well-being with and without the impact of other events. The number of ACE was summed for each respondent and the analyses were repeated with the cumulative score as a continuous variable. The cumulative model was repeated with the addition of an interaction term between ACE score and medical home access. All analyses were conducted separately for children ages 6-11 and adolescents 12-17. Over half (53 %) of US children ages 6-17 have experienced some adverse experience during childhood. Over a quarter (28 %) has experienced at least two adverse experiences, while 15 % have experienced three or more hardships. Results suggest that the accumulation of ACE reduces well-being in children. The associations remained significant after controlling for gender, race/ethnicity, age, parental education, special health condition, and medical home access. Medical home access was consistently associated with higher levels of child well-being and was a significant moderator of the relationship between the total ACE and child well-being among children ages 6-11. Children with ACE exposure and access to a medical home have higher levels of well-being than comparable children without access to a medical home. Children exposed to adverse experiences have measurably lower levels of well-being, although younger children with access to a medical home are protected at increasing exposure.

Modeling life course pathways from adverse childhood experiences to adult mental health.

PubMed

Jones, Tiffany M; Nurius, Paula; Song, Chiho; Fleming, Christopher M

2018-06-01

Although the association between adverse childhood experiences (ACEs) and adult mental health is becoming well established, less is known about the complex and multiple pathways through which ACEs exert their influence. Growing evidence suggests that adversity early in life conveys not only early impacts, but also augments risk of stress-related life course cascades that continue to undermine health. The present study aims to test pathways of stress proliferation and stress embodiment processes linking ACEs to mental health impairment in adulthood. Data are from the 2011 Behavioral Risk Factor Surveillance Survey, a representative sample of Washington State adults ages 18 and over (N = 14,001). Structural equation modeling allowed for testing of direct and indirect effects from ACEs though low income status, experiences of adversity in adulthood, and social support. The model demonstrated that adult low income, social support and adult adversity are in fact conduits through which ACEs exert their influence on mental health impairment in adulthood. Significant indirect pathways through these variables supported hypotheses that the effect of ACEs is carried through these variables. This is among the first models that demonstrates multiple stress-related life course pathways through which early life adversity compromises adult mental health. Discussion elaborates multiple service system opportunities for intervention in early and later life to interrupt direct and indirect pathways of ACE effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adverse Childhood Experiences and the Health of University Students in Eight Provinces of Vietnam.

PubMed

Tran, Quynh Anh; Dunne, Michael P; Vo, Thang Van; Luu, Ngoc Hoat

2015-11-01

Recent systematic reviews have emphasized the need for more research into the health and social impacts of adverse childhood experiences (ACEs) in the Asia-Pacific region. This cross-sectional study was conducted with 2099 young adult students in 8 medical universities throughout Vietnam. An anonymous, self-report questionnaire included the World Health Organization ACE-International Questionnaire and standardized measures of mental and physical health. Three quarters (76%) of the students reported at least one exposure to ACEs; 21% had 4 or more ACEs. The most commonly reported adversities were emotional abuse, physical abuse, and witnessing a household member being treated violently (42.3%, 39.9%, and 34.6%, respectively). Co-occurrence of ACEs had dose-response relationships with poor mental health, suicidal ideation, and low physical health-related quality of life. This first multisite study of ACEs among Vietnamese university students provided evidence that childhood adversity is common and is significantly linked with impaired health and well-being into the early adult years. © 2015 APJPH.

Distributions and Seasonal Variations of Tropospheric Ethene (C2H4) from Atmospheric Chemistry Experiment (ACE-FTS) Solar Occultation Spectra

NASA Technical Reports Server (NTRS)

Herbin, H.; Hurtmans, D.; Clarisse, L.; Turquety, S.; Clerbaux, C.; Rinsland, Curtis P.; Boone, C.; Bernath, P. F.; Coheur, P.-F.

2009-01-01

This work reports the first measurements of ethene (C2H4) distributions in the upper troposphere. These are obtained by retrieving vertical profiles from 5 to 20 km from infrared solar occultation spectra recorded in 2005 and 2006 by the Atmospheric Chemistry Experiment-Fourier Transform Spectrometer (ACE-FTS). Background volume mixin^ ratios (vmrs) ranging from a few to about 50 pptv (10(exp -1) are measured at the different altitudes, while for certain occultations, vmrs as high as 200 pptv are observed. Zonal distributions and vertically resolved latitudinal distributions are derived for the two year period analyzed, highlighting spatial - including a North-South gradient - as well as seasonal variations. We show the latter to be more pronounced at the highest latitudes, presumably as a result of less active photochemistry during winter. The observation of C2H4 enhancements in remote Arctic regions at high latitudes is consistent with the occurrence of fast transport processes of gaseous pollution from the continents leading to Arctic haze. Citation: Herbin, H., D. Hurtmans, L. Clarisse, S. Turquety, C. Clerbaux, C. P. Rinsland, C. Boone, P. F. Bernath, and P.-F. Colieur (2009), Distributions and seasonal variations of tropospheric ethene (C2H4) from Atmospheric Chemistry Experiment (ACE-FTS) solar occultation spectra,

The Altus Cumulus Electrification Study (ACES): A UAV-based Investigation of Thunderstorms

NASA Technical Reports Server (NTRS)

Blakeslee, Richard; Arnold, James E. (Technical Monitor)

2001-01-01

The Altus Cumulus Electrification Study (ACES) is a NASA-sponsored and -led science investigation that utilizes an uninhabited aerial vehicle (UAV) to investigate thunderstorms in the vicinity of the NASA Kennedy Space Center, Florida. As part of NASA's UAV-based science demonstration program, ACES will provide a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. ACES will employ the Altus 11 aircraft, built by General Atomics-Aeronautical Systems, Inc. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high-altitude flight (up to 55,000 feet), the Altus will be flown near, and when possible, above (but never into) thunderstorms for long periods of time, allowing investigations to be conducted over entire storm life cycles. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and (3) provide Lightning Imaging Sensor validation. The ACES payload, already developed and flown on Altus, includes electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. The ACES field campaign will be conducted during July 2002 with a goal of performing 8 to 10 UAV flights. Each flight will require about 4 to 5 hours on station at altitudes from 40,000 ft to 55,000 ft. The ACES team is comprised of scientists from the NASA Marshall Space Flight Center and NASA Goddard Space Flight Centers partnered with General Atomics and IDEA, LLC.

Advanced Colloids Experiment (ACE-T1)

NASA Technical Reports Server (NTRS)

Meyer, William V.; Sicker, Ron; Brown, Dan; Eustace, John

2015-01-01

Increment 45 - 46 Science Symposium presentation of Advanced Colloids Experiment (ACE-T1) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

Recent Observations of Clouds and Precipitation by the Airborne Precipitation Radar 2nd Generation in Support of the GPM and ACE Missions

NASA Technical Reports Server (NTRS)

Durden, Stephen L.; Tanelli, Simone; Im, Eastwood

2012-01-01

In this paper we illustrate the unique dataset collected during the Global Precipitation Measurement Cold-season Precipitation Experiment (GCPEx, US/Canada Jan/Feb 2012). We will focus on the significance of these observations for the development of algorithms for GPM and ACE, with particular attention to classification and retrievals of frozen and mixed phase hydrometeors.

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.

Characterization of dipeptidylcarboxypeptidase of Leishmania donovani: a molecular model for structure based design of antileishmanials

NASA Astrophysics Data System (ADS)

Baig, Mirza Saqib; Kumar, Ashutosh; Siddiqi, Mohammad Imran; Goyal, Neena

2010-01-01

Leishmania donovani dipeptidylcarboxypeptidsae (LdDCP), an angiotensin converting enzyme (ACE) related metallopeptidase has been identified and characterized as a putative drug target for antileishmanial chemotherapy. The kinetic parameters for LdDCP with substrate, Hip-His-Leu were determined as, Km, 4 mM and Vmax, 1.173 μmole/ml/min. Inhibition studies revealed that known ACE inhibitors (captopril and bradykinin potentiating peptide; BPP1) were weak inhibitors for LdDCP as compared to human testicular ACE (htACE) with Ki values of 35.8 nM and 3.9 μM, respectively. Three dimensional model of LdDCP was generated based on crystal structure of Escherichia coli DCP (EcDCP) by means of comparative modeling and assessed using PROSAII, PROCHECK and WHATIF. Captopril docking with htACE, LdDCP and EcDCP and analysis of molecular electrostatic potentials (MEP) suggested that the active site domain of three enzymes has several minor but potentially important structural differences. These differences could be exploited for designing selective inhibitor of LdDCP thereby antileishmanial compounds either by denovo drug design or virtual screening of small molecule databases.

ACE-1 experiment

NASA Image and Video Library

2013-06-24

ISS036-E-019760 (24 June 2013) --- In the International Space Station’s Destiny laboratory, NASA astronaut Karen Nyberg, Expedition 36 flight engineer, conducts a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

Adverse childhood experiences among children placed in and adopted from foster care: Evidence from a nationally representative survey.

PubMed

Turney, Kristin; Wildeman, Christopher

2017-02-01

Despite good reason to believe that children in foster care are disproportionately exposed to adverse childhood experiences (ACEs), relatively little research considers exposure to ACEs among this group of vulnerable children. In this article, we use data from the 2011-2012 National Survey of Children's Health (NSCH), a nationally representative sample of non-institutionalized children ages 0-17 in the United States, to estimate the association between foster care placement and exposure to an array of ACEs. In adjusted logistic regression models, we find that children placed in foster care or adopted from foster care, compared to their counterparts, were more likely to experience parental divorce or separation, parental death, parental incarceration, parental abuse, violence exposure, household member mental illness, and household member substance abuse. These children were also more likely to experience ACEs than children across different thresholds of socioeconomic disadvantage (e.g., children in households with incomes below the poverty line) and across different family structures (e.g., children in single-mother families). These results advance our understanding of how children in foster care, an already vulnerable population, are disproportionately exposed to ACEs. This exposure, given the link between ACEs and health, may have implications for children's health and wellbeing throughout the life course. Copyright © 2016 Elsevier Ltd. All rights reserved.

Kinetic and structural characterization of amyloid-β peptide hydrolysis by human angiotensin-1-converting enzyme.

PubMed

Larmuth, Kate M; Masuyer, Geoffrey; Douglas, Ross G; Schwager, Sylva L; Acharya, K Ravi; Sturrock, Edward D

2016-03-01

Angiotensin-1-converting enzyme (ACE), a zinc metallopeptidase, consists of two homologous catalytic domains (N and C) with different substrate specificities. Here we report kinetic parameters of five different forms of human ACE with various amyloid beta (Aβ) substrates together with high resolution crystal structures of the N-domain in complex with Aβ fragments. For the physiological Aβ(1-16) peptide, a novel ACE cleavage site was found at His14-Gln15. Furthermore, Aβ(1-16) was preferentially cleaved by the individual N-domain; however, the presence of an inactive C-domain in full-length somatic ACE (sACE) greatly reduced enzyme activity and affected apparent selectivity. Two fluorogenic substrates, Aβ(4-10)Q and Aβ(4-10)Y, underwent endoproteolytic cleavage at the Asp7-Ser8 bond with all ACE constructs showing greater catalytic efficiency for Aβ(4-10)Y. Surprisingly, in contrast to Aβ(1-16) and Aβ(4-10)Q, sACE showed positive domain cooperativity and the double C-domain (CC-sACE) construct no cooperativity towards Aβ(4-10)Y. The structures of the Aβ peptide-ACE complexes revealed a common mode of peptide binding for both domains which principally targets the C-terminal P2' position to the S2' pocket and recognizes the main chain of the P1' peptide. It is likely that N-domain selectivity for the amyloid peptide is conferred through the N-domain specific S2' residue Thr358. Additionally, the N-domain can accommodate larger substrates through movement of the N-terminal helices, as suggested by the disorder of the hinge region in the crystal structures. Our findings are important for the design of domain selective inhibitors as the differences in domain selectivity are more pronounced with the truncated domains compared to the more physiological full-length forms. The atomic coordinates and structure factors for N-domain ACE with Aβ peptides 4-10 (5AM8), 10-16 (5AM9), 1-16 (5AMA), 35-42 (5AMB) and (4-10)Y (5AMC) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, USA (http://www.rcsb.org/). © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Requirements for an Advanced Ocean Radiometer

NASA Technical Reports Server (NTRS)

Meister, Gerhard; McClain, Charles R.; Ahmad, Ziauddin; Bailey, Sean W.; Barnes, Robert A.; Brown, Steven; Eplee, Robert E.; Franz, Bryan; Holmes, Alan; Monosmith, W. Bryan;

Cooling Properties of the Shuttle Advanced Crew Escape Spacesuit: Results of an Environmental Chamber Experiment

NASA Technical Reports Server (NTRS)

Hamilton, Douglas; Gillis, David; Bue, Grant; Son, Chan; Norcross, Jason; Kuznetz, Larry; Chapman, Kirt; Chhipwadia, Ketan; McBride, Tim

2008-01-01

The shuttle crew wears the Advanced Crew Escape Spacesuit (ACES) to protect themselves from cabin decompression and to support bail out during landing. ACES is cooled by a liquid-cooled garment (LCG) that interfaces to a heat exchanger that dumps heat into the cabin. The ACES outer layer is made of Gore-Tex(Registered TradeMark), permitting water vapor to escape while containing oxygen. The crew can only lose heat via insensible water losses and the LCG. Under nominal landing operations, the average cabin temperature rarely exceeds 75 F, which is adequate for the ACES to function. Problem A rescue shuttle will need to return 11 crew members if the previous mission suffers a thermal protection system failure, preventing it from returning safely to Earth. Initial analysis revealed that 11 crew members in the shuttle will increase cabin temperature at wheel stop above 80 F, which decreases the ACES ability to keep crew members cool. Air flow in the middeck of the shuttle is inhomogeneous and some ACES may experience much higher temperatures that could cause excessive thermal stress to crew members. Methods A ground study was conducted to measure the cooling efficiency of the ACES at 75 F, 85 F, and 95 F at 50% relative humidity. Test subjects representing 5, 50, and 95 percentile body habitus of the astronaut corps performed hand ergometry keeping their metabolic rate at 400, 600, and 800 BTU/hr for one hour. Core temperature was measured by rectal probe and skin, while inside and outside the suit. Environmental chamber wall and cooling unit inlet and outlet temperatures were measured using high-resolution thermistors ( 0.2 C). Conclusions Under these test conditions, the ACES was able to protect the core temperature of all test subjects, however thermal stress due to high insensible losses and skin temperature and skin heat flow may impact crew performance. Further research should be performed to understand the impact on cognitive performance.

Family Adversity and Resilience Measures in Pediatric Acute Care Settings.

PubMed

O'Malley, Donna M; Randell, Kimberly A; Dowd, M Denise

2016-01-01

Adverse childhood experiences (ACEs) impact health across the life course. The purpose of this study was to identify caregiver ACEs, current adversity, and resilience in families seeking care in pediatric acute care settings. Study aims included identifying demographic characteristics, current adversities, and resilience measures associated with caregiver ACEs ≥4. A cross-sectional survey study design was used and a convenience sample (n = 470) recruited at emergency and urgent care settings of a large Midwest pediatric hospital system. Measures were self-reported. The original 10-item ACEs questionnaire measured caregiver past adversity. Current adversity was measured using the 10-item IHELP. The six-item Brief Resiliency Scale measured resilience, and WHO-5 Well-Being Index was used to measure depressive affect. Compared to participants with ACEs score of 0-3 participants with ACEs ≥4 were more likely to have multiple current adversities, increased risk of depression, and lower resilience. Caregivers using pediatric acute care settings carry a high burden of ACEs and current adversities. Caregiver ACEs are associated with current child experiences of adversity. Caregivers socioeconomic status and education level may not be an accurate indicator of a family's risks or needs. Pediatric acute care settings offer opportunities to access, intervene, and prevent childhood adversity. © 2016 Wiley Periodicals, Inc.

Managing fecal incontinence in patients with myelomeningocele in Sub-Saharan Africa: Role of antegrade continence enema (ACE).

PubMed

Ibrahim, Musa; Ismail, Nasiru Jinjiri; Mohammad, Mohammad Aminu; Ismail, Hassan; Ahmed, Misbahu Haruna; Femi, Owolabi Lukman; Suwaid, Mohammed Abba

2017-04-01

Neural tube defects (NTDs) are among the major causes of sphincter dysfunctions. Fecal incontinence (FI) because of myelomeningocele (MMC) leads to problems with social acceptability and decreased quality of life (QOL), life satisfaction in addition to other morbidities. This is a report of experience with antegrade continence enema (ACE) in the management of FI in patients with MMC in an African set-up. A retrospective review of 23 children and young adults with FI because of MMC managed with ACE from October 2008 to September 2015 from African Specialist Hospital. The clinical outcomes have been analyzed. From October 2008 to September 2015, a total of thirty-two n=32 patients underwent ACE procedure after repair of MMC associated with FI. Available data of 23 (71.87%) patients were reviewed retrospectively. Mean age at which ACE was created was 6.43±3.83years, range (3.5-17.8) years, median 5years. Follow-up after ACE creation was (0.5-6.9) years, median 2.6years. There were full continence in 13 (56.52%), partial continence in 8 (34.78%) and failure in 2 (8.69%). There were 16 (69.56%) complications and 4 (17.39%) minor post ACE surgery revisions. Mean PedQOL ( ™ ) score before ACE and then 5, 10, and 15months after ACE were 47.86±13.83, range (20.4-66.0) vs 88.34±7.11, range (77.9-98.6); p=0.000, 88.9±6.44 range (76.9-98.5); p=0.000, 89.01±6.50, range (76.9-98.88) p=0.000 respectively. Mean parental/caregiver satisfaction score for 15 (65.21%) patients aged 6years and below using modified visual analogue scale (VAS) 1 to 10 before ACE and after were 3.06±0.79, range (2-4), median 3 vs 8.0±1.30, range (5-10), median 8; (p=0.000) while 8 (34.78%) patients aged above 6years were able to assess their satisfactions score before and after ACE creation with mean of 1.75±0.70, range (1-3), median 2 vs 7.75±1.03, range (6-9) median 8; (p=0.000). ACE has satisfactory outcomes in an African set-up in patients with MMC associated with FI. Multidisciplinary approach to neurogenic FI should be encouraged in such set-ups. Copyright © 2017 Elsevier Inc. All rights reserved.

Daughter-Specific Transcription Factors Regulate Cell Size Control in Budding Yeast

PubMed Central

Di Talia, Stefano; Wang, Hongyin; Skotheim, Jan M.; Rosebrock, Adam P.; Futcher, Bruce; Cross, Frederick R.

2009-01-01

In budding yeast, asymmetric cell division yields a larger mother and a smaller daughter cell, which transcribe different genes due to the daughter-specific transcription factors Ace2 and Ash1. Cell size control at the Start checkpoint has long been considered to be a main regulator of the length of the G1 phase of the cell cycle, resulting in longer G1 in the smaller daughter cells. Our recent data confirmed this concept using quantitative time-lapse microscopy. However, it has been proposed that daughter-specific, Ace2-dependent repression of expression of the G1 cyclin CLN3 had a dominant role in delaying daughters in G1. We wanted to reconcile these two divergent perspectives on the origin of long daughter G1 times. We quantified size control using single-cell time-lapse imaging of fluorescently labeled budding yeast, in the presence or absence of the daughter-specific transcriptional regulators Ace2 and Ash1. Ace2 and Ash1 are not required for efficient size control, but they shift the domain of efficient size control to larger cell size, thus increasing cell size requirement for Start in daughters. Microarray and chromatin immunoprecipitation experiments show that Ace2 and Ash1 are direct transcriptional regulators of the G1 cyclin gene CLN3. Quantification of cell size control in cells expressing titrated levels of Cln3 from ectopic promoters, and from cells with mutated Ace2 and Ash1 sites in the CLN3 promoter, showed that regulation of CLN3 expression by Ace2 and Ash1 can account for the differential regulation of Start in response to cell size in mothers and daughters. We show how daughter-specific transcriptional programs can interact with intrinsic cell size control to differentially regulate Start in mother and daughter cells. This work demonstrates mechanistically how asymmetric localization of cell fate determinants results in cell-type-specific regulation of the cell cycle. PMID:19841732

A novel angiotensin-І converting enzyme (ACE) inhibitory peptide from gastrointestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein: Biochemical characterization and molecular docking study.

PubMed

Wu, Qiongying; Jia, Junqiang; Yan, Hui; Du, Jinjuan; Gui, Zhongzheng

2015-06-01

Silkworm pupa (Bombyx mori) protein was hydrolyzed using gastrointestinal endopeptidases (pepsin, trypsin and α-chymotrypsin). Then, the hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and RP-HPLC. A novel ACE inhibitory peptide, Ala-Ser-Leu, with the IC50 value of 102.15μM, was identified by IT-MS/MS. This is the first report of Ala-Ser-Leu from natural protein. Lineweaver-Burk plots suggest that the peptide is a competitive inhibitor against ACE. The molecular docking studies revealed that the ACE inhibition of Ala-Ser-Leu is mainly attributed to forming very strong hydrogen bonds with the S1 pocket (Ala354) and the S2 pocket (Gln281 and His353). The results indicate that silkworm pupa (B. mori) protein or its gastrointestinal protease hydrolysate could be used as a functional ingredient in auxiliary therapeutic foods against hypertension. Copyright © 2014 Elsevier Inc. All rights reserved.

Joseph Rudinger memorial lecture: Unexpected functions of angiotensin converting enzyme, beyond its enzymatic activity.

PubMed

Martinez, Jean

2017-10-01

Angiotensin converting enzyme (ACE) is a well-known enzyme, largely studied for its action on hypertension, as it produces angiotensin II from angiotensin I. This paper describes two original behaviours of ACE. We showed that ACE could hydrolyse gastrin, a neuropeptide from the gastrointestinal tract, releasing the C-terminal amidated dipeptide H-Asp-Phe-NH 2 . This dipeptide is believed to be involved in the gastrin-induced acid secretion in the stomach. This hypothetic mechanism of action of gastrin resulted in a strategy to rationally design gastrin receptor antagonists. Beyond, we showed that the brain renin angiotensin system (RAS) could be activated by a new characterized peptide named acein, resulting in stimulation of dopamine release within the striatum. This new and original 'receptor-like' activity for brain membrane-bound ACE is quite significant taking into account the role of dopamine in the brain, particularly in neurodegenerative diseases. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

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

Advanced Colloids Experiment (Temperature Controlled) - ACE-T9

NASA Technical Reports Server (NTRS)

Marr, David W. M.; Meyer, William V.; Sicker, Ronald; Bailey, Kelly; Eustace, John G.

2017-01-01

Increment 53 - 54 Science Symposium presentation of Advanced Colloids Experiment (ACE-T9) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

Advanced Colloids Experiment (Temperature Controlled) - ACE-T6

NASA Technical Reports Server (NTRS)

Meyer, William V.; Sicker, Ron; Bailey, Kelly; Eustace, John; Abbott-Hearn, Amber; Lynch, Matthew

2016-01-01

Increment 51 - 52 Science Symposium presentation of Advanced Colloids Experiment (ACE-T6) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

Advanced Colloids Experiment (Temperature Controlled) - ACE-T6

NASA Technical Reports Server (NTRS)

Meyer, William V.; Sicker, Ronald J.; Bailey, Kelly; Eustace, John; Lynch, Matthew

2017-01-01

Increment 53 - 54 Science Symposium presentation of Advanced Colloids Experiment (ACE-T6) to RPO. The purpose of this event is for Principal Investigators to present their science objectives, testing approach, and measurement methods to agency scientists, managers, and other investigators.

Light Microscopy Module: International Space Station Premier Automated Microscope

NASA Technical Reports Server (NTRS)

Sicker, Ronald J.; Foster, William M.; Motil, Brian J.; Meyer, William V.; Chiaramonte, Francis P.; Abbott-Hearn, Amber; Atherton, Arthur; Beltram, Alexander; Bodzioney, Christopher; Brinkman, John;

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.

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.

The Mini Alcohol Craving Experience Questionnaire: Development and Clinical Application.

PubMed

Coates, Jason M; Gullo, Matthew J; Feeney, Gerald F X; Kavanagh, David J; Young, Ross McD; Dingle, Genevieve A; May, Jon; Andrade, Jackie; Statham, Dixie J; Connor, Jason P

2017-01-01

Standardized alcohol craving scales are rarely used outside of research environments despite recognized clinical utility. Scale length is a key barrier to more widespread application. A brief measure of alcohol craving is needed to improve research and treatment of alcohol use disorders (AUDs). Grounded in the Elaborated Intrusion Theory of Desire, the Alcohol Craving Experience (ACE) Questionnaire comprises two 11-item self-report scales that assess past-week frequency and maximum strength of alcohol craving. This study aimed to create a brief version of the ACE while maintaining psychometric integrity and clinical utility. Patients attending a university hospital alcohol and drug outpatient service for the treatment of AUD completed the ACE as part of a questionnaire battery. Three patient samples were utilized: 519 patients with pretreatment and outcome data, 228 patients with pretreatment data, and 66 patients who completed the ACE at treatment sessions 1 and 2. The Frequency scale of the ACE possessed greater clinical utility and predictive validity than the Strength scale. Revision of the Frequency measure produced a 5-item "Mini Alcohol Craving Experience" (MACE) Questionnaire. Satisfactory validity (construct, predictive, concurrent, convergent, and incremental) and reliability (internal and test-retest) were maintained. A 1 standard deviation increase in pretreatment MACE score was associated with a 54 percentage increase in the odds of patient lapse or dropout. The MACE provides a brief, theoretically, and psychometrically robust measure of alcohol craving suitable for use with AUD populations in time-limited clinical and research settings. Copyright © 2016 by the Research Society on Alcoholism.

Adverse childhood experiences and psychosocial well-being of women who were in foster care as children.

PubMed

Bruskas, Delilah; Tessin, Dale H

2013-01-01

Research has shown that many children in foster care later have psychosocial problems as adults; this is often attributed to cumulative adversities and a lack of supportive caregivers. The risk factors associated with foster care, such as maternal separation and multiple placements, often counteract many protective factors that can ameliorate the effects of childhood adversities. This study assessed the relationship between adverse childhood experiences (ACEs) and psychosocial well-being in women who were in foster care as children. A total of 101 women aged 18-71 years (mean, 36.83 [12.95] years) completed an anonymous online survey based on the 10-item ACE Questionnaire, the Sense of Coherence questionnaire, and the General Health Questionnaire. More than 56% of respondents were identified as experiencing current psychological distress. Sense of coherence scores (mean, 54.26 [15.35]) showed a significant inverse association with both General Health Questionnaire (mean, 14.83 [5.88]) and ACE (mean, 5.68 [2.90]) scores (r = -0.64 and -0.31, respectively) and 97% reported at least 1 ACE, 70% reported ≥ 5 and 33% reported ≥ 8. Linear regressions indicated that ACEs reported to occur before foster care were associated with lower levels of sense of coherence (8%) and higher levels of psychological distress (6%). Physical neglect and living in a dysfunctional household (parental loss, maternal abuse, or household member associated with substance abuse or prison) significantly decreased during foster care by 16 and 19 percentage points, respectively. Rates of emotional and physical abuse did not change. The number of ACEs was associated with the level of psychological distress. Our findings suggest that children entering the foster care system are already vulnerable and at risk of experiencing ACEs during foster care and psychological distress during adulthood. Measures implemented to protect children must not cause more harm than good. Social services that preserve and strengthen the family unit and reduce the number of ACEs both before and during foster care are recommended. Social workers and clinicians who are trained to address and manage the unique developmental needs of children in foster care may help reduce the effects of ACEs and optimize developmental health.

ACE-1 experiment

NASA Image and Video Library

2013-06-24

ISS036-E-019830 (24 June 2013) --- In the International Space Station’s Destiny laboratory, NASA astronaut Karen Nyberg, Expedition 36 flight engineer, speaks into a microphone while conducting a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

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.

Atmospheric Chemistry Experiment (ACE) Measurements of Tropospheric and Stratospheric Chemistry and Long-Term Trends

NASA Technical Reports Server (NTRS)

Rinsland, Curtis P.; Bernath, Peter; Boone, Chris; Nassar, Ray

2007-01-01

We highlight chemistry and trend measurement results from the Atmospheric Chemistry Experiment (ACE) which is providing precise middle troposphere to the lower thermosphere measurements with a 0.02/cm resolution Fourier transform spectrometer covering 750-4400/cm

Corticolimbic Connectivity Mediates the Relationship between Adverse Childhood Experiences and Symptom Severity in Borderline Personality Disorder.

PubMed

Vai, Benedetta; Sforzini, Laura; Visintini, Raffaele; Riberto, Martina; Bulgarelli, Chiara; Ghiglino, Davide; Melloni, Elisa; Bollettini, Irene; Poletti, Sara; Maffei, Cesare; Benedetti, Francesco

2018-06-01

The interaction between biological and environmental factors (especially adverse childhood experiences, ACEs) plays a crucial role in the development and maintenance of borderline personality disorder (BPD). These factors act influencing BPD core features such as pervasive instability in affect regulation, impulse control, social cognition, and interpersonal relationships. In line with this perspective, abnormalities in social cognition and related neurobiological underpinnings could mediate the relationship between ACEs and psychopathological manifestations in adulthood. In a sample of 14 females, functional connectivity (FC) analyses were performed modeling the interaction between ACEs and corticolimbic dysregulation during emotional processing and its relationship with BPD symptom severity. ACEs were associated with a dampening of the negative FC between (1) the right amygdala (Amy) and right dorsolateral prefrontal cortex (DLPFC) and between (2) the left Amy and bilateral DLPFC, right precuneus, left cerebellum and left dorsomedial prefrontal cortex during emotional processing. The connectivity between right Amy and DLPFC mediates the relationship between childhood adversities and BPD symptomatology. Furthermore, the negative FC between Amy and DLPFC, postcentral gyrus, the vermis of cerebellum and precuneus was also associated with BPD symptom severity, with a weaker negative coupling between Amy and these regions being related to a worse BPD psychopathology. Our results confirm the role of ACEs in contributing to social cognition impairments in BPD and related symptomatology from a neurobiological perspective. © 2018 S. Karger AG, Basel.

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.

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.

Impact of Adverse Childhood Experiences on Intimate Partner Violence Perpetration among Sri Lankan Men

PubMed Central

Fonseka, Ruvani W.; Minnis, Alexandra M.; Gomez, Anu Manchikanti

2015-01-01

In Sri Lanka, over one in three women experience intimate partner violence (IPV) victimization in their lifetime, making it a serious public health concern. Adverse childhood experiences (ACEs) such as child abuse and neglect, witnessing domestic violence, parental separation, and bullying are also widespread. Studies in Western settings have shown positive associations between ACEs and IPV perpetration in adulthood, but few have examined this relationship in a non-Western context. In the present study, we examined the association of ACEs with IPV perpetration among Sri Lankan men surveyed for the UN Multi-Country Study on Men and Violence in Asia and the Pacific. We found statistically significant positive associations between the number of ACE categories (ACE score) and emotional, financial, physical, and sexual IPV perpetration among Sri Lankan men. We analyzed the contributions of each ACE category and found that childhood abuse was strongly associated with perpetration of IPV in adulthood, with sexual abuse associated with the greatest increase in odds of perpetration (Adjusted odds ratio 2.36; 95% confidence interval: 1.69, 3.30). Witnessing abuse of one’s mother was associated with the greatest increase in the odds of perpetrating physical IPV (AOR 1.82; 95% CI: 1.29, 2.58), while lack of a male parental figure was not associated with physical IPV perpetration (AOR 0.76; 95% CI: 0.53, 1.09). These findings support a social learning theory of IPV perpetration, in which children who are exposed to violence learn to perpetrate IPV in adulthood. They also suggest that in Sri Lanka, being raised in a female-headed household does not increase the risk of IPV perpetration in adulthood compared to being raised in a household with a male parental figure. The relationship between being raised in a female-headed household (the number of which increased dramatically during Sri Lanka’s recent civil war) and perpetration of IPV warrants further study. Interventions that aim to decrease childhood abuse in Sri Lanka could both protect children now and reduce IPV in the future, decreasing violence on multiple fronts. PMID:26295577

Family-centered prevention ameliorates the association between adverse childhood experiences and prediabetes status in young black adults.

PubMed

Brody, Gene H; Yu, Tianyi; Chen, Edith; Miller, Gregory E

2017-07-01

Individuals exposed to adverse childhood experiences (ACEs) are vulnerable to various health problems later in life. This study was designed to determine whether participation in an efficacious program to enhance supportive parenting would ameliorate the association between ACEs and prediabetes status at age 25. Rural African American parents and their 11-year-old children (N=390) participated in the Strong African American Families (SAAF) program or a control condition. Each youth at age 25 provided a total ACEs score and a blood sample from which overnight fasting glucose was assayed. Logistic regression equations were used to test the hypotheses. The logistic regression analyses revealed a significant interaction between total ACEs and random assignment to SAAF or control, OR=0.56, 95% CI [0.36, 0.88]. Follow-up analyses indicated that, for participants in the control condition, a 1-point increase in ACEs was associated with a 37.3% increase in risk of having prediabetes. ACEs were not associated with the likelihood of having prediabetes among participants in the SAAF condition. Control participants with high total ACEs scores were 3.54 times more likely to have prediabetes than were SAAF participants with similar scores. This study indicated that participation at age 11 in a randomized controlled trial designed to enhance supportive parenting ameliorated the association of ACEs with prediabetes at age 25. If substantiated, these findings may provide a strategy for preventing negative health consequences of ACEs. Copyright © 2017 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.

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.

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.

Adverse childhood experiences in children with autism spectrum disorder.

PubMed

Hoover, Daniel W; Kaufman, Joan

2018-03-01

Recent years have shown an uptick in studies assessing bullying and other adverse childhood experiences (ACEs) in children with autism spectrum disorder (ASD). This article reviews extant findings, and points to gaps in the literature. Children with ASD are bullied by peers at a rate three to four times that of nondisabled peers with negative impacts on academic functioning and mental health symptoms, including increased risk for suicidality. Children with ASD are also at enhanced risk for other ACES, particularly parental divorce and income insufficiency, and as observed in the general population, children with ASD who experience an increased number of ACES are at elevated risk for comorbid psychiatric and medical health problems. Children with ASD with an elevated number of ACES also experience a delay in ASD diagnosis and treatment initiation. There is no evidence of increased risk of child maltreatment within the ASD population. As bullying and other adverse experiences are common and associated with deleterious outcomes in children with ASD, there is a need for additional research on intervention strategies to prevent and mitigate the impact of these experiences. Ongoing work on the assessment of trauma experiences and PTSD symptoms in children on the spectrum is also needed.

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

Correlations among self-esteem, aggression, adverse childhood experiences and depression in inmates of a female juvenile correctional facility in Japan.

PubMed

Matsuura, Naomi; Hashimoto, Toshiaki; Toichi, Motomi

2009-08-01

The purpose of this study was to examine the following hypothesis: (i) Self-esteem and aggressiveness, adverse childhood experiences (ACE), and a depressive tendency interact with each other. (ii) The subjects show a strong depressive tendency, and each of the other factors exerts a main effect on, and interacts with, the depressive tendency. The subjects were 91 juveniles (all female) admitted to a female juvenile correctional facility between November 2005 and December 2006. They were aged 15-19 years, with a mean age of 17.0 (SD = 1.18) years. Self-esteem scale, aggression scale, ACE questionnaire, and depression scale were conducted. Significant main effects (R(2) = 0.50, P < 0.001) on the depression score were observed in self-esteem (beta = -0.41, P < 0.001) and aggression (beta = 0.21, P < 0.05). Self-esteem, aggression, ACE, and depression were found to be interrelated. Low self-esteem was also shown to exert marked effects on various factors. About half of the inmates of the facility were depressed, and the main effects of self-esteem, aggression, and the ACE score were shown to influence the depression score.

Relationship between adverse childhood experiences and homelessness and the impact of axis I and II disorders.

PubMed

Roos, Leslie E; Mota, Natalie; Afifi, Tracie O; Katz, Laurence Y; Distasio, Jino; Sareen, Jitender

2013-12-01

We investigated the links between homelessness associated with serious mental and physical healthy disparities and adverse childhood experiences (ACEs) in nationally representative data, with Axis I and II disorders as potential mediators. We examined data from the National Epidemiologic Survey of Alcohol and Related Conditions in 2001-2002 and 2004-2005, and included 34,653 participants representative of the noninstitutionalized US population who were 20 years old or older. We studied the variables related to 4 classes of Axis I disorders, all 10 Axis II personality disorders, a wide range of ACEs, and a lifetime history of homelessness. Analyses revealed high prevalences of each ACE in individuals experiencing lifetime homelessness (17%-60%). A mediation model with Axis I and II disorders determined that childhood adversities were significantly related to homelessness through direct effects (adjusted odd ratios = 2.04, 4.24) and indirect effects, indicating partial mediation. Population attributable fractions were also reported. Although Axis I and II disorders partially mediated the relationship between ACEs and homelessness, a strong direct association remained. This novel finding has implications for interventions and policy. Additional research is needed to understand relevant causal pathways.

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

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.

Association between Adverse Childhood Experiences and Diagnosis of Cancer

PubMed Central

Brown, Monique J.; Thacker, Leroy R.; Cohen, Steven A.

2013-01-01

Objective Adverse childhood experiences (ACEs) are linked to multiple adverse health outcomes. This study examined the association between ACEs and cancer diagnosis. Methods Data from the 2010 Behavioral Risk Factor Surveillance System (BRFSS) survey were used. The BRFSS is the largest ongoing telephone health survey, conducted in all US states, the District of Columbia, Puerto Rico, Guam and the U.S. Virgin Islands, and provides data on a variety of health issues among the non-institutionalized adult population. Principal component analysis (PCA) was used to derive components for ACEs. Multivariable logistic regression models were used to provide adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between ACE components and overall, childhood and adulthood cancer, adjusting for confounders such as age, gender, race/ethnicity, income, educational status, marital status, and insurance status. Results Approximately 62% of respondents reported being exposed to ACEs and about one in ten respondents reported ever having been diagnosed with cancer. Component 1, which had the sexual abuse variables with the highest weights, was significantly associated with adulthood cancer (adjusted OR: 1.21; 95% CI: 1.03–1.43). Conclusion The association between ACEs and adulthood cancer may be attributable to disease progression through association of ACEs with risk factors for other chronic diseases. More research should focus on the impact of sexual abuse ACEs and adverse health outcomes. PMID:23776494

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

Arctic Stratus Cloud Properties and Their Effect on the Surface Radiation Budget: Selected Cases from FIRE ACE

NASA Technical Reports Server (NTRS)

Doug, Xiquan; Mace, Gerald G.; Minnis, Patrick; Young, David F.

2001-01-01

To study Arctic stratus cloud properties and their effect on the surface radiation balance during the spring transition season, analyses are performed using data taken during three cloudy and two clear days in May 1998 as part of the First ISCCP Regional Experiment (FIRE) Arctic Cloud Experiment (ACE). Radiative transfer models are used in conjunction with surface- and satellite-based measurements to retrieve the layer-averaged microphysical and shortwave radiative properties. The surface-retrieved cloud properties in Cases 1 and 2 agree well with the in situ and satellite retrievals. Discrepancies in Case 3 are due to spatial mismatches between the aircraft and the surface measurements in a highly variable cloud field. Also, the vertical structure in the cloud layer is not fully characterized by the aircraft measurements. Satellite data are critical for understanding some of the observed discrepancies. The satellite-derived particle sizes agree well with the coincident surface retrievals and with the aircraft data when they were collocated. Optical depths derived from visible-channel data over snow backgrounds were overestimated in all three cases, suggesting that methods currently used in satellite cloud climatologies derive optical depths that are too large. Use of a near-infrared channel with a solar infrared channel to simultaneously derive optical depth and particle size appears to alleviate this overestimation problem. Further study of the optical depth retrieval is needed. The surface-based radiometer data reveal that the Arctic stratus clouds produce a net warming of 20 W m(exp -2) in the surface layer during the transition season suggesting that these clouds may accelerate the spring time melting of the ice pack. This surface warming contrasts with the net cooling at the top of the atmosphere (TOA) during the same period. All analysis of the complete FIRE ACE data sets will be valuable for understanding the role of clouds during the entire melting and refreezing process that occurs annually in the Arctic.

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

Adverse Childhood Experiences and Hallucinations

ERIC Educational Resources Information Center

Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

2005-01-01

Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

Accelerated Cartesian expansion (ACE) based framework for the rapid evaluation of diffusion, lossy wave, and Klein-Gordon potentials

DOE PAGES

Baczewski, Andrew David; Vikram, Melapudi; Shanker, Balasubramaniam; ...

2010-08-27

Diffusion, lossy wave, and Klein–Gordon equations find numerous applications in practical problems across a range of diverse disciplines. The temporal dependence of all three Green’s functions are characterized by an infinite tail. This implies that the cost complexity of the spatio-temporal convolutions, associated with evaluating the potentials, scales as O(N s 2N t 2), where N s and N t are the number of spatial and temporal degrees of freedom, respectively. In this paper, we discuss two new methods to rapidly evaluate these spatio-temporal convolutions by exploiting their block-Toeplitz nature within the framework of accelerated Cartesian expansions (ACE). The firstmore » scheme identifies a convolution relation in time amongst ACE harmonics and the fast Fourier transform (FFT) is used for efficient evaluation of these convolutions. The second method exploits the rank deficiency of the ACE translation operators with respect to time and develops a recursive numerical compression scheme for the efficient representation and evaluation of temporal convolutions. It is shown that the cost of both methods scales as O(N sN tlog 2N t). Furthermore, several numerical results are presented for the diffusion equation to validate the accuracy and efficacy of the fast algorithms developed here.« less

Adverse childhood experiences and the association with ever using alcohol and initiating alcohol use during adolescence.

PubMed

Dube, Shanta R; Miller, Jacqueline W; Brown, David W; Giles, Wayne H; Felitti, Vincent J; Dong, Maxia; Anda, Robert F

2006-04-01

Alcohol is the most common and frequently used drug and has the potential to cause multiple deleterious effects throughout the lifespan. Because early age at initiation of alcohol use increases this potential and programs and laws are in place to attempt to delay the onset of alcohol use, we studied the relationship between multiple adverse childhood experiences (ACEs) and both the likelihood of ever drinking and the age at initiating alcohol use. This was a retrospective cohort study of 8417 adult health maintenance organization (HMO) members in California who completed a survey about ACEs, which included childhood abuse and neglect, growing up with various forms of household dysfunction and alcohol use in adolescence and adulthood. The main outcomes measured were ever drinking and age at initiating alcohol use among ever-drinkers for four age categories: < or = 14 years (early adolescence), 15 to 17 years (mid adolescence), and 18 to 20 years (late adolescence); age > or = 21 years was the referent. The relationship between the total number of adverse childhood experiences (ACE score) and early initiation of alcohol use (< or =14 years) among four birth cohorts dating back to 1900 was also examined. Eighty-nine percent of the cohort reported ever drinking; all individual ACEs except physical neglect increased the risk of ever using alcohol (p < .05). Among ever drinkers, initiating alcohol use by age 14 years was increased two- to threefold by individual ACEs (p < .05). ACEs also accounted for a 20% to 70% increased likelihood of alcohol use initiated during mid adolescence (15-17 years). The total number of ACEs (ACE score) had a very strong graded relationship to initiating alcohol use during early adolescence and a robust but somewhat less strong relationship to initiation during mid adolescence. For each of the four birth cohorts, the ACE score had a strong, graded relationship to initiating alcohol use by age 14 years (p < .05). Adverse childhood experiences are strongly related to ever drinking alcohol and to alcohol initiation in early and mid adolescence, and the ACE score had a graded or "dose-response" relationship to these alcohol use behaviors. The persistent graded relationship between the ACE score and initiation of alcohol use by age 14 for four successive birth cohorts dating back to 1900 suggests that the stressful effects of ACEs transcend secular changes, including the increased availability of alcohol, alcohol advertising, and the recent campaigns and health education programs to prevent alcohol use. These findings strongly suggest that efforts to delay the age of onset of drinking must recognize the contribution of multiple traumatic and stressful events to alcohol-seeking behavior among children and adolescents.

Structural Evidence for a Dehydrated Intermediate in Green Fluorescent Protein Chromophore Biosynthesis

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

Pletneva, Nadya V.; Pletnev, Vladimir Z.; Lukyanov, Konstantin A.

2010-11-03

The acGFPL is the first-identified member of a novel, colorless and non-fluorescent group of green fluorescent protein (GFP)-like proteins. Its mutant aceGFP, with Gly replacing the invariant catalytic Glu-222, demonstrates a relatively fast maturation rate and bright green fluorescence ({lambda}{sub ex} = 480 nm, {lambda}{sub em} = 505 nm). The reverse G222E single mutation in aceGFP results in the immature, colorless variant aceGFP-G222E, which undergoes irreversible photoconversion to a green fluorescent state under UV light exposure. Here we present a high resolution crystallographic study of aceGFP and aceGFP-G222E in the immature and UV-photoconverted states. A unique and striking feature ofmore » the colorless aceGFP-G222E structure is the chromophore in the trapped intermediate state, where cyclization of the protein backbone has occurred, but Tyr-66 still stays in the native, non-oxidized form, with C{sup {alpha}} and C{sup {beta}} atoms in the sp{sup 3} hybridization. This experimentally observed immature aceGFP-G222E structure, characterized by the non-coplanar arrangement of the imidazolone and phenolic rings, has been attributed to one of the intermediate states in the GFP chromophore biosynthesis. The UV irradiation ({lambda} = 250-300 nm) of aceGFP-G222E drives the chromophore maturation further to a green fluorescent state, characterized by the conventional coplanar bicyclic structure with the oxidized double Tyr-66 C{sup {alpha}} = C{sup {beta}} bond and the conjugated system of {pi}-electrons. Structure-based site-directed mutagenesis has revealed a critical role of the proximal Tyr-220 in the observed effects. In particular, an alternative reaction pathway via Tyr-220 rather than conventional wild type Glu-222 has been proposed for aceGFP maturation.« 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 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

Biodegradation of the artificial sweetener acesulfame in biological wastewater treatment and sandfilters.

PubMed

Castronovo, Sandro; Wick, Arne; Scheurer, Marco; Nödler, Karsten; Schulz, Manoj; Ternes, Thomas A

2017-03-01

A considerable removal of the artificial sweetener acesulfame (ACE) was observed during activated sludge processes at 13 wastewater treatment plants (WWTPs) as well as in a full-scale sand filter of a water works. A long-term sampling campaign over a period of almost two years revealed that ACE removal in WWTPs can be highly variable over time. Nitrifying/denitrifying sequencing batch reactors (SBR) as well as aerobic batch experiments with activated sludge and filter sand from a water works confirmed that both activated sludge as well as filter sand can efficiently remove ACE and that the removal can be attributed to biologically mediated degradation processes. The lab results strongly indicated that varying ACE removal in WWTPs is not associated with nitrification processes. Neither an enhancement of the nitrification rate nor the availability of ammonium or the inhibition of ammonium monooxygenase by N-allylthiourea (ATU) affected the degradation. Moreover, ACE was found to be also degradable by activated sludge under denitrifying conditions, while being persistent in the absence of both dissolved oxygen and nitrate. Using ion chromatography coupled with high resolution mass spectrometry, sulfamic acid (SA) was identified as the predominant transformation product (TP). Quantitative analysis of ACE and SA revealed a closed mass balance during the entire test period and confirmed that ACE was quantitatively transformed to SA. Measurements of dissolved organic carbon (DOC) revealed an almost complete removal of the carbon originating from ACE, thereby further confirming that SA is the only relevant final TP in the assumed degradation pathway of ACE. A first analysis of SA in three municipal WWTP revealed similar concentrations in influents and effluents with maximum concentrations of up to 2.3 mg/L. The high concentrations of SA in wastewater are in accordance with the extensive use of SA in acid cleaners, while the degradation of ACE in WWTPs adds only a very small portion of the total load of SA discharged into surface waters. No removal of SA was observed by the biological treatment applied at these WWTPs. Moreover, SA was also stable in the aerobic batch experiments conducted with the filter sand from a water works. Hence, SA might be a more appropriate wastewater tracer than ACE due to its chemical and microbiological persistence, the negligible sorbing affinity (high negative charge density) and its elevated concentrations in WWTP effluents. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Application of plug-plug technique to ACE experiments for discovery of peptides binding to a larger target protein: a model study of calmodulin-binding fragments selected from a digested mixture of reduced BSA.

PubMed

Saito, Kazuki; Nakato, Mamiko; Mizuguchi, Takaaki; Wada, Shinji; Uchimura, Hiromasa; Kataoka, Hiroshi; Yokoyama, Shigeyuki; Hirota, Hiroshi; Kiso, Yoshiaki

2014-03-01

To discover peptide ligands that bind to a target protein with a higher molecular mass, a concise screening methodology has been established, by applying a "plug-plug" technique to ACE experiments. Exploratory experiments using three mixed peptides, mastoparan-X, β-endorphin, and oxytocin, as candidates for calmodulin-binding ligands, revealed that the technique not only reduces the consumption of the protein sample, but also increases the flexibility of the experimental conditions, by allowing the use of MS detection in the ACE experiments. With the plug-plug technique, the ACE-MS screening methodology successfully selected calmodulin-binding peptides from a random library with diverse constituents, such as protease digests of BSA. Three peptides with Kd values between 8-147 μM for calmodulin were obtained from a Glu-C endoprotease digest of reduced BSA, although the digest showed more than 70 peaks in its ACE-MS electropherogram. The method established here will be quite useful for the screening of peptide ligands, which have only low affinities due to their flexible chain structures but could potentially provide primary information for designing inhibitors against the target protein. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Psychometric properties of the Adverse Childhood Experiences Abuse Short Form (ACE-ASF) among Romanian high school students.

PubMed

Meinck, Franziska; Cosma, Alina Paula; Mikton, Christopher; Baban, Adriana

2017-10-01

Child abuse is a major public health problem. In order to establish the prevalence of abuse exposure among children, measures need to be age-appropriate, sensitive, reliable and valid. This study aimed to investigate the psychometric properties of the Adverse Childhood Experiences Questionnaire Abuse Short Form (ACE-ASF). The ACE-ASF is an 8-item, retrospective self-report questionnaire measuring lifetime physical, emotional and sexual abuse. Data from a nationally representative sample of 15-year-old, school-going adolescents (n=1733, 55.5% female) from the Romanian Health Behavior in School-Based Children Study 2014 (HBSC) were analyzed. The factorial structure of the ACE-ASF was tested with Exploratory Factor Analysis (EFA) and confirmed using Confirmatory Factor Analysis (CFA). Measurement invariance was examined across sex, and internal reliability and concurrent criterion validity were established. Violence exposure was high: 39.7% physical, 32.2% emotional and 13.1% sexual abuse. EFA established a two-factor structure: physical/emotional abuse and sexual abuse. CFA confirmed this model fitted the data well [χ2(df)=60.526(19); RMSEA=0.036; CFI/TLI=0.990/0.986]. Metric invariance was supported across sexes. Internal consistency was good (0.83) for the sexual abuse scale and poor (0.57) for the physical/emotional abuse scale. Concurrent criterion validity confirmed hypothesized relationships between childhood abuse and health-related quality of life, life satisfaction, self-perceived health, bullying victimization and perpetration, externalizing and internalizing behaviors, and multiple health complaints. Results support the ACE-ASF as a valid measure of physical, emotional and sexual abuse in school-aged adolescents. However, the ACE-ASF combines spanking with other types of physical abuse when this should be assessed separately instead. Future research is needed to replicate findings in different youth populations and across age groups. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

ACE-1 experiment

NASA Image and Video Library

2013-06-24

ISS036-E-019783 (24 June 2013) --- In the International Space Station’s Destiny laboratory, a fisheye lens attached to an electronic still camera was used to capture this image of NASA astronaut Karen Nyberg, Expedition 36 flight engineer, as she conducts a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

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.

FIR ACE samples

NASA Image and Video Library

2014-06-04

ISS040-E-007368 (5 June 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, works with Advanced Colloids Experiment (ACE) samples in the Destiny laboratory of the International Space Station.

Art, Chaos, Ethics, and Science (ACES): a doctoring curriculum for emergency medicine.

PubMed

Van Groenou, Aneema A; Bakes, Katherine Mary

2006-11-01

ACES (Art, Chaos, Ethics, and Science) is a curriculum developed by 2 residents and a faculty mentor at the Denver Health Medical Center Emergency Medicine Residency Program. The goal of the ACES curriculum is 2-fold: (1) to discuss areas of clinical consequence typically outside the scope of the regular academic curriculum, such as ethical dilemmas and the challenges of professionalism; and (2) to encourage reflection on our roles as caregivers on a personal, public health, and political level. Each bimonthly "doctoring roundtable" session focuses on one of these goals, bringing local and national leaders in the field to the forum to enrich discussion. Attending physicians from academic and private settings within the residency, residents at all levels, rotating medical students, and, for the past year, emergency department nurses participate in the meetings. Thus far, regular voluntary participation has been the only measure of the ongoing program's success. In this descriptive article, we discuss the aim of the program, the curriculum, and how the ACES program enriches the residency's educational goals. Recent accreditation requirements for residency training programs mandate educational experiences that allow residents to demonstrate competency in professionalism and ethical principles. The ACES curriculum developed a unique niche in our residency, creating an open forum for passionate discussion of challenging clinical encounters, unpressured reflection on ethics and decisionmaking, and constructive personal and professional development.

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

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.

The relationship between family-based adverse childhood experiences and substance use behaviors among a diverse sample of college students.

PubMed

Forster, Myriam; Grigsby, Timothy J; Rogers, Christopher J; Benjamin, Stephanie M

2018-01-01

Research suggests that college students are an especially vulnerable subset of the population for substance use and misuse. However, despite evidence of the high prevalence of adverse childhood experiences (ACE) among students and the link between family-based ACE and substance use among older adults, this relationship remains understudied in college populations. Moreover, whether ACE represents a shared risk across substance use behaviors and ethnic groups is unknown. Data are student responses (n=2953) on the 2015 American College Health Association's National College Health Assessment II (ACHA-NCHA II) administered at one of the largest, most diverse public universities in California. Multivariable logistic and negative binomial regression models tested the association between individual and accumulated ACE and past 30-day alcohol, tobacco, marijuana, and illicit drug use, past 12-month prescription medication misuse and polysubstance use. Between 50% and 75% of students involved in substance use were ACE exposed. There was a significant dose-response relationship between ACE and substance use and polysubstance use. Although accumulated ACE increased risk for substance use, there was considerable ethnic variability in these associations. The graded effects of ACE for substance use underscore the link between family-based stressors and these behaviors in emergent adult college students. Our findings make a compelling case for investing in health initiatives that prioritize ACE screening and access to trauma-informed care in campus communities. Continued research with college populations is needed to replicate findings and clarify the role of ethnicity and culture in trauma response and help seeking behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Advanced Colloids Experiment-1 (ACE-1)

NASA Image and Video Library

2013-07-22

ISS036-E-023770 (22 July 2013) --- NASA astronaut Chris Cassidy, Expedition 36 flight engineer, conducts science work with the ongoing experiment Advanced Colloids Experiment-1 (ACE-1) inside the Fluids Integrated Rack. The experiment observes colloids, microscopic particles evenly dispersed throughout materials, with the potential for manufacturing improved materials and products on Earth. Cassidy is working at the Light Microscopy Module (LMM) in the Destiny laboratory of the International Space Station.

Multifunctional gold nanoparticles for targeted imaging of angiotensin converting enzyme design, characterization, and application

NASA Astrophysics Data System (ADS)

Ghann, William Emmanuel

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the United States with approximately one in every three death being attributed to these diseases. The overarching problem with heart diseases is that once a person has suffered from an attack, there is a high likelihood of a recurrent attack. According to the American Heart Association, approximately 785,000 Americans per year suffer from heart attacks for the first time and about half of the aforementioned experience an ensuing attack. The second attack is often fatal, and therefore relapse prevention is crucial. One of the possible ways of averting the recurrence of such an attack is through the precise monitoring of the preceding biomarkers or risk indicators. This project encompasses the design, synthesis, characterization, and application of nanoparticle-based contrast agents that can potentially be used in the monitoring of the reemergence of a biomarker expressed after a person has suffered myocardial infarction. The overexpression of this biomarker, angiotensin converting enzyme (ACE), is also associated with development of cardiac and pulmonary fibrosis. To this end, highly concentrated gold nanoparticles have been synthesized and conjugated to Lisinopril, an ACE inhibitor, for the molecular imaging of ACE using X-ray CT. Various stabilities studies were conducted to verify the resistance of this gold nanoprobe in biological relevant media. They have also been successfully used in X-ray computed tomography to visualize tissue ACE and thus render them potentially versatile in the monitoring of cardiovascular diseases. An MRI tag was also conjugated to the gold nanoparticle affording the opportunity for bimodal imaging of ACE. This contrast agent could further be used for the quantification using K-edge CT of the relationship between the amount of the said marker and its role in predicting the possibility of a successive heart attack. The prepared nanoparticle-based contrast agent could ultimately be used to monitor the levels of this biomarker in people predisposed to cardiovascular diseases due to genetic biases. It is anticipated that the targeted gold nanoparticle system could be applied in the design of similar multifunctional nanoparticles through the use of other disease-specific imaging nanoprobes.

Validation of Aura Microwave Limb Sounder HCl Measurements

NASA Technical Reports Server (NTRS)

Froidevaux, L.; Jiang, Y. B.; Lambert, A.; Livesey, N. J.; Read, W. G.; Waters, J. W.; Fuller, R. A.; Marcy, T. P.; Popp, P. J.; Gao, R. S.;

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

Transformation of acesulfame in chlorination: Kinetics study, identification of byproducts, and toxicity assessment.

PubMed

Li, Adela Jing; Wu, Pengran; Law, Japhet Cheuk-Fung; Chow, Chi-Hang; Postigo, Cristina; Guo, Ying; Leung, Kelvin Sze-Yin

2017-06-15

Acesulfame (ACE) is one of the most commonly used artificial sweeteners. Because it is not metabolized in the human gut, it reaches the aquatic environment unchanged. In the present study, the reactivity of ACE in free chlorine-containing water was investigated for the first time. The degradation of ACE was found to follow pseudo-first-order kinetics. The first-order rate increased with decreasing pH from 9.4 to 4.8 with estimated half-lives from 693 min to 2 min. Structural elucidation of the detected transformation products (TPs) was performed by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Integration of MS/MS fragments, isotopic pattern and exact mass allowed the characterization of up to 5 different TPs in the ultrapure water extracts analyzed, including two proposed new chlorinated compounds reported for the first time. Unexpectedly, several known and regulated disinfection by-products (DBPs) were present in the ACE chlorinated solution. In addition, two of the six DBPs are proposed as N-DBPs. Time-course profiles of ACE and the identified by-products in tap water and wastewater samples were followed in order to simulate the actual disinfection process. Tap water did not significantly affect degradation, but wastewater did; it reacted with the ACE to produce several brominated-DBPs. A preliminary assessment of chlorinated mixtures by luminescence inhibition of Vibrio fischeri showed that these by-products were up to 1.8-fold more toxic than the parent compound. The generation of these DBPs, both regulated and not, representing enhanced toxicity, make chlorine disinfection a controversial treatment for ACE. Further efforts are urgently needed to both assess the consequences of current water treatment processes on ACE and to develop new processes that will safely treat ACE. Human health and the health of our aquatic ecosystems are at stake. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Adverse Childhood Experiences and Behavioral Problems in Middle Childhood

PubMed Central

Berger, Lawrence M.; Slack, Kristen S.

2016-01-01

Children who have been exposed to maltreatment and other adverse childhood experiences (ACEs) are at increased risk for various negative adult health outcomes, including cancer, liver disease, substance abuse, and depression. However, the proximal associations between ACEs and behavioral outcomes during the middle childhood years have been understudied. In addition, many of the ACE studies contain methodological limitations such as reliance on retrospective reports and limited generalizability to populations of lower socioeconomic advantage. The current study uses data from the Fragile Families and Child Well being Study, a national urban birth cohort, to prospectively assess the adverse experiences and subsequent behavior problems of over 3,000 children. Eight ACE categories to which a child was exposed by age 5 were investigated: childhood abuse (emotional and physical), neglect (emotional and physical), and parental domestic violence, anxiety or depression, substance abuse, or incarceration. Results from bivariate analyses indicated that Black children and children with mothers of low education were particularly likely to have been exposed to multiple ACE categories. Regression analyses showed that exposure to ACEs is strongly associated with externalizing and internalizing behaviors and likelihood of ADHD diagnosis in middle childhood. Variation in these associations by racial/ethnic, gender, and maternal education subgroups are examined. This study provides evidence that children as young as 9 begin to show behavioral problems after exposure to early childhood adversities. PMID:27884508

Adverse childhood experiences and behavioral problems in middle childhood.

PubMed

Hunt, Tenah K A; Slack, Kristen S; Berger, Lawrence M

2017-05-01

Children who have been exposed to maltreatment and other adverse childhood experiences (ACEs) are at increased risk for various negative adult health outcomes, including cancer, liver disease, substance abuse, and depression. However, the proximal associations between ACEs and behavioral outcomes during the middle childhood years have been understudied. In addition, many of the ACE studies contain methodological limitations such as reliance on retrospective reports and limited generalizability to populations of lower socioeconomic advantage. The current study uses data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort, to prospectively assess the adverse experiences and subsequent behavior problems of over 3000 children. Eight ACE categories to which a child was exposed by age 5 were investigated: childhood abuse (emotional and physical), neglect (emotional and physical), and parental domestic violence, anxiety or depression, substance abuse, or incarceration. Results from bivariate analyses indicated that Black children and children with mothers of low education were particularly likely to have been exposed to multiple ACE categories. Regression analyses showed that exposure to ACEs is strongly associated with externalizing and internalizing behaviors and likelihood of ADHD diagnosis in middle childhood. Variation in these associations by racial/ethnic, gender, and maternal education subgroups are examined. This study provides evidence that children as young as 9 begin to show behavioral problems after exposure to early childhood adversities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sex and sexual orientation disparities in adverse childhood experiences and early age at sexual debut in the United States: results from a nationally representative sample.

PubMed

Brown, Monique J; Masho, Saba W; Perera, Robert A; Mezuk, Briana; Cohen, Steven A

2015-08-01

Adverse childhood experiences (ACEs) have been linked to early sexual debut, which has been found to be associated with multiple adverse health outcomes. Sexual minorities and men tend to have earlier sexual debut compared to heterosexual populations and women, respectively. However, studies examining the association between ACEs and early sexual debut among men and sexual minorities are lacking. The aim of this study was to examine the sex and sexual orientation disparities in the association between ACEs and age at sexual debut. Data were obtained from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic and linear regression models were used to obtain crude and adjusted estimates and 95% confidence intervals adjusting for age, race/ethnicity, income, education, insurance and marital status for the association between ACEs (neglect, physical/psychological abuse, sexual abuse, parental violence, and parental incarceration and psychopathology) and early sexual debut. Analyses were stratified by sex and sexual orientation. Larger effect estimates depicting the association between ACEs and sexual debut were seen for women compared to men, and among sexual minorities, particularly among men who have sex with men (MSM) and women who have sex with women (WSW), compared to heterosexuals. Sexual health education programs with a focus on delaying sexual debut among children and adolescents should also consider addressing ACEs, such as neglect, physical, psychological and sexual abuse, witnessing parental violence, and parental incarceration and psychopathology. Public health practitioners, researchers and sexual health education curriculum coordinators should consider these differences by sex and sexual orientation when designing these programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Sex and sexual orientation disparities in adverse childhood experiences and early age at sexual debut in the United States: Results from a nationally representative sample☆

PubMed Central

Brown, Monique J.; Masho, Saba W.; Perera, Robert A.; Mezuk, Briana; Cohen, Steven A.

2015-01-01

Adverse childhood experiences (ACEs) have been linked to early sexual debut, which has been found to be associated with multiple adverse health outcomes. Sexual minorities and men tend to have earlier sexual debut compared to heterosexual populations and women, respectively. However, studies examining the association between ACEs and early sexual debut among men and sexual minorities are lacking. The aim of this study was to examine the sex and sexual orientation disparities in the association between ACEs and age at sexual debut. Data were obtained from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Logistic and linear regression model were used to obtain crude and adjusted estimates and 95% confidence intervals adjusting for age, race/ethnicity, income, education, insurance and marital status for the association between ACEs (neglect, physical/psychological abuse, sexual abuse, parental violence, and parental incarceration and psychopathology) and early sexual debut. Analyses were stratified by sex and sexual orientation. Larger effect estimates depicting the association between ACEs and sexual debut were seen for women compared to men, and among sexual minorities, particularly among men who have sex with men (MSM) and women who have sex with women (WSW), compared to heterosexuals. Sexual health education programs with a focus on delaying sexual debut among children and adolescents should also consider addressing ACEs, such as neglect, physical, psychological and sexual abuse, witnessing parental violence, and parental incarceration and psychopathology. Public health practitioners, researchers and sexual health education curriculum coordinators should consider these differences by sex and sexual orientation when designing these programs. PMID:25804435

Relationship between breastfeeding and asthma prevalence in young children exposed to adverse childhood experiences.

PubMed

Abarca, Nancy E; Garro, Aris C; Pearlman, Deborah N

2018-03-13

To investigate if duration of supplemental breastfeeding is associated with a lower asthma risk and whether adverse childhood experiences (ACEs) early in life influence this relationship in children ages 3 to 5 years. Data were from the 2011-2012 National Survey of Children's Health, a nationally representative cross-sectional survey. Modified Poisson regression models were used to estimate incident risk ratios (IRR) for lifetime and current asthma in young children aged 3 to 5 years (n = 15,642). We tested for effect measure modification using stratified analyses. Exclusive breastfeeding for at least 6 months or supplemental breastfeeding for children ≥12 months significantly reduced the risk of lifetime asthma prevalence compared to never breastfed children (IRR 0.64; 95% CI: 0.46-0.88, p = 0.007; and IRR 0.68; 95% CI: 0.47-0.99, p = 0.044, respectively), adjusted for covariates. In stratified analyses, breastfeeding reduced the risk of lifetime asthma for children who experienced 1 ACE but not for children who experienced 2 or more ACEs. Exclusive breastfeeding for at least 6 months, with and without supplementation, appears to prevent asthma or delay its onset. The protective effect of breastfeeding was attenuated among children who experienced more than 2 ACEs. The known harmful effects that ACEs have on children's health may outweigh the benefits of breastfeeding in reducing the risk of a child developing asthma. Understanding how specific time periods in a child's life may be most affected by exposure to early life adversities, along with the protective effect of breastfeeding against asthma, are important areas of further study.

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.

Adverse childhood experiences among women prisoners: relationships to suicide attempts and drug abuse.

PubMed

Friestad, Christine; Åse-Bente, Rustad; Kjelsberg, Ellen

2014-02-01

Women prisoners are known to suffer from an accumulation of factors known to increase the risk for several major health problems. This study examines the prevalence of adverse childhood experiences (ACE) and the relationship between such experiences and suicide attempts and drug use among incarcerated women in Norway. A total of 141 women inmates (75% of all eligible) were interviewed using a structured interview guide covering information on demographics and a range of ACE related to abuse and neglect, and household dysfunction. The main outcome variables were attempted suicide and adult drug abuse. Emotional, physical and sexual abuse during childhood was experienced by 39%, 36% and 19%, respectively, and emotional and physical neglect by 31% and 33%, respectively. Looking at the full range of ACE, 17% reported having experienced none, while 34% reported having experienced more than five ACEs. After controlling for age, immigrant background and marital status, the number of ACEs significantly increased the risk of attempted suicide and current drug abuse. The associations observed between early life trauma and later health risk behaviour indicate the need for early prevention. The findings also emphasize the important role of prison health services in secondary prevention among women inmates.

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.

Pathways from childhood abuse and other adversities to adult health risks: The role of adult socioeconomic conditions.

PubMed

Font, Sarah A; Maguire-Jack, Kathryn

2016-01-01

Adverse childhood experiences (ACEs), including child abuse, have been linked with poor health outcomes in adulthood. The mechanisms that explain these relations are less understood. This study assesses whether associations of ACEs and health risks are mediated by adult socioeconomic conditions, and whether these pathways are different for maltreatment than for other types of adversities. Using the Behavioral Risk Factor Surveillance System 2012 survey (N=29,229), we employ structural equation modeling to (1) estimate associations of the number and type of ACEs with five health risks-depression, obesity, tobacco use, binge drinking, and self-reported sub-optimal health; and (2) assess whether adult socioeconomic conditions-marriage, divorce and separation, educational attainment, income and insurance status-mediate those associations. Findings suggest both direct and indirect associations between ACEs and health risks. At high numbers of ACEs, 15-20% of the association between number of ACEs and adult health risks was attributable to socioeconomic conditions. Associations of three ACEs (exposure to domestic violence, parental divorce, and residing with a person who was incarcerated) with health risks were nearly entirely explained by socioeconomic conditions in adulthood. However, child physical, emotional, and sexual abuse were significantly associated with several adult health risks, beyond the effects of other adversities, and socioeconomic conditions explained only a small portion of these associations. These findings suggest that the pathways to poor adult health differ by types of ACEs, and that childhood abuse is more likely than other adversities to have a direct impact. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence: A Putative Mechanistic Neurodevelopmental Pathway.

PubMed

Luby, Joan L; Barch, Deanna; Whalen, Diana; Tillman, Rebecca; Belden, Andy

2017-12-01

Adverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood. To investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes. A prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit. Early life adversity. Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years. The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively. Study findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.

Advancements for Active Remote Sensing of Carbon Dioxide from Space using the ASCENDS CarbonHawk Experiment Simulator: First Results

NASA Astrophysics Data System (ADS)

Obland, M. D.; Nehrir, A. R.; Lin, B.; Harrison, F. W.; Kooi, S. A.; Choi, Y.; Plant, J.; Yang, M. M.; Antill, C.; Campbell, J. F.; Ismail, S.; Browell, E. V.; Meadows, B.; Dobler, J. T.; Zaccheo, T. S.; Moore, B., III; Crowell, S.

2014-12-01

The ASCENDS CarbonHawk Experiment Simulator (ACES) is an Intensity-Modulated Continuous-Wave lidar system recently developed at NASA Langley Research Center that seeks to advance technologies and techniques critical to measuring atmospheric column carbon dioxide (CO2) mixing ratios in support of the NASA Active Sensing of CO2 Emissions over Nights, Days, and Seasons (ASCENDS) mission. These advancements include: (1) increasing the power-aperture product to approach ASCENDS mission requirements by implementing multi-aperture telescopes and multiple co-aligned laser transmitters; (2) incorporating high-efficiency, high-power Erbium-Doped Fiber Amplifiers (EDFAs); (3) developing and incorporating a high-bandwidth, low-noise HgCdTe detector and transimpedence amplifier (TIA) subsystem capable of long-duration operation on Global Hawk aircraft, and (4) advancing algorithms for cloud and aerosol discrimination. The ACES instrument architecture is being developed for operation on high-altitude aircraft and will be directly scalable to meet the ASCENDS mission requirements. ACES simultaneously transmits five laser beams: three from commercial EDFAs operating near 1571 nm, and two from the Exelis oxygen (O2) Raman fiber laser amplifier system operating near 1260 nm. The Integrated-Path Differential Absorption (IPDA) lidar approach is used at both wavelengths to independently measure the CO2 and O2 column number densities and retrieve the average column CO2 mixing ratio. The outgoing laser beams are aligned to the field of view of ACES' three fiber-coupled 17.8-cm diameter athermal telescopes. The backscattered light collected by the three telescopes is sent to the detector/TIA subsystem, which has a bandwidth of 4.7 MHz and operates service-free using a tactical dewar and cryocooler. Two key laser modulation approaches are being tested to significantly mitigate the effects of thin clouds on the retrieved CO2 column amounts. Full instrument development concluded in the spring of 2014. After ground range tests of the instrument, ACES successfully completed six test flights on the Langley Hu-25 aircraft in July, 2014, and recorded data at multiple altitudes over land and ocean surfaces with and without intervening clouds. Preliminary results from these flights will be presented in this paper.

First Measurements of the HCFC-142b Trend from Atmospheric Chemistry Experiment (ACE) Solar Occultation Spectra

NASA Technical Reports Server (NTRS)

Rinsland, Curtis P.; Chiou, Linda; Boone,Chris; Bernath, Peter; Mahieu, Emmanuel

2009-01-01

The first measurement of the HCFC-142b (CH3CClF2) trend near the tropopause has been derived from volume mixing ratio (VMR) measurements at northern and southern hemisphere mid-latitudes for the 2004-2008 time period from spaceborne solar occultation observations recorded at 0.02/cm resolution with the ACE (atmospheric chemistry experiment) Fourier transform spectrometer. The HCFC-142b molecule is currently the third most abundant HCFC (hydrochlorofluorocarbon) in the atmosphere and ACE measurements over this time span show a continuous rise in its volume mixing ratio. Monthly average measurements at northern and southern hemisphere midlatitudes have similar increase rates that are consistent with surface trend measurements for a similar time span. A mean northern hemisphere profile for the time span shows a near constant VMR at 8-20km altitude range, consistent on average for the same time span with in situ results. The nearly constant vertical VMR profile also agrees with model predictions of a long lifetime in the lower atmosphere.

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.

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

Adverse Childhood Experiences and Psychosocial Well-Being of Women Who Were in Foster Care as Children

PubMed Central

Bruskas, Delilah; Tessin, Dale H

2013-01-01

Background and Objective: Research has shown that many children in foster care later have psychosocial problems as adults; this is often attributed to cumulative adversities and a lack of supportive caregivers. The risk factors associated with foster care, such as maternal separation and multiple placements, often counteract many protective factors that can ameliorate the effects of childhood adversities. This study assessed the relationship between adverse childhood experiences (ACEs) and psychosocial well-being in women who were in foster care as children. Methods: A total of 101 women aged 18–71 years (mean, 36.83 [12.95] years) completed an anonymous online survey based on the 10-item ACE Questionnaire, the Sense of Coherence questionnaire, and the General Health Questionnaire. Results: More than 56% of respondents were identified as experiencing current psychological distress. Sense of coherence scores (mean, 54.26 [15.35]) showed a significant inverse association with both General Health Questionnaire (mean, 14.83 [5.88]) and ACE (mean, 5.68 [2.90]) scores (r = −0.64 and −0.31, respectively) and 97% reported at least 1 ACE, 70% reported ≥ 5 and 33% reported ≥ 8. Linear regressions indicated that ACEs reported to occur before foster care were associated with lower levels of sense of coherence (8%) and higher levels of psychological distress (6%). Physical neglect and living in a dysfunctional household (parental loss, maternal abuse, or household member associated with substance abuse or prison) significantly decreased during foster care by 16 and 19 percentage points, respectively. Rates of emotional and physical abuse did not change. Conclusion: The number of ACEs was associated with the level of psychological distress. Our findings suggest that children entering the foster care system are already vulnerable and at risk of experiencing ACEs during foster care and psychological distress during adulthood. Measures implemented to protect children must not cause more harm than good. Social services that preserve and strengthen the family unit and reduce the number of ACEs both before and during foster care are recommended. Social workers and clinicians who are trained to address and manage the unique developmental needs of children in foster care may help reduce the effects of ACEs and optimize developmental health. PMID:24355905

Retrieval of carbon dioxide vertical profiles from solar occultation observations and associated error budgets for ACE-FTS and CASS-FTS

NASA Astrophysics Data System (ADS)

Sioris, C. E.; Boone, C. D.; Nassar, R.; Sutton, K. J.; Gordon, I. E.; Walker, K. A.; Bernath, P. F.

2014-02-01

An algorithm is developed to retrieve the vertical profile of carbon dioxide in the 5 to 25 km altitude range using mid-infrared solar occultation spectra from the main instrument of the ACE (Atmospheric Chemistry Experiment) mission, namely the Fourier Transform Spectrometer (FTS). The main challenge is to find an atmospheric phenomenon which can be used for accurate tangent height determination in the lower atmosphere, where the tangent heights (THs) calculated from geometric and timing information is not of sufficient accuracy. Error budgets for the retrieval of CO2 from ACE-FTS and the FTS on a potential follow-on mission named CASS (Chemical and Aerosol Sounding Satellite) are calculated and contrasted. Retrieved THs are typically within 60 m of those retrieved using the ACE version 3.x software after revisiting the temperature dependence of the N2 CIA (Collision-Induced Absorption) laboratory measurements and accounting for sulfate aerosol extinction. After correcting for the known residual high bias of ACE version 3.x THs expected from CO2 spectroscopic/isotopic inconsistencies, the remaining bias for tangent heights determined with the N2 CIA is -20m. CO2 in the 5-13 km range in the 2009-2011 time frame is validated against aircraft measurements from CARIBIC, CONTRAIL and HIPPO, yielding typical biases of -1.7 ppm in the 5-13 km range. The standard error of these biases in this vertical range is 0.4 ppm. The multi-year ACE-FTS dataset is valuable in determining the seasonal variation of the latitudinal gradient which arises from the strong seasonal cycle in the Northern Hemisphere troposphere. The annual growth of CO2 in this time frame is determined to be 2.5 ± 0.7 ppm yr-1, in agreement with the currently accepted global growth rate based on ground-based measurements.

AceCloud: Molecular Dynamics Simulations in the Cloud.

PubMed

Harvey, M J; De Fabritiis, G

2015-05-26

We present AceCloud, an on-demand service for molecular dynamics simulations. AceCloud is designed to facilitate the secure execution of large ensembles of simulations on an external cloud computing service (currently Amazon Web Services). The AceCloud client, integrated into the ACEMD molecular dynamics package, provides an easy-to-use interface that abstracts all aspects of interaction with the cloud services. This gives the user the experience that all simulations are running on their local machine, minimizing the learning curve typically associated with the transition to using high performance computing services.

High-ACE Low Wage Workers: Occupational Health Nursing Research and Praxis Through a Trauma-Informed Lens.

PubMed

Rosemberg, Marie-Anne; Gultekin, Laura; Pardee, Michelle

2018-05-01

Individuals with a history of adverse childhood experiences (ACEs) disproportionately have poor mental and physical health outcomes. These experiences affect individuals across the life span extending beyond health with deleterious impact on work-related outcomes. Low-wage workers are particularly at risk. Social service and health organizations are becoming aware of the extent to which the populations they serve have been affected by these experiences. Employment support programs may serve high-ACE individuals but likely are unaware of their histories and the developmental or health deficits that result and can impinge on successful employment. Occupational health nurses may be well-positioned not only to implement trauma-informed care in workplaces but also to influence the ways in which employment services for this vulnerable group are delivered. The purpose of this article is to consider how ACEs could affect vulnerable workers. The need for trauma-informed research and praxis to advance occupational health nursing is discussed.

Adverse Childhood Experiences Are Linked to Age of Onset and Reading Recognition in Multiple Sclerosis.

PubMed

Shaw, Michael T; Pawlak, Natalie O; Frontario, Ariana; Sherman, Kathleen; Krupp, Lauren B; Charvet, Leigh E

2017-01-01

Adverse childhood experiences (ACEs) exert a psychological and physiological toll that increases risk of chronic conditions, poorer social functioning, and cognitive impairment in adulthood. To investigate the relationship between childhood adversity and clinical disease features in multiple sclerosis (MS). Sixty-seven participants with MS completed the ACE assessment and neuropsychological assessments as part of a larger clinical trial of cognitive remediation. Adverse childhood experience scores, a measure of exposure to adverse events in childhood, significantly predicted age of MS onset ( r  = -0.30, p  = 0.04). ACEs were also linked to reading recognition (a proxy for premorbid IQ) ( r  = -0.25, p  = 0.04). ACE scores were not related to age, current disability, or current level of cognitive impairment measured by the Symbol Digit Modalities Test (SDMT). Childhood adversity may increase the likelihood of earlier age of onset and poorer estimated premorbid IQ in MS.

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

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.

[Association between adverse childhood experiences with depression in adults consulting in primary care].

PubMed

Vitriol, Verónica; Cancino, Alfredo; Leiva-Bianchi, Marcelo; Serrano, Carlos; Ballesteros, Soledad; Potthoff, Soledad; Cáceres, Cristián; Ormazábal, Marcela; Asenjo, Andrea

2017-09-01

Traumatic experiences during childhood may influence the development of mental disorders during adulthood. To determine clinical and psychosocial variables that are associated with a higher frequency of adverse childhood experiences (ACE) in patients who consult for depression in Primary Health Care clinics in Chile. A socio-demographic interview, the mini international neuropsychiatric interview (MINI), a screening for ACE, a questionnaire for partner violence (PV), the Life Experiences Survey (LES) and the Hamilton Rating Scale for Depression (HRDS) were applied to 394 patients with major depression (87% women). Eighty two percent of patients had experienced at least one ACE and 43% of them reported three or more. Positive correlations were observed between the number of ACE and severity of depressive symptoms (r = 0.19; p < 0.01), psychiatric comorbidities (r = 0.23; p < 0.01), partner violence events (r = 0.31; p < 0.01), vital stressful events (r = 0.12; p < 0.01), number of depressive episodes (r = 0.16; p < 0.01), duration of the longer depressive episode (r = 0.12; p < 0.05) and suicidal tendency according to HDRS (r = 0.16; p < 0.01). An inverse correlation was observed between frequency of ACE and age at the first depressive episode (r = -0.12; p < 0.05). These data are consistent with the hypothesis that early trauma is associated with more severe and complex depressive episodes during adulthood.

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.

Relationship Between Adverse Childhood Experiences and Homelessness and the Impact of Axis I and II Disorders

PubMed Central

Roos, Leslie E.; Mota, Natalie; Afifi, Tracie O.; Katz, Laurence Y.; Distasio, Jino

2013-01-01

Objectives. We investigated the links between homelessness associated with serious mental and physical healthy disparities and adverse childhood experiences (ACEs) in nationally representative data, with Axis I and II disorders as potential mediators. Methods. We examined data from the National Epidemiologic Survey of Alcohol and Related Conditions in 2001–2002 and 2004–2005, and included 34 653 participants representative of the noninstitutionalized US population who were 20 years old or older. We studied the variables related to 4 classes of Axis I disorders, all 10 Axis II personality disorders, a wide range of ACEs, and a lifetime history of homelessness. Results. Analyses revealed high prevalences of each ACE in individuals experiencing lifetime homelessness (17%–60%). A mediation model with Axis I and II disorders determined that childhood adversities were significantly related to homelessness through direct effects (adjusted odd ratios = 2.04, 4.24) and indirect effects, indicating partial mediation. Population attributable fractions were also reported. Conclusions. Although Axis I and II disorders partially mediated the relationship between ACEs and homelessness, a strong direct association remained. This novel finding has implications for interventions and policy. Additional research is needed to understand relevant causal pathways. PMID:24148049

The Feasibility of Using Large-Scale Text Mining to Detect Adverse Childhood Experiences in a VA-Treated Population.

PubMed

Hammond, Kenric W; Ben-Ari, Alon Y; Laundry, Ryan J; Boyko, Edward J; Samore, Matthew H

2015-12-01

Free text in electronic health records resists large-scale analysis. Text records facts of interest not found in encoded data, and text mining enables their retrieval and quantification. The U.S. Department of Veterans Affairs (VA) clinical data repository affords an opportunity to apply text-mining methodology to study clinical questions in large populations. To assess the feasibility of text mining, investigation of the relationship between exposure to adverse childhood experiences (ACEs) and recorded diagnoses was conducted among all VA-treated Gulf war veterans, utilizing all progress notes recorded from 2000-2011. Text processing extracted ACE exposures recorded among 44.7 million clinical notes belonging to 243,973 veterans. The relationship of ACE exposure to adult illnesses was analyzed using logistic regression. Bias considerations were assessed. ACE score was strongly associated with suicide attempts and serious mental disorders (ORs = 1.84 to 1.97), and less so with behaviorally mediated and somatic conditions (ORs = 1.02 to 1.36) per unit. Bias adjustments did not remove persistent associations between ACE score and most illnesses. Text mining to detect ACE exposure in a large population was feasible. Analysis of the relationship between ACE score and adult health conditions yielded patterns of association consistent with prior research. Copyright © 2015 International Society for Traumatic Stress Studies.

Adverse childhood experiences and risk for suicidal behavior in male Iraq and Afghanistan veterans seeking PTSD treatment.

PubMed

Carroll, Timothy D; Currier, Joseph M; McCormick, Wesley H; Drescher, Kent D

2017-09-01

Adverse childhood experiences (ACEs) are associated with increased risk for suicide and appear to occur in disproportionately high rates among men who served in the U.S. military. However, research has yet to examine a comprehensive range of ACEs among Iraq/Afghanistan veterans with combat-related posttraumatic stress disorder (PTSD) or whether these premilitary stressors may contribute to suicidal behavior in this highly vulnerable population. A sample of 217 men entering a residential program for combat-related PTSD completed measures for ACEs, combat exposure, and lifetime suicidal ideation and attempts. The majority of patients had experienced multiple types of adversity or traumas during childhood/adolescence. In particular, 83.4% endorsed at least 1 ACE category and 41.5% reported experiencing 4 or more ACEs. When accounting for effects of deployment-related stressors, we further found that accumulation of ACEs was uniquely linked with thoughts of suicide or attempts among these patients. Namely, for every 1-point increase on the ACE Questionnaire, veterans' risk of suicidal ideation and attempts increased by 23% and 24%, respectively. This brief report provides initial evidence that veterans seeking treatment for combat-related PTSD often have extensive histories of premilitary stressors that may increase suicide risk beyond probable deployment-related traumas. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

The synthesis of 2-(5-(3-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol using sodium impregnated on activated chicken eggshells catalyst

NASA Astrophysics Data System (ADS)

Mardiana, L.; Bakri, R.; Septiarti, A.; Ardiansah, B.

2017-04-01

The novel compound of 2-(5-(3-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol as a pyrazoline derivative has been synthesized by two-steps reaction using sodium impregnated on activated chicken eggshells (Na-ACE) catalyst. Na-ACE was primarily prepared by a simple wet impregnation of NaOH solution on activated chicken eggshells solid support. The Na-ACE catalyst produced was characterized using FTIR spectrophotometer, XRD and SEM then applied in pyrazoline synthesis. First, chalcone was prepared from the reaction of 2-hydroxyacetophenone and 3-methoxybenzaldehyde by base-catalyzed aldol condensation. This product was subsequently reacted with hydrazine hydrate to give corresponding pyrazoline. The structure elucidation of the compound using FTIR, UV-Vis, LC-ESI-MS and 1H-NMR indicated the desired product has been successfully synthesized. Furthermore, the potential antioxidant activities of chalcone and pyrazoline have also been studied in-vitro using DPPH radical scavenging method. The results revealed that pyrazoline has a greater antioxidant activity than chalcone.

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

Is there a relationship between adverse childhood experiences and problem drinking behaviors? Findings from a population-based sample.

PubMed

Fang, Lin; McNeil, Sandra

2017-09-01

The study investigated the relationships between adverse childhood experiences (ACEs) and heavy and binge drinking, stratified by gender. Population-based cross-sectional study. Data were retrieved from 2012 Behavioral Risk Factor Surveillance System. Over 39,000 individuals from five states were included in the study. Multiple logistic regression models were used to analyze the weighted data to determine factors associated with heavy and binge drinking for men and women. Each model included ACEs and controlled for sociodemographic variables, depression and smoking status. Bonferroni method was used to correct multiple comparisons. Only a few relationships between ACEs and problem drinking were observed. Among men, living with a drug abuser as a child was significantly associated with both heavy and binge drinking compared to men who did not reside with a drug abuser as a child. Childhood verbal abuse was linked with men's binge drinking compared to men who were not verbally abused as children. Among women, none of the nine ACEs examined in the study were associated with their heavy drinking. Only one ACE, verbal abuse, was found to be correlated with binge drinking, compared to women who did not experience childhood verbal abuse. In addition, we did not find the hypothesized, step-wise, graded relationship between the number of ACEs and heavy and binge drinking. However, the risk of heavy drinking was greater if the individual was exposed to four or more childhood adversities among both men and women. Study hypotheses were only partially supported. Future studies should unpack the interplay among gender, socio-economic status, ACEs, and problem alcohol consumption. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Impact of early and recent stress on white matter microstructure in major depressive disorder.

PubMed

Poletti, Sara; Aggio, Veronica; Brioschi, Silvia; Bollettini, Irene; Falini, Andrea; Colombo, Cristina; Benedetti, Francesco

2018-01-01

Major Depressive Disorder (MDD) is a worldwide-spread pathology, characterized by lifetime-recurrent episodes. Adverse childhood experiences (ACE) increase the lifetime risk of developing depression and affect the structure of the brain. Recent stressful events (RSE) can trigger the onset of depressive episodes, and affect grey matter volume. The aim of our study is to analyse the effect of both early and recent stress events on white matter microstructure in MDD patients and healthy volunteers. Sixty-five MDD inpatients and fifty-nine healthy controls underwent MRI acquisition of diffusion tensor images with a 3.0T scanner. Severity of ACE and RSE was rated, respectively, on the Risky Families Questionnaire and on the Social Readjustment Rating Scale. A significant effect of diagnosis was observed, with MDD subjects showing reduced fractional anisotropy (FA) and axial diffusivity (AD) compared to healthy controls in all the major association, projection and commissural tracts. In patients with MDD, but not in healthy controls, both ACE and RSE correlated with measures of WM microstructure: ACE correlated negatively with AD and MD, whereas RSE correlated negatively with FA. The two diagnostic groups differed for age and education, previous and current medications, and treatment periods. Exposure to both early and recent stress exerts a widespread effect on WM microstructure of MDD patients, with a different impact possibly depending from the developmental period in which the stress has occurred. Copyright © 2017 Elsevier B.V. All rights reserved.

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

ALTUS Cumulus Electrification Study (ACES)

NASA Technical Reports Server (NTRS)

Kim, Tony; Blakeslee, Richard; Russell, Larry W. (Technical Monitor)

2002-01-01

The ALTUS Cumulus Electrification Study (ACES) is an uninhabited aerial vehicle (UAV)-based project that will investigate thunderstorms in the vicinity of the Florida Everglades in August 2002. ACES is being conducted to both investigate storm electrical activity and its relationship to storm morphology, and validate Tropical Rainfall Measurement Mission (TRMM) satellite measurements. In addition, as part of NASA's UAV-based science demonstration program, this project will provide a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. Part of the demonstration involves getting approvals from the Federal Aviation Administration and the NASA airworthiness flight safety review board. ACES will employ the ALTUS II aircraft, built by General Atomics - Aeronautical Systems, Inc. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and (3) provide Lightning Imaging Sensor validation. The ACES payload, already developed and flown on ALTUS, includes electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. ACES will contribute important electrical and optical measurements not available from other sources. Also, the high altitude vantage point of the UAV observing platform (up to 55,000 feet) offers a useful 'cloud-top' perspective. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high altitude flight, the ALTUS will be flown near, and when possible, above (but never into) thunderstorms for long periods of time, allowing investigations to be conducted over entire storm life cycles. In addition, concurrent ground-based observations will enable the UAV measurements to be more completely interpreted and evaluated in the context of the thunderstorm structure, evolution, and environment.

Improved ACE-FTS observations of carbon tetrachloride (CCl4)

NASA Astrophysics Data System (ADS)

Harrison, Jeremy; Chipperfield, Martyn; Boone, Chris; Bernath, Peter

2016-04-01

The Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS), on board the SCISAT satellite, has been recording solar occultation spectra through the Earth's atmosphere since 2004 and continues to take measurements with only minor loss in performance. ACE-FTS time series are available for a range of chlorine 'source' gases, including CCl3F (CFC-11), CCl2F2 (CFC-12), CHF2Cl (HCFC-22), CH3Cl and CCl4. Recently there has been much community interest in carbon tetrachloride (CCl4), a substance regulated by the Montreal Protocol because it leads to the catalytic destruction of stratospheric ozone. Estimated sources and sinks of CCl4 remain inconsistent with observations of its abundance. Satellite observations of CCl4 in the stratosphere are particularly useful in validating stratospheric loss (photolysis) rates; in fact the atmospheric loss of CCl4 is essentially all due to photolysis in the stratosphere. However, the latest ACE-FTS v3.5 CCl4 retrieval is biased high by ˜ 20-30%. A new ACE-FTS retrieval scheme utilising new laboratory spectroscopic measurements of CCl4 and improved microwindow selection has recently been developed. This improves upon the v3.5 retrieval and resolves the issue of the high bias; this new scheme will form the basis for the upcoming v4 processing version of ACE-FTS data. This presentation will outline the improvements made in the retrieval, and a subset of data will be compared with modelled CCl4 distributions from SLIMCAT, a state-of-the-art three-dimensional chemical transport model. The use of ACE-FTS data to evaluate the modelled stratospheric loss rate of CCl4 will also be discussed. The evaluated model, which also includes a treatment of surface soil and ocean sinks, will then be used to quantify current uncertainties in the global budget of CCl4.

Characterization of angiotensin-I converting enzyme inhibiting peptide from Venerupis philippinarum with nano-liquid chromatography in combination with orbitrap mass spectrum detection and molecular docking

NASA Astrophysics Data System (ADS)

Shi, Lei; Wu, Tizhi; Sheng, Naijuan; Yang, Li; Wang, Qian; Liu, Rui; Wu, Hao

2017-06-01

The complexity and diversity of peptide mixture from protein hydrolysates make their characterization difficult. In this study, a method combining nano LC-MS/MS with molecular docking was applied to identifying and characterizing a peptide with angiotensin-I converting enzyme (ACE-I) inhibiting activity from Venerupis philippinarum hydrolysate. Firstly, ethanol supernatant of V. philippinarum hydrolysate was separated into active fractions with chromatographic methods such as ion-exchange chromatography and high performance liquid chromatography in combination. Then seven peptides from active fraction were identified according to the searching result of the MS/MS spectra against protein databases. Peptides were synthesized and subjected to ACE-I-inhibition assay. The peptide NTLTLIDTGIGMTK showed the highest potency with an IC50 of 5.75 μmol L-1. The molecular docking analysis showed that the ACE-I inhibiting peptide NTLTLIDTGIGMTK bond with residues Glu123, Glu403, Arg522, Glu376, Gln281 and Asn285 of ACE-I. Therefore, active peptides could be identified with the present method rather than the traditional purification and identification strategies. It may also be feasible to identify other food-derived peptides which target other enzymes and receptors with the method developed in this study.

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.

Delayed Diagnosis and Treatment among Children with Autism Who Experience Adversity

ERIC Educational Resources Information Center

Berg, Kristin L.; Acharya, Kruti; Shiu, Cheng-Shi; Msall, Michael E.

2018-01-01

The effects of family adverse childhood experiences (ACEs) on timing of ASD diagnoses and receipt of therapies were measured using data from the 2011-2012 National Survey of Children's Health. Parametric accelerated failure time models estimated the relationship between family ACEs and both timing of ASD diagnosis and receipt of therapies among US…

The Impact of Adverse Childhood Experiences on an Urban Pediatric Population

ERIC Educational Resources Information Center

Burke, Nadine J.; Hellman, Julia L.; Scott, Brandon G.; Weems, Carl F.; Carrion, Victor G.

2011-01-01

Objective: The goal of this study was to investigate the adverse childhood experiences (ACEs) in youth in a low-income, urban community. Study design: Data from a retrospective chart review of 701 subjects from the Bayview Child Health Center in San Francisco are presented. Medical chart documentation of ACEs as defined in previous studies were…

Stress reactivity and its effects on subsequent food intake in depressed and healthy women with and without adverse childhood experiences.

PubMed

Wingenfeld, Katja; Kuehl, Linn K; Boeker, Anita; Schultebraucks, Katharina; Ritter, Kristin; Hellmann-Regen, Julian; Otte, Christian; Spitzer, Carsten

2017-06-01

Adverse childhood experiences (ACE) increase the risk to develop major depressive disorder (MDD) and obesity or metabolic syndrome in adulthood. In addition, ACE may be associated with an exaggerated endocrine response to stress, which, in turn, may lead to enhanced food intake resulting in obesity and metabolic problems. We systematically examined the stress response and consecutive food intake in 32 women with MDD and ACE as determined by a clinical interview (Early Trauma Inventory), 52 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD and 37 healthy women without either MDD or ACE. All participants underwent a psychosocial stress test (Trier Social Stress Test, TSST) and a control condition (Placebo-TSST) before they were offered a buffet of snacks. Participants were not aware that the primary outcome variable was the amount of consumed kilocalories (kcal). The four groups did not differ in demographic variables. Stress resulted in higher cortisol release and higher blood pressure compared to the control condition. Patients with MDD without ACE had a significantly lower cortisol response to stress compared to controls. Across groups, we found higher kcal intake after stress compared to the control condition. Comparing high and low cortisol responders to stress, higher kcal intake after stress was only seen in those with low cortisol release. This study provides evidence that blunted rather than enhanced cortisol release to stress might lead to increased food intake, independent from MDD and ACE. Copyright © 2017 Elsevier Ltd. All rights reserved.

Racial and ethnic differences in the prevalence of adverse childhood experiences: Findings from a low-income sample of U.S. women.

PubMed

Mersky, Joshua P; Janczewski, Colleen E

2018-02-01

Despite great interest in adverse childhood experiences (ACEs), there has been limited research on racial and ethnic differences in their prevalence. Prior research in the United States suggests that the prevalence of ACEs varies along socioeconomic lines, but it is uncertain whether there are racial/ethnic differences in ACE rates among low-income populations. This study examined the distribution of ACEs in a sample of 1523 low-income women in Wisconsin that received home visiting services. Participants ranging in age from 16 to 50 years were coded into five racial/ethnic groups, including Hispanics and four non-Hispanic groups: blacks, whites, American Indians, and other race. Following measurement conventions, ten dichotomous indicators of child maltreatment and household dysfunction were used to create a composite ACE score. Five other potential childhood adversities were also assessed: food insecurity, homelessness, prolonged parental absence, peer victimization, and violent crime victimization. Results from bivariate and multivariate analyses revealed that, while rates of adversity were high overall, there were significant racial/ethnic differences. Total ACE scores of American Indians were comparable to the ACE scores of non-Hispanic whites, which were significantly higher than the ACE scores of non-Hispanic blacks and Hispanics. Whites were more likely than blacks to report any abuse or neglect, and they were more likely than blacks and Hispanics to report any household dysfunction. The results underscore the need to account for socioeconomic differences when making racial/ethnic comparisons. Potential explanations for the observed differences are examined. Copyright © 2017 Elsevier Ltd. 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.

Modeling of the relationship between dipeptide structure and dipeptide stability, permeability, and ACE inhibitory activity.

PubMed

Foltz, Martin; van Buren, Leo; Klaffke, Werner; Duchateau, Guus S M J E

2009-09-01

Selected di- and tripeptides exhibit angiotensin-I converting enzyme (ACE) inhibitory activity in vitro. However, the efficacy in vivo is most likely limited for most peptides due to low bioavailability. The purpose of this study was to identify descriptors of intestinal stability, permeability, and ACE inhibitory activity of dipeptides. A total of 228 dipeptides were synthesized; intestinal stability was obtained by in vitro digestion, intestinal permeability using Caco-2 cells and ACE inhibitory activity by an in vitro assay. Databases were constructed to study the relationship between structure and activity, permeability, and stability. Quantitative structure-activity relationship (QSAR) modeling was performed based on computed models using partial least squares regression based on 400 molecular descriptors. QSAR modeling of dipeptide stability revealed high correlation coefficients (R > 0.65) for models based on Z and X scales. However, amino acid (AA) clustering showed the best results in describing stability of dipeptides. The N-terminal AA residues Asp, Gly, and Pro as well as the C-terminal residues Pro, Ser, Thr, and Asp stabilize dipeptides toward luminal enzymatic peptide hydrolysis. QSAR modeling did not reveal significant correlation models for intestinal permeability. 2D-fingerprint models were identified describing ACE inhibitory activity of dipeptides. The intestinal stability of 12 peptides was predicted. Peptides were synthesized and stability was confirmed in simulated digestion experiments. Based on the results, specific dipeptides can be designed to meet both stability and activity criteria. However, postabsorptive ACE inhibitory activities of dipeptides in vivo are most likely limited due to the very low intestinal permeability of dipeptides.

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

[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.

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.

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.

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.

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.

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

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.

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.

The Atmospheric Chemistry Experiment (ACE): Mission Overview

NASA Astrophysics Data System (ADS)

Bernath, P. F.; Boone, C.; Walker, K.; McLeod, S.; Nassar, R.

2003-12-01

The ACE mission goals are: (1) to measure and to understand the chemical and dynamical processes that control the distribution of ozone in the upper troposphere and stratosphere, with a particular emphasis on the Arctic region; (2) to explore the relationship between atmospheric chemistry and climate change; (3) to study the effects of biomass burning in the free troposphere; (4) to measure aerosol number density, size distribution and composition in order to reduce the uncertainties in their effects on the global energy balance. ACE will make a comprehensive set of simultaneous measurements of trace gases, thin clouds, aerosols, and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74 degrees) low earth orbit (650 km) gives ACE coverage of tropical, mid-latitudes and polar regions. The solar occultation advantages are high sensitivity and self-calibration. A high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4100 cm-1) will measure the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. The ACE concept is derived from the now-retired ATMOS FTS instrument, which flew on the Space Shuttle in 1985, 1992, 1993, 1994. Climate-chemistry coupling may lead to the formation of an Arctic ozone hole. ACE will provide high quality data to confront these model predictions and will monitor polar chemistry as chlorine levels decline. The ACE-FTS can measure water vapor and HDO in the tropical tropopause region to study dehydration and strat-trop exchange. The molecular signatures of massive forest fires will evident in the ACE infrared spectra. The CO2 in our spectra can be used to either retrieve atmospheric pressure or (if the instrument pointing knowledge proves to be satisfactory) for an independent retrieval of a CO2 profile for carbon cycle science. Aerosols and clouds will be monitored using the extinction of solar radiation at 0.525 and 1.02 microns as measured by two filtered imagers as well as by their infrared spectra. A dual spectrograph called MAESTRO has been added to the mission to extend the wavelength coverage to the 280-1000 nm spectral region. The broad-band atmospheric extinction measured with high signal-to-noise ratio by MAESTRO is particularly useful for the derivation of aerosol and cloud physical properties. The PI for the MAESTRO instrument is T. McElroy from the Meteorological Service of Canada (MSC). ACE is unique in that MAESTRO, the ACE-FTS and the imagers all share the same suntracker and make simultaneous measurements of the same scene. The FTS and imagers have been built by ABB-Bomem in Quebec City, while the satellite bus has been made by Bristol Aerospace in Winnipeg. ACE was selected in the Canadian Space Agency's SCISAT-1 program, and was successfully launched by NASA on August 12, 2003 for a 2 year mission. The main international partners for ACE are NASA, for the launch and algorithm work at NASA-Langley, and Belgium/ESA, for the CMOS imaging arrays and scientific support.

The Atmospheric Chemistry Experiment (ACE): Mission Overview

NASA Astrophysics Data System (ADS)

Bernath, P.

2003-04-01

The ACE mission goals are: (1) to measure and to understand the chemical and dynamical processes that control the distribution of ozone in the upper troposphere and stratosphere, with a particular emphasis on the Arctic region; (2) to explore the relationship between atmospheric chemistry and climate change; (3) to study the effects of biomass burning in the free troposphere; (4) to measure aerosol number density, size distribution and composition in order to reduce the uncertainties in their effects on the global energy balance. ACE will make a comprehensive set of simultaneous measurements of trace gases, thin clouds, aerosols, and temperature by solar occultation from a satellite in low earth orbit. A high inclination (74 degrees) low earth orbit (650 km) will give ACE coverage of tropical, mid-latitudes and polar regions. The solar occultation advantages are high sensitivity and self-calibration. A high-resolution (0.02 cm-1) infrared Fourier Transform Spectrometer (FTS) operating from 2 to 13 microns (750-4100 cm-1) will measure the vertical distribution of trace gases, and the meteorological variables of temperature and pressure. The ACE concept is derived from the now-retired ATMOS FTS instrument, which flew on the Space Shuttle in 1985, 1992, 1993, 1994. Climate-chemistry coupling may lead to the formation of an Arctic ozone hole. ACE will provide high quality data to confront these model predictions and will monitor polar chemistry as chlorine levels decline. The ACE-FTS can measure water vapor and HDO in the tropical tropopause region to study dehydration and strat-trop exchange. The molecular signatures of massive forest fires will evident in the ACE infrared spectra. The CO_2 in our spectra can be used to either retrieve atmospheric pressure or (if the instrument pointing knowledge proves to be satisfactory) for an independent retrieval of a CO_2 profile for carbon cycle science. Aerosols and clouds will be monitored using the extinction of solar radiation at 0.525 and 1.02 microns as measured by two filtered imagers as well as by their infrared spectra. A dual spectrograph called MAESTRO has been added to the mission to extend the wavelength coverage to the 280-1000 nm spectral region. The broad-band atmospheric extinction measured with high signal-to-noise ratio by MAESTRO is particularly useful for the derivation of aerosol and cloud physical properties. The PI for the MAESTRO instrument is T. McElroy from the Meteorological Service of Canada. ACE is unique in that MAESTRO, the ACE-FTS and the imagers all share the same suntracker and make simultaneous measurements of the same scene. The FTS and imagers have been built by ABB-Bomem in Quebec City, while the satellite bus has been made by Bristol Aerospace in Winnipeg. ACE has been selected in the Canadian Space Agency's SCISAT-1 program for a planned launch by NASA in May 2003 for a 2 year mission. The main international partners for ACE are NASA, for the launch and algorithm work at NASA-Langley, and Belgium/ESA, for the CMOS imaging arrays and scientific support.

The Relationship of Adverse Childhood Experiences to PTSD, Depression, Poly-Drug Use and Suicide Attempt in Reservation-Based Native American Adolescents and Young Adults.

PubMed

Brockie, Teresa N; Dana-Sacco, Gail; Wallen, Gwenyth R; Wilcox, Holly C; Campbell, Jacquelyn C

2015-06-01

Adverse childhood experiences (ACEs) are associated with numerous risk behaviors and mental health outcomes among youth. This study examines the relationship between the number of types of exposures to ACEs and risk behaviors and mental health outcomes among reservation-based Native Americans. In 2011, data were collected from Native American (N = 288; 15-24 years of age) tribal members from a remote plains reservation using an anonymous web-based questionnaire. We analyzed the relationship between six ACEs, emotional, physical, and sexual abuse, physical and emotional neglect, witness to intimate partner violence, for those <18 years, and included historical loss associated symptoms, and perceived discrimination for those <19 years; and four risk behavior/mental health outcomes: post-traumatic stress disorder (PTSD) symptoms, depression symptoms, poly-drug use, and suicide attempt. Seventy-eight percent of the sample reported at least one ACE and 40 % reported at least two. The cumulative impact of the ACEs were significant (p < .001) for the four outcomes with each additional ACE increasing the odds of suicide attempt (37 %), poly-drug use (51 %), PTSD symptoms (55 %), and depression symptoms (57 %). To address these findings culturally appropriate childhood and adolescent interventions for reservation-based populations must be developed, tested and evaluated longitudinally.

Adverse Childhood Experiences and Criminal Propensity Among Intimate Partner Violence Offenders.

PubMed

Hilton, N Zoe; Ham, Elke; Green, Michelle M

2016-10-01

Adverse childhood experiences (ACEs), defined as exposure to abuse and adverse household events, are prevalent among certain offenders including those who commit intimate partner violence (IPV). However, it is not clear how ACEs relate to criminal propensity among IPV offenders, who have been shown to exhibit less antisociality and institutional violence than other offenders. We compared 99 male offenders with a current or previous offense of IPV with 233 non-IPV violent offenders and 103 nonviolent offenders undergoing institutional forensic assessment. This convenience sample allowed for use of extensive psychosocial records as well as study of institutional violence. IPV offenders had the highest mean ACE score and more extensive criminal propensity on some measures (violent and nonviolent criminal history and psychopathy) than both other groups. ACEs were associated with most measures of criminal propensity in the whole sample but with only one (actuarial risk of violent recidivism) in the subsample of IPV offenders. Finding that ACEs are prevalent among IPV offenders even in this sample with extensive mental illness demonstrates the robustness of this phenomenon. IPV offenders, though, are similar to other violent offenders in this respect, and there is insufficient evidence that ACEs represent a criminogenic need among IPV offenders specifically. Further research could draw from the batterer typology literature and attend to IPV offenders' broader criminal careers.

Developing a Community-Wide Initiative to Address Childhood Adversity and Toxic Stress: A Case Study of The Philadelphia ACE Task Force.

PubMed

Pachter, Lee M; Lieberman, Leslie; Bloom, Sandra L; Fein, Joel A

The Philadelphia ACE Task Force is a community based collaborative of health care providers, researchers, community-based organizations, funders, and public sector representatives. The mission of the task force is to provide a venue to address childhood adversity and its consequences in the Philadelphia metropolitan region. In this article we describe the origins and metamorphosis of the Philadelphia ACE Task Force, which initially was narrowly focused on screening for adverse childhood experiences (ACEs) in health care settings but expanded its focus to better represent a true community-based approach to sharing experiences with addressing childhood adversity in multiple sectors of the city and region. The task force has been successful in developing a research agenda and conducting research on ACEs in the urban context, and has identified foci of local activity in the areas of professional training and workforce development, community education, and local practical interventions around adversity, trauma, and resiliency. In this article we also address the lessons learned over the first 5 years of the task force's existence and offers recommendations for future efforts to build a local community-based ACEs collaborative. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Design and implementation of robust decentralized control laws for the ACES structure at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Collins, Emmanuel G., Jr.; Phillips, Douglas J.; Hyland, David C.

1990-01-01

Many large space system concepts will require active vibration control to satisfy critical performance requirements such as line-of-sight accuracy. In order for these concepts to become operational it is imperative that the benefits of active vibration control be practically demonstrated in ground based experiments. The results of the experiment successfully demonstrate active vibration control for a flexible structure. The testbed is the Active Control Technique Evaluation for Spacecraft (ACES) structure at NASA Marshall Space Flight Center. The ACES structure is dynamically traceable to future space systems and especially allows the study of line-of-sight control issues.

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

Positive childhood experiences predict less psychopathology and stress in pregnant women with childhood adversity: A pilot study of the benevolent childhood experiences (BCEs) scale.

PubMed

Narayan, Angela J; Rivera, Luisa M; Bernstein, Rosemary E; Harris, William W; Lieberman, Alicia F

2018-04-01

This pilot study examined the psychometric properties of the Benevolent Childhood Experiences (BCEs) scale, a new instrument designed to assess positive early life experiences in adults with histories of childhood maltreatment and other adversities. A counterpart to the Adverse Childhood Experiences (ACEs) questionnaire, the BCEs was developed to be multiculturally-sensitive and applicable regardless of socioeconomic position, urban-rural background, or immigration status. Higher levels of BCEs were hypothesized to predict lower levels of psychopathology and stress beyond the effects of ACES in a sample of ethnically diverse, low-income pregnant women. BCEs were also expected to show adequate internal validity across racial/ethnic groups and test-retest stability from the prenatal to the postnatal period. Participants were 101 pregnant women (M=29.10years, SD=6.56, range=18-44; 37% Latina, 22% African-American, 20% White, 21% biracial/multiracial/other; 37% foreign-born, 26% Spanish-speaking) who completed the BCEs and ACEs scales; assessments of prenatal depression and post-traumatic stress disorder (PTSD) symptoms, perceived stress, and exposure to stressful life events (SLEs) during pregnancy; and demographic information. Higher levels of BCEs predicted less PTSD symptoms and SLEs, above and beyond ACEs. The BCEs showed excellent test-retest reliability, and mean levels were comparable across racial/ethnic and Spanish-English groups of women. Person-oriented analyses also showed that higher levels of BCEs offset the effects of ACEs on prenatal stress and psychopathology. The BCEs scale indexes promising promotive factors associated with lower trauma-related symptomatology and stress exposure during pregnancy and illuminates how favorable childhood experiences may counteract long-term effects of childhood adversity. Copyright © 2017 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.

FIRE III ACE Data Sets

Atmospheric Science Data Center

2017-12-22

... in conjunction with the Surface Heat Budget of the Arctic Ocean (SHEBA) Experiment. The FIRE-ACE focused on all aspects of Arctic cloud ... Alaska with measurements extending well over the Arctic Ocean (ship and aircraft). Guide Documents:  FIRE Project ...

Leadership for the 21st Century: Effectiveness of Mentorship in the Development of Senior Leaders for U.S. Higher Education

ERIC Educational Resources Information Center

Brown, Kneeland Charles

2010-01-01

This study examined whether the ACE fellows' mentorship experiences facilitated leadership development, the achievement of contract goals, and career benefits. The objective of the present study was to determine how former ACE fellows viewed the effectiveness of their mentorship experiences during their fellowship year in preparing them for future…

Health consequences of adverse childhood experiences: a systematic review.

PubMed

Kalmakis, Karen A; Chandler, Genevieve E

2015-08-01

Adverse childhood experiences (ACEs) have been associated with negative health outcomes, but the evidence has had limited application in primary care practice. The purpose of this study was to systematically review the research on associations between ACEs and adult health outcomes to inform nurse practitioners (NPs) in primary care practice. The databases PubMed, CINAHL, PsycINFO, and Social Abstracts were searched for articles published in English between 2008 and 2013 using the search term "adverse childhood experiences." Forty-two research articles were included in the synthesis. The evidence was synthesized and is reported following the preferred reporting items for systematic reviews and meta-analysis procedure (PRISMA). ACEs have been associated with health consequences including physical and psychological conditions, risk behaviors, developmental disruption, and increased healthcare utilization. Generalization of the results is limited by a majority of studies (41/42) measuring childhood adversity using self-report measures. NPs are encouraged to incorporate assessment of patients' childhood history in routine primary care and to consider the evidence that supports a relationship between ACEs and health. Although difficult, talking about patient's childhood experiences may positively influence health outcomes. ©2015 American Association of Nurse Practitioners.

The mediating sex-specific effect of psychological distress on the relationship between adverse childhood experiences and current smoking among adults

PubMed Central

2012-01-01

Background Research suggests that ACEs have a long-term impact on the behavioral, emotional, and cognitive development of children. These disruptions can lead to adoption of unhealthy coping behaviors throughout the lifespan. The present study sought to examine psychological distress as a potential mediator of sex-specific associations between adverse childhood experiences (ACEs) and adult smoking. Method Data from 7,210 Kaiser-Permanente members in San Diego California collected between April and October 1997 were used. Results Among women, psychological distress mediated a significant portion of the association between ACEs and smoking (21% for emotional abuse, 16% for physical abuse, 15% for physical neglect, 10% for parental separation or divorce). Among men, the associations between ACEs and smoking were not significant. Conclusions These findings suggest that for women, current smoking cessation strategies may benefit from understanding the potential role of childhood trauma. PMID:22788356

Health Status of Adolescents Reporting Experiences of Adversity

PubMed Central

Duke, Naomi N.; Borowsky, Iris W.

2018-01-01

This study examines relationships between adverse childhood experiences (ACEs) and adolescent health indicators among a sample of 8th, 9th, and 11th graders participating in the 2016 Minnesota Student Survey. Logistic regression was used to determine whether 10 types of ACEs were associated with health indicators that may link to health in adulthood, including self-rated health, body mass index (BMI), sleep duration, and dietary and physical activity participation after adjustment for demographic covariates. Individual and cumulative ACEs measures were significantly associated with adverse health indicators, including poorer self-rated health, increased odds of BMI ≥85% and frequent fast food intake, and reduced odds of adequate sleep duration, daily fruit intake, and physical activity participation on most days of the week. Findings advocate screening for ACEs as a means to inform anticipatory guidance strategies and to support development of care models that are relevant and responsive to youth and family needs. PMID:29687049

Factors Associated with Whether Pediatricians Inquire about Parents’ Adverse Childhood Experiences

PubMed Central

Szilagyi, Moira; Kerker, Bonnie D.; Storfer-Isser, Amy; Stein, Ruth E.K.; Garner, Andrew; O’Connor, Karen G.; Hoagwood, Kimberly E.; Horwitz, Sarah McCue

2017-01-01

Objective Cumulative adverse childhood experiences (ACE) can have profound and lasting effects on parenting. Parents with a history of multiple ACE have greater challenges modulating their own stress responses and helping their children adapt to life stressors. This paper examines pediatric practice in inquiring about parents’ childhood adversities as of 2013. Methods Using data from the 85th Periodic Survey of the American Academy of Pediatrics (AAP), we restricted analyses to the 302 pediatricians exclusively practicing general pediatrics who answered questions regarding their beliefs about childhood stressors, their role in advising parents, and whether they asked about parents’ ACE. Weighted descriptive and logistic regression analyses were conducted. Results Despite endorsing the influence of positive parenting on a child’s life-course trajectory (96%), that their advice can impact parenting skills (79%), and that screening for social-emotional risks is within their scope of practice ((81%), most pediatricians (61%) did not inquire about parents’ ACE. Pediatricians who believed that their advice influences positive parenting skills inquired about more parents’ ACE Conclusion As of 2013, few pediatricians inquired about parents’ ACE despite recognizing their negative impact on parenting behaviors and child development‥ Research is needed regarding the best approaches to the prevention and amelioration of ACE and the promotion of family and child resilience. Pediatricians need resources and education about the AAP’s proposed dyadic approach to assessing family and child risk factors and strengths and to providing guidance and management. PMID:27157045

Thinking Across Generations: Unique Contributions of Maternal Early Life and Prenatal Stress to Infant Physiology.

PubMed

Gray, Sarah A O; Jones, Christopher W; Theall, Katherine P; Glackin, Erin; Drury, Stacy S

2017-11-01

Respiratory sinus arrhythmia (RSA) is a parasympathetic-mediated biomarker of self-regulation linked to lifespan mental and physical health outcomes. Intergenerational impacts of mothers' exposure to prenatal stress have been demonstrated, but evidence for biological embedding of maternal preconception stress, including adverse childhood experiences (ACEs), on infant RSA is lacking. We examine the independent effects of maternal ACEs and prenatal stress on infant RSA, seeking to broaden the understanding of the earliest origins of mental and physical health risk. Mothers reported on ACEs and prenatal stress. RSA was recorded in a sample of 167 4-month-old infants (49% female and 51% male) during a dyadic stressor, the Still Face Paradigm. Independent contributions of maternal ACEs and prenatal stress to infant RSA were observed. High maternal ACEs were associated with lower RSA, whereas prenatal stress was associated with failure to recover following the stressor. Sex but not race differences were observed. Prenatal stress was associated with higher RSA among boys but lower RSA among girls. Infants' RSA is affected by mothers' life course experiences of stress, with ACEs predicting a lower set point and prenatal stress dampening recovery from stress. For prenatal stress but not ACEs, patterns vary across sex. Findings underscore that stress-reducing interventions for pregnant women or those considering pregnancy may lead to decreased physical and mental health risk across generations. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Factors Associated With Whether Pediatricians Inquire About Parents' Adverse Childhood Experiences.

PubMed

Szilagyi, Moira; Kerker, Bonnie D; Storfer-Isser, Amy; Stein, Ruth E K; Garner, Andrew; O'Connor, Karen G; Hoagwood, Kimberly E; McCue Horwitz, Sarah

2016-01-01

Cumulative adverse childhood experiences (ACE) can have profound and lasting effects on parenting. Parents with a history of multiple ACE have greater challenges modulating their own stress responses and helping their children adapt to life stressors. We examined pediatric practice in inquiring about parents' childhood adversities as of 2013. Using data from the 85th Periodic Survey of the American Academy of Pediatrics (AAP), we restricted analyses to the 302 pediatricians exclusively practicing general pediatrics who answered questions regarding their beliefs about childhood stressors, their role in advising parents, and whether they asked about parents' ACEs. Weighted descriptive and logistic regression analyses were conducted. Despite endorsing the influence of positive parenting on a child's life-course trajectory (96%), that their advice can impact parenting skills (79%), and that screening for social-emotional risks is within their scope of practice (81%), most pediatricians (61%) did not inquire about parents' ACE. Pediatricians who believed that their advice influences positive parenting skills inquired about more parents' ACE. As of 2013, few pediatricians inquired about parents' ACEs despite recognizing their negative impact on parenting behaviors and child development. Research is needed regarding the best approaches to the prevention and amelioration of ACEs and the promotion of family and child resilience. Pediatricians need resources and education about the AAP's proposed dyadic approach to assessing family and child risk factors and strengths and to providing guidance and management. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

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

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa

PubMed Central

Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C

2014-01-01

Purpose Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. Methods We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Key Findings Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. Significance There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed. PMID:24116877

Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

PubMed

Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C; Twine, Rhian; Gómez Olivé, F Xavier; Collinson, Mark; Kahn, Kathleen; Tollman, Stephen; Masanja, Honratio; Mathew, Alexander; Pariyo, George; Peterson, Stefan; Ndyomughenyi, Donald; Bauni, Evasius; Kamuyu, Gathoni; Odera, Victor Mung'ala; Mageto, James O; Ae-Ngibise, Ken; Akpalu, Bright; Agbokey, Francis; Adjei, Patrick; Owusu-Agyei, Seth; Kleinschmidt, Immo; Doku, Victor C K; Odermatt, Peter; Nutman, Thomas; Wilkins, Patricia; Noh, John

2014-01-01

Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and cognitive and neurologic deficits are common in people with ACE and should be integrated into the management of epilepsy in this region. Consequences of epilepsy such as burns, lack of education, poor marriage prospects, and unemployment need to be addressed. Wiley Periodicals, Inc. © 2013 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of the International League Against Epilepsy.

Functional characterization of the recombinant antimicrobial peptide Trx-Ace-AMP1 and its application on the control of tomato early blight disease.

PubMed

Wu, Yin; He, Yue; Ge, Xiaochun

2011-05-01

Ace-AMP1 is a potent antifungal peptide found in onion (Allium cepa) seeds with sequence similarity to plant lipid transfer proteins. Transgenic plants over-expressing Ace-AMP1 gene have enhanced disease resistance to some fungal pathogens. However, mass production in heterologous systems and in vitro application of this peptide have not been reported. In this study, Ace-AMP1 was highly expressed in a prokaryotic Escherichia coli system as a fusion protein. The purified protein inhibited the growth of many plant fungal pathogens, especially Alternaria solani, Fusarium oxysporum f. sp. vasinfectum, and Verticillium dahliae. The inhibitory effect was accompanied by hyphal hyperbranching for V. dahliae but not for F. oxysporum f. sp. vasinfectum and A. solani, suggesting that the mode of action of Ace-AMP1 on different fungi might be different. Application of Ace-AMP1 on tomato leaves showed that the recombinant protein conferred strong resistance to the tomato pathogen A. solani and could be used as an effective fungicide.

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.

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.

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.

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.

Adverse childhood experiences in relation to mood and anxiety disorders in a population-based sample of active military personnel.

PubMed

Sareen, J; Henriksen, C A; Bolton, S L; Afifi, T O; Stein, M B; Asmundson, G J G

2013-01-01

Although it has been posited that exposure to adverse childhood experiences (ACEs) increases vulnerability to deployment stress, previous literature in this area has demonstrated conflicting results. Using a cross-sectional population-based sample of active military personnel, the present study examined the relationship between ACEs, deployment related stressors and mood and anxiety disorders. Data were analyzed from the 2002 Canadian Community Health Survey-Canadian Forces Supplement (CCHS-CFS; n = 8340, age 18-54 years, response rate 81%). The following ACEs were self-reported retrospectively: childhood physical abuse, childhood sexual abuse, economic deprivation, exposure to domestic violence, parental divorce/separation, parental substance abuse problems, hospitalization as a child, and apprehension by a child protection service. DSM-IV mood and anxiety disorders [major depressive disorder, post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic attacks/disorder and social phobia] were assessed using the composite international diagnostic interview (CIDI). Even after adjusting for the effects of deployment-related traumatic exposures (DRTEs), exposure to ACEs was significantly associated with past-year mood or anxiety disorder among men [adjusted odds ratio (aOR) 1.34, 99% confidence interval (CI) 1.03-1.73, p < 0.01] and women [aOR 1.37, 99% CI 1.00-1.89, p = 0.01]. Participants exposed to both ACEs and DRTEs had the highest prevalence of past-year mood or anxiety disorder in comparison to those who were exposed to either ACEs alone, DRTEs alone, or no exposure. ACEs are associated with several mood and anxiety disorders among active military personnel. Intervention strategies to prevent mental health problems should consider the utility of targeting soldiers with exposure to ACEs.

Adverse Childhood Experiences and Higher-Level Functional Limitations Among Older Japanese People: Results From the JAGES Study.

PubMed

Amemiya, Airi; Fujiwara, Takeo; Murayama, Hiroshi; Tani, Yukako; Kondo, Katsunori

2018-01-16

A life-course perspective is essential in understanding the determinants of higher-level functional limitations. We examine the impact of adverse childhood experiences (ACEs) on higher-level functional limitations in older people. Data were from the Japan Gerontological Evaluation Study 2013, a population-based cohort of independent people aged 65 years or older across Japan (n = 19,220). ACEs before the age of 18 were assessed in terms of seven adversities: parental death, parental divorce, parental mental illness, family violence, physical abuse, psychological neglect, and psychological abuse. Associations between the cumulative number of ACEs and higher-level functional limitations were investigated by multivariate Poisson regression with robust error variances, adjusted for age, gender, childhood disadvantage, adult sociodemographics, adult health behaviors, and health status. Of the older people, 36.3% reported at least one ACE. Older people who had experienced two or more ACEs showed significantly greater higher-level functional limitations than those with no ACE in a crude model (prevalence ratio, PR = 1.61, 95% confidence interval, CI = 1.51-1.71). After adjusting the covariates, this association remained (PR = 1.19, 95% CI = 1.12-1.27). ACEs showed robust independent effects on higher-level functional limitations among older Japanese without disabilities, even after adjusting for potential covariates in childhood and adulthood. The current findings may help in understanding the impact of the latent effects of ACEs on functional limitations in older people. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PP2ARts1 is a master regulator of pathways that control cell size

PubMed Central

Zapata, Jessica; Dephoure, Noah; MacDonough, Tracy; Yu, Yaxin; Parnell, Emily J.; Mooring, Meghan; Gygi, Steven P.; Stillman, David J.

2014-01-01

Cell size checkpoints ensure that passage through G1 and mitosis occurs only when sufficient growth has occurred. The mechanisms by which these checkpoints work are largely unknown. PP2A associated with the Rts1 regulatory subunit (PP2ARts1) is required for cell size control in budding yeast, but the relevant targets are unknown. In this paper, we used quantitative proteome-wide mass spectrometry to identify proteins controlled by PP2ARts1. This revealed that PP2ARts1 controls the two key checkpoint pathways thought to regulate the cell cycle in response to cell growth. To investigate the role of PP2ARts1 in these pathways, we focused on the Ace2 transcription factor, which is thought to delay cell cycle entry by repressing transcription of the G1 cyclin CLN3. Diverse experiments suggest that PP2ARts1 promotes cell cycle entry by inhibiting the repressor functions of Ace2. We hypothesize that control of Ace2 by PP2ARts1 plays a role in mechanisms that link G1 cyclin accumulation to cell growth. PMID:24493588

Nyberg working with ACE in U.S. Laboratory

NASA Image and Video Library

2013-08-18

ISS036-E-035770 (18 Aug. 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, works with new test samples for the Advanced Colloids Experiment, or ACE, housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station?s Destiny laboratory. Results from ACE will help researchers understand how to optimize stabilizers to extend the shelf life of products like laundry detergent, paint, ketchup and even salad dressing.

Nyberg working with ACE in U.S. Laboratory

NASA Image and Video Library

2013-08-18

ISS036-E-035767 (18 Aug. 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, works with new test samples for the Advanced Colloids Experiment, or ACE, housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station?s Destiny laboratory. Results from ACE will help researchers understand how to optimize stabilizers to extend the shelf life of products like laundry detergent, paint, ketchup and even salad dressing.

Nyberg working with ACE in U.S. Laboratory

NASA Image and Video Library

2013-08-18

ISS036-E-035780 (18 Aug. 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, works with new test samples for the Advanced Colloids Experiment, or ACE, housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station?s Destiny laboratory. Results from ACE will help researchers understand how to optimize stabilizers to extend the shelf life of products like laundry detergent, paint, ketchup and even salad dressing.

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.

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.

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.

[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.

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.

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.

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.

Adverse Childhood Experiences and Adult Criminality: How Long Must We Live before We Possess Our Own Lives?

PubMed Central

Reavis, James A; Looman, Jan; Franco, Kristina A; Rojas, Briana

2013-01-01

Background: Empirical research associated with the Kaiser Permanente and Centers for Disease Control and Prevention Adverse Childhood Experiences (ACE) Study has demonstrated that ACE are associated with a range of negative outcomes in adulthood, including physical and mental health disorders and aggressive behavior. Methods: Subjects from 4 different offender groups (N = 151) who were referred for treatment at an outpatient clinic in San Diego, CA, subsequent to conviction in criminal court, completed the ACE Questionnaire. Groups (nonsexual child abusers, domestic violence offenders, sexual offenders, and stalkers) were compared on the incidence of ACE, and comparisons were made between the group offenders and a normative sample. Results: Results indicated that the offender group reported nearly four times as many adverse events in childhood than an adult male normative sample. Eight of ten events were found at significantly higher levels among the criminal population. In addition, convicted sexual offenders and child abusers were more likely to report experiencing sexual abuse in childhood than other offender types. Conclusions: On the basis of a review of the literature and current findings, criminal behavior can be added to the host of negative outcomes associated with scores on the ACE Questionnaire. Childhood adversity is associated with adult criminality. We suggest that to decrease criminal recidivism, treatment interventions must focus on the effects of early life experiences. PMID:23704843

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.

Endothelial function in pigs transgenic for human complement regulating factor.

PubMed

Warnecke, Gregor; Severson, Sandra R; Ugurlu, Mustafa M; Taner, Cemal B; Logan, John S; Diamond, Lisa E; Miller, Virginia M; McGregor, Christopher G A

2002-04-15

Expression of human complement regulating factor (hCRF) in porcine organs prevents hyperacute rejection of these organs after xenotransplantation to nonhuman primates. Experiments were designed to characterize endothelial and smooth muscle function of arteries from pigs transgenic for hCD46. Arterial blood from outbred pigs transgenic for hCD46 expression and nontransgenic animals of the same lineage was analyzed for angiotensin-converting enzyme (ACE), C-type natriuretic peptide (CNP), and nitric oxide. Aortic endothelial cells were prepared for measurement of mRNA or activity for nitric oxide synthase (NOS). Rings cut from femoral and pulmonary arteries were suspended in organ chambers for measurement of isometric tension. CNP was significantly greater, ACE was similar, and nitric oxide was significantly less in plasma from transgenic compared with nontransgenic pigs. Neither mRNA nor activity of NOS differed between the groups. Endothelium-dependent relaxations to bradykinin and acetylcholine but not the calcium ionophore were shifted significantly to the left in femoral and pulmonary arteries from hCD46 transgenic pigs compared with nontransgenic pigs. The ACE-inhibitor captopril augmented relaxations similarly in both groups, but NG-monomethyl-L-arginine (L-NMMA) did not inhibit relaxations in rings from transgenic pigs. Data suggest that expression of hCD46 on endothelium of pigs selectively augments endothelium-dependent relaxations to bradykinin by increased release of endothelium-derived factors other than nitric oxide. There does not seem to be any change in activity of ACE or NOS with expression of the human protein. Increased relaxations to bradykinin may be beneficial in lowering vascular resistance when transgenic organs are used for xenotransplantation.

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

Retrieval of carbon dioxide vertical profiles from solar occultation observations and associated error budgets for ACE-FTS and CASS-FTS

NASA Astrophysics Data System (ADS)

Sioris, C. E.; Boone, C. D.; Nassar, R.; Sutton, K. J.; Gordon, I. E.; Walker, K. A.; Bernath, P. F.

2014-07-01

An algorithm is developed to retrieve the vertical profile of carbon dioxide in the 5 to 25 km altitude range using mid-infrared solar occultation spectra from the main instrument of the ACE (Atmospheric Chemistry Experiment) mission, namely the Fourier transform spectrometer (FTS). The main challenge is to find an atmospheric phenomenon which can be used for accurate tangent height determination in the lower atmosphere, where the tangent heights (THs) calculated from geometric and timing information are not of sufficient accuracy. Error budgets for the retrieval of CO2 from ACE-FTS and the FTS on a potential follow-on mission named CASS (Chemical and Aerosol Sounding Satellite) are calculated and contrasted. Retrieved THs have typical biases of 60 m relative to those retrieved using the ACE version 3.x software after revisiting the temperature dependence of the N2 CIA (collision-induced absorption) laboratory measurements and accounting for sulfate aerosol extinction. After correcting for the known residual high bias of ACE version 3.x THs expected from CO2 spectroscopic/isotopic inconsistencies, the remaining bias for tangent heights determined with the N2 CIA is -20 m. CO2 in the 5-13 km range in the 2009-2011 time frame is validated against aircraft measurements from CARIBIC (Civil Aircraft for the Regular Investigation of the atmosphere Based on an Instrument Container), CONTRAIL (Comprehensive Observation Network for Trace gases by Airline), and HIPPO (HIAPER Pole-to-Pole Observations), yielding typical biases of -1.7 ppm in the 5-13 km range. The standard error of these biases in this vertical range is 0.4 ppm. The multi-year ACE-FTS data set is valuable in determining the seasonal variation of the latitudinal gradient which arises from the strong seasonal cycle in the Northern Hemisphere troposphere. The annual growth of CO2 in this time frame is determined to be 2.6 ± 0.4 ppm year-1, in agreement with the currently accepted global growth rate based on ground-based measurements.

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

Preparation of lisinopril-capped gold nanoparticles for molecular imaging of angiotensin-converting enzyme

NASA Astrophysics Data System (ADS)

Li, Yuan; Baeta, Cesar; Aras, Omer; Daniel, Marie-Christine

2009-05-01

Overexpression of angiotensin-converting enzyme (ACE) has been associated with the pathophysiology of cardiac and pulmonary fibrosis. Moreover, the prescription of ACE inhibitors, such as lisinopril, has shown a favorable effect on patient outcome for patients with heart failure or systemic hypertension. Thus targeted imaging of the ACE would be of crucial importance for monitoring tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-coated gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. The preparation involved non-modified lisinopril, using its primary amine group as the anchoring function on the gold nanoparticles surface. The stable lisinopril-coated gold nanoparticles obtained were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM). Their zeta potential was also measured in order to assess the charge density on the modified gold nanoparticles (GNPs).

Chronobiology and Pharmacologic Modulation of the Renin-Angiotensin-Aldosterone System in Dogs: What Have We Learned?

PubMed

Mochel, Jonathan P; Danhof, Meindert

2015-01-01

Congestive heart failure (CHF) is a primary cause of morbidity and mortality with an increasing prevalence in human and canine populations. Recognition of the role of renin-angiotensin-aldosterone system (RAAS) overactivation in the pathophysiology of CHF has led to significant medical advances. By decreasing systemic vascular resistance and angiotensin II (AII) production, angiotensin-converting enzyme (ACE) inhibitors such as benazepril improve cardiac hemodynamics and reduce mortality in human and dog CHF patients. Although several experiments have pointed out that efficacy of ACE inhibitors depends on the time of administration, little attention is paid to the optimum time of dosing of these medications. A thorough characterization of the chronobiology of the renin cascade has the potential to streamline the therapeutic management of RAAS-related diseases and to help determining the optimal time of drug administration that maximizes efficacy of ACE inhibitors, while minimizing the occurrence of adverse effects. We have developed an integrated pharmacokinetic-pharmacodynamic model that adequately captures the disposition kinetics of the paradigm drug benazeprilat, as well as the time-varying changes of systemic renin-angiotensin-aldosterone biomarkers, without and with ACE inhibition therapy. Based on these chronobiological investigations, the optimal efficacy of ACE inhibitors is expected with bedtime dosing. The data further show that benazepril influences the dynamics of the renin-angiotensin-aldosterone cascade, resulting in a profound decrease in AII and aldosterone (ALD), while increasing renin activity for about 24 h. From the results of recent investigations in human, it is hypothesized that reduction of AII and ALD is one of the drivers of increased survival and improved quality of life in dogs receiving ACE inhibitors. To support and consolidate this hypothesis, additional efforts should be directed toward the collection of circulating RAAS peptides in spontaneous cases of canine CHF. If such a link could be established, profiling of these biomarkers could support determination of the severity of heart failure, complement clinical and echocardiographic findings, and be used for therapeutic drug monitoring purposes.

Elevated plasma angiotensin converting enzyme 2 activity is an independent predictor of major adverse cardiac events in patients with obstructive coronary artery disease.

PubMed

Ramchand, Jay; Patel, Sheila K; Srivastava, Piyush M; Farouque, Omar; Burrell, Louise M

2018-01-01

Angiotensin converting enzyme 2 (ACE2) is an endogenous regulator of the renin angiotensin system. Increased circulating ACE2 predicts adverse outcomes in patients with heart failure (HF), but it is unknown if elevated plasma ACE2 activity predicts major adverse cardiovascular events (MACE) in patients with obstructive coronary artery disease (CAD). We prospectively recruited patients with obstructive CAD (defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis in ≥ 1 other major epicardial vessel on invasive coronary angiography) and measured plasma ACE2 activity. Patients were followed up to determine if circulating ACE2 activity levels predicted the primary endpoint of MACE (cardiovascular mortality, HF or myocardial infarction). We recruited 79 patients with obstructive coronary artery disease. The median (IQR) plasma ACE2 activity was 29.3 pmol/ml/min [21.2-41.2]. Over a median follow up of 10.5 years [9.6-10.8years], MACE occurred in 46% of patients (36 events). On Kaplan-Meier analysis, above-median plasma ACE2 activity was associated with MACE (log-rank test, p = 0.035) and HF hospitalisation (p = 0.01). After Cox multivariable adjustment, log ACE2 activity remained an independent predictor of MACE (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.24-4.72, p = 0.009) and HF hospitalisation (HR: 4.03, 95% CI: 1.42-11.5, p = 0.009). Plasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD.

Spanking and adult mental health impairment: The case for the designation of spanking as an adverse childhood experience.

PubMed

Afifi, Tracie O; Ford, Derek; Gershoff, Elizabeth T; Merrick, Melissa; Grogan-Kaylor, Andrew; Ports, Katie A; MacMillan, Harriet L; Holden, George W; Taylor, Catherine A; Lee, Shawna J; Peters Bennett, Robbyn

2017-09-01

Adverse Childhood Experiences (ACEs) such as child abuse are related to poor health outcomes. Spanking has indicated a similar association with health outcomes, but to date has not been considered an ACE. Physical and emotional abuse have been shown in previous research to correlate highly and may be similar in nature to spanking. To determine if spanking should be considered an ACE, this study aimed to examine 1): the grouping of spanking with physical and emotional abuse; and 2) if spanking has similar associations with poor adult health problems and accounts for additional model variance. Adult mental health problems included depressive affect, suicide attempts, moderate to heavy drinking, and street drug use. Data were from the CDC-Kaiser ACE study (N=8316, response rate=65%). Spanking loaded on the same factor as the physical and emotional abuse items. Additionally, spanking was associated with increased odds of suicide attempts (Adjusted Odds Ratios (AOR)=1.37; 95% CI=1.02 to1.86), moderate to heavy drinking (AOR)=1.23; 95% CI=1.07 to 1.41), and the use of street drugs (AOR)=1.32; 95% CI=1.4 to 1.52) in adulthood over and above experiencing physical and emotional abuse. This indicates spanking accounts for additional model variance and improves our understanding of these outcomes. Thus, spanking is empirically similar to physical and emotional abuse and including spanking with abuse adds to our understanding of these mental health problems. Spanking should also be considered an ACE and addressed in efforts to prevent violence. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Parental perspectives of screening for adverse childhood experiences in pediatric primary care.

PubMed

Conn, Anne-Marie; Szilagyi, Moira A; Jee, Sandra H; Manly, Jody T; Briggs, Rahil; Szilagyi, Peter G

2018-03-01

Pediatricians recognize a need to mitigate the negative impact that adverse childhood experiences (ACEs) can have on health and development. However, ACEs screening and interventions in primary care pediatrics may be inhibited by concerns about parental perceptions. We assessed parent perspectives of screening for ACEs in the pediatric primary care setting, to understand their views on the potential impact of their ACEs on their parenting and to identify opportunities for pediatric anticipatory guidance. We used purposive sampling to recruit parents of children <6 years receiving care at an urban, pediatric clinic. Semistructured questions guided 1:1 interviews that were later coded by multiple researchers to verify reliability. A thematic framework approach guided analysis and identified main themes and subthemes. We reached thematic saturation after 15 parent interviews, which consistently revealed 3 interrelated themes. First, parents strongly supported ACEs screening as a bridge to needed services, and they recommended using a trauma-sensitive, person-centered approach in pediatric practices. Second, parents understood the intergenerational impact of ACEs and expressed a desire to break the cycle of adversity. Finally, parents saw their child's pediatrician as a potential change-agent who could provide support to meet their parenting goals. Parents want to discuss their ACEs and receive help and guidance from pediatricians. Furthermore, they perceive their child's pediatrician as having an important role to play in meeting their parenting goals. It is important to ensure that pediatricians have the training, skills and familiarity with available resources to meet parental expectations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Associations between adverse childhood experiences, student-teacher relationships, and non-medical use of prescription medications among adolescents.

PubMed

Forster, Myriam; Gower, Amy L; Borowsky, Iris W; McMorris, Barbara J

2017-05-01

Few studies have investigated associations between adverse childhood experiences (ACE) and nonmedical use of prescription medication (NMUPM) in population-based samples of adolescents, and even fewer have examined whether promotive factors might buffer these effects. The present study assesses the direct effects of ACE and positive student-teacher relationships on NUMPD and whether positive student-teacher relationships moderate this association. Data were from the 2013 Minnesota Student Survey (MSS), an in-school survey administered every three years to students throughout Minnesota. The analytic sample (n=104,332) was comprised of 8th, 9th, and 11th graders. Approximately 3% of students acknowledged past year NMUPM, the majority of whom reported at least one ACE. The most frequently used prescription drug was Ritalin/ADHD medications (1.71%) followed by opiate-based painkillers (1.67%), tranquilizers (0.92%), and stimulants (0.75%). Students who reported any use tended to use more than one medication. For every additional ACE, there was a 56%, 51%, 47%, and 52% increase in the odds of past year stimulant use, ADHD medication, pain reliever, and tranquilizer use, respectively. The estimated rate of the number of prescription drugs used increased by 62% for every additional ACE. Positive student- teacher relationships buffered the association between ACE and NMUPD, especially at higher levels of ACEs. Our findings have important implications for prevention work. Training educators to recognize trauma symptomology and cultivating strong student-teacher relationships are important considerations for future school-based substance use prevention initiatives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adverse childhood experiences influence the detrimental effect of bipolar disorder and schizophrenia on cortico-limbic grey matter volumes.

PubMed

Poletti, Sara; Vai, Benedetta; Smeraldi, Enrico; Cavallaro, Roberto; Colombo, Cristina; Benedetti, Francesco

2016-01-01

Adverse childhood experiences (ACE) can lead to several negative consequences in adult life, are highly prevalent in psychiatric disorders where they associate with clinical and brain morphological features. Grey matter volume loss is a central characteristic of bipolar disorder (BD) and schizophrenia (SCZ). The aim of this study is to measure the effect of diagnosis and ACE on GM volume in a sample of patients with BD or SCZ compared with healthy controls (HC). We studied 206 depressed BD patients, 96 SCZ patients and 136 healthy subjects. GM volumes were estimated with 3.0 Tesla MRI and analyzed with VBM technique. The effect of diagnosis was investigated in the whole sample and separately exposed to high and low ACE subjects. An effect of diagnosis was observed in orbitofrontal cortex encompassing BA 47 and insula, and in the thalamus. HC had the highest volume and SCZ patients the lowest with BD patients showing an intermediate volume. This pattern persisted only in subjects with high ACE. No differences were observed for low ACE subjects. The three diagnostic groups differ for age and education, previous and current medications, and treatment periods. Our results underline the importance of ACE on the neural underpinnings of psychiatric psychopathology and suggest a major role of exposure to ACE for the GM deficits to reveal in clinical populations. Exposure to early stress is a crucial factor that must be taken in to account when searching for biomarkers of BD and SCZ. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Targeting the Vasoprotective Axis of the Renin-Angiotensin System: A Novel Strategic Approach to Pulmonary Hypertensive Therapy

PubMed Central

Bradford, Chastity N.; Ely, Debra R.

2010-01-01

A decade has passed since the discovery of angiotensin-converting enzyme 2 (ACE2), a component of the ACE2–angiotensin (Ang)-(1-7)–Mas counterregulatory axis of the renin angiotensin system (RAS). ACE2 is considered an endogenous regulator of the vasoconstrictive, proliferative, fibrotic, and proinflammatory effects of the ACE–Ang II–angiotensin II type 1 receptor (AT1R) axis. Both animal and clinical studies have emerged to define a role for ACE2 in pulmonary arterial hypertension (PAH). There is scientific evidence supporting the concept that ACE2 maintains the RAS balance and plays a protective role in PAH. The activation of pulmonary ACE2 could influence the pathogenesis of PAH and serve as a novel therapeutic target in PAH. Current therapeutic strategies and interventions have limited success, and PAH remains a fatal disease. Thus, more research that establishes the novel therapeutic potential and defines the mechanism of the ACE2–Ang-(1-7)–Mas counterregulatory axis in PAH is needed. PMID:20556668

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

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

InSPACE-3 experiment

NASA Image and Video Library

2013-08-18

ISS036-E-033948 (18 Aug. 2013) --- NASA astronaut Karen Nyberg, Expedition 36 flight engineer, works with new test samples for the Advanced Colloids Experiment, or ACE, housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack of the International Space Station?s Destiny laboratory. Results from ACE will help researchers understand how to optimize stabilizers to extend the shelf life of products like laundry detergent, paint, ketchup and even salad dressing.

Using affinity capillary electrophoresis and computational models for binding studies of heparinoids with p-selectin and other proteins.

PubMed

Mozafari, Mona; Balasupramaniam, Shantheya; Preu, Lutz; El Deeb, Sami; Reiter, Christian G; Wätzig, Hermann

2017-06-01

A fast and precise affinity capillary electrophoresis (ACE) method has been developed and applied for the investigation of the binding interactions between P-selectin and heparinoids as potential P-selectin inhibitors in the presence and absence of calcium ions. Furthermore, model proteins and vitronectin were used to appraise the binding behavior of P-selectin. The normalized mobility ratios (∆R/R f ), which provided information about the binding strength and the overall charge of the protein-ligand complex, were used to evaluate the binding affinities. It was found that P-selectin interacts more strongly with heparinoids in the presence of calcium ions. P-selectin was affected by heparinoids at the concentration of 3 mg/L. In addition, the results of the ACE experiments showed that among other investigated proteins, albumins and vitronectin exhibited strong interactions with heparinoids. Especially with P-selectin and vitronectin, the interaction may additionally induce conformational changes. Subsequently, computational models were applied to interpret the ACE experiments. Docking experiments explained that the binding of heparinoids on P-selectin is promoted by calcium ions. These docking models proved to be particularly well suited to investigate the interaction of charged compounds, and are therefore complementary to ACE experiments. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

The Altus Cumulus Electrification Study (ACES): A UAV-Based Science Demonstration

NASA Technical Reports Server (NTRS)

Blakeslee, R. J.; Croskey, C. L.; Desch, M. D.; Farrell, W. M.; Goldberg, R. A.; Houser, J. G.; Kim, H. S.; Mach, D. M.; Mitchell, J. D.; Stoneburner, J. C.

2003-01-01

The Altus Cumulus Electrification Study (ACES) is an unmanned aerial vehicle (UAV)- based project that investigated thunderstorms in the vicinity of the Florida Everglades in August 2002. ACES was conducted to investigate storm electrical activity and its relationship to storm morphology, and to validate satellite-based lightning measurements. In addition, as part of the NASA sponsored UAV-based science demonstration program, this project provided a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. ACES employed the Altus II aircraft, built by General Atomics - Aeronautical Systems, Inc. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and provide Lightning Imaging Sensor validation. The ACES payload included electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. ACES contributed important electrical and optical measurements not available from other sources. Also, the high altitude vantage point of the UAV observing platform (up to 55,000 feet) provided cloud-top perspective. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high altitude flight, the Altus was flown near, and when possible, over (but never into) thunderstorms for long periods of time that allowed investigations to be conducted over entire storm life cycles. An innovative real time weather system was used to identify and vector the aircraft to selected thunderstorms and safely fly around these storms, while, at the same time monitor the weather near our base of operations. In addition, concurrent ground-based observations that included radar (Miami and Key West WSRBD, NASA NPOL), satellite imagery, and lightning (NALDN and Los Alamos EDOT) enable the UAV measurements to be more completely interpreted and evaluated in the context of the thunderstorm structure, evolution, and environment.

Insertion/Deletion Polymorphisms and Serum Angiotensin-converting Enzyme Levels in Iranian Patients with Sarcoidosis

PubMed Central

JAVADI, Alireza; SHAMAEI, Masoud; ZAREI, Masoud; REZAEIAN, Lida; KIANI, Arda; ABEDINI, Atefeh

2016-01-01

Background: Sarcoidosis is a multisystem inflammatory disease of unknown origin with characterization of small granulomas. Angiotensin-converting enzyme (ACE) is a pathophysiologic marker of sarcoidosis. We present the ACE insertion/deletion (I/D) polymorphism in correlation with serum ACE level in Iranian patients with sarcoidosis. Methods: From Jan 2014 to Jan 2015, 102 Iranian patients who histopathologically diagnosed for sarcoidosis and 192 healthy age and sex-matched controls were recruited. PCR was used for detection of I/D polymorphism in ACE gene. Results: Frequency of II/ID/DD genotype in sarcoidosis disease was 17%, 35.5%, and 47.1%, respectively. The frequency of D allele was 0.65. A significant association between I/D genotypes and mean of sACE level was seen (DD=85.2±22.9, P<0.001). More frequent genotype in sarcoidosis patients was DD (47%), ID genotype (45.9%) was found more in controls. Logistic regression analysis adjusting age and sex showed that ID to II (OR=0.35, 95%CI=0.17–0.73, P=0.005) and DD to II (OR=2.11, 95%CI=0.98–4.54, P=0.05) could be considered as a predictor factor for the disease activity. No significant model for men in sarcoidosis group was seen, while women with II/ID were associated with a reduced risk for the disease. Conclusion: Although more regional studies with appropriate statistical scale must be done to provide a better diagnosis and prognostic tool for this disease, this study demonstrates that ID and DD genotype could be predictive factors for sarcoidosis. PMID:28032065

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.

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.

iss038e055240

NASA Image and Video Library

2014-02-24

ISS038-E-055240 (24 Feb. 2014) --- In the International Space Station's Destiny laboratory, NASA astronaut Mike Hopkins, Expedition 38 flight engineer, sets up the Advanced Colloids Experiment (ACE) housed in the Light Microscopy Module (LMM) inside the Fluids Integrated Rack. ACE studies microscopic particles suspended in a liquid.

Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.

PubMed

Fan, Jinqi; Zou, Lili; Cui, Kun; Woo, Kamsang; Du, Huaan; Chen, Shaojie; Ling, Zhiyu; Zhang, Quanjun; Zhang, Bo; Lan, Xianbin; Su, Li; Zrenner, Bernhard; Yin, Yuehui

2015-01-01

The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1-7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-β1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin-angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF.

Interleukin-2 Receptor and Angiotensin-Converting Enzyme as Markers for Ocular Sarcoidosis

PubMed Central

Gundlach, Enken; Hoffmann, Michael Marcus; Prasse, Antje; Heinzelmann, Sonja; Ness, Thomas

2016-01-01

Purpose To study the impact of soluble IL2 receptor (sIL2R), chest x-ray (CxR), and angiotensin-converting enzyme (ACE) as markers for sarcoidosis in uveitis patients. Design Retrospective study. Methods Serum concentrations of sIL2R and ACE were measured in patients with active uveitis. Those with elevated sIL2R and /or ACE values were examined for suspected systemic sarcoidosis. Main Outcome Measure Our main outcome parameters were the specificity and sensitivity of sIL2R, CxR and ACE in screening for ocular sarcoidosis. Results We measured 261 patients with uveitis for sarcoidosis using sIL2R and ACE between January 2008 and November 2011; sarcoidosis was been diagnosed using other tests (e.g. computer tomography, brochoalveolar lavage, biopsy) in 41 of 53 patients with elevated sIL2R values (>639 U/ml) and in one patient with normal sIL2R (582 U/ml). Their mean sIL2R value was 1310 U/ml, extending from 582 to 8659 U/ml. Only 9 patients, however, presented elevated ACE (>82 U/l). Their mean ACE value was 116.4 U/l, ranging from 84.1 to 175.5 U/l. IL2R specificity was 94% with 98% sensitivity. In contrast, ACE had a specificity of 99.5%, but a sensitivity of only 22%; the chest x-ray had a specificity of 100% with 50% sensitivity in detecting sarcoidosis. We observed the entire spectrum of uveitis: sixteen patients suffered from anterior, 8 from intermediate, 16 from posterior, and 2 from panuveitis. Conclusions An elevated level of soluble IL2R suggests sarcoidosis with uveitis more convincingly than ACE, making sIL2R a more effective marker parameter for sarcoidosis than ACE or chest x-ray in uveitis patients. PMID:26799486

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

Paricalcitol modulates ACE2 shedding and renal ADAM17 in NOD mice beyond proteinuria.

PubMed

Riera, Marta; Anguiano, Lidia; Clotet, Sergi; Roca-Ho, Heleia; Rebull, Marta; Pascual, Julio; Soler, Maria Jose

2016-03-15

Circulating and renal activity of angiotensin-converting enzyme 2 (ACE2) is increased in non-obese diabetic (NOD) mice. Because paricalcitol has been reported to protect against diabetic nephropathy, we investigated the role of paricalcitol in modulating ACE2 in these mice. In addition, renal ADAM17, a metalloprotease implied in ACE2 shedding, was assessed. NOD female and non-diabetic control mice were studied for 21 days after diabetes onset and divided into various treatment groups. Diabetic animals received either vehicle; 0.4 or 0.8 μg/kg paricalcitol, aliskiren, or a combination of paricalcitol and aliskiren. We then studied the effect of paricalcitol on ACE2 expression in proximal tubular epithelial cells. Paricalcitol alone or in combination with aliskiren resulted in significantly reduced circulating ACE2 activity in NOD mice but there were no changes in urinary albumin excretion. Serum renin activity was significantly decreased in mice that received aliskiren but no effect was found when paricalcitol was used alone. Renal content of ADAM17 was significantly decreased in animals that received a high dose of paricalcitol. Renal and circulating oxidative stress (quantified by plasma H2O2 levels and immunolocalization of nitrotyrosine) were reduced in high-dose paricalcitol-treated mice compared with non-treated diabetic mice. In culture, paricalcitol incubation resulted in a significant increase in ACE2 expression compared with nontreated cells. In NOD mice with type 1 diabetes, paricalcitol modulates ACE2 activity, ADAM17, and oxidative stress renal content independently from the glycemic profile and urinary albumin excretion. In tubular cells, paricalcitol may modulate ACE2 by blocking its shedding. In the early stage of diabetic nephropathy, paricalcitol treatment counterbalances the effect of diabetes on circulating ACE2 activity. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies. Copyright © 2016 the American Physiological Society.

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.

Anoctamin 6 Contributes to Cl- Secretion in Accessory Cholera Enterotoxin (Ace)-stimulated Diarrhea: AN ESSENTIAL ROLE FOR PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE (PIP2) SIGNALING IN CHOLERA.

PubMed

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

2016-12-23

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 I Cl 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 I Cl 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 [Ca 2+ ] i rise in Caco-2 cells, but cellular abundance of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) increased. Identification of the PIP 2 -binding motif at the N-terminal sequence among human and mouse ANO6 variants along with binding of PIP 2 directly to ANO6 in HEK293 cells indicate likely PIP 2 regulation of ANO6. The biophysical and pharmacological properties of Ace stimulated Cl - current along with intestinal fluid accumulation, and binding of PIP 2 to the proximal KR motif of channel proteins, whose mutagenesis correlates with altered binding of PIP 2 , 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-PIP 2 signaling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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

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

Social work and adverse childhood experiences research: implications for practice and health policy.

PubMed

Larkin, Heather; Felitti, Vincent J; Anda, Robert F

2014-01-01

Medical research on "adverse childhood experiences" (ACEs) reveals a compelling relationship between the extent of childhood adversity, adult health risk behaviors, and principal causes of death in the United States. This article provides a selective review of the ACE Study and related social science research to describe how effective social work practice that prevents ACEs and mobilizes resilience and recovery from childhood adversity could support the achievement of national health policy goals. This article applies a biopsychosocial perspective, with an emphasis on mind-body coping processes to demonstrate that social work responses to adverse childhood experiences may contribute to improvement in overall health. Consistent with this framework, the article sets forth prevention and intervention response strategies with individuals, families, communities, and the larger society. Economic research on human capital development is reviewed that suggests significant cost savings may result from effective implementation of these strategies.

Validation of ACE-FTS measurements of CFC-11, CFC-12, and HCFC-22 using ground-based FTIR spectrometers

NASA Astrophysics Data System (ADS)

Kolonjari, F.; Walker, K. A.; Mahieu, E.; Batchelor, R. L.; Bernath, P. F.; Boone, C.; Conway, S. A.; Dan, L.; Griffin, D.; Harrett, A.; Kasai, Y.; Kagawa, A.; Lindenmaier, R.; Strong, K.; Whaley, C.

2013-12-01

Satellite datasets can be an effective global monitoring tool for long-lived compounds in the atmosphere. The Atmospheric Chemistry Experiment (ACE) is a mission on-board the Canadian satellite SCISAT-1. The primary instrument on SCISAT-1 is a high-resolution infrared Fourier transform spectrometer (ACE-FTS) which is capable of measuring a range of gases including key chlorofluorocarbon (CFC) and hydrochlorofluorocarbon (HCFC) species. These families of species are of interest because of their significant contribution to anthropogenic ozone depletion and to global warming. To assess the quality of data derived from satellite measurements, validation using other data sources is essential. Ground-based Fourier transform infrared (FTIR) spectrometers are particularly useful for this purpose. In this study, five FTIR spectrometers located at four sites around the world are used to validate the CFC-11 (CCl3F), CFC-12 (CCl2F2), and HCFC-22 (CHClF2) retrieved profiles from ACE-FTS measurements. These species are related because HCFC-22 was the primary replacement for CFC-11 and CFC-12 in refrigerant and propellant applications. The FTIR spectrometers used in this study record solar absorption spectra at Eureka (Canada), Jungfraujoch (Switzerland), Poker Flat (USA), and Toronto (Canada). The retrieval of CFC-11, CFC-12, and HCFC-22 are not standard products for many of these instruments, and as such, a harmonization of retrieval parameters between the sites has been conducted. The retrievals of these species from the FTIR spectra are sensitive from the surface to approximately 20 km, while the ACE-FTS profiles extend from approximately 6 to 30 km. For each site, partial column comparisons between coincident measurements of the three species and a validation of the observed trends will be discussed.

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

Renin-angiotensin system phenotyping as a guidance toward personalized medicine for ACE inhibitors: can the response to ACE inhibition be predicted on the basis of plasma renin or ACE?

PubMed

Schilders, Joyce E M; Wu, Haiyan; Boomsma, Frans; van den Meiracker, Anton H; Danser, A H Jan

2014-08-01

Not all hypertensive patients respond well to ACE inhibition. Here we determined whether renin-angiotensin system (RAS) phenotyping, i.e., the measurement of renin or ACE, can predict the individual response to RAS blockade, either chronically (enalapril vs. enalapril + candesartan) or acutely (enalapril ± hydrochlorothiazide, HCT). Chronic enalapril + candesartan induced larger renin rises, but did not lower blood pressure (BP) more than enalapril. Similar observations were made for enalapril + HCT vs. enalapril when given acutely. Baseline renin predicted the peak changes in BP chronically, but not acutely. Baseline ACE levels had no predictive value. Yet, after acute drug intake, the degree of ACE inhibition, like Δrenin, did correlate with ΔBP. Only the relationship with Δrenin remained significant after chronic RAS blockade. Thus, a high degree of ACE inhibition and a steep renin rise associate with larger acute responses to enalapril. However, variation was large, ranging >50 mm Hg for a given degree of ACE inhibition or Δrenin. The same was true for the relationships between Δrenin and ΔBP, and between baseline renin and the maximum reduction in BP in the chronic study. Our data do not support that RAS phenotyping will help to predict the individual BP response to RAS blockade. Notably, these conclusions were reached in a carefully characterized, homogenous population, and when taking into account the known fluctuations in renin that relate to gender, age, ethnicity, salt intake and diuretic treatment, it seems unlikely that a cut-off renin level can be defined that has predictive value.

Dietary calcium intake and renin angiotensin system polymorphisms alter the blood pressure response to aerobic exercise: a randomized control design.

PubMed

Pescatello, Linda S; Turner, Debbie; Rodriguez, Nancy; Blanchard, Bruce E; Tsongalis, Gregory J; Maresh, Carl M; Duffy, Valerie; Thompson, Paul D

2007-01-04

Dietary calcium intake and the renin angiotensin system (RAS) regulate blood pressure (BP) by modulating calcium homeostasis. Despite similar BP regulatory effects, the influence of dietary calcium intake alone and combined with RAS polymorphisms on the BP response following acute aerobic exercise (i.e., postexercise hypotension) has not been studied. Thus, we examined the effect of dietary calcium intake and selected RAS polymorphisms on postexercise hypotension. Subjects were men (n = 50, 43.8 +/- 1.3 yr) with high BP (145.3 +/- 1.5/85.9 +/- 1.1 mm Hg). They completed three experiments: non-exercise control and two cycle bouts at 40% and 60% of maximal oxygen consumption (VO2max). Subjects provided 3 d food records on five protocol-specific occasions. Dietary calcium intake was averaged and categorized as low (<880 mg/d = LowCa) or high (> or = 880 mg/d = HighCa). RAS polymorphisms (angiotensin converting enzyme insertion/deletion, ACE I/D; angiotensin II type 1 receptor, AT1R A/C) were analyzed with molecular methods. Genotypes were reduced from three to two: ACE II/ID and ACE DD; or AT1R AA and AT1R CC/AC. Repeated measure ANCOVA tested if BP differed among experiments, dietary calcium intake level and RAS polymorphisms. Systolic BP (SBP) decreased 6 mm Hg after 40% and 60% VO2max compared to non-exercise control for 10 h with LowCa (p < 0.01), but not with HighCa (p > or = 0.05). Under these conditions, diastolic BP (DBP) did not differ between dietary calcium intake levels (p > or = 0.05). With LowCa, SBP decreased after 60% VO2max versus non-exercise control for 10 h among ACE II/ID (6 mm Hg) and AT1R AA (8 mm Hg); and by 8 mm Hg after 40% VO2max among ACE DD and AT1R CC/CA (p < 0.01). With HighCa, SBP (8 mm Hg) and DBP (4 mm Hg) decreased after 60% VO2max compared to non-exercise control for 10 h (p < 0.05), but not after 40% VO2max (p > or = 0.05). SBP decreased after exercise compared to non-exercise control among men with low but not high dietary calcium intake. Dietary calcium intake interacted with the ACE I/D and AT1R A/C polymorphisms to further modulate postexercise hypotension. Interactions among dietary calcium intake, exercise intensity and RAS polymorphisms account for some of the variability in the BP response to exercise.

Adverse Childhood Experiences and the Risk of Criminal Justice Involvement and Victimization Among Homeless Adults With Mental Illness.

PubMed

Edalati, Hanie; Nicholls, Tonia L; Crocker, Anne G; Roy, Laurence; Somers, Julian M; Patterson, Michelle L

2017-12-01

Exposure to adverse childhood experiences (ACEs) is highly prevalent among homeless individuals and is associated with negative consequences during homelessness. This study examined the effect of ACEs on the risk of criminal justice involvement and victimization among homeless individuals with mental illness. The study used baseline data from a demonstration project (At Home/Chez Soi) that provided Housing First and recovery-oriented services to homeless adults with mental illness. The sample was recruited from five Canadian cities and included participants who provided valid responses on an ACEs questionnaire (N=1,888). Fifty percent reported more than four types of ACE, 19% reported three or four types, 19% reported one or two, and 12% reported none. Rates of criminal justice involvement and victimization were significantly higher among those with a history of ACEs. For victimization, the association was significant for all ten types of ACE, and for justice involvement, it was significant for seven types. Logistic regression models indicated that the effect of cumulative childhood adversity on the two outcomes was significant regardless of sociodemographic factors, duration of homelessness, and psychiatric diagnosis, with one exception: the relationship between cumulative childhood adversity and criminal justice involvement did not remain significant when the analysis controlled for a diagnosis of posttraumatic stress disorder and substance dependence. Findings support the need for early interventions for at-risk youths and trauma-informed practice and violence prevention policies that specifically target homeless populations.

Structure-function studies of BPP-BrachyNH2 and synthetic analogues thereof with Angiotensin I-Converting Enzyme.

PubMed

Arcanjo, Daniel D R; Vasconcelos, Andreanne G; Nascimento, Lucas A; Mafud, Ana Carolina; Plácido, Alexandra; Alves, Michel M M; Delerue-Matos, Cristina; Bemquerer, Marcelo P; Vale, Nuno; Gomes, Paula; Oliveira, Eduardo B; Lima, Francisco C A; Mascarenhas, Yvonne P; Carvalho, Fernando Aécio A; Simonsen, Ulf; Ramos, Ricardo M; Leite, José Roberto S A

2017-10-20

The vasoactive proline-rich oligopeptide termed BPP-BrachyNH 2 (H-WPPPKVSP-NH 2 ) induces in vitro inhibitory activity of angiotensin I-converting enzyme (ACE) in rat blood serum. In the present study, the removal of N-terminal tryptophan or C-terminal proline from BPP-BrachyNH 2 was investigated in order to predict which structural components are important or required for interaction with ACE. Furthermore, the toxicological profile was assessed by in silico prediction and in vitro MTT assay. Two BPP-BrachyNH 2 analogues (des-Trp 1 -BPP-BrachyNH 2 and des-Pro 8 -BPP-BrachyNH 2 ) were synthesized, and in vitro and in silico ACE inhibitory activity and toxicological profile were assessed. The des-Trp 1 -BPP-BrachyNH 2 and des-Pro 8 -BPP-BrachyNH 2 were respectively 3.2- and 29.5-fold less active than the BPP-BrachyNH 2 -induced ACE inhibitory activity. Molecular Dynamic and Molecular Mechanics Poisson-Boltzmann Surface Area simulations (MM-PBSA) demonstrated that the ACE/BBP-BrachyNH 2 complex showed lower binding and van der Wall energies than the ACE/des-Pro 8 -BPP-BrachyNH 2 complex, therefore having better stability. The removal of the N-terminal tryptophan increased the in silico predicted toxicological effects and cytotoxicity when compared with BPP-BrachyNH 2 or des-Pro 8 -BPP-BrachyNH 2 . Otherwise, des-Pro 8 -BPP-BrachyNH 2 was 190-fold less cytotoxic than BPP-BrachyNH 2 . Thus, the removal of C-terminal proline residue was able to markedly decrease both the BPP-BrachyNH 2 -induced ACE inhibitory and cytotoxic effects assessed by in vitro and in silico approaches. In conclusion, the aminoacid sequence of BPP-BrachyNH 2 is essential for its ACE inhibitory activity and associated with an acceptable toxicological profile. The perspective of the interactions of BPP-BrachyNH 2 with ACE found in the present study can be used for development of drugs with differential therapeutic profile than current ACE inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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.

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.

Characterization of renin-angiotensin system enzyme activities in cultured mouse podocytes.

PubMed

Velez, Juan Carlos Q; Bland, Alison M; Arthur, John M; Raymond, John R; Janech, Michael G

2007-07-01

Intraglomerular ANG II has been linked to glomerular injury. However, little is known about the contribution of podocytes (POD) to intraglomerular ANG II homeostasis. The aim of the present study was to examine the processing of angiotensin substrates by cultured POD. Our approach was to use matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for peptide determination from conditioned cell media and customized AQUA peptides for quantification. Immortalized mouse POD were incubated with 1-2 microM ANG I, ANG II, or the renin substrate ANG-(1-14) for different time intervals and coincubated in parallel with various inhibitors. Human mesangial cells (MES) were used as controls. POD incubated with 1 microM ANG I primarily formed ANG-(1-9) and ANG-(1-7). In contrast, MES incubated with ANG I primarily generated ANG II. In POD, ANG-(1-7) was the predominant product, and its formation was inhibited by a neprilysin inhibitor. Modest angiotensin-converting enzyme (ACE) activity was also detected in POD, although only after cells were incubated with 2 microM ANG I. In addition, we observed that POD degraded ANG II into ANG III and ANG-(1-7). An aminopeptidase A inhibitor inhibited ANG III formation, and an ACE2 inhibitor led to ANG II accumulation. Furthermore, we found that POD converted ANG-(1-14) to ANG I and ANG-(1-7). This conversion was inhibited by a renin inhibitor. These findings demonstrate that POD express a functional intrinsic renin-angiotensin system characterized by neprilysin, aminopeptidase A, ACE2, and renin activities, which predominantly lead to ANG-(1-7) and ANG-(1-9) formation, as well as ANG II degradation. These findings may reflect a specific role of POD in maintenance of intraglomerular renin-angiotensin system balance.

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

A Multivariate Analysis of Adverse Childhood Experiences and Health Behaviors and Outcomes among College Students

ERIC Educational Resources Information Center

Windle, Michael; Haardörfer, Regine; Getachew, Beth; Shah, Jean; Payne, Jackie; Pillai, Dina; Berg, Carla J.

2018-01-01

Objective: This study investigated associations between adverse childhood experiences (ACE) prior to age 18 years and multiple health behaviors (eg, cigarette and other substance use) and outcomes (eg, obesity, depression) for a large college sample. Participants: 2,969 college students from seven universities in the state of Georgia were included…

Artificial sweeteners as waste water markers in a shallow unconfined aquifer

NASA Astrophysics Data System (ADS)

Bichler, Andrea; Muellegger, Christian; Hofmann, Thilo

2013-04-01

One key factor in groundwater quality management is the knowledge of flow paths and recharge. In coupled ground- and surface water systems the understanding of infiltration processes is therefore of paramount importance. Recent studies show that artificial sweeteners - which are used as sugar substitutes in food and beverages - are suitable tracers for domestic wastewater in the aquatic environment. As most rivers receive sewage discharges, artificial sweeteners might be used for tracking surface waters in groundwater. In this study artificial sweeteners are used in combination with conventional tracers (inert anions Cl-, SO42-, stable water isotopes δ18O, δ2H) to identify river water infiltration and the influence of waste water on a shallow unconfined aquifer used for drinking water production. The investigation area is situated in a mesoscale alpine head water catchment. The alluvial aquifer consists of quaternary gravel deposits and is characterized by high hydraulic permeability (kfmax 5 x 10-2 ms-1), high flow velocities (vmax 250 md-1) and a considerable productivity (2,5 m3s-1). A losing stream follows the aquifer in close proximity and is susceptible to infiltrate substantial volumes of water into the alluvial sediments. Water sampling campaigns in March and July 2012 confirmed the occurrence of artificial sweeteners (Acesulfam ACE, Sucralose SUC, Saccharin SAC and Cyclamat CYC) at the investigated site. The local sewage treatment plant was identified as point source of artificial sweeteners in the river water, with ACE concentrations up to 0,6 μgL-1. ACE concentrations in groundwater where approximately of one order of magnitude lower: ACE was present in 33 out of 40 sampled groundwater wells with concentrations up to 0,07 μgL-1, thus indicating considerable influence of sewage water loaded surface water throughout the aquifer. Elevated concentrations of ACE and SAC in single observation wells denote other sources of locally limited contamination. Also, the temporal variability of sweeteners in surface water and the drinking water production well is compared with other tracers. ACE, Cl-and SO42- exhibit similar patterns in the river water. However, this behaviour cannot be observed in the production well, where ACE concentrations are varying compared to Cl- and SO42-.This suggests that the production well does receive groundwater being infiltrated prior to the sewage water treatment plant. Time series analysis of 18O, δ2H will give more insight in travel times and the location of infiltration zones.

LSS systems planning and performance program

NASA Technical Reports Server (NTRS)

Mckenna, Victoria Jones; Dendy, Michael J.; Naumann, Charles B.; Rice, Sally A.; Weathers, John M.

1993-01-01

This report describes, using viewgraphs, the Marshall Space Flight Center's Large Space Structures Ground Test Facilities located in building 4619. Major topics include the Active Control Evaluation of Systems (ACES) Laboratory; the Control-Structures Interaction/Controls, Astrophysics, and Structures Experiment in Space (CSI/CASES); Advanced Development Facility; and the ACES Guest Investigator Program.

A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

PubMed

Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

2011-10-01

A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

Optical effects produced by running onboard engines of low-earth-orbit spacecraft

NASA Astrophysics Data System (ADS)

Beletskiy, A. B.; Mihalev, A. V.; Hahinov, V. V.; Lebedev, V. P.

2016-12-01

This paper presents results of optical observations made during Radar-Progress Experiment performed on April 17, 2013 and July 30, 2014 after approach-correction engines (ACE) of Progress M-17M and Progress M-23M cargo spacecraft in the thermosphere had been started. A region of enhanced emission intensity was recorded during engine operation. This may have been related to the scatter of twilight solar emission along the cargo spacecraft exhaust and to the emergence of additional atomic oxygen [OI] emission at 630 nm. The maximum dimension of the observed emission region was ~330-350 km and ~250-270 km along and across the orbit respectively. For the first time after ACE had been started, an expansion rate of emission region was ~ 7 and ~ 3.5 km/s along and across the orbit respectively. The maximum intensity of the disturbance area for Progress M-17M is estimated as ~40-60 R at 2 nm. Progress M-23M Space Experiment recorded a minor disturbance of atmospheric [OI] 630.0 nm emissions, both in near and in far cargo spacecraft flight paths, which might have been associated with the ACE exhaust gas injection.

Overexpression of heterogeneous nuclear ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes.

PubMed

Lo, Chao-Sheng; Shi, Yixuan; Chang, Shiao-Ying; Abdo, Shaaban; Chenier, Isabelle; Filep, Janos G; Ingelfinger, Julie R; Zhang, Shao-Ling; Chan, John S D

2015-10-01

We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes. Adult male Akita transgenic (Tg) mice overexpressing specifically hnRNP F in their renal proximal tubular cells (RPTCs) were studied. Non-Akita littermates and Akita mice served as controls. Immortalised rat RPTCs stably transfected with plasmid containing either rat Hnrnpf cDNA or rat Ace-2 gene promoter were also studied. Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf-β1, TGF-β receptor II [Tgf-βrII]) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1-7 receptor [MasR]) expression, and normalised urinary Ang 1-7 level in Akita Hnrnpf-Tg mice as compared with Akita mice. In vitro, hnRNP F overexpression stimulated Ace-2 gene promoter activity, mRNA and protein expression, and attenuated Agt, Tgf-β1 and Tgf-βrII gene expression. Furthermore, hnRNP F overexpression prevented TGF-β1 signalling and TGF-β1 inhibition of Ace-2 gene expression. These data demonstrate that hnRNP F stimulates Ace-2 gene transcription, prevents TGF-β1 inhibition of Ace-2 gene transcription and induction of kidney injury in diabetes. HnRNP F may be a potential target for treating hypertension and renal fibrosis in diabetes.

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.

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.

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

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.

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.;

Implications of Advanced Crew Escape Suit Transpiration for the Orion Program

NASA Technical Reports Server (NTRS)

Bue, Grant; Kuznetz, Lawrence

2009-01-01

Human testing was conducted to more fully characterize the integrated performance of the Advanced Crew Escape Suit (ACES) with liquid cooling provide by an Individual Cooling Unit (ICU) across a broad range of environmental conditions and metabolic rates. Together with a correlation for the ACES Liquid Cooling Garment as a function of inlet temperature, metabolic rate, and crew size, a reasonably conservative correlation for core temperature was achieved for the human thermal model applied to the ACES with ICU cooling. A key observation for this correlation was accounting for transpiration of evaporated sweat through the Gortex(Registered TradeMark) liner of the ACES indicated by as much as 0.6 lbm of sweat evaporated over the course of the 1 hour test profile, most of which could not be attributed to respiration or head sweat evaporation of the crew. Historically it has been assumed that transpiration was not an important design feature of the ACES suit. The correlated human thermal model will show transpiration to be highly useful in hot survival situations for the Orion Program when adequate liquid cooling is not available.

Serum and tissue angiotensin-converting enzyme in patients with alopecia areata.

PubMed

Fahim, Shabnam; Montazer, Fatemeh; Tohidinik, Hamid Reza; Naraghi, Zahra Safaei; Abedini, Robabeh; Nasimi, Maryam; Ghandi, Narges

2018-03-27

Alopecia areata is an immune-dependent disorder characterized by the interaction of T-lymphocytes with follicular antigens. Recent studies have shown the existence of a local renin-angiotensin system in the skin, where angiotensin-converting enzyme (ACE) plays a role in autoimmunity and inflammation. The objective of this study was to evaluate serum and tissue ACE activity in patients with alopecia areata. This case-control study was conducted on patients with alopecia areata and healthy controls. Serum and tissue ACE activity were assessed and compared between the two groups. Twenty-five alopecia areata patients (60% male, mean age 32.1 ± 9.9 years) and 24 controls (50% male, mean age 37.4 ± 8.8 years) were included. Mean serum ACE activity was 52.1 ± 9 U/L in cases and 55.3 ± 14.7 U/L in controls (P = 0.37). Tissue ACE activity was significantly lower in cases in all parts of the skin i.e. epidermis (P = 0.016), follicular epithelium (P = 0.004), and endothelium (P = 0.037). Among cases, serum ACE activity was significantly higher in patients with more severe disease (P = 0.030), nonpatchy alopecia areata (alopecia universalis; ophiasis, patchy and ophiasis, diffuse) (P = 0.029), and with nail involvement (P = 0.027). The sample size was too small to draw definite conclusions. Further, most of the patients had only mild or moderate alopecia areata. Unlike in some other inflammatory diseases, the tissue level of ACE seems to be significantly lower in alopecia areata compared to normal controls. Serum ACE was significantly higher in patients with more severe disease.

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

Regional-Scale Chemical Transport Modeling in Support of the Ace-Asia Experiment

NASA Astrophysics Data System (ADS)

Guttikunda, S.; Uno, I.; Carmichael, G.; Streets, D. G.; Tang, Y.; Yienger, J. J.; Woo, J.; Thongboonchoo, N.; Clarke, A.; Blomquist, B.; McNaughton, C.

2002-12-01

Chemical Transport Models (CTMs) are playing increasingly important roles in the design, execution, and analysis of large-scale atmospheric chemistry field studies. They are being used in forecast-mode to enhance flight planning by enabling the representation of important three-dimensional atmospheric chemical structures (such as dust storm plumes, polluted air masses associated with large cities, and widespread biomass burning events) and how they evolve over time. CTM forecasts play the additional important roles of providing a 4-dimensional contextual representation of the experiment, and facilitating a quicker analysis of the field results. CTMs also facilitate the integration of the different measurements and measurement platforms (e.g., aircraft, ground stations and satellite observations). Finally, CTMs play an important role in evaluating and helping to improve emission estimates. We developed the Chemical weather FORecasting System (CFORS) to assist in the analysis of field experiments. CFORS was applied in the design and execution of the TRACE-P, ACE-Asia and the ITCT-Y2K intensive field experiments. In this paper we present a brief overview of the CFORS system, and focus on the use of the CTM on the analysis of the Ace-Asia data. ACE-Asia produced a high density of data from multiple independent measurements, and a wide variety of different types of data. These include: a) in-situ measurements from ground stations, on board ships, and on various aircraft platforms; b) remote sensed data from satellites; and c) vertical distributions from ground based lidars. This data spans vast temporal and spatial scales, and illustrates the needs and challenges of integrating these data into a consistent data analysis set. In this paper we plan to illustrate efforts to integrate measured and modeled data into a comprehensive data set for analysis by measurers and modelers. We will also outline future directions and challenges.

Evaluation of Aerosol Properties over Ocean from Moderate Resolution Imaging Spectroradiometer (MODIS) during ACE-Asia

NASA Technical Reports Server (NTRS)

Chu, D. A.; Remer, L. A.; Kaufman, Y. J.; Schmid, B.; Redemann, J.; Knobelspiesse, K.; Chern, J.-D.; Livingston, J.; Russell, P. B.; Xiong, X.;

No association between ACE I/D polymorphism and cardiovascular hemodynamics during exercise in young women.

PubMed

Roltsch, M H; Brown, M D; Hand, B D; Kostek, M C; Phares, D A; Huberty, A; Douglass, L W; Ferrell, R E; Hagberg, J M

2005-10-01

The ACE I/D polymorphism has been shown to interact with habitual physical activity levels in postmenopausal women to associate with submaximal and with maximal exercise hemodynamics. This investigation was designed to assess the potential relationships between ACE genotype and oxygen consumption (VO2), cardiac output (Q), stroke volume (SV), heart rate (HR), blood pressure (BP), total peripheral resistance (TPR), and arteriovenous oxygen difference ([a-v]O2 diff) during submaximal and maximal exercise in young sedentary and endurance-trained women. Seventy-seven 18-35-yr-old women underwent a maximal exercise test and a number of cardiac output tests on a treadmill using the acetylene rebreathing technique. ACE genotype was not significantly associated with VO2max (II 41.4+/-1.2, ID 39.8+/-0.9, DD 39.8+/-1.1 ml/kg/min, p=ns) or maximal HR (II 191+/-2, ID 191+/-1, DD 193+/-2 bpm, p=ns). In addition, systolic and diastolic BP, (a-v)O2 diff, TPR, SV, and Q during maximal exercise were not significantly associated with ACE genotype. During submaximal exercise, SBP, Q, SV, HR, TPR, and (a-v)O2 diff were not significantly associated with ACE genotype. However, the association between diastolic BP during submaximal exercise and ACE genotype approached significance (p=0.08). In addition, there were no statistically significant interactions between ACE genotype and habitual physical activity (PA) levels for any of the submaximal or the maximal exercise hemodynamic variables. We conclude that the ACE I/D polymorphism was not associated, independently or interacting with habitual PA levels, submaximal, or maximal cardiovascular hemodynamics in young women.

ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension.

PubMed

Mendoza-Torres, Evelyn; Oyarzún, Alejandra; Mondaca-Ruff, David; Azocar, Andrés; Castro, Pablo F; Jalil, Jorge E; Chiong, Mario; Lavandero, Sergio; Ocaranza, María Paz

2015-08-01

The renin-angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE-Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling. © The Author(s), 2015.

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.

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.

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

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.

Design and implementation of robust decentralized control laws for the ACES structure at Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Collins, Emmanuel G., Jr.; Phillips, Douglas; Hyland, David C.

1990-01-01

An experiment was conducted to design controllers that would provide substantial reduction of line-of-sight control errors. The satisfaction of this objective required the controllers to attenuate the beam vibration significantly. Particular emphasis was placed on controller simplicity (i.e., reduced-order and decentralized controller architectures). Complexity reduction in control law implementation is of paramount interest due to stringent limitations on throughput of even state-of-the-art space qualified processors. The results of this experiment successfully demonstrate active vibrator control for a flexible structure. The testbed is the ACES structure at the NASA Marshall Space Flight Center. The ACES structure is dynamically traceable to future space systems and especially allows the study of line-of-sight control issues.

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

Wu, Kailang; Li, Weikai; Peng, Guiqing

NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel {beta}-sandwich core structure consisting of 2 layers of {beta}-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homologymore » in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a 'virus-binding hotspot' on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions.« less

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

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.

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

Atmospheric Climate Experiment Plus

NASA Astrophysics Data System (ADS)

Lundahl, K.

ACE+ is an atmospheric sounding mission using radio occultation techniques and is a combination of the two Earth Explorer missions ACE and WATS earlier proposed to ESA. ACE was highly rated by ESA in the Call for Earth Explorer Opportunity Missions in 1999 and was prioritised as number three and selected as a "hot-stand-by". A phase A study was carried out during 2000 and 2001. ACE will observe atmospheric parameters using radio occultations from an array of 6 micro-satellites which track the L- band signal of GPS satellites to map the detailed refractivity and thermal structure of the global atmosphere from surface to space. Water vapour and wind in Atmospheric Troposphere and Stratosphere WATS was the response to ESA's Call for Ideas for the next Earth Explorer Core Missions in 2001. WATS combines ACE GPS atmospheric occultations and LEO-LEO cross-link occultations. Cross-links strongly enhance the capability of measuring humidity relative to the ACE mission. The Earth Science Advisory Committée at ESA noted that the LEO-GNSS occultation technique is already well established through several missions in recent years and could not recommend WATS for a Phase A study as an Earth Explorer Core Mission. The ESAC was, however, deeply impressed by the LEO-LEO component of the WATS proposal and would regard it as regrettable if this science would be lost and encourages the ACE/WATS team to explore other means to achieve its scientific goal. ACE+ is therefore the response to ESA's 2nd Call for Earth Explorer Opportunity Missions in 2001 and will contribute in a significant manner to ESA's Living Planet Programme. ACE+ will considerably advance our knowledge about atmosphere physics and climate change processes. The mission will demonstrate a highly innovative approach using radio occultations for globally measuring profiles of humidity and temperature throughout the atmosphere and stratosphere. A constellation of 4 small satellites, tracking L-band GPS/GALILEO signals and X/K-band LEO-LEO cross-link signals, will be launched in 2 counter-rotating orbits with 2 satellites in each at 650 and 850 km respectively. Several aspects drive the spacecraft design. The GRAS+ and CALL+ instruments have a relatively high power consumption. The pointing and stability requirements call for a fully capable 3-axis attitude control system. Satellite characteristics include a mass of 130 kg, and available power of 80 W. The bus is based on the SMART-1 satellite from Swedish Space Corporation. In order to meet the cost envelope of the Earth Explorer Opportunity Missions the spacecraft should be a simple and robust design and makes use of the latest, but proven, technical developments as CAN-bus, GaAs solar cells and Li-Ion batteries. Low cost launch with a mix of START-1 and Rockot is also foreseen and could take place in 2006-2007. This paper describes mission characteristics and technical solutions for ACE+ .

The effect of acute angiotensin-converting enzyme and neutral endopeptidase 24.11 inhibition on plasma extravasation in the rat.

PubMed

Sulpizio, Anthony C; Pullen, Mark A; Edwards, Richard M; Brooks, David P

2004-06-01

The effect of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) inhibition on microvascular plasma leakage (extravasation) was evaluated in a rat model. Progressive inhibition of ACE using captopril caused increased extravasation when lung ACE was inhibited by >55%. In contrast, the selective inhibition of renal NEP by >90% using ecadotril did not increase extravasation. In NEP-inhibited rats, extravasation produced by the ACE inhibitors captopril and lisinopril was markedly enhanced. The dual ACE and NEP inhibitor omapatrilat, at oral doses of 0.03, 0.1, and 0.3 mg/kg, selectively inhibited lung ACE by 19, 61, and 76%, respectively, and did not cause significant extravasation. Doses of 1 and 10 mg/kg omapatrilat, which produced >90% inhibition of ACE and also inhibited renal NEP by 54 and 78%, respectively, significantly increased extravasation. In this model, bradykinin and substance P produced extravasation that could be abolished by the bradykinin 2 (B2) receptor antagonist Hoe 140 (icatibant) or the neurokinin1 (NK1) antagonist CP99994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine], respectively. Bradykinin induced extravasation was also partially ( approximately 40%) inhibited by CP99994, indicating that a portion of the response involves B2 receptor-mediated release of substance P. In conclusion, this study is the first to relate the degree of ACE and/or NEP inhibition to extravasation liability in the rat model. Our data clearly demonstrate that ACE inhibitor-induced plasma extravasation is enhanced by concomitant inhibition of NEP. In addition, this study provides further evidence for the role for B2 and NK1 receptors in mediating plasma extravasation in the rat.

Optimization of Bromelain-Aided Production of Angiotensin I-Converting Enzyme Inhibitory Hydrolysates from Stone Fish Using Response Surface Methodology.

PubMed

Muhammad Auwal, Shehu; Zarei, Mohammad; Abdul-Hamid, Azizah; Saari, Nazamid

2017-03-31

The stone fish is an under-utilized sea cucumber with many nutritional and ethno-medicinal values. This study aimed to establish the conditions for its optimum hydrolysis with bromelain to generate angiotensin I-converting enzyme (ACE)-inhibitory hydrolysates. Response surface methodology (RSM) based on a central composite design was used to model and optimize the degree of hydrolysis (DH) and ACE-inhibitory activity. Process conditions including pH (4-7), temperature (40-70 °C), enzyme/substrate (E/S) ratio (0.5%-2%) and time (30-360 min) were used. A pH of 7.0, temperature of 40 °C, E/S ratio of 2% and time of 240 min were determined using a response surface model as the optimum levels to obtain the maximum ACE-inhibitory activity of 84.26% at 44.59% degree of hydrolysis. Hence, RSM can serve as an effective approach in the design of experiments to improve the antihypertensive effect of stone fish hydrolysates, which can thus be used as a value-added ingredient for various applications in the functional foods industries.

After the honeymoon comes divorce: long-term use of the antegrade continence enema procedure.

PubMed

Yardley, Iain E; Pauniaho, Satu-Liisa; Baillie, Colin T; Turnock, Rick R; Coldicutt, Pat; Lamont, Graham L; Kenny, Simon E

2009-06-01

Having reported that 18% of children discontinue use of the antegrade continence enema (ACE) after 5 years, we aimed to determine long-term use after an ACE procedure. A postal/telephone questionnaire was conducted. Subjects were consecutive children undergoing an ACE between 1993 and 1999. Outcome measures were use of ACE, reasons for nonuse, complications, and overall satisfaction. Of 84 eligible subjects, data were available on 61 (73%) aged 22.4 years (15.5-35.1 years). Underlying diagnoses included spina bifida (n = 27), anorectal malformations (n = 18), constipation (n = 11), Hirschsprung's disease (n = 1), sacral agenesis (n = 2), and trauma/tumor (n = 2). Follow-up was 11.02 years (8.34-14.39 years). Thirty-six (59%) of 61 patients were still using their ACE. Reasons for nonuse were lack of effectiveness (n = 14), complications (n = 5), psychologic issues (n = 2), and poor compliance (n = 2). There was no association between diagnosis and nonuse (chi(2), P = .63). In those still using ACE, the overall satisfaction score was 4.1 (1-5). Several individuals reported feeling abandoned on becoming adults and losing the support they had in childhood. There is a late "failure" rate for the ACE procedure. However, satisfaction was high among those still using the ACE. This study further emphasizes the need for robust transitional care arrangements.

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

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.

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

Exercise-induced changes in insulin action are associated with ACE gene polymorphisms in older adults.

PubMed

Dengel, Donald R; Brown, Michael D; Ferrell, Robert E; Reynolds, Thomas H; Supiano, Mark A

2002-10-29

We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 +/- 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (S(I)), assessed by the frequently sampled intravenous glucose tolerance test, was significantly (P = 0.0001) increased following AEX. In addition, there was a significant (P = 0.001) interaction between AEX and ACE genotype. S(I) increased significantly (P < 0.05) more in those with the II (2.5 +/- 0.8 microU x 10(-4) x min(-1) x ml(-1)) ACE genotype compared with both the DD and ID (0.7 +/- 0.1 and 0.7 +/- 0.2 microU x 10(-4) x min(-1) x ml(-1), respectively) ACE genotypes. Similarly, there was a significant (P = 0.036) decrease in the acute insulin response to glucose (AIR(G)) and a significant (P = 0.05) interaction between AEX and ACE genotype. AIR(G) decreased significantly (P < 0.05) more in those with the II (-17.6 +/- 5.6 mU/ml) ACE genotype compared with both the DD and ID (-1.4 +/- 6.2 and -3.6 +/- 2.5 mU/ml) ACE genotypes. In conclusion, we demonstrated that those older hypertensives with the ACE II genotype have the greatest improvement in insulin action following AEX.

Aronia melanocarpa Elliot reduces the activity of angiotensin i-converting enzyme-in vitro and ex vivo studies.

PubMed

Sikora, Joanna; Broncel, Marlena; Mikiciuk-Olasik, Elżbieta

2014-01-01

The aim of the study was to analyze the effects of two-month supplementation with chokeberry preparation on the activity of angiotensin I-converting enzyme (ACE) in patients with metabolic syndrome (MS). During the in vitro stage of the study, we determined the concentration of chokeberry extract, which inhibited the activity of ACE by 50% (IC50). The participants (n = 70) were divided into three groups: I-patients with MS who received chokeberry extract supplements, II-healthy controls, and III-patients with MS treated with ACE inhibitors. After one and two months of the experiment, a decrease in ACE activity corresponded to 25% and 30%, respectively. We documented significant positive correlations between the ACE activity and the systolic (r = 0.459, P = 0.048) and diastolic blood pressure, (r = 0.603, P = 0.005) and CRP. The IC50 of chokeberry extract and captopril amounted to 155.4 ± 12.1 μg/mL and 0.52 ± 0.18 μg/mL, respectively. Our in vitro study revealed that chokeberry extract is a relatively weak ACE inhibitor. However, the results of clinical observations suggest that the favorable hypotensive action of chokeberry polyphenols may be an outcome of both ACE inhibition and other pleotropic effects, for example, antioxidative effect.

Addressing Adverse Childhood Experiences Through the Affordable Care Act: Promising Advances and Missed Opportunities.

PubMed

Srivastav, Aditi; Fairbrother, Gerry; Simpson, Lisa A

Adverse childhood experiences (ACEs) occur when children are exposed to trauma and/or toxic stress and may have a lifelong effect. Studies have shown that ACEs are linked with poor adult health outcomes and could eventually raise already high health care costs. National policy interest in ACEs has recently increased, as many key players are engaged in community-, state-, and hospital-based efforts to reduce factors that contribute to childhood trauma and/or toxic stress in children. The Affordable Care Act (ACA) has provided a promising foundation for advancing the prevention, diagnosis, and management of ACEs and their consequences. Although the ACA's future is unclear and it does not adequately address the needs of the pediatric population, many of the changes it spurred will continue regardless of legislative action (or inaction), and it therefore remains an important component of our health care system and national strategy to reduce ACEs. We review ways in which some of the current health care policy initiatives launched as part of the implementation of the ACA could accelerate progress in addressing ACEs by fully engaging and aligning various health care stakeholders while recognizing limitations in the law that may cause challenges in our attempts to improve child health and well-being. Specifically, we discuss coverage expansion, investments in the health workforce, a family-centered care approach, increased access to care, emphasis on preventive services, new population models, and improved provider payment models. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Forkhead Box Transcription Factors of the FOXA Class Are Required for Basal Transcription of Angiotensin-Converting Enzyme 2

PubMed Central

Pedersen, Kim Brint; Chodavarapu, Harshita

2017-01-01

Angiotensin-converting enzyme 2 (ACE2) has protective effects on a wide range of morbidities associated with elevated angiotensin-II signaling. Most tissues, including pancreatic islets, express ACE2 mainly from the proximal promoter region. We previously found that hepatocyte nuclear factors 1α and 1β stimulate ACE2 expression from three highly conserved hepatocyte nuclear factor 1 binding motifs in the proximal promoter region. We hypothesized that other highly conserved motifs would also affect ACE2 expression. By systematic mutation of conserved elements, we identified five regions affecting ACE2 expression, of which two regions bound transcriptional activators. One of these is a functional FOXA binding motif. We further identified the main protein binding the FOXA motif in 832/13 insulinoma cells as well as in mouse pancreatic islets as FOXA2. PMID:29082356

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.

Four Fourier transform spectrometers and the Arctic polar vortex: instrument intercomparison and ACE-FTS validation at Eureka during the IPY springs of 2007 and 2008

NASA Astrophysics Data System (ADS)

Batchelor, R. L.; Kolonjari, F.; Lindenmaier, R.; Mittermeier, R. L.; Daffer, W.; Fast, H.; Manney, G.; Strong, K.; Walker, K. A.

2010-01-01

The Canadian Arctic Atmospheric Chemistry Experiment Validation Campaigns have been carried out at Eureka, Nunavut (80.05° N, 86.42° W) during the polar sunrise period since 2004. During the International Polar Year (IPY) springs of 2007 and 2008, three ground-based Fourier transform infrared (FTIR) spectrometers were operated simultaneously. This paper presents a comparison of trace gas measurements of stratospherically important species involved in ozone depletion, namely O3, HCl, ClONO2, HNO3 and HF, recorded with these three spectrometers. Total column densities of the gases measured with the new Canadian Network for the Detection of Atmospheric Change (CANDAC) Bruker 125HR are shown to agree to within 3.5% with the existing Environment Canada Bomem DA8 measurements. After smoothing both of these sets of measurements to account for the lower spectral resolution of the University of Waterloo Portable Atmospheric Research Interferometric Spectrometer for the Infrared (PARIS-IR), the measurements were likewise shown to agree with PARIS-IR to within 7%. Concurrent measurements of these gases were also made with the satellite-based Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) during overpasses of Eureka during these time periods. While one of the mandates of the ACE satellite mission is to study ozone depletion in the polar spring, previous validation exercises have identified the highly variable polar vortex conditions of the spring period to be a challenge for validation efforts. In this work, comparisons between the CANDAC Bruker 125HR and ACE-FTS have been used to develop strict criteria that allow the ground- and satellite-based instruments to be confidently compared. When these criteria are taken into consideration, the observed biases between the ACE-FTS and ground-based FTIR spectrometer are not persistent for both years and are generally insignificant, though small positive biases of ~5%, comparable in magnitude to those seen in previous validation exercises, are observed for HCl and HF in 2007, and negative biases of -15.3%, -4.8% and -1.5% are seen for ClONO2, HNO3 and O3 in 2008.

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.

ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy.

PubMed

Vorselaars, Adriane D M; van Moorsel, Coline H M; Zanen, Pieter; Ruven, Henk J T; Claessen, Anke M E; van Velzen-Blad, Heleen; Grutters, Jan C

2015-02-01

In sarcoidosis, the search for disease activity markers that correlate with treatment response is ongoing. The aim of this study was to investigate the pattern of two proposed markers, serum angiotensin-converting enzyme (ACE) and soluble IL-2 receptor (sIL-2R) during methotrexate (MTX) therapy in sarcoidosis patients. We analysed 114 sarcoidosis patients who used MTX for six months, consisting of a subgroup of 76 patients with a pulmonary indication for treatment and a subgroup of 38 patients with an extra-pulmonary indication. ACE and sIL-2R serum levels were measured at baseline and after six months of treatment. Correlation coefficients (R) and odds ratios (ORs) were calculated to study the correlation and predictive effect of serum ACE and sIL-2R levels for pulmonary improvement. High baseline levels of ACE correlated significantly with lung function improvement after treatment (R = 0.45, p < 0.0001; stronger in the pulmonary subgroup R 0.57, p < 0.0001). ACE baseline levels >90 U/l predicted a 10% improvement in overall lung function (OR 3.55; CI 1.34-9.38), with the highest prediction level for 10% improvement in DLCO (OR 4.63; CI 1.23-17.4). After six months of MTX, mean ACE decreased with 17.2 U/l (p < 0.0001) and sIL-2R with 1850 pg/ml (p < 0.0001). Decreases in both ACE and sIL-2R correlated with an increase in lung function. The strongest correlation was found with change in DLCO in the pulmonary subgroup (ACE R = 0.63, P < 0.0001; sIL-2R R = 0.56, P < 0.0001). Baseline and serial serum ACE and sIL-2R levels correlate well with lung function improvement during MTX treatment. Serial measurements of these biomarkers are helpful in monitoring treatment effects in sarcoidosis patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association between angiotensin-converting enzyme gene polymorphisms and exercise performance in patients with COPD.

PubMed

Zhang, Xiaolei; Wang, Chen; Dai, Huaping; Lin, Yingxiang; Zhang, Jun

2008-09-01

Recent studies have shown that polymorphisms of the angiotensin-converting enzyme (ACE) gene are closely associated with pulmonary disorders. The ACE gene is involved in the regulation of inflammatory reactions to lung injury, respiratory drive, erythropoiesis and tissue oxygenation. The hypothesis for this study was that the ACE gene may be associated with the ventilatory response to exercise and the aerobic work efficiency of skeletal muscle in patients with COPD. Sixty-one Chinese Han COPD patients and 57 healthy control subjects performed incremental cardiopulmonary exercise testing on a cycle ergometer. ACE genotypes were determined using PCR amplification. Resting lung function and blood gas index were not significantly different among the three ACE genotype COPD groups. Similarly, there were no significant differences in AT, maximal O(2) uptake, maximal O(2) pulse, maximal dyspnoea index, ventilatory response (DeltaVE/DeltaVCO(2)), O(2) cost of ventilation (VO(2)/W/VE), end-tidal partial pressure of carbon dioxide at maximal exercise and maximal SaO(2) among the three ACE genotype COPD patients. Maximal work load and aerobic work efficiency were higher in the COPD group with the II genotype than in those with the ID or DD genotype. There were no significant differences in resting lung function and cardiopulmonary exercise testing parameters among the three ACE genotype control groups. The ACE gene may be involved in the regulation of skeletal muscle aerobic work efficiency, but is not associated with the ventilatory responses to exercise in COPD patients.

New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?

PubMed Central

Szoka, Piotr; Kolodziejczyk, Patrycjusz; Kramkowski, Karol; Wojewodzka-Zelezniakowicz, Marzena; Chabielska, Ewa

2016-01-01

The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT1 receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure. The ACE2-Ang-(1-7)-Mas receptor axis has a different role, since it often opposes the effects induced by the classical ACE-Ang II-AT1 axis. Once the positive effects of the ACE2-Ang-(1-7)-Mas axis were discovered, the alternative ways of pharmacotherapy activating this axis of RAAS appeared. This article briefly describes new molecules affecting the RAAS, namely: recombinant human ACE2, ACE2 activators, angiotensin-(1-7) peptide and non-peptide analogs, aldosterone synthase inhibitors, and the third and fourth generation of mineralocorticoid receptor antagonists. The results of the experimental and clinical studies are encouraging, which leads us to believe that these new molecules can support the treatment of cardiovascular diseases as well as cardiometabolic disorders. PMID:27439538

Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia.

PubMed

Shunmugam, Vicneswari; Say, Yee-How

2016-02-01

α-adrenergic receptor 2A (ADRA2A) and angiotensin-converting enzyme (ACE) genes have been variably associated with obesity and its related phenotypes in different populations worldwide. This cross-sectional study aims to investigate the association of adrenergic receptor α2A (ADRA2A) rs553668 and angiotensin-converting enzyme (ACE) I/D single nucleotide polymorphisms (SNPs) with obesity traits (body mass index-BMI; waist-hip ratio-WHR; total body fat percentage - TBF) in a Malaysian population. Demographic and clinical variables were initially collected from 230 subjects via convenience sampling among residents and workers in Setapak, Malaysia, but in the end only 214 multi-ethnic Malaysians (99 males; 45 Malays, 116 ethnic Chinese, and 53 ethnic Indians) were available for statistical analysis. Genotyping was performed by polymerase chain reaction using DNA extracted from mouthwash samples. The overall minor allele frequencies (MAFs) for ADRA2A rs553668 and ACE I/D were 0.55 and 0.56, respectively. Allele distribution of ACE I/D was significantly associated with ethnicity and WHR class. Logistic regression analysis showed that subjects with the ACE II genotype and I allele were, respectively, 2.15 and 1.55 times more likely to be centrally obese, but when adjusted for age and ethnicity, this association was abolished. Covariate analysis controlling for age, gender, and ethnicity also showed similar results, where subjects carrying the II genotype or I allele did not have significantly higher WHR. Combinatory genotype and allele analysis for ADRA2A rs553668 and ACE I/D showed that subjects with both ADRA2A rs553668 GG and ACE I/D II genotypes had significant lowest WHR compared to other genotype combinations. The ACE II genotype might be a protective factor against central adiposity risk among the Malaysian population when in combination with the ADRA2A rs553668 GG genotype.

Four Fourier transform spectrometers and the Arctic polar vortex: instrument intercomparison and ACE-FTS validation at Eureka during the IPY springs of 2007 and 2008

NASA Astrophysics Data System (ADS)

Batchelor, R. L.; Kolonjari, F.; Lindenmaier, R.; Mittermeier, R. L.; Daffer, W.; Fast, H.; Manney, G.; Strong, K.; Walker, K. A.

2009-11-01

The Canadian Arctic Atmospheric Chemistry Experiment Validation Campaigns have been carried out at Eureka, Nunavut (80.05° N, 86.42° W) during the polar sunrise period since 2004. During the International Polar Year (IPY) springs of 2007 and 2008, three ground-based Fourier transform infrared (FTIR) spectrometers were operated simultaneously. This paper presents a comparison of trace gas measurements of stratospherically important species involved in ozone depletion, namely O3, HCl, ClONO2, HNO3 and HF, recorded with these three spectrometers. Total column densities of the gases measured with the new Canadian Network for the Detection of Atmospheric Change (CANDAC) Bruker 125HR are shown to agree to within 3.5% with the existing Environment Canada Bomem DA8 measurements. After smoothing both of these sets of measurements to account for the lower spectral resolution of the University of Waterloo Portable Atmospheric Research Interferometric Spectrometer for the Infrared (PARIS-IR), the measurements were likewise shown to agree with PARIS-IR to within 7%. Concurrent measurements of these gases were also made with the satellite-based Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) during overpasses of Eureka during these time periods. While one of the mandates of the ACE satellite mission is to study ozone depletion in the polar spring, previous validation exercises have identified the highly variable polar vortex conditions of the spring period to be a challenge for validation efforts. In this work, comparisons between the CANDAC Bruker 125HR and ACE-FTS have been used to develop strict criteria that allow the ground- and satellite-based instruments to be confidently compared. When these criteria are taken into consideration, there is shown to be no significant bias between the ACE-FTS and ground-based FTIR spectrometer for any of these gases.

Gentamicin induces efaA expression and biofilm formation in Enterococcus faecalis.

PubMed

Kafil, Hossein Samadi; Mobarez, Ashraf Mohabati; Moghadam, Mehdi Forouzandeh; Hashemi, Zahra Sadat; Yousefi, Mehdi

2016-03-01

Enterococci have been ranked among the leading causes of nosocomial bacteremia and urinary tract infection. This study aimed to investigate the effect of ampicillin, vancomycin, gentamicin and ceftizoxime on biofilm formation and gene expression of colonization factors on Enterococcus faecalis. Twelve clinical isolates of E. faecalis were used to investigate the effect of antibiotics on biofilm formation and gene expression of efaA, asa1, ebpA, esp and ace. Flow system assay and Microtiter plates were used for biofilm assay. Two hundred clinical isolates were used for confirming the effect of antibiotics on biofilm formation. Ampicillin, vancomycin and ceftizoxime did not have any significant effect on biofilm formation, but gentamicin induced biofilm formation in 89% of isolates. In twelve selected isolate gentamicin increased expression of esp (+50.9%) and efaA (+33.9%) genes and reduced or maintained expression of others (asa1:-47.4%, ebpA: 0, ace:-19.2%). Vancomycin increased expression of esp (+89.1%) but reduced the others (asa1: -34.9%, ebpA:-11%, ace:-30%, efaA:-60%). Ceftizoxime increased slightly ebpA (+19.7%) and reduced others (asa1:-66.2%, esp:-35%, ace:-28.1%, efaA:-38.4%). and ampicillin strongly increased expression of ace (+231%), esp (+131%) and ebpA (+83%) but reduced others (asa1:-85.5%, efaA:-47.4%). The findings of the present study showed that antibiotics may have a role in biofilm formation and sustainability of enterococci, especially in case of gentamicin. efaA gene may have an important role, especially in antibiotic induced biofilm formation by gentamicin. Experiments with efaA mutants are needed to investigate the exact effect of efaA on biofilm formation with antibiotic induced cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Colorectal cancer screening and adverse childhood experiences: Which adversities matter?

PubMed

Alcalá, Héctor E; Keim-Malpass, Jessica; Mitchell, Emma

2017-07-01

Adverse Childhood Experiences (ACEs) have been associated with an increased risk of a variety of diseases, including cancer. However, research has not paid enough attention to the association between ACEs and cancer screening. As such, the present study examined the association between ACEs and ever using colorectal cancer (CRC) screening, among adults age 50 and over. Analyses used the 2011 Behavioral Risk Factor Surveillance System (n=24,938) to model odds of ever engaging in CRC screening from nine different adversities. Bivariate and multivariate models were fit. In bivariate models, physical abuse, having parents that were divorced or separated, and living in a household where adults treated each other violently were associated with lower odds of engaging in CRC. In multivariate models that accounted for potential confounders, emotional and sexual abuse were each associated with higher odds of engaging in CRC. Results suggest potential pathways by which early childhood experiences can impact future health behaviors. Future research should examine this association longitudinally. Copyright © 2017 Elsevier Ltd. 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.

Integrating a Data Center and Resident Archive into the Emerging Virtual Observatiry System: Practical experience and perspectives

NASA Astrophysics Data System (ADS)

Davis, A. J.; Kanekal, S. G.; Looper, M. D.; Mason, G. M.; Mewaldt, R. A.

2006-12-01

The SAMPEX Resident Archive is currently under construction, and will be co-hosted at Caltech with the ACE Science Center. With SAMPEX in low earth orbit, and ACE at L1, and a suite of instruments on each spacecraft, the combined data cover a very broad range in species, energy, location, and time. The data include 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 these data via the emerging virtual observatory system, including work with the Space Physics Archive Search and Extract (SPASE) Consortium to ensure that the ACE and SAMPEX data can be adequately described using the SPASE data model, development of a SOAP web services interface between the ACE Science Center and the virtual observatories, and ideas for combining the ACE and SAMPEx data in useful ways.

Adverse childhood experiences, mental health, and quality of life of Chilean girls placed in foster care: An exploratory study.

PubMed

Seiler, Annina; Kohler, Stefanie; Ruf-Leuschner, Martina; Landolt, Markus A

2016-03-01

In Latin America, little research has been conducted regarding exposure to adverse childhood experiences (ACEs), mental health, and health-related quality of life (HRQoL) among foster children. This study examined the association between ACEs and mental health, posttraumatic stress disorder (PTSD), and HRQoL in Chilean foster girls relative to age-matched Chilean family girls. Data were obtained from 27 Chilean foster girls and 27 Chilean girls ages 6 to 17 years living in family homes. Standardized self- and proxy-report measures were used. Foster girls reported more ACEs than controls in terms of familial and nonfamilial sexual abuse and both emotional and physical neglect. Girls living in foster care had a significantly higher rate of PTSD, displayed greater behavioral and emotional problems, and reported a lower HRQoL. Analysis confirmed the well-known cumulative risk hypothesis by demonstrating a significant positive association between the number of ACEs and PTSD symptom severity and a significant negative association with HRQoL. Chilean foster girls endured more ACEs that impair mental health and HRQoL than age-matched peers living with their families. These findings have implications for out-of-home care services in Latin America, highlighting the need to implement not only appropriate trauma-focused treatments but also appropriate prevention strategies. (c) 2016 APA, all rights reserved).

Children and Caregivers’ Exposure to Adverse Childhood Experiences (ACES): Association with Children’s and Caregivers’ Psychological Outcomes in a Therapeutic Preschool Program

PubMed Central

Ziv, Yair; Sofri, Inbar; Capps Umphlet, Kristen L.; Olarte, Stephanie; Venza, Jimmy

2018-01-01

Exposure to adverse childhood experiences (ACE) has been found to have a profound negative impact on multiple child outcomes, including academic achievement, social cognition patterns, and behavioral adjustment. However, these links have yet to be examined in preschool children that are already experiencing behavior or social-emotional problems. Thus, the present study examined the links between the caregiver’s and the child’s exposure to ACE and multiple child and caregiver’s outcomes in a sample of 30 preschool children enrolled in a Therapeutic Nursery Program (TNP). Children are typically referred to this TNP due to significant delays in their social emotional development that often result in difficulty functioning in typical childcare, home, and community settings. Analyses revealed some contradictory patterns that may be specific to this clinical sample. Children with higher exposure to ACE showed more biased social information processing patterns and their caregivers reported lower child social skills than caregivers of children with less exposure, however their inhibitory control levels were higher (better control) and staff reported that these children exhibited better social skills as well as better approaches to learning than children with less exposure. No such contradictions were found in relation to the caregiver’s exposure to ACE, as it was positively associated with a number of negative child and caregiver outcomes. PMID:29614735

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.

Marketing ACE in Victoria.

ERIC Educational Resources Information Center

2001

This publication presents options raised through various forums for marketing adult and community education (ACE) in Victoria, Australia, and suggested strategies. After an introduction (chapter 1), chapters 2 and 3 provide a broad view of the current situation for marketing ACE. Chapter 2 discusses general issues in the current position--ACE…

Coupling of anodic oxidation and adsorption by granular activated carbon for chemical oxygen demand removal from 4,4'-diaminostilbene-2,2'-disulfonic acid wastewater.

PubMed

Wang, Lizhang; Zhao, Yuemin

2010-01-01

Experiments were performed to reduce chemical oxygen demand (COD) from 4,4'-diaminostilbene-2,2'-disulfonic (DSD) acid manufacturing wastewater using electrochemical oxidation coupled with adsorption by granular activated carbon. The COD removal is affected by the residence time and applied voltage. When the residence time is increased, lower value of COD effluent could be obtained, however, the average current efficiency (ACE) decreased rapidly, and so does the applied voltage. In addition, aeration could effectively enhance COD removal efficiency and protect anodes from corrosion. Furthermore, the acidic condition is beneficial to the rapid decrease of COD and the values of pH effluent are independent of the initial solution pH. The optimization conditions obtained from these experiments are applied voltage of 4.8 V, residence time of 180 min and air-liquid ratio of 4.2 with the COD effluent of about 690 mg L⁻¹. In these cases, the ACE and energy consumption are 388% and 4.144 kW h kg⁻¹ COD, respectively. These perfect results from the experiments illustrate that the combined process is a considerable alternative for the treatment of industrial wastewater containing high concentration of organic pollutants and salinity.

Alterations in Circulatory and Renal Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 in Fetal Programmed Hypertension

PubMed Central

Shaltout, Hossam A.; Figueroa, Jorge P.; Rose, James C.; Diz, Debra I.; Chappell, Mark C.

2009-01-01

Antenatal betamethasone treatment is a widely accepted therapy to accelerate lung development and improve survival in preterm infants. However, there are reports that infants who receive antenatal glucocorticoids exhibit higher systolic blood pressure in their early adolescent years. We have developed an experimental model of programming whereby the offspring of pregnant sheep administered clinically relevant doses of betamethasone exhibit elevated blood pressure. We tested the hypothesis as to whether alterations in angiotensin-converting enzyme (ACE), ACE2, and neprilysin in serum, urine, and proximal tubules are associated with this increase in mean arterial pressure. Male sheep were administered betamethasone (2 doses of 0.17 mg/kg, 24 hours apart) or vehicle at the 80th day of gestation and delivered at term. Sheep were instrumented at adulthood (1.8 years) for direct conscious recording of mean arterial pressure. Serum and urine were collected and proximal tubules isolated from the renal cortex. Betamethasone-treated animals had elevated mean arterial pressure (97±3 versus 83±2 mm Hg; P<0.05) and a 25% increase in serum ACE activity (48.4±7.0 versus 36.0±2.7 fmol/mL per minute) but a 40% reduction in serum ACE2 activity (18.8±1.2 versus 31.4±4.4 fmol/mL per minute). In isolated proximal tubules, ACE2 activity and expression were 50% lower in the treated sheep with no significant change in ACE or neprilysin activities. We conclude that antenatal steroid treatment results in the chronic alteration of ACE and ACE2 in the circulatory and tubular compartments, which may contribute to the higher blood pressure in this model of fetal programming-induced hypertension. PMID:19047579

ACE DD genotype: a predisposing factor for abdominal aortic aneurysm.

PubMed

Fatini, C; Pratesi, G; Sofi, F; Gensini, F; Sticchi, E; Lari, B; Pulli, R; Dorigo, W; Azas, L; Pratesi, C; Gensini, G F; Abbate, R

2005-03-01

To examine the role of polymorphisms in angiotensin converting enzyme (ACE, I/D) and angiotensin II receptor (AT1R, A1166C) in the development of abdominal aortic aneurysm (AAA). We investigated 250 consecutive patients, 217 males and 33 females (median age 72, range 50-83), undergone AAA elective repair and 250 healthy controls, comparable for sex and age. ACE and AT1R polymorphisms were studied by PCR-RFLP analysis. The genotype distribution was in Hardy-Weinberg equilibrium for all polymorphisms. The genotype distribution and allele frequency of ACE I/D, but not AT1R A1166C polymorphism were significantly different between patients and controls (ACE I/D: p=0.0002 and p<0.0001, respectively, and AT1R A1166C: p=0.6 and p=0.4, respectively). An association between the ACE DD genotype and the predisposition to AAA was found (OR DD vs. ID+II=1.9 95% CI 1.3-2.9, p<0.0001). Multivariate analysis adjusted for age, sex, traditional vascular risk factors and other atherosclerotic localizations, showed ACE DD genotype to be independently related to the disease (OR DD vs. ID+II=2.4, 95% CI 1.3-4.2 p=0.003). Our findings document that ACE DD genotype represents a susceptibility factor for AAA.

Association of angiotensin-converting enzyme (ACE) and fatty acid binding protein 2 (FABP2) genes polymorphism with type 2 diabetes mellitus in Northern India.

PubMed

Raza, Syed Tasleem; Fatima, Jalees; Ahmed, Faisal; Abbas, Shania; Zaidi, Zeashan Haider; Singh, Seema; Mahdi, Farzana

2014-12-01

Type 2 diabetes mellitus (T2DM) is growing in an epidemic manner across the world with an expected doubling of the incidence to millions of affected individuals in the last decades. At present, adequate data are not available regarding the ACE and FABP2 polymorphisms and their susceptibility with T2DM cases in the North Indian population. Thus we conceived the need for further study of ACE (I/D) and FABP2 (Ala54Thr) genes polymorphism and its susceptibility to T2DM in the North Indian population. In this study, a total of 300 subjects (including 190 T2DM cases and 110 controls) participated. ACE and FABP2 gene polymorphisms in the cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism. The frequencies of ACE I/I, I/D and D/D genotypes in T2DM cases and controls were 28.73%, 55.17%, 16.09% and 13.63%, 57.95%, 28.40%, respectively. The frequencies of FABP2 Ala54Ala, Ala54Thr and Thr54Thr in T2DM cases were 18.39%, 66.66%, 14.94% and 22.72%, 61.36%, 15.90% in controls, respectively. ACE I/I genotype was significantly more frequent in cases as compared to controls (p = 0.003, χ(2) = 9.13). It appears that the ACE I/I genotype frequency was significantly higher in the T2DM cases as compared to the controls. © The Author(s) 2013.

[Application of Chinese version of ACE-Ⅲ in type 2 diabetes mellitus patients with mild cognitive impairment].

PubMed

Xin, J W; Xiao, X L; Chen, X C; Pan, X D

2017-11-28

Objective: To investigate the application and best cut-off value of Chinese version of Addenbrooke's cognitive examination-Ⅲ(ACE-Ⅲ) in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment. Methods: A total of 18 T2DM patients with normal cognitive function (NCI group) and 40 T2DM patients with mild cognitive impairment (MCI group) treated in outpatient clinic or ward of Department of Neurology and Endocrinology in Fujian Medical University Union Hospital between January 2015 and February 2016 were enrolled. Mini Mental State Scale (MMSE), Montreal cognitive assessment scale (MoCA), Activity of Daily Living Scale (ADL) and the Chinese version of ACE-Ⅲ were used to assess cognitive function of subjects and to assess the value of ACE-Ⅲ in the diagnosis of T2DM patients with mild cognitive impairment. Results: The Cronbach's alpha of the Chinese version of ACE-Ⅲ is 0.768. ACE-Ⅲ and MoCA were correlative ( r =0.768, P <0.001). The area under the receiver operating characteristic (ROC) curve for ACE-Ⅲ was 0.906 (95% CI : 0.827-0.985). When the cut-off value for diagnosis was 87.5, the maximum Youden index was 0.769, with a sensitivity of 0.825 and a specificity of 0.944. Patients in MCI group got a lower score in the sub-items of attention/orientation, memory, verbal fluency, language and visual space of ACE-Ⅲ compared to those in NCI group, and the differences were statistically significant ( t =5.336, P <0.001; t =5.530, P <0.001; t =4.556, P <0.001; t =5.301, P <0.001; t =2.821, P =0.008). Conclusion: The Chinese version of ACE-Ⅲ had good internal consistency reliability, and it could effectively detect impairment of general cognitive function and single cognitive domains in T2DM patients.

78 FR 25229 - Proposed Establishment of Class E Airspace; Stockton, KS

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-30

...-0274; Airspace Docket No. 13-ACE-2] Proposed Establishment of Class E Airspace; Stockton, KS AGENCY... the docket number FAA-2013-0274/Airspace Docket No. 13- ACE-2, at the beginning of your comments. You... No. FAA-2013-0274/ Airspace Docket No. 13-ACE-2.'' The postcard will be date/time stamped and...

Original Research: ACE2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis

PubMed Central

Prata, Luana O; Rodrigues, Carolina R; Martins, Jéssica M; Vasconcelos, Paula C; Oliveira, Fabrício Marcus S; Ferreira, Anderson J; Rodrigues-Machado, Maria da Glória

2016-01-01

The interstitial lung diseases are poorly understood and there are currently no studies evaluating the association of physical exercise with an ACE2 activator (DIZE) as a possible treatment for this group of diseases. We evaluate the effects of pharmacological treatment with an angiotensin-converting enzyme 2 activator drug, associated with exercise, on the pulmonary lesions induced by bleomycin. From the 96 male Balb/c mice used in the experiment, only 49 received 8 U/kg of bleomycin (BLM, intratracheally). The mice were divided into control (C) and bleomycin (BLM) groups, sedentary and trained (C-SED, C-EXE, BLM-SED, BLM-EXE), control and bleomycin and also sedentary and trained treated with diminazene (C-SED/E, C-EXE/E, BLM-SED/E, BLM-EXE/E). The animals were trained five days/week, 1 h/day with 60% of the maximum load obtained in a functional capacity test, for four weeks. Diminazene groups were treated (1 mg/kg, by gavage) daily until the end of the experiment. The lungs were collected 48 h after the training program, set in buffered formalin and investigated by Gomori’s trichrome, immunohistochemistry of collagen type I, TGF-β1, beta-prolyl-4-hydroxylase, MMP-1 and -2. The BLM-EXE/E group obtained a significant increase in functional capacity, reduced amount of fibrosis and type I collagen, decreased expression of TGF-β1 and beta-prolyl-4-hydroxylase and an increase of metalloproteinase −1, −2 when compared with the other groups. The present research shows, for the first time, that exercise training associated with the activation of ACE2 potentially reduces pulmonary fibrosis. PMID:27550926

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.

Expression and regulation of the neutral amino acid transporter B0AT1 in rat small intestine

PubMed Central

Jando, Julia; Camargo, Simone M. R.; Herzog, Brigitte

2017-01-01

Absorption of neutral amino acids across the luminal membrane of intestinal enterocytes is mediated by the broad neutral amino acid transporter B0AT1 (SLC6A19). Its intestinal expression depends on co-expression of the membrane-anchored peptidase angiotensin converting enzyme 2 (ACE2) and is additionally enhanced by aminopeptidase N (CD13). We investigated in this study the expression of B0AT1 and its auxiliary peptidases as well as its transport function along the rat small intestine. Additionally, we tested its possible short- and long-term regulation by dietary proteins and amino acids. We showed by immunofluorescence that B0AT1, ACE2 and CD13 co-localize on the luminal membrane of small intestinal villi and by Western blotting that their protein expression increases in distal direction. Furthermore, we observed an elevated transport activity of the neutral amino acid L-isoleucine during the nocturnal active phase compared to the inactive one. Gastric emptying was delayed by intragastric application of an amino acid cocktail but we observed no acute dietary regulation of B0AT1 protein expression and L-isoleucine transport. Investigation of the chronic dietary regulation of B0AT1, ACE2 and CD13 by different diets revealed an increased B0AT1 protein expression under amino acid-supplemented diet in the proximal section but not in the distal one and for ACE2 protein expression a reverse localization of the effect. Dietary regulation for CD13 protein expression was not as distinct as for the two other proteins. Ring uptake experiments showed a tendency for increased L-isoleucine uptake under amino acid-supplemented diet and in vivo L-isoleucine absorption was more efficient under high protein and amino acid-supplemented diet. Additionally, plasma levels of branched-chain amino acids were elevated under high protein and amino acid diet. Taken together, our experiments did not reveal an acute amino acid-induced regulation of B0AT1 but revealed a chronic dietary adaptation mainly restricted to the proximal segment of the small intestine. PMID:28915252

Molecular and thermodynamic mechanisms of the chloride-dependent human angiotensin-I-converting enzyme (ACE).

PubMed

Yates, Christopher J; Masuyer, Geoffrey; Schwager, Sylva L U; Akif, Mohd; Sturrock, Edward D; Acharya, K Ravi

2014-01-17

Somatic angiotensin-converting enzyme (sACE), a key regulator of blood pressure and electrolyte fluid homeostasis, cleaves the vasoactive angiotensin-I, bradykinin, and a number of other physiologically relevant peptides. sACE consists of two homologous and catalytically active N- and C-domains, which display marked differences in substrate specificities and chloride activation. A series of single substitution mutants were generated and evaluated under varying chloride concentrations using isothermal titration calorimetry. The x-ray crystal structures of the mutants provided details on the chloride-dependent interactions with ACE. Chloride binding in the chloride 1 pocket of C-domain ACE was found to affect positioning of residues from the active site. Analysis of the chloride 2 pocket R522Q and R522K mutations revealed the key interactions with the catalytic site that are stabilized via chloride coordination of Arg(522). Substrate interactions in the S2 subsite were shown to affect chloride affinity in the chloride 2 pocket. The Glu(403)-Lys(118) salt bridge in C-domain ACE was shown to stabilize the hinge-bending region and reduce chloride affinity by constraining the chloride 2 pocket. This work demonstrated that substrate composition to the C-terminal side of the scissile bond as well as interactions of larger substrates in the S2 subsite moderate chloride affinity in the chloride 2 pocket of the ACE C-domain, providing a rationale for the substrate-selective nature of chloride dependence in ACE and how this varies between the N- and C-domains.

Molecular and Thermodynamic Mechanisms of the Chloride-dependent Human Angiotensin-I-converting Enzyme (ACE)*

PubMed Central

Yates, Christopher J.; Masuyer, Geoffrey; Schwager, Sylva L. U.; Akif, Mohd; Sturrock, Edward D.; Acharya, K. Ravi

2014-01-01

Somatic angiotensin-converting enzyme (sACE), a key regulator of blood pressure and electrolyte fluid homeostasis, cleaves the vasoactive angiotensin-I, bradykinin, and a number of other physiologically relevant peptides. sACE consists of two homologous and catalytically active N- and C-domains, which display marked differences in substrate specificities and chloride activation. A series of single substitution mutants were generated and evaluated under varying chloride concentrations using isothermal titration calorimetry. The x-ray crystal structures of the mutants provided details on the chloride-dependent interactions with ACE. Chloride binding in the chloride 1 pocket of C-domain ACE was found to affect positioning of residues from the active site. Analysis of the chloride 2 pocket R522Q and R522K mutations revealed the key interactions with the catalytic site that are stabilized via chloride coordination of Arg522. Substrate interactions in the S2 subsite were shown to affect chloride affinity in the chloride 2 pocket. The Glu403-Lys118 salt bridge in C-domain ACE was shown to stabilize the hinge-bending region and reduce chloride affinity by constraining the chloride 2 pocket. This work demonstrated that substrate composition to the C-terminal side of the scissile bond as well as interactions of larger substrates in the S2 subsite moderate chloride affinity in the chloride 2 pocket of the ACE C-domain, providing a rationale for the substrate-selective nature of chloride dependence in ACE and how this varies between the N- and C-domains. PMID:24297181

ACE2 and the Homolog Collectrin in the Modulation of Nitric Oxide and Oxidative Stress in Blood Pressure Homeostasis and Vascular Injury.

PubMed

Yang, Guang; Chu, Pei-Lun; Rump, Lars C; Le, Thu H; Stegbauer, Johannes

2017-04-20

Hypertension is the leading risk factor causing mortality and morbidity worldwide. Angiotensin (Ang) II, the most active metabolite of the renin-angiotensin system, plays an outstanding role in the pathogenesis of hypertension and vascular injury. Activation of angiotensin converting enzyme 2 (ACE2) has shown to attenuate devastating effects of Ang II in the cardiovascular system by reducing Ang II degradation and increasing Ang-(1-7) generation leading to Mas receptor activation. Recent Advances: Activation of the ACE2/Ang-(1-7)/Mas receptor axis reduces hypertension and improves vascular injury mainly through an increased nitric oxide (NO) bioavailability and decreased reactive oxygen species production. Recent studies reported that shedding of the enzymatically active ectodomain of ACE2 from the cell surface seems to regulate its activity and serves as an interorgan communicator in cardiovascular disease. In addition, collectrin, an ACE2 homolog with no catalytic activity, regulates blood pressure through an NO-dependent mechanism. Large body of experimental data confirmed sustained beneficial effects of ACE2/Ang-(1-7)/Mas receptor axis activation on hypertension and vascular injury. Experimental studies also suggest that activation of collectrin might be beneficial in hypertension and endothelial dysfunction. Their role in clinical hypertension is unclear as selective and reliable activators of both axes are not yet available. This review will highlight the results of recent research progress that illustrate the role of both ACE and collectrin in the modulation of NO and oxidative stress in blood pressure homeostasis and vascular injury, providing evidence for the potential therapeutic application of ACE2 and collectrin in hypertension and vascular disease. Antioxid. Redox Signal. 26, 645-659.

The transcription factor Ace2 and its paralog Swi5 regulate ethanol production during static fermentation through their targets Cts1 and Rps4a in Saccharomyces cerevisiae.

PubMed

Wu, Yao; Du, Jie; Xu, Guoqiang; Jiang, Linghuo

2016-05-01

Saccharomyces cerevisiae is the most widely used fermentation organism for ethanol production. However, the gene expression regulatory networks behind the ethanol fermentation are still not fully understood. Using a static fermentation model, we examined the ethanol yields on biomass of deletion mutants for 77 yeast genes encoding nonessential transcription factors, and found that deletion mutants for ACE2 and SWI5 showed dramatically increased ethanol yields. Overexpression of ACE2 or SWI5 in wild type cells reduced their ethanol yields. Furthermore, among the 34 target genes regulated by Ace2 and Swi5, deletion of CTS1,RPS4a,SIC1,EGT2,DSE2, or SCP160 led to increased ethanol yields, with the former two showing higher effects. Overexpression of CTS1 or RPS4a in both ace2/ace2 and swi5/swi5 mutants reduced their ethanol yields. In contrast, deletion of MCR1 or HO significantly decreased ethanol yields, with the former one showing the highest effect. Therefore, Ace2 and Swi5 are two negative regulators of ethanol yield during static fermentation of yeast cells, and both CTS1 and RPS4a are major effectors mediating these two transcription factors in regulating ethanol production. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Typologies of adverse childhood experiences and their relationship to incarceration in U.S. military veterans.

PubMed

Ross, Jana; Waterhouse-Bradley, Bethany; Contractor, Ateka A; Armour, Cherie

2018-05-01

Numerous studies have reported that adverse childhood experiences (ACEs) are associated with negative psychosocial outcomes in adulthood, but no study has examined the different typologies of ACEs and the relationship of these with adult incarceration in military veterans. The current study used latent class analysis to examine the existence of different childhood maltreatment and household dysfunction typologies in a sample of U.S. military veterans identified through the National Epidemiological Survey on Alcohol and Related Conditions-III ((NESARC-III)). A total of 60.73% of veterans reported one or more ACEs. Four latent classes were identified and were named Low adversities, Moderate maltreatment with high household substance use, Severe maltreatment with moderate household dysfunction and Severe multi-type adversities. Relative to the Low adversities class, the three maltreatment/dysfunction classes had significantly elevated odds ratios (1.72-2.29) for adult incarceration, when controlling for sociodemographic characteristics and alcohol and drug use. The results point to the importance of examining childhood risk factors for incarceration and suggest that a certain sub-group of military personnel who are about to transition into the civilian life may need additional support to adjust and live successful lives. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adverse childhood experiences and intimate partner aggression in the US: sex differences and similarities in psychosocial mediation.

PubMed

Brown, Monique J; Perera, Robert A; Masho, Saba W; Mezuk, Briana; Cohen, Steven A

2015-04-01

Six in ten people in the general population have been exposed to adverse childhood experiences (ACEs). Intimate partner violence (IPV) is a major public health problem in the US. The main objective of this study was to assess sex differences in the role of posttraumatic stress disorder (PTSD), substance abuse, and depression as mediators in the association between ACEs and intimate partner aggression. Data were obtained from Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Structural equation modeling was used to determine the mediational role of PTSD, substance abuse and depression in the association between ACE constructs (neglect, physical/psychological abuse, sexual abuse, parental violence, and parental incarceration/psychopathology) and intimate partner aggression. Among men, PTSD mediated the relationship between sexual abuse and intimate partner aggression. However, among men and women, substance abuse mediated the relationship between physical and psychological abuse and intimate partner aggression. IPV programs geared towards aggressors should address abuse (sexual, physical and psychological), which occurred during childhood and recent substance abuse and PTSD. These programs should be implemented for men and women. Programs aimed at preventing abuse of children may help to reduce rates of depression and PTSD in adulthood, and subsequent intimate partner aggression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adverse childhood experiences and intimate partner aggression in the US: Sex differences and similarities in psychosocial mediation

PubMed Central

Brown, Monique J.; Perera, Robert A.; Masho, Saba W.; Mezuk, Briana; Cohen, Steven A.

2015-01-01

Six in ten people in the general population have been exposed to adverse childhood experiences (ACEs). Intimate partner violence (IPV) is a major public health problem in the US. The main objective of this study was to assess sex differences in the role of posttraumatic stress disorder (PTSD), substance abuse, and depression as mediators in the association between ACEs and intimate partner aggression. Data were obtained from Wave 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Structural equation modeling was used to determine the mediational role of PTSD, substance abuse and depression in the association between ACE constructs (neglect, physical/psychological abuse, sexual abuse, parental violence, and parental incarceration/psychopathology) and intimate partner aggression. Among men, PTSD mediated the relationship between sexual abuse and intimate partner aggression. However, among men and women, substance abuse mediated the relationship between physical and psychological abuse and intimate partner aggression. IPV programs geared towards aggressors should address abuse (sexual, physical and psychological), which occurred during childhood and recent substance abuse and PTSD. These programs should be implemented for men and women. Programs aimed at preventing abuse of children may help to reduce rates of depression and PTSD in adulthood, and subsequent intimate partner aggression. PMID:25753285

ACE and AGTR1 polymorphisms and left ventricular hypertrophy in endurance athletes.

PubMed

Di Mauro, Michele; Izzicupo, Pascal; Santarelli, Francesco; Falone, Stefano; Pennelli, Alfonso; Amicarelli, Fernanda; Calafiore, Antonio M; Di Baldassarre, Angela; Gallina, Sabina

2010-05-01

This study aimed to evaluate the role of angiotensin type 1 receptor gene (AGTR1) polymorphism (A1166C) in left ventricular hypertrophy (LVH) mediated by the angiotensin-converting enzyme (ACE) in endurance athletes. A group of 74 white, healthy male endurance athletes, aged between 25 and 40 yr, were enrolled in this study. All of them participated primarily in isotonic sports, training for at least >10 h x wk(-1), for at least 5 yr. The ACE genotype (insertion [I] or deletion [D] alleles) was ascertained by polymerase chain reaction (DD in 35, ID in 36, and II in 3). Group II was excluded from the analysis because of its small size. No difference was found between the two groups as regards age, blood pressure, HR, and echocardiographic data. The left ventricular mass index (LVMI) was significantly higher in group DD rather than in group ID (P = 0.029). The group DD showed a slightly higher prevalence of subjects with LVH (LVMI > 131 g x m(-2); 62.9%) than group ID (44.4%, P = 0.120). No association was found between ACE-DD and LVH (odds ratio (OR) = 2.12, 95% confidence interval = 0.82-5.46). Concerning the role of AGTR1 polymorphism, the highest LVMI was found in 15 athletes with ACE-DD and AGTR1-AC/CC genotypes (150 +/- 23 g x m(-2)); the lowest value of LVMI was found in the case of ACE-ID and AGTR1-AA (127 g x m(-2) +/- 18 g x m(-2)), whereas LVMI in subjects with ACE-DD + AGTR1-AA was similar to that in the ACE-ID + AGTR1-AC/CC group (134 +/- 18 g x m(-2) vs 133 +/- 20 g x m(-2), P = 0.880). The presence of ACE-DD + AGTR1 + AC/CC was strongly associated with LVH (OR = 4.6, P = 0.029). Moreover, subjects with LVH showed longer left ventricular isovolumetric relaxation time and higher end-systolic wall stress. The latter was strongly correlated to LVMI (r = 0.588), especially in the presence of ACE-DD + AGTR1 + AC/CC (r = 0.728). LVMI may be greater in the presence of ACE- DD and AGTR1-AC/CC polymorphisms.

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

Effects of exercise training on circulating and skeletal muscle renin-angiotensin system in chronic heart failure rats.

PubMed

Gomes-Santos, Igor Lucas; Fernandes, Tiago; Couto, Gisele Kruger; Ferreira-Filho, Julio César Ayres; Salemi, Vera Maria Cury; Fernandes, Fernanda Barrinha; Casarini, Dulce Elena; Brum, Patricia Chakur; Rossoni, Luciana Venturini; de Oliveira, Edilamar Menezes; Negrao, Carlos Eduardo

2014-01-01

Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal muscle.

Gender differences in adverse childhood experiences, collective violence, and the risk for addictive behaviors among university students in Tunisia.

PubMed

El Mhamdi, Sana; Lemieux, Andrine; Bouanene, Ines; Ben Salah, Arwa; Nakajima, Motohiro; Ben Salem, Kamel; al'Absi, Mustafa

2017-06-01

Adverse childhood experiences (ACE) have been linked to a variety of addictive behaviors. The recent adaptation of the ACE measure by the World Health Organization (WHO) allows for the assessment of the negative role of additional adverse experiences, such as extra-familial violence. To date, the relationship between extra-familial violence and addictive behaviors has not been assessed. We report the contribution of ACEs, including the new scales for extra-familial violence, on the risk for mental health problems and addictive behaviors by gender in a sample of young adults in Tunisia. We conducted a cross sectional study in Tunisia during 2014, where we recruited 1200 young university adults who completed the validated Arabic version of the WHO ACE questionnaire in a university setting. Results indicated that intra-familial adversities were associated with increased risk for addictive behaviors, particularly in males. ACEs were also associated with increased risk for mental health problems with women showing more difficulties than men. Exposure to peer, community and collective violence was higher in males than in females and logistic regression confirms that exposure to extra-familial violence increased the risk for addictive behaviors both in male and females by two to three-fold. Mental health problems were associated with peer violence and substance abuse in males, but not in females. Results demonstrate for the first time the contribution of exposure to extra-familial violence on risk for addictive behaviors. Results highlight the need for addressing mental health and addiction in a community with high burden of adversity and violence. Copyright © 2017 Elsevier Inc. All rights reserved.

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension.

PubMed

Makris, T K; Stavroulakis, G A; Dafni, U G; Gialeraki, A E; Krespi, P G; Hatzizacharias, A N; Tsoukala, C G; Vythoulkas, J S; Kyriakidis, M K

2000-11-01

Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.

Adverse childhood experiences and disability in U.S. adults.

PubMed

Schüssler-Fiorenza Rose, Sophia Miryam; Xie, Dawei; Stineman, Margaret

2014-08-01

To assess relationships between adverse childhood experiences and self-reported disabilities in adult life. Cross-sectional, random-digit-dialed, state-population-based survey (Behavioral Risk Factor Surveillance System). Fourteen states and the District of Columbia. Noninstitutionalized adults ages ≥18 years surveyed in 2009 and/or in 2010 (n = 81,184). The Behavioral Risk Factor Surveillance System Adverse Childhood Experience (ACE) Module asks about abuse (physical, sexual, emotional), family dysfunction (exposures to domestic violence, living with mentally ill, substance abusing, or incarcerated family member(s), and/or parental separation and/or divorce) that occurred before age 18 years. The ACE score sums affirmed ACE categories (range, 0-8). We controlled for demographic characteristics (age, race, education, income, and marital status) and self-reported physical health conditions (stroke, myocardial infarction, diabetes, coronary heart disease, asthma). Five states asked participants about mental health conditions (anxiety, depression). A subset analysis of participants in these states evaluated the effect of adjusting for these conditions. The primary outcome was disability (self-reported activity limitation and/or assistive device use). More than half of participants (57%) reported at least 1 adverse childhood experience category, and 23.2% reported disability. The odds ratio (95% confidence interval) of disability increased in a graded fashion from odds ratio 1.3 (95% confidence interval, 1.2-1.4) among those who experienced 1 adverse experience to odds ratio 5.8 (95% confidence interval, 4.6-7.5) among those with 7-8 adverse experiences compared with those with no such experiences when adjusting for demographic factors. The relationship between adverse experiences and disability remained strong after adjusting for physical and mental health conditions. There is a strong graded relationship between childhood exposure to abuse and household dysfunction and self-reported disability in adulthood, even after adjusting for potentially mediating health conditions. Greater clinician, researcher, and policymaker awareness of the impact of childhood adversity on disability is crucial to help those affected by childhood adversity lead more functional lives. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Angiotensin-Converting Enzyme Inhibitor Use and Major Cardiovascular Outcomes in Type 2 Diabetes Mellitus Treated With the Dipeptidyl Peptidase 4 Inhibitor Alogliptin.

PubMed

White, William B; Wilson, Craig A; Bakris, George L; Bergenstal, Richard M; Cannon, Christopher P; Cushman, William C; Heller, Simon K; Mehta, Cyrus R; Nissen, Steven E; Zannad, Faiez; Kupfer, Stuart

2016-09-01

Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors. © 2016 American Heart Association, Inc.

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.

Aronia melanocarpa Elliot Reduces the Activity of Angiotensin I-Converting Enzyme—In Vitro and Ex Vivo Studies

PubMed Central

Sikora, Joanna; Broncel, Marlena; Mikiciuk-Olasik, Elżbieta

2014-01-01

Purpose. The aim of the study was to analyze the effects of two-month supplementation with chokeberry preparation on the activity of angiotensin I-converting enzyme (ACE) in patients with metabolic syndrome (MS). During the in vitro stage of the study, we determined the concentration of chokeberry extract, which inhibited the activity of ACE by 50% (IC50). Methods. The participants (n = 70) were divided into three groups: I—patients with MS who received chokeberry extract supplements, II—healthy controls, and III—patients with MS treated with ACE inhibitors. Results. After one and two months of the experiment, a decrease in ACE activity corresponded to 25% and 30%, respectively. We documented significant positive correlations between the ACE activity and the systolic (r = 0.459, P = 0.048) and diastolic blood pressure, (r = 0.603, P = 0.005) and CRP. The IC50 of chokeberry extract and captopril amounted to 155.4 ± 12.1 μg/mL and 0.52 ± 0.18 μg/mL, respectively. Conclusions. Our in vitro study revealed that chokeberry extract is a relatively weak ACE inhibitor. However, the results of clinical observations suggest that the favorable hypotensive action of chokeberry polyphenols may be an outcome of both ACE inhibition and other pleotropic effects, for example, antioxidative effect. PMID:25050143

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.

Purification of angiotensin I-converting enzyme (ACE) inhibitory peptides from casein hydrolysate by IMAC-Ni2.

PubMed

Wu, Shanguang; Feng, Xuezhen; Lu, Yuan; Lu, Yuting; Liu, Saisai; Tian, Yuhong

2017-10-01

Casein proteins were hydrolyzed by papain to identify inhibitory peptides of angiotensin I-converting enzyme (ACE). The hydrolysate was fractionized by immobilized metal affinity chromatography (IMAC-Ni 2+ ). The fraction with high ACE inhibitory activity was enriched and further chromatographed on a reverse-phase column to yield four fractions. Among the fractions, the L4 fraction exhibited the highest ACE inhibitory activity and was identified by sequence analysis as Trp-Tyr-Leu-His-Tyr-Ala (WYLHYA), with IC 50 value of 16.22 ± 0.83 µM in vitro. This peptide was expected to be applied as an ingredient for preventing hypertension and IMAC-Ni 2+ may provide a simple method for purification of ACE inhibitory peptides.

CO2 Washout Testing of NASA Space Suits

NASA Technical Reports Server (NTRS)

Norcross, Jason

2012-01-01

During the presentation "CO2 Washout Testing of NASA Spacesuits," Jason Norcross discussed the results of recent carbon dioxide CO2 washout testing of NASA spacesuits including the Rear Entry I-suit (REI), Enhanced Mobility Advanced Crew Escape Suit (EM-ACES), and possibly the ACES and Z-1 EVA prototype. When a spacesuit is used during ground testing, adequate CO2 washout must be provided for the suited subject. Symptoms of acute CO2 exposure depend on the partial pressure of CO2 (ppCO2) available to enter the lungs during respiration. The primary factors during ground-based testing that influence the ppCO2 level in the oronasal area include the metabolic rate of the subject and air flow through the suit. These tests were done to characterize inspired oronasal ppCO2 for a range of workloads and flow rates for which ground testing is nominally performed. During this presentation, Norcross provided descriptions of the spacesuits, test hardware, methodology, and results, as well as implications for future ground testing and verification of flight requirements.

Production, optimisation and characterisation of angiotensin converting enzyme inhibitory peptides from sea cucumber (Stichopus japonicus) gonad.

PubMed

Zhong, Chan; Sun, Le-Chang; Yan, Long-Jie; Lin, Yi-Chen; Liu, Guang-Ming; Cao, Min-Jie

2018-01-24

In this study, production of bioactive peptides with angiotensin converting enzyme (ACE) inhibitory activity from sea cucumber (Stichopus japonicus) gonad using commercial protamex was optimised by response surface methodology (RSM). As a result, the optimal condition to achieve the highest ACE inhibitory activity in sea cucumber gonad hydrolysate (SCGH) was hydrolysis for 1.95 h and E/S of 0.75%. For further characterisation, three individual peptides (EIYR, LF and NAPHMR) were purified and identified. The peptide NAPHMR showed the highest ACE inhibitory activity with IC 50 of 260.22 ± 3.71 μM. NAPHMR was stable against simulated gastrointestinal digestion and revealed no significant cytotoxicity toward Caco-2 cells. Molecular docking study suggested that Arg, His and Asn residues in NAPHMR interact with the S2 pocket or Zn 2+ binding motifs of ACE via hydrogen or π-bonds, potentially contributing to ACE inhibitory effect. Sea cucumber gonad is thus a potential resource to produce ACE inhibitory peptides for preparation of functional foods.

Lactoferricin-related peptides with inhibitory effects on ACE-dependent vasoconstriction.

PubMed

Centeno, José M; Burguete, María C; Castelló-Ruiz, María; Enrique, María; Vallés, Salvador; Salom, Juan B; Torregrosa, Germán; Marcos, José F; Alborch, Enrique; Manzanares, Paloma

2006-07-26

A selection of lactoferricin B (LfcinB)-related peptides with an angiotensin I-converting enzyme (ACE) inhibitory effect have been examined using in vitro and ex vivo functional assays. Peptides that were analyzed included a set of sequence-related antimicrobial hexapeptides previously reported and two representative LfcinB-derived peptides. In vitro assays using hippuryl-L-histidyl-L-leucine (HHL) and angiotensin I as substrates allowed us to select two hexapeptides, PACEI32 (Ac-RKWHFW-NH2) and PACEI34 (Ac-RKWLFW-NH2), and also a LfcinB-derived peptide, LfcinB17-31 (Ac-FKCRRWQWRMKKLGA-NH2). Ex vivo functional assays using rabbit carotid arterial segments showed PACEI32 (both D- and L-enantiomers) and LfcinB17-31 have inhibitory effects on ACE-dependent angiotensin I-induced contraction. None of the peptides exhibited in vitro ACE inhibitory activity using bradykinin as the substrate. In conclusion, three bioactive lactoferricin-related peptides exhibit inhibitory effects on both ACE activity and ACE-dependent vasoconstriction with potential to modulate hypertension that deserves further investigation.

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.

Disparities in adverse childhood experiences among sexual minority and heterosexual adults: results from a multi-state probability-based sample.

PubMed

Andersen, Judith P; Blosnich, John

2013-01-01

Adverse childhood experiences (e.g., physical, sexual and emotional abuse, neglect, exposure to domestic violence, parental discord, familial mental illness, incarceration and substance abuse) constitute a major public health problem in the United States. The Adverse Childhood Experiences (ACE) scale is a standardized measure that captures multiple developmental risk factors beyond sexual, physical and emotional abuse. Lesbian, gay, and bisexual (i.e., sexual minority) individuals may experience disproportionately higher prevalence of adverse childhood experiences. To examine, using the ACE scale, prevalence of childhood physical, emotional, and sexual abuse and childhood household dysfunction among sexual minority and heterosexual adults. Analyses were conducted using a probability-based sample of data pooled from three U.S. states' Behavioral Risk Factor Surveillance System (BRFSS) surveys (Maine, Washington, Wisconsin) that administered the ACE scale and collected information on sexual identity (n = 22,071). Compared with heterosexual respondents, gay/lesbian and bisexual individuals experienced increased odds of six of eight and seven of eight adverse childhood experiences, respectively. Sexual minority persons had higher rates of adverse childhood experiences (IRR = 1.66 gay/lesbian; 1.58 bisexual) compared to their heterosexual peers. Sexual minority individuals have increased exposure to multiple developmental risk factors beyond physical, sexual and emotional abuse. We recommend the use of the Adverse Childhood Experiences scale in future research examining health disparities among this minority population.

Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

PubMed

Raza, Syed Tasleem; Abbas, Shania; Siddiqi, Zeba; Mahdi, Farzana

2017-01-01

Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR , FABP2 , FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE , FABP2 , FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

The Interrelatedness of Multiple Forms of Childhood Abuse, Neglect, and Household Dysfunction

ERIC Educational Resources Information Center

Dong, Maxia; Anda, Robert .F.; Felitti, Vincent , J.; Dube, Shanta R.; Williamson, David F.; Thompson, Theodore, J.; Loo, Clifton , M.; Giles, Wayne, H.

2004-01-01

Objective: Childhood abuse and other adverse childhood experiences (ACEs) have historically been studied individually, and relatively little is known about the co-occurrence of these events. The purpose of this study is to examine the degree to which ACEs co-occur as well as the nature of their co-occurrence. Method: We used data from 8,629 adult…

Adverse Childhood Experiences, Resilience and Mindfulness-Based Approaches: Common Denominator Issues for Children with Emotional, Mental, or Behavioral Problems

PubMed Central

Bethell, Christina; Gombojav, Narangerel; Solloway, Michele; Wissow, Lawrence

2016-01-01

Synopsis US children with emotional, mental, or behavioral conditions (EMB) have disproportionate exposure to potentially traumatizing adverse childhood experiences (ACEs) (70.7% EMB vs. 46.9% non-EMB). Neuroscience, epigenetic, developmental, social, epidemiologic, and other sciences provide theoretical and empirical explanations for observed early and lifelong physical, mental, emotional, educational, and social impacts of the trauma and chronic stress that can result from ACEs. Together, these sciences point to possibilities to strengthen families and promote child resilience and school and life success using mindfulness-based, mind-body approaches (MBMB) that neuroscience and other studies show promote healthy regulation of stress, resilience, and healing from emotional trauma. This paper examines US population-based associations between prevalence of EMB, ACEs, and risk regulating protective factors that are potentially malleable using MBMB, such as child resilience, parental coping and stress, and parent-child engagement. US rates of MBMB use among children with EMB are estimated. Findings encourage family-centered and mindfulness-based approaches to address social and emotional trauma and potentially interrupt intergenerational cycles of ACEs and prevalence of EMB among children and youth. PMID:26980120

The effects of different angiotensin II type 1 receptor blockers on the regulation of the ACE-AngII-AT1 and ACE2-Ang(1-7)-Mas axes in pressure overload-induced cardiac remodeling in male mice.

PubMed

Wang, Xingxu; Ye, Yong; Gong, Hui; Wu, Jian; Yuan, Jie; Wang, Shijun; Yin, Peipei; Ding, Zhiwen; Kang, Le; Jiang, Qiu; Zhang, Weijing; Li, Yang; Ge, Junbo; Zou, Yunzeng

2016-08-01

Angiotensin II (AngII) type 1 receptor blockers (ARBs) have been effectively used in hypertension and cardiac remodeling. However, the differences among them are still unclear. We designed this study to examine and compare the effects of several ARBs widely used in clinics, including Olmesartan, Candesartan, Telmisartan, Losartan, Valsartan and Irbesartan, on the ACE-AngII-AT1 axis and the ACE2-Ang(1-7)-Mas axis during the development of cardiac remodeling after pressure overload. Although all of the six ARBs, attenuated the development of cardiac hypertrophy and heart failure induced by transverse aortic constriction (TAC) for 2 or 4weeks in the wild-type mice evaluated by echocardiography and hemodynamic measurements, the degree of attenuation by Olmesartan, Candesartan and Losartan tended to be larger than that of the other three drugs tested. Additionally, the degree of downregulation of the ACE-AngII-AT1 axis and upregulation of the ACE2-Ang(1-7)-Mas axis was higher in response to Olmesartan, Candesartan and Losartan administration in vivo and in vitro. Moreover, in angiotensinogen-knockdown mice, TAC-induced cardiac hypertrophy and heart failure were inhibited by Olmesartan, Candesartan and Losartan but not by Telmisartan, Valsartan and Irbesartan administration. Furthermore, only Olmesartan and Candesartan could downregulate the ACE-AngII-AT1 axis and upregulate the ACE2-Ang(1-7)-Mas axis in vitro. Our data suggest that Olmesartan, Candesartan and Losartan could effectively inhibit pressure overload-induced cardiac remodeling even when with knockdown of Ang II, possibly through upregulation of the expression of the ACE2-Ang(1-7)-Mas axis and downregulation of the expression of the ACE-AngII-AT1 axis. In contrast, Telmisartan, Valsartan and Irbesartan only played a role in the presence of AngII, and Losartan had no effect in the presence of AngII in vitro. Copyright © 2016 Elsevier Ltd. All rights reserved.

Potentiation of kinin analogues by ramiprilat is exclusively related to their degradation.

PubMed

Dendorfer, A; Reibetamann, S; Wolfrum, S; Raasch, W; Dominiak, P

2001-07-01

The potentiation of kinin actions represents a cardioprotective property of ACE inhibitors. Although a clear contribution to this effect is related to the inhibition of bradykinin (BK) breakdown, the high efficacy of potentiation and the ability of ACE inhibitors to provoke a B(2)-receptor-mediated response even after receptor desensitization has also triggered hypotheses concerning additional mechanisms of kinin potentiation. The application of kinin analogues with enhanced metabolic stability for the demonstration of degradation-independent mechanisms of potentiation, however, has yielded inconsistent results. Therefore, the relation between the susceptibility of B(2)-agonists to ACE and the potentiation of their actions by ACE inhibitors was investigated with the use of minimally modified kinin derivatives that varied in their degree of ACE resistance. The B(2)-agonists BK, D-Arg-[Hyp(3)]-BK, [Hyp,(3) Tyr(Me)(8)]-BK, [DeltaPhe(5)]-BK, [D-NMF(7)]-BK, and [Phe(8)psi(CH(2)-NH)Arg(9)]-BK were tested for degradation by purified rabbit ACE and for their potency in contracting the endothelium-denuded rabbit jugular vein in the absence and presence of ramiprilat. Purified ACE degraded D-Arg-[Hyp(3)]-BK and [Hyp,(3) Tyr(Me)(8)]-BK at 81% and 71% of BK degradation activity, respectively, whereas other peptides were highly ([DeltaPhe(5)]-BK) or completely ([D-NMF(7)]-BK, [Phe(8)psi(CH(2)-NH)Arg(9)]-BK) resistant. The EC(50) of BK-induced venoconstriction (1.15+/-0.2 nmol/L) was reduced by a factor of 5.7 in the presence of ramiprilat. Likewise, D-Arg-[Hyp(3)]-BK and [Hyp,(3) Tyr(Me)(8)]-BK were both significantly potentiated by a factor of 4.4, whereas the activities of the other agonists were not affected. Ramiprilat exerted no influence on the maximum contraction induced by any of the agonists. It is concluded that the potentiation of kinin analogues during ACE inhibition correlates quantitatively with the susceptibility of each substance to degradation by ACE. As such, no evidence of degradation-independent potentiating actions of ACE inhibitors could be obtained.

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies.

PubMed

Dhamrait, Sukhbir S; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik; Brull, David J; Gohlke, Peter; Payne, John R; World, Michael; Thorsteinsson, Birger; Humphries, Steve E; Montgomery, Hugh E

2016-07-01

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8-fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role. © 2016 The Authors. BioEssays published by WILEY Periodicals, Inc.

Mitochondrial uncoupling proteins regulate angiotensin‐converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies

PubMed Central

Maubaret, Cecilia; Pedersen‐Bjergaard, Ulrik; Brull, David J.; Gohlke, Peter; Payne, John R.; World, Michael; Thorsteinsson, Birger; Humphries, Steve E.; Montgomery, Hugh E.

2015-01-01

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin‐converting enzyme (ACE) is the central component of endocrine and local tissue renin–angiotensin systems (RAS), which also regulate diverse aspects of whole‐body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3‐55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8‐fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role. PMID:27347560

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies.

PubMed

Dhamrait, Sukhbir S; Maubaret, Cecilia; Pedersen-Bjergaard, Ulrik; Brull, David J; Gohlke, Peter; Payne, John R; World, Michael; Thorsteinsson, Birger; Humphries, Steve E; Montgomery, Hugh E

2016-01-01

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations ( healthy young UK men and Scandinavian diabetic patients ) serum ACE (sACE) activity was significantly higher amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold ( P  < 0·01) whilst increasing ACE expression within a physiological range (<1·8-fold at 48 h; P  < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role.