Uterine Wound Healing: A Complex Process Mediated by Proteins and Peptides.

PubMed

Lofrumento, Dario D; Di Nardo, Maria A; De Falco, Marianna; Di Lieto, Andrea

2017-01-01

Wound healing is the process by which a complex cascade of biochemical events is responsible of the repair the damage. In vivo, studies in humans and mice suggest that healing and post-healing heterogeneous behavior of the surgically wounded myometrium is both phenotype and genotype dependent. Uterine wound healing process involves many cells: endothelial cells, neutrophils, monocytes/macrophages, lymphocytes, fibroblasts, myometrial cells as well a stem cell population found in the myometrium, myoSP (side population of myometrial cells). Transforming growth factor beta (TGF-β) isoforms, connective tissue growth factor (CTGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha (TNF-β) are involved in the wound healing mechanisms. The increased TGF- β1/β3 ratio reduces scarring and fibrosis. The CTGF altered expression may be a factor involved in the abnormal scars formation of low uterine segment after cesarean section and of the formation of uterine dehiscence. The lack of bFGF is involved in the reduction of collagen deposition in the wound site and thicker scabs. The altered expression of TNF-β, VEGF, and PDGF in human myometrial smooth muscle cells in case of uterine dehiscence, it is implicated in the uterine healing process. The over-and under-expressions of growth factors genes involved in uterine scarring process could represent patient's specific features, increasing the risk of cesarean scar complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Perpetual factors involved in performance of air traffic controllers using a microwave landing system

NASA Technical Reports Server (NTRS)

Gershzohn, G.

1978-01-01

The task involved the control of two simulated aircraft targets per trial, in a 37.0 -km radius terminal area, by means of conventional radar vectoring and/or speed control. The goal was to insure that the two targets crossed the Missed Approach Point (MAP) at the runway threshold exactly 60 sec apart. The effects on controller performance of the MLS configuration under wind and no-wind conditions were examined. The data for mean separation time between targets at the MAP and the range about that mean were analyzed by appropriate analyses of variance. Significant effects were found for mean separation times as a result of the configuration of the MLS and for interaction between the configuration and wind conditions. The analysis of variance for range indicated significantly poorer performance under the wind condition. These findings are believed to be a result of certain perceptual factors involved in radar air traffic control (ATC) using the MLS with separation of targets in time.

Organizational member involvement in physical activity coalitions across the United States: development and testing of a novel survey instrument for assessing coalition functioning.

PubMed

Bornstein, Daniel B; Pate, Russell R; Beets, Michael W; Saunders, Ruth P; Blair, Steven N

2015-06-01

Coalitions are often composed of member organizations. Member involvement is thought to be associated with coalition success. No instrument currently exists for evaluating organizational member involvement in physical activity coalitions. This study aimed to develop a survey instrument for evaluating organizational member involvement in physical activity coalitions. The study was carried out in three phases: (a) developing a draft survey, (b) assessing the content validity of the draft survey, and (c) assessing the underlying factor structure, reliability, and validity of the survey. A cross-sectional design was employed. In Phase 1, a team of experts in survey development produced a draft survey. In Phase 2, the content validity of the draft survey was evaluated by a panel of individuals with expertise in physical activity coalitions. In Phase 3, the survey was administered to 120 individuals on local-, state-, and national-level physical activity coalitions. Responses were subjected to an exploratory factor analysis in order to determine the survey's underlying factor structure, reliability, and validity. Phases 1 and 2yielded a survey instrument with demonstrated content validity. Phase 3 yielded a three-factor model with three subscales: Strategic Alignment, Organizational Alignment, and Providing Input. Each subscale demonstrated high internal consistency reliability and construct validity. The survey instrument developed here demonstrated sound psychometric properties and provides new insight into organizational member involvement in physical activity coalitions. This instrument may be an important tool in developing a more complete picture of coalition functioning in physical activity coalitions specifically and health-based coalitions overall. © 2014 Society for Public Health Education.

Chemical Stress Cracking of Acrylic Fibers.

DTIC Science & Technology

1982-05-01

stress, high fiber permeability, moderate fibe orientation, and water- plasticization . The proposed mechanism for bond cleava e involves cyclization of...tensile stress, high fiber permeability, moderate fiber orientation, and water- plasticization . The proposed mechanism for bond cleavage involves...chemical composition, plasticization , and other factors. It will be shown that the etching behavior does not reflect underlying hetero- geneities in the

HIF-2α-ILK Is Involved in Mesenchymal Stromal Cell Angiogenesis in Multiple Myeloma Under Hypoxic Conditions

PubMed Central

Zhang, Xiaoying; Xu, Yinhui; Liu, Hongbo; Zhao, Pan; Chen, Yafang; Yue, Zhijie; Zhang, Zhiqing; Wang, Xiaofang

2018-01-01

Mesenchymal stromal cells are proven to be likely induce the angiogenic response in multiple myeloma and thus represent an enticing target for antiangiogenesis therapies for multiple myeloma. Substantial evidence indicates that angiogenesis in multiple myeloma is complex and involves direct production of angiogenic cytokines by abnormal plasma cells and these B-cell neoplasia generated pathophysiology change within the microenvironment. In this study, we demonstrated that mesenchymal stromal cells cultured with U266/Lp-1 under hypoxic conditions resulted in an increased α-smooth muscle actin expression and high productive levels of both hypoxia-inducible factor-2α and integrin-linked kinase proteins. Moreover, inhibition of hypoxia-inducible factor-2α by Small interfering RNA (siRNA) in mesenchymal stromal cells decreased the protein levels of both α-smooth muscle actin and integrin-linked kinase after mesenchymal stromal cells cultured with U266 under hypoxic conditions. We further demonstrated that transfection of integrin-linked kinase-siRNA reduced the protein level of α-smooth muscle actin and attenuated angiogenesis in vitro by decreasing the attachment of Q-dot labeled cells and secretion of angiogenic factors. In conclusion, our research showed that mesenchymal stromal cells cultured with myeloma cells under hypoxia participated in the angiogenesis of multiple myeloma, which is regulated by the hypoxia-inducible factor-2α-integrin-linked kinase pathway. Thus, targeting integrin-linked kinase may represent an effective strategy to block hypoxia-inducible factor-2α-induced angiogenesis in the treatment of multiple myeloma. PMID:29656700

Using Game Theory to Predict Supply Chain Cooperation

ERIC Educational Resources Information Center

Lutz, Heather; Vang, David O.; Raffield, William D.

2012-01-01

The motivation for this research was to understand under what conditions supply chain cooperation might be feasible and under what circumstances it is not. Whereas previous research focuses on dyads in a supply chain, our research seeks to examine a possible factor that can explain why truly cooperative supply chains involving more than two firms…

On the Evolution of the Cardiac Pacemaker

PubMed Central

Burkhard, Silja; van Eif, Vincent; Garric, Laurence; Christoffels, Vincent M.; Bakkers, Jeroen

2017-01-01

The rhythmic contraction of the heart is initiated and controlled by an intrinsic pacemaker system. Cardiac contractions commence at very early embryonic stages and coordination remains crucial for survival. The underlying molecular mechanisms of pacemaker cell development and function are still not fully understood. Heart form and function show high evolutionary conservation. Even in simple contractile cardiac tubes in primitive invertebrates, cardiac function is controlled by intrinsic, autonomous pacemaker cells. Understanding the evolutionary origin and development of cardiac pacemaker cells will help us outline the important pathways and factors involved. Key patterning factors, such as the homeodomain transcription factors Nkx2.5 and Shox2, and the LIM-homeodomain transcription factor Islet-1, components of the T-box (Tbx), and bone morphogenic protein (Bmp) families are well conserved. Here we compare the dominant pacemaking systems in various organisms with respect to the underlying molecular regulation. Comparative analysis of the pathways involved in patterning the pacemaker domain in an evolutionary context might help us outline a common fundamental pacemaker cell gene programme. Special focus is given to pacemaker development in zebrafish, an extensively used model for vertebrate development. Finally, we conclude with a summary of highly conserved key factors in pacemaker cell development and function. PMID:29367536

Impact of intravitreal pharmacotherapies including antivascular endothelial growth factor and corticosteroid agents on diabetic retinopathy.

PubMed

Wykoff, Charles C

2017-05-01

Diabetic retinopathy is common and increasing in prevalence. Pharmacologic management of diabetic macular edema (DME) has improved tremendously over the last decade with the use of two families of intravitreally administered medications: antivascular endothelial growth factor-specific agents and corticosteroids. Clinical evaluation of these pharmaceuticals has demonstrated that they can have a substantial impact on diabetic retinopathy severity levels and the underlying retinal vasculature itself. Phase 3 trials employing ranibizumab, aflibercept, and fluocinolone acetonide enrolling eyes with center-involving DME causing visual acuity loss have demonstrated impressive alteration of the natural history of progressive diabetic retinopathy worsening over time through blunted progression to proliferative diabetic retinopathy, improving diabetic retinopathy severity levels, and slowing progressive retinal nonperfusion, the underlying disease process central to diabetic retinopathy itself. Accumulating data indicate that the threshold to initiate ocular-specific pharmacologic treatment for diabetic retinopathy, previously predominately limited to eyes with visual loss because of center-involved DME or proliferative diabetic retinopathy, is being lowered to earlier stages of diabetic retinopathy. Ongoing clinical trials and secondary analyses continue to further explore the impact and durability of vascular endothelial growth factor blockade and corticosteroids on modification of diabetic retinopathy and the underlying retinal vasculature itself.

Time from last chemotherapy to death and its correlation with the end of life care in a referral hospital

PubMed Central

Karim, Syed Mustafa; Zekri, Jamal; Abdelghany, Ehab; Dada, Reyad; Munsoor, Husna; Ahmad, Imran

2015-01-01

Background: A substantial number of cancer patients receive chemotherapy until the end of life (EoL). Various factors have been shown to be associated with receipt of chemotherapy until near death. In this study, we determine our average time from last chemotherapy to death (TLCD) and explore different factors that may be associated with decreased TLCD. Materials and Methods: A retrospective review of medical records of adult cancer patients who received chemotherapy during their illness and died in our hospital between January 2010 and January 2012 was conducted. Chi-square test and t-test were used to examine the correlation between selected factors and use of chemotherapy within 60 days of death. Multivariate analysis was used to test independent significance of factors testing positive in univariate analysis. Kaplan-Meier method was used to perform survival analysis. Results: Of the 115 cancer patients who died in the hospital, 41 (35.6%) had TLCD of 60 days or less. Patients with better performance status and those dying under medical oncology service were more likely to be in this group of patients. Univariate analysis showed that these patients were less likely to have palliative care involvement, were more likely to die of treatment related causes, and more likely to have died in the Intensive Care Unit. Multivariate analysis confirmed lack of palliative care involvement and better performance status as independent factors for TLCD less than 60 days. Survival analyses showed that patients with palliative care involvement and those dying under palliative care service were likely to have significantly longer TLCD. Conclusions: Cancer patients who have no involvement of palliative care team in their management tend to receive chemotherapy near the EoL, have more aggressive EoL care, and have higher risk of dying die from treatment related complications. Palliative care should be involved early in the care of cancer patients. PMID:25810576

Participation of Children in Medical Decision-Making: Challenges and Potential Solutions.

PubMed

Jeremic, Vida; Sénécal, Karine; Borry, Pascal; Chokoshvili, Davit; Vears, Danya F

2016-12-01

Participation in healthcare decision-making is considered to be an important right of minors, and is highlighted in both international legislation and public policies. However, despite the legal recognition of children's rights to participation, and also the benefits that children experience by their involvement, there is evidence that legislation is not always translated into healthcare practice. There are a number of factors that may impact on the ability of the child to be involved in decisions regarding their medical care. Some of these factors relate to the child, including their capacity to be actively involved in these decisions. Others relate to the family situation, sociocultural context, or the underlying beliefs and practices of the healthcare provider involved. In spite of these challenges to including children in decisions regarding their clinical care, we argue that it is an important factor in their treatment. The extent to which children should participate in this process should be determined on a case-by-case basis, taking all of the potential barriers into account.

The Factor Structure and Sources of Variation Underlying the Social Learning Environment Rating Scales: Monograph 1.

ERIC Educational Resources Information Center

Warshow, Joyce P.; Bepko, Raymond A.

Seventeen intermediate level classes for the educable mentally retarded were involved in an investigation of the factor structure of the Social Learning Environment Rating Scale (SLERS), an instrument designed to quantify teacher-student behavior based on the Social Learning Curriculum (SLC). The 17 classes were observed implementing six…

Depression in adult patients with primary brain tumours: a review of independent risk factors.

PubMed

Pidani, Anum Sadruddin; Rao, Aaida Mumtaz; Shamim, Muhammad Shahzad

2018-04-01

Depression is considered an under-diagnosed problem, especially in patients with malignancies. Patients with brain tumours in particular, have a relatively higher risk of developing depression, which is multifactorial. Herein, the authors review the recent literature on the prevalence of depression in patients with brain tumours, and explore the various risk factors involved. .

Does Teaching-Experience Matters? A Study on Female Teachers Involved in Engineering-Education through ODL Mode

ERIC Educational Resources Information Center

Roy, Rajarshi; Paira, Anjana

2013-01-01

Irrespective of discipline and trade-boundaries, pedagogy of Engineering-Education demands specialty in most of the cases. Teachers' style of assisting in the process of students' learning accords influence of sequel of factors and variables some of which may be clubbed under "psychopedagogical attributes". Among the many other factors,…

Implementing e-Learning in the Jordanian Higher Education System: Factors Affecting Impact

ERIC Educational Resources Information Center

Al-adwan, Ahmad; Smedley, Jo

2012-01-01

The increased involvement of technology in all aspects of our lives places educational institutions under pressure to include these aspects at the heart of their learning. This ensures that they continue to be competitive in a constantly changing market with international and cultural links. This study explores the factors that influenced the…

Groundwater Resources Assessment under the Pressures of Humanity and Climate Changes

Treesearch

Bret Bruce; Diana Allen; Henrique Chaves; Gordon Grant; Gualbert Oude Essink; Henk Kooi; Ian White; Jason Gurdak; Jay Famiglietti; Jose Luis Martin-Bordes; Kevin Hiscock; Matthew Rodell; Neno Kukuric; Peter B. McMahon; Richard Taylor; Timothy Green; Yoseph Yechieli

2008-01-01

Given the vision and mission statements for GRAPHIC above, this document provides an updated framework for the GRAPHIC program. The approach to addressing global issues under the GRAPHIC umbrella involves case studies designed to cover a broad range of the identified Subjects, Methods, and Regions. Interdependencies of factors and processes affecting subsurface water...

Measuring risky adolescent cycling behaviour.

PubMed

Feenstra, Hans; Ruiter, Robert A C; Schepers, Jan; Peters, Gjalt-Jorn; Kok, Gerjo

2011-09-01

Adolescents are at a greater risk of being involved in traffic accidents than most other age groups, even before they start driving cars. This article aims to determine the factor structure of a self-report questionnaire measuring adolescent risky cycling behaviour, the ACBQ (Adolescent Cycling Behaviour Questionnaire). The questionnaire's structure was based on the widely used Driver Behaviour Questionnaire (DBQ). A sample of secondary school students (N = 1749; age range: 13-18 years) filled out the questionnaire. Factor analysis revealed a three-factor structure underlying the questionnaire, which was confirmed on two equally large portions of the entire sample. These three underlying factors were identified as errors, common violations and exceptional violations. The ACBQ is a useful instrument for measuring adolescents' risky cycling behaviour.

Prospects of engineering thermotolerance in crops through modulation of heat stress transcription factor and heat shock protein networks.

PubMed

Fragkostefanakis, Sotirios; Röth, Sascha; Schleiff, Enrico; Scharf, Klaus-Dieter

2015-09-01

Cell survival under high temperature conditions involves the activation of heat stress response (HSR), which in principle is highly conserved among different organisms, but shows remarkable complexity and unique features in plant systems. The transcriptional reprogramming at higher temperatures is controlled by the activity of the heat stress transcription factors (Hsfs). Hsfs allow the transcriptional activation of HSR genes, among which heat shock proteins (Hsps) are best characterized. Hsps belong to multigene families encoding for molecular chaperones involved in various processes including maintenance of protein homeostasis as a requisite for optimal development and survival under stress conditions. Hsfs form complex networks to activate downstream responses, but are concomitantly subjected to cell-type-dependent feedback regulation through factor-specific physical and functional interactions with chaperones belonging to Hsp90, Hsp70 and small Hsp families. There is increasing evidence that the originally assumed specialized function of Hsf/chaperone networks in the HSR turns out to be a complex central stress response system that is involved in the regulation of a broad variety of other stress responses and may also have substantial impact on various developmental processes. Understanding in detail the function of such regulatory networks is prerequisite for sustained improvement of thermotolerance in important agricultural crops. © 2014 John Wiley & Sons Ltd.

Scaling of Advanced Theory-of-Mind Tasks.

PubMed

Osterhaus, Christopher; Koerber, Susanne; Sodian, Beate

2016-11-01

Advanced theory-of-mind (AToM) development was investigated in three separate studies involving 82, 466, and 402 elementary school children (8-, 9-, and 10-year-olds). Rasch and factor analyses assessed whether common conceptual development underlies higher-order false-belief understanding, social understanding, emotion recognition, and perspective-taking abilities. The results refuted a unidimensional scale and revealed three distinct AToM factors: social reasoning, reasoning about ambiguity, and recognizing transgressions of social norms. Developmental progressions emerged for the two reasoning factors but not for recognizing transgressions of social norms. Both social factors were significantly related to inhibition, whereas language development only predicted performance on social reasoning. These findings suggest that AToM comprises multiple abilities, which are subject to distinct cognitive influences. Importantly, only two AToM factors involve conceptual development. © 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.

Review of Rail Behavior Under Wheel/Rail Impact Loading

DOT National Transportation Integrated Search

1986-04-01

The report discusses several studies involving factors that significantly affect rail life, particularly wheel impact loads. Parameters that characterize the effect of wheel impact loads on rail behavior are examined in terms of system variables such...

Transcription factors WRKY11 and WRKY17 are involved in abiotic stress responses in Arabidopsis.

PubMed

Ali, Muhammad Amjad; Azeem, Farrukh; Nawaz, Muhammad Amjad; Acet, Tuba; Abbas, Amjad; Imran, Qari Muhammad; Shah, Kausar Hussain; Rehman, Hafiz Mamoon; Chung, Gyuhwa; Yang, Seung Hwan; Bohlmann, Holger

2018-04-17

Plant WRKY transcription factors play a vital role in abiotic stress tolerance and regulation of plant defense responses. This study examined AtWRKY11 and AtWRKY17 expression under ABA, salt, and osmotic stress at different developmental stages in Arabidopsis. We used reverse transcriptase PCR, quantitative real-time PCR, and promoter:GUS lines to analyze expression. Both genes were upregulated in response to abiotic stress. Next, we applied the same stressors to seedlings of T-DNA insertion wrky11 and 17 knock-out mutants (single and double). Under stress, the mutants exhibited slower germination and compromised root growth compared with the wild type. In most cases, double-mutant seedlings were more affected than single mutants. These results suggest that wrky11 and wrky17 are not strictly limited to plant defense responses but are also involved in conferring stress tolerance. Copyright © 2018 Elsevier GmbH. All rights reserved.

Production and Testing of Transgenic Cotton that Expresses Transcription Factors for Enhanced Seed and Fiber Traits and Productivity Under Drought Stress

USDA-ARS?s Scientific Manuscript database

Abscisic acid (ABA) is a plant hormone involved in abiotic and biotic stress adaptation and seed development. We have previously shown that Basic3 (B3) domain and basic leucine zipper (b-ZIP) transcription factors from the model plant species maize and Arabidopsis thaliana can transactivate monocot...

Thrombin-dependent Incorporation of von Willebrand Factor into a Fibrin Network*

PubMed Central

Miszta, Adam; Pelkmans, Leonie; Lindhout, Theo; Krishnamoorthy, Ganeshram; de Groot, Philip G.; Hemker, Coenraad H.; Heemskerk, Johan W. M.; Kelchtermans, Hilde; de Laat, Bas

2014-01-01

Attachment of platelets from the circulation onto a growing thrombus is a process involving multiple platelet receptors, endothelial matrix components, and coagulation factors. It has been indicated previously that during a transglutaminase reaction activated factor XIII (FXIIIa) covalently cross-links von Willebrand factor (VWF) to polymerizing fibrin. Bound VWF further recruits and activates platelets via interactions with the platelet receptor complex glycoprotein Ib (GPIb). In the present study we found proof for binding of VWF to a fibrin monomer layer during the process of fibrinogen-to-fibrin conversion in the presence of thrombin, arvin, or a snake venom from Crotalus atrox. Using a domain deletion mutant we demonstrated the involvement of the C domains of VWF in this binding. Substantial binding of VWF to fibrin monomers persisted in the presence of the FXIIIa inhibitor K9-DON, illustrating that cross-linking via factor XIII is not essential for this phenomenon and suggesting the identification of a second mechanism through which VWF multimers incorporate into a fibrin network. Under high shear conditions, platelets were shown to adhere to fibrin only if VWF had been incorporated. In conclusion, our experiments show that the C domains of VWF and the E domain of fibrin monomers are involved in the incorporation of VWF during the polymerization of fibrin and that this incorporation fosters binding and activation of platelets. Fibrin thus is not an inert end product but partakes in further thrombus growth. Our findings help to elucidate the mechanism of thrombus growth and platelet adhesion under conditions of arterial shear rate. PMID:25381443

Exploring the relationship between alcohol and the driver characteristics in motor vehicle accidents.

PubMed

Abdel-Aty, M A; Abdelwahab, H T

2000-07-01

This study examines the differences in alcohol-related accident involvement among different driver groups in the state of Florida. The driver characteristics considered in this study are: age, gender, race, and residency of the driver of a motor vehicle involved in an accident while under the influence of alcohol, drugs, or alcohol and drugs. The main objective of this study is to test whether there are associations between the different driver characteristics and alcohol involvement in traffic accidents, and to identify the high-risk group within each driver factor. This would improve our understanding of the relationship between alcohol involvement, accidents, and the four aforementioned driver factors. It would also enable us to better design educational and awareness programs targeting specific groups in the population to reduce drinking and driving in the state. The relationship between alcohol-related accident involvement and the driver factors are investigated using general descriptive statistics, conditional probabilities and log-linear models. The results showed that the 25-34 age group experience the highest rate of alcohol/drug involvement in accidents. The rates decline with the increase in the age of the drivers. The results also indicated that there are significant relationships between the driver characteristics and alcohol/drug involvement in accidents. Male, white, and in-state drivers were also more involved in alcohol/drugs-related traffic accidents.

Redox homeostasis: the linchpin in stem cell self-renewal and differentiation.

PubMed

Wang, Kui; Zhang, Tao; Dong, Qiang; Nice, Edouard Collins; Huang, Canhua; Wei, Yuquan

2013-03-14

Stem cells are characterized by their unique ability of self-renewal to maintain the so-called stem cell pool. Over the past decades, reactive oxygen species (ROS) have been recognized as toxic aerobic metabolism byproducts that are harmful to stem cells, leading to DNA damage, senescence or cell death. Recently, a growing body of literature has shown that stem cells reside in redox niches with low ROS levels. The balance of Redox homeostasis facilitates stem cell self-renewal by an intricate network. Thus, to fully decipher the underlying molecular mechanisms involved in the maintenance of stem cell self-renewal, it is critical to address the important role of redox homeostasis in the regulation of self-renewal and differentiation of stem cells. In this regard, we will discuss the regulatory mechanisms involved in the subtly orchestrated balance of redox status in stem cells by scavenger antioxidant enzyme systems that are well monitored by the hypoxia niches and crucial redox regulators including forkhead homeobox type O family (FoxOs), apurinic/apyrimidinic (AP) endonuclease1/redox factor-1 (APE1/Ref-1), nuclear factor erythroid-2-related factor 2 (Nrf2) and ataxia telangiectasia mutated (ATM). We will also introduce several pivotal ROS-sensitive molecules, such as hypoxia-inducible factors, p38 mitogen-activated protein kinase (p38) and p53, involved in the redox-regulated stem cell self-renewal. Specifically, all the aforementioned molecules can act as 'redox sensors' by virtue of redox modifications of their cysteine residues, which are critically important in the control of protein function. Given the importance of redox homeostasis in the regulation of stem cell self-renewal, understanding the underlying molecular mechanisms involved will provide important new insights into stem cell biology.

Redox homeostasis: the linchpin in stem cell self-renewal and differentiation

PubMed Central

Wang, Kui; Zhang, Tao; Dong, Qiang; Nice, Edouard Collins; Huang, Canhua; Wei, Yuquan

2013-01-01

Stem cells are characterized by their unique ability of self-renewal to maintain the so-called stem cell pool. Over the past decades, reactive oxygen species (ROS) have been recognized as toxic aerobic metabolism byproducts that are harmful to stem cells, leading to DNA damage, senescence or cell death. Recently, a growing body of literature has shown that stem cells reside in redox niches with low ROS levels. The balance of Redox homeostasis facilitates stem cell self-renewal by an intricate network. Thus, to fully decipher the underlying molecular mechanisms involved in the maintenance of stem cell self-renewal, it is critical to address the important role of redox homeostasis in the regulation of self-renewal and differentiation of stem cells. In this regard, we will discuss the regulatory mechanisms involved in the subtly orchestrated balance of redox status in stem cells by scavenger antioxidant enzyme systems that are well monitored by the hypoxia niches and crucial redox regulators including forkhead homeobox type O family (FoxOs), apurinic/apyrimidinic (AP) endonuclease1/redox factor-1 (APE1/Ref-1), nuclear factor erythroid-2-related factor 2 (Nrf2) and ataxia telangiectasia mutated (ATM). We will also introduce several pivotal ROS-sensitive molecules, such as hypoxia-inducible factors, p38 mitogen-activated protein kinase (p38) and p53, involved in the redox-regulated stem cell self-renewal. Specifically, all the aforementioned molecules can act as ‘redox sensors' by virtue of redox modifications of their cysteine residues, which are critically important in the control of protein function. Given the importance of redox homeostasis in the regulation of stem cell self-renewal, understanding the underlying molecular mechanisms involved will provide important new insights into stem cell biology. PMID:23492768

Risk factors associated with sexually transmitted infections among women under community supervision in New York City.

PubMed

Davis, Alissa; Goddard-Eckrich, Dawn; Dasgupta, Anindita; El-Bassel, Nabila

2018-01-01

The number of women under community supervision in the United States has increased, and this population has a high risk for sexually transmitted infections (STIs). We examined STI prevalence and multiple risk factors among drug-involved women under community supervision in New York City. Data were from a randomized controlled trial testing the efficacy of a behavioral HIV/STI intervention (Women on the Road to Health [WORTH]) among drug-involved women in the community corrections system in New York City from 2009 to 2012. To be eligible for inclusion, women had to be under community supervision within the past 90 days, have used illicit drugs at least once in the past six months, and have unprotected sex at least once in the past 90 days. Participants completed a survey containing items on STI risk factors and were tested for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. Multivariable regression was used to examine associations between risk factors and STI diagnosis. Of 333 women tested, 89 (26.7%) tested positive for an STI. Ten (3.0%) were positive for C. trachomatis, 4 (1.2%) for N. gonorrhoeae, and 77 (23.1%) for T. vaginalis. Women with any STI were more likely to be black (AOR: 2.02; 95% CI: 1.08-3.77), homeless in the past 90 days (AOR: 2.07; 95% CI: 1.01-4.26), arrested in the past 90 days (AOR: 1.97; 95% CI: 1.14-3.39), and have a greater number of sexual partners in the past 90 days (AOR: 1.24; 95% CI: 1.08-1.42). Drug-using women under community supervision have a high burden of STIs driven by multiple risk factors. Implementing STI screening, prevention, and treatment programs in community supervision settings could facilitate a reduction in STIs among this population.

Perceived threat and perceived neglect: Couples' underlying concerns during conflict.

PubMed

Sanford, Keith

2010-06-01

The Couples Underlying Concern Inventory assesses 2 fundamental types of distress that couples experience during interpersonal conflict. Perceived threat involves a perception that one's partner is blaming and controlling the self. Perceived neglect involves a perception that one's partner is failing to make desired contributions or investments. Scales measuring these 2 underlying concerns were developed in Study 1, where a sample of 1,224 married people rated a pool of 57 words describing oneself and perceptions of a partner during a specific episode of conflict. Factor analysis identified 2 dimensions, and 2 brief 8-item scales were created. In Study 2, a sample of 2,315 married people completed the resulting 16-item inventory along with 10 self-report scales measuring types of emotion, cognition, and behavior during conflict. A 2-dimensional factor structure was confirmed, and measurement invariance was demonstrated across 4 racial/ethnic groups. Both perceived threat and perceived neglect correlated with relationship satisfaction and conflict communication. More importantly, each concern was associated with a different, and theoretically expected, set of variables regarding self emotion, emotion perceived in a partner, and cognition during conflict.

Chronic Pancreatitis.

PubMed

Stram, Michelle; Liu, Shu; Singhi, Aatur D

2016-12-01

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Involvement of {gamma}-secretase in postnatal angiogenesis

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

Hayashi, Hiroki; Nakagami, Hironori; Takami, Yoichi

2007-11-23

{gamma}-Secretase cleaves the transmembrane domains of several integral membrane proteins involved in vasculogenesis. Here, we investigated the role of {gamma}-secretase in the regulation of postnatal angiogenesis using {gamma}-secretase inhibitors (GSI). In endothelial cell (EC), {gamma}-secretase activity was up-regulated under hypoxia or the treatment of vascular endothelial growth factor (VEGF). The treatment of GSI significantly attenuated growth factor-induced EC proliferation and migration as well as c-fos promoter activity in a dose-dependent manner. In vascular smooth muscle cell (VSMC), treatment of GSI significantly attenuated growth factor-induced VEGF and fibroblast growth factor-2 (FGF-2) expression. Indeed, GSI attenuated VEGF-induced tube formation and inhibited FGF-2-inducedmore » angiogenesis on matrigel in mice as quantified by FITC-lectin staining of EC. Overall, we demonstrated that {gamma}-secretase may be key molecule in postnatal angiogenesis which may be downstream molecule of growth factor-induced growth and migration in EC, and regulate the expression of angiogenic growth factors in VSMC.« less

Liability for Personal Injury Caused by Defective Medical Computer Programs

PubMed Central

Brannigan, Vincent M.

1980-01-01

Defective medical computer programs can cause personal injury. Financial responsibility for the injury under tort law will turn on several factors: whether the program is a product or a service, what types of defect exist in the product, and who produced the program. The factors involved in making these decisions are complex, but knowledge of the relevant issues can assist computer personnel in avoiding liability.

Functional Differentiation of Uterine Stromal Cells Involves Cross-regulation between Bone Morphogenetic Protein 2 and Kruppel-like Factor (KLF) Family Members KLF9 and KLF13

USDA-ARS?s Scientific Manuscript database

The inability of the uterine epithelium to enter a state of receptivity for the embryo to implant is a significant underlying cause of early pregnancy loss. We previously showed that mice null for the Progesterone Receptor (PGR)-interacting protein Kruppel-like Factor (KLF) 9 are subfertile and exhi...

Genes associated with thermosensitive genic male sterility in rice identified by comparative expression profiling.

PubMed

Pan, Yufang; Li, Qiaofeng; Wang, Zhizheng; Wang, Yang; Ma, Rui; Zhu, Lili; He, Guangcun; Chen, Rongzhi

2014-12-16

Thermosensitive genic male sterile (TGMS) lines and photoperiod-sensitive genic male sterile (PGMS) lines have been successfully used in hybridization to improve rice yields. However, the molecular mechanisms underlying male sterility transitions in most PGMS/TGMS rice lines are unclear. In the recently developed TGMS-Co27 line, the male sterility is based on co-suppression of a UDP-glucose pyrophosphorylase gene (Ugp1), but further study is needed to fully elucidate the molecular mechanisms involved. Microarray-based transcriptome profiling of TGMS-Co27 and wild-type Hejiang 19 (H1493) plants grown at high and low temperatures revealed that 15462 probe sets representing 8303 genes were differentially expressed in the two lines, under the two conditions, or both. Environmental factors strongly affected global gene expression. Some genes important for pollen development were strongly repressed in TGMS-Co27 at high temperature. More significantly, series-cluster analysis of differentially expressed genes (DEGs) between TGMS-Co27 plants grown under the two conditions showed that low temperature induced the expression of a gene cluster. This cluster was found to be essential for sterility transition. It includes many meiosis stage-related genes that are probably important for thermosensitive male sterility in TGMS-Co27, inter alia: Arg/Ser-rich domain (RS)-containing zinc finger proteins, polypyrimidine tract-binding proteins (PTBs), DEAD/DEAH box RNA helicases, ZOS (C2H2 zinc finger proteins of Oryza sativa), at least one polyadenylate-binding protein and some other RNA recognition motif (RRM) domain-containing proteins involved in post-transcriptional processes, eukaryotic initiation factor 5B (eIF5B), ribosomal proteins (L37, L1p/L10e, L27 and L24), aminoacyl-tRNA synthetases (ARSs), eukaryotic elongation factor Tu (eEF-Tu) and a peptide chain release factor protein involved in translation. The differential expression of 12 DEGs that are important for pollen development, low temperature responses or TGMS was validated by quantitative RT-PCR (qRT-PCR). Temperature strongly affects global gene expression and may be the common regulator of fertility in PGMS/TGMS rice lines. The identified expression changes reflect perturbations in the transcriptomic regulation of pollen development networks in TGMS-Co27. Findings from this and previous studies indicate that sets of genes involved in post-transcriptional and translation processes are involved in thermosensitive male sterility transitions in TGMS-Co27.

DUII control system performance measures for Oregon counties 1991-2001

DOT National Transportation Integrated Search

2002-06-01

Driving Under the Influence of Intoxicants (DUII) is a complex social problem that has origins in both internal and external system factors. Due to its complexity, Oregon communities and involved agencies must concentrate on addressing the negative r...

Summer Doldrums.

ERIC Educational Resources Information Center

Muchnick, Bruce

2002-01-01

For camp staff, factors that contribute to the summer doldrums are weather, level of general fatigue, unsatisfied expectations, sensory overload, accumulation of negative "self-talk," and an underlying sense of hurry. Strategies for overcoming summer doldrums involve novelty and stress management, and include promoting health, challenging…

The Role of Psychological and Physiological Factors in Decision Making under Risk and in a Dilemma

PubMed Central

Fooken, Jonas; Schaffner, Markus

2016-01-01

Different methods to elicit risk attitudes of individuals often provide differing results despite a common theory. Reasons for such inconsistencies may be the different influence of underlying factors in risk-taking decisions. In order to evaluate this conjecture, a better understanding of underlying factors across methods and decision contexts is desirable. In this paper we study the difference in result of two different risk elicitation methods by linking estimates of risk attitudes to gender, age, and personality traits, which have been shown to be related. We also investigate the role of these factors during decision-making in a dilemma situation. For these two decision contexts we also investigate the decision-maker's physiological state during the decision, measured by heart rate variability (HRV), which we use as an indicator of emotional involvement. We found that the two elicitation methods provide different individual risk attitude measures which is partly reflected in a different gender effect between the methods. Personality traits explain only relatively little in terms of driving risk attitudes and the difference between methods. We also found that risk taking and the physiological state are related for one of the methods, suggesting that more emotionally involved individuals are more risk averse in the experiment. Finally, we found evidence that personality traits are connected to whether individuals made a decision in the dilemma situation, but risk attitudes and the physiological state were not indicative for the ability to decide in this decision context. PMID:26834591

Cellular and molecular mechanisms of age-related macular degeneration: from impaired autophagy to neovascularization.

PubMed

Klettner, Alexa; Kauppinen, Anu; Blasiak, Janusz; Roider, Johan; Salminen, Antero; Kaarniranta, Kai

2013-07-01

Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularization e.g. in wet AMD. This review ties together these crucial pathological threads in AMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

HIV Tat/P-TEFb Interaction: A Potential Target for Novel Anti-HIV Therapies.

PubMed

Asamitsu, Kaori; Fujinaga, Koh; Okamoto, Takashi

2018-04-17

Transcription is a crucial step in the life cycle of the human immunodeficiency virus type 1 (HIV 1) and is primarily involved in the maintenance of viral latency. Both viral and cellular transcription factors, including transcriptional activators, suppressor proteins and epigenetic factors, are involved in HIV transcription from the proviral DNA integrated within the host cell genome. Among them, the virus-encoded transcriptional activator Tat is the master regulator of HIV transcription. Interestingly, unlike other known transcriptional activators, Tat primarily activates transcriptional elongation and initiation by interacting with the cellular positive transcriptional elongation factor b (P-TEFb). In this review, we describe the molecular mechanism underlying how Tat activates viral transcription through interaction with P-TEFb. We propose a novel therapeutic strategy against HIV replication through blocking Tat action.

Mycobacterium biofilms: factors involved in development, dispersal, and therapeutic strategies against biofilm-relevant pathogens.

PubMed

Xiang, Xiaohong; Deng, Wanyan; Liu, Minqiang; Xie, Jianping

2014-01-01

Many bacteria can develop biofilm (BF), a multicellular structure largely combining bacteria and their extracellular polymeric substances (EPS). The formation of biofilm results in an alternative existence in which microbes ensure their survival in adverse environments. Biofilm-relevant infections are more persistent, resistant to most antibiotics, and more recalcitrant to host immunity. Mycobacterium tuberculosis, the causative agent of tuberculosis, can develop biofilm, though whether M. tuberculosis can form biofilm within tuberculosis patients has yet to be determined. Here, we summarize the factors involved in the development and dispersal of mycobacterial biofilms, as well as underlying regulatory factors and inhibitors against biofilm to deepen our understanding of their development and to elucidate potential novel modes of action for future antibiotics. Key factors in biofilm formation identified as drug targets represent a novel and promising avenue for developing better antibiotics.

A cytokine axis regulates elastin formation and degradation

PubMed Central

Sproul, Erin P.; Argraves, W. Scott

2013-01-01

Underlying the dynamic regulation of tropoelastin expression and elastin formation in development and disease are transcriptional and post-transcriptional mechanisms that have been the focus of much research. Of particular importance is the cytokine–governed elastin regulatory axis in which the pro-elastogenic activities of transforming growth factor β-1 (TGFβ1) and insulin-like growth factor-I (IGF-I) are opposed by anti-elastogenic activities of basic fibroblast growth factor (bFGF/FGF-2), heparin-binding epidermal growth factor-like growth factor (HB-EGF), EGF, PDGF-BB, TGFα, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and noncanonical TGFβ1 signaling. A key mechanistic feature of the regulatory axis is that cytokines influence elastin formation through effects on the cell cycle involving control of cyclin–cyclin dependent kinase complexes and activation of the Ras/MEK/ERK signaling pathway. In this article we provide an overview of the major cytokines/growth factors that modulate elastogenesis and describe the underlying molecular mechanisms for their action on elastin production. PMID:23160093

Leaf-to-branch scaling of C-gain in field-grown almond trees under different soil moisture regimes.

PubMed

Egea, Gregorio; González-Real, María M; Martin-Gorriz, Bernardo; Baille, Alain

2014-06-01

Branch/tree-level measurements of carbon (C)-acquisition provide an integration of the physical and biological processes driving the C gain of all individual leaves. Most research dealing with the interacting effects of high-irradiance environments and soil-induced water stress on the C-gain of fruit tree species has focused on leaf-level measurements. The C-gain of both sun-exposed leaves and branches of adult almond trees growing in a semi-arid climate was investigated to determine the respective costs of structural and biochemical/physiological protective mechanisms involved in the behaviour at branch scale. Measurements were performed on well-watered (fully irrigated, FI) and drought-stressed (deficit irrigated, DI) trees. Leaf-to-branch scaling for net CO2 assimilation was quantified by a global scaling factor (fg), defined as the product of two specific scaling factors: (i) a structural scaling factor (fs), determined under well-watered conditions, mainly involving leaf mutual shading; and (ii) a water stress scaling factor (fws,b) involving the limitations in C-acquisition due to soil water deficit. The contribution of structural mechanisms to limiting branch net C-gain was high (mean fs ∼0.33) and close to the projected-to-total leaf area ratio of almond branches (ε = 0.31), while the contribution of water stress mechanisms was moderate (mean fws,b ∼0.85), thus supplying an fg ranging between 0.25 and 0.33 with slightly higher values for FI trees with respect to DI trees. These results suggest that the almond tree (a drought-tolerant species) has acquired mechanisms of defensive strategy (survival) mainly based on a specific branch architectural design. This strategy allows the potential for C-gain to be preserved at branch scale under a large range of soil water deficits. In other words, almond tree branches exhibit an architecture that is suboptimal for C-acquisition under well-watered conditions, but remarkably efficient to counteract the impact of DI and drought events. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hepatitis C virus utilizes VLDLR as a novel entry pathway.

PubMed

Ujino, Saneyuki; Nishitsuji, Hironori; Hishiki, Takayuki; Sugiyama, Kazuo; Takaku, Hiroshi; Shimotohno, Kunitada

2016-01-05

Various host factors are involved in the cellular entry of hepatitis C virus (HCV). In addition to the factors previously reported, we discovered that the very-low-density lipoprotein receptor (VLDLR) mediates HCV entry independent of CD81. Culturing Huh7.5 cells under hypoxic conditions significantly increased HCV entry as a result of the expression of VLDLR, which was not expressed under normoxic conditions in this cell line. Ectopic VLDLR expression conferred susceptibility to HCV entry of CD81-deficient Huh7.5 cells. Additionally, VLDLR-mediated HCV entry was not affected by the knockdown of cellular factors known to act as HCV receptors or HCV entry factors. Because VLDLR is expressed in primary human hepatocytes, our results suggest that VLDLR functions in vivo as an HCV receptor independent of canonical CD81-mediated HCV entry.

Significant weight loss following clozapine use, how is it possible? A case report and review of published cases and literature relevant to the subject.

PubMed

Tungaraza, Tongeji E

2016-10-01

It has been repeatedly shown that clozapine is more efficacious than other antipsychotics in the management of treatment-resistant schizophrenia. However, clozapine is associated with a number of side effects including weight gain. Antipsychotic-induced weight gain has been linked with a number of untoward events including psychological factors such as stigma and low self-esteem, and physical factors such as metabolic syndromes and untimely death. The mechanism underlying antipsychotic (including clozapine)-induced weight gain is not clearly understood, although it is said to involve several brain areas, several neurotransmitters, neuropeptides and genetic factors. To some individuals however, clozapine use is associated with significant weight loss (13.5-50% of body weight). The observed weight loss in these groups of patients has not been attributed to any underlying diagnosable physical disorders. There have been a handful cases published with this phenomenon, which seems to be contrary to what is expected when clozapine is prescribed. From the currently published cases three groups emerge - those who lost weight simply by taking clozapine, those who lost weight due to improved mental state, engaging in diet and increased exercise, and those for whom weight loss was a sign of a poor response to clozapine. A case of JX who has a diagnosis of schizoaffective disorder is presented. JX lost over 26% of her body weight when she was prescribed clozapine. A detailed review of other published cases is undertaken. The underlying mechanisms involving weight loss are discussed and the implications to clinicians are highlighted. Coordinated studies to examine these groups of patients may provide some insight, not only in the mechanism of clozapine-induced weight loss, but also in the better management of patients with treatment-resistant schizophrenia involving clozapine use.

Synergistic effects of abiotic stresses in plants: a case study of nitrogen limitation and saturating light intensity in Arabidopsis thaliana.

PubMed

Cohen, Itay; Rapaport, Tal; Chalifa-Caspi, Vered; Rachmilevitch, Shimon

2018-05-22

Under natural conditions, plants are regularly exposed to combinations of stress factors. A common example is the conjunction between nitrogen (N) deficiency and excess light. The combined effect of stress factors is often ignored in studies using controlled conditions, possibly resulting in misleading conclusions. To address this issue, the current study examined the physiological behavior of Arabidopsis thaliana under the effect of varying nitrogen levels and light intensities. The joint influence of low N and excess light had an adverse effect on plant growth, chlorophyll and anthocyanin concentrations, photochemical capacity, and the abundance of proteins involved in carbon assimilation and anti-oxidative metabolism. In contrast, no adverse physiological responses were observed for plants under either nitrogen limitation or high light intensity conditions (i.e., single stress). The underline mechanisms for the increased growth in conditions of high light and sufficient nitrogen was due to a combination of chlorophyll accumulation and an increased number of proteins involved in C3 carbon assimilation, amino acids biosynthesis and chloroplast development. In contrast, combined stress conditions caused anthocyanin accumulation and increased number proteins involved in catabolism of lipids and amino acids as energy substrates. Ultimately switching plants from growth to survival. Our results suggest that an assessment of the physiological response to the combined effect of multiple stresses cannot be directly extrapolated from the physiological response to a single stress. Specifically, the synergistic interaction between N deficiency and saturating light in Arabidopsis plants could not have been modeled via only one of the stress factors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Epigenetic Mechanisms Impacting Aging: A Focus on Histone Levels and Telomeres

PubMed Central

Song, Shufei

2018-01-01

Aging and age-related diseases pose some of the most significant and difficult challenges to modern society as well as to the scientific and medical communities. Biological aging is a complex, and, under normal circumstances, seemingly irreversible collection of processes that involves numerous underlying mechanisms. Among these, chromatin-based processes have emerged as major regulators of cellular and organismal aging. These include DNA methylation, histone modifications, nucleosome positioning, and telomere regulation, including how these are influenced by environmental factors such as diet. Here we focus on two interconnected categories of chromatin-based mechanisms impacting aging: those involving changes in the levels of histones or in the functions of telomeres. PMID:29642537

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

Evaluating the Effectiveness of an Educational Intervention to Improve the Patient Safety Attitudes of Intern Pharmacists

PubMed Central

Fois, Romano A.; McLachlan, Andrew J.; Chen, Timothy F.

2017-01-01

Objective. To evaluate the effectiveness of a face-to-face educational intervention in improving the patient safety attitudes of intern pharmacists. Methods. A patient safety education program was delivered to intern pharmacists undertaking The University of Sydney Intern Training Program in 2014. Their patient safety attitudes were evaluated immediately prior to, immediately after, and three-months post-intervention. Underlying attitudinal factors were identified using exploratory factor analysis. Changes in factor scores were examined using analysis of variance. Results. Of the 120 interns enrolled, 95 (78.7%) completed all three surveys. Four underlying attitudinal factors were identified: attitudes towards addressing errors, questioning behaviors, blaming individuals, and reporting errors. Improvements in all attitudinal factors were evident immediately after the intervention. However, only improvements in attitudes towards blaming individuals involved in errors were sustained at three months post-intervention. Conclusion. The educational intervention was associated with short-term improvements in pharmacist interns’ patient safety attitudes. However, other factors likely influenced their attitudes in the longer term. PMID:28289295

Evaluating the Effectiveness of an Educational Intervention to Improve the Patient Safety Attitudes of Intern Pharmacists.

PubMed

Walpola, Ramesh L; Fois, Romano A; McLachlan, Andrew J; Chen, Timothy F

2017-02-25

Objective. To evaluate the effectiveness of a face-to-face educational intervention in improving the patient safety attitudes of intern pharmacists. Methods. A patient safety education program was delivered to intern pharmacists undertaking The University of Sydney Intern Training Program in 2014. Their patient safety attitudes were evaluated immediately prior to, immediately after, and three-months post-intervention. Underlying attitudinal factors were identified using exploratory factor analysis. Changes in factor scores were examined using analysis of variance. Results. Of the 120 interns enrolled, 95 (78.7%) completed all three surveys. Four underlying attitudinal factors were identified: attitudes towards addressing errors, questioning behaviors, blaming individuals, and reporting errors. Improvements in all attitudinal factors were evident immediately after the intervention. However, only improvements in attitudes towards blaming individuals involved in errors were sustained at three months post-intervention. Conclusion. The educational intervention was associated with short-term improvements in pharmacist interns' patient safety attitudes. However, other factors likely influenced their attitudes in the longer term.

Connectivity constraints on cortical reorganization of neural circuits involved in object naming.

PubMed

Papagno, Costanza; Gallucci, Marcello; Casarotti, Alessandra; Castellano, Antonella; Falini, Andrea; Fava, Enrica; Giussani, Carlo; Carrabba, Giorgio; Bello, Lorenzo; Caramazza, Alfonso

2011-04-01

The brain's plasticity in response to sensory deprivation and other perturbations is well established. While the functional properties of the reorganized areas are under vigorous investigation, the factors that constrain cortical reorganization remain poorly understood. One factor constraining such reorganization may be long-distance subcortical connectivity between relevant cortical regions-reorganization attempts to preserve the functionality of subcortical connections. Here we provide human neurophysiological evidence for the role of the subcortical connections in shaping cortical reorganization of the networks involved in object naming following perturbation of normal function. We used direct electrical stimulation (DES) during surgical removal of gliomas to identify the sites that are involved in naming different categories of objects. The sites that were selectively inhibited in naming either living or non-living objects were displaced relative to those observed with other subject populations, possibly reflecting cortical reorganization due to slowly evolving brain damage. Subcortical DES applied to the white matter underlying these regions also led to category-specific naming deficits. The existence of these subcortical fiber pathways was confirmed using diffusion tensor tractography. These results constitute the first neurophysiological evidence for the critical role of subcortical pathways as part of the neural circuits that are involved in object naming; they also highlight the importance of subcortical connectivity in shaping cortical reorganization following perturbations of normal function. Copyright © 2011 Elsevier Inc. All rights reserved.

A novel transcription factor gene FHS1 is involved in the DNA damage response in Fusarium graminearum

PubMed Central

Son, Hokyoung; Fu, Minmin; Lee, Yoonji; Lim, Jae Yun; Min, Kyunghun; Kim, Jin-Cheol; Choi, Gyung Ja; Lee, Yin-Won

2016-01-01

Cell cycle regulation and the maintenance of genome integrity are crucial for the development and virulence of the pathogenic plant fungus Fusarium graminearum. To identify transcription factors (TFs) related to these processes, four DNA-damaging agents were applied to screen a F. graminearum TF mutant library. Sixteen TFs were identified to be likely involved in DNA damage responses. Fhs1 is a fungal specific Zn(II)2Cys6 TF that localises exclusively to nuclei. fhs1 deletion mutants were hypersensitive to hydroxyurea and defective in mitotic cell division. Moreover, deletion of FHS1 resulted in defects in perithecia production and virulence and led to the accumulation of DNA damage. Our genetic evidence demonstrated that the FHS1-associated signalling pathway for DNA damage response is independent of the ATM or ATR pathways. This study identified sixteen genes involved in the DNA damage response and is the first to characterise the novel transcription factor gene FHS1, which is involved in the DNA damage response. The results provide new insights into mechanisms underlying DNA damage responses in fungi, including F. graminearum. PMID:26888604

Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

PubMed

Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

2016-07-01

Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

RNA-Seq analysis of Gtf2ird1 knockout epidermal tissue provides potential insights into molecular mechanisms underpinning Williams-Beuren syndrome.

PubMed

Corley, Susan M; Canales, Cesar P; Carmona-Mora, Paulina; Mendoza-Reinosa, Veronica; Beverdam, Annemiek; Hardeman, Edna C; Wilkins, Marc R; Palmer, Stephen J

2016-06-13

Williams-Beuren Syndrome (WBS) is a genetic disorder associated with multisystemic abnormalities, including craniofacial dysmorphology and cognitive defects. It is caused by a hemizygous microdeletion involving up to 28 genes in chromosome 7q11.23. Genotype/phenotype analysis of atypical microdeletions implicates two evolutionary-related transcription factors, GTF2I and GTF2IRD1, as prime candidates for the cause of the facial dysmorphology. Using a targeted Gtf2ird1 knockout mouse, we employed massively-parallel sequencing of mRNA (RNA-Seq) to understand changes in the transcriptional landscape associated with inactivation of Gtf2ird1 in lip tissue. We found widespread dysregulation of genes including differential expression of 78 transcription factors or coactivators, several involved in organ development including Hey1, Myf6, Myog, Dlx2, Gli1, Gli2, Lhx2, Pou3f3, Sox2, Foxp3. We also found that the absence of GTF2IRD1 is associated with increased expression of genes involved in cellular proliferation, including growth factors consistent with the observed phenotype of extreme thickening of the epidermis. At the same time, there was a decrease in the expression of genes involved in other signalling mechanisms, including the Wnt pathway, indicating dysregulation in the complex networks necessary for epidermal differentiation and facial skin patterning. Several of the differentially expressed genes have known roles in both tissue development and neurological function, such as the transcription factor Lhx2 which regulates several genes involved in both skin and brain development. Gtf2ird1 inactivation results in widespread gene dysregulation, some of which may be due to the secondary consequences of gene regulatory network disruptions involving several transcription factors and signalling molecules. Genes involved in growth factor signalling and cell cycle progression were identified as particularly important for explaining the skin dysmorphology observed in this mouse model. We have noted that a number of the dysregulated genes have known roles in brain development as well as epidermal differentiation and maintenance. Therefore, this study provides clues as to the underlying mechanisms that may be involved in the broader profile of WBS.

Effect of endogenous carotenoids on “adaptive” mutation in Escherichia coli FC40

PubMed Central

Bridges, Bryn A.; Foster, Patricia L.; Timms, Andrew R.

2010-01-01

The appearance over many days of Lac+ frameshift mutations in Escherichia coli strain FC40 incubated on lactose selection plates is a classic example of apparent “adaptive” mutation in an episomal gene. We show that endogenously overproduced carotenoids reduce adaptive mutation under selective conditions by a factor of around two. Carotenoids are known to scavenge singlet oxygen suggesting that the accumulation of oxidative base damage may be an integral part of the adaptive mutation phenomenon. If so, the lesion cannot be 7,8-dihydro-8-oxoguanine since adaptive mutation in FC40 is unaffected by mutM and mutY mutations. If active oxygen species such as singlet oxygen are involved in adaptive mutation then they should also induce frameshift mutations in FC40 under non-selective conditions. We show that such mutations can be induced under non-selective conditions by protoporphyrin photosensitisation and that this photodynamic induction is reduced by a factor of just over two when endogenous carotenoids are present. We argue that the involvement of oxidative damage would in no way be inconsistent with current understanding of the mechanism of adaptive mutation and the role of DNA polymerases. PMID:11166030

HsfB2b-mediated repression of PRR7 directs abiotic stress responses of the circadian clock.

PubMed

Kolmos, Elsebeth; Chow, Brenda Y; Pruneda-Paz, Jose L; Kay, Steve A

2014-11-11

The circadian clock perceives environmental signals to reset to local time, but the underlying molecular mechanisms are not well understood. Here we present data revealing that a member of the heat shock factor (Hsf) family is involved in the input pathway to the plant circadian clock. Using the yeast one-hybrid approach, we isolated several Hsfs, including Heat Shock Factor B2b (HsfB2b), a transcriptional repressor that binds the promoter of Pseudo Response Regulator 7 (PRR7) at a conserved binding site. The constitutive expression of HsfB2b leads to severely reduced levels of the PRR7 transcript and late flowering and elongated hypocotyls. HsfB2b function is important during heat and salt stress because HsfB2b overexpression sustains circadian rhythms, and the hsfB2b mutant has a short circadian period under these conditions. HsfB2b is also involved in the regulation of hypocotyl growth under warm, short days. Our findings highlight the role of the circadian clock as an integrator of ambient abiotic stress signals important for the growth and fitness of plants.

Scaling of Advanced Theory-of-Mind Tasks

ERIC Educational Resources Information Center

Osterhaus, Christopher; Koerber, Susanne; Sodian, Beate

2016-01-01

Advanced theory-of-mind (AToM) development was investigated in three separate studies involving 82, 466, and 402 elementary school children (8-, 9-, and 10-year-olds). Rasch and factor analyses assessed whether common conceptual development underlies higher-order false-belief understanding, social understanding, emotion recognition, and…

Behavior of fiber reinforced sandy slopes under seepage

USDA-ARS?s Scientific Manuscript database

Seepage flow is a major contributor to instability of natural hill slopes, river banks and engineered embankments. In order to increase the factor of safety, an emerging technology involves the inclusion of synthetic fibers in the soil. The addition of tension resisting fibers has a favorable effec...

Paternal programming of offspring cardiometabolic diseases in later life

PubMed Central

Li, Jian; Tsuprykov, Oleg; Yang, Xiaoping; Hocher, Berthold

2016-01-01

Early – intrauterine – environmental factors are linked to the development of cardiovascular disease in later life. Traditionally, these factors are considered to be maternal factors such as maternal under and overnutrition, exposure to toxins, lack of micronutrients, and stress during pregnancy. However, in the recent years, it became obvious that also paternal environmental factors before conception and during sperm development determine the health of the offspring in later life. We will first describe clinical observational studies providing evidence for paternal programming of adulthood diseases in progeny. Next, we describe key animal studies proving this relationship, followed by a detailed analysis of our current understanding of the underlying molecular mechanisms of paternal programming. Alterations of noncoding sperm micro-RNAs, histone acetylation, and targeted as well as global DNA methylation seem to be in particular involved in paternal programming of offspring's diseases in later life. PMID:27457668

Developing a 'critical' approach to patient and public involvement in patient safety in the NHS: learning lessons from other parts of the public sector?

PubMed

Ocloo, Josephine E; Fulop, Naomi J

2012-12-01

There has been considerable momentum within the NHS over the last 10 years to develop greater patient and public involvement (PPI). This commitment has been reflected in numerous policy initiatives. In patient safety, the drive to increase involvement has increasingly been seen as an important way of building a safety culture. Evidence suggests, however, that progress has been slow and even more variable than in health care generally. Given this context, the paper analyses some of the key underlying drivers for involvement in the wider context of health and social care and makes some suggestions on what lessons can be learned for developing the PPI agenda in patient safety. To develop PPI further, it is argued that a greater understanding is needed of the contested nature of involvement in patient safety and how this has similarities to the emergence of user involvement in other parts of the public services. This understanding has led to the development of a range of critical theories to guide involvement that also make more explicit the underlying factors that support and hinder involvement processes, often related to power inequities and control. Achieving greater PPI in patient safety is therefore seen to require a more critical framework for understanding processes of involvement that can also help guide and evaluate involvement practices. © 2011 Blackwell Publishing Ltd.

Autoimmunity-Basics and link with periodontal disease.

PubMed

Kaur, Gagandeep; Mohindra, Kanika; Singla, Shifali

2017-01-01

Autoimmune reactions reflect an imbalance between effector and regulatory immune responses, typically develop through stages of initiation and propagation, and often show phases of resolution (indicated by clinical remissions) and exacerbations (indicated by symptomatic flares). The fundamental underlying mechanism of autoimmunity is defective elimination and/or control of self-reactive lymphocytes. Periodontal diseases are characterized by inflammatory conditions that directly affect teeth-supporting structures, which are the major cause of tooth loss. Several studies have demonstrated the involvement of autoimmune responses in periodontal disease. Evidence of involvement of immunopathology has been reported in periodontal disease. Bacteria in the dental plaque induce antibody formation. Autoreactive T-cells, natural killer cells, ANCA, heat shock proteins, autoantibodies, and genetic factors are reported to have an important role in the autoimmune component of periodontal disease. The present review describes the involvement of autoimmune responses in periodontal diseases and also the mechanisms underlying these responses. Copyright © 2016 Elsevier B.V. All rights reserved.

Advancements in the Underlying Pathogenesis of Schizophrenia: Implications of DNA Methylation in Glial Cells.

PubMed

Chen, Xing-Shu; Huang, Nanxin; Michael, Namaka; Xiao, Lan

2015-01-01

Schizophrenia (SZ) is a chronic and severe mental illness for which currently there is no cure. At present, the exact molecular mechanism involved in the underlying pathogenesis of SZ is unknown. The disease is thought to be caused by a combination of genetic, biological, psychological, and environmental factors. Recent studies have shown that epigenetic regulation is involved in SZ pathology. Specifically, DNA methylation, one of the earliest found epigenetic modifications, has been extensively linked to modulation of neuronal function, leading to psychiatric disorders such as SZ. However, increasing evidence indicates that glial cells, especially dysfunctional oligodendrocytes undergo DNA methylation changes that contribute to the pathogenesis of SZ. This review primarily focuses on DNA methylation involved in glial dysfunctions in SZ. Clarifying this mechanism may lead to the development of new therapeutic interventional strategies for the treatment of SZ and other illnesses by correcting abnormal methylation in glial cells.

The Rachitic Tooth

PubMed Central

Nociti, Francisco H.; Somerman, Martha J.

2014-01-01

Teeth are mineralized organs composed of three unique hard tissues, enamel, dentin, and cementum, and supported by the surrounding alveolar bone. Although odontogenesis differs from osteogenesis in several respects, tooth mineralization is susceptible to similar developmental failures as bone. Here we discuss conditions fitting under the umbrella of rickets, which traditionally referred to skeletal disease associated with vitamin D deficiency but has been more recently expanded to include newly identified factors involved in endocrine regulation of vitamin D, phosphate, and calcium, including phosphate-regulating endopeptidase homolog, X-linked, fibroblast growth factor 23, and dentin matrix protein 1. Systemic mineral metabolism intersects with local regulation of mineralization, and factors including tissue nonspecific alkaline phosphatase are necessary for proper mineralization, where rickets can result from loss of activity of tissue nonspecific alkaline phosphatase. Individuals suffering from rickets often bear the additional burden of a defective dentition, and transgenic mouse models have aided in understanding the nature and mechanisms involved in tooth defects, which may or may not parallel rachitic bone defects. This report reviews dental effects of the range of rachitic disorders, including discussion of etiologies of hereditary forms of rickets, a survey of resulting bone and tooth mineralization disorders, and a discussion of mechanisms, known and hypothesized, involved in the observed dental pathologies. Descriptions of human pathology are augmented by analysis of transgenic mouse models, and new interpretations are brought to bear on questions of how teeth are affected under conditions of rickets. In short, the rachitic tooth will be revealed. PMID:23939820

Transcriptional regulation of drought response: a tortuous network of transcriptional factors

PubMed Central

Singh, Dhriti; Laxmi, Ashverya

2015-01-01

Drought is one of the leading factors responsible for the reduction in crop yield worldwide. Due to climate change, in future, more areas are going to be affected by drought and for prolonged periods. Therefore, understanding the mechanisms underlying the drought response is one of the major scientific concerns for improving crop yield. Plants deploy diverse strategies and mechanisms to respond and tolerate drought stress. Expression of numerous genes is modulated in different plants under drought stress that help them to optimize their growth and development. Plant hormone abscisic acid (ABA) plays a major role in plant response and tolerance by regulating the expression of many genes under drought stress. Transcription factors being the major regulator of gene expression play a crucial role in stress response. ABA regulates the expression of most of the target genes through ABA-responsive element (ABRE) binding protein/ABRE binding factor (AREB/ABF) transcription factors. Genes regulated by AREB/ABFs constitute a regulon termed as AREB/ABF regulon. In addition to this, drought responsive genes are also regulated by ABA-independent mechanisms. In ABA-independent regulation, dehydration-responsive element binding protein (DREB), NAM, ATAF, and CUC regulons play an important role by regulating many drought-responsive genes. Apart from these major regulons, MYB/MYC, WRKY, and nuclear factor-Y (NF-Y) transcription factors are also involved in drought response and tolerance. Our understanding about transcriptional regulation of drought is still evolving. Recent reports have suggested the existence of crosstalk between different transcription factors operating under drought stress. In this article, we have reviewed various regulons working under drought stress and their crosstalk with each other. PMID:26579147

The Role of Social Work in the Context of Social Disintegration and Violence

ERIC Educational Resources Information Center

Moller, Kurt

2008-01-01

Violence and the violence discourse are very similar from country to country: focus on youth, preponderance of males among perpetrators and victims, disproportionate involvement of migrants and indigenous people, greater prevalence with socioeconomic disadvantage and low education, and the impact of underlying factors such as political…

42 CFR 416.171 - Determination of payment rates for ASC services.

Code of Federal Regulations, 2012 CFR

2012-10-01

... payment rates for office-based surgical procedures and covered ancillary radiology services... relative value units under § 414.22(b)(5)(i)(B) of this subchapter multiplied by the conversion factor... ancillary radiology services that involve certain nuclear medicine procedures will be the amount determined...

High-throughput SuperSAGE for gene expression analysis of Nicotiana tabacum - Rhizoctonia solani interaction

USDA-ARS?s Scientific Manuscript database

Plants are under continuous threat of infection by pathogens endowed with diverse strategies to colonize their host. Knowledge of plant susceptibility factors and the molecular processes involved in the infection process are critical for understanding plant-pathogen interactions. We used SuperSAGE t...

The Relationship between Career Motivation and Self-Efficacy with Protege Career Success

ERIC Educational Resources Information Center

Day, Rachel; Allen, Tammy D.

2004-01-01

Research exploring the underlying processes involved in successful mentorships has been lacking. In the present study, the roles of career motivation and career self-efficacy as explanatory factors were examined. Career motivation mediated the relationship between career mentoring and performance effectiveness. Contrary to prediction, only…

Stupid Tutoring Systems, Intelligent Humans

ERIC Educational Resources Information Center

Baker, Ryan S.

2016-01-01

The initial vision for intelligent tutoring systems involved powerful, multi-faceted systems that would leverage rich models of students and pedagogies to create complex learning interactions. But the intelligent tutoring systems used at scale today are much simpler. In this article, I present hypotheses on the factors underlying this development,…

Processes and Power in School Budgeting across Four Large Urban School Districts.

ERIC Educational Resources Information Center

Goertz, Margaret E.; Hess, G. Alfred, Jr.

1998-01-01

Uses data from four cities (Chicago, Fort Worth, New York, and Rochester) to explore schools' budgetary and personnel discretion under school-based budgeting; how resource-allocation decisions are made; and factors influencing expenditure decisions. A school-based-budgeting process may increase stakeholder involvement and satisfaction without…

Father involvement in early child-rearing and behavioural outcomes in their pre-adolescent children: evidence from the ALSPAC UK birth cohort.

PubMed

Opondo, Charles; Redshaw, Maggie; Savage-McGlynn, Emily; Quigley, Maria A

2016-11-22

To explore the nature of paternal involvement in early child-rearing adopting a social developmental perspective, and estimate its effect on behavioural outcomes of children aged 9 and 11 years. The data come from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort recruited in the former county of Avon in the southwest of England. Out of the 14 701 children in this cohort who were alive at 1 year, 10 440 children were living with both parents at 8 months and were therefore eligible. Outcome data were available for 6898 children at 9 years and 6328 children at 11 years. Paternal involvement was measured using factor scores obtained through factor analysis of fathers' responses on their participation in, understanding of, and feelings about their child's early upbringing. Behavioural problems were measured using the Strengths and Difficulties Questionnaire (SDQ) total difficulties score. 3 factors were identified in the factor analysis: Factor 1 described fathers' emotional response to the child; factor 2 measured the frequency of fathers' involvement in domestic and childcare activities; factor 3 characterised fathers' feelings of security in their role as parent and partner. Children of fathers with high scores on factors 1 and 3 had 14% (OR 0.86, 95% CI 0.79 to 0.94, p=0.001) and 13% (OR 0.87, 95% CI 0.79 to 0.96, p=0.006), respectively, lower adjusted odds of behavioural problems at 9 years. Factors 1 and 3 were associated with comparable reduction in adjusted odds of behavioural problems at 11 years (OR 0.89, 95% CI 0.81 to 0.98, p=0.017 and OR 0.89, 95% CI 0.81 to 0.99, p=0.034, respectively). Factor 2 was not associated with the outcome. Psychological and emotional aspects of paternal involvement in children's early upbringing, particularly how new fathers see themselves as parents and adjust to the role, rather than the quantity of direct involvement in childcare, is associated with positive behavioural outcomes in children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Immunohistochemical profile of cytokines and growth factors expressed in vestibular schwannoma and in normal vestibular nerve tissue.

PubMed

Taurone, Samanta; Bianchi, Enrica; Attanasio, Giuseppe; Di Gioia, Cira; Ierinó, Rocco; Carubbi, Cecilia; Galli, Daniela; Pastore, Francesco Saverio; Giangaspero, Felice; Filipo, Roberto; Zanza, Christian; Artico, Marco

2015-07-01

Vestibular schwannomas, also known as acoustic neuromas, are benign tumors, which originate from myelin-forming Schwann cells. They develop in the vestibular branch of the eighth cranial nerve in the internal auditory canal or cerebellopontine angle. The clinical progression of the condition involves slow and progressive growth, eventually resulting in brainstem compression. The objective of the present study was to investigate the expression level and the localization of the pro-inflammatory cytokines, transforming growth factor-β1 (TGF-β1) interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α), as well as the adhesion molecules, intracellular adhesion molecule-1 and vascular endothelial growth factor (VEGF), in order to determine whether these factors are involved in the transformation and development of human vestibular schwannoma. The present study investigated whether changes in inflammation are involved in tumor growth and if so, the mechanisms underlying this process. The results of the current study demonstrated that pro-inflammatory cytokines, including TGF-β1, IL-1β and IL-6 exhibited increased expression in human vestibular schwannoma tissue compared with normal vestibular nerve samples. TNF-α was weakly expressed in Schwann cells, confirming that a lower level of this cytokine is involved in the proliferation of Schwann cells. Neoplastic Schwann cells produce pro-inflammatory cytokines that may act in an autocrine manner, stimulating cellular proliferation. In addition, the increased expression of VEGF in vestibular schwannoma compared with that in normal vestibular nerve tissue, suggests that this factor may induce neoplastic growth via the promotion of angiogenesis. The present findings suggest that inflammation may promote angiogenesis and consequently contribute to tumor progression. In conclusion, the results of the present study indicated that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in vestibular schwannoma. Further studies are necessary to confirm the involvement of these factors in the growth of neoplasms and to develop inhibitors of pro-inflammatory cytokines as a potential treatment option in the future.

Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

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

Kerkhoven, Eduard J.; Kim, Young-Mo; Wei, Siwei

ABSTRACT The yeastYarrowia lipolyticais a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis inY. lipolyticaand identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase (DGA1) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination ofDGA1overexpression with nitrogen limitationmore » resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor. IMPORTANCEThe ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeastYarrowia lipolytica. Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors involving regulators that are highly conserved among eukaryotes. Given that lipid metabolism is involved in many diseases but is also vital to the development of microbial cell factories that can provide us with sustainable fuels and oleochemicals, we envision that our report introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells.« less

Failure to Deliver and Translate-New Insights into RNA Dysregulation in ALS.

PubMed

Coyne, Alyssa N; Zaepfel, Benjamin L; Zarnescu, Daniela C

2017-01-01

Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease affecting both upper and lower motor neurons. The molecular mechanisms underlying disease pathogenesis remain largely unknown. Multiple genetic loci including genes involved in proteostasis and ribostasis have been linked to ALS providing key insights into the molecular mechanisms underlying disease. In particular, the identification of the RNA binding proteins TDP-43 and fused in sarcoma (FUS) as causative factors of ALS resulted in a paradigm shift centered on the study of RNA dysregulation as a major mechanism of disease. With wild-type TDP-43 pathology being found in ~97% of ALS cases and the identification of disease causing mutations within its sequence, TDP-43 has emerged as a prominent player in ALS. More recently, studies of the newly discovered C9orf72 repeat expansion are lending further support to the notion of defects in RNA metabolism as a key factor underlying ALS. RNA binding proteins are involved in all aspects of RNA metabolism ranging from splicing, transcription, transport, storage into RNA/protein granules, and translation. How these processes are affected by disease-associated mutations is just beginning to be understood. Considerable work has gone into the identification of splicing and transcription defects resulting from mutations in RNA binding proteins associated with disease. More recently, defects in RNA transport and translation have been shown to be involved in the pathomechanism of ALS. A central hypothesis in the field is that disease causing mutations lead to the persistence of RNA/protein complexes known as stress granules. Under times of prolonged cellular stress these granules sequester specific mRNAs preventing them from translation, and are thought to evolve into pathological aggregates. Here we will review recent efforts directed at understanding how altered RNA metabolism contributes to ALS pathogenesis.

Alcohol and Other Risk Factors for Drowning among Male Active Duty U.S. Army Soldiers

PubMed Central

Bell, Nicole S.; Amoroso, Paul J.; Yore, Michelle M.; Senier, Laura; Williams, Jeffrey O.; Smith, Gordon S.; Theriault, Alexis

2007-01-01

Background Risk factors for drowning are largely undocumented among military populations. Hypothesis Accident report narratives will provide important information about the role of alcohol use and other behaviors in drownings among active duty male U.S. Army soldiers. Methods Using a case series design, we describe drowning deaths reported to the U.S. Army Safety Center (1980–1997), documenting associated demographic factors, alcohol use, and other risk-taking behaviors. Results Drowning victims (n = 352) were disproportionately young, black, and single, with less time-in-service, and no college experience. Most drownings occurred off-duty (89%). Alcohol use was involved in at least 31% of the cases overall. Alcohol use was also associated with a 10-fold increase in reckless behavior (OR 9.6, 95% CI 4.5–20.7) and was most common among drownings in Europe (OR = 4.3, 95% CI 1.5–13.4). Most drownings occurred where no lifeguard was present (68%), but almost two-thirds occurred in the presence of others, with CPR initiated in less than one-third of these cases. Drownings involving minority victims were less likely to involve alcohol, but more likely to occur in unauthorized swimming areas. While most drownings did not involve violations of safety rules, over one-third of the cases involved some form of reckless behavior, particularly for those under age 21. Conclusions Intervention programs should be tailored to meet the needs of the demographic subgroups at highest risk since behavioral risk factors vary by race and age. CPR training and skills maintenance can improve survival rates. Narrative data are important for developing hypotheses and understanding risk factors for injuries. PMID:11763109

The factors impacted to local contractor from Foreign Direct Investment in advancing economic hub development in Iskandar Malaysia

NASA Astrophysics Data System (ADS)

Syafiq Salim, Muhamad; Zakaria, Rozana; Aminuddin, Eeydzah; Hamid, Abdul Rahim Abdul; Abdullah, Redzuan; Shahzaib Khan, Jam

2018-04-01

Iskandar Malaysia is an advanced economic hub which is rapidly growing in the State of Johor. It has been an attractive place for Foreign Direct Investment (FDI) to invest. Many sectors are affected by the presence of FDI including the construction sector. This paper highlights the investigation on the effects of FDI to the local contractor in the Iskandar Malaysia Development. In this study, a questionnaire survey was carried out to gain the information on problems from internal factors and external factors that caused the limitation on involvement in FDI project by local contractors. 73 numbers of local contractor registered under CIDB in class G5, G6 and G7 are the respondents. Frequency analysis and Average Index Analysis are used for the results. This study provides the factors that impacted local construction players in Iskandar Malaysia Development. This study has portrayed that FDI plays a vital and significant role in spearheading the active involvement of local contractors in an urban sustainable development.

Intracellular concentrations of 65 species of transcription factors with known regulatory functions in Escherichia coli.

PubMed

Ishihama, Akira; Kori, Ayako; Koshio, Etsuko; Yamada, Kayoko; Maeda, Hiroto; Shimada, Tomohiro; Makinoshima, Hideki; Iwata, Akira; Fujita, Nobuyuki

2014-08-01

The expression pattern of the Escherichia coli genome is controlled in part by regulating the utilization of a limited number of RNA polymerases among a total of its approximately 4,600 genes. The distribution pattern of RNA polymerase changes from modulation of two types of protein-protein interactions: the interaction of core RNA polymerase with seven species of the sigma subunit for differential promoter recognition and the interaction of RNA polymerase holoenzyme with about 300 different species of transcription factors (TFs) with regulatory functions. We have been involved in the systematic search for the target promoters recognized by each sigma factor and each TF using the newly developed Genomic SELEX system. In parallel, we developed the promoter-specific (PS)-TF screening system for identification of the whole set of TFs involved in regulation of each promoter. Understanding the regulation of genome transcription also requires knowing the intracellular concentrations of the sigma subunits and TFs under various growth conditions. This report describes the intracellular levels of 65 species of TF with known function in E. coli K-12 W3110 at various phases of cell growth and at various temperatures. The list of intracellular concentrations of the sigma factors and TFs provides a community resource for understanding the transcription regulation of E. coli under various stressful conditions in nature. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Ascl1 as a Novel Player in the Ptf1a Transcriptional Network for GABAergic Cell Specification in the Retina

PubMed Central

Parlier, Damien; Pretto, Silvia; Hamdache, Johanna; Vernier, Philippe; Locker, Morgane; Bellefroid, Eric; Perron, Muriel

2014-01-01

In contrast with the wealth of data involving bHLH and homeodomain transcription factors in retinal cell type determination, the molecular bases underlying neurotransmitter subtype specification is far less understood. Using both gain and loss of function analyses in Xenopus, we investigated the putative implication of the bHLH factor Ascl1 in this process. We found that in addition to its previously characterized proneural function, Ascl1 also contributes to the specification of the GABAergic phenotype. We showed that it is necessary for retinal GABAergic cell genesis and sufficient in overexpression experiments to bias a subset of retinal precursor cells towards a GABAergic fate. We also analysed the relationships between Ascl1 and a set of other bHLH factors using an in vivo ectopic neurogenic assay. We demonstrated that Ascl1 has unique features as a GABAergic inducer and is epistatic over factors endowed with glutamatergic potentialities such as Neurog2, NeuroD1 or Atoh7. This functional specificity is conferred by the basic DNA binding domain of Ascl1 and involves a specific genetic network, distinct from that underlying its previously demonstrated effects on catecholaminergic differentiation. Our data show that GABAergic inducing activity of Ascl1 requires the direct transcriptional regulation of Ptf1a, providing therefore a new piece of the network governing neurotransmitter subtype specification during retinogenesis. PMID:24643195

Seed-specific transcription factor HSFA9 links late embryogenesis and early photomorphogenesis

PubMed Central

Prieto-Dapena, Pilar; Almoguera, Concepción; Personat, José-María; Merchan, Francisco

2017-01-01

Abstract HSFA9 is a seed-specific transcription factor that in sunflower (Helianthus annuus) is involved in desiccation tolerance and longevity. Here we show that the constitutive overexpression of HSFA9 in tobacco (Nicotiana tabacum) seedlings attenuated hypocotyl growth under darkness and accelerated the initial photosynthetic development. Plants overexpressing HSFA9 increased accumulation of carotenoids, chlorophyllide, and chlorophyll, and displayed earlier unfolding of the cotyledons. HSFA9 enhanced phytochrome-dependent light responses, as shown by an intensified hypocotyl length reduction after treatments with continuous far-red or red light. This observation indicated the involvement of at least two phytochromes: PHYA and PHYB. Reduced hypocotyl length under darkness did not depend on phytochrome photo-activation; this was inferred from the lack of effect observed using far-red light pulses applied before the dark treatment. HSFA9 increased the expression of genes that activate photomorphogenesis, including PHYA, PHYB, and HY5. HSFA9 might directly upregulate PHYA and indirectly affect PHYB transcription, as suggested by transient expression assays. Converse effects on gene expression, greening, and cotyledon unfolding were observed using a dominant-negative form of HSFA9, which was overexpressed under a seed-specific promoter. This work uncovers a novel transcriptional link, through HSFA9, between seed maturation and early photomorphogenesis. In all, our data suggest that HSFA9 enhances photomorphogenesis via early transcriptional effects that start in seeds under darkness. PMID:28207924

Neural mechanism underlying autobiographical memory modulated by remoteness and emotion

NASA Astrophysics Data System (ADS)

Ge, Ruiyang; Fu, Yan; Wang, DaHua; Yao, Li; Long, Zhiying

2012-03-01

Autobiographical memory is the ability to recollect past events from one's own life. Both emotional tone and memory remoteness can influence autobiographical memory retrieval along the time axis of one's life. Although numerous studies have been performed to investigate brain regions involved in retrieving processes of autobiographical memory, the effect of emotional tone and memory age on autobiographical memory retrieval remains to be clarified. Moreover, whether the involvement of hippocampus in consolidation of autobiographical events is time dependent or independent has been controversial. In this study, we investigated the effect of memory remoteness (factor1: recent and remote) and emotional valence (factor2: positive and negative) on neural correlates underlying autobiographical memory by using functional magnetic resonance imaging (fMRI) technique. Although all four conditions activated some common regions known as "core" regions in autobiographical memory retrieval, there are some other regions showing significantly different activation for recent versus remote and positive versus negative memories. In particular, we found that bilateral hippocampal regions were activated in the four conditions regardless of memory remoteness and emotional valence. Thus, our study confirmed some findings of previous studies and provided further evidence to support the multi-trace theory which believes that the role of hippocampus involved in autobiographical memory retrieval is time-independent and permanent in memory consolidation.

Identification of gonadal soma-derived factor involvement in Monopterus albus (protogynous rice field eel) sex change.

PubMed

Zhu, Yefei; Wang, Chunlei; Chen, Xiaowu; Guan, Guijun

2016-07-01

We studied molecular events and potential mechanisms underlying the process of female-to-male sex transformation in the rice field eel (Monopterus albus), a protogynous hermaphrodite fish in which the gonad is initially a female ovary and transforms into male testes. We cloned and identified a novel gonadal soma derived factor (GSDF), which encodes a member of the transforming growth factor-beta superfamily. gsdf expression was measured in gonads of female, intersex and male with reverse transcription-PCR and gsdf's role in sex transformation was studied with qPCR, histological analysis and dual-color in situ hybridization assays and compared to other sex-related genes. gsdf was correlated to Sertoli cell differentiation, indicating involvement in testicular differentiation and sex transformation from female to male in this species. A unique expression pattern reveals a potential role of gsdf essential for the sex transformation of rice field eels.

MicroRNAs in Palatogenesis and Cleft Palate

PubMed Central

Schoen, Christian; Aschrafi, Armaz; Thonissen, Michelle; Poelmans, Geert; Von den Hoff, Johannes W.; Carels, Carine E. L.

2017-01-01

Palatogenesis requires a precise spatiotemporal regulation of gene expression, which is controlled by an intricate network of transcription factors and their corresponding DNA motifs. Even minor perturbations of this network may cause cleft palate, the most common congenital craniofacial defect in humans. MicroRNAs (miRNAs), a class of small regulatory non-coding RNAs, have elicited strong interest as key regulators of embryological development, and as etiological factors in disease. MiRNAs function as post-transcriptional repressors of gene expression and are therefore able to fine-tune gene regulatory networks. Several miRNAs are already identified to be involved in congenital diseases. Recent evidence from research in zebrafish and mice indicates that miRNAs are key factors in both normal palatogenesis and cleft palate formation. Here, we provide an overview of recently identified molecular mechanisms underlying palatogenesis involving specific miRNAs, and discuss how dysregulation of these miRNAs may result in cleft palate. PMID:28420997

Safety assessment for hair-spray resins: risk assessment based on rodent inhalation studies.

PubMed

Carthew, Philip; Griffiths, Heather; Keech, Stephen; Hartop, Peter

2002-04-01

The methods involved in the safety assessment of resins used in hair-spray products have received little peer review, or debate in the published literature, despite their widespread use, in both hairdressing salons and the home. The safety assessment for these resins currently involves determining the type of lung pathology that can be caused in animal inhalation exposure studies, and establishing the no-observable-effect level (NOEL) for these pathologies. The likely human consumer exposure is determined by techniques that model the simulated exposure under "in use" conditions. From these values it is then possible to derive the likely safety factors for human exposure. An important part of this process would be to recognize the intrinsic differences between rodents and humans in terms of the respiratory doses that each species experiences during inhalation exposures, for the purpose of the safety assessment. Interspecies scaling factors become necessary when comparing the exposure doses experienced by rats, compared to humans, because of basic differences between species in lung clearance rates and the alveolar area in the lungs. The rodent inhalation data and modeled human exposure to Resin 6965, a resin polymer that is based on vinyl acetate, has been used to calculate the safety factor for human consumer exposure to this resin, under a range of "in use" exposure conditions. The use of this safety assessment process clearly demonstrates that Resin 6965 is acceptable for human consumer exposure under the conditions considered in this risk assessment.

Development and Initial Validation of the Five-Factor Model Adolescent Personality Questionnaire (FFM-APQ).

PubMed

Rogers, Mary E; Glendon, A Ian

2018-01-01

This research reports on the 4-phase development of the 25-item Five-Factor Model Adolescent Personality Questionnaire (FFM-APQ). The purpose was to develop and determine initial evidence for validity of a brief adolescent personality inventory using a vocabulary that could be understood by adolescents up to 18 years old. Phase 1 (N = 48) consisted of item generation and expert (N = 5) review of items; Phase 2 (N = 179) involved item analyses; in Phase 3 (N = 496) exploratory factor analysis assessed the underlying structure; in Phase 4 (N = 405) confirmatory factor analyses resulted in a 25-item inventory with 5 subscales.

Nod factor supply under water stress conditions modulates cytokinin biosynthesis and enhances nodule formation and N nutrition in soybean.

PubMed

Prudent, Marion; Salon, Christophe; Smith, Donald L; Emery, R J Neil

2016-09-01

Nod factors (NF) are molecules produced by rhizobia which are involved in the N 2 -fixing symbiosis with legume plants, enabling the formation of specific organs called nodules. Under drought conditions, nitrogen acquisition by N 2 -fixation is depressed, resulting in low legume productivity. In this study, we evaluated the effects of NF supply on nitrogen acquisition and on cytokinin biosynthesis of soybean plants grown under drought. NF supply to water stressed soybeans increased the CK content of all organs. The profile of CK metabolites also shifted from t-Z to cis-Z and an accumulation of nucleotide and glucoside conjugates. The changes in CK coincided with enhanced nodule formation with sustained nodule specific activity, which ultimately increased the total nitrogen fixed by the plant.

Integrated analysis of transcriptome and metabolites reveals an essential role of metabolic flux in starch accumulation under nitrogen starvation in duckweed.

PubMed

Yu, Changjiang; Zhao, Xiaowen; Qi, Guang; Bai, Zetao; Wang, Yu; Wang, Shumin; Ma, Yubin; Liu, Qian; Hu, Ruibo; Zhou, Gongke

2017-01-01

Duckweed is considered a promising source of energy due to its high starch content and rapid growth rate. Starch accumulation in duckweed involves complex processes that depend on the balanced expression of genes controlled by various environmental and endogenous factors. Previous studies showed that nitrogen starvation induces a global stress response and results in the accumulation of starch in duckweed. However, relatively little is known about the mechanisms underlying the regulation of starch accumulation under conditions of nitrogen starvation. In this study, we used next-generation sequencing technology to examine the transcriptome responses of Lemna aequinoctialis 6000 at three stages (0, 3, and 7 days) during nitrogen starvation in the presence of exogenously applied sucrose. Overall, 2522, 628, and 1832 differentially expressed unigenes (DEGs) were discovered for the treated and control samples. Clustering and enrichment analysis of DEGs revealed several biological processes occurring under nitrogen starvation. Genes involved in nitrogen metabolism showed the earliest responses to nitrogen starvation, whereas genes involved in carbohydrate biosynthesis were responded subsequently. The expression of genes encoding nitrate reductase, glutamine synthetase, and glutamate synthase was down-regulated under nitrogen starvation. The expression of unigenes encoding enzymes involved in gluconeogenesis was up-regulated, while the majority of unigenes involved in glycolysis were down-regulated. The metabolite results showed that more ADP-Glc was accumulated and lower levels of UDP-Glc were accumulated under nitrogen starvation, the activity of AGPase was significantly increased while the activity of UGPase was dramatically decreased. These changes in metabolite levels under nitrogen starvation are roughly consistent with the gene expression changes in the transcriptome. Based on these results, it can be concluded that the increase of ADP-glucose and starch contents under nitrogen starvation is a consequence of increased output from the gluconeogenesis and TCA pathways, accompanied with the reduction of lipids and pectin biosynthesis. The results provide novel insights into the underlying mechanisms of starch accumulation during nitrogen starvation, which provide a foundation for the improvement of advanced bioethanol production in duckweed.

Retention and attrition factors for female certified athletic trainers in the National Collegiate Athletic Association Division I Football Bowl Subdivision setting.

PubMed

Goodman, Ashley; Mensch, James M; Jay, Michelle; French, Karen E; Mitchell, Murray F; Fritz, Stacy L

2010-01-01

Organizational effectiveness and the continuity of patient care can be affected by certain levels of attrition. However, little is known about the retention and attrition of female certified athletic trainers (ATs) in certain settings. To gain insight and understanding into the factors and circumstances affecting female ATs' decisions to persist in or leave the National Collegiate Athletic Association Division I Football Bowl Subdivision (NCAA D-I FBS) setting. Qualitative study. The 12 NCAA D-I FBS institutions within the Southeastern Conference. A total of 23 women who were current full-time ATs (n = 12) or former full-time ATs (n = 11) at Southeastern Conference institutions participated. Data were collected via in-depth, semistructured interviews, transcribed verbatim, and analyzed via a grounded theory approach. Peer review and member checking methods were performed to establish trustworthiness. The decision to persist involved 4 main factors: (1) increased autonomy, (2) increased social support, (3) enjoyment of job/fitting the NCAA D-I mold, and (4) kinship responsibility. Two subfactors of persistence, the NCAA D-I atmosphere and positive athlete dynamics, emerged under the main factor of enjoyment of job/fitting the NCAA D-I mold. The decision to leave included 3 main factors: (1) life balance issues, (2) role conflict and role overload, and (3) kinship responsibility. Two subfactors of leaving, supervisory/coach conflict and decreased autonomy, emerged under the main factor of role conflict and role overload. A female AT's decision to persist in or leave the NCAA D-I FBS setting can involve several factors. In order to retain capable ATs long term in the NCAA D-I setting, an individual's attributes and obligations, the setting's cultural issues, and an organization's social support paradigm should be considered.

Overexpression of a Common Wheat Gene TaSnRK2.8 Enhances Tolerance to Drought, Salt and Low Temperature in Arabidopsis

PubMed Central

Zhang, Hongying; Mao, Xinguo; Wang, Chengshe; Jing, Ruilian

2010-01-01

Drought, salinity and low temperatures are major factors limiting crop productivity and quality. Sucrose non-fermenting1-related protein kinase 2 (SnRK2) plays a key role in abiotic stress signaling in plants. In this study, TaSnRK2.8, a SnRK2 member in wheat, was cloned and its functions under multi-stress conditions were characterized. Subcellular localization showed the presence of TaSnRK2.8 in the cell membrane, cytoplasm and nucleus. Expression pattern analyses in wheat revealed that TaSnRK2.8 was involved in response to PEG, NaCl and cold stresses, and possibly participates in ABA-dependent signal transduction pathways. To investigate its role under various environmental stresses, TaSnRK2.8 was transferred to Arabidopsis under control of the CaMV-35S promoter. Overexpression of TaSnRK2.8 resulted in enhanced tolerance to drought, salt and cold stresses, further confirmed by longer primary roots and various physiological characteristics, including higher relative water content, strengthened cell membrane stability, significantly lower osmotic potential, more chlorophyll content, and enhanced PSII activity. Meanwhile, TaSnRK2.8 plants had significantly lower total soluble sugar levels under normal growing conditions, suggesting that TaSnRK2.8 might be involved in carbohydrate metabolism. Moreover, the transcript levels of ABA biosynthesis (ABA1, ABA2), ABA signaling (ABI3, ABI4, ABI5), stress-responsive genes, including two ABA-dependent genes (RD20A, RD29B) and three ABA-independent genes (CBF1, CBF2, CBF3), were generally higher in TaSnRK2.8 plants than in WT/GFP controls under normal/stress conditions. Our results suggest that TaSnRK2.8 may act as a regulatory factor involved in a multiple stress response pathways. PMID:21209856

Predicting Pathways into Criminal Behavior: The Intersection of Race, Gender, Poverty, Psychological Factors.

PubMed

Walt, Lisa Christine; Jason, Leonard A

2017-01-01

Women's incarceration rates have increased dramatically over recent years; with Black women's rates disproportionately and significantly higher than other races. Researchers have attempted to understand this criminal justice involvement disparity, and have suggested two major theoretical pathways Differential Involvement and Differential Selection Theories to explain these racial differences. We use the Differential Involvement Theory as a framework to discuss how the objective experience of economic disadvantage as measured by indicators of structural hardship including educational and employment under-attainment and the experience of psychological stress related to resource loss (because of this disadvantage) may explain women's engagement in criminal activity. In order to conceptualize psychological stress, we used Hobfoll's Conservation of Resource's (COR) Theory and measure. Next, we investigated the link between these factors and the degree (number of times incarcerated, number of months incarcerated in lifetime) of criminal behavior using baseline data collected from a NIH study that drew from a racially diverse sample of former substance abusing, criminally involved urban women. Results indicated potential racial differences in the perception of resource loss, and underscore the complex interaction of the experience of race, poverty, and the unique experience of stress on women's decision making and criminal justice involvement.

Intervening on risk factors for coronary heart disease: an application of the parametric g-formula.

PubMed

Taubman, Sarah L; Robins, James M; Mittleman, Murray A; Hernán, Miguel A

2009-12-01

Estimating the population risk of disease under hypothetical interventions--such as the population risk of coronary heart disease (CHD) were everyone to quit smoking and start exercising or to start exercising if diagnosed with diabetes--may not be possible using standard analytic techniques. The parametric g-formula, which appropriately adjusts for time-varying confounders affected by prior exposures, is especially well suited to estimating effects when the intervention involves multiple factors (joint interventions) or when the intervention involves decisions that depend on the value of evolving time-dependent factors (dynamic interventions). We describe the parametric g-formula, and use it to estimate the effect of various hypothetical lifestyle interventions on the risk of CHD using data from the Nurses' Health Study. Over the period 1982-2002, the 20-year risk of CHD in this cohort was 3.50%. Under a joint intervention of no smoking, increased exercise, improved diet, moderate alcohol consumption and reduced body mass index, the estimated risk was 1.89% (95% confidence interval: 1.46-2.41). We discuss whether the assumptions required for the validity of the parametric g-formula hold in the Nurses' Health Study data. This work represents the first large-scale application of the parametric g-formula in an epidemiologic cohort study.

Recombinant expression of extracellular domain of mutant Epidermal Growth Factor Receptor in prokaryotic and baculovirus expression systems.

PubMed

Vettath, Sunitha Kodengil; Shivashankar, Gaganashree; Menon, Krishnakumar N; Vijayachandran, Lakshmi S

2018-04-15

Epidermal Growth Factor Receptor variant III (EGFRvIII) is a tumor specific antigen detected in various tumors including gliomas, breast cancer, lung cancer, head and neck squamous cell carcinoma (HNSCC). Screening of EGFRvIII targeting drug molecules can be accelerated by developing drug screening platforms using recombinantly expressed protein. Choice of expression system is one of the major factors deciding the success of recombinant expression of a protein. In our study, we have tried to express and purify the extracellular domain (ECD) of this highly unstable protein using bacterial and baculovirus expression systems to select the expression system suited for our purpose. Even though the protein was successfully expressed in prokaryotic system, purification could be done only under denaturing conditions. But in the baculovirus expression system, the protein was expressed in soluble form and could be purified under native conditions, with single step of purification. Based on our results, we conclude that insect cells are better choice over E. coli cells for expressing EGFRvIII ECD in soluble form. This study provides insights for other researchers involved in expression of similar unstable membrane proteins, on selecting the best expression system and challenges involved. Copyright © 2018 Elsevier B.V. All rights reserved.

Hypoxia and fetal heart development.

PubMed

Patterson, A J; Zhang, L

2010-10-01

Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation.

Effects of Differential Feedback on Students' Examination Performance

ERIC Educational Resources Information Center

Lipnevich, Anastasiya A.; Smith, Jeffrey K.

2009-01-01

The effects of feedback on performance and factors associated with it were examined in a large introductory psychology course. The experiment involved college students (N = 464) working on an essay examination under 3 conditions: no feedback, detailed feedback that was perceived by participants to be provided by the course instructor, and detailed…

Individual Differences in Learning and Memory. Final Report.

ERIC Educational Resources Information Center

Wimer, Richard E.

A battery of behavioral tests yielding 79 measures, many of which were presumably related to learning and memory, was administered to house mice of seven inbred strains. An analysis of the factorial structure indicated that the two principal and most pervasive factors underlying performance on the battery involved the initiation and maintenance of…

Father Influences on Employed Mothers' Work-Family Balance

ERIC Educational Resources Information Center

Fagan, Jay; Press, Julie

2008-01-01

This study employed the ecological systems perspective and gender ideology theory to examine the influence of fathers' paid work-family crossover and family involvement on self-reports of work-family balance by employed mothers with children under the age of 13 (N = 179). Multiple regression analyses revealed that fathers' crossover factors had a…

BDSM Disclosure and Stigma Management: Identifying Opportunities for Sex Education

ERIC Educational Resources Information Center

Bezreh, Tanya; Weinberg, Thomas S.; Edgar, Timothy

2012-01-01

While participation in the activities like bondage, domination, submission/sadism, masochism that fall under the umbrella term BDSM is widespread, stigma surrounding BDSM poses risks to practitioners who wish to disclose their interest. We examined risk factors involved with disclosure to posit how sex education might diffuse stigma and warn of…

Family Adult Awareness of Adolescents' Premarital Romantic and Sexual Relationships in Ghana

ERIC Educational Resources Information Center

Bingenheimer, Jeffrey B.; Roche, Kathleen M.; Blake, Susan M.

2017-01-01

This study examined the circumstances under which family adults in Ghana were aware of their adolescent children's involvement in premarital relationships. It was hypothesized that factors related to the seriousness and social acceptability of the relationship would influence the likelihood of family adults' awareness in gender-specific ways. Data…

Drought-responsive protein profiles reveal diverse defense pathways in corn kernels under field drought atress

USDA-ARS?s Scientific Manuscript database

Drought stress is a major factor which contributes to disease susceptibility and yield loss in agricultural crops. To identify drought responsive proteins and explore metabolic pathways involved in maize tolerance to drought stress, two lines (B73 and Lo964) with contrasting drought sensitivity were...

Pragmatic Ability and Disability as Emergent Phenomena

ERIC Educational Resources Information Center

Perkins, Michael R.

2005-01-01

A holistic approach to pragmatic ability and disability is outlined which takes account both of the behaviour of individuals involved in the communicative process, and also of the underlying factors which contribute to such behaviour. Rather than being seen as resulting directly from a dysfunction in some kind of discrete pragmatic "module" or…

Interpersonal Violence and Alcohol and Other Drug Use. Infofacts/Resources

ERIC Educational Resources Information Center

Higher Education Center for Alcohol and Other Drug Abuse and Violence Prevention, 2008

2008-01-01

Because alcohol and other drugs are involved in most acts of violence on campus, college and university administrators are under increasing pressure to acknowledge this connection and reduce alcohol consumption on campus. But because alcohol alone does not cause violence, campuses must also address other contributing factors. Since research has…

Comprehensive analysis of NAC transcription factors and their expression during cucumber fruit spine development

USDA-ARS?s Scientific Manuscript database

Cucumber (Cucumis sativus L.) is an important vegetable crop worldwide, and fruit trichomes ir spines are an important trait for external fruit quality. The mechanisms underlying spine formation are not well understood, but there is evidence of the involvement of the plant-specific NAC family of tra...

Ethanol and thermotolerance in the bioconversion of xylose by yeasts

Treesearch

Thomas W. Jeffries; Yong-Su Jin

2000-01-01

The mechanisms underlying ethanol and heat tolerance are complex. Many different genes are involved, and the exact basis is not fully understood. The integrity of cytoplasmic and mitochondrial membranes is critical to maintain proton gradients for metabolic energy and nutrient uptake. Heat and ethanol stress adversely affect membrane integrity. These factors are...

Growth factor involvement in tension-induced skeletal muscle growth

NASA Technical Reports Server (NTRS)

Vandenburgh, H. H.

1987-01-01

Muscle tissue culture techniques were developed to grow skeletal myofibers which differentiate into more adult-like myofibers. Mechanical simulation studies of these muscle cells in a newly developed mechanical cell simulator can now be performed to study growth processes in skeletal muscle. Conditions in the mechanical cell simulator were defined where mechanical activity can either prevent muscle wasting or stimulate muscle growth. The role of endogenous and exogenous growth factors in tension-induced muscle growth is being investigated under the defined conditions of tissue culture.

Methods and Measurements in Real-Time Air Traffic Control System Simulation

DTIC Science & Technology

1983-04-01

Percent of Variance Consumed by Factors 28 7 Correlations Between ABM II Factor Scores and SE14 1 30 Sector-Density Cell -Based Facter Scores 8 SEX I Cell ...runs for each of 31 subjects under each of 6 sector geometry-traffic density combinations ( cells ). Initial analyses, involving correlations between the...two runs in each cell , indicated very low correlations between the replicates. It was decided that before going further it would be best to conduct a

Neuropeptide cycloprolylglycine increases the levels of brain-derived neurotrophic factor in neuronal cells.

PubMed

Gudasheva, T A; Koliasnikova, K N; Antipova, T A; Seredenin, S B

2016-07-01

It was shown for the first time that the endogenous cyclic dipeptide cycloprolylglycine (CPG) at concentrations of 10(-7) and 10(-3) M and piracetam at a concentration of 10(-3) M increased the content of brainderived neurotrophic factor (BDNF) in the culture of neuronal cells in normal state and under conditions of glutamate and 6-oxydopamine neurotoxicity. This may indicate the possible involvement of BDNF in the mechanism of action of neuropeptide CPG and piracetam.

[The temperature factor and magnetic noise under the conditions of stochastic resonance of magnetosomes].

PubMed

Bingi, V N; Chernavskiĭ, D S; Rubin, A B

2006-01-01

The influence of magnetic noise on the dynamics of magnetic nanoparticles under the conditions of stochastic resonance is considered. The effect of the magnetic noise is shown to be equivalent to the growth of the effective thermostat temperature for the particles at the permanent actual temperature of the medium. This regularity may be used for testing the hypothesis on the involvement of magnetic nanoparticles in the formation of biological effects of weak magnetic fields.

Genomic and transcriptomic characterization of the transcription factor family R2R3-MYB in soybean and its involvement in the resistance responses to Phakopsora pachyrhizi.

PubMed

Aoyagi, Luciano N; Lopes-Caitar, Valéria S; de Carvalho, Mayra C C G; Darben, Luana M; Polizel-Podanosqui, Adriana; Kuwahara, Marcia K; Nepomuceno, Alexandre L; Abdelnoor, Ricardo V; Marcelino-Guimarães, Francismar C

2014-12-01

Myb genes constitute one of the largest transcription factor families in the plant kingdom. Soybean MYB transcription factors have been related to the plant response to biotic stresses. Their involvement in response to Phakopsora pachyrhizi infection has been reported by several transcriptional studies. Due to their apparently highly diverse functions, these genes are promising targets for developing crop varieties resistant to diseases. In the present study, the identification and phylogenetic analysis of the soybean R2R3-MYB (GmMYB) transcription factor family was performed and the expression profiles of these genes under biotic stress were determined. GmMYBs were identified from the soybean genome using bioinformatic tools, and their putative functions were determined based on the phylogenetic tree and classified into subfamilies using guides AtMYBs describing known functions. The transcriptional profiles of GmMYBs upon infection with different pathogen were revealed by in vivo and in silico analyses. Selected target genes potentially involved in disease responses were assessed by RT-qPCR after different times of inoculation with P. pachyrhizi using different genetic backgrounds related to resistance genes (Rpp2 and Rpp5). R2R3-MYB transcription factors related to lignin synthesis and genes responsive to chitin were significantly induced in the resistant genotypes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Community perceptions of home environments that lead children & youth to the street in semi-rural Kenya.

PubMed

Seidel, Sarah; Muciimi, James; Chang, James; Gitari, Stanley; Keiser, Philip; Goodman, Michael L

2018-05-28

Research with street-involved children and youth (SICY) in Sub-Saharan Africa over the past three decades has established a complex web of both micro and macro-level factors that simultaneously "push" and "pull" children and youth to the street. There is still little research with adult family and community members in communities from which SICY originate. Forty men and women from five semi-rural villages in Meru County, Kenya participated in a Rapid Rural Appraisal utilizing a fishbone diagram to explore main and underlying reasons for why children may be or may feel unwelcome in the home and thus migrate to the street. Responses were analyzed in terms of ecological levels, child or parent perspective, and the push/pull framework. Overall, community members identified families and households experiencing stress and lacking the necessary resources to successfully adjust and adapt. Four ecological levels of influence were proposed as main reasons, with parent and caregiver factors mentioned most often, followed by household factors, children's intrapersonal factors, and interpersonal (family) factors. Community and environmental level factors were also proposed as underlying factors. Analysis by gender revealed that both men and women emphasized push factors over pull factors, though men proposed more pull factors (from peers and street life) than women did. Men placed more responsibility on the children than women did, citing children's negative behaviors, dissatisfaction with home, and a desire for independence and work/income. Women, in contrast, emphasized children's feelings of being unloved and the experience of harsh punishment or abuse from caregivers. Findings suggest that interventions to reduce street involvement should support economically, medically, and psychologically vulnerable families and households through comprehensive family strengthening programs that build financial capacity, improve parenting and communication skills, and promote education over child work and labor. Copyright © 2018 Elsevier Ltd. All rights reserved.

Shared Genetic Factors Involved in Celiac Disease, Type 2 Diabetes and Anorexia Nervosa Suggest Common Molecular Pathways for Chronic Diseases.

PubMed

Mostowy, Joanna; Montén, Caroline; Gudjonsdottir, Audur H; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel; Torinsson Naluai, Åsa

2016-01-01

Genome-wide association studies (GWAS) have identified several genetic regions involved in immune-regulatory mechanisms to be associated with celiac disease. Previous GWAS also revealed an over-representation of genes involved in type 2 diabetes and anorexia nervosa associated with celiac disease, suggesting involvement of common metabolic pathways for development of these chronic diseases. The aim of this study was to extend these previous analyses to study the gene expression in the gut from children with active celiac disease. Thirty six target genes involved in type 2 diabetes and four genes associated with anorexia nervosa were investigated for gene expression in small intestinal biopsies from 144 children with celiac disease at median (range) age of 7.4 years (1.6-17.8) and from 154 disease controls at a median (range) age 11.4.years (1.4-18.3). A total of eleven of genes were differently expressed in celiac patients compared with disease controls of which CD36, CD38, FOXP1, SELL, PPARA, PPARG, AGT previously associated with type 2 diabetes and AKAP6, NTNG1 with anorexia nervosa remained significant after correction for multiple testing. Shared genetic factors involved in celiac disease, type 2 diabetes and anorexia nervosa suggest common underlying molecular pathways for these diseases.

Risk factors for the severity of injury incurred in crashes involving on-duty police cars.

PubMed

Chu, Hsing-Chung

2016-07-03

This article explores the risk factors associated with police cars on routine patrol and/or on an emergency run and their effects on the severity of injuries in crashes. The binary probit model is used to examine the effects of important factors on the risk of injuries sustained in crashes involving on-duty police cars. Several factors significantly increase the probability of crashes that cause severe injuries. Among those causes are police officers who drive at excessive speeds, traffic violations during emergency responses or pursuits, and driving during the evening (6 to 12 p.m.) or in rainy weather. Findings also indicate some potential issues associated with an increase in the probability of crashes that cause injuries. Younger police drivers were found to be more likely to be involved in crashes causing injuries than middle-aged drivers were. Distracted driving by on-duty police officers as well as civilian drivers who did not pull over to let a police car pass in emergency situations also caused serious crashes. Police cars are exempted from certain traffic laws under emergency circumstances. However, to reduce the probability of being involved in a crash resulting in severe injuries, officers are still obligated to drive safely and follow safety procedures when responding to emergencies or pursuing a car. Enhancement of training techniques for emergency situations or driving in pursuit of an offender and following the safety procedures are essential for safety in driving during an emergency run by police.

Elevated temperature biaxial fatigue

NASA Technical Reports Server (NTRS)

Jordan, E. H.

1983-01-01

Biaxial fatigue is often encountered in the complex thermo-mechanical loadings present in gas turbine engines. Engine strain histories can involve non-constant temperature, mean stress, creep, environmental effects, both isotropic and anisotropic materials and non-proportional loading. Life prediction for the general case involving all the above factors is not a practicable research project. The current research program is limited to isothermal fatigue at room temperature and 1200 F of Hastalloy-X for both proportional and non-proportional loading. An improved method for predicting the fatigue life and deformation response under biaxial cycle loading is sought.

Involvement of HLDF protein and anti-HLDF antibodies in the mechanisms of blood pressure regulation in healthy individuals and patients with stable hypertension and hypertensive crisis.

PubMed

Elistratova, E I; Gruden, M A; Sherstnev, V V

2012-09-01

We studied the relationships between the blood serum levels of human leukemia differentiation factor HLDF, idiotypic and anti-idiotypic antibodies to HLDF, and clinical indicators of cardiovascular function in apparently healthy individuals and patients with essential hypertension and cerebral hypertensive crisis. Markedly reduced HLDF levels and anti-HLDF antibody titers were found in the blood of the examined patients. Correlations between HLDF levels, duration of hypertension, and systolic and diastolic BP were revealed. These findings suggest that the studied molecular factors are involved in the mechanisms of BP regulation under normal conditions and during hypertension development. The protein HLDF and anti-HLDF antibodies can be considered as biomarkers for early diagnosis of hypertension and its cerebral complications.

The Iron-Dependent Regulation of the Candida albicans Oxidative Stress Response by the CCAAT-Binding Factor

PubMed Central

Chakravarti, Ananya; Camp, Kyle; McNabb, David S.

2017-01-01

Candida albicans is the most frequently encountered fungal pathogen in humans, capable of causing mucocutaneous and systemic infections in immunocompromised individuals. C. albicans virulence is influenced by multiple factors. Importantly, iron acquisition and avoidance of the immune oxidative burst are two critical barriers for survival in the host. Prior studies using whole genome microarray expression data indicated that the CCAAT-binding factor is involved in the regulation of iron uptake/utilization and the oxidative stress response. This study examines directly the role of the CCAAT-binding factor in regulating the expression of oxidative stress genes in response to iron availability. The CCAAT-binding factor is a heterooligomeric transcription factor previously shown to regulate genes involved in respiration and iron uptake/utilization in C. albicans. Since these pathways directly influence the level of free radicals, it seemed plausible the CCAAT-binding factor regulates genes necessary for the oxidative stress response. In this study, we show the CCAAT-binding factor is involved in regulating some oxidative stress genes in response to iron availability, including CAT1, SOD4, GRX5, and TRX1. We also show that CAT1 expression and catalase activity correlate with the survival of C. albicans to oxidative stress, providing a connection between iron obtainability and the oxidative stress response. We further explore the role of the various CCAAT-binding factor subunits in the formation of distinct protein complexes that modulate the transcription of CAT1 in response to iron. We find that Hap31 and Hap32 can compensate for each other in the formation of an active transcriptional complex; however, they play distinct roles in the oxidative stress response during iron limitation. Moreover, Hap43 was found to be solely responsible for the repression observed under iron deprivation. PMID:28122000

The effect of granulocyte factor and grass pollen allergen on T-lymphocytes from atopic patients in vitro.

PubMed

Kocur, E; Zeman, K; Tchorzewski, H

1993-01-01

In allergy the immune response is significantly modified by inflammatory processes. Polymorphonuclear leukocytes (PMNLs) are involved in inflammatory processes. Activated PMNLs release many substances, including granulocyte factor (GF), which exerts immunomodulating effects. The present study was performed to determine the effects of allergens and/or GF on the expression of lymphocyte differentiation antigens in short-term cultures and to evaluate the production of migration inhibitory factor (MIF) under the influence of these substances. The studies were carried out on peripheral blood mononuclear cells isolated from patients with type I hypersensitivity, before and after the grass pollen season, and from healthy subjects. GF and allergens were found to increase the CD8 cell number, particularly in 7-day cultures and in patients before exposure to allergens, which correlated with MIF release in these patients under the influence of these factors. The results suggest that the PMNLs may participate in allergic inflammatory reactions.

Invasion-Related Factors as Potential Diagnostic and Therapeutic Targets in Oral Squamous Cell Carcinoma—A Review

PubMed Central

Siriwardena, Samadarani B. S. M.; Tsunematsu, Takaaki; Qi, Guangying; Ishimaru, Naozumi; Kudo, Yasusei

2018-01-01

It is well recognized that the presence of cervical lymph node metastasis is the most important prognostic factor in oral squamous cell carcinoma (OSCC). In solid epithelial cancer, the first step during the process of metastasis is the invasion of cancer cells into the underlying stroma, breaching the basement membrane (BM)—the natural barrier between epithelium and the underlying extracellular matrix (ECM). The ability to invade and metastasize is a key hallmark of cancer progression, and the most complicated and least understood. These topics continue to be very active fields of cancer research. A number of processes, factors, and signaling pathways are involved in regulating invasion and metastasis. However, appropriate clinical trials for anti-cancer drugs targeting the invasion of OSCC are incomplete. In this review, we summarize the recent progress on invasion-related factors and emerging molecular determinants which can be used as potential for diagnostic and therapeutic targets in OSCC. PMID:29758011

Role of exercise in maintaining the integrity of the neuromuscular junction

PubMed Central

Nishimune, Hiroshi; Stanford, John A.; Mori, Yasuo

2014-01-01

Physical activity plays an important role in preventing chronic disease in adults and the elderly. Exercise has beneficial effects on the nervous system, including at the neuromuscular junction (NMJ). Exercise causes hypertrophy of NMJs and improves recovery from peripheral nerve injuries, whereas decreased physical activity causes degenerative changes in NMJs. Recent studies have begun to elucidate molecular mechanisms underlying the beneficial effects of exercise. These mechanisms involve Bassoon, neuregulin-1, peroxisome proliferator-activated receptor gamma coactivator 1α, Insulin-like growth factor-1, glial cell line-derived neurotrophic factor, neurotrophin 4, Homer, and nuclear factor of activated T cells c1. For example, NMJ denervation and active zone decreases have been observed in aged NMJs, but these age-dependent degenerative changes can be ameliorated by exercise. This review will discuss the effects of exercise on the maintenance and regeneration of NMJs and will highlight recent insights into the molecular mechanisms underlying these exercise effects. PMID:24122772

Flight investigation of cockpit-displayed traffic information utilizing coded symbology in an advanced operational environment

NASA Technical Reports Server (NTRS)

Abbott, T. S.; Moen, G. C.; Person, L. H., Jr.; Keyser, G. L., Jr.; Yenni, K. R.; Garren, J. F., Jr.

1980-01-01

Traffic symbology was encoded to provide additional information concerning the traffic, which was displayed on the pilot's electronic horizontal situation indicators (EHSI). A research airplane representing an advanced operational environment was used to assess the benefit of coded traffic symbology in a realistic work-load environment. Traffic scenarios, involving both conflict-free and conflict situations, were employed. Subjective pilot commentary was obtained through the use of a questionnaire and extensive pilot debriefings. These results grouped conveniently under two categories: display factors and task performance. A major item under the display factor category was the problem of display clutter. The primary contributors to clutter were the use of large map-scale factors, the use of traffic data blocks, and the presentation of more than a few airplanes. In terms of task performance, the cockpit-displayed traffic information was found to provide excellent overall situation awareness. Additionally, mile separation prescribed during these tests.

Toddlers’ dysregulated fear predicts delta-beta coupling during preschool

PubMed Central

Phelps, Randi A.; Brooker, Rebecca J.; Buss, Kristin A.

2015-01-01

Dysregulated fear, or the persistence of high levels of fear in low-threat contexts, is an early risk factor for the development of anxiety symptoms. Previous work has suggested both propensities for over-control and under-control of fearfulness as risk factors for anxiety problems, each of which may be relevant to observations of dysregulated fear. Given difficulty disentangling over-control and under-control through traditional behavioral measures, we used delta-beta coupling to begin to understand the degree to which dysregulated fear may reflect propensities for over- or under-control. We found that toddlers who showed high levels of dysregulated fear evidenced greater delta-beta coupling at frontal and central electrode sites as preschoolers relative to children who were low in dysregulated fear. Importantly, these differences were not observed when comparisons were made based on fear levels in high threat contexts. Results suggest dysregulated fear may involve tendencies toward over-control at the neural level. PMID:26624221

Coordinated regulation of photosynthesis in rice increases yield and tolerance to environmental stress

PubMed Central

Ambavaram, Madana M. R.; Basu, Supratim; Krishnan, Arjun; Ramegowda, Venkategowda; Batlang, Utlwang; Rahman, Lutfor; Baisakh, Niranjan; Pereira, Andy

2014-01-01

Plants capture solar energy and atmospheric carbon dioxide (CO2) through photosynthesis, which is the primary component of crop yield, and needs to be increased considerably to meet the growing global demand for food. Environmental stresses, which are increasing with climate change, adversely affect photosynthetic carbon metabolism (PCM) and limit yield of cereals such as rice (Oryza sativa) that feeds half the world. To study the regulation of photosynthesis, we developed a rice gene regulatory network and identified a transcription factor HYR (HIGHER YIELD RICE) associated with PCM, which on expression in rice enhances photosynthesis under multiple environmental conditions, determining a morpho-physiological programme leading to higher grain yield under normal, drought and high-temperature stress conditions. We show HYR is a master regulator, directly activating photosynthesis genes, cascades of transcription factors and other downstream genes involved in PCM and yield stability under drought and high-temperature environmental stress conditions. PMID:25358745

A designed screening study with prespecified combinations of factor settings

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

Anderson-cook, Christine M; Robinson, Timothy J

2009-01-01

In many applications, the experimenter has limited options about what factor combinations can be chosen for a designed study. Consider a screening study for a production process involving five input factors whose levels have been previously established. The goal of the study is to understand the effect of each factor on the response, a variable that is expensive to measure and results in destruction of the part. From an inventory of available parts with known factor values, we wish to identify a best collection of factor combinations with which to estimate the factor effects. Though the observational nature of themore » study cannot establish a causal relationship involving the response and the factors, the study can increase understanding of the underlying process. The study can also help determine where investment should be made to control input factors during production that will maximally influence the response. Because the factor combinations are observational, the chosen model matrix will be nonorthogonal and will not allow independent estimation of factor effects. In this manuscript we borrow principles from design of experiments to suggest an 'optimal' selection of factor combinations. Specifically, we consider precision of model parameter estimates, the issue of replication, and abilities to detect lack of fit and to estimate two-factor interactions. Through an example, we present strategies for selecting a subset of factor combinations that simultaneously balance multiple objectives, conduct a limited sensitivity analysis, and provide practical guidance for implementing our techniques across a variety of quality engineering disciplines.« less

Cardiovascular involvement in systemic rheumatic diseases: An integrated view for the treating physicians.

PubMed

Lee, Kwang Seob; Kronbichler, Andreas; Eisenhut, Michael; Lee, Keum Hwa; Shin, Jae Il

2018-03-01

Systemic autoimmune diseases can affect various kinds of organs including the kidney, the skin, soft tissue and the bone. Among others, cardiovascular involvement in rheumatic diseases has been shown to affect myocardium, pericardium, cardiac vessels, conduction system and valves, eventually leading to increased mortality. In general, underlying chronic inflammation leads to premature atherosclerosis, but also other manifestations such as arrhythmia and heart failure may have a 'silent' progress. Traditional cardiovascular risk factors play a secondary role, while disease-specific factors (i.e. disease duration, severity, antibody positivity, persistent disease activity) can directly influence the cardiovascular system. Therefore, early diagnosis is critical to optimize management and to control inflammatory activity and recent data suggest that risk factors (i.e. hypercholesterolemia and hypertension) need intensive treatment as well. With the advent of immunosuppressive agents, most rheumatic diseases are well controlled on treatment, but information related to their cardioprotective efficacy is not well-defined. In this review, we focus on cardiovascular involvement in rheumatic diseases and highlight current evidence which should be of help for the treating physicians. Moreover, cardiotoxicity of immunosuppressive drugs is a rare issue and such potential adverse events will be briefly discussed. Copyright © 2018. Published by Elsevier B.V.

Biological Networks Underlying Abiotic Stress Tolerance in Temperate Crops—A Proteomic Perspective

PubMed Central

Kosová, Klára; Vítámvás, Pavel; Urban, Milan Oldřich; Klíma, Miroslav; Roy, Amitava; Prášil, Ilja Tom

2015-01-01

Abiotic stress factors, especially low temperatures, drought, and salinity, represent the major constraints limiting agricultural production in temperate climate. Under the conditions of global climate change, the risk of damaging effects of abiotic stresses on crop production increases. Plant stress response represents an active process aimed at an establishment of novel homeostasis under altered environmental conditions. Proteins play a crucial role in plant stress response since they are directly involved in shaping the final phenotype. In the review, results of proteomic studies focused on stress response of major crops grown in temperate climate including cereals: common wheat (Triticum aestivum), durum wheat (Triticum durum), barley (Hordeum vulgare), maize (Zea mays); leguminous plants: alfalfa (Medicago sativa), soybean (Glycine max), common bean (Phaseolus vulgaris), pea (Pisum sativum); oilseed rape (Brassica napus); potato (Solanum tuberosum); tobacco (Nicotiana tabaccum); tomato (Lycopersicon esculentum); and others, to a wide range of abiotic stresses (cold, drought, salinity, heat, imbalances in mineral nutrition and heavy metals) are summarized. The dynamics of changes in various protein functional groups including signaling and regulatory proteins, transcription factors, proteins involved in protein metabolism, amino acid metabolism, metabolism of several stress-related compounds, proteins with chaperone and protective functions as well as structural proteins (cell wall components, cytoskeleton) are briefly overviewed. Attention is paid to the differences found between differentially tolerant genotypes. In addition, proteomic studies aimed at proteomic investigation of multiple stress factors are discussed. In conclusion, contribution of proteomic studies to understanding the complexity of crop response to abiotic stresses as well as possibilities to identify and utilize protein markers in crop breeding processes are discussed. PMID:26340626

Bacterial pneumonia in dogs and cats.

PubMed

Dear, Jonathan D

2014-01-01

Bacterial pneumonia is a common clinical diagnosis in dogs but seems to occur less commonly in cats. Underlying causes include viral infection, aspiration injury, and foreign body inhalation. Identification of the organisms involved in disease, appropriate use of antibiotics and adjunct therapy, and control of risk factors for pneumonia improve management. Copyright © 2014 Elsevier Inc. All rights reserved.

What Makes a Top-Selling Textbook? Comparing Characteristics of AIS Textbooks

ERIC Educational Resources Information Center

Badua, Frank; Sharifi, Mohsen; Mendez Mediavilla, Francis

2014-01-01

The factors involved in the selection of accounting textbooks are under-investigated, and most of the research is survey-based, largely ignoring the information that could be analyzed by direct inspection of textbook content and its impact on textbook selection. In this study the authors fill this lacuna by deploying content analysis of the…

Equal Pay Act: Wage Differentials for Time of Day Worked

ERIC Educational Resources Information Center

Stanford, Richard Alan

1974-01-01

The Supreme Court held in Corning Glass Works cases involving male only employees for night shifts that the time of day worked could constitute a factor other than sex whereby the wage differential might qualify as an exception under the Equal Pay Act. Shift differentials could be legal if proven to be nondiscriminatory. (LBH)

Processes and Factors Underlying Adolescent Males' Attitudes and Decision-Making in Relation to an Unplanned Pregnancy

ERIC Educational Resources Information Center

Condon, John T.; Corkindale, Carolyn J.; Russell, Alan; Quinlivan, Julie A.

2006-01-01

This research examined adolescent males' decision-making when confronted with a hypothetical unplanned pregnancy in a sexual partner. An innovative methodology, involving a computerized simulation game was utilized with 386 Australian males (mean age of 15 years). Data were gathered from responses made during the simulation, and questionnaires…

Transcription factors involved in retinogenesis are co-opted by the circadian clock following photoreceptor differentiation

PubMed Central

Laranjeiro, Ricardo; Whitmore, David

2014-01-01

The circadian clock is known to regulate a wide range of physiological and cellular processes, yet remarkably little is known about its role during embryo development. Zebrafish offer a unique opportunity to explore this issue, not only because a great deal is known about key developmental events in this species, but also because the clock starts on the very first day of development. In this study, we identified numerous rhythmic genes in zebrafish larvae, including the key transcriptional regulators neurod and cdx1b, which are involved in neuronal and intestinal differentiation, respectively. Rhythmic expression of neurod and several additional transcription factors was only observed in the developing retina. Surprisingly, these rhythms in expression commenced at a stage of development after these transcription factors are known to have played their essential role in photoreceptor differentiation. Furthermore, this circadian regulation was maintained in adult retina. Thus, once mature photoreceptors are formed, multiple retinal transcription factors fall under circadian clock control, at which point they appear to play a new and important role in regulating rhythmic elements in the phototransduction pathway. PMID:24924194

Risk factors of erectile dysfunction and penile vascular changes after surgical repair of penile fracture.

PubMed

El-Assmy, A; El-Tholoth, H S; Abou-El-Ghar, M E; Mohsen, T; Ibrahiem, E H I

2012-01-01

This study was conducted to determine the preoperative and intraoperative risk factors of ED and the underlying penile vascular abnormalities among patients with penile fracture treated surgically. In all, 180 patients with penile fracture were treated surgically and followed up in one center. None of our patients had ED before the penile trauma and only two of them had risk factors for systemic vascular diseases, such as diabetes mellitus (one patient) and hypertension (one patient). After a mean follow-up of 106 months, 11 patients (6.6%) developed ED, 7 had mild ED and 4 had moderate ED. The main risk factors for subsequent ED were aging, >50 years, and bilateral corporal involvement. Among the 11 patients with ED, color Doppler ultrasonography (CDU) showed normal Doppler indices in 4 (36.4%), veno-occlusive dysfunction in 4 (36.4%) and arterial insufficiency in the remaining 3 (27.2%) patients. CDU assessments from the injured and intact sides were comparable. ED of either a psychological or vascular origin can be encountered as a long-term sequel of surgical treatment of penile fracture. Aging, >50 years, at presentation and bilateral corporal involvement is the main risk factors for subsequent development of ED.

Towards an Integrated View of Early Molecular Changes Underlying Vulnerability to Social Stress in Psychosis.

PubMed

Barron, Henry; Hafizi, Sina; Mizrahi, Romina

2017-01-01

Psychotic disorders are heterogeneous and complex, involving many putative causal factors interacting along the course of disease development. Many of the factors implicated in the pathogenesis of psychosis also appear to be involved in disease onset and subsequent neuroprogression. Herein, we highlight the pertinent literature implicating inflammation and oxidative stress in the pathogenesis of psychosis, and the potential contribution of N-methyl-D-aspartate receptors (NMDARs). We also emphasize the role of peripubertal social stress in psychosis, and the ways in which hippocampal dysfunction can mediate dysregulation of the hypothalamic-pituitary-adrenal axis and cortisol release. Finally, we propose a model wherein inflammation and oxidative stress act as a first hit, producing altered parvalbumin interneuron development, NMDAR hypofunction, microglial priming, and sensitivity to a second hit of peripubertal social stress. With a greater understanding of how these factors interact, it may be possible to detect, prevent, and treat psychosis more effectively. © 2017 S. Karger AG, Basel.

Impact of Leishmania metalloprotease GP63 on macrophage signaling

PubMed Central

Isnard, Amandine; Shio, Marina T.; Olivier, Martin

2012-01-01

The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions. PMID:22919663

Impact of Leishmania metalloprotease GP63 on macrophage signaling.

PubMed

Isnard, Amandine; Shio, Marina T; Olivier, Martin

2012-01-01

The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions.

Epigenetic changes in neurology: DNA methylation in multiple sclerosis.

PubMed

Iridoy Zulet, M; Pulido Fontes, L; Ayuso Blanco, T; Lacruz Bescos, F; Mendioroz Iriarte, M

2017-09-01

Epigenetics is defined as the study of the mechanisms that regulate gene expression without altering the underlying DNA sequence. The best known is DNA methylation. Multiple Sclerosis (MS) is a disease with no entirely known etiology, in which it is stated that the involvement of environmental factors on people with a genetic predisposition, may be key to the development of the disease. It is at this intersection between genetic predisposition and environmental factors where DNA methylation may play a pathogenic role. A literature review of the effects of environmental risk factors for the development of MS can have on the different epigenetic mechanisms as well as the implication that such changes have on the development of the disease. Knowledge of epigenetic modifications involved in the pathogenesis of MS, opens a new avenue of research for identification of potential biomarkers, as well as finding new therapeutic targets. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Predicting Pathways into Criminal Behavior: The Intersection of Race, Gender, Poverty, Psychological Factors

PubMed Central

Walt, Lisa Christine; Jason, Leonard A.

2017-01-01

Women’s incarceration rates have increased dramatically over recent years; with Black women’s rates disproportionately and significantly higher than other races. Researchers have attempted to understand this criminal justice involvement disparity, and have suggested two major theoretical pathways Differential Involvement and Differential Selection Theories to explain these racial differences. We use the Differential Involvement Theory as a framework to discuss how the objective experience of economic disadvantage as measured by indicators of structural hardship including educational and employment under-attainment and the experience of psychological stress related to resource loss (because of this disadvantage) may explain women’s engagement in criminal activity. In order to conceptualize psychological stress, we used Hobfoll’s Conservation of Resource’s (COR) Theory and measure. Next, we investigated the link between these factors and the degree (number of times incarcerated, number of months incarcerated in lifetime) of criminal behavior using baseline data collected from a NIH study that drew from a racially diverse sample of former substance abusing, criminally involved urban women. Results indicated potential racial differences in the perception of resource loss, and underscore the complex interaction of the experience of race, poverty, and the unique experience of stress on women’s decision making and criminal justice involvement. PMID:29651468

Development of raphe serotonin neurons from specification to guidance.

PubMed

Kiyasova, Vera; Gaspar, Patricia

2011-11-01

The main features of the development of the serotonin (5-HT) raphe neurons have been known for many years but more recent molecular studies, using mouse genetics, have since unveiled several intriguing aspects of the specification of the raphe serotonergic system. These studies indicated that, although all 5-HT neurons in the raphe follow the same general program for their specification, there are also clear regional differences in the way that these neurons are specified and are guided towards different brain targets. Here we overview recent progress made in the understanding of the developmental programming of serotonergic neurons in the mouse raphe, emphasizing data showing how heterogeneous subsets of 5-HT neurons may be generated. Serotonergic progenitors are produced in the brainstem in different rhombomeres under the influence of a set of secreted factors, sonic hedgehog and fibroblast growth factors, which determine their position in the neural tube. Two main transcriptional gene networks are involved in the specification of 5-HT identity, with Lmx1b and Pet1 transcription factors as main players. A differential requirement for Pet1 was, however, revealed, which underlies an anatomical and functional diversity. Transcriptional programs controlling 5-HT identity could also impact axon guidance mechanisms directing 5-HT neurons to their targets. Although no direct links have yet been established, a large set of molecular determinants have already been shown to be involved in the growth, axon guidance and targeting of 5-HT raphe neurons, particularly within the forebrain. Alterations in the molecular mechanisms involved in 5-HT development are likely to have significant roles in mood disease predisposition. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Establishment of paclitaxel-resistant breast cancer cell line and nude mice models, and underlying multidrug resistance mechanisms in vitro and in vivo.

PubMed

Chen, Si-Ying; Hu, Sa-Sa; Dong, Qian; Cai, Jiang-Xia; Zhang, Wei-Peng; Sun, Jin-Yao; Wang, Tao-Tao; Xie, Jiao; He, Hai-Rong; Xing, Jian-Feng; Lu, Jun; Dong, Ya-Lin

2013-01-01

Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR. The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteins related to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxel treatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry. Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor (ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and glutathione-S-transferase-π (GST-π) involved in the MDR phenotype of resistant cells and tumors were all overexpressed. The underlying MDR mechanism of breast cancer may involve increased expression of P-gp, LRP and GST-π.

Gene expression networks underlying ovarian development in wild largemouth bass (Micropterus salmoides).

PubMed

Martyniuk, Christopher J; Prucha, Melinda S; Doperalski, Nicholas J; Antczak, Philipp; Kroll, Kevin J; Falciani, Francesco; Barber, David S; Denslow, Nancy D

2013-01-01

Oocyte maturation in fish involves numerous cell signaling cascades that are activated or inhibited during specific stages of oocyte development. The objectives of this study were to characterize molecular pathways and temporal gene expression patterns throughout a complete breeding cycle in wild female largemouth bass to improve understanding of the molecular sequence of events underlying oocyte maturation. Transcriptomic analysis was performed on eight morphologically diverse stages of the ovary, including primary and secondary stages of oocyte growth, ovulation, and atresia. Ovary histology, plasma vitellogenin, 17β-estradiol, and testosterone were also measured to correlate with gene networks. Global expression patterns revealed dramatic differences across ovarian development, with 552 and 2070 genes being differentially expressed during both ovulation and atresia respectively. Gene set enrichment analysis (GSEA) revealed that early primary stages of oocyte growth involved increases in expression of genes involved in pathways of B-cell and T-cell receptor-mediated signaling cascades and fibronectin regulation. These pathways as well as pathways that included adrenergic receptor signaling, sphingolipid metabolism and natural killer cell activation were down-regulated at ovulation. At atresia, down-regulated pathways included gap junction and actin cytoskeleton regulation, gonadotrope and mast cell activation, and vasopressin receptor signaling and up-regulated pathways included oxidative phosphorylation and reactive oxygen species metabolism. Expression targets for luteinizing hormone signaling were low during vitellogenesis but increased 150% at ovulation. Other networks found to play a significant role in oocyte maturation included those with genes regulated by members of the TGF-beta superfamily (activins, inhibins, bone morphogenic protein 7 and growth differentiation factor 9), neuregulin 1, retinoid X receptor, and nerve growth factor family. This study offers novel insight into the gene networks underlying vitellogenesis, ovulation and atresia and generates new hypotheses about the cellular pathways regulating oocyte maturation.

Down-regulation of fibroblast growth factor 2 and its co-receptors heparan sulfate proteoglycans by resveratrol underlies the improvement of cardiac dysfunction in experimental diabetes.

PubMed

Strunz, Célia Maria Cássaro; Roggerio, Alessandra; Cruz, Paula Lázara; Pacanaro, Ana Paula; Salemi, Vera Maria Cury; Benvenuti, Luiz Alberto; Mansur, Antonio de Pádua; Irigoyen, Maria Cláudia

2017-02-01

Cardiac remodeling in diabetes involves cardiac hypertrophy and fibrosis, and fibroblast growth factor 2 (FGF2) is an important mediator of this process. Resveratrol, a polyphenolic antioxidant, reportedly promotes the improvement of cardiac dysfunction in diabetic rats. However, little information exists linking the amelioration of the cardiac function promoted by resveratrol and the expression of FGF2 and its co-receptors, heparan sulfate proteoglycans (HSPGs: Glypican-1 and Syndecan-4), in cardiac muscle of Type 2 diabetic rats. Diabetes was induced experimentally by the injection of streptozotocin and nicotinamide, and the rats were treated with resveratrol for 6 weeks. According to our results, there is an up-regulation of the expression of genes and/or proteins of Glypican-1, Syndecan-4, FGF2, peroxisome proliferator-activated receptor gamma and AMP-activated protein kinase in diabetic rats. On the other hand, resveratrol treatment promoted the attenuation of left ventricular diastolic dysfunction and the down-regulation of the expression of all proteins under study. The trigger for the changes in gene expression and protein synthesis promoted by resveratrol was the presence of diabetes. The negative modulation conducted by resveratrol on FGF2 and HSPGs expression, which are involved in cardiac remodeling, underlies the amelioration of cardiac function. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Land Resources Allocation Strategies in an Urban Area Involving Uncertainty: A Case Study of Suzhou, in the Yangtze River Delta of China

NASA Astrophysics Data System (ADS)

Lu, Shasha; Guan, Xingliang; Zhou, Min; Wang, Yang

2014-05-01

A large number of mathematical models have been developed to support land resource allocation decisions and land management needs; however, few of them can address various uncertainties that exist in relation to many factors presented in such decisions (e.g., land resource availabilities, land demands, land-use patterns, and social demands, as well as ecological requirements). In this study, a multi-objective interval-stochastic land resource allocation model (MOISLAM) was developed for tackling uncertainty that presents as discrete intervals and/or probability distributions. The developed model improves upon the existing multi-objective programming and inexact optimization approaches. The MOISLAM not only considers economic factors, but also involves food security and eco-environmental constraints; it can, therefore, effectively reflect various interrelations among different aspects in a land resource management system. Moreover, the model can also help examine the reliability of satisfying (or the risk of violating) system constraints under uncertainty. In this study, the MOISLAM was applied to a real case of long-term urban land resource allocation planning in Suzhou, in the Yangtze River Delta of China. Interval solutions associated with different risk levels of constraint violation were obtained. The results are considered useful for generating a range of decision alternatives under various system conditions, and thus helping decision makers to identify a desirable land resource allocation strategy under uncertainty.

Whole-tumour diffusion kurtosis MR imaging histogram analysis of rectal adenocarcinoma: Correlation with clinical pathologic prognostic factors.

PubMed

Cui, Yanfen; Yang, Xiaotang; Du, Xiaosong; Zhuo, Zhizheng; Xin, Lei; Cheng, Xintao

2018-04-01

To investigate potential relationships between diffusion kurtosis imaging (DKI)-derived parameters using whole-tumour volume histogram analysis and clinicopathological prognostic factors in patients with rectal adenocarcinoma. 79 consecutive patients who underwent MRI examination with rectal adenocarcinoma were retrospectively evaluated. Parameters D, K and conventional ADC were measured using whole-tumour volume histogram analysis. Student's t-test or Mann-Whitney U-test, receiver operating characteristic curves and Spearman's correlation were used for statistical analysis. Almost all the percentile metrics of K were correlated positively with nodal involvement, higher histological grades, the presence of lymphangiovascular invasion (LVI) and circumferential margin (CRM) (p<0.05), with the exception of between K 10th , K 90th and histological grades. In contrast, significant negative correlations were observed between 25th, 50th percentiles and mean values of ADC and D, as well as ADC 10th , with tumour T stages (p< 0.05). Meanwhile, lower 75th and 90th percentiles of ADC and D values were also correlated inversely with nodal involvement (p< 0.05). K mean showed a relatively higher area under the curve (AUC) and higher specificity than other percentiles for differentiation of lesions with nodal involvement. DKI metrics with whole-tumour volume histogram analysis, especially K parameters, were associated with important prognostic factors of rectal cancer. • K correlated positively with some important prognostic factors of rectal cancer. • K mean showed higher AUC and specificity for differentiation of nodal involvement. • DKI metrics with whole-tumour volume histogram analysis depicted tumour heterogeneity.

[Latent factors aggravating airway allergic symptom in urban population: the involvement of urban living environments].

PubMed

Azuma, E; Nakajima, T; Hashimoto, M; Toyoshima, K; Hayashida, M; Komachi, Y

1999-03-01

The involvement of urban living environments in IgE-increase (atopy) and ECP-increase (enhanced eosinophil activity), the inter-relationship of IgE-increase and ECP-increase, and their involvement in developing airway allergic symptoms were studied on a population of adult nonsmoking women, in order to elucidate the latent factors aggravating airway allergic symptoms in an urban population. In our earlier study on child asthma in 1994, we examined the relationship between living environments and mite proliferation in asthma and non-asthma groups and the involvement of mite proliferation in developing atopy in the non-asthma group. The asthma group consisted of 190 children under 12 years old who had been recently diagnosed as having bronchial asthma and under the care of Osaka Prefectural Habikino Hospital. The non-asthma group consisted of 78 children under 12 years old who had been under care at Osaka Prefectural Hospital but had no present history of allergic symptom. The adult woman group consisted of 423 non-smoking women who had been diagnosed as having no allergic disease by the medical examination done at Yao City, Osaka, each March from 1995 to 1997. Individual living environments such as housing and heating styles were surveyed by questionnaire. Also, the amount of mite allergen (Dp: Dermatophagoides pteronyssinus, Df: Dermatophagoides farinae) in room and bedding dust (only in the case of children) and the concentration of continine in urine were examined as objective indicators for the load of environmental allergen and the indoor air pollution by tobacco smoke, respectively. Atopy was diagnosed according to whether Dp-specific immunoglobulin E (Dp-IgE) was present/absent (positive/negative), and ECP-increase was defined as serum ECP concentration over 10 ng/ml. The results were as follows: 1. An environment of higher humidity (dampness) causing a room to become moldy appeared to enhance mite proliferation, while heating only with an electric heater or kotatsu appeared to suppress it. 2. Living environments were involved in the development of atopy in children and adult women through the effects on mite proliferation. In the case of children, heating with oil or gas heater appeared to have a positive effect while reinforced concrete housing a negative effect, probably by effects on the immune system. However, in the case of adult women, such modification was not observed. 3. Passive smoking in adult women was related to ECP-increase. 4. IgE-increase and ECP-increase appeared to be involved in each other. 5. Among airway allergic symptoms such as cough, sputum and wheeze, atopy was involved in wheeze, and ECP-increase in cough.

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening[OPEN

PubMed Central

Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui

2017-01-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple (Malus domestica). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1, an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2, encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3, encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1. This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1. Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. PMID:28550149

Association of main driver-dependent risk factors with the risk of causing a vehicle collision in Spain, 1990-1999.

PubMed

Lardelli-Claret, Pablo; Luna-Del-Castillo, Juan de Dios; Jiménez-Moleón, José Juan; Rueda-Domínguez, Trinidad; García-Martín, Miguel; Femia-Marzo, Pedro; Bueno-Cavanillas, Aurora

2003-08-01

To assess the strength of association of main driver-dependent risk factors with the risk of causing a collision between vehicles in Spain, from 1990 to 1999. The data for this paired-by-collision, case-control study were obtained from the Spanish Dirección General de Tráfico traffic crash database. The study included all 220284 collisions involving two or more vehicles with four or more wheels, in which only one of the drivers involved committed an infraction. Infractor drivers comprised the case group; noninfractor drivers involved in the same collision were their corresponding paired controls. All driver-dependent factors were associated with the risk of causing a collision. The highest adjusted odds ratio estimates were obtained for sleepiness (64.35; CI, 45.12-91.79), inappropriate speed (28.33; CI, 26.37-30.44), and driving under the influence of alcohol with a positive breath test (22.32; CI, 19.64-25.37). An increase in the number of years in possession of a driving license showed a protective effect, albeit the strength of the effect decreased as age increased. Our results emphasize the urgent need to implement strategies aimed mainly at controlling speeding, sleepiness, and alcohol consumption before driving-the main driver-dependent risk factors for causing a vehicle collision.

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening.

PubMed

Li, Tong; Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui; Wang, Aide

2017-06-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple ( Malus domestica ). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1 , an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2 , encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3 , encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1 This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1 Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. © 2017 American Society of Plant Biologists. All rights reserved.

Maturation of Atriplex halimus L. leaves involves changes in the molecular regulation of stomatal conductance under high evaporative demand and high but not low soil water content.

PubMed

Nada, Reham M; Khedr, Abdel Hamid A; Serag, Mamdouh S; El-Qashlan, Nesma R; Abogadallah, Gaber M

2018-06-19

Under high water availability, the maximum gas exchange was observed at noon in the expanding and expanded leaves. The expanded leaves showed lower gas exchange capacity due to the regulation of stomatal-movement genes. Under well-watered condition, stomatal conductance (g s ) and photosynthetic rate (A) of expanding and expanded leaves of Atriplex halimus peaked at noon despite the midday decline in the leaf relative water content, suggesting deviation from typical isohydric behaviour. However, the expanding leaves had higher g s and A than the expanded ones. When light intensity was temporarily increased, A and g s were enhanced in both types of leaves though to a higher level in the expanding leaves. In well-watered expanded leaves: (1) A was mainly dependent on g s rather than photosynthetic capacity; g s was controlled by internal factors, thereby limiting water loss via transpiration (E); (2) the accumulation of total soluble sugars (TSS) along with increased Rubisco protein could be a subsidiary factor limiting A; (3) TSS and ABA seem to act in co-ordination to up-regulate ABA-dependent genes controlling g s and (4) the significant induction of DREBs suggests a role in maintaining high relative water content in these leaves compared to the expanding ones. In expanding leaves of well-watered plants, high A along with Rubisco down-regulation and elevated TSS suggests that A was regulated by signals coordinating carbon and nitrogen balance and the elevated ABA could be involved in regulating the hydraulic activity to enhance cell expansion and facilitate leaf growth. Both expanded and expanding leaves behaved in typical isohydric manner under water stress, which did not involve the accumulation of ABA suggesting that stomatal closure was primarily stimulated by hydraulic rather than chemical signals.

Influence of elevated atmospheric carbon dioxide on transcriptional responses of Bradyrhizobium japonicum in the soybean rhizoplane.

PubMed

Sugawara, Masayuki; Sadowsky, Michael J

2013-01-01

Elevated atmospheric CO2 can influence the structure and function of rhizoplane and rhizosphere microorganisms by altering root growth and the quality and quantity of compounds released into the rhizoplane and rhizosphere via root exudation. In these studies we investigated the transcriptional responses of Bradyrhizobium japonicum cells growing in the rhizoplane of soybean plants exposed to elevated atmospheric CO2. The results of microarray analyses indicated that elevated atmospheric CO2 concentration indirectly influenced the expression of a large number of genes in Bradyrhizobium attached to soybean roots. In addition, relative to plants and bacteria grown under ambient CO2 growth conditions, genes involved in C1 metabolism, denitrification and FixK2-associated genes, including those involved in nitrogen fixation, microaerobic respiration, respiratory nitrite reductase, and heme biosynthesis, were significantly up-regulated under conditions of elevated CO2 in the rhizosphere. The expression profile of genes involved in lipochitooligosaccharide Nod factor biosynthesis and negative transcriptional regulators of nodulation genes, nolA and nodD2, were also influenced by plant growth under conditions of elevated CO2. Taken together, the results of these studies indicate that the growth of soybeans under conditions of elevated atmospheric CO2 influences gene expressions in B. japonicum in the soybean rhizoplane, resulting in changes to carbon/nitrogen metabolism, respiration, and nodulation efficiency.

Influence of Elevated Atmospheric Carbon Dioxide on Transcriptional Responses of Bradyrhizobium japonicum in the Soybean Rhizoplane

PubMed Central

Sugawara, Masayuki; Sadowsky, Michael J.

2013-01-01

Elevated atmospheric CO2 can influence the structure and function of rhizoplane and rhizosphere microorganisms by altering root growth and the quality and quantity of compounds released into the rhizoplane and rhizosphere via root exudation. In these studies we investigated the transcriptional responses of Bradyrhizobium japonicum cells growing in the rhizoplane of soybean plants exposed to elevated atmospheric CO2. The results of microarray analyses indicated that elevated atmospheric CO2 concentration indirectly influenced the expression of a large number of genes in Bradyrhizobium attached to soybean roots. In addition, relative to plants and bacteria grown under ambient CO2 growth conditions, genes involved in C1 metabolism, denitrification and FixK2-associated genes, including those involved in nitrogen fixation, microaerobic respiration, respiratory nitrite reductase, and heme biosynthesis, were significantly up-regulated under conditions of elevated CO2 in the rhizosphere. The expression profile of genes involved in lipochitooligosaccharide Nod factor biosynthesis and negative transcriptional regulators of nodulation genes, nolA and nodD2, were also influenced by plant growth under conditions of elevated CO2. Taken together, the results of these studies indicate that the growth of soybeans under conditions of elevated atmospheric CO2 influences gene expressions in B. japonicum in the soybean rhizoplane, resulting in changes to carbon/nitrogen metabolism, respiration, and nodulation efficiency. PMID:23666536

Sociocultural Determinants of Risky Sexual Behaviors among Adult Latinas: A Longitudinal Study of a Community-Based Sample.

PubMed

Rojas, Patria; Huang, Hui; Li, Tan; Ravelo, Gira J; Sanchez, Mariana; Dawson, Christyl; Brook, Judith; Kanamori, Mariano; De La Rosa, Mario

2016-11-23

Few studies have examined the sociocultural determinants of risky sexual behavior trajectories among adult Latinas. To longitudinally examine the link between sociocultural determinants of risky sexual behaviors, we followed a sample of adult Latina mother-daughter dyads ( n = 267) across a 10-year span through four waves of data collection. The present study investigates how risky sexual behavior (operationalized as sex under the influence of alcohol or other drugs, sex without a condom, or multiple sex partners) is affected by: (a) socioeconomic conditions; (b) mental health; (c) medical health; (d) acculturation to U.S. culture; (e) interpersonal support; (f) relationship stress; (g) mother-daughter attachment; (h) intimate partner violence; (i) religious involvement; and (j) criminal justice involvement. Results indicate the following factors are negatively associated with risky sexual behavior: drug and alcohol use, treating a physical problem with prescription drugs, religious involvement, and mother-daughter attachment. The following factors are positively associated with risky sexual behavior: higher number of mental health symptoms, being U.S.-born, and criminal justice involvement. We discuss implications for the future development of culturally relevant interventions based on the study findings.

Sociocultural Determinants of Risky Sexual Behaviors among Adult Latinas: A Longitudinal Study of a Community-Based Sample

PubMed Central

Rojas, Patria; Huang, Hui; Li, Tan; Ravelo, Gira J.; Sanchez, Mariana; Dawson, Christyl; Brook, Judith; Kanamori, Mariano; De La Rosa, Mario

2016-01-01

Few studies have examined the sociocultural determinants of risky sexual behavior trajectories among adult Latinas. To longitudinally examine the link between sociocultural determinants of risky sexual behaviors, we followed a sample of adult Latina mother-daughter dyads (n = 267) across a 10-year span through four waves of data collection. The present study investigates how risky sexual behavior (operationalized as sex under the influence of alcohol or other drugs, sex without a condom, or multiple sex partners) is affected by: (a) socioeconomic conditions; (b) mental health; (c) medical health; (d) acculturation to U.S. culture; (e) interpersonal support; (f) relationship stress; (g) mother-daughter attachment; (h) intimate partner violence; (i) religious involvement; and (j) criminal justice involvement. Results indicate the following factors are negatively associated with risky sexual behavior: drug and alcohol use, treating a physical problem with prescription drugs, religious involvement, and mother–daughter attachment. The following factors are positively associated with risky sexual behavior: higher number of mental health symptoms, being U.S.-born, and criminal justice involvement. We discuss implications for the future development of culturally relevant interventions based on the study findings. PMID:27886095

The Economic Education of Young People

ERIC Educational Resources Information Center

Prutchenkov, A.; Teriukova, T.

2010-01-01

Under the economic conditions that are new to Russia, young people are subjected to the influence of many factors. On the one hand, they are compelled to put up opposition to the economic system, while on the other hand they are compelled to be actively involved in it. In either case they have to solve the problem of how to survive in the system.…

Depression and Anger as Risk Factors Underlying the Relationship between Maternal Substance Involvement and Child Abuse Potential

ERIC Educational Resources Information Center

Hien, Denise; Cohen, Lisa R.; Caldeira, Nathilee A.; Flom, Peter; Wasserman, Gail

2010-01-01

Objective: This study examines how emotion regulation deficits in the area of anger arousal and reactivity are associated with child abuse potential in mothers with substance use and depressive disorders in order to identify targeted areas for prevention and treatment. Methods: A sample of 152 urban mothers was interviewed on measures of substance…

Identification of a novel pathway involving a GATA transcription factor in yeast and possibly plant Zn uptake and homeostasis

USDA-ARS?s Scientific Manuscript database

To gain a better understanding of the regulation of Zn homeostasis in plants and the degree of conservation of Zn homeostasis between plants and yeast, a cDNA library from the Zn/Cd hyperaccumulating plant species, Nocceae caerulescens, was screened for its ability to restore growth under Zn limitin...

Factors for MPD Thrustors.

DTIC Science & Technology

1986-05-01

sense that no wave proption is involved. To look for the Hall hpq62 1,I1 K 1, W111,1,1,1 I pamsmet’ under which condition the plasma with heat...is by a three- body c-c-i process. n, ~ o = r v- - c( n r), (applS ( ,A 1 are function of electron temperature only.) In equilibrium. r~e - 0 (Let us

Some human factors issues in the development and evaluation of cockpit alerting and warning systems

NASA Technical Reports Server (NTRS)

Randle, R. J., Jr.; Larsen, W. E.; Williams, D. H.

1980-01-01

A set of general guidelines for evaluating a newly developed cockpit alerting and warning system in terms of human factors issues are provided. Although the discussion centers around a general methodology, it is made specifically to the issues involved in alerting systems. An overall statement of the current operational problem is presented. Human factors problems with reference to existing alerting and warning systems are described. The methodology for proceeding through system development to system test is discussed. The differences between traditional human factors laboratory evaluations and those required for evaluation of complex man-machine systems under development are emphasized. Performance evaluation in the alerting and warning subsystem using a hypothetical sample system is explained.

Alternative Oxidase Transcription Factors AOD2 and AOD5 of Neurospora crassa Control the Expression of Genes Involved in Energy Production and Metabolism.

PubMed

Qi, Zhigang; Smith, Kristina M; Bredeweg, Erin L; Bosnjak, Natasa; Freitag, Michael; Nargang, Frank E

2017-02-09

In Neurospora crassa , blocking the function of the standard mitochondrial electron transport chain results in the induction of an alternative oxidase (AOX). AOX transfers electrons directly from ubiquinol to molecular oxygen. AOX serves as a model of retrograde regulation since it is encoded by a nuclear gene that is regulated in response to signals from mitochondria. The N. crassa transcription factors AOD2 and AOD5 are necessary for the expression of the AOX gene. To gain insight into the mechanism by which these factors function, and to determine if they have roles in the expression of additional genes in N. crassa , we constructed strains expressing only tagged versions of the proteins. Cell fractionation experiments showed that both proteins are localized to the nucleus under both AOX inducing and noninducing conditions. Furthermore, chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) analysis revealed that the proteins are bound to the promoter region of the AOX gene under both conditions. ChIP-seq also showed that the transcription factors bind to the upstream regions of a number of genes that are involved in energy production and metabolism. Dependence on AOD2 and AOD5 for the expression of several of these genes was verified by quantitative PCR. The majority of ChIP-seq peaks observed were enriched for both AOD2 and AOD5. However, we also observed occasional sites where one factor appeared to bind preferentially. The most striking of these was a conserved sequence that bound large amounts of AOD2 but little AOD5. This sequence was found within a 310 bp repeat unit that occurs at several locations in the genome. Copyright © 2017 Qi et al.

Risk factors affecting fatal bus accident severity: Their impact on different types of bus drivers.

PubMed

Feng, Shumin; Li, Zhenning; Ci, Yusheng; Zhang, Guohui

2016-01-01

While the bus is generally considered to be a relatively safe means of transportation, the property losses and casualties caused by bus accidents, especially fatal ones, are far from negligible. The reasons for a driver to incur fatalities are different in each case, and it is essential to discover the underlying risk factors of bus fatality severity for different types of drivers in order to improve bus safety. The current study investigates the underlying risk factors of fatal bus accident severity to different types of drivers in the U.S. by estimating an ordered logistic model. Data for the analysis are retrieved from the Buses Involved in Fatal Accidents (BIFA) database from the USA for the years 2006-2010. Accidents are divided into three levels by counting their equivalent fatalities, and the drivers are classified into three clusters by the K-means cluster analysis. The analysis shows that some risk factors have the same impact on different types of drivers, they are: (a) season; (b) day of week; (c) time period; (d) number of vehicles involved; (e) land use; (f) manner of collision; (g) speed limit; (h) snow or ice surface condition; (i) school bus; (j) bus type and seating capacity; (k) driver's age; (l) driver's gender; (m) risky behaviors; and (n) restraint system. Results also show that some risk factors only have impact on the "young and elder drivers with history of traffic violations", they are: (a) section type; (b) number of lanes per direction; (c) roadway profile; (d) wet road surface; and (e) cyclist-bus accident. Notably, history of traffic violations has different impact on different types of bus drivers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genome-Wide Analysis of the RAV Family in Soybean and Functional Identification of GmRAV-03 Involvement in Salt and Drought Stresses and Exogenous ABA Treatment

PubMed Central

Zhao, Shu-Ping; Xu, Zhao-Shi; Zheng, Wei-Jun; Zhao, Wan; Wang, Yan-Xia; Yu, Tai-Fei; Chen, Ming; Zhou, Yong-Bin; Min, Dong-Hong; Ma, You-Zhi; Chai, Shou-Cheng; Zhang, Xiao-Hong

2017-01-01

Transcription factors play vital roles in plant growth and in plant responses to abiotic stresses. The RAV transcription factors contain a B3 DNA binding domain and/or an APETALA2 (AP2) DNA binding domain. Although genome-wide analyses of RAV family genes have been performed in several species, little is known about the family in soybean (Glycine max L.). In this study, a total of 13 RAV genes, named as GmRAVs, were identified in the soybean genome. We predicted and analyzed the amino acid compositions, phylogenetic relationships, and folding states of conserved domain sequences of soybean RAV transcription factors. These soybean RAV transcription factors were phylogenetically clustered into three classes based on their amino acid sequences. Subcellular localization analysis revealed that the soybean RAV proteins were located in the nucleus. The expression patterns of 13 RAV genes were analyzed by quantitative real-time PCR. Under drought stresses, the RAV genes expressed diversely, up- or down-regulated. Following NaCl treatments, all RAV genes were down-regulated excepting GmRAV-03 which was up-regulated. Under abscisic acid (ABA) treatment, the expression of all of the soybean RAV genes increased dramatically. These results suggested that the soybean RAV genes may be involved in diverse signaling pathways and may be responsive to abiotic stresses and exogenous ABA. Further analysis indicated that GmRAV-03 could increase the transgenic lines resistance to high salt and drought and result in the transgenic plants insensitive to exogenous ABA. This present study provides valuable information for understanding the classification and putative functions of the RAV transcription factors in soybean. PMID:28634481

Attacks by packs of dogs involving predation on human beings

PubMed Central

Borchelt, Peter L.; Lockwood, Randall; Beck, Alan M.; Voith, Victoria L.

1983-01-01

Dog bites are a medical problem for millions of people, children being the most common victims. Human deaths attributable to dog bite injury (not rabies) are relatively infrequent. There have been some epidemiologic reviews, but this study is the first attempt to arrive at an understanding of bites involving predation on human beings by conducting behavioral examinations under controlled conditions of the dogs involved, and by interviewing victims, witnesses, and people familiar with the animals. The three cases studied involved two fatalities and an attack that was nearly fatal. The victims were 11, 14, and 81. In each case, owned pet dogs consumed some human tissue. The severity of the victims' injuries was not the consequence of a single dog bite, but the result of repeated attacks by dogs behaving as a social group. Factors that might contribute to a dog's regarding human beings as potential prey were examined, including hunger, prior predation, group behaviors, defense of territory, previous interactions with people, the presence of estrous female dogs, and environmental stimuli. In two of the cases, it was possible, by using similar stimuli, to duplicate the circumstances at the time of the attack. The results of the observations showed the value of behavioral analysis and simulations methods in evaluating possible factors in dog attacks. Among the many factors probably involved in severe dog attacks are the size, number, and nutritional status of the dogs; the dogs' previous aggressive contacts with people; the victim's age, size, health, and behavior; and the absence of other human beings in the vicinity. Imagesp61-ap61-bp61-c PMID:6828639

Pulse wave velocity is associated with cognitive impairment in hemodialysis patients.

PubMed

Angermann, Susanne; Baumann, Marcus; Wassertheurer, Siegfried; Mayer, Christopher Clemens; Steubl, Dominik; Hauser, Christine; Suttmann, Yana; Reichelt, Anna-Lena; Satanovskij, Robin; Lorenz, Georg; Lukas, Moritz; Haller, Bernhard; Heemann, Uwe; Grimmer, Timo; Schmaderer, Christoph

2017-07-01

Cognitive impairment in hemodialysis patients is common and associated with adverse outcomes. So far, the underlying pathogenesis remains unclear. Therefore, we examined the potential relationship between cognitive impairment and three different categories of risk factors with particular focus on arterial stiffness measured by pulse wave velocity (PWV). A total of 201 chronic hemodialysis patients underwent cognitive testing under standardized conditions using the Montreal Cognitive Assessment (MoCA). Demographic data including cardiovascular risk factors, dialysis-associated factors as well as factors related to chronic kidney disease (CKD) were analyzed. To account for arterial stiffness, PWV was measured by ambulatory blood pressure monitoried with an oscillometric device that records brachial blood pressure along with pulse waves. In our cohort, 60.2% of patients showed pathological MoCA test results indicating cognitive impairment. PWV was significantly associated with cognitive impairment apart from age, educational level, diabetes, and hypercholesterolemia. High prevalence of cognitive impairment in hemodialysis patients was confirmed. For the first time, an association between cognitive impairment and arterial stiffness was detected in a larger cohort of hemodialysis patients. Concerning the underlying pathogenesis of cognitive impairment, current results revealed a potential involvement of arterial stiffness, which has to be further evaluated in future studies. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The cognitive psychology of Internet gaming disorder.

PubMed

King, Daniel L; Delfabbro, Paul H

2014-06-01

Internet gaming disorder (IGD) has received nomenclatural recognition as a potential mental health disorder, despite evident variability in its core psychopathology and psychometric assessment. Although cognitive-behavioural therapy (CBT) is considered an efficacious treatment for IGD, the underlying cognitions of the disorder are not well understood. This review aimed to synthesise research evidence on Internet gaming cognition toward identification of cognitive factors underlying IGD. A systematic review of 29 quantitative studies on Internet gaming cognition and 7 treatment studies employing cognitive therapy for IGD was conducted. Four cognitive factors underlying IGD were identified. Factors included (a) beliefs about game reward value and tangibility, (b) maladaptive and inflexible rules about gaming behaviour, (c) over-reliance on gaming to meet self-esteem needs, and (d) gaming as a method of gaining social acceptance. It is proposed that IGD-related cognition may be more complex than "preoccupation" (i.e., criterion A of IGD). IGD cognition may involve the persistent overvaluation of video gaming rewards, activities, and identities, combined with a need to adhere to maladaptive rules governing use and completion of video games. Greater understanding of the proposed cognitive factors may advance clinical research agendas on identification of individuals with IGD, as well as the expansion and improvement of cognitive therapies for the disorder. Copyright © 2014 Elsevier Ltd. All rights reserved.

Retention and Attrition Factors for Female Certified Athletic Trainers in the National Collegiate Athletic Association Division I Football Bowl Subdivision Setting

PubMed Central

Goodman, Ashley; Mensch, James M.; Jay, Michelle; French, Karen E.; Mitchell, Murray F.; Fritz, Stacy L.

2010-01-01

Abstract Context: Organizational effectiveness and the continuity of patient care can be affected by certain levels of attrition. However, little is known about the retention and attrition of female certified athletic trainers (ATs) in certain settings. Objective: To gain insight and understanding into the factors and circumstances affecting female ATs' decisions to persist in or leave the National Collegiate Athletic Association Division I Football Bowl Subdivision (NCAA D-I FBS) setting. Design: Qualitative study. Setting: The 12 NCAA D-I FBS institutions within the Southeastern Conference. Patients or Other Participants: A total of 23 women who were current full-time ATs (n  =  12) or former full-time ATs (n  =  11) at Southeastern Conference institutions participated. Data Collection and Analysis: Data were collected via in-depth, semistructured interviews, transcribed verbatim, and analyzed via a grounded theory approach. Peer review and member checking methods were performed to establish trustworthiness. Results: The decision to persist involved 4 main factors: (1) increased autonomy, (2) increased social support, (3) enjoyment of job/fitting the NCAA D-I mold, and (4) kinship responsibility. Two subfactors of persistence, the NCAA D-I atmosphere and positive athlete dynamics, emerged under the main factor of enjoyment of job/fitting the NCAA D-I mold. The decision to leave included 3 main factors: (1) life balance issues, (2) role conflict and role overload, and (3) kinship responsibility. Two subfactors of leaving, supervisory/coach conflict and decreased autonomy, emerged under the main factor of role conflict and role overload. Conclusions: A female AT's decision to persist in or leave the NCAA D-I FBS setting can involve several factors. In order to retain capable ATs long term in the NCAA D-I setting, an individual's attributes and obligations, the setting's cultural issues, and an organization's social support paradigm should be considered. PMID:20446843

Bright versus dim ambient light affects subjective well-being but not serotonin-related biological factors.

PubMed

Stemer, Bettina; Melmer, Andreas; Fuchs, Dietmar; Ebenbichler, Christoph; Kemmler, Georg; Deisenhammer, Eberhard A

2015-10-30

Light falling on the retina is converted into an electrical signal which stimulates serotonin synthesis. Previous studies described an increase of plasma and CNS serotonin levels after bright light exposure. Ghrelin and leptin are peptide hormones which are involved in the regulation of hunger/satiety and are related to serotonin. Neopterin and kynurenine are immunological markers which are also linked to serotonin biosynthesis. In this study, 29 healthy male volunteers were exposed to bright (5000lx) and dim (50lx) light conditions for 120min in a cross-over manner. Subjective well-being and hunger as well as various serotonin associated plasma factors were assessed before and after light exposure. Subjective well-being showed a small increase under bright light and a small decrease under dim light, resulting in a significant interaction between light condition and time. Ghrelin concentrations increased significantly under both light conditions, but there was no interaction between light and time. Correspondingly, leptin decreased significantly under both light conditions. Hunger increased significantly with no light-time interaction. We also found a significant decrease of neopterin, tryptophan and tyrosine levels, but no interaction between light and time. In conclusion, ambient light was affecting subjective well-being rather than serotonin associated biological factors. Copyright © 2015. Published by Elsevier Ireland Ltd.

Epidermal growth factor- and hepatocyte growth factor-receptor activity in serum-free cultures of human hepatocytes.

PubMed

Runge, D M; Runge, D; Dorko, K; Pisarov, L A; Leckel, K; Kostrubsky, V E; Thomas, D; Strom, S C; Michalopoulos, G K

1999-02-01

Serum-free primary cultures of hepatocytes are a useful tool to study factors triggering hepatocyte proliferation and regeneration. We have developed a chemically defined serum-free system that allows human hepatocyte proliferation in the presence of epidermal growth factor and hepatocyte growth factor. DNA synthesis and accumulation were determined by [3H]thymidine incorporation and fluorometry, respectively. Western blot analyses and co-immunoprecipitations were used to investigate the association of proteins involved in epidermal growth factor and hepatocyte growth factor activation and signaling: epidermal growth factor receptor, hepatocyte growth factor receptor (MET), urokinase-type plasminogen activator and its receptor, and a member of the signal transducer and activator of transcription family, STAT-3. Primary human hepatocytes proliferated under serum-free conditions in a chemically defined medium for up to 12 days. Epidermal growth factor-receptor and MET were present and functional, decreasing over time. MET, urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor co-precipitated to varying degrees during the culture period. STAT-3 co-precipitated with epidermal growth factor-receptor and MET to varying degrees. Proliferation of human hepatocytes can improve by modification of a chemically defined medium originally used for rat hepatocyte cultures. In these long-term cultures of human hepatocytes, hepatocyte growth factor and epidermal growth factor can stimulate growth and differentiation by interacting with their receptors and initiating downstream signaling. This involves complex formation of the receptors with other plasma membrane components for MET (urokinase-type plasminogen activator in context of its receptor) and activation of STAT-3 for both receptors.

ERK1/2 and Akt phosphorylation were essential for MGF E peptide regulating cell morphology and mobility but not proangiogenic capacity of BMSCs under severe hypoxia.

PubMed

Sha, Yongqiang; Yang, Li; Lv, Yonggang

2018-04-01

Severe hypoxia inhibits the adhesion and mobility of bone marrow-derived mesenchymal stem cells (BMSCs) and limits their application in bone tissue engineering. In this study, CoCl 2 was used to simulate severe hypoxia and the effects of mechano-growth factor (MGF) E peptide on the morphology, adhesion, migration, and proangiogenic capacity of BMSCs under hypoxia were measured. It was demonstrated that severe hypoxia (500-μM CoCl 2 ) significantly caused cell contraction and reduced cell area, roundness, adhesion, and migration of BMSCs. RhoA and ROCK1 expression levels were upregulated by severe hypoxia, but p-RhoA and mobility-relevant protein (integrin β1, p-FAK and fibronectin) expression levels in BMSCs were inhibited. Fortunately, MGF E peptide could restore all abovementioned indexes except RhoA expression. MEK-ERK1/2 pathway was involved in MGF E peptide regulating cell morphological changes, mobility, and relevant proteins (except p-FAK). PI3K-Akt pathway was involved in MGF E peptide regulating cell area, mobility, and relevant proteins. Besides, severe hypoxia upregulated vascular endothelial growth factor α expression but was harmful for proangiogenic capacity of BMSCs. Our study suggested that MGF E peptide might be helpful for the clinical application of tissue engineering strategy in bone defect repair. Sever hypoxia impairs bone defect repair with bone marrow-derived mesenchymal stem cells (BMSCs). This study proved that mechano-growth factor E (MGF E) peptide could improve the severe hypoxia-induced cell contraction and decline of cell adhesion and migration of BMSCs. Besides, MGF E peptide weakened the effects of severe hypoxia on the cytoskeleton arrangement- and mobility-relevant protein expression levels in BMSCs. The underlying molecular mechanism was also verified. Finally, it was confirmed that MGF E peptide showed an adverse effect on the expression level of vascular endothelial growth factor α in BMSCs under severe hypoxia but could make up for this deficiency through accelerating cell proliferation. Copyright © 2018 John Wiley & Sons, Ltd.

Factors Regulating Vagal Sensory Development: Potential Role in Obesities of Developmental Origin

PubMed Central

Fox, Edward A.; Murphy, Michelle C.

2008-01-01

Contributors to increased obesity in children may include perinatal under- or overnutrition. Humans and rodents raised under these conditions develop obesity, which like obesities of other etiologies has been associated with increased meal size. Since vagal sensory innervation of the gastrointestinal (GI) tract transmits satiation signals that regulate meal size, one mechanism through which abnormal perinatal nutrition could increase meal size is by altering vagal development, possibly by causing changes in the expression of factors that control it. Therefore, we have begun to characterize development of vagal innervation of the GI tract and the expression patterns and functions of the genes involved in this process. Important events in development of mouse vagal GI innervation occurred between midgestation and the second postnatal week, suggesting they could be vulnerable to effects of abnormal nutrition preor postnatally. One gene investigated was brain- derived neurotrophic factor (BDNF), which regulates survival of a subpopulation of vagal sensory neurons. BDNF was expressed in some developing stomach wall tissues innervated by vagal afferents. At birth, mice deficient in BDNF exhibited a 50% reduction of putative intraganglionic laminar ending mechanoreceptor precursors, and a 50% increase in axons that had exited fiber bundles. Additionally, BDNF was required for patterning of individual axons and fiber bundles in the antrum and differentiation of intramuscular array mechanoreceptors in the forestomach. It will be important to determine whether abnormal perinatal environments alter development of vagal sensory innervation of the GI tract, involving effects on expression of BDNF, or other factors regulating vagal development. PMID:18234244

Early flight test experience with Cockpit Displayed Traffic Information (CDTI)

NASA Technical Reports Server (NTRS)

Abbott, T. S.; Moen, G. C.; Person, L. H., Jr.; Keyser, G. L., Jr.; Yenni, K. R.; Garren, J. F., Jr.

1980-01-01

Coded symbology, based on the results of early human factors studies, was displayed on the electronic horizontal situation indicator and flight tested on an advanced research aircraft in order to subject the coded traffic symbology to a realistic flight environment and to assess its value by means of a direct comparison with simple, uncoded traffic symbology. The tests consisted of 28 curved, decelerating approaches, flown by research-pilot flight crews. The traffic scenarios involved both conflict-free and blunder situations. Subjective pilot commentary was obtained through the use of a questionnaire and extensive pilot debriefing sessions. The results of these debriefing sessions group conveniently under either of two categories: display factors or task performance. A major item under the display factor category was the problem of display clutter. The primary contributors to clutter were the use of large map-scale factors, the use of traffic data blocks, and the presentation of more than a few aircraft. In terms of task performance, the cockpit displayed traffic information was found to provide excellent overall situation awareness.

Potential Mechanisms of Cancer Prevention by Weight Control

NASA Astrophysics Data System (ADS)

Jiang, Yu; Wang, Weiqun

Weight control via dietary caloric restriction and/or physical activity has been demonstrated in animal models for cancer prevention. However, the underlying mechanisms are not fully understood. Body weight loss due to negative energy balance significantly reduces some metabolic growth factors and endocrinal hormones such as IGF-1, leptin, and adiponectin, but enhances glucocorticoids, that may be associated with anti-cancer mechanisms. In this review, we summarized the recent studies related to weight control and growth factors. The potential molecular targets focused on those growth factors- and hormones-dependent cellular signaling pathways are further discussed. It appears that multiple factors and multiple signaling cascades, especially for Ras-MAPK-proliferation and PI3K-Akt-anti-apoptosis, could be involved in response to weight change by dietary calorie restriction and/or exercise training. Considering prevalence of obesity or overweight that becomes apparent over the world, understanding the underlying mechanisms among weight control, endocrine change and cancer risk is critically important. Future studies using "-omics" technologies will be warrant for a broader and deeper mechanistic information regarding cancer prevention by weight control.

Cholesterol metabolism and transport in the pathogenesis of Alzheimer's disease.

PubMed

Martins, Ian J; Berger, Tamar; Sharman, Matthew J; Verdile, Giuseppe; Fuller, Stephanie J; Martins, Ralph N

2009-12-01

Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting millions of people worldwide. Apart from age, the major risk factor identified so far for the sporadic form of AD is possession of the epsilon4 allele of apolipoprotein E (APOE), which is also a risk factor for coronary artery disease (CAD). Other apolipoproteins known to play an important role in CAD such as apolipoprotein B are now gaining attention for their role in AD as well. AD and CAD share other risk factors, such as altered cholesterol levels, particularly high levels of low density lipoproteins together with low levels of high density lipoproteins. Statins--drugs that have been used to lower cholesterol levels in CAD, have been shown to protect against AD, although the protective mechanism(s) involved are still under debate. Enzymatic production of the beta amyloid peptide, the peptide thought to play a major role in AD pathogenesis, is affected by membrane cholesterol levels. In addition, polymorphisms in several proteins and enzymes involved in cholesterol and lipoprotein transport and metabolism have been linked to risk of AD. Taken together, these findings provide strong evidence that changes in cholesterol metabolism are intimately involved in AD pathogenic processes. This paper reviews cholesterol metabolism and transport, as well as those aspects of cholesterol metabolism that have been linked with AD.

Embryo Microinjection of Selenomethionine Reduces Hatchability and Modifies Oxidant Responsive Gene Expression in Zebrafish

NASA Astrophysics Data System (ADS)

Thomas, J. K.; Janz, D. M.

2016-05-01

In previous studies we demonstrated that exposure to selenomethionine (SeMet) causes developmental toxicities in zebrafish (Danio rerio). The objectives of this study were to establish a dose-response relationship for developmental toxicities in zebrafish after embryo microinjection of Se (8, 16 or 32 μg/g dry mass of eggs) in the form of SeMet, and to investigate potential underlying mechanism(s) of SeMet-induced developmental toxicities. A dose-dependent increase in frequencies of mortality and total deformities, and reduced hatchability were observed in zebrafish exposed to excess Se via embryo microinjection. The egg Se concentration causing 20% mortality was then used to investigate transcript abundance of proteins involved in antioxidant protection and methylation. Excess Se exposure modified gene expression of oxidant-responsive transcription factors (nuclear factor erythroid 2-related factor nrf2a and nrf2b), and enzymes involved in cellular methylation (methionine adenosyltransferase mat1a and mat2ab) in zebrafish larvae. Notably, excess Se exposure up-regulated transcript abundance of aryl hydrocarbon receptor 2 (ahr2), a signalling pathway involved in the toxicity of dioxin-related compounds. Our findings suggest that oxidative stress or modification of methylation, or a combination of these mechanisms, might be responsible for Se-induced developmental toxicities in fishes.

MicroRNA and Transcription Factor: Key Players in Plant Regulatory Network.

PubMed

Samad, Abdul F A; Sajad, Muhammad; Nazaruddin, Nazaruddin; Fauzi, Izzat A; Murad, Abdul M A; Zainal, Zamri; Ismail, Ismanizan

2017-01-01

Recent achievements in plant microRNA (miRNA), a large class of small and non-coding RNAs, are very exciting. A wide array of techniques involving forward genetic, molecular cloning, bioinformatic analysis, and the latest technology, deep sequencing have greatly advanced miRNA discovery. A tiny miRNA sequence has the ability to target single/multiple mRNA targets. Most of the miRNA targets are transcription factors (TFs) which have paramount importance in regulating the plant growth and development. Various families of TFs, which have regulated a range of regulatory networks, may assist plants to grow under normal and stress environmental conditions. This present review focuses on the regulatory relationships between miRNAs and different families of TFs like; NF-Y, MYB, AP2, TCP, WRKY, NAC, GRF, and SPL. For instance NF-Y play important role during drought tolerance and flower development, MYB are involved in signal transduction and biosynthesis of secondary metabolites, AP2 regulate the floral development and nodule formation, TCP direct leaf development and growth hormones signaling. WRKY have known roles in multiple stress tolerances, NAC regulate lateral root formation, GRF are involved in root growth, flower, and seed development, and SPL regulate plant transition from juvenile to adult. We also studied the relation between miRNAs and TFs by consolidating the research findings from different plant species which will help plant scientists in understanding the mechanism of action and interaction between these regulators in the plant growth and development under normal and stress environmental conditions.

Impact of Cardiac Rehabilitation and Exercise Training on Psychological Risk Factors and Subsequent Prognosis in Patients With Cardiovascular Disease.

PubMed

Lavie, Carl J; Menezes, Arthur R; De Schutter, Alban; Milani, Richard V; Blumenthal, James A

2016-10-01

The role of psychological risk factors has been under-recognized in most subspecialties of medicine, as well as in general medicine practices. However, considerable evidence indicates that psychosocial factors are involved in the pathogenesis and progression of cardiovascular disease (CVD). Emerging data from cardiac rehabilitation (CR) settings and CR exercise training (CRET) programs have demonstrated the value of comprehensive CRET to improve psychological functioning and reduce all-cause mortality. Recent evidence also supports the role of CRET and the added value of stress management training in the secondary prevention of CVD. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Role of exercise in maintaining the integrity of the neuromuscular junction.

PubMed

Nishimune, Hiroshi; Stanford, John A; Mori, Yasuo

2014-03-01

Physical activity plays an important role in preventing chronic disease in adults and the elderly. Exercise has beneficial effects on the nervous system, including at the neuromuscular junction (NMJ). Exercise causes hypertrophy of NMJs and improves recovery from peripheral nerve injuries, whereas decreased physical activity causes degenerative changes in NMJs. Recent studies have begun to elucidate molecular mechanisms underlying the beneficial effects of exercise. These mechanisms involve Bassoon, neuregulin-1, peroxisome proliferator-activated receptor gamma coactivator 1α, insulin-like growth factor-1, glial cell line-derived neurotrophic factor, neurotrophin 4, Homer, and nuclear factor of activated T cells c1. For example, NMJ denervation and active zone decreases have been observed in aged NMJs, but these age-dependent degenerative changes can be ameliorated by exercise. In this review we assess the effects of exercise on the maintenance and regeneration of NMJs and highlight recent insights into the molecular mechanisms underlying these exercise effects. Copyright © 2013 Wiley Periodicals, Inc.

Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation

PubMed Central

Horita, Henrick; Wysoczynski, Christina L.; Walker, Lori A.; Moulton, Karen S.; Li, Marcella; Ostriker, Allison; Tucker, Rebecca; McKinsey, Timothy A.; Churchill, Mair E. A.; Nemenoff, Raphael A.; Weiser-Evans, Mary C. M.

2016-01-01

Vascular disease progression is associated with marked changes in vascular smooth muscle cell (SMC) phenotype and function. SMC contractile gene expression and, thus differentiation, is under direct transcriptional control by the transcription factor, serum response factor (SRF); however, the mechanisms dynamically regulating SMC phenotype are not fully defined. Here we report that the lipid and protein phosphatase, PTEN, has a novel role in the nucleus by functioning as an indispensible regulator with SRF to maintain the differentiated SM phenotype. PTEN interacts with the N-terminal domain of SRF and PTEN–SRF interaction promotes SRF binding to essential promoter elements in SM-specific genes. Factors inducing phenotypic switching promote loss of nuclear PTEN through nucleo-cytoplasmic translocation resulting in reduced myogenically active SRF, but enhanced SRF activity on target genes involved in proliferation. Overall decreased expression of PTEN was observed in intimal SMCs of human atherosclerotic lesions underlying the potential clinical importance of these findings. PMID:26940659

Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation.

PubMed

Horita, Henrick; Wysoczynski, Christina L; Walker, Lori A; Moulton, Karen S; Li, Marcella; Ostriker, Allison; Tucker, Rebecca; McKinsey, Timothy A; Churchill, Mair E A; Nemenoff, Raphael A; Weiser-Evans, Mary C M

2016-03-04

Vascular disease progression is associated with marked changes in vascular smooth muscle cell (SMC) phenotype and function. SMC contractile gene expression and, thus differentiation, is under direct transcriptional control by the transcription factor, serum response factor (SRF); however, the mechanisms dynamically regulating SMC phenotype are not fully defined. Here we report that the lipid and protein phosphatase, PTEN, has a novel role in the nucleus by functioning as an indispensible regulator with SRF to maintain the differentiated SM phenotype. PTEN interacts with the N-terminal domain of SRF and PTEN-SRF interaction promotes SRF binding to essential promoter elements in SM-specific genes. Factors inducing phenotypic switching promote loss of nuclear PTEN through nucleo-cytoplasmic translocation resulting in reduced myogenically active SRF, but enhanced SRF activity on target genes involved in proliferation. Overall decreased expression of PTEN was observed in intimal SMCs of human atherosclerotic lesions underlying the potential clinical importance of these findings.

Understanding brassinosteroid-regulated mechanisms to improve stress tolerance in plants: a critical review.

PubMed

Nawaz, Fahim; Naeem, Muhammad; Zulfiqar, Bilal; Akram, Asim; Ashraf, Muhammad Yasin; Raheel, Muhammad; Shabbir, Rana Nauman; Hussain, Rai Altaf; Anwar, Irfan; Aurangzaib, Muhammad

2017-07-01

Brassinosteroids (BRs) are steroidal plant hormones involved in regulation of physiological and molecular processes to ameliorate various biotic and abiotic stresses. Exogenous application of BRs to improve stress tolerance in plants has recently become a high research priority. Several studies have revealed the involvement of these steroidal hormones in upregulation of stress-related defense genes and their cross talk with other metabolic pathways. This is likely to stimulate research on many unanswered questions regarding their role in enhancing the ability of plants to tolerate adverse environmental conditions. Thus, this review appraises new insights on mechanisms mediating BR-regulated changes in plants, focused mainly on their involvement in regulation of physiological and molecular mechanisms under stress conditions. Herein, examples of BR-stimulated modulation of antioxidant defense system and upregulation of transcription factors in plants exposed to various biotic (bacterial, viral, and fungal attack) and abiotic stresses (drought, salinity, heat, low temperature, and heavy metal stress) are discussed. Based on these insights, future research in the current direction can be helpful to increase our understanding of BR-mediated complex and interrelated processes under stress conditions.

The Developmental Regulator SEEDSTICK Controls Structural and Mechanical Properties of the Arabidopsis Seed Coat

PubMed Central

Beauzamy, Léna; Caporali, Elisabetta; Koroney, Abdoul-Salam

2016-01-01

Although many transcription factors involved in cell wall morphogenesis have been identified and studied, it is still unknown how genetic and molecular regulation of cell wall biosynthesis is integrated into developmental programs. We demonstrate by molecular genetic studies that SEEDSTICK (STK), a transcription factor controlling ovule and seed integument identity, directly regulates PMEI6 and other genes involved in the biogenesis of the cellulose-pectin matrix of the cell wall. Based on atomic force microscopy, immunocytochemistry, and chemical analyses, we propose that structural modifications of the cell wall matrix in the stk mutant contribute to defects in mucilage release and seed germination under water-stress conditions. Our studies reveal a molecular network controlled by STK that regulates cell wall properties of the seed coat, demonstrating that developmental regulators controlling organ identity also coordinate specific aspects of cell wall characteristics. PMID:27624758

Molecular biology of testicular germ cell tumors.

PubMed

Gonzalez-Exposito, R; Merino, M; Aguayo, C

2016-06-01

Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men. They constitute a unique pathology because of their embryonic and germ origin and their special behavior. Genetic predisposition, environmental factors involved in their development and genetic aberrations have been under study in many works throughout the last years trying to explain the susceptibility and the transformation mechanism of TGCTs. Despite the high rate of cure in this type of tumors because its particular sensitivity to cisplatin, there are tumors resistant to chemotherapy for which it is needed to find new therapies. In the present work, it has been carried out a literature review on the most important molecular aspects involved in the onset and development of such tumors, as well as a review of the major developments regarding prognostic factors, new prognostic biomarkers and the possibility of new targeted therapies.

Ecm33 is a novel factor involved in efficient glucose uptake for nutrition-responsive TORC1 signaling in yeast.

PubMed

Umekawa, Midori; Ujihara, Masato; Nakai, Daiki; Takematsu, Hiromu; Wakayama, Mamoru

2017-11-01

Glucose uptake is crucial for providing both an energy source and a signal that regulates cell proliferation. Therefore, it is important to clarify the mechanisms underlying glucose uptake and its transmission to intracellular signaling pathways. In this study, we searched for a novel regulatory factor involved in glucose-induced signaling by using Saccharomyces cerevisiae as a eukaryotic model. Requirement of the extracellular protein Ecm33 in efficient glucose uptake and full activation of the nutrient-responsive TOR kinase complex 1 (TORC1) signaling pathway is shown. Cells lacking Ecm33 elicit a series of starvation-induced pathways even in the presence of extracellular high glucose concentration. This results in delayed cell proliferation, reduced ATP, induction of autophagy, and dephosphorylation of the TORC1 substrates Atg13 and Sch9. © 2017 Federation of European Biochemical Societies.

Behavioural Outcomes of Four-Year-Old Children Prenatally Exposed to Methadone or Buprenorphine: A Test of Three Risk Models

ERIC Educational Resources Information Center

Konijnenberg, Carolien; Lund, Ingunn Olea; Melinder, Annika

2015-01-01

It is still under debate whether the reported effects of opioid maintenance therapy (OMT) on child behaviour are a direct effect of prenatal exposure, or whether other factors are involved. This prospective cohort study investigated three models: the teratogenic risk model, the maternal risk model, and a combined risk model in a group of 35…

The Arabidopsis NAC Transcription Factor ANAC096 Cooperates with bZIP-Type Transcription Factors in Dehydration and Osmotic Stress Responses[W

PubMed Central

Xu, Zheng-Yi; Kim, Soo Youn; Hyeon, Do Young; Kim, Dae Heon; Dong, Ting; Park, Youngmin; Jin, Jing Bo; Joo, Se-Hwan; Kim, Seong-Ki; Hong, Jong Chan; Hwang, Daehee; Hwang, Inhwan

2013-01-01

Multiple transcription factors (TFs) play essential roles in plants under abiotic stress, but how these multiple TFs cooperate in abiotic stress responses remains largely unknown. In this study, we provide evidence that the NAC (for NAM, ATAF1/2, and CUC2) TF ANAC096 cooperates with the bZIP-type TFs ABRE binding factor and ABRE binding protein (ABF/AREB) to help plants survive under dehydration and osmotic stress conditions. ANAC096 directly interacts with ABF2 and ABF4, but not with ABF3, both in vitro and in vivo. ANAC096 and ABF2 synergistically activate RD29A transcription. Our genome-wide gene expression analysis revealed that a major proportion of abscisic acid (ABA)–responsive genes are under the transcriptional regulation of ANAC096. We found that the Arabidopsis thaliana anac096 mutant is hyposensitive to exogenous ABA and shows impaired ABA-induced stomatal closure and increased water loss under dehydration stress conditions. Furthermore, we found the anac096 abf2 abf4 triple mutant is much more sensitive to dehydration and osmotic stresses than the anac096 single mutant or the abf2 abf4 double mutant. Based on these results, we propose that ANAC096 is involved in a synergistic relationship with a subset of ABFs for the transcriptional activation of ABA-inducible genes in response to dehydration and osmotic stresses. PMID:24285786

Transcription factors involved in retinogenesis are co-opted by the circadian clock following photoreceptor differentiation.

PubMed

Laranjeiro, Ricardo; Whitmore, David

2014-07-01

The circadian clock is known to regulate a wide range of physiological and cellular processes, yet remarkably little is known about its role during embryo development. Zebrafish offer a unique opportunity to explore this issue, not only because a great deal is known about key developmental events in this species, but also because the clock starts on the very first day of development. In this study, we identified numerous rhythmic genes in zebrafish larvae, including the key transcriptional regulators neurod and cdx1b, which are involved in neuronal and intestinal differentiation, respectively. Rhythmic expression of neurod and several additional transcription factors was only observed in the developing retina. Surprisingly, these rhythms in expression commenced at a stage of development after these transcription factors are known to have played their essential role in photoreceptor differentiation. Furthermore, this circadian regulation was maintained in adult retina. Thus, once mature photoreceptors are formed, multiple retinal transcription factors fall under circadian clock control, at which point they appear to play a new and important role in regulating rhythmic elements in the phototransduction pathway. © 2014. Published by The Company of Biologists Ltd.

Understanding Neurological Disease Mechanisms in the Era of Epigenetics

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2015-01-01

The burgeoning field of epigenetics is making a significant impact on our understanding of brain evolution, development, and function. In fact, it is now clear that epigenetic mechanisms promote seminal neurobiological processes, ranging from neural stem cell maintenance and differentiation to learning and memory. At the molecular level, epigenetic mechanisms regulate the structure and activity of the genome in response to intracellular and environmental cues, including the deployment of cell type–specific gene networks and those underlying synaptic plasticity. Pharmacological and genetic manipulation of epigenetic factors can, in turn, induce remarkable changes in neural cell identity and cognitive and behavioral phenotypes. Not surprisingly, it is also becoming apparent that epigenetics is intimately involved in neurological disease pathogenesis. Herein, we highlight emerging paradigms for linking epigenetic machinery and processes with neurological disease states, including how (1) mutations in genes encoding epigenetic factors cause disease, (2) genetic variation in genes encoding epigenetic factors modify disease risk, (3) abnormalities in epigenetic factor expression, localization, or function are involved in disease pathophysiology, (4) epigenetic mechanisms regulate disease-associated genomic loci, gene products, and cellular pathways, and (5) differential epigenetic profiles are present in patient-derived central and peripheral tissues. PMID:23571666

FOXN1 Transcription Factor in Epithelial Growth and Wound Healing.

PubMed

Grabowska, Anna I; Wilanowski, Tomasz

2017-09-01

FOXN1 is a prodifferentiation transcription factor in the skin epithelium. Recently, it has also emerged as an important player in controlling the skin wound healing process, as it actively participates in reepithelialization and is thought to be responsible for scar formation. FOXN1 positivity is also a feature of pigmented keratinocytes, including nevi, and FOXN1 is an attribute of benign epithelial tumors. The lack of FOXN1 favors the skin regeneration process displayed by nude mice, pointing to FOXN1 as a switch between regeneration and reparative processes. The stem cell niche provides a functional source of cells after the loss of tissue following wounding. The involvement of prodifferentiation factors in the regulation of this pool of stem cells is suggested. However, the exact mechanism is still under question, and we speculate that the FOXN1 transcription factor is involved in this process. This review analyzes the pleiotropic effects of FOXN1 in the skin, its function in the tumorigenesis process, and its potential role in depletion of the stem cell niche after injury, as well as its suggested mechanistic role, acting in a cell-autonomous and a non-cell-autonomous manner during skin self-renewal. Copyright © 2017 American Society for Microbiology.

Driver dependent factors and the risk of causing a collision for two wheeled motor vehicles

PubMed Central

Lardelli-Claret, P; Jimenez-Moleon, J; de Dios, Luna-del-... J; Garcia-Martin, M; Bueno-Cavanillas, A; Galvez-Vargas, R

2005-01-01

Objective: To assess the effect of driver dependent factors on the risk of causing a collision for two wheeled motor vehicles (TWMVs). Design: Case control study. Setting: Spain, from 1993 to 2002. Subjects: All drivers of TWMVs involved in the 181 551 collisions between two vehicles recorded in the Spanish registry which did not involve pedestrians, and in which at least one of the vehicles was a TWMV and only one driver had committed a driving infraction. The infractor and non-infractor drivers constituted the case and control groups, respectively. Main outcome measures: Logistic regression analyses were used to obtain crude and adjusted odds ratio estimates for each of the driver related factors recorded in the registry (age, sex, nationality, psychophysical factors, and speeding infractions, among others). Results: Inappropriate speed was the variable with the greatest influence on the risk of causing a collision, followed by excessive speed and driving under the influence of alcohol. Younger and older drivers, foreign drivers, and driving without a valid license were also associated with a higher risk of causing a collision. In contrast, helmet use, female sex, and longer time in possession of a driving license were associated with a lower risk. Conclusions: Although the main driver dependent factors related to the risk of causing a collision for a TWMV were similar to those documented for four wheeled vehicles, several differences in the pattern of associations support the need to study moped and motorcycle crashes separately from crashes involving other types of vehicles. PMID:16081752

Nitric oxide donor restores lung growth factor and receptor expression in hyperoxia-exposed rat pups.

PubMed

Lopez, Emmanuel; Boucherat, Olivier; Franco-Montoya, Marie-Laure; Bourbon, Jacques R; Delacourt, Christophe; Jarreau, Pierre-Henri

2006-06-01

Exposure of newborn rats to hyperoxia impairs alveolarization. Nitric oxide (NO) may prevent this evolution. Angiogenesis and factors involved in this process, but also other growth factors (GFs) involved in alveolar development, are likely potential therapeutic targets for NO. We studied the effects of the NO donor, [Z]-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen-1-ium-1, 2-diolate, also termed DETANONOate (D-NO), on hyperoxia-induced changes in key regulatory factors of alveolar development in neonatal rats, and its possible preventive effect on the physiologic consequences of hyperoxia. Newborn rat pups were randomized at birth to hyperoxia (> 95% O2) or room air exposure for 6 or 10 d, while receiving D-NO or its diluent. On Day 6, several GFs and their receptors were studied at pre- and/or post-translational levels. Elastin transcript determination on Day 6, and elastin deposition in tissue and morphometric analysis of the lungs on Day 10, were also performed. Hyperoxia decreased the expression of vascular endothelial growth factor (VEGF) receptor (VEGFR) 2, fibroblast growth factor (FGF)-18, and FGF receptors (FGFRs) FGFR3 and FGFR4, increased mortality, and impaired alveolarization and capillary growth. D-NO treatment of hyperoxia-exposed pups restored the expression level of FGF18 and FGFR4, induced an increase of both VEGF mRNA and protein, enhanced elastin expression, and partially restored elastin deposition in alveolar walls. Although, under the present conditions, D-NO failed to prevent the physiologic consequences of hyperoxia in terms of survival and lung alveolarization, our findings demonstrate molecular effects of NO on GFs involved in alveolar development that may have contributed to the protective effects previously reported for NO.

Factor and prevention method of landslide event at FELCRA Semungkis, Hulu Langat, Selangor

NASA Astrophysics Data System (ADS)

Manap, N.; Jeyaramah, N.; Syahrom, N.

2017-12-01

Landslide is known as one of the powerful geological events that happens unpredictably due to natural or human factors. A study was carried out at FELCRA Semungkis, Hulu Langat which is known as one of the areas that has been affected by landslide that involving 16 causalities. The purpose of this study is to identify the main factor that causes the landslide at FELCRA Semungkis, Hulu Langat and to identify the protection method. Data was collected from three respondents working under government bodies through interview sessions. The data collected were analysed by using the content analysis method. From the results, it can be concluded that the main factors that caused the landslide to happened are the human factor and nature factor. The protection method that can be applied to stabilize the FELCRA Semungkis, Hulu Langat is by using the soil nailing method with the support of soil create system.

Obesity and Associated Comorbidities in People and Companion Animals: A One Health Perspective.

PubMed

Chandler, M; Cunningham, S; Lund, E M; Khanna, C; Naramore, R; Patel, A; Day, M J

2017-05-01

This article reviews the biology, prevalence and risks for obesity in people and companion dogs and cats, and explores the links between obesity and diabetes mellitus and cancer across these species. Obesity is a major healthcare problem in both human and veterinary medicine and there is an increasing prevalence of obesity in people and pets. In people and animals, obesity is a complex disorder involving diet, level of physical activity, behavioural factors, socioeconomic factors, environment exposures, genetics, metabolism and the microbiome. Pets and people share a number of obesity-related comorbidities. Obesity is a major risk factor for type 2 diabetes mellitus in people and in cats, but this association is not recognized in dogs. Obesity is a recognized risk factor for a number of human cancers, but there are fewer data available describing this association with canine neoplastic disease. One approach to addressing the problem of obesity is by taking a 'One Health' perspective. Comparative clinical research examining shared lifestyle and environmental risk factors and the reasons underlying species differences should provide new perspectives on the fundamental biology of obesity. One Health programmes involving human healthcare professionals and veterinarians could help address obesity with simple interventions at the community level. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Risk Factors Associated with Injury and Mortality from Paediatric Low Speed Vehicle Incidents: A Systematic Review

PubMed Central

Paul Anthikkat, Anne; Page, Andrew; Barker, Ruth

2013-01-01

Objective. This study reviews modifiable risk factors associated with fatal and nonfatal injury from low-speed vehicle runover (LSVRO) incidents involving children aged 0–15 years. Data Sources. Electronic searches for child pedestrian and driveway injuries from the peer-reviewed literature and transport-related websites from 1955 to 2012. Study Selection. 41 studies met the study inclusion criteria. Data Extraction. A systematic narrative summary was conducted that included study design, methodology, risk factors, and other study variables. Results. The most commonly reported risk factors for LSVRO incidents included age under 5 years, male gender, and reversing vehicles. The majority of reported incidents involved residential driveways, but several studies identified other traffic and nontraffic locations. Low socioeconomic status and rental accommodation were also associated with LSVRO injury. Vehicles were most commonly driven by a family member, predominantly a parent. Conclusion. There are a number of modifiable vehicular, environmental, and behavioural factors associated with LSVRO injuries in young children that have been identified in the literature to date. Strategies relating to vehicle design (devices for increased rearward visibility and crash avoidance systems), housing design (physical separation of driveway and play areas), and behaviour (driver behaviour, supervision of young children) are discussed. PMID:23781251

Management of atrial fibrillation.

PubMed

Moukabary, Talal; Gonzalez, Mario D

2015-07-01

Atrial fibrillation is a very common clinical problem with a high prevalence that is expected to rise over time because of increasing risk factors (eg, age, obesity, hypertension). This high prevalence is also associated with high cost, because atrial fibrillation represents about 1% of overall health care spending. The management of atrial fibrillation involves multiple facets: (1) management of underlying disease if present and the management of atrial fibrillation risk factors, (2) prevention of thromboembolism, (3) control of the ventricular rate during atrial fibrillation, and (4) restoration and maintenance of normal sinus rhythm. Copyright © 2015 Elsevier Inc. All rights reserved.

Workers' involvement--a missing component in the implementation of occupational safety and health management systems in enterprises.

PubMed

Podgórski, Daniel

2005-01-01

Effective implementation of occupational safety and health (OSH) legislation based on European Union directives requires promotion of OSH management systems (OSH MS). To this end, voluntary Polish standards (PN-N-18000) have been adopted, setting forth OSH MS specifications and guidelines. However, the number of enterprises implementing OSH MS has increased slowly, falling short of expectations, which call for a new national policy on OSH MS promotion. To develop a national policy in this area, a survey was conducted in 40 enterprises with OSH MS in place. The survey was aimed at identifying motivational factors underlying OSH MS implementation decisions. Specifically, workers' and their representatives' involvement in OSH MS implementation was investigated. The results showed that the level of workers' involvement was relatively low, which may result in a low effectiveness of those systems. The same result also applies to the involvement of workers' representatives and that of trade unions.

RNA Polymerase II Elongation Control

PubMed Central

Zhou, Qiang; Li, Tiandao; Price, David H.

2014-01-01

Regulation of the elongation phase of transcription by RNA Polymerase II (Pol II) is utilized extensively to generate the pattern of mRNAs needed to specify cell types and to respond to environmental changes. After Pol II initiates, negative elongation factors cause it to pause in a promoter proximal position. These polymerases are poised to respond to the positive transcription elongation factor, P-TEFb, and then enter productive elongation only under the appropriate set of signals to generate full length properly processed mRNAs. Recent global analyses of Pol II and elongation factors, mechanisms that regulate P-TEFb involving the 7SK snRNP, factors that control both the negative and positive elongation properties of Pol II and the mRNA processing events that are coupled with elongation are discussed. PMID:22404626

Acceptability of Family Violence: Underlying Ties Between Intimate Partner Violence and Child Abuse.

PubMed

Gracia, Enrique; Rodriguez, Christina M; Martín-Fernández, Manuel; Lila, Marisol

2017-05-01

Intimate partner violence (IPV) and child abuse (CA) are two forms of family violence with shared qualities and risk factors, and are forms of violence that tend to overlap. Acceptability of violence in partner relationships is a known risk factor in IPV just as acceptability of parent-child aggression is a risk factor in CA. We hypothesized that these acceptability attitudes may be linked and represent the expression of a general, underlying nonspecific acceptance of violence in close family relationships. The sample involved 164 male IPV offenders participating in a batterer intervention program. Implicit measures, which assess constructs covertly to minimize response distortions, were administered to assess acceptability of partner violence against women and acceptability of parent-child aggression. To determine whether acceptability attitudes regarding both forms of violence were related to a higher order construct tapping general acceptance of family violence, Bayesian confirmatory factor analyses were conducted. Findings supported a hierarchical (bifactor) model with a general factor expressing a nonspecific acceptance of family violence, and two specific factors reflecting acceptability of violence in intimate partner and parent-child relationships, respectively. This hierarchical model supporting a general acceptance of violence in close family relationships can inform future research aiming to better understand the connections between IPV and CA.

Arabidopsis WRKY Transcription Factors WRKY12 and WRKY13 Oppositely Regulate Flowering under Short-Day Conditions.

PubMed

Li, Wei; Wang, Houping; Yu, Diqiu

2016-11-07

In plants, photoperiod is an important cue for determining flowering. The floral transition in Arabidopsis thaliana is earlier under long-day (LD) than under short-day (SD) conditions. Flowering of Arabidopsis plants under SD conditions is mainly regulated by the plant hormone gibberellin (GA). Here, we report two WRKY transcription factors function oppositely in controlling flowering time under SD conditions. Phenotypic analysis showed that disruption of WRKY12 caused a delay in flowering, while loss of WRKY13 function promoted flowering. WRKY12 and WRKY13 displayed negatively correlated expression profiles and function successively to regulate flowering. Molecular and genetic analyses demonstrated that FRUITFULL (FUL) is a direct downstream target gene of WRKY12 and WRKY13. Interestingly, we found that DELLA proteins GIBBERELLIN INSENSITIVE (GAI) and RGA-LIKE1 (RGL1) interacted with WRKY12 and WRKY13, and their interactions interfered with the transcriptional activity of the WRKY12 and WRKY13. Further studies suggested thatWRKY12 and WRKY13 partly mediated the effect of GA 3 on controlling flowering time. Taken together, our results indicate that WRKY12 and WRKY13 oppositely modulate flowering time under SD conditions, which at least partially involves the action of GA. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Flowering in space

NASA Astrophysics Data System (ADS)

Zheng, Hui Qiong

2018-05-01

The reproductive success of plants is often dependent on their flowering time being adapted to the terrestrial environment, in which gravity remain constant. Whether plants can follow the same rule to determine their flowering time under microgravity in space is unknown. Although numerous attempts have been made to grow a plant through a complete life cycle in space, apparently no published information exists concerning the flowering control of plants under microgravity in space. Here, we focused on two aspects. Firstly the environmental and intrinsic factors under microgravity related to flowering control. Secondly, the plant-derived regulators are involved in flowering control under microgravity condition. The potential environmental and intrinsic factors affect plant flowering under microgravity may include light, biological circadian clock as well as long-distance signaling, while the plant-derived flowering regulators in response to microgravity could include gibberellic acid, ethylene, microRNA and sugar. The results we have obtained from the space experiments on board the Chinese recoverable satellites (the SJ-8 and the SJ-10) and the experiment on the Chinese space lab TG-2 are also introduced. We conclude by suggesting that long-term space experiments from successive generations and a systematic analysis of regulatory networks at the molecular level is needed to understand the mechanism of plant flowering control under microgravity conditions in space.

Beneficial impact of exercise and obesity interventions on erectile function and its risk factors.

PubMed

Hannan, Johanna L; Maio, M Tina; Komolova, Marina; Adams, Michael A

2009-03-01

Erectile dysfunction (ED) is a multifaceted disease involving cardiovascular, metabolic, and hormonal factors and affects over 100 million men worldwide. ED has been shown to be a harbinger of underlying cardiovascular diseases (CVD), as there are common risk factors (aging, hypertension, obesity) and mechanistic basis. To provide an update on clinical and experimental evidence regarding the impact of lifestyle modifications, such as exercise and diet, with respect to changes in erectile function. Published evidence regarding the impact of aging, hypertension, and obesity on ED and CVD, as well as new experimental data linking obesity and diminished erectile responses. We reviewed the literature regarding common risk factors of ED and CVD, particularly involving obesity, as well as performed new analysis on the findings of other experimental studies involving diet and exercise interventions. Physical inactivity negatively impacts on erectile function, and experimental and clinical exercise interventions have been shown to improve sexual responses and overall cardiovascular health. Mediterranean-style diets and a reduction in caloric intake have been found to improve erectile function in men with the aspects of the metabolic syndrome. In addition, both clinical and experimental studies have confirmed that combining the two interventions provides additional benefit to erectile function, likely via reduced metabolic disturbances (e.g., inflammatory markers, insulin resistance), decreased visceral adipose tissue, and improvement in vascular function (e.g., increased endothelial function). Lifestyle modifications provide significant benefits to vascular health and erectile function in a population that is increasingly aged and more obese.

Factors associated with the hospital admission of consumer product-related injuries treated in U.S. hospital emergency departments.

PubMed

Schroeder, Thomas J; Rodgers, Gregory B

2013-10-01

While unintentional injuries and hazard patterns involving consumer products have been studied extensively in recent years, little attention has focused on the characteristics of those who are hospitalized after treatment in emergency departments, as opposed to those treated and released. This study quantifies the impact of the age and sex of the injury victims, and other factors, on the likelihood of hospitalization. The analysis focuses on consumer product injuries, and was based on approximately 400,000 injury cases reported through the U.S. Consumer Product Safety Commission's National Electronic Injury Surveillance System, a national probability sample of U.S. hospital emergency departments. Logistic regression was used to quantify the factors associated with the likelihood of hospitalization. The analysis suggests a smooth U-shaped relationship between the age of the victim and the likelihood of hospitalization, declining from about 3.4% for children under age 5 years to 1.9% for 15-24 year-olds, but then rising to more than 25% for those ages 75 years and older. The likelihood of hospitalization was also significantly affected by the victim's sex, as well as by the types of products involved, fire involvement, and the size and type of hospital at which the injury was treated. This study shows that the probability of hospitalization is strongly correlated with the characteristics of those who are injured, as well as other factors. Published by Elsevier Ltd.

Iron-heme-Bach1 axis is involved in erythroblast adaptation to iron deficiency.

PubMed

Kobayashi, Masahiro; Kato, Hiroki; Hada, Hiroshi; Itoh-Nakadai, Ari; Fujiwara, Tohru; Muto, Akihiko; Inoguchi, Yukihiro; Ichiyanagi, Kenji; Hojo, Wataru; Tomosugi, Naohisa; Sasaki, Hiroyuki; Harigae, Hideo; Igarashi, Kazuhiko

2017-03-01

Iron plays the central role in oxygen transport by erythrocytes as a constituent of heme and hemoglobin. The importance of iron and heme is also to be found in their regulatory roles during erythroblast maturation. The transcription factor Bach1 may be involved in their regulatory roles since it is deactivated by direct binding of heme. To address whether Bach1 is involved in the responses of erythroblasts to iron status, low iron conditions that induced severe iron deficiency in mice were established. Under iron deficiency, extensive gene expression changes and mitophagy disorder were induced during maturation of erythroblasts. Bach1 -/- mice showed more severe iron deficiency anemia in the developmental phase of mice and a retarded recovery once iron was replenished when compared with wild-type mice. In the absence of Bach1, the expression of globin genes and Hmox1 (encoding heme oxygenase-1) was de-repressed in erythroblasts under iron deficiency, suggesting that Bach1 represses these genes in erythroblasts under iron deficiency to balance the levels of heme and globin. Moreover, an increase in genome-wide DNA methylation was observed in erythroblasts of Bach1 -/- mice under iron deficiency. These findings reveal the principle role of iron as a regulator of gene expression in erythroblast maturation and suggest that the iron-heme-Bach1 axis is important for a proper adaptation of erythroblast to iron deficiency to avoid toxic aggregates of non-heme globin. Copyright© Ferrata Storti Foundation.

Effects of carbon, nitrogen and ambient pH on patulin production and related gene expression in Penicillium expansum.

PubMed

Zong, Yuanyuan; Li, Boqiang; Tian, Shiping

2015-08-03

Patulin, a potent mycotoxin which can cause serious health concerns, is mainly produced in foods by Penicillium expansum. Environmental factors play important roles in regulating biosynthesis of mycotoxins; however, information about the effects of environmental factors on patulin production and the involved mechanisms in P. expansum is limited. Here, we investigated the effects of different carbon (C) and nitrogen (N) sources, and ambient pH on patulin production in three P. expansum strains T01, M1 and Pe21, and the expression profile of 15 genes involved in patulin biosynthetic pathway. It was found that C and N sources and pH had great influence on patulin production in P. expansum. In general, patulin production of all three P. expansum strains showed similar trends under different C and N sources and pH conditions, though there were some differences in the optimal conditions among these strains. Glucose-containing sugars, complex N sources, and acidic conditions were favorable conditions for patulin production. The results of RT-qPCR showed that the relative expressions of most of the patulin genes were up-regulated under patulin-permissive conditions, indicating that patulin biosynthesis was mainly regulated at transcriptional level by these environmental factors. These findings will provide useful information to better understand the regulation mechanisms of patulin biosynthesis, and be helpful in developing effective means for controlling patulin contamination. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of ankle joint plantarflexion and dorsiflexion on lateral ankle sprain: A computational study.

PubMed

Purevsuren, Tserenchimed; Kim, Kyungsoo; Batbaatar, Myagmarbayar; Lee, SuKyoung; Kim, Yoon Hyuk

2018-05-01

Understanding the mechanism of injury involved in lateral ankle sprain is essential to prevent injury, to establish surgical repair and reconstruction, and to plan reliable rehabilitation protocols. Most studies for lateral ankle sprain posit that ankle inversion, internal rotation, and plantarflexion are involved in the mechanism of injury. However, recent studies indicated that ankle dorsiflexion also plays an important role in the lateral ankle sprain mechanism. In this study, the contributions of ankle plantarflexion and dorsiflexion on the ankle joint were evaluated under complex combinations of internal and inversion moments. A multibody ankle joint model including 24 ligaments was developed and validated against two experimental cadaveric studies. The effects of ankle plantarflexion (up to 60°) and dorsiflexion (up to 30°) on the lateral ankle sprain mechanism under ankle inversion moment coupled with internal rotational moment were investigated using the validated model. Lateral ankle sprain injuries can occur during ankle dorsiflexion, in which the calcaneofibular ligament and anterior talofibular ligament tears may occur associated with excessive inversion and internal rotational moment, respectively. Various combinations of inversion and internal moment may lead to anterior talofibular ligament injuries at early ankle plantarflexion, while the inversion moment acts as a primary factor to tear the anterior talofibular ligament in early plantarflexion. It is better to consider inversion and internal rotation as primary factors of the lateral ankle sprain mechanism, while plantarflexion or dorsiflexion can be secondary factor. This information will help to clarify the lateral ankle sprain mechanism of injury.

Sonic hedgehog promotes neurite outgrowth of cortical neurons under oxidative stress: Involving of mitochondria and energy metabolism.

PubMed

He, Weiliang; Cui, Lili; Zhang, Cong; Zhang, Xiangjian; He, Junna; Xie, Yanzhao; Chen, Yanxia

2017-01-01

Oxidative stress has been demonstrated to be involved in the etiology of several neurobiological disorders. Sonic hedgehog (Shh), a secreted glycoprotein factor, has been implicated in promoting several aspects of brain remodeling process. Mitochondria may play an important role in controlling fundamental processes in neuroplasticity. However, little evidence is available about the effect and the potential mechanism of Shh on neurite outgrowth in primary cortical neurons under oxidative stress. Here, we revealed that Shh treatment significantly increased the viability of cortical neurons in a dose-dependent manner, which was damaged by hydrogen peroxide (H 2 O 2 ). Shh alleviated the apoptosis rate of H 2 O 2 -induced neurons. Shh also increased neuritogenesis injuried by H 2 O 2 in primary cortical neurons. Moreover, Shh reduced the generation of reactive oxygen species (ROS), increased the activities of SOD and and decreased the productions of MDA. In addition, Shh protected mitochondrial functions, elevated the cellular ATP levels and amelioratesd the impairment of mitochondrial complex II activities of cortical neurons induced by H 2 O 2 . In conclusion, all these results suggest that Shh acts as a prosurvival factor playing an essential role to neurite outgrowth of cortical neuron under H 2 O 2 -induced oxidative stress, possibly through counteracting ROS release and preventing mitochondrial dysfunction and ATP as well as mitochondrial complex II activities against oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of ischaemic preconditioning in liver regeneration following major liver resection and transplantation

PubMed Central

Gomez, D; Homer-Vanniasinkam, S; Graham, AM; Prasad, KR

2007-01-01

Liver ischaemic preconditioning (IPC) is known to protect the liver from the detrimental effects of ischaemic-reperfusion injury (IRI), which contributes significantly to the morbidity and mortality following major liver surgery. Recent studies have focused on the role of IPC in liver regeneration, the precise mechanism of which are not completely understood. This review discusses the current understanding of the mechanism of liver regeneration and the role of IPC in this setting. Relevant articles were reviewed from the published literature using the Medline database. The search was performed using the keywords “liver”, “ischaemic reperfusion”, “ischaemic preconditioning”, “regeneration”, “hepatectomy” and “transplantation”. The underlying mechanism of liver regeneration is a complex process involving the interaction of cytokines, growth factors and the metabolic demand of the liver. IPC, through various mediators, promotes liver regeneration by up-regulating growth-promoting factors and suppresses growth-inhibiting factors as well as damaging stresses. The increased understanding of the cellular mechanisms involved in IPC will enable the development of alternative treatment modalities aimed at promoting liver regeneration following major liver resection and transplantation. PMID:17278187

Factors promoting a successful return to work: from an employer and employee perspective.

PubMed

Jakobsen, Klara; Lillefjell, Monica

2014-01-01

Efforts have been made to explain the inability to return to work (RTW) due to employees' chronic musculoskeletal pain. Knowledge of factors facilitating the RTW process is however still limited. Based on the experiences of employees and employers, this study aims to identify factors promoting a successful return process for persons with chronic musculoskeletal pain. The findings from interviews, involving six employees with musculoskeletal pain, and five employers with various work experience, were analysed by Giorgi's phenomenological analysis through four stages. The major themes underlying the employees' comments for a successful RTW were identifying and mobilizing their personal resources, adapting a balanced daily life, and requiring a positive dialogue with family and their employer, while the employers underlined the need for a helpful adjustment at work and how they wanted to become more involved in the rehabilitation process. In conclusion our findings underline the need for extended collaboration between the employees, employer, and rehabilitation staff, and should encourage occupational therapists to direct even more of their expertise towards the situation at the workplace.

EGF does not induce Msx-1 and Msx-2 in dental mesenchyme.

PubMed

Wang, Y H; Kollar, E J; Upholt, W B; Mina, M

1998-01-01

Previous heterospecific tissue recombinations indicate that mandibular epithelium exerts the first known inductive signal for odontogenesis in mouse embryos. BMP-4 and EGF are two growth factors implicated as signaling molecules mediating the initial inductive epithelial-mesenchymal interactions during odontogenesis. The purpose of the present study was to examine and compare the effects of these growth factors and mouse mandibular epithelium on expression of Msx-1 and Msx-2 genes in molar-forming mesenchyme. Agarose beads soaked in growth factors or pieces of mouse mandibular epithelium (E11) were placed in contact with E11 molar-forming mesenchyme and cultured for 24 h. Whole-mount in situ hybridization analysis revealed that, in contrast to mouse mandibular epithelium and BMP-4-releasing beads, EGF-releasing beads did not induce the expression of Msx-1 and Msx-2 in E11 molar-forming mesenchyme. These observations suggest that whereas BMP-4 may be involved in activation of Msx-1 and Msx-2 in the underlying mesenchyme, EGF may regulate events involved in the formation of dental lamina.

Evolution of Genes Involved in Gamete Interaction: Evidence for Positive Selection, Duplications and Losses in Vertebrates

PubMed Central

Callebaut, Isabelle; Laurin, Michel; Pascal, Géraldine; Poupon, Anne; Goudet, Ghylène; Monget, Philippe

2012-01-01

Genes encoding proteins involved in sperm-egg interaction and fertilization exhibit a particularly fast evolution and may participate in prezygotic species isolation [1], [2]. Some of them (ZP3, ADAM1, ADAM2, ACR and CD9) have individually been shown to evolve under positive selection [3], [4], suggesting a role of positive Darwinian selection on sperm-egg interaction. However, the genes involved in this biological function have not been systematically and exhaustively studied with an evolutionary perspective, in particular across vertebrates with internal and external fertilization. Here we show that 33 genes among the 69 that have been experimentally shown to be involved in fertilization in at least one taxon in vertebrates are under positive selection. Moreover, we identified 17 pseudogenes and 39 genes that have at least one duplicate in one species. For 15 genes, we found neither positive selection, nor gene copies or pseudogenes. Genes of teleosts, especially genes involved in sperm-oolemma fusion, appear to be more frequently under positive selection than genes of birds and eutherians. In contrast, pseudogenization, gene loss and gene gain are more frequent in eutherians. Thus, each of the 19 studied vertebrate species exhibits a unique signature characterized by gene gain and loss, as well as position of amino acids under positive selection. Reflecting these clade-specific signatures, teleosts and eutherian mammals are recovered as clades in a parsimony analysis. Interestingly the same analysis places Xenopus apart from teleosts, with which it shares the primitive external fertilization, and locates it along with amniotes (which share internal fertilization), suggesting that external or internal environmental conditions of germ cell interaction may not be the unique factors that drive the evolution of fertilization genes. Our work should improve our understanding of the fertilization process and on the establishment of reproductive barriers, for example by offering new leads for experiments on genes identified as positively selected. PMID:22957080

A qualitative study of DRG coding practice in hospitals under the Thai Universal Coverage scheme.

PubMed

Pongpirul, Krit; Walker, Damian G; Winch, Peter J; Robinson, Courtland

2011-04-08

In the Thai Universal Coverage health insurance scheme, hospital providers are paid for their inpatient care using Diagnosis Related Group-based retrospective payment, for which quality of the diagnosis and procedure codes is crucial. However, there has been limited understandings on which health care professions are involved and how the diagnosis and procedure coding is actually done within hospital settings. The objective of this study is to detail hospital coding structure and process, and to describe the roles of key hospital staff, and other related internal dynamics in Thai hospitals that affect quality of data submitted for inpatient care reimbursement. Research involved qualitative semi-structured interview with 43 participants at 10 hospitals chosen to represent a range of hospital sizes (small/medium/large), location (urban/rural), and type (public/private). Hospital Coding Practice has structural and process components. While the structural component includes human resources, hospital committee, and information technology infrastructure, the process component comprises all activities from patient discharge to submission of the diagnosis and procedure codes. At least eight health care professional disciplines are involved in the coding process which comprises seven major steps, each of which involves different hospital staff: 1) Discharge Summarization, 2) Completeness Checking, 3) Diagnosis and Procedure Coding, 4) Code Checking, 5) Relative Weight Challenging, 6) Coding Report, and 7) Internal Audit. The hospital coding practice can be affected by at least five main factors: 1) Internal Dynamics, 2) Management Context, 3) Financial Dependency, 4) Resource and Capacity, and 5) External Factors. Hospital coding practice comprises both structural and process components, involves many health care professional disciplines, and is greatly varied across hospitals as a result of five main factors.

A qualitative study of DRG coding practice in hospitals under the Thai Universal Coverage Scheme

PubMed Central

2011-01-01

Background In the Thai Universal Coverage health insurance scheme, hospital providers are paid for their inpatient care using Diagnosis Related Group-based retrospective payment, for which quality of the diagnosis and procedure codes is crucial. However, there has been limited understandings on which health care professions are involved and how the diagnosis and procedure coding is actually done within hospital settings. The objective of this study is to detail hospital coding structure and process, and to describe the roles of key hospital staff, and other related internal dynamics in Thai hospitals that affect quality of data submitted for inpatient care reimbursement. Methods Research involved qualitative semi-structured interview with 43 participants at 10 hospitals chosen to represent a range of hospital sizes (small/medium/large), location (urban/rural), and type (public/private). Results Hospital Coding Practice has structural and process components. While the structural component includes human resources, hospital committee, and information technology infrastructure, the process component comprises all activities from patient discharge to submission of the diagnosis and procedure codes. At least eight health care professional disciplines are involved in the coding process which comprises seven major steps, each of which involves different hospital staff: 1) Discharge Summarization, 2) Completeness Checking, 3) Diagnosis and Procedure Coding, 4) Code Checking, 5) Relative Weight Challenging, 6) Coding Report, and 7) Internal Audit. The hospital coding practice can be affected by at least five main factors: 1) Internal Dynamics, 2) Management Context, 3) Financial Dependency, 4) Resource and Capacity, and 5) External Factors. Conclusions Hospital coding practice comprises both structural and process components, involves many health care professional disciplines, and is greatly varied across hospitals as a result of five main factors. PMID:21477310

Electrophoresis and spectrometric analyses of adaptation-related proteins in thermally stressed Chromobacterium violaceum.

PubMed

Cordeiro, I B; Castro, D P; Nogueira, P P O; Angelo, P C S; Nogueira, P A; Gonçalves, J F C; Pereira, A M R F; Garcia, J S; Souza, G H M F; Arruda, M A Z; Eberlin, M N; Astolfi-Filho, S; Andrade, E V; López-Lozano, J L

2013-10-29

Chromobacterium violaceum is a Gram-negative proteobacteria found in water and soil; it is widely distributed in tropical and subtropical regions, such as the Amazon rainforest. We examined protein expression changes that occur in C. violaceum at different growth temperatures using electrophoresis and mass spectrometry. The total number of spots detected was 1985; the number ranged from 99 to 380 in each assay. The proteins that were identified spectrometrically were categorized as chaperones, proteins expressed exclusively under heat stress, enzymes involved in the respiratory and fermentation cycles, ribosomal proteins, and proteins related to transport and secretion. Controlling inverted repeat of chaperone expression and inverted repeat DNA binding sequences, as well as regions recognized by sigma factor 32, elements involved in the genetic regulation of the bacterial stress response, were identified in the promoter regions of several of the genes coding proteins, involved in the C. violaceum stress response. We found that 30 °C is the optimal growth temperature for C. violaceum, whereas 25, 35, and 40 °C are stressful temperatures that trigger the expression of chaperones, superoxide dismutase, a probable small heat shock protein, a probable phasing, ferrichrome-iron receptor protein, elongation factor P, and an ornithine carbamoyltransferase catabolite. This information improves our comprehension of the mechanisms involved in stress adaptation by C. violaceum.

A case-control study of boat-related injuries and fatalities in Washington State.

PubMed

Stempski, Sarah; Schiff, Melissa; Bennett, Elizabeth; Quan, Linda

2014-08-01

To identify risk factors associated with boat-related injuries and deaths. We performed a case-control study using the Washington Boat Accident Investigation Report Database for 2003-2010. Cases were fatally injured boat occupants, and controls were non-fatally injured boat occupants involved in a boating incident. We evaluated the association between victim, boat and incident factors and risk of death using Poisson regression to estimate RRs and 95% CIs. Of 968 injured boaters, 26% died. Fatalities were 2.6 times more likely to not be wearing a personal flotation device (PFD) and 2.2 times more likely to not have any safety features on their boat compared with those who survived. Boating fatalities were more likely to be in a non-motorised boat, to have alcohol involved in the incident, to be in an incident that involved capsizing, sinking, flooding or swamping, and to involve a person leaving the boat voluntarily, being ejected or falling than those who survived. Increasing PFD use, safety features on the boat and alcohol non-use are key strategies and non-motorised boaters are key target populations to prevent boating deaths. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Differential gene expression profiling through transcriptome approach of Saccharum spontaneum L. under low temperature stress reveals genes potentially involved in cold acclimation.

PubMed

Selvarajan, Dharshini; Mohan, Chakravarthi; Dhandapani, Vignesh; Nerkar, Gauri; Jayanarayanan, Ashwin Narayan; Vadakkancherry Mohanan, Manoj; Murugan, Naveenarani; Kaur, Lovejot; Chennappa, Mahadevaiah; Kumar, Ravinder; Meena, Minturam; Ram, Bakshi; Chinnaswamy, Appunu

2018-04-01

Sugarcane ( Saccharum sp.) is predominantly grown in both tropics and subtropics in India, and the subtropics alone contribute more than half of sugarcane production. Sugarcane active growth period in subtropics is restricted to 8-9 months mainly due to winter's low temperature stress prevailing during November to February every year. Being a commercial crop, tolerance to low temperature is important in sugarcane improvement programs. Development of cold tolerant sugarcane varieties require a deep knowledge on molecular mechanism naturally adapted by cold tolerant genotypes during low temperature stress. To understand gene regulation under low temperature stress, control and stressed (10 °C, 24 h) leaf samples of cold tolerant S. spontaneum IND 00-1037 collected from high altitude region in Arunachal Pradesh were used for transcriptome analysis using the Illumina NextSeq 500 platform with paired-end sequencing method. Raw reads of 5.1 GB (control) and 5.3 GB (stressed) obtained were assembled using trinity and annotated with UNIPROT, KEGG, GO, COG and SUCEST databases, and transcriptome was validated using qRT-PCR. The differential gene expression (DGE) analysis showed that 2583 genes were upregulated and 3302 genes were down-regulated upon low temperature stress. A total of 170 cold responsive transcriptional factors belonging to 30 families were differentially regulated. CBF6 (C-binding factor), a DNA binding transcriptional activation protein associated with cold acclimation and freezing tolerance was differentially upregulated. Many low temperature responsive genes involved in various metabolic pathways, viz. cold sensing through membrane fluidity, calcium and lipid signaling genes, MAP kinases, phytohormone signaling and biosynthetic genes, antioxidative enzymes, membrane and cellular stabilizing genes, genes involved in biosynthesis of polyunsaturated fatty acids, chaperones, LEA proteins, soluble sugars, osmoprotectants, lignin and pectin biosynthetic genes were also differentially upregulated. Potential cold responsive genes and transcriptional factors involved in cold tolerance mechanism in cold tolerant S. spontaneum IND 00-1037 were identified. Together, this study provides insights into the cold tolerance to low temperature stress in S. spontaneum , thus opening applications in the genetic improvement of cold stress tolerance in sugarcane.

Analysis of DNA replication associated chromatin decondensation: in vivo assay for understanding chromatin remodeling mechanisms of selected proteins.

PubMed

Borysov, Sergiy; Bryant, Victoria L; Alexandrow, Mark G

2015-01-01

Of critical importance to many of the events underlying transcriptional control of gene expression are modifications to core and linker histones that regulate the accessibility of trans-acting factors to the DNA substrate within the context of chromatin. Likewise, control over the initiation of DNA replication, as well as the ability of the replication machinery to proceed during elongation through the multiple levels of chromatin condensation that are likely to be encountered, is known to involve the creation of chromatin accessibility. In the latter case, chromatin access will likely need to be a transient event so as to prevent total genomic unraveling of the chromatin that would be deleterious to cells. While there are many molecular and biochemical approaches in use to study histone changes and their relationship to transcription and chromatin accessibility, few techniques exist that allow a molecular dissection of the events underlying DNA replication control as it pertains to chromatin changes and accessibility. Here, we outline a novel experimental strategy for addressing the ability of specific proteins to induce large-scale chromatin unfolding (decondensation) in vivo upon site-specific targeting to an engineered locus. Our laboratory has used this powerful system in novel ways to directly address the ability of DNA replication proteins to create chromatin accessibility, and have incorporated modifications to the basic approach that allow for a molecular genetic analysis of the mechanisms and associated factors involved in causing chromatin decondensation by a protein of interest. Alternative approaches involving co-expression of other proteins (competitors or stimulators), concurrent drug treatments, and analysis of co-localizing histone modifications are also addressed, all of which are illustrative of the utility of this experimental system for extending basic findings to physiologically relevant mechanisms. Although used by our group to analyze mechanisms underlying DNA replication associated chromatin accessibility, this unique and powerful experimental system has the propensity to be a valuable tool for understanding chromatin remodeling mechanisms orchestrated by other cellular processes such as DNA repair, recombination, mitotic chromosome condensation, or other chromosome dynamics involving chromatin alterations and accessibility.

[Progressive renal insufficiency in a 55-year-old man with psoriasis].

PubMed

Herfurth, K; Busch, M; Gröne, H J; Wolf, G

2018-06-05

Treatment with tumor necrosis factor alpha (TNF-α) inhibitors is a well-established therapeutic strategy for various autoimmune diseases. However, little is known about renal complications and possible causality of renal injury due to this treatment. The following case of a patient with psoriasis demonstrates the difficulties in classifying renal complications of anti-TNF-α therapy versus kidney involvement caused by the underlying disease.

Area Handbook Series: Sudan: A Country Study

DTIC Science & Technology

1991-06-01

major courts and mag- istrate’s courts. Special courts, under military jurisdiction, dealt with offenses affecting national security or involving...treating African southerners as a minority group. Another major factor that has affected Sudan’s evolution is the country’s relationship with Egypt. As early...civilian governments. The conflict appeared likely to continue to affect Sudan’s people and institutions for the rest of the twentieth century. Early

SnapShot: Fanconi anemia and associated proteins.

PubMed

Wang, Anderson T; Smogorzewska, Agata

2015-01-15

Fanconi anemia is a genetic disorder resulting from biallelic mutations in one of the 17 FANC genes. It is characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. The underlying cause is genomic instability resulting from the deficiency in replication-dependent DNA interstrand crosslink repair pathway commonly referred to as the Fanconi anemia-BRCA pathway. This SnapShot presents the key factors involved. Copyright © 2015 Elsevier Inc. All rights reserved.

Eye-hand exercise: new variant in amblyopia management.

PubMed

Svĕrák, J; Peregrin, J; Juran, J

1990-01-01

A total of 50 children with unilateral amblyopia was treated by short term 10 minute-lasting weekly occlusions of visually well eye. During the occlusion the child is providing the intensive detailed activities under patient's supervision. After an approximately half-a-year lasting interval, the "eye-hand" exercise resulted in the mean improvement of visual acuity for 2.44 normalised lines. The visual motor factor is involved in amblyopia treatment.

Integrated analysis of rice transcriptomic and metabolomic responses to elevated night temperatures identifies sensitivity- and tolerance-related profiles.

PubMed

Glaubitz, Ulrike; Li, Xia; Schaedel, Sandra; Erban, Alexander; Sulpice, Ronan; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

2017-01-01

Transcript and metabolite profiling were performed on leaves from six rice cultivars under high night temperature (HNT) condition. Six genes were identified as central for HNT response encoding proteins involved in transcription regulation, signal transduction, protein-protein interactions, jasmonate response and the biosynthesis of secondary metabolites. Sensitive cultivars showed specific changes in transcript abundance including abiotic stress responses, changes of cell wall-related genes, of ABA signaling and secondary metabolism. Additionally, metabolite profiles revealed a highly activated TCA cycle under HNT and concomitantly increased levels in pathways branching off that could be corroborated by enzyme activity measurements. Integrated data analysis using clustering based on one-dimensional self-organizing maps identified two profiles highly correlated with HNT sensitivity. The sensitivity profile included genes of the functional bins abiotic stress, hormone metabolism, cell wall, signaling, redox state, transcription factors, secondary metabolites and defence genes. In the tolerance profile, similar bins were affected with slight differences in hormone metabolism and transcription factor responses. Metabolites of the two profiles revealed involvement of GABA signaling, thus providing a link to the TCA cycle status in sensitive cultivars and of myo-inositol as precursor for inositol phosphates linking jasmonate signaling to the HNT response specifically in tolerant cultivars. © 2016 John Wiley & Sons Ltd.

The impact of Polycomb group (PcG) and Trithorax group (TrxG) epigenetic factors in plant plasticity.

PubMed

de la Paz Sanchez, Maria; Aceves-García, Pamela; Petrone, Emilio; Steckenborn, Stefan; Vega-León, Rosario; Álvarez-Buylla, Elena R; Garay-Arroyo, Adriana; García-Ponce, Berenice

2015-11-01

Current advances indicate that epigenetic mechanisms play important roles in the regulatory networks involved in plant developmental responses to environmental conditions. Hence, understanding the role of such components becomes crucial to understanding the mechanisms underlying the plasticity and variability of plant traits, and thus the ecology and evolution of plant development. We now know that important components of phenotypic variation may result from heritable and reversible epigenetic mechanisms without genetic alterations. The epigenetic factors Polycomb group (PcG) and Trithorax group (TrxG) are involved in developmental processes that respond to environmental signals, playing important roles in plant plasticity. In this review, we discuss current knowledge of TrxG and PcG functions in different developmental processes in response to internal and environmental cues and we also integrate the emerging evidence concerning their function in plant plasticity. Many such plastic responses rely on meristematic cell behavior, including stem cell niche maintenance, cellular reprogramming, flowering and dormancy as well as stress memory. This information will help to determine how to integrate the role of epigenetic regulation into models of gene regulatory networks, which have mostly included transcriptional interactions underlying various aspects of plant development and its plastic response to environmental conditions. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Transcription Factors as Therapeutic Targets in Chronic Kidney Disease.

PubMed

Hishikawa, Akihito; Hayashi, Kaori; Itoh, Hiroshi

2018-05-09

The growing number of patients with chronic kidney disease (CKD) is recognized as an emerging problem worldwide. Recent studies have indicated that deregulation of transcription factors is associated with the onset or progression of kidney disease. Several clinical trials indicated that regression of CKD may be feasible via activation of the transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2), which suggests that transcription factors may be potential drug targets for CKD. Agents stabilizing hypoxia-inducible factor (HIF), which may be beneficial for renal anemia and renal protection, are also now under clinical trial. Recently, we have reported that the transcription factor Kruppel-like factor 4 (KLF4) regulates the glomerular podocyte epigenome, and that the antiproteinuric effect of the renin⁻angiotensin system blockade may be partially mediated by KLF4. KLF4 is one of the Yamanaka factors that induces iPS cells and is reported to be involved in epigenetic remodeling. In this article, we summarize the transcription factors associated with CKD and particularly focus on the possibility of transcription factors being novel drug targets for CKD through epigenetic modulation.

Production of Macrophage Inhibitory Factor (MIF) by Primary Sertoli Cells; Its Possible Involvement in Migration of Spermatogonial Cells.

PubMed

Huleihel, Mahmoud; Abofoul-Azab, Maram; Abarbanel, Yael; Einav, Iris; Levitas, Elyahu; Lunenfeld, Eitan

2017-10-01

Macrophage migration inhibitory factor (MIF) is a multifunctional molecule. MIF was originally identified as a T-cell-derived factor responsible for the inhibition of macrophage migration. In testicular tissue of adult rats, MIF is constitutively expressed by Leydig cells under physiological conditions. The aim of this study was to examine MIF levels in testicular homogenates from different aged mice, and the capacity of Sertoli cells to produce it. We also examined MIF involvement in spermatogonial cell migration. Similar levels of MIF protein were detected in testicular homogenates of mice of different ages (1-8-week-old). However, the RNA expression levels of MIF were high in 1-week-old mice and significantly decreased with age compared to 1-week-old mice. MIF was stained in Sertoli, Leydig cells, and developed germ cells in the seminiferous tubules. Isolated Sertoli cells from 1-week-old mice stained to MIF. Cultures of Sertoli cells from 1-week-old mice produced and expressed high levels of MIF which significantly decreased with age. MIF was localized in the cytoplasm and nucleus of Sertoli cell cultures isolated from 1-week-old mice; however, it was localized only in the cytoplasm and branches of cultures isolated from 8-week-old mice. MIFR was detected in GFRα1 and Sertoli cells. MIF could induce migration of spermatogonial cells, and this effect was synergistic with glial cell-line neurotrophic factor. Our results show, for the first time, the capacity of Sertoli cells to produce MIF under normal conditions and that MIFR expressed in GFRα1 and Sertoli cells. We also showed that MIF induced spermatogonial cell migration. J. Cell. Physiol. 232: 2869-2877, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Factors associated with acute respiratory infection in children under the age of 5 years: evidence from the 2011 Ethiopia Demographic and Health Survey.

PubMed

Geberetsadik, Achamyelesh; Worku, Alemayehu; Berhane, Yemane

2015-01-01

Acute respiratory tract infection (ARI) remains the major cause of child mortality in Sub-Saharan Africa. Various factors are associated with its occurrence and vary by context. However, available large-scale, population-based data are not fully exploited to identify locally relevant risk factors. The objective of this study was to identify factors associated with ARI in children under the age of 5 years in Ethiopia. Further analysis of the 2011 Ethiopia Demographic and Health Survey was carried out involving 11,645 children under the age of 5 years and their mothers. Information relevant to the current study was extracted from the main data set and a working data set was prepared. A complex survey logistic regression analysis was applied. Acute ARI in this study was associated with severe malnutrition. Children who were severely wasted were highly likely to develop ARI (adjusted odds ratio [AOR] 1.7; 95% confidence interval [CI] 1.1-2.5). ARI was less likely to occur in children from families with an educated father and professional mother (AOR 0.4; 95% CI 0.2-0.6 and AOR 0.1; 95% CI 0.01-0.6, respectively). Malnourished children from a lower socioeconomic category are more likely to suffer from ARI. Targeting disadvantaged children for effective interventions can help reduce the burden of morbidity and death due to ARI.

Ectopic Expression of CDF3 Genes in Tomato Enhances Biomass Production and Yield under Salinity Stress Conditions

PubMed Central

Renau-Morata, Begoña; Molina, Rosa V.; Carrillo, Laura; Cebolla-Cornejo, Jaime; Sánchez-Perales, Manuel; Pollmann, Stephan; Domínguez-Figueroa, José; Corrales, Alba R.; Flexas, Jaume; Vicente-Carbajosa, Jesús; Medina, Joaquín; Nebauer, Sergio G.

2017-01-01

Cycling Dof Factor (CDF) transcription factors (TFs) are involved in multiple processes related to plant growth and development. A member of this family, CDF3, has recently been linked in Arabidopsis to the regulation of primary metabolism and abiotic stress responses, but its role in crop production under stress is still unknown. In this study, we characterized tomato plants overexpressing the CDF3 genes from Arabidopsis and tomato and analyzed their effects on growth and yield under salinity, additionally gaining deeper insights into the molecular function of these TFs. Our results provide evidence for higher biomass production and yield in the 35S::AtCDF3 and 35S::SlCDF3 plants, likely due to a higher photosynthetic capacity resulting in increased sucrose availability. Transcriptome analysis revealed that CDF3 genes regulate a set of genes involved in redox homeostasis, photosynthesis performance and primary metabolism that lead to enhanced biomass production. Consistently, metabolomic profiling revealed that CDF3 evokes changes in the primary metabolism triggering enhanced nitrogen assimilation, and disclosed that the amount of some protective metabolites including sucrose, GABA and asparagine were higher in vegetative tissues of CDF3 overexpressing plants. Altogether these changes improved performance of 35S::AtCDF3 and 35S::SlCDF3 plants under salinity conditions. Moreover, the overexpression of CDF3 genes modified organic acid and sugar content in fruits, improving variables related to flavor perception and fruit quality. Overall, our results associate the CDF3 TF with a role in the control of growth and C/N metabolism, and highlight that overexpression of CDF3 genes can substantially improve plant yield. PMID:28515731

Insufficiency of pro-heparin-binding epidermal growth factor-like growth factor shedding enhances hypoxic cell death in H9c2 cardiomyoblasts via the activation of caspase-3 and c-Jun N-terminal kinase.

PubMed

Uetani, Teruyoshi; Nakayama, Hironao; Okayama, Hideki; Okura, Takafumi; Higaki, Jitsuo; Inoue, Hirofumi; Higashiyama, Shigeki

2009-05-01

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a cardiogenic and cardiohypertrophic growth factor. ProHB-EGF, a product of the Hb-egf gene and the precursor of HB-EGF, is anchored to the plasma membrane. Its ectodomain region is shed by a disintegrin and metalloproteases (ADAMs) when activated by various stimulations. It has been reported that an uncleavable mutant of Hb-egf, uc-Hb-egf, produces uc-proHB-EGF, which is not cleaved by ADAMs and causes dilation of the heart in knock-in mice. This suggests that the shedding of proHB-EGF is essential for the development and survival of cardiomyocytes: however, the molecular mechanism involved has remained unclear. In this study, we investigated the relationship between uc-proHB-EGF expression and cardiomyocyte survival. Human uc-proHB-EGF was adenovirally introduced into the rat cardiomyoblast cell line H9c2, and the cells were cultured under normoxic and hypoxic conditions. Uc-proHB-EGF-expressing H9c2 cells underwent apoptosis under normoxic conditions, which distinctly increased under hypoxic conditions. Furthermore, we observed an increased Caspase-3 activity, reactive oxygen species accumulation, and an increased c-Jun N-terminal kinase (JNK) activity in the uc-proHB-EGF-expressing H9c2 cells. Treatment of the uc-proHB-EGF transfectants with inhibitors of Caspase-3, reactive oxygen species, and JNK, namely, Z-VAD-fmk, N-acetylcysteine, and SP600125, respectively, significantly reduced hypoxic cell death. These data indicate that insufficiency of proHB-EGF shedding under hypoxic stress leads to cardiomyocyte apoptosis via Caspase-3- and JNK-dependent pathways.

Micronutrient bioavailability: Dietary Reference Intakes and a future perspective1234

PubMed Central

2010-01-01

This article provides a review of how the challenge of bioavailability was approached in establishing the Dietary Reference Intakes, with a special focus on folic acid, vitamin B-12, β-carotene, iron, selenium, and zinc, the targeted micronutrients for this workshop. In a future perspective, the necessity of having a clear working definition of bioavailability is emphasized. The bioavailability of micronutrients should be considered, with advantage, under subheadings determined by the broad factors that affect bioavailability. Special emphasis is given to giving greater and specific attention to factors involved in the maintenance of homeostasis. These factors, it is argued, are best considered separately from even a broad definition of bioavailability and have the potential to provide new insights into some micronutrient requirements. PMID:20200261

Patient-specific risk factors for infection in arthroplasty procedure.

PubMed

Marmor, S; Kerroumi, Y

2016-02-01

All patients are not equally at risk when it comes to postoperative infections, whether the risks are related to the environment or the patient. Patient-specific infection risk factors for arthroplasty should be a focal point during the preoperative consultation as they impact the treatment decision. Eighty percent of patients have at least one modifiable infection risk factor. These risk factors must be corrected preoperatively whenever possible so that the patient is operated under the best possible conditions, with the lowest possible infection risk. The screenings and preoperative preparations are multidisciplinary but must also involve the patient. The information provided to the patient must match the patient's infectious risk profile. This lecture will review every infection risk factor, whether it is modifiable or not, and then suggest how the treatment decision should be adapted to each patient's infection risk. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Using HFACS-Healthcare to Identify Systemic Vulnerabilities During Surgery.

PubMed

Cohen, Tara N; Francis, Sarah E; Wiegmann, Douglas A; Shappell, Scott A; Gewertz, Bruce L

2018-03-01

The Human Factors Analysis and Classification System for Healthcare (HFACS-Healthcare) was used to classify surgical near miss events reported via a hospital's event reporting system over the course of 1 year. Two trained analysts identified causal factors within each event narrative and subsequently categorized the events using HFACS-Healthcare. Of 910 original events, 592 could be analyzed further using HFACS-Healthcare, resulting in the identification of 726 causal factors. Most issues (n = 436, 60.00%) involved preconditions for unsafe acts, followed by unsafe acts (n = 257, 35.39%), organizational influences (n = 27, 3.72%), and supervisory factors (n = 6, 0.82%). These findings go beyond the traditional methods of trending incident data that typically focus on documenting the frequency of their occurrence. Analyzing near misses based on their underlying contributing human factors affords a greater opportunity to develop process improvements to reduce reoccurrence and better provide patient safety approaches.

A sequential factorial analysis approach to characterize the effects of uncertainties for supporting air quality management

NASA Astrophysics Data System (ADS)

Wang, S.; Huang, G. H.; Veawab, A.

2013-03-01

This study proposes a sequential factorial analysis (SFA) approach for supporting regional air quality management under uncertainty. SFA is capable not only of examining the interactive effects of input parameters, but also of analyzing the effects of constraints. When there are too many factors involved in practical applications, SFA has the advantage of conducting a sequence of factorial analyses for characterizing the effects of factors in a systematic manner. The factor-screening strategy employed in SFA is effective in greatly reducing the computational effort. The proposed SFA approach is applied to a regional air quality management problem for demonstrating its applicability. The results indicate that the effects of factors are evaluated quantitatively, which can help decision makers identify the key factors that have significant influence on system performance and explore the valuable information that may be veiled beneath their interrelationships.

Man, road and vehicle: risk factors associated with the severity of traffic accidents.

PubMed

Almeida, Rosa Lívia Freitas de; Bezerra Filho, José Gomes; Braga, José Ueleres; Magalhães, Francismeire Brasileiro; Macedo, Marinila Calderaro Munguba; Silva, Kellyanne Abreu

2013-08-01

To describe the main characteristics of victims, roads and vehicles involved in traffic accidents and the risk factors involved in accidents resulting in death. METHODS A non-concurrent cohort study of traffic accidents in Fortaleza, CE, Northeastern Brazil, in the period from January 2004 to December 2008. Data from the Fortaleza Traffic Accidents Information System, the Mortality Information System, the Hospital Information System and the State Traffic Department Driving Licenses and Vehicle database. Deterministic and probabilistic relationship techniques were used to integrate the databases. First, descriptive analysis of data relating to people, roads, vehicles and weather was carried out. In the investigation of risk factors for death by traffic accident, generalized linear models were used. The fit of the model was verified by likelihood ratio and ROC analysis. RESULTS There were 118,830 accidents recorded in the period. The most common types of accidents were crashes/collisions (78.1%), running over pedestrians (11.9%), colliding with a fixed obstacle (3.9%), and with motorcycles (18.1%). Deaths occurred in 1.4% of accidents. The factors that were independently associated with death by traffic accident in the final model were bicycles (OR = 21.2, 95%CI 16.1;27.8), running over pedestrians OR = 5.9 (95%CI 3.7;9.2), collision with a fixed obstacle (OR = 5.7, 95%CI 3.1;10.5) and accidents involving motorcyclists (OR = 3.5, 95%CI 2.6;4.6). The main contributing factors were a single person being involved (OR = 6.6, 95%CI 4.1;10.73), presence of unskilled drivers (OR = 4.1, 95%CI 2.9;5.5) a single vehicle (OR = 3.9, 95%CI 2,3;6,4), male (OR = 2.5, 95%CI 1.9;3.3), traffic on roads under federal jurisdiction (OR = 2.4, 95%CI 1.8;3.7), early morning hours (OR = 2.4, 95%CI 1.8;3.0), and Sundays (OR = 1.7, 95%CI 1.3;2.2), adjusted according to the log-binomial model. CONCLUSIONS Activities promoting the prevention of traffic accidents should primarily focus on accidents involving two-wheeled vehicles that most often involves a single person, unskilled, male, at nighttime, on weekends and on roads where they travel at higher speeds.

Assay of Plasma Membrane H+-ATPase in Plant Tissues under Abiotic Stresses.

PubMed

Janicka, Małgorzata; Wdowikowska, Anna; Kłobus, Grażyna

2018-01-01

Plasma membrane (PM) H + -ATPase, which generates the proton gradient across the outer membrane of plant cells, plays a fundamental role in the regulation of many physiological processes fundamental for growth and development of plants. It is involved in the uptake of nutrients from external solutions, their loading into phloem and long-distance transport, stomata aperture and gas exchange, pH homeostasis in cytosol, cell wall loosening, and cell expansion. The crucial role of the enzyme in resistance of plants to abiotic and biotic stress factors has also been well documented. Such great diversity of physiological functions linked to the activity of one enzyme requires a suitable and complex regulation of H + -ATPase. This regulation comprises the transcriptional as well as post-transcriptional levels. Herein, we describe the techniques that can be useful for the analysis of the plasma membrane proton pump modifications at genetic and protein levels under environmental factors.

Hemichannel composition and electrical synaptic transmission: molecular diversity and its implications for electrical rectification

PubMed Central

Palacios-Prado, Nicolás; Huetteroth, Wolf; Pereda, Alberto E.

2014-01-01

Unapposed hemichannels (HCs) formed by hexamers of gap junction proteins are now known to be involved in various cellular processes under both physiological and pathological conditions. On the other hand, less is known regarding how differences in the molecular composition of HCs impact electrical synaptic transmission between neurons when they form intercellular heterotypic gap junctions (GJs). Here we review data indicating that molecular differences between apposed HCs at electrical synapses are generally associated with rectification of electrical transmission. Furthermore, this association has been observed at both innexin and connexin (Cx) based electrical synapses. We discuss the possible molecular mechanisms underlying electrical rectification, as well as the potential contribution of intracellular soluble factors to this phenomenon. We conclude that asymmetries in molecular composition and sensitivity to cellular factors of each contributing hemichannel can profoundly influence the transmission of electrical signals, endowing electrical synapses with more complex functional properties. PMID:25360082

Neighborhood and community factors: effects on deviant behavior and social competence.

PubMed

Fariña, Francisca; Arce, Ramón; Novo, Mercedes

2008-05-01

Socialization in a neighborhood and community at risk, defined in terms of violence, social alienation, school failure, and disruptive behavior, is a risk factor for the acquisition of antisocial and delinquent behavior. In order to test this hypothesis and examine the underlying mechanisms involved, 346 participants, 155 high-risk and 191 low-risk, aged 11 to 13, that is, under the age of criminal responsibility as established by the Spanish Law 5/2000 were selected. The results reveal that high-risk youngsters had higher rates of antisocial behavior and lower levels of social skills (i.e., greater tendency to externalize attribution of responsibility, fewer conflict resolution strategies, lower self esteem, and a lower degrees of emotional intelligence) in comparison to the lower-risk group. Finally, the results and implications of the study are discussed in the light of designing prevention programs.

[Prevention and therapy of sarcopenia in the ageing].

PubMed

Zadák, Zdeněk

Sarcopenia is one of the severe disorders associated with nutritional imbalance. While sarcopenia is an inseparable part of the process of ageing as people get older, it plays a vital role in pathological situations such as protein-calorie and kwashiorkor malnutrition, it accompanies various diseases of rheumatic character and is an almost ever-present feature of the clinical picture of oncological patients. Sarcopenia in people under strain is fatally manifested mainly in the elderly, medically fragile patients. In view of the fact that sarcopenia is the decisive factor regarding the course of chronic as well as acute illnesses, it must be diagnosed, monitored and appropriately treated in time. Although nutrition is not the only factor involved especially in older age in the development of sarcopenia, the type of nutritional support and, in the new era, particularly nutritional pharmacology, form the underlying principles of the approach to the comprehensive care of the patient. ageing - lipids - malnutrition - proteosynthesis - sarcopenia.

Pharmacology of Vagal Afferent Influences on Disordered Breathing During Sleep

PubMed Central

Carley, David W; Radulovacki, Miodrag

2008-01-01

Sleep related breathing disorders (SRBD) are a significant public health concern, with a prevalence in the US general population of ∼2% of women and ∼4% of men. Although significant strides have been made in our understanding of these disorders with respect to epidemiology, risk factors, pathogenesis and consequences, work to understand these factors in terms of the underlying cellular, molecular and neuromodulatory processes remains in its infancy. Current primary treatments are surgical or mechanical, with no drug treatments available. Basic investigations into the neurochemistry and neuropharmacology of sleep-related changes in respiratory pattern generation and modulation will be essential to clarify the pathogenic processes underlying SRBD and to identify rational and specific pharmacotherapeutic opportunities. Here we summarize emerging work suggesting the importance of vagal afferent feedback systems in sleep related respiratory pattern disturbances and pointing toward a rich but complex array of neurochemical and neuromodulatory processes that may be involved. PMID:18694851

Vesiculation from Pseudomonas aeruginosa under SOS.

PubMed

Maredia, Reshma; Devineni, Navya; Lentz, Peter; Dallo, Shatha F; Yu, Jiehjuen; Guentzel, Neal; Chambers, James; Arulanandam, Bernard; Haskins, William E; Weitao, Tao

2012-01-01

Bacterial infections can be aggravated by antibiotic treatment that induces SOS response and vesiculation. This leads to a hypothesis concerning association of SOS with vesiculation. To test it, we conducted multiple analyses of outer membrane vesicles (OMVs) produced from the Pseudomonas aeruginosa wild type in which SOS is induced by ciprofloxacin and from the LexA noncleavable (lexAN) strain in which SOS is repressed. The levels of OMV proteins, lipids, and cytotoxicity increased for both the treated strains, demonstrating vesiculation stimulation by the antibiotic treatment. However, the further increase was suppressed in the lexAN strains, suggesting the SOS involvement. Obviously, the stimulated vesiculation is attributed by both SOS-related and unrelated factors. OMV subproteomic analysis was performed to examine these factors, which reflected the OMV-mediated cytotoxicity and the physiology of the vesiculating cells under treatment and SOS. Thus, SOS plays a role in the vesiculation stimulation that contributes to cytotoxicity.

Vesiculation from Pseudomonas aeruginosa under SOS

PubMed Central

Maredia, Reshma; Devineni, Navya; Lentz, Peter; Dallo, Shatha F.; Yu, JiehJuen; Guentzel, Neal; Chambers, James; Arulanandam, Bernard; Haskins, William E.; Weitao, Tao

2012-01-01

Bacterial infections can be aggravated by antibiotic treatment that induces SOS response and vesiculation. This leads to a hypothesis concerning association of SOS with vesiculation. To test it, we conducted multiple analyses of outer membrane vesicles (OMVs) produced from the Pseudomonas aeruginosa wild type in which SOS is induced by ciprofloxacin and from the LexA noncleavable (lexAN) strain in which SOS is repressed. The levels of OMV proteins, lipids, and cytotoxicity increased for both the treated strains, demonstrating vesiculation stimulation by the antibiotic treatment. However, the further increase was suppressed in the lexAN strains, suggesting the SOS involvement. Obviously, the stimulated vesiculation is attributed by both SOS-related and unrelated factors. OMV subproteomic analysis was performed to examine these factors, which reflected the OMV-mediated cytotoxicity and the physiology of the vesiculating cells under treatment and SOS. Thus, SOS plays a role in the vesiculation stimulation that contributes to cytotoxicity. PMID:22448133

Fibroblast growth factor receptors in breast cancer: expression, downstream effects, and possible drug targets.

PubMed

Tenhagen, M; van Diest, P J; Ivanova, I A; van der Wall, E; van der Groep, P

2012-08-01

Cancer treatments are increasingly focusing on the molecular mechanisms underlying the oncogenic processes present in tumors of individual patients. Fibroblast growth factor receptors (FGFRs) are among the many molecules that are involved in oncogenesis and are currently under investigation for their potential as drug targets in breast cancer patients. These receptor tyrosine kinases play a role in several processes including proliferation, angiogenesis, and migration. Alterations in these basal processes can contribute to the development and progression of tumors. Among breast cancer patients, several subgroups have been shown to harbor genetic aberrations in FGFRs, including amplifications of FGFR1, FGFR2, and FGFR4 and mutations in FGFR2 and FGFR4. Here, we review in vitro and in vivo models that have partly elucidated the molecular implications of these different genetic aberrations, the resulting tumor characteristics, and the potential of FGFRs as therapeutic targets for breast cancer treatment.

Future reef decalcification under a business-as-usual CO2 emission scenario

PubMed Central

Dove, Sophie G.; Kline, David I.; Pantos, Olga; Angly, Florent E.; Tyson, Gene W.; Hoegh-Guldberg, Ove

2013-01-01

Increasing atmospheric partial pressure of CO2 (pCO2) is a major threat to coral reefs, but some argue that the threat is mitigated by factors such as the variability in the response of coral calcification to acidification, differences in bleaching susceptibility, and the potential for rapid adaptation to anthropogenic warming. However the evidence for these mitigating factors tends to involve experimental studies on corals, as opposed to coral reefs, and rarely includes the influence of multiple variables (e.g., temperature and acidification) within regimes that include diurnal and seasonal variability. Here, we demonstrate that the inclusion of all these factors results in the decalcification of patch-reefs under business-as-usual scenarios and reduced, although positive, calcification under reduced-emission scenarios. Primary productivity was found to remain constant across all scenarios, despite significant bleaching and coral mortality under both future scenarios. Daylight calcification decreased and nocturnal decalcification increased sharply from the preindustrial and control conditions to the future scenarios of low (reduced emissions) and high (business-as-usual) increases in pCO2. These changes coincided with deeply negative carbonate budgets, a shift toward smaller carbonate sediments, and an increase in the abundance of sediment microbes under the business-as-usual emission scenario. Experimental coral reefs demonstrated highest net calcification rates and lowest rates of coral mortality under preindustrial conditions, suggesting that reef processes may not have been able to keep pace with the relatively minor environmental changes that have occurred during the last century. Taken together, our results have serious implications for the future of coral reefs under business-as-usual environmental changes projected for the coming decades and century. PMID:24003127

Future reef decalcification under a business-as-usual CO2 emission scenario.

PubMed

Dove, Sophie G; Kline, David I; Pantos, Olga; Angly, Florent E; Tyson, Gene W; Hoegh-Guldberg, Ove

2013-09-17

Increasing atmospheric partial pressure of CO2 (pCO2) is a major threat to coral reefs, but some argue that the threat is mitigated by factors such as the variability in the response of coral calcification to acidification, differences in bleaching susceptibility, and the potential for rapid adaptation to anthropogenic warming. However the evidence for these mitigating factors tends to involve experimental studies on corals, as opposed to coral reefs, and rarely includes the influence of multiple variables (e.g., temperature and acidification) within regimes that include diurnal and seasonal variability. Here, we demonstrate that the inclusion of all these factors results in the decalcification of patch-reefs under business-as-usual scenarios and reduced, although positive, calcification under reduced-emission scenarios. Primary productivity was found to remain constant across all scenarios, despite significant bleaching and coral mortality under both future scenarios. Daylight calcification decreased and nocturnal decalcification increased sharply from the preindustrial and control conditions to the future scenarios of low (reduced emissions) and high (business-as-usual) increases in pCO2. These changes coincided with deeply negative carbonate budgets, a shift toward smaller carbonate sediments, and an increase in the abundance of sediment microbes under the business-as-usual emission scenario. Experimental coral reefs demonstrated highest net calcification rates and lowest rates of coral mortality under preindustrial conditions, suggesting that reef processes may not have been able to keep pace with the relatively minor environmental changes that have occurred during the last century. Taken together, our results have serious implications for the future of coral reefs under business-as-usual environmental changes projected for the coming decades and century.

Vascular Endothelial Growth Factor (VEGF) and Platelet (PF-4) Factor 4 Inputs Modulate Human Microvascular Endothelial Signaling in a Three-Dimensional Matrix Migration Context*

PubMed Central

Hang, Ta-Chun; Tedford, Nathan C.; Reddy, Raven J.; Rimchala, Tharathorn; Wells, Alan; White, Forest M.; Kamm, Roger D.; Lauffenburger, Douglas A.

2013-01-01

The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial postwound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage before progression of wound healing toward tissue homeostasis. Because of its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 h of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment. PMID:24023389

MicroRNA and Transcription Factor: Key Players in Plant Regulatory Network

PubMed Central

Samad, Abdul F. A.; Sajad, Muhammad; Nazaruddin, Nazaruddin; Fauzi, Izzat A.; Murad, Abdul M. A.; Zainal, Zamri; Ismail, Ismanizan

2017-01-01

Recent achievements in plant microRNA (miRNA), a large class of small and non-coding RNAs, are very exciting. A wide array of techniques involving forward genetic, molecular cloning, bioinformatic analysis, and the latest technology, deep sequencing have greatly advanced miRNA discovery. A tiny miRNA sequence has the ability to target single/multiple mRNA targets. Most of the miRNA targets are transcription factors (TFs) which have paramount importance in regulating the plant growth and development. Various families of TFs, which have regulated a range of regulatory networks, may assist plants to grow under normal and stress environmental conditions. This present review focuses on the regulatory relationships between miRNAs and different families of TFs like; NF-Y, MYB, AP2, TCP, WRKY, NAC, GRF, and SPL. For instance NF-Y play important role during drought tolerance and flower development, MYB are involved in signal transduction and biosynthesis of secondary metabolites, AP2 regulate the floral development and nodule formation, TCP direct leaf development and growth hormones signaling. WRKY have known roles in multiple stress tolerances, NAC regulate lateral root formation, GRF are involved in root growth, flower, and seed development, and SPL regulate plant transition from juvenile to adult. We also studied the relation between miRNAs and TFs by consolidating the research findings from different plant species which will help plant scientists in understanding the mechanism of action and interaction between these regulators in the plant growth and development under normal and stress environmental conditions. PMID:28446918

Common Genetic Denominators for Ca++-Based Skeleton in Metazoa: Role of Osteoclast-Stimulating Factor and of Carbonic Anhydrase in a Calcareous Sponge

PubMed Central

Müller, Werner E. G.; Wang, Xiaohong; Grebenjuk, Vlad A.; Korzhev, Michael; Wiens, Matthias; Schloßmacher, Ute; Schröder, Heinz C.

2012-01-01

Calcium-based matrices serve predominantly as inorganic, hard skeletal systems in Metazoa from calcareous sponges [phylum Porifera; class Calcarea] to proto- and deuterostomian multicellular animals. The calcareous sponges form their skeletal elements, the spicules, from amorphous calcium carbonate (ACC). Treatment of spicules from Sycon raphanus with sodium hypochlorite (NaOCl) results in the disintegration of the ACC in those skeletal elements. Until now a distinct protein/enzyme involved in ACC metabolism could not been identified in those animals. We applied the technique of phage display combinatorial libraries to identify oligopeptides that bind to NaOCl-treated spicules: those oligopeptides allowed us to detect proteins that bind to those spicules. Two molecules have been identified, the (putative) enzyme carbonic anhydrase and the (putative) osteoclast-stimulating factor (OSTF), that are involved in the catabolism of ACC. The complete cDNAs were isolated and the recombinant proteins were prepared to raise antibodies. In turn, immunofluorescence staining of tissue slices and qPCR analyses have been performed. The data show that sponges, cultivated under standard condition (10 mM CaCl2) show low levels of transcripts/proteins for carbonic anhydrase or OSTF, compared to those animals that had been cultivated under Ca2+-depletion condition (1 mM CaCl2). Our data identify with the carbonic anhydrase and the OSTF the first two molecules which remain conserved in cells, potentially involved in Ca-based skeletal dissolution, from sponges (sclerocytes) to human (osteoclast). PMID:22506035

Risks, Outcomes, and Evidence-based Interventions for Girls in the U.S. Juvenile Justice System

PubMed Central

Leve, Leslie D.; Chamberlain, Patricia; Kim, Hyoun K.

2015-01-01

The proportion of the juvenile justice population that is comprised of females is increasing, yet few evidence-based models have been evaluated and implemented with girls in the juvenile justice system. Although much is known about the risk and protective factors for girls who participate in serious delinquency, significant gaps in the research base hamper the development and implementation of theoretically based intervention approaches. In this review, we first summarize the extant empirical work about the predictors and sequelae of juvenile justice involvement for girls. Identified risk and protective factors that correspond to girls’ involvement in the juvenile justice system have been shown to largely parallel those of boys, although exposure rates and magnitudes of association sometimes differ by sex. Second, we summarize findings from empirically validated, evidence-based interventions for juvenile justice–involved youths that have been tested with girls. The interventions include Functional Family Therapy, Multisystemic Therapy, Multidimensional Family Therapy, and Treatment Foster Care Oregon (formerly known as Multidimensional Treatment Foster Care). We conclude that existing evidence-based practices appear to be effective for girls. However, few studies have been sufficiently designed to permit conclusions about whether sex-specific interventions would yield any better outcomes for girls than would interventions that already exist for both sexes and that have a strong base of evidence to support them. Third, we propose recommendations for feasible, cost-efficient next steps to advance the research and intervention agendas for this under-researched, under-served population of highly vulnerable youths. PMID:26119215

The productivity and cost-efficiency of models for involving nurse practitioners in primary care: a perspective from queueing analysis.

PubMed

Liu, Nan; D'Aunno, Thomas

2012-04-01

To develop simple stylized models for evaluating the productivity and cost-efficiencies of different practice models to involve nurse practitioners (NPs) in primary care, and in particular to generate insights on what affects the performance of these models and how. The productivity of a practice model is defined as the maximum number of patients that can be accounted for by the model under a given timeliness-to-care requirement; cost-efficiency is measured by the corresponding annual cost per patient in that model. Appropriate queueing analysis is conducted to generate formulas and values for these two performance measures. Model parameters for the analysis are extracted from the previous literature and survey reports. Sensitivity analysis is conducted to investigate the model performance under different scenarios and to verify the robustness of findings. Employing an NP, whose salary is usually lower than a primary care physician, may not be cost-efficient, in particular when the NP's capacity is underutilized. Besides provider service rates, workload allocation among providers is one of the most important determinants for the cost-efficiency of a practice model involving NPs. Capacity pooling among providers could be a helpful strategy to improve efficiency in care delivery. The productivity and cost-efficiency of a practice model depend heavily on how providers organize their work and a variety of other factors related to the practice environment. Queueing theory provides useful tools to take into account these factors in making strategic decisions on staffing and panel size selection for a practice model. © Health Research and Educational Trust.

First insights into the pleiotropic role of vrf (yedF), a newly characterized gene of Salmonella Typhimurium.

PubMed

Ballesté-Delpierre, Clara; Fernandez-Orth, Dietmar; Ferrer-Navarro, Mario; Díaz-Peña, Ramón; Odena-Caballol, Antonia; Oliveira, Eliandre; Fàbrega, Anna; Vila, Jordi

2017-11-10

Salmonella possesses virulence determinants that allow replication under extreme conditions and invasion of host cells, causing disease. Here, we examined four putative genes predicted to encode membrane proteins (ydiY, ybdJ, STM1441 and ynaJ) and a putative transcriptional factor (yedF). These genes were identified in a previous study of a S. Typhimurium clinical isolate and its multidrug-resistant counterpart. For STM1441 and yedF a reduced ability to interact with HeLa cells was observed in the knock-out mutants, but an increase in this ability was absent when these genes were overexpressed, except for yedF which phenotype was rescued when yedF was restored. In the absence of yedF, decreased expression was seen for: i) virulence-related genes involved in motility, chemotaxis, attachment and survival inside the host cell; ii) global regulators of the invasion process (hilA, hilC and hilD); and iii) factors involved in LPS biosynthesis. In contrast, an increased expression was observed for anaerobic metabolism genes. We propose yedF is involved in the regulation of Salmonella pathogenesis and contributes to the activation of the virulence machinery. Moreover, we propose that, when oxygen is available, yedF contributes sustained repression of the anaerobic pathway. Therefore, we recommend this gene be named vrf, for virulence-related factor.

Ventral striatal response during decision making involving risk and reward is associated with future binge drinking in adolescents.

PubMed

Morales, Angelica M; Jones, Scott A; Ehlers, Alissa; Lavine, Jessye B; Nagel, Bonnie J

2018-05-07

Beginning to engage in heavy alcohol use during adolescence, as opposed to later in life, is associated with elevated risk for a variety of negative consequences, including the development of an alcohol use disorder. Behavioral studies suggest that poor decision making predicts alcohol use during adolescence; however, more research is needed to determine the neurobiological risk factors that underlie this association. Using functional magnetic resonance imaging, brain activation during decision making involving risk and reward was assessed in 47 adolescents (14-15 years old) with no significant history or alcohol or drug use. After baseline assessment, participants completed follow-up interviews every 3 months to assess the duration to onset of binge drinking. Adolescents who made a greater number of risky selections and had greater activation in the nucleus accumbens, precuneus, and occipital cortex during decision making involving greater potential for risk and reward began binge drinking sooner. Findings suggest that heightened activation of reward circuitry during decision making under risk is a neurobiological risk factor for earlier onset of binge drinking. Furthermore, brain activation was a significant predictor of onset to binge drinking, even after controlling for decision-making behavior, suggesting that neurobiological markers may provide additional predictive validity over behavioral assessments. Interventions designed to modify these behavioral and neurobiological risk factors may be useful for curbing heavy alcohol use during adolescence.

Lipotoxicity Mediated Cell Dysfunction and Death Involves Lysosomal Membrane Permeabilization and Cathepsin L Activity

PubMed Central

Almaguel, Frankis G.; Liu, Jo-Wen; Pacheco, Fabio J.; De Leon, Daisy; Casiano, Carlos A.; De Leon, Marino

2010-01-01

Lipotoxicity, which is triggered when cells are exposed to elevated levels of free fatty acids, involves cell dysfunction and apoptosis and is emerging as an underlying factor contributing to various pathological conditions including disorders of the central nervous system and diabetes. We have shown that palmitic acid (PA)-induced lipotoxicity (PA-LTx) in nerve growth factor-differentiated PC12 (NGFDPC12) cells is linked to an augmented state of cellular oxidative stress (ASCOS) and apoptosis, and that these events are inhibited by docosahexanoic acid (DHA). The mechanisms of PA-LTx in nerve cells are not well understood, but our previous findings indicate that it involves ROS generation, mitochondrial membrane permeabilization (MMP), and caspase activation. The present study used nerve growth factor differentiated PC12 cells (NGFDPC12 cells) and found that lysosomal membrane permeabilization (LMP) is an early event during PA-induced lipotoxicity that precedes MMP and apoptosis. Cathepsin L, but not cathepsin B, is an important contributor in this process since its pharmacological inhibition significantly attenuated LMP, MMP, and apoptosis. In addition, co-treatment of NGFDPC12 cells undergoing lipotoxicity with DHA significantly reduced LMP, suggesting that DHA acts by antagonizing upstream signals leading to lysosomal dysfunction. These results suggest that LMP is a key early mediator of lipotoxicity, and underscore the value of interventions targeting upstream signals leading to LMP for the treatment of pathological conditions associated with lipotoxicity. PMID:20043885

Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis of Endogenous Sepsis Mediators.

PubMed

Bedet, Alexandre; Razazi, Keyvan; Boissier, Florence; Surenaud, Mathieu; Hue, Sophie; Giraudier, Stéphane; Brun-Buisson, Christian; Mekontso Dessap, Armand

2018-06-01

Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded. Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia. Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.

A clinical tool for predicting survival in ALS.

PubMed

Knibb, Jonathan A; Keren, Noa; Kulka, Anna; Leigh, P Nigel; Martin, Sarah; Shaw, Christopher E; Tsuda, Miho; Al-Chalabi, Ammar

2016-12-01

Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis. 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval. Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median. A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Depletion of histone demethylase KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of stem cells from apical papilla

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

Dong, Rui; Yao, Rui; Du, Juan

Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. The histone demethylase, lysine (K)-specific demethylase 2A (KDM2A), is evolutionarily conserved and ubiquitously expressed members of the JmjC-domain-containing histone demethylase family. A previous study determined that KDM2A can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2A is involved in the other cell lineages differentiation of MSCs. Here, we show that depletion of KDM2A by short hairpin RNAs can enhance adipogenic and chondrogenic differentiation potentials in human stemmore » cells from apical papilla (SCAPs). We found that the stemness-related genes, SOX2, and the embryonic stem cell master transcription factor, NANOG were significantly increased after silence of KDM2A in SCAPs. Moreover, we found that knock-down of the KDM2A co-factor, BCOR also up-regulated the mRNA levels of SOX2 and NANOG. Furthermore, Chromatin immunoprecipitation assays demonstrate that silence of KDM2A increased the histone H3 Lysine 4 (H3K4) trimethylation in the SOX2 and NANOG locus and regulates its expression. In conclusion, our results suggested that depletion of KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of SCAPs by up-regulated SOX2 and NANOG, BCOR also involved in this regulation as co-factor, and provided useful information to understand the molecular mechanism underlying directed differentiation in MSCs. - Highlights: • Depletion of KDM2A enhances adipogenic/chondrogenic differentiation in SCAPs. • Depletion of KDM2A enhances the differentiation of SCAPs by activate SOX2 and NANOG. • Silence of KDM2A increases histone H3 Lysine 4 trimethylation in SOX2 and NANOG. • BCOR is co-factor of KDM2A involved in the differentiation regulation.« less

A mathematical model of case-ascertainment bias: Applied to case-control studies nested within a randomized screening trial.

PubMed

Jansen, Rick J; Alexander, Bruce H; Hayes, Richard B; Miller, Anthony B; Wacholder, Sholom; Church, Timothy R

2018-01-01

When some individuals are screen-detected before the beginning of the study, but otherwise would have been diagnosed symptomatically during the study, this results in different case-ascertainment probabilities among screened and unscreened participants, referred to here as lead-time-biased case-ascertainment (LTBCA). In fact, this issue can arise even in risk-factor studies nested within a randomized screening trial; even though the screening intervention is randomly allocated to trial arms, there is no randomization to potential risk-factors and uptake of screening can differ by risk-factor strata. Under the assumptions that neither screening nor the risk factor affects underlying incidence and no other forms of bias operate, we simulate and compare the underlying cumulative incidence and that observed in the study due to LTBCA. The example used will be constructed from the randomized Prostate, Lung, Colorectal, and Ovarian cancer screening trial. The derived mathematical model is applied to simulating two nested studies to evaluate the potential for screening bias in observational lung cancer studies. Because of differential screening under plausible assumptions about preclinical incidence and duration, the simulations presented here show that LTBCA due to chest x-ray screening can significantly increase the estimated risk of lung cancer due to smoking by 1% and 50%. Traditional adjustment methods cannot account for this bias, as the influence screening has on observational study estimates involves events outside of the study observation window (enrollment and follow-up) that change eligibility for potential participants, thus biasing case ascertainment.

Delayed recovery from anesthesia: A postgraduate educational review.

PubMed

Misal, Ullhas Sudhakarrao; Joshi, Suchita Annasaheb; Shaikh, Mudassir Mohd

2016-01-01

Delayed awakening from anesthesia remains one of the biggest challenges that involve an anesthesiologist. With the general use of fast-acting anesthetic agents, patients usually awaken quickly in the postoperative period. The time to emerge from anesthesia is affected by patient factors, anesthetic factors, duration of surgery, and painful stimulation. The principal factors responsible for delayed awakening following anesthesia are anesthetic agents and medications used in the perioperative period. Nonpharmacological causes may have a serious sequel, hence recognizing these organic conditions is important. Certain underlying metabolic disorders such as hypoglycemia, severe hyperglycemia, and electrolyte imbalance, especially hypernatremia, hypoxia, hypercapnia, central anticholinergic syndrome, chronic hypertension, liver disease, hypoalbuminemia, uremia, and severe hypothyroidism may also be responsible for delayed recovery following anesthesia. Unexpected delayed emergence after general anesthesia may also be due to intraoperative cerebral hypoxia, hemorrhage, embolism, or thrombosis. Accurate diagnosis of the underlying cause is the key for the institution of appropriate therapy, but primary management is to maintain airway, breathing, and circulation. This comprehensive review discusses the risk factors, causes, evaluation and management of delayed recovery based on our clinical experience, and literature search on the internet, supported by the standard textbooks of anesthesiology.

Rough set approach for accident chains exploration.

PubMed

Wong, Jinn-Tsai; Chung, Yi-Shih

2007-05-01

This paper presents a novel non-parametric methodology--rough set theory--for accident occurrence exploration. The rough set theory allows researchers to analyze accidents in multiple dimensions and to model accident occurrence as factor chains. Factor chains are composed of driver characteristics, trip characteristics, driver behavior and environment factors that imply typical accident occurrence. A real-world database (2003 Taiwan single auto-vehicle accidents) is used as an example to demonstrate the proposed approach. The results show that although most accident patterns are unique, some accident patterns are significant and worth noting. Student drivers who are young and less experienced exhibit a relatively high possibility of being involved in off-road accidents on roads with a speed limit between 51 and 79 km/h under normal driving circumstances. Notably, for bump-into-facility accidents, wet surface is a distinctive environmental factor.

Protein accumulation in leaves and roots associated with improved drought tolerance in creeping bentgrass expressing an ipt gene for cytokinin synthesis

PubMed Central

Merewitz, Emily B.; Gianfagna, Thomas; Huang, Bingru

2011-01-01

Cytokinins (CKs) may be involved in the regulation of plant adaptation to drought stress. The objectives of the study were to identify proteomic changes in leaves and roots in relation to improved drought tolerance in transgenic creeping bentgrass (Agrostis stolonifera) containing a senescence-activated promoter (SAG12) and the isopentyl transferase (ipt) transgene that increases endogenous CK content. Leaves of SAG12-ipt bentgrass exhibited less severe senescence under water stress, as demonstrated by maintaining lower electrolyte leakage and lipid peroxidation, and higher photochemical efficiency (Fv/Fm), compared with the null transformant (NT) plants. SAG12-ipt plants had higher root/shoot ratios and lower lipid peroxidation in leaves under water stress than the NT plants. The suppression of drought-induced leaf senescence and root dieback in the transgenic plants was associated with the maintenance of greater antioxidant enzyme activities (superoxide dismutase, peroxidase, and catalase). The SAG12-ipt and NT plants exhibited differential protein expression patterns under well-watered and drought conditions in both leaves and roots. Under equivalent leaf water deficit (47% relative water content), SAG12-ipt plants maintained higher abundance of proteins involved in (i) energy production within both photosynthesis and respiration [ribulose 1,5-bisphosphate carboxylase (RuBisCO) and glyceraldehyde phosphate dehydrogenase (GAPDH)]; (ii) amino acid synthesis (methionine and glutamine); (iii) protein synthesis and destination [chloroplastic elongation factor (EF-Tu) and protein disulphide isomerases (PDIs)]; and (iv) antioxidant defence system (catalase and peroxidase) than the NT plants. These results suggest that increased endogenous CKs under drought stress may directly or indirectly regulate protein abundance and enzymatic activities involved in the above-mentioned metabolic processes, thereby enhancing plant drought tolerance. PMID:21831843

A Fatigue Life Prediction Method Based on Strain Intensity Factor

PubMed Central

Zhang, Wei; Liu, Huili; Wang, Qiang; He, Jingjing

2017-01-01

In this paper, a strain-intensity-factor-based method is proposed to calculate the fatigue crack growth under the fully reversed loading condition. A theoretical analysis is conducted in detail to demonstrate that the strain intensity factor is likely to be a better driving parameter correlated with the fatigue crack growth rate than the stress intensity factor (SIF), especially for some metallic materials (such as 316 austenitic stainless steel) in the low cycle fatigue region with negative stress ratios R (typically R = −1). For fully reversed cyclic loading, the constitutive relation between stress and strain should follow the cyclic stress-strain curve rather than the monotonic one (it is a nonlinear function even within the elastic region). Based on that, a transformation algorithm between the SIF and the strain intensity factor is developed, and the fatigue crack growth rate testing data of 316 austenitic stainless steel and AZ31 magnesium alloy are employed to validate the proposed model. It is clearly observed that the scatter band width of crack growth rate vs. strain intensity factor is narrower than that vs. the SIF for different load ranges (which indicates that the strain intensity factor is a better parameter than the stress intensity factor under the fully reversed load condition). It is also shown that the crack growth rate is not uniquely determined by the SIF range even under the same R, but is also influenced by the maximum loading. Additionally, the fatigue life data (strain-life curve) of smooth cylindrical specimens are also used for further comparison, where a modified Paris equation and the equivalent initial flaw size (EIFS) are involved. The results of the proposed method have a better agreement with the experimental data compared to the stress intensity factor based method. Overall, the strain intensity factor method shows a fairly good ability in calculating the fatigue crack propagation, especially for the fully reversed cyclic loading condition. PMID:28773049

Facilitating Factors and Barriers to the Use of Emerging Technologies for Suicide Prevention in Europe: Multicountry Exploratory Study

PubMed Central

Delgado, Carmen; Sánchez-Prada, Andrés; Parra-Vidales, Esther; de Leo, Diego; Franco-Martín, Manuel

2018-01-01

Background This study provides an analysis on the use of emerging technologies for the prevention of suicide in 8 different European countries. Objective The objective of this study was to analyze the potentiality of using emerging technologies in the area of suicide prevention based on the opinion of different professionals involved in suicide prevention. Methods Opinions of 3 groups of stakeholders (ie, relevant professionals in suicide field) were gathered using a specifically designed questionnaire to explore dimensions underlying perceptions of facilitating factors and barriers in relation to the use of emerging technologies for suicide prevention. Results Goal 1 involved facilitating factors for the use of emerging technologies in suicide prevention. Northern European countries, except for Belgium, attach greater relevance to those that optimize implementation and benefits. On the other hand, Southern European countries attach greater importance to professionally oriented and user-centered facilitating factors. According to different stakeholders, the analysis of these facilitating factors suggest that professionals in the field of social work attach greater relevance to those that optimize implementation and benefits. However, professionals involved in the area of mental health, policy makers, and political decision makers give greater importance to professionally oriented and user-centered facilitating factors. Goal 2 was related to barriers to the usability of emerging technologies for suicide prevention. Both countries and stakeholders attach greater importance to barriers associated with resource constraints than to those centered on personal limitations. There are no differences between countries or between stakeholders. Nevertheless, there is a certain stakeholders-countries interaction that indicates that the opinions on resource constraints expressed by different stakeholders do not follow a uniform pattern in different countries, but they differ depending on the country. Conclusions Although all countries and stakeholders agree in identifying resource constraints as the main barrier to the use of emerging technologies, factors facilitating their use in suicide prevention differ among countries and among stakeholders. PMID:29367183

The targets of curcumin.

PubMed

Zhou, Hongyu; Beevers, Christopher S; Huang, Shile

2011-03-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-kB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer's disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here.

Livedoid vasculopathy in a patient with factor V mutation (Leiden).

PubMed

Biedermann, T; Flaig, M J; Sander, C A

2000-09-01

Frequently, no underlying disease can be detected in patients with livedoid vasculopathy. For these forms, an unknown vaso-occlusive or thrombogenic process has been accused to play a role. Thus, a patient with livedoid vasculopathy was examined for different parameters which can be involved in coagulopathies. Laboratory studies for different autoantigen reactive immunoglobulins, cryoglobulins, and circulating immune complexes were carried out. Besides dermatopathologic examination, a biopsy specimen was analyzed by direct immunofluorescence for immunoglobulin (Ig) and complement deposits. Furthermore, hemostaseological function tests including activated protein C (APC) resistance were undertaken. Positive only at very low titres were antinuclear antibodies and c-ANCA, all other parameters were within normal ranges or negative. Direct immunofluorescence revealed IgM, C3 and fibrogen deposits. Hemostaseological function tests demonstrated a pathologic activated protein c resistance and PCR analysis a heterozygous defect of the factor V (Leiden). The diagnosis of livedoid vasculopathy associated with factor V mutation (Leiden) was made. Since the underlying cause for livedoid vasculopathy often remains unknown, we suggest that hemostaseological function tests including APC resistance and factor V gene mutation analysis should be carried out. Further studies have to follow in order to elucidate the role of mutant factor V in livedoid vasculopathy and in cutaneous ulcerations.

Targets of curcumin

PubMed Central

Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

2010-01-01

Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

Word Naming in the L1 and L2: A Dynamic Perspective on Automatization and the Degree of Semantic Involvement in Naming.

PubMed

Plat, Rika; Lowie, Wander; de Bot, Kees

2017-01-01

Reaction time data have long been collected in order to gain insight into the underlying mechanisms involved in language processing. Means analyses often attempt to break down what factors relate to what portion of the total reaction time. From a dynamic systems theory perspective or an interaction dominant view of language processing, it is impossible to isolate discrete factors contributing to language processing, since these continually and interactively play a role. Non-linear analyses offer the tools to investigate the underlying process of language use in time, without having to isolate discrete factors. Patterns of variability in reaction time data may disclose the relative contribution of automatic (grapheme-to-phoneme conversion) processing and attention-demanding (semantic) processing. The presence of a fractal structure in the variability of a reaction time series indicates automaticity in the mental structures contributing to a task. A decorrelated pattern of variability will indicate a higher degree of attention-demanding processing. A focus on variability patterns allows us to examine the relative contribution of automatic and attention-demanding processing when a speaker is using the mother tongue (L1) or a second language (L2). A word naming task conducted in the L1 (Dutch) and L2 (English) shows L1 word processing to rely more on automatic spelling-to-sound conversion than L2 word processing. A word naming task with a semantic categorization subtask showed more reliance on attention-demanding semantic processing when using the L2. A comparison to L1 English data shows this was not only due to the amount of language use or language dominance, but also to the difference in orthographic depth between Dutch and English. An important implication of this finding is that when the same task is used to test and compare different languages, one cannot straightforwardly assume the same cognitive sub processes are involved to an equal degree using the same task in different languages.

Gene Expression Networks Underlying Ovarian Development in Wild Largemouth Bass (Micropterus salmoides)

PubMed Central

Martyniuk, Christopher J.; Prucha, Melinda S.; Doperalski, Nicholas J.; Antczak, Philipp; Kroll, Kevin J.; Falciani, Francesco; Barber, David S.; Denslow, Nancy D.

2013-01-01

Background Oocyte maturation in fish involves numerous cell signaling cascades that are activated or inhibited during specific stages of oocyte development. The objectives of this study were to characterize molecular pathways and temporal gene expression patterns throughout a complete breeding cycle in wild female largemouth bass to improve understanding of the molecular sequence of events underlying oocyte maturation. Methods Transcriptomic analysis was performed on eight morphologically diverse stages of the ovary, including primary and secondary stages of oocyte growth, ovulation, and atresia. Ovary histology, plasma vitellogenin, 17β-estradiol, and testosterone were also measured to correlate with gene networks. Results Global expression patterns revealed dramatic differences across ovarian development, with 552 and 2070 genes being differentially expressed during both ovulation and atresia respectively. Gene set enrichment analysis (GSEA) revealed that early primary stages of oocyte growth involved increases in expression of genes involved in pathways of B-cell and T-cell receptor-mediated signaling cascades and fibronectin regulation. These pathways as well as pathways that included adrenergic receptor signaling, sphingolipid metabolism and natural killer cell activation were down-regulated at ovulation. At atresia, down-regulated pathways included gap junction and actin cytoskeleton regulation, gonadotrope and mast cell activation, and vasopressin receptor signaling and up-regulated pathways included oxidative phosphorylation and reactive oxygen species metabolism. Expression targets for luteinizing hormone signaling were low during vitellogenesis but increased 150% at ovulation. Other networks found to play a significant role in oocyte maturation included those with genes regulated by members of the TGF-beta superfamily (activins, inhibins, bone morphogenic protein 7 and growth differentiation factor 9), neuregulin 1, retinoid X receptor, and nerve growth factor family. Conclusions This study offers novel insight into the gene networks underlying vitellogenesis, ovulation and atresia and generates new hypotheses about the cellular pathways regulating oocyte maturation. PMID:23527095

Upper extremity paraesthesia: clinical assessment and reasoning.

PubMed

Muscolino, Joseph E

2008-07-01

The art of clinical assessment involves an accurate determination of the cause(s) of a patient's symptoms. Given that a set of symptoms can be influenced by many contributing factors and features, assessment needs to differentially evaluate these. Accurate and appropriate treatment depends on differential assessment based on sound clinical reasoning. Many conditions derive from multiple causes demanding evaluation of as many etiological features as can be identified. The case review presented here involves a patient presenting with paraesthesia spreading into her right upper extremity. A complex history, involving her neck and contralateral upper extremity was assessed. The patient was found to have at least seven underlying, predisposing, and etiological, conditions capable of initiating, aggravating, or maintaining the presenting symptoms. Weighing the relative contributions of these often interacting features, and correlating this with the history, helped to identify a successful course of treatment.

Determination of stress intensity factors for interface cracks under mixed-mode loading

NASA Technical Reports Server (NTRS)

Naik, Rajiv A.; Crews, John H., Jr.

1992-01-01

A simple technique was developed using conventional finite element analysis to determine stress intensity factors, K1 and K2, for interface cracks under mixed-mode loading. This technique involves the calculation of crack tip stresses using non-singular finite elements. These stresses are then combined and used in a linear regression procedure to calculate K1 and K2. The technique was demonstrated by calculating three different bimaterial combinations. For the normal loading case, the K's were within 2.6 percent of an exact solution. The normalized K's under shear loading were shown to be related to the normalized K's under normal loading. Based on these relations, a simple equation was derived for calculating K1 and K2 for mixed-mode loading from knowledge of the K's under normal loading. The equation was verified by computing the K's for a mixed-mode case with equal and normal shear loading. The correlation between exact and finite element solutions is within 3.7 percent. This study provides a simple procedure to compute K2/K1 ratio which has been used to characterize the stress state at the crack tip for various combinations of materials and loadings. Tests conducted over a range of K2/K1 ratios could be used to fully characterize interface fracture toughness.

Cell type-selective disease-association of genes under high regulatory load

PubMed Central

Galhardo, Mafalda; Berninger, Philipp; Nguyen, Thanh-Phuong; Sauter, Thomas; Sinkkonen, Lasse

2015-01-01

We previously showed that disease-linked metabolic genes are often under combinatorial regulation. Using the genome-wide ChIP-Seq binding profiles for 93 transcription factors in nine different cell lines, we show that genes under high regulatory load are significantly enriched for disease-association across cell types. We find that transcription factor load correlates with the enhancer load of the genes and thereby allows the identification of genes under high regulatory load by epigenomic mapping of active enhancers. Identification of the high enhancer load genes across 139 samples from 96 different cell and tissue types reveals a consistent enrichment for disease-associated genes in a cell type-selective manner. The underlying genes are not limited to super-enhancer genes and show several types of disease-association evidence beyond genetic variation (such as biomarkers). Interestingly, the high regulatory load genes are involved in more KEGG pathways than expected by chance, exhibit increased betweenness centrality in the interaction network of liver disease genes, and carry longer 3′ UTRs with more microRNA (miRNA) binding sites than genes on average, suggesting a role as hubs integrating signals within regulatory networks. In summary, epigenetic mapping of active enhancers presents a promising and unbiased approach for identification of novel disease genes in a cell type-selective manner. PMID:26338775

Transcriptome analysis of two recombinant inbred lines of common bean contrasting for symbiotic nitrogen fixation

PubMed Central

Kamfwa, Kelvin; Zhao, Dongyan; Kelly, James D.

2017-01-01

Common bean (Phaseolus vulgaris L.) fixes atmospheric nitrogen (N2) through symbiotic nitrogen fixation (SNF) at levels lower than other grain legume crops. An understanding of the genes and molecular mechanisms underlying SNF will enable more effective strategies for the genetic improvement of SNF traits in common bean. In this study, transcriptome profiling was used to identify genes and molecular mechanisms underlying SNF differences between two common bean recombinant inbred lines that differed in their N-fixing abilities. Differential gene expression and functional enrichment analyses were performed on leaves, nodules and roots of the two lines when grown under N-fixing and non-fixing conditions. Receptor kinases, transmembrane transporters, and transcription factors were among the differentially expressed genes identified under N-fixing conditions, but not under non-fixing conditions. Genes up-regulated in the stronger nitrogen fixer, SA36, included those involved in molecular functions such as purine nucleoside binding, oxidoreductase and transmembrane receptor activities in nodules, and transport activity in roots. Transcription factors identified in this study are candidates for future work aimed at understanding the functional role of these genes in SNF. Information generated in this study will support the development of gene-based markers to accelerate genetic improvement of SNF in common bean. PMID:28192540

AIDS and human sexuality.

PubMed

Smith, L L; Lathrop, L M

1993-01-01

The sexual behaviours placing an individual at risk for HIV infection are those also placing him/her at risk for gonorrhoea, syphilis, hepatitis B, chlamydia and unplanned pregnancy. This article proposes that approaches to HIV prevention must be included within a broad context of human sexuality. To address disease prevention in the absence of including people's relationships, social, behavioural and emotional needs is futile. Compartmentalization, denial of risk by various populations, and societal barriers are all factors to be overcome in the fight against HIV transmission. Specific strategies involved in a comprehensive approach are outlined under the categories of predisposing, enabling and reinforcing factors contributing to healthy sexual behaviour.

Densification and Electrical Properties of Zinc Oxide Varistors Microwave-Sintered Under Different Oxygen Partial Pressures

NASA Astrophysics Data System (ADS)

Lin, Cong; Wang, Bo; Xu, Zheng; Peng, Hu

2012-11-01

ZnO varistors were prepared by microwave sintering under different oxygen partial pressures. The temperature profile and the densification behavior in different atmospheres were investigated. It was found that the density of ZnO varistors during sintering was the key factor affecting the absorption of microwave energy. The electrical properties, including the nonlinear properties and capacitance-voltage ( C- V) characteristics, were also carefully studied. The results showed that the oxygen partial pressure has significant effects on the electrical properties of ZnO varistors by changing the concentration of defects through a series of reactions involving oxygen during sintering.

β-Thalassemia Intermedia: A Clinical Perspective

PubMed Central

Musallam, Khaled M.; Taher, Ali T.; Rachmilewitz, Eliezer A.

2012-01-01

Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with β-thalassemia intermedia has substantially increased over the past decade. Earlier studies observed that patients with β-thalassemia intermedia experience a clinical-complications profile that is different from that in patients with β-thalassemia major. In this article, a variety of clinical morbidities are explored, and their associations with the underlying disease pathophysiology and risk factors are examined. These involve several organs and organ systems including the vasculature, heart, liver, endocrine glands, bone, and the extramedullary hematopoietic system. The effects of some therapeutic interventions on the development of clinical complications are also discussed. PMID:22762026

Mechanisms of Osteoarthritic Pain. Studies in Humans and Experimental Models

PubMed Central

Eitner, Annett; Hofmann, Gunther O.; Schaible, Hans-Georg

2017-01-01

Pain due to osteoarthritis (OA) is one of the most frequent causes of chronic pain. However, the mechanisms of OA pain are poorly understood. This review addresses the mechanisms which are thought to be involved in OA pain, derived from studies on pain mechanisms in humans and in experimental models of OA. Three areas will be considered, namely local processes in the joint associated with OA pain, neuronal mechanisms involved in OA pain, and general factors which influence OA pain. Except the cartilage all structures of the joints are innervated by nociceptors. Although the hallmark of OA is the degradation of the cartilage, OA joints show multiple structural alterations of cartilage, bone and synovial tissue. In particular synovitis and bone marrow lesions have been proposed to determine OA pain whereas the contribution of the other pathologies to pain generation has been studied less. Concerning the peripheral neuronal mechanisms of OA pain, peripheral nociceptive sensitization was shown, and neuropathic mechanisms may be involved at some stages. Structural changes of joint innervation such as local loss and/or sprouting of nerve fibers were shown. In addition, central sensitization, reduction of descending inhibition, descending excitation and cortical atrophies were observed in OA. The combination of different neuronal mechanisms may define the particular pain phenotype in an OA patient. Among mediators involved in OA pain, nerve growth factor (NGF) is in the focus because antibodies against NGF significantly reduce OA pain. Several studies show that neutralization of interleukin-1β and TNF may reduce OA pain. Many patients with OA exhibit comorbidities such as obesity, low grade systemic inflammation and diabetes mellitus. These comorbidities can significantly influence the course of OA, and pain research just began to study the significance of such factors in pain generation. In addition, psychologic and socioeconomic factors may aggravate OA pain, and in some cases genetic factors influencing OA pain were found. Considering the local factors in the joint, the neuronal processes and the comorbidities, a better definition of OA pain phenotypes may become possible. Studies are under way in order to improve OA and OA pain monitoring. PMID:29163027

Genetic basis of hybrid male sterility among three closely related species of Drosophila.

PubMed

Mishra, Paras Kumar; Singh, B N

2005-05-01

The genetic basis of hybrid male sterility among three closely related species, Drosophila bipectinata, D. parabipectinata and D. malerkotliana has been investigated by using backcross analysis methods. The role of Y chromosome, major hybrid sterility (MHS) genes (genetic factors) and cytoplasm (non-genetic factor) have been studied in the hybrids of these three species. In the species pair, bipectinata--parabipectinata, Y chromosome introgression of parabipectinata in the genomic background of bipectinata and the reciprocal Y chromosome introgression were unsuccessful as all males in second backcross generation were sterile. Neither MHS genes nor cytoplasm was found important for sterility. This suggests the involvement of X-Y, X-autosomes or polygenic interactions in hybrid male sterility. In bipectinata--malerkotliana and parabipectinata--malerkotliana species pairs, Y chromosome substitution in reciprocal crosses did not affect male fertility. Backcross analyses also show no involvement of MHS genes or cytoplasm in hybrid male sterility in these two species pairs. Therefore, X- autosome interaction or polygenic interaction is supposed to be involved in hybrid male sterility in these two species pairs. These findings also provide evidence that even in closely related species, genetic interactions underlying hybrid male sterility may vary.

Stress, Depression, Resilience and Ageing: A Role for the LPA-LPA1 Pathway.

PubMed

Moreno-Fernandez, Roman Dario; Tabbai, Sara; Castilla-Ortega, Estela; Perez-Martin, Margarita; Estivill-Torrus, Guillermo; Rodriguez de Fonseca, Fernando; Santin, Luis Javier; Pedraza, Carmen

2018-03-05

Chronic stress affects health and the quality of life, with its effects being particularly relevant in ageing due to the psychobiological characteristics of this population. However, while some people develop psychiatric disorders, especially depression, others seem very capable of dealing with adversity. There is no doubt that along with the identification of neurobiological mechanisms involved in developing depression, discovering which factors are involved in positive adaptation under circumstances of extreme difficulty will be crucial for promoting resilience. Here, we review recent work in our laboratory, using an animal model lacking the LPA1 receptor, together with pharmacological studies and clinical evidence for the possible participation of the LPA1 receptor in mood and resilience to stress. Substantial evidence has shown that the LPA1 receptor is involved in emotional regulation and in coping responses to chronic stress, which, if dysfunctional, may induce vulnerability to stress and predisposition to the development of depression. Given that there is commonality of mechanisms between those involved in negative consequences of stress and in ageing, this is not surprising, considering that the LPA1 receptor may be involved in coping with adversity during ageing. Alterations in this receptor may be a susceptibility factor for the presence of depression and cognitive deficits in the elderly population. However, because this is only a promising hypothesis based on previous data, future studies should focus on the involvement of the LPA-LPA1 pathway in coping with stress and resilience in ageing. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Social and cultural barriers to husbands' involvement in maternal health in rural Gambia.

PubMed

Lowe, Mat

2017-01-01

While many studies have documented a number of socio-cultural barriers to male involvement in maternal health, in The Gambia very little information is known about the social and cultural practices that characterized male involvement in maternal health. This study aims to explore some of the underlying social and cultural factors affecting husbands' involvement in maternal health issues pertaining to pregnancy and delivery in rural Gambia. Five focus group discussions and six in-depth interviews were conducted among rural men and traditional birth attendants in five areas of rural Gambia. The discussion was directed to the roles of male partners in pregnancy and delivery and the difficulties they face regarding taking care of their wives. The data resulting from the discussion was audio-recorded, transcribed verbatim, and analyzed thematically. In general, rural Gambian men and traditional birth attendants (TBAs) reported that husbands' involvement in maternal health is highly desirable, but is influenced by many factors, such as the traditional conceptualization associated with pregnancy and delivery as women's domain. In addition, many men do not believe that pregnancy chores warrant their efforts compared to other competing social responsibilities. This issue may be more complicated in polygamous marriages where there is rivalry among co-wives and in neighborhoods where men who help with house chores may be subjected to mockery. These findings suggest that husbands' involvement in maternal health in The Gambia is influenced by the prevailing social and cultural practices of gender role and norms, which are also at the root of maternal health problems.

Establishing the role of rare coding variants in known Parkinson's disease risk loci.

PubMed

Jansen, Iris E; Gibbs, J Raphael; Nalls, Mike A; Price, T Ryan; Lubbe, Steven; van Rooij, Jeroen; Uitterlinden, André G; Kraaij, Robert; Williams, Nigel M; Brice, Alexis; Hardy, John; Wood, Nicholas W; Morris, Huw R; Gasser, Thomas; Singleton, Andrew B; Heutink, Peter; Sharma, Manu

2017-11-01

Many common genetic factors have been identified to contribute to Parkinson's disease (PD) susceptibility, improving our understanding of the related underlying biological mechanisms. The involvement of rarer variants in these loci has been poorly studied. Using International Parkinson's Disease Genomics Consortium data sets, we performed a comprehensive study to determine the impact of rare variants in 23 previously published genome-wide association studies (GWAS) loci in PD. We applied Prix fixe to select the putative causal genes underneath the GWAS peaks, which was based on underlying functional similarities. The Sequence Kernel Association Test was used to analyze the joint effect of rare, common, or both types of variants on PD susceptibility. All genes were tested simultaneously as a gene set and each gene individually. We observed a moderate association of common variants, confirming the involvement of the known PD risk loci within our genetic data sets. Focusing on rare variants, we identified additional association signals for LRRK2, STBD1, and SPATA19. Our study suggests an involvement of rare variants within several putatively causal genes underneath previously identified PD GWAS peaks. Copyright © 2017 Elsevier Inc. All rights reserved.

An Exploration of Dual Systems via Time Pressure Manipulation in Decision-making Problems

NASA Astrophysics Data System (ADS)

Guo, Lisa

Every day, decisions need to be made where time is a limiting factor. Regardless of situation, time constraints often place a premium on rapid decision-making. Researchers have been interested in studying this human behavior and understanding its underlying cognitive processes. In previous studies, scientists have believed that the cognitive processes underlying decision-making behavior were consistent with dual-process modes of thinking. Critics of dual-process theory question the vagueness of its definition, and claim that single-process accounts can explain the data just as well. My aim is to elucidate the cognitive processes that underlie decisions which involve some level of risk through the experimental manipulation of time pressure. Using this method, I hope to distinguish between competing hypotheses related to the origin of the effect. I will explore three types of decisions that illustrate these concepts: risky decision-making involving gambles, intertemporal choice, and one-shot public goods games involving social cooperation. In our experiments, participants made decisions about gambles framed as either gains or losses; decided upon intertemporal choices for smaller but sooner rewards or larger but later rewards; and played a one-shot public goods game involving social cooperation and contributing an amount of money to a group. In each case, we experimentally manipulated time pressure, either within subjects or among individuals. Results showed under time pressure, increased framing effects under in both hypothetical and incentivized choices; and greater contributions and cooperation among individuals, lending support to the dual process hypothesis that these effects arise from a fast, intuitive system. However, our intertemporal choice experiment showed that time constraints led to increased selection of the larger but later options, which suggests that the magnitude of the reward may play larger role in choice selection under cognitive load than previously studied. This diverges from the current dual-process interpretation that myopic choices under time pressure favor smaller but sooner rewards, and suggests that more studies are needed in this realm to disentangle the intuitive from the deliberative system through the manipulation of cognitive load.

"It's overwhelming... everything seems to be too much:" A theory of crisis for individuals with severe persistent mental illness.

PubMed

Ball, Jeffrey S; Links, Paul S; Strike, Carol; Boydell, Katherine M

2005-01-01

Crisis in individuals with severe persistent mental illness (SPMI) is a poorly understood phenomenon for which traditional crisis models do not apply. In this study we explored the crisis experience using in-depth interviews conducted with individuals with severe persistent mental illness from two community support programs. A grounded theory of the crisis experience was developed and the results illustrate that underlying vulnerability sets the stage for crisis occurrence which involves feeling overwhelmed and lacking control and manifests as agitation/anger/aggression, being low, feeling anxious, or euphoria. Immediate responses to crises involve getting help or managing alone and numerous factors contribute to crisis resolution and prevention.

[Initial subretinal localization of acute myeloblastic leukemia (AML5) recurrence].

PubMed

Le Gall, S; François, S; Urier, N; Genevieve, F; d'Hermies, F; Rachieru, P; Ifrah, N

2001-10-13

Reduced visual acuity in patients with acute leucemia can result from many causes including an ocular localization. A patient previously treated for acute myeloblastic leucemia-5 (AML5) developed bilateral vision impairment related to a subretinal localization of the leucemia. Meningeal and bone marrow relapse followed. The subretinal localization responded only to massive systemic steroid treatment. Although asymptomatic, ocular localizations are frequent in leucemia. Their prognostic impact depends on the ocular structure involved and on the chronology of onset--early or late in the leucemia course. The underlying pathophysiological mechanism of ocular involvement remains unexplained but hyperleucocytosis at presentation may be a risk factor and would justify at least systematic specialized examinations and discussion of prophylactic treatment.

Isolation of Signaling Molecules Involved in Angiogenic Pathways Mediated Alpha v Integrins

DTIC Science & Technology

2004-05-01

67 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19. SECURITY CLASSIFICATION 20. UMITATION OF ABSTRACT OF REPORT OF THIS PAGE... comparison to the controls (Figure 7C). Penetratin or the VVISYSMPD peptide alone were used as negative controls and had no effect under identical...A., O’Connor, W., King , K., Overholser, J., Hooper, A., Pytowski, B., Witte, L. et al., 1999. Antivascular endothelial growth factor receptor (fetal

The Impact of Special Education Litigation upon the Key Factors of Job Satisfaction, Level of Stress, and Self-Esteem That Lead to Teacher Attrition and Retention

ERIC Educational Resources Information Center

DeSio, Mary Jo Ann

2011-01-01

This research study reveals the stories of 19 special educators who participated in, or were summoned to testify, in one of the forms of special education litigation in the state of California. For most participants, their involvement was in a due process hearing conducted by the Office of Administrative Hearings under contract with the California…

The Hispanic Stress Inventory--Adolescent Version: a culturally informed psychosocial assessment.

PubMed

Cervantes, Richard C; Fisher, Dennis G; Córdova, David; Napper, Lucy E

2012-03-01

A 2-phase study was conducted to develop a culturally informed measure of psychosocial stress for adolescents: the Hispanic Stress Inventory--Adolescent Version (HSI-A). Phase 1 involved item development through the collection of open-ended focus group interview data (n = 170) from a heterogeneous sample of Hispanic youths residing in the southwest and northeast United States. In Phase 2, we examined the psychometric properties of the HSI-A (n = 1,651), which involved the use of factor analytic procedures to determine the underlying scale structure of the HSI-A for foreign-born and U.S.-born participants in an aggregated analytic approach. An 8-factor solution was established, with factors that include Family Economic Stress, Acculturation-Gap Stress, Culture and Educational Stress, Immigration-Related Stress, Discrimination Stress, Family Immigration Stress, Community and Gang-Related Stress, and Family and Drug-Related Stress. Concurrent, related validity estimates were calculated to determine relations between HSI-A and other measures of child psychopathology and behavioral and emotional disturbances. HSI-A total stress appraisal scores were significantly correlated with both the Children's Depression Inventory and the Youth Self Report (p < .001). Reliability estimates for the HSI-A were conducted, and they yielded high reliability coefficients for most factor subscales, with the HSI-A total stress appraisal score reliability alpha at .92.

The Hispanic Stress Inventory-Adolescent Version: A Culturally Informed Psychosocial Assessment

PubMed Central

Cervantes, Richard C.; Fisher, Dennis G.; Córdova, David; Napper, Lucy

2012-01-01

A 2-phase study was conducted to develop a culturally informed measure of psychosocial stress for adolescents, the Hispanic Stress Inventory-Adolescent Version (HSI-A). Phase I involved item development through the collection of open-ended focus group interview data (n=170) from a heterogeneous sample of Hispanic youth residing in the southwest and northeast United States. Phase 2 examined the psychometric properties of the HSI-A (n=1651) involving the use of factor analytic procedures to determine the underlying scale structure of the HSI-A, for foreign-born and U.S.-born participants in an aggregated analytic approach. An eight factor solution was established with factors that include Family Economic Stress, Acculturation Gaps Stress, Culture and Educational Stress, Immigration Related Stress, Discrimination Stress, Family Immigration Stress, Community and Gang Violence Stress and Family Drug Related Stress. Concurrent related validity estimates were calculated to determine relationships between HSI-A and other measures of child psychopathology, behavioral and emotional disturbances. HSI-A Total Stress Appraisal Scores were significantly correlated with both the CDI and YSR (p<.001 respectively). Reliability estimates for the HSI-A were conducted and yielded high reliability coefficients for most all factor sub-scales with HSI-A Total Stress Appraisal score reliability at alpha=.92. PMID:21942232

The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications

PubMed Central

Ayerst, Bethanie I.; Merry, Catherine L.R.; Day, Anthony J.

2017-01-01

High sulfation, low cost, and the status of heparin as an already FDA- and EMA- approved product, mean that its inclusion in tissue engineering (TE) strategies is becoming increasingly popular. However, the use of heparin may represent a naïve approach. This is because tissue formation is a highly orchestrated process, involving the temporal expression of numerous growth factors and complex signaling networks. While heparin may enhance the retention and activity of certain growth factors under particular conditions, its binding ‘promiscuity’ means that it may also inhibit other factors that, for example, play an important role in tissue maintenance and repair. Within this review we focus on articular cartilage, highlighting the complexities and highly regulated processes that are involved in its formation, and the challenges that exist in trying to effectively engineer this tissue. Here we discuss the opportunities that glycosaminoglycans (GAGs) may provide in advancing this important area of regenerative medicine, placing emphasis on the need to move away from the common use of heparin, and instead focus research towards the utility of specific GAG preparations that are able to modulate the activity of growth factors in a more controlled and defined manner, with less off-target effects. PMID:28608822

Factors associated with high-rise evacuation: qualitative results from the World Trade Center Evacuation Study.

PubMed

Gershon, Robyn R M; Qureshi, Kristine A; Rubin, Marcie S; Raveis, Victoria H

2007-01-01

Due to the fact that most high-rise structures (i.e., >75 feet high, or eight to ten stories) are constructed with extensive and redundant fire safety features, current fire safety procedures typically only involve limited evacuation during minor to moderate fire emergencies. Therefore, full-scale evacuation of high-rise buildings is highly unusual and consequently, little is known about how readily and rapidly high-rise structures can be evacuated fully. Factors that either facilitate or inhibit the evacuation process remain under-studied. This paper presents results from the qualitative phase of the World Trade Center Evacuation Study, a three-year, five-phase study designed to improve our understanding of the individual, organizational, and environmental factors that helped or hindered evacuation from the World Trade Center (WTC) Towers 1 and 2, on 11 September 2001. Qualitative data from semi-structured, in-depth interviews and focus groups involving WTC evacuees were collected and analyzed. On the individual level, factors that affected evacuation included perception of risk (formed largely by sensory cues), preparedness training, degree of familiarity with the building, physical condition, health status, and footwear. Individual behavior also was affected by group behavior and leadership. At the organizational level, evacuation was affected by worksite preparedness planning, including the training and education of building occupants, and risk communication. The environmental conditions affecting evacuation included smoke, flames, debris, general condition and degree of crowdedness on staircases, and communication infrastructure systems (e.g., public address, landline, cellular and fire warden's telephones). Various factors at the individual, organizational, and environmental levels were identified that affected evacuation. Interventions that address the barriers to evacuation may improve the full-scale evacuation of other high-rise buildings under extreme conditions. Further studies should focus on the development and evaluation of targeted interventions, including model emergency preparedness planning for high-rise occupancies.

Genetic and neurodevelopmental influences in autistic disorder.

PubMed

Nicolson, Rob; Szatmari, Peter

2003-09-01

In the past, autism was considered to be largely psychogenic. However, research in the last 2 decades indicates that autism is largely caused by genetic factors that lead to abnormal brain development. This article reviews research into the genetic and neurodevelopmental factors underlying autism. We review the findings from genetic and brain-imaging studies of autism over the past 15 years and synthesize these findings as a guide for future research. Genome scans and association studies have suggested potential genomic regions and genes, respectively, that may be involved in the etiology of autism, and there have been some replications of these results. Similarly, the findings that brain volume is exaggerated in autism and corpus callosum size is reduced have also been independently replicated. Unfortunately, studies of other subcortical structures remain inconclusive or contradictory. Overwhelming evidence now supports a neurobiological basis for autism. However, further refinements will be needed to guide future studies, particularly to identify the most informative phenotypes to investigate. Additionally, studies examining the role of genetic factors in the brain abnormalities underlying autism will likely lead to further findings that will enhance our understanding of autism's causes.

Factors influencing evidence-based practice in prosthetics and orthotics.

PubMed

Andrysek, Jan; Christensen, James; Dupuis, Annie

2011-03-01

The importance of evidence-based practice is being recognized across a broad range of healthcare disciplines as a means for improving patient outcomes and also efficiently managing healthcare resources. The objective of this work was to obtain information from clinicians about the underlying barriers and facilitators relating to evidence-based practice in prosthetics and orthotics. Cross sectional survey. An internet survey was developed and distributed to 300 prosthetists and orthotists currently practicing in Canada. A principal component factor analysis of the survey results revealed ten primary factors affecting evidence-based practice. These include time constraints, workload and system demands, limited relevant evidence from research, and gaps in skills and knowledge required to perform evidence-based practice. Clinicians value research as a means of improving clinical practice, but they are faced with a number of practical barriers in performing evidence-based practice. This study provides empirical data about the underlying barriers and facilitators relating to evidence-based practice in prosthetics and orthotics. Such data are essential in order to inform those involved in improving existing clinical practices, including educators, professional organizations, and governing bodies.

Who Shot Ya? How Emergency Departments Can Collect Reliable Police Shooting Data.

PubMed

Richardson, Joseph B; St Vil, Christopher; Cooper, Carnell

2016-04-01

This paper examines an alternative solution for collecting reliable police shooting data. One alternative is the collection of police shooting data from hospital trauma units, specifically hospital-based violence intervention programs. These programs are situated in Level I trauma units in many major cities in USA. While the intent of these programs is to reduce the risk factors associated with trauma recidivism among victims of violent injury, they also collect reliable data on the number of individuals treated for gunshot wounds. While most trauma units do a great job collecting data on mode of injury, many do not collect data on the circumstances surrounding the injury, particularly police-involved shootings. Research protocol on firearm-related injury conducted in emergency departments typically does not allow researchers to interview victims of violent injury who are under arrest. Most victims of nonfatal police-involved shootings are under arrest at the time they are treated by the ED for their injury. Research protocol on victims of violent injury often excludes individuals under arrest; they fall under the exclusion criteria when recruiting potential participants for research on violence. Researchers working in hospital emergency departments are prohibited from recruited individuals under arrests. The trauma staff, particularly ED physicians and nurses, are in a strategic position to collect this kind of data. Thus, this paper examines how trauma units can serve as an alternative in the reliable collection of police shooting data.

pH-Signaling Transcription Factor AopacC Regulates Ochratoxin A Biosynthesis in Aspergillus ochraceus.

PubMed

Wang, Yan; Liu, Fei; Wang, Liuqing; Wang, Qi; Selvaraj, Jonathan Nimal; Zhao, Yueju; Wang, Yun; Xing, Fuguo; Liu, Yang

2018-05-02

In Aspergillus and Penicillium species, an essential pH-response transcription factor pacC is involved in growth, pathogenicity, and toxigenicity. To investigate the connection between ochratoxin A (OTA) biosynthesis and ambient pH, the AopacC in Aspergillus ochraceus was functionally characterized using a loss-of-function mutant. The mycelium growth was inhibited under pH 4.5 and 10.0, while the sporulation increased under alkaline condition. A reduction of mycelium growth and an elevation of sporulation was observed in Δ AopacC mutant. Compared to neutral condition, OTA contents were respectively reduced by 71.6 and 79.8% under acidic and alkaline conditions. The expression of AopacC increased with the elevated pH, and deleting AopacC dramatically decreased OTA production and biosynthetic genes Aopks expression. Additionally, the Δ AopacC mutant exhibited attenuated infection ability toward pear fruits. These results suggest that AopacC is an alkaline-induced regulator responsible for growth and OTA biosynthesis in A. ochraceus and this regulatory mechanism might be pH-dependent.

Astrocyte transforming growth factor beta 1 promotes inhibitory synapse formation via CaM kinase II signaling.

PubMed

Diniz, Luan Pereira; Tortelli, Vanessa; Garcia, Matheus Nunes; Araújo, Ana Paula Bérgamo; Melo, Helen M; Silva, Gisele S Seixas da; Felice, Fernanda G De; Alves-Leon, Soniza Vieira; Souza, Jorge Marcondes de; Romão, Luciana Ferreira; Castro, Newton Gonçalves; Gomes, Flávia Carvalho Alcantara

2014-12-01

The balance between excitatory and inhibitory synaptic inputs is critical for the control of brain function. Astrocytes play important role in the development and maintenance of neuronal circuitry. Whereas astrocytes-derived molecules involved in excitatory synapses are recognized, molecules and molecular mechanisms underlying astrocyte-induced inhibitory synapses remain unknown. Here, we identified transforming growth factor beta 1 (TGF-β1), derived from human and murine astrocytes, as regulator of inhibitory synapse in vitro and in vivo. Conditioned media derived from human and murine astrocytes induce inhibitory synapse formation in cerebral cortex neurons, an event inhibited by pharmacologic and genetic manipulation of the TGF-β pathway. TGF-β1-induction of inhibitory synapse depends on glutamatergic activity and activation of CaM kinase II, which thus induces localization and cluster formation of the synaptic adhesion protein, Neuroligin 2, in inhibitory postsynaptic terminals. Additionally, intraventricular injection of TGF-β1 enhanced inhibitory synapse number in the cerebral cortex. Our results identify TGF-β1/CaMKII pathway as a novel molecular mechanism underlying astrocyte control of inhibitory synapse formation. We propose here that the balance between excitatory and inhibitory inputs might be provided by astrocyte signals, at least partly achieved via TGF-β1 downstream pathways. Our work contributes to the understanding of the GABAergic synapse formation and may be of relevance to further the current knowledge on the mechanisms underlying the development of various neurological disorders, which commonly involve impairment of inhibitory synapse transmission. © 2014 Wiley Periodicals, Inc.

Managerial and environmental factors in the continuity of mental health care across institutions.

PubMed

Greenberg, Greg A; Rosenheck, Robert A

2003-04-01

The authors examined the association of continuity of care with factors assumed to be under the control of health care administrators and environmental factors not under managerial control. The authors used a facility-level administrative data set for 139 Department of Veterans Affairs medical centers over a six-year period and supplemental data on environmental factors to conduct two types of analysis. First, simple correlations were used to examine bivariate associations between eight continuity-of-care measures and nine measures of the institutional environment and the social context. Second, to control for potential autocorrelation, multivariate hierarchical linear models with all nine independent measures were created. The strongest predictors of continuity of care were per capita outpatient expenditure and the degree of emphasis on outpatient care as measured by the percentage of all mental health expenditures devoted to outpatient care. The former was significantly associated with greater continuity of care on six of eight measures and the latter on seven of eight measures. The environmental factor of social capital (the degree of civic involvement and trust at the state level) was associated with greater continuity of care on five measures. The degree to which non-VA mental health services were funded in a state was unexpectedly found to be positively associated with greater continuity of care. In multivariate analysis using hierarchical linear modeling, significant relationships with continuity of care remained for per capita outpatient expenditures, overall outpatient emphasis, and social capital, but not for non-VA mental health funding. A linear term representing the year was positively and significantly associated with six of the eight examined continuity-of-care measures, indicating improvement in continuity of care for the period under study, although the explanation for this trend over time is unclear. Several factors potentially under managerial control are associated with increased mental health continuity of care.

Alginate Sulfates Mitigate Binding Kinetics of Proangiogenic Growth Factors with Receptors toward Revascularization.

PubMed

Schmidt, John; Lee, Min Kyung; Ko, Eunkyung; Jeong, Jae Hyun; DiPietro, Luisa A; Kong, Hyunjoon

2016-07-05

Ever since proangiogenic growth factors have been used as a vascular medicine to treat tissue ischemia, efforts have been increasingly made to develop a method to enhance efficacy of growth factors in recreating microvascular networks, especially at low dose. To this end, we hypothesized that polysaccharides substituted with sulfate groups would amplify growth factor receptor activation and stimulate phenotypic activities of endothelial cells involved in neovascularization. We examined this hypothesis by modifying alginate with a controlled number of sulfates and using it to derive a complex with vascular endothelial growth factor (VEGF), as confirmed with fluorescence resonance energy transfer (FRET) assay. Compared with the bare VEGF and with a mixture of VEGF and unmodified alginates, the VEGF complexed with alginate sulfates significantly reduced the dissociation rate with the VEGFR-2, elevated VEGFR-2 phosphorylation level, and increased the number of endothelial sprouts in vitro. Furthermore, the VEGF-alginate sulfate complex improved recovery of perfusion in an ischemic hindlimb of a mouse due to the increase of the capillary density. Overall, this study not only demonstrates an important cofactor of VEGF but also uncovers an underlying mechanism by which the cofactor mitigates the VEGF-induced signaling involved in the binding kinetics and activation of VEGFR. We therefore believe that the results of this study will be highly useful in improving the therapeutic efficacy of various growth factors and expediting their uses in clinical treatments of wounds and tissue defects.

Persisting mild hypothermia suppresses hypoxia-inducible factor-1alpha protein synthesis and hypoxia-inducible factor-1-mediated gene expression.

PubMed

Tanaka, Tomoharu; Wakamatsu, Takuhiko; Daijo, Hiroki; Oda, Seiko; Kai, Shinichi; Adachi, Takehiko; Kizaka-Kondoh, Shinae; Fukuda, Kazuhiko; Hirota, Kiichi

2010-03-01

The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses at different organizational levels in the body, little is known about how hypoxia-induced responses are affected by low temperature. We examined the influence of mild hypothermic conditions (28-32 degrees C) on HIF-1 in both in vitro and in vivo settings. In vitro experiments adopting cultured cells elucidated that hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low temperature. In contrast, exposure to the low temperature as long as 24 h suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes such as VEGF or GLUT-1. HIF-1alpha protein stability in the cell was not affected by hypothermic treatment. Furthermore, intracellular ATP content was reduced under 1% O(2) conditions but was not largely affected by hypothermic treatment. The evidence indicates that reduction of oxygen consumption is not largely involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA-binding activity and HIF-1-dependent gene expressions induced under 10% O(2) atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic temperature but were inhibited under 5-h treatment. On the other hand, we indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity. In this report we describe for the first time that persisting low temperature significantly reduced HIF-1alpha neosynthesis under hypoxic conditions, leading to a decrease in gene expression for adaptation to hypoxia in both in vitro and in vivo settings.

Factors associated with single-vehicle and multi-vehicle road traffic collision injuries in Ireland.

PubMed

Donnelly-Swift, Erica; Kelly, Alan

2016-12-01

Generalised linear regression models were used to identify factors associated with fatal/serious road traffic collision injuries for single- and multi-vehicle collisions. Single-vehicle collisions and multi-vehicle collisions occurring during the hours of darkness or on a wet road surface had reduced likelihood of a fatal/serious injury. Single-vehicle 'driver with passengers' collisions occurring at junctions or on a hill/gradient were less likely to result in a fatal/serious injury. Multi-vehicle rear-end/angle collisions had reduced likelihood of a fatal/serious injury. Single-vehicle 'driver only' collisions and multi-vehicle collisions occurring on a public/bank holiday or on a hill/gradient were more likely to result in a fatal/serious injury. Single-vehicle collisions involving male drivers had increased likelihood of a fatal/serious injury and single-vehicle 'driver with passengers' collisions involving drivers under the age of 25 years also had increased likelihood of a fatal/serious injury. Findings can enlighten decision-makers to circumstances leading to fatal/serious injuries.

Involvement of Fibroblast Growth Factors and Their Receptors in Epididymo-Testicular Descent and Maldescent

PubMed Central

Hadziselimovic, Faruk

2016-01-01

Maldescent of the epididymo-testicular unit can occur as an isolated event or as a component of various syndromes. When part of a syndrome, crypto-epididymis is usually accompanied by other genital and/or extragenital features. Epididymis development is primarily regulated by androgens, and successful epididymo-testicular unit development and descent requires an intact hypothalamic-pituitary-gonadal axis. The developing gonadotropin-releasing hormone system is essential for epididymo-testicular descent and is highly sensitive to reduced fibroblast growth factor (FGF) signaling. Our understanding of the impact of FGFR1 in the process of epididymo-testicular descent has recently improved. At later stages of embryonic development, the undifferentiated epididymal mesenchyme is a specific domain for FGFR1 expression. The majority of individuals with syndromic crypto-epididymis, as well as individuals with isolated maldescent of the epididymo-testicular unit, exhibit some disturbance of FGF, FGFR1 and/or genes involved in hypothalamic-pituitary-gonadal axis regulation. However, the mechanisms underlying FGF dysregulation may differ between various syndromes. PMID:27022326

Involvement of Fibroblast Growth Factors and Their Receptors in Epididymo-Testicular Descent and Maldescent.

PubMed

Hadziselimovic, Faruk

2016-02-01

Maldescent of the epididymo-testicular unit can occur as an isolated event or as a component of various syndromes. When part of a syndrome, crypto-epididymis is usually accompanied by other genital and/or extragenital features. Epididymis development is primarily regulated by androgens, and successful epididymo-testicular unit development and descent requires an intact hypothalamic-pituitary-gonadal axis. The developing gonadotropin-releasing hormone system is essential for epididymo-testicular descent and is highly sensitive to reduced fibroblast growth factor (FGF) signaling. Our understanding of the impact of FGFR1 in the process of epididymo-testicular descent has recently improved. At later stages of embryonic development, the undifferentiated epididymal mesenchyme is a specific domain for FGFR1 expression. The majority of individuals with syndromic crypto-epididymis, as well as individuals with isolated maldescent of the epididymo-testicular unit, exhibit some disturbance of FGF, FGFR1 and/or genes involved in hypothalamic-pituitary-gonadal axis regulation. However, the mechanisms underlying FGF dysregulation may differ between various syndromes.

Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico.

PubMed

Larsen, Christopher P; Beggs, Marjorie L; Wilson, Jon D; Lathrop, Sarah L

2016-06-01

Leukocyte chemotactic factor 2 (LECT2) amyloidosis is one of the most recently described types of amyloidosis. Since its description, it has been found to be one the most common types of amyloidosis in large series of amyloid cases involving the kidney and liver in the United States, where it primarily affects patients of Hispanic ethnicity. We sought to investigate the prevalence of this disease among Hispanic adult decedents who had an autopsy performed at the New Mexico Office of the Medical Investigator and determine the organ distribution of amyloid deposition. LECT2 amyloid deposits were identified within the kidney in 3.1% of Hispanic decedents. It was consistently deposited in the liver, spleen, adrenals, and lungs but did not involve the myocardium or brain. LECT2 amyloidosis is likely not rare among Hispanics in the Southwest United States and could represent an important but under-recognized etiology of chronic kidney disease in this population.

A Mangifera indica L. extract could be used to treat neuropathic pain and implication of mangiferin.

PubMed

Garrido-Suárez, Bárbara B; Garrido, Gabino; Delgado, Rene; Bosch, Fe; del C Rabí, María

2010-12-09

It has been accepted that neuroinflammation, oxidative stress and glial activation are involved in the central sensitization underlying neuropathic pain. Vimang is an aqueous extract of Mangifera indica L. traditionally used in Cuba for its analgesic, anti-inflammatory, antioxidant and immunomodulatory properties. Several formulations are available, and also for mangiferin, its major component. Preclinical studies demonstrated that these products prevented tumor necrosis factor α -induced IκB degradation and the binding of nuclear factor κB to DNA, which induces the transcription of genes implicated in the expression of some mediators and enzymes involved in inflammation, pain, oxidative stress and synaptic plasticity. In this paper we propose its potential utility in the neuropathic pain treatment. This hypothesis is supported in the cumulus of preclinical and clinical evidence around the extract and mangiferin, its major component, and speculates about the possible mechanism of action according to recent advances in the physiopathology of neuropathic pain.

Bioinformatics Identification of Modules of Transcription Factor Binding Sites in Alzheimer's Disease-Related Genes by In Silico Promoter Analysis and Microarrays

PubMed Central

Augustin, Regina; Lichtenthaler, Stefan F.; Greeff, Michael; Hansen, Jens; Wurst, Wolfgang; Trümbach, Dietrich

2011-01-01

The molecular mechanisms and genetic risk factors underlying Alzheimer's disease (AD) pathogenesis are only partly understood. To identify new factors, which may contribute to AD, different approaches are taken including proteomics, genetics, and functional genomics. Here, we used a bioinformatics approach and found that distinct AD-related genes share modules of transcription factor binding sites, suggesting a transcriptional coregulation. To detect additional coregulated genes, which may potentially contribute to AD, we established a new bioinformatics workflow with known multivariate methods like support vector machines, biclustering, and predicted transcription factor binding site modules by using in silico analysis and over 400 expression arrays from human and mouse. Two significant modules are composed of three transcription factor families: CTCF, SP1F, and EGRF/ZBPF, which are conserved between human and mouse APP promoter sequences. The specific combination of in silico promoter and multivariate analysis can identify regulation mechanisms of genes involved in multifactorial diseases. PMID:21559189

Protective upregulation of activating transcription factor-3 against glutamate neurotoxicity in neuronal cells under ischemia.

PubMed

Takarada, Takeshi; Kou, Miki; Hida, Miho; Fukumori, Ryo; Nakamura, Saki; Kutsukake, Takaya; Kuramoto, Nobuyuki; Hinoi, Eiichi; Yoneda, Yukio

2016-05-01

This study evaluates the pathological role of the stress sensor activating transcription factor-3 (ATF3) in ischemic neurotoxicity. Upregulation of the transcript and protein for ATF3 was seen 2-10 hr after reperfusion in the ipsilateral cerebral hemisphere of mice with transient middle cerebral artery occlusion for 2 hr. Immunohistochemical analysis confirmed the expression of ATF3 by cells immunoreactive for a neuronal marker in neocortex, hippocampus, and striatum within 2 hr after reperfusion. In murine neocortical neurons previously cultured under ischemic conditions for 2 hr, transient upregulation of both Atf3 and ATF3 expression was similarly found during subsequent culture for 2-24 hr under normoxia. Lentiviral overexpression of ATF3 ameliorated the neurotoxicity of glutamate (Glu) in cultured murine neurons along with a slight but statistically significant inhibition of both Fluo-3 and rhodamine-2 fluorescence increases by N-methyl-D-aspartate. Similarly, transient upregulation was seen in Atf3 and ATF3 expression during the culture for 48 hr in neuronal Neuro2A cells previously cultured under ischemic conditions for 2 hr. Luciferase reporter analysis with ATF3 promoter together with immunoblotting revealed the possible involvement of several transcription factors responsive to extracellular and intracellular stressors in the transactivation of the Atf3 gene in Neuro2A cells. ATF3 could be upregulated to play a role in mechanisms underlying mitigation of the neurotoxicity mediated by the endogenous neurotoxin Glu at an early stage after ischemic signal inputs. © 2016 Wiley Periodicals, Inc.

The sleepy adolescent: causes and consequences of sleepiness in teens.

PubMed

Moore, Melisa; Meltzer, Lisa J

2008-06-01

The majority of adolescents do not obtain the recommended amount of sleep, resulting in significant daytime sleepiness. For most adolescents, insufficient sleep results from the interaction between intrinsic factors such as puberty and extrinsic factors such as school start times. Insufficient sleep and sleepiness impact all areas of adolescent functioning, including academic, psychological and behavioural, which underscores the importance of evaluating sleepy adolescents. While polysomnography is required for the diagnosis of certain sleep disorders, causes of sleepiness are generally best identified with a detailed sleep history and daily sleep diary. The management of sleep problems in adolescents involves treating any underlying sleep disorders, increasing total sleep time and improving other environmental factors that impact sleep. Recognition and management of insufficient sleep and sleepiness is important for the health and functioning of adolescents.

Hypoxia enhances the protective effects of placenta-derived mesenchymal stem cells against scar formation through hypoxia-inducible factor-1α.

PubMed

Du, Lili; Lv, Runxiao; Yang, Xiaoyi; Cheng, Shaohang; Xu, Jing; Ma, Tingxian

2016-06-01

To explore the effect of placenta-derived mesenchymal stem cells on scar formation as well as the underlying mechanism. The isolated placenta-derived mesenchymal stem cells from mice were distributed in the wounded areas of scalded mouse models, attenuated inflammatory responses and decreased the deposition of collagens, thus performing a beneficial effect against scar formation. Hypoxia enhanced the protective effect of placenta-derived mesenchymal stem cells and hypoxia-inducible factor-1α was involved in the protective effect of placenta-derived mesenchymal stem cells in hypoxic condition. Hypoxia enhanced the protective effect of placenta-derived mesenchymal stem cells through hypoxia-inducible factor-1α and PMSCs may have a potential application in the treatment of wound.

[Drug use and involvement in risky driving styles in a sample of university students. The uniHcos project].

PubMed

Jiménez-Mejías, Eladio; Medina-García, Miguel Ángel; Martínez-Ruiz, Virginia; Pulido-Manzanero, José; Fernández-Villa, Tania

2015-09-01

Drug and alcohol use are known to increase the risk of traffic accidents, especially among youth. However, the association between habitual drug use and the adoption of risky driving behavior is not well known. The aim of this study was to identify and quantify the association between habitual drug use and involvement in risky driving practices overall and by gender among university students. A cross sectional study was conducted. The study population was composed of 559 car drivers younger than 31 years who completed an online questionnaire during the 2011-2012 academic year. Among other factors, the questionnaire assessed the following items: habitual drug consumption (20 or more days) during the last year and involvement in other risky driving practices during the last month. A total of 27.7% of students reported they had used drugs regularly during the last year. Drug use was associated with a higher frequency of involvement in risky driving practices. In men, the factors most strongly associated with drug consumption were speeding, driving under influence of alcohol, and feeling drowsy while driving. In women, drug consumption was mainly associated with smoking while driving, drunk driving, and driving without rest. The results of our study support the hypothesis that habitual drug use is associated with an increased frequency of risky driving behavior. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Accident-precipitating factors for crashes in turbine-powered general aviation aircraft.

PubMed

Boyd, Douglas D; Stolzer, Alan

2016-01-01

General aviation (14CFR Part 91) accounts for 83% of civil aviation fatalities. While much research has focused on accident causes/pilot demographics in this aviation sector, studies to identify factors leading up to the crash (accident-precipitating factors) are few. Such information could inform on pre-emptive remedial action. With this in mind and considering the paucity of research on turbine-powered aircraft accidents the study objectives were to identify accident-precipitating factors and determine if the accident rate has changed over time for such aircraft operating under 14CFR Part 91. The NTSB Access database was queried for accidents in airplanes (<12,501lb) powered by 1-2 turbine engines and occurring between 1989 and 2013. We developed and utilized an accident-precipitating factor taxonomy. Statistical analyses employed logistic regression, contingency tables and a generalized linear model with Poisson distribution. The "Checklist/Flight Manual Not Followed" was the most frequent accident-precipitating factor category and carried an excess risk (OR 2.34) for an accident with a fatal and/or serious occupant injury. This elevated risk reflected an over-representation of accidents with fatal and/or serious injury outcomes (p<0.001) in the "non-adherence to V Speeds" sub-category. For accidents grouped in the "Inadequate Pre-Flight Planning/Inspection/Procedure" the "inadequate weather planning" sub-category accounted (p=0.036) for the elevated risk (OR 2.22) of an accident involving fatal and/or serious injuries. The "Violation FARs/AIM Deviation" category was also associated with a greater risk for fatal and/or serious injury (OR 2.59) with "Descent below the MDA/failure to execute the missed approach" representing the largest sub-category. Accidents in multi-engine aircraft are more frequent than their single engine counterparts and the decline (50%) in the turbine aircraft accident rate over the study period was likely due, in part, to a 6-fold increased representation of single engine airplanes. In conclusion, our study is the first to identify novel precursive factors for accidents involving turbine aircraft operating under 14CFR Part 91. This research highlights areas that should receive further emphasis in training/recurrency in a pre-emptive attempt to nullify candidate accident-precipitating factor(s). Copyright © 2015 Elsevier Ltd. All rights reserved.

An extracytoplasmic function sigma factor-dependent periplasmic glutathione peroxidase is involved in oxidative stress response of Shewanella oneidensis

DOE PAGES

Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan; ...

2015-01-01

Background: Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. Results: RpoE was important for bacterial growth at low and high temperatures, in the minimal medium, and high salinity. The degP/htrA orthologue, required for growth of Escherichia coli and Pseudomonas aeruginosa at high temperature, is absent in Shewanella, while the degQ gene is RpoE-regulated and is required for bacterial growth at high temperature. RpoE2 was essentialmore » for the optimal growth in oxidative stress conditions because the rpoE2 mutant was sensitive to hydrogen peroxide and paraquat. The operon encoding a ferrochelatase paralogue (HemH2) and a periplasmic glutathione peroxidase (PgpD) was identified as RpoE2-dependent. PgpD exhibited higher activities and played a more important role in the oxidative stress responses than the cytoplasmic glutathione peroxidase CgpD under tested conditions. The rpoE2-chrR operon and the identified regulon genes, including pgpD and hemH2, are coincidently absent in several psychrophilic and/or deep-sea Shewanella strains. Conclusion: In S. oneidensis MR-1, the RpoE-dependent degQ gene is required for optimal growth under high temperature. The rpoE2 and RpoE2-dependent pgpD gene encoding a periplasmic glutathione peroxidase are involved in oxidative stress responses. But rpoE2 is not required for bacterial growth at low temperature and it even affected bacterial growth under salt stress, indicating that there is a tradeoff between the salt resistance and RpoE2-mediated oxidative stress responses.« less

An extracytoplasmic function sigma factor-dependent periplasmic glutathione peroxidase is involved in oxidative stress response of Shewanella oneidensis

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

Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan

Background: Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. Results: RpoE was important for bacterial growth at low and high temperatures, in the minimal medium, and high salinity. The degP/htrA orthologue, required for growth of Escherichia coli and Pseudomonas aeruginosa at high temperature, is absent in Shewanella, while the degQ gene is RpoE-regulated and is required for bacterial growth at high temperature. RpoE2 was essentialmore » for the optimal growth in oxidative stress conditions because the rpoE2 mutant was sensitive to hydrogen peroxide and paraquat. The operon encoding a ferrochelatase paralogue (HemH2) and a periplasmic glutathione peroxidase (PgpD) was identified as RpoE2-dependent. PgpD exhibited higher activities and played a more important role in the oxidative stress responses than the cytoplasmic glutathione peroxidase CgpD under tested conditions. The rpoE2-chrR operon and the identified regulon genes, including pgpD and hemH2, are coincidently absent in several psychrophilic and/or deep-sea Shewanella strains. Conclusion: In S. oneidensis MR-1, the RpoE-dependent degQ gene is required for optimal growth under high temperature. The rpoE2 and RpoE2-dependent pgpD gene encoding a periplasmic glutathione peroxidase are involved in oxidative stress responses. But rpoE2 is not required for bacterial growth at low temperature and it even affected bacterial growth under salt stress, indicating that there is a tradeoff between the salt resistance and RpoE2-mediated oxidative stress responses.« less

Redox-Dependent Modulation of Anthocyanin Biosynthesis by the TCP Transcription Factor TCP15 during Exposure to High Light Intensity Conditions in Arabidopsis1[OPEN

PubMed Central

Viola, Ivana L.; Gonzalez, Daniel H.

2016-01-01

TCP proteins integrate a family of transcription factors involved in the regulation of developmental processes and hormone responses. It has been shown that most members of class I, one of the two classes in which the TCP family is divided, contain a conserved Cys that leads to inhibition of DNA binding when oxidized. In this work, we describe that the class-I TCP protein TCP15 inhibits anthocyanin accumulation during exposure of plants to high light intensity by modulating the expression of transcription factors involved in the induction of anthocyanin biosynthesis genes, as suggested by the study of plants that express TCP15 from the 35SCaMV promoter and mutants in TCP15 and the related gene TCP14. In addition, the effect of TCP15 on anthocyanin accumulation is lost after prolonged incubation under high light intensity conditions. We provide evidence that this is due to inactivation of TCP15 by oxidation of Cys-20 of the TCP domain. Thus, redox modulation of TCP15 activity in vivo by high light intensity may serve to adjust anthocyanin accumulation to the duration of exposure to high irradiation conditions. PMID:26574599

Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone.

PubMed

Tolkachov, Alexander; Fischer, Cornelius; Ambrosi, Thomas H; Bothe, Melissa; Han, Chung-Ting; Muenzner, Matthias; Mathia, Susanne; Salminen, Marjo; Seifert, Georg; Thiele, Mario; Duda, Georg N; Meijsing, Sebastiaan H; Sauer, Sascha; Schulz, Tim J; Schupp, Michael

2018-03-26

The transcription factor GATA2 is required for expansion and differentiation of hematopoietic stem cells (HSCs). In mesenchymal stem cells (MSCs) GATA2 blocks adipogenesis, but its biological relevance and underlying genomic events are unknown. We report a dual function of GATA2 in bone homeostasis. GATA2 in MSCs binds near genes involved in skeletal system development and co-localizes with motifs for FOX and HOX transcription factors, known regulators of skeletal development. Ectopic GATA2 blocks osteoblastogenesis by interfering with SMAD1/5/8 activation. MSC-specific deletion of GATA2 in mice increases numbers and differentiation capacity of bone-derived precursors, resulting in elevated bone formation. Surprisingly, MSC-specific GATA2 deficiency impairs trabecularization and mechanical strength of bone, involving reduced MSC expression of the osteoclast inhibitor osteoprotegerin and increased osteoclast numbers. Thus, GATA2 affects bone turnover via MSC-autonomous and indirect effects. By regulating bone trabecularization, GATA2 expression in the osteogenic lineage may contribute to the anatomical and cellular microenvironment of the HSC niche required for hematopoiesis. Copyright © 2018 American Society for Microbiology.

Molecular mechanisms of liver preconditioning

PubMed Central

Alchera, Elisa; Dal Ponte, Caterina; Imarisio, Chiara; Albano, Emanuele; Carini, Rita

2010-01-01

Ischemia/reperfusion (I/R) injury still represents an important cause of morbidity following hepatic surgery and limits the use of marginal livers in hepatic transplantation. Transient blood flow interruption followed by reperfusion protects tissues against damage induced by subsequent I/R. This process known as ischemic preconditioning (IP) depends upon intrinsic cytoprotective systems whose activation can inhibit the progression of irreversible tissue damage. Compared to other organs, liver IP has additional features as it reduces inflammation and promotes hepatic regeneration. Our present understanding of the molecular mechanisms involved in liver IP is still largely incomplete. Experimental studies have shown that the protective effects of liver IP are triggered by the release of adenosine and nitric oxide and the subsequent activation of signal networks involving protein kinases such as phosphatidylinositol 3-kinase, protein kinase C δ/ε and p38 MAP kinase, and transcription factors such as signal transducer and activator of transcription 3, nuclear factor-κB and hypoxia-inducible factor 1. This article offers an overview of the molecular events underlying the preconditioning effects in the liver and points to the possibility of developing pharmacological approaches aimed at activating the intrinsic protective systems in patients undergoing liver surgery. PMID:21182220

Intra- and Interorgan Communication in the Cardiovascular System: A Special View on Redox Regulation.

PubMed

Gödecke, Axel; Haendeler, Judith

2017-04-20

Intraorgan communication in the cardiovascular system is exerted not only by direct cell-cell contacts but also by locally released factors, which modulate neighboring cells by paracrine signals (e.g., NO, vascular endothelial growth factor, adenosine, reactive oxygen species). Moreover, cells in close proximity to the typical cardiovascular cells such as fibroblasts, red blood cells, as well as resident and invading immune cells must be considered in attempts to understand cardiovascular function in physiology and pathology. The second level of communication is the interorgan communication, which may be distinguished from intraorgan communication, since it involves signaling from remote organs to the heart and circulation. Therefore, mediators released by, for example, the kidney or skeletal muscle reach the heart and modulate its function. This is not only the case under physiological conditions, because there is increasing evidence that the organ-specific response to a primary insult may affect also the function of remote organs by the release of factors. This Forum will summarize novel mechanisms involved in intraorgan and interorgan communication of the cardiovascular system, with a special view on the remote organs, skeletal muscle and kidney. Antioxid. Redox Signal. 26, 613-615.

Peptides derived from transcription factor EB bind to calcineurin at a similar region as the NFAT-type motif

PubMed Central

Song, Ruiwen; Li, Jing; Zhang, Jin; Wang, Lu; Tong, Li; Wang, Ping; Yang, Huan; Wei, Qun; Cai, Huaibin; Luo, Jing

2018-01-01

Calcineurin (CN) is involved in many physiological processes and interacts with multiple substrates. Most of the substrates contain similar motifs recognized by CN. Recent studies revealed a new CN substrate, transcription factor EB (TFEB), which is involved in autophagy. We showed that a 15-mer QSYLENPTSYHLQQS peptide from TFEB (TFEB-YLENP) bound to CN. When the TFEB-YLENP peptide was changed to YLAVP, its affinity for CN increased and it had stronger CN inhibitory activity. Molecular dynamics simulations revealed that the TFEB-YLENP peptide has the same docking sites in CN as the 15-mer DQYLAVPQHPYQWAK motif of the nuclear factor of activated T cells, cytoplasmic 1 (NFATc1-YLAVP). Moreover expression of the NFATc1-YLAVP peptide suppressed the TFEB activation in starved Hela cells. Our studies first identified a CN binding site in TFEB and compared the inhibitory capability of various peptides derived from CN substrates. The data uncovered a diversity in recognition sequences that underlies the CN signaling within the cell. Studies of CN-substrate interactions should lay the groundwork for developing selective CN peptide inhibitors that target CN-substrate interaction in vitro experiments. PMID:28890387

Long noncoding RNA NORAD regulates transforming growth factor -β signaling and epithelial-to-mesenchymal transition-like phenotype.

PubMed

Kawasaki, Natsumi; Miwa, Toshiki; Hokari, Satoshi; Sakurai, Tsubasa; Ohmori, Kazuho; Miyauchi, Kensuke; Miyazono, Kohei; Koinuma, Daizo

2018-05-02

Long noncoding RNAs are involved in a variety of cellular functions. In particular, an increasing number of studies have revealed the functions of long noncoding RNAs in various cancers; however, their precise roles and mechanisms of action remain to be elucidated. NORAD, a cytoplasmic long noncoding RNA, is upregulated by irradiation and functions as a potential oncogenic factor by binding and inhibiting Pumilio proteins (PUM1/PUM2). Here, we show that NORAD upregulates transforming growth factor-β (TGF-β) signaling and regulates TGF-β-induced epithelial-to-mesenchymal transition (EMT)-like phenotype, which is a critical step in the progression of lung adenocarcinoma, A549 cells. However, PUM1 does not appear to be involved in this process. We thus focused on importin β1 as a binding partner of NORAD and found that knock down of NORAD partially inhibits the physical interaction of importin β1 with Smad3, inhibiting the nuclear accumulation of Smad complexes in response to TGF-β. Our findings may provide a new mechanism underlying the function of NORAD in cancer cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Body-related sport and exercise motives and disturbed eating attitudes and behaviours in adolescents.

PubMed

Maïano, Christophe; Morin, Alexandre J S; Lanfranchi, Marie-Christine; Therme, Pierre

2015-07-01

Motives underlying sport and exercise involvement have recently been hypothesized as potential factors influencing the positive association between sports/exercises involvement and disturbed eating attitudes and behaviours (DEAB) among adolescents. Nevertheless, very few studies have examined this hypothesis or the moderating role of gender, context of practice, performance levels and sport type on these relationships. In this study, these questions were addressed among 168 male and 167 female French adolescents involved in various types, contexts and performance levels of sport and exercise. Participants were asked to indicate their main motives for involvement in sport practice and to self-report DEAB (generic DEAB, vomiting-purging behaviours, and eating-related control) on a French adaptation of the Eating Attitudes Test-26. The results shared positive associations between body-related sport and exercise motives and most of the DEAB subscales. Furthermore, they show that the relationship between body-related sport and exercise motives and Vomiting-Purging Behaviours differs according to involvement in individual and competitive sports and exercises. Copyright ©2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Developmental changes in decision making under risk: The role of executive functions and reasoning abilities in 8- to 19-year-old decision makers.

PubMed

Schiebener, Johannes; García-Arias, María; García-Villamisar, Domingo; Cabanyes-Truffino, Javier; Brand, Matthias

2015-01-01

Previous studies have shown that children and adolescents often tend toward risky decisions despite explicit knowledge about the potential negative consequences. This phenomenon has been suggested to be associated with the immaturity of brain areas involved in cognitive control functions. Particularly, "frontal lobe functions," such as executive functions and reasoning, mature until young adulthood and are thought to be involved in age-related changes in decision making under explicit risk conditions. We investigated 112 participants, aged 8-19 years, with a frequently used task assessing decisions under risk, the Game of Dice Task (GDT). Additionally, we administered the Modified Card Sorting Test assessing executive functioning (categorization, cognitive flexibility, and strategy maintenance) as well as the Ravens Progressive Matrices assessing reasoning. The results showed that risk taking in the GDT decreased with increasing age and this effect was not moderated by reasoning but by executive functions: Particularly, young persons with weak executive functioning showed very risky decision making. Thus, the individual maturation of executive functions, associated with areas in the prefrontal cortex, seems to be an important factor in young peoples' behavior in risky decision-making situations.

Factors associated with acute respiratory infection in children under the age of 5 years: evidence from the 2011 Ethiopia Demographic and Health Survey

PubMed Central

Geberetsadik, Achamyelesh; Worku, Alemayehu; Berhane, Yemane

2015-01-01

Background Acute respiratory tract infection (ARI) remains the major cause of child mortality in Sub-Saharan Africa. Various factors are associated with its occurrence and vary by context. However, available large-scale, population-based data are not fully exploited to identify locally relevant risk factors. The objective of this study was to identify factors associated with ARI in children under the age of 5 years in Ethiopia. Methods Further analysis of the 2011 Ethiopia Demographic and Health Survey was carried out involving 11,645 children under the age of 5 years and their mothers. Information relevant to the current study was extracted from the main data set and a working data set was prepared. A complex survey logistic regression analysis was applied. Results Acute ARI in this study was associated with severe malnutrition. Children who were severely wasted were highly likely to develop ARI (adjusted odds ratio [AOR] 1.7; 95% confidence interval [CI] 1.1–2.5). ARI was less likely to occur in children from families with an educated father and professional mother (AOR 0.4; 95% CI 0.2–0.6 and AOR 0.1; 95% CI 0.01–0.6, respectively). Conclusion Malnourished children from a lower socioeconomic category are more likely to suffer from ARI. Targeting disadvantaged children for effective interventions can help reduce the burden of morbidity and death due to ARI. PMID:29388598

Long non-coding RNA nuclear paraspeckle assembly transcript 1 inhibits the apoptosis of retina Müller cells after diabetic retinopathy through regulating miR-497/brain-derived neurotrophic factor axis.

PubMed

Li, Xiu-Juan

2018-05-01

The role of long non-coding RNA in diabetic retinopathy, a serious complication of diabetes mellitus, has attracted increasing attention in recent years. The purpose of this study was to explore whether long non-coding RNA nuclear paraspeckle assembly transcript 1 was involved in the context of diabetic retinopathy and its underlying mechanisms. Our results revealed that nuclear paraspeckle assembly transcript 1 was significantly downregulated in the retina of diabetes mellitus rats. Meanwhile, miR-497 was significantly increased in diabetes mellitus rats' retina and high glucose-treated Müller cells, but brain-derived neurotrophic factor was increased. We also found that high glucose-induced apoptosis of Müller cells was accompanied by the significant downregulation of nuclear paraspeckle assembly transcript 1 in vitro. Further study demonstrated that high glucose-promoted Müller cells apoptosis through downregulating nuclear paraspeckle assembly transcript 1 and downregulated nuclear paraspeckle assembly transcript 1 mediated this effect via negative regulating miR-497. Moreover, brain-derived neurotrophic factor was negatively regulated by miR-497 and associated with the apoptosis of Müller cells under high glucose. Our results suggested that under diabetic conditions, downregulated nuclear paraspeckle assembly transcript 1 decreased the expression of brain-derived neurotrophic factor through elevating miR-497, thereby promoting Müller cells apoptosis and aggravating diabetic retinopathy.

Molecular mechanisms of ulcer healing.

PubMed

Tarnawski, A

2000-04-01

An ulcer in the gastrointestinal tract is a deep necrotic lesion penetrating the entire mucosal thickness and muscularis mucosae. Ulcer healing is an active process of filling the mucosal defect with proliferating and migrating epithelial and connective tissue cells. At the ulcer margin, epithelial cells proliferate and migrate onto the granulation tissue to cover (reepithelialize) the ulcer and also invade granulation tissue to reconstruct glandular structures within the ulcer scar. The reepithelialization and reconstruction of glandular structures is controlled by growth factors: trefoil peptides, EGF, HGF, bFGF and PDGF; and locally produced cytokines by regenerating cells in an orderly fashion and integrated manner to ensure the quality of mucosal restoration. These growth factors, most notably EGF, trigger cell proliferation via signal transduction pathways involving EGF-R, adapter proteins (Grb2, Shc and Sos), Ras, Raf1 and MAP (Erk1/Erk2) kinases, which, after translocation to nuclei, activate transcription factors and cell proliferation. Cell migration requires cytoskeletal rearrangements and is controlled by growth factors via Rho/Rac and signaling pathways involving PLC-gamma, PI-3 K and phosphorylation of focal adhesion proteins. Granulation tissue develops at the ulcer base. It consists of connective tissue cells: fibroblasts, macrophages and proliferating endothelial cells forming microvessels under the control of angiogenic growth factors: bFGF, VEGF and angiopoietins, which all promote angiogenesiscapillary vessel formation, essential for the restoration of microvascular network in the mucosa and thus crucial for oxygen and nutrient supply. The major mechanism of activation of angiogenic growth factors and their receptor expression appears to be hypoxia, which activates hypoxia-inducible factor, which binds to VEGF promoter.

Developmental vitamin D deficiency and autism: Putative pathogenic mechanisms.

PubMed

Ali, Asad; Cui, Xiaoying; Eyles, Darryl

2018-01-01

Autism is a neurodevelopmental disease that presents in early life. Despite a considerable amount of studies, the neurobiological mechanisms underlying autism remain obscure. Both genetic and environmental factors are involved in the development of autism. Vitamin D deficiency is emerging as a consistently reported risk factor in children. One reason for the prominence now being given to this risk factor is that it would appear to interact with several other epidemiological risk factors for autism. Vitamin D is an active neurosteroid and plays crucial neuroprotective roles in the developing brain. It has important roles in cell proliferation and differentiation, immunomodulation, regulation of neurotransmission and steroidogenesis. Animal studies have suggested that transient prenatal vitamin D deficiency is associated with altered brain development. Here we review the potential neurobiological mechanisms linking prenatal vitamin D deficiency and autism and also discuss what future research targets must now be addressed. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Regulation of wound healing and fibrosis by hypoxia and hypoxia-inducible factor-1.

PubMed

Ruthenborg, Robin J; Ban, Jae-Jun; Wazir, Anum; Takeda, Norihiko; Kim, Jung-Whan

2014-09-01

Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

Human Papilloma Virus in Oral Squamous Cell Carcinoma - The Enigma Unravelled.

PubMed

Khot, Komal P; Deshmane, Swati; Choudhari, Sheetal

2016-03-01

Squamous cell carcinoma of the head and neck (HNSCC) has long been regarded as a disease entity having a remarkable incidence worldwide and a fairly onerous prognosis; thus encouraging further research on factors that might modify disease outcome. Squamous cell carcinomas encompass at least 90% of all oral malignancies. Several factors like tobacco and tobacco-related products, alcohol, genetic predisposition and hormonal factors are suspected as possible causative factors. Human papilloma virus (HPV), the causal agent of cervical cancer also appears to be involved in the aetiology of oral and oropharyngeal cancer. HPVpositive squamous cell carcinoma (SCC) seems to differ from HPV-negative SCC. Many questions about the natural history of oral HPV infection remain under investigation. The aim of this review is to highlight the current understanding of HPV-associated oral cancer with an emphasis on its prognosis, detection and management.

Analysis of a Contingency Model: Effects of Management Style and Situational Environment on Organizational Effectiveness.

DTIC Science & Technology

1980-09-01

conclusion reached by this study was that more than one criteria of effectiveness was necessary to evaluate any leadership style ( Szilagyi and Wallace ... Szilagyi and Wallace , 1980). Diagnostic skills involve the ability to identify and under- stand the influence of situational factors that arise in- ternal...are being called upon to do things differently (Margulies and Wallace , 1973, p. 2)." Thus, reference to changing organizations must also be directed

The Attitudes of Navy Corrections Staff Members: What they Think About Confinees and their Jobs

DTIC Science & Technology

1994-02-01

and socially involved citizens (Irwin, 1974). The attitudes and behaviors of the custodial and program staff are thought to be essential factors for...developed. Initially, we have proceeded with the underlying theoretical assumption (supported by previous research) that both the attitudes and behaviors of...suggested that one of the contextual variables related to attitudes about a group was the views of persons with reward power. It may be that negative

Thrombosis of the inferior vena cava and malignant disease.

PubMed

Kraft, Christiane; Schuettfort, Gundolf; Weil, Yvonne; Tirneci, Vanessa; Kasper, Alexander; Haberichter, Barbara; Schwonberg, Jan; Schindewolf, Marc; Lindhoff-Last, Edelgard; Linnemann, Birgit

2014-09-01

Inferior vena cava thrombosis (IVCT) is a rare event, and studies detailing its underlying aetiologies are scarce. One hundred and forty-one IVCT patients (57% females, median age 47 years) were analysed with a focus on malignancy-related thrombosis and compared with 141 age- and sex-matched control patients with isolated lower-extremity deep vein thrombosis. Malignancies were more prevalent among IVCT patients compared with the control group (39% vs. 7.8%; P<0.001). Malignancy-related IVCT more frequently involved the suprarenal and hepatic segments of the IVC and extended more often to the right atrium than IVCT did in non-cancer patients. Among IVCT patients with malignancies, renal cell carcinoma (38%) and other malignancies of the genitourinary tract (25%) were the most common tumours. Analysis of the underlying pathological mechanisms of malignancy-related thrombosis identified external compression of the IVC by tumour masses in 9 cases (16%), and progression of malignancy into the IVC (so-called "tumour thrombosis") in 24 cases (44%). The remaining 22 cases (40%) were attributed to malignancy-related hypercoagulability and the presence of additional venous thromboembolism risk factors, such as previous surgery, immobilisation, or chemotherapy. Malignancies substantially contribute to the risk of thrombosis involving the IVC. Tumour invasion, especially in cases of renal cell cancer and malignancy-related hypercoagulability are major triggering factors for thrombogenesis. Copyright © 2014. Published by Elsevier Ltd.

Nesfatin-1 - More than a food intake regulatory peptide.

PubMed

Stengel, Andreas

2015-10-01

Nesfatin-1 was discovered a decade ago and despite the fact that it represents just one of a multitude of food intake-inhibiting factors it received increasing attention. This led to a detailed characterization of NUCB2/nesfatin-1's physiological property to reduce food intake and also gave rise to an involvement in the long term regulation of body weight, especially under conditions of obesity. In addition, studies indicated the involvement of NUCB2/nesfatin-1 in other homeostatic functions as well: glucose homeostasis, water intake, gastrointestinal functions, temperature regulation, cardiovascular functions, puberty onset and sleep. These pleiotropic actions underline the physiological relevance of this peptide. Recently, the involvement of NUCB2/nesfatin-1 in psychiatric disorders such as anxiety has been investigated giving rise to the speculation that NUCB2/nesfatin-1 represents a peptidergic link between eating and anxiety/depression disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain-Derived Neurotrophic Factor Induces Cell Survival and the Migration of Murine Adult Hippocampal Precursor Cells During Differentiation In Vitro.

PubMed

Ortiz-López, Leonardo; Vega-Rivera, Nelly Maritza; Babu, Harish; Ramírez-Rodríguez, Gerardo Bernabé

2017-01-01

The generation of new neurons during adulthood involves local precursor cell migration and terminal differentiation in the dentate gyrus. These events are influenced by the hippocampal microenvironment. Brain-derived neurotrophic factor (BDNF) is relevant for hippocampal neuronal development and behavior. Interestingly, studies that have been performed in controlled in vitro systems that involve isolated precursor cells that were derived from the dentate gyrus (AHPCs) have shown that BDNF induces the activation of the TrkB receptor and, consequentially, might activate signaling pathways that favor survival and neuronal differentiation. Based on the fact that the cellular events of AHPCs that are induced by single factors can be studied in this controlled in vitro system, we investigated the ability of BDNF and the involvement of protein kinase C (PKC), as one of the TrkB-downstream activated signaling proteins, in the regulation of migration, here reflected by motility, of AHPCs. Precursor cells were cultured following a concentration-response curve (1-640 ng/ml) for 24 or 96 h. We found that BDNF favored cell survival without altering the viability under culture proliferative conditions of the AHPCs. Concomitantly, glial- and neuronal-differentiated precursor cells increased as a consequence of survival promoted by BDNF. Additionally, pharmacological approaches showed that BDNF (40 ng/ml)-induced migration of AHPCs was blocked with the compounds K252a and GF109203x, which prevent the activation of TrkB and PKC, respectively. The results indicate that in the in vitro migration of differentiated AHPCs it is involved the BDNF and TrkB cascade. Our results provide additional information about the mechanism by which BDNF impacts adult neurogenesis in the hippocampus.

Risk factor assessment and prognosis of eye involvement in Behcet's disease in Turkey.

PubMed

Demiroğlu, H; Barişta, I; Dündar, S

1997-04-01

Behcet's disease (BD) shows great regional differences in clinical manifestations and prognosis, including eye involvement. Thus, it is hard to predict in which patient the eyes will be involved and what the outcome will be. In this study we assessed various risk factors for eye involvement and attempted to predict the visual outcome in our patient population in Turkey. Data from a total of 224 patients with BD, diagnosed between 1982 and 1996, were analyzed retrospectively. A detailed physical examination and ophthalmologic work up were performed on each patient. Factors that might contribute to eye involvement were investigated, after which prognostic factors for vision were evaluated. Eighty-eight patients had eye involvement during a median follow-up of 32 months. The risk of involvement was highest within the first year of diagnosis. Young age was the most significant factor for eye involvement (P < 0.0001), but vascular thrombosis, central nervous system (CNS) involvement, and male gender were other risk factors (P < 0.001; P < 0.01; and P < 0.05, respectively). The most important determinant for the prognosis of vision was CNS involvement (P < 0.0001). Vascular thrombosis and an age of < or = 32 were other risk factors for visual impairment (P < 0.001 and P < 0.05, respectively). The risk of eye involvement and prognosis for vision were similar with different treatment regimens (P > 0.05). It is suggested that the first 2 years after diagnosis is the most critical period for eye involvement, and conventional forms of therapy generally are unsuccessful in preventing such involvement. It seems reasonable to treat patients who are at increased risk for eye involvement more aggressively, especially within the first 2 years of disease onset.

Egr-1: A Candidate Transcription Factor Involved in Molecular Processes Underlying Time-Memory.

PubMed

Shah, Aridni; Jain, Rikesh; Brockmann, Axel

2018-01-01

In honey bees, continuous foraging is accompanied by a sustained up-regulation of the immediate early gene Egr-1 (early growth response protein-1) and candidate downstream genes involved in learning and memory. Here, we present a series of feeder training experiments indicating that Egr-1 expression is highly correlated with the time and duration of training even in the absence of the food reward. Foragers that were trained to visit a feeder over the whole day and then collected on a day without food presentation showed Egr-1 up-regulation over the whole day with a peak expression around 14:00. When exposed to a time-restricted feeder presentation, either 2 h in the morning or 2 h in the evening, Egr-1 expression in the brain was up-regulated only during the hours of training. Foragers that visited a feeder in the morning as well as in the evening showed two peaks of Egr-1 expression. Finally, when we prevented time-trained foragers from leaving the colony using artificial rain, Egr-1 expression in the brains was still slightly but significantly up-regulated around the time of feeder training. In situ hybridization studies showed that active foraging and time-training induced Egr-1 up-regulation occurred in the same brain areas, preferentially the small Kenyon cells of the mushroom bodies and the antennal and optic lobes. Based on these findings we propose that foraging induced Egr-1 expression can get regulated by the circadian clock after time-training over several days and Egr-1 is a candidate transcription factor involved in molecular processes underlying time-memory.

The Productivity and Cost-Efficiency of Models for Involving Nurse Practitioners in Primary Care: A Perspective from Queueing Analysis

PubMed Central

Liu, Nan; D'Aunno, Thomas

2012-01-01

Objective To develop simple stylized models for evaluating the productivity and cost-efficiencies of different practice models to involve nurse practitioners (NPs) in primary care, and in particular to generate insights on what affects the performance of these models and how. Data Sources and Study Design The productivity of a practice model is defined as the maximum number of patients that can be accounted for by the model under a given timeliness-to-care requirement; cost-efficiency is measured by the corresponding annual cost per patient in that model. Appropriate queueing analysis is conducted to generate formulas and values for these two performance measures. Model parameters for the analysis are extracted from the previous literature and survey reports. Sensitivity analysis is conducted to investigate the model performance under different scenarios and to verify the robustness of findings. Principal Findings Employing an NP, whose salary is usually lower than a primary care physician, may not be cost-efficient, in particular when the NP's capacity is underutilized. Besides provider service rates, workload allocation among providers is one of the most important determinants for the cost-efficiency of a practice model involving NPs. Capacity pooling among providers could be a helpful strategy to improve efficiency in care delivery. Conclusions The productivity and cost-efficiency of a practice model depend heavily on how providers organize their work and a variety of other factors related to the practice environment. Queueing theory provides useful tools to take into account these factors in making strategic decisions on staffing and panel size selection for a practice model. PMID:22092009

Control of Diapause in Calanid Copepods: Identification of Regulatory Pathways using In Silico Data Mining

NASA Astrophysics Data System (ADS)

Lenz, P. H.; Roncalli, V.; Hopcroft, R. R.; Christie, A. E.

2016-02-01

As water temperatures and seasonal cycles change with global warming, questions are being raised on how these factors might affect the life cycles of copepods in the family Calanidae. These species depend on the completion of a seasonal diapause for the annual recruitment of the spring population. Diapause is a developmental program that includes induction, preparation, initiation, maintenance and termination. A lipid hypothesis has been proposed to explain the regulation of diapause in Calanus finmarchicus. While lipids may be critical for the diapause program, lipid metabolism is typically under neuroendocrine control. In insects, there is an extensive literature showing that juvenile hormone, ecdysteroids, and many neuropeptides are involved in the regulation of diapause. In particular, insulin signaling has been proposed as a key component in the diapause phenotype in a wide variety of insects, and through the actions of the transcription factor FOXO, many features of diapause can be linked to the insulin pathway, e.g., fat accumulation and enhancement of stress tolerance. Using the insects as models, we identified transcripts and predicted the protein components of the insulin/FOXO pathway (e.g., insulin-like peptide precursors, insulin receptors, juvenile hormone acid O-methyltransferase and FOXO), as well as a wide variety of neuropeptides (e.g., members of the diapause hormone family) and other proteins (e.g., those putatively involved in biological timing such as circadian and seasonal rhythmicity) that might be involved in the regulation of lipid metabolism and diapause in the calanid copepods C. finmarchicus and Neocalanus flemingeri. Our goal is to use the identified transcripts to start to understand the physiological processes underlying diapause in these calanids.

Proteomics Identification of Potential Candidates Involved in Cell Proliferation for Early Stage of Brain Regeneration in the Adult Zebrafish.

PubMed

Lim, Fei Tieng; Ogawa, Satoshi; Smith, A Ian; Parhar, Ishwar S

2017-02-01

The central nervous system (CNS) of the non-mammalian vertebrates has better neuroregenerative capability as compared with the mammalian CNS. Regeneration of habenula was observed 40 days after damage in zebrafish. During the early stage of regeneration, we found a significant increase of apoptotic cells on day-1 post-damage and of proliferative cells on day-3 post-damage. To identify the molecular factor(s) involved in the early stages of neuroregeneration, differentially expressed proteins during sham, 20- and 40-h post-habenula damage were investigated by proteomic approach by using two-dimensional differential gel electrophoresis (2D-DIGE) coupled with Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight (MALDI-ToF) and tandem mass spectrometry. Protein profiles revealed 17 differentially (>1.5-fold) expressed proteins: 10 upregulated, 4 downregulated, 2 proteins were found to be downregulated at the early stage but upregulated at a later stage, and 1 protein was found to be upregulated at 2 different time points. All proteins identified can be summarized under few molecular processes involved in the early stages of neuroregeneration in zebrafish CNS: apoptosis regulation (Wnt inhibitory factor 1 [WIF1]), neuroprotection (metallothionein), cell proliferation (Spred2, ependymin, Lhx1, and Wnts), differentiation (Spred2, Lhx9, and Wnts), and morphogenesis (cytoplasmic actins and draculin). These protein profiling results suggest that drastic molecular changes occur in the neuroregenerative process during this period, which includes cell proliferation, differentiation, and protection.

Evaluating patient care communication in integrated care settings: application of a mixed method approach in cerebral palsy programs.

PubMed

Gulmans, J; Vollenbroek-Hutten, M M R; Van Gemert-Pijnen, J E W C; Van Harten, W H

2009-02-01

In this study, we evaluated patient care communication in the integrated care setting of children with cerebral palsy in three Dutch regions in order to identify relevant communication gaps experienced by both parents and involved professionals. A three-step mixed method approach was used starting with a questionnaire to identify communication links in which parents experienced gaps. In subsequent in-depth interviews with parents and focus group meetings with professionals underlying factors were evaluated. In total, 197 parents completed the questionnaire (response 67%); 6% scored negative on parent-professional communication, whereas 17% scored negative on inter-professional communication, especially between the rehabilitation physician and primary care physiotherapy (16%) and (special) education/day care (15%). In-depth interviews among a subset of 20 parents revealed various sources of dissatisfaction such as lack of cooperation and patient centeredness, inappropriate amount of information exchange and professional use of parents as messenger of information. Focus group meetings revealed that professionals recognized these gaps. They attributed them to capacity problems, lack of interdisciplinary guidelines and clear definition of roles, but also a certain hesitance for contact due to unfamiliarity with involved professionals in the care network. Parents particularly identified gaps in inter-professional communication between (rehabilitation) hospitals and primary care settings. Involved professionals recognized these gaps and primarily attributed them to organizational factors. Improvement initiatives should focus on these factors as well as facilitation of low-threshold contact across the patient's care network.

Ability to monitor driving under the influence of marijuana among non-fatal motor-vehicle crashes: An evaluation of the Colorado electronic accident reporting system.

PubMed

Peterson, Alexis B; Sauber-Schatz, Erin K; Mack, Karin A

2018-06-01

As more states legalize medical/recreational marijuana use, it is important to determine if state motor-vehicle surveillance systems can effectively monitor and track driving under the influence (DUI) of marijuana. This study assessed Colorado's Department of Revenue motor-vehicle crash data system, Electronic Accident Reporting System (EARS), to monitor non-fatal crashes involving driving under the influence (DUI) of marijuana. Centers for Disease Control and Prevention guidelines on surveillance system evaluation were used to assess EARS' usefulness, flexibility, timeliness, simplicity, acceptability, and data quality. We assessed system components, interviewed key stakeholders, and analyzed completeness of Colorado statewide 2014 motor-vehicle crash records. EARS contains timely and complete data, but does not effectively monitor non-fatal motor-vehicle crashes related to DUI of marijuana. Information on biological sample type collected from drivers and toxicology results were not recorded into EARS; however, EARS is a flexible system that can incorporate new data without increasing surveillance system burden. States, including Colorado, could consider standardization of drug testing and mandatory reporting policies for drivers involved in motor-vehicle crashes and proactively address the narrow window of time for sample collection to improve DUI of marijuana surveillance. Practical applications: The evaluation of state motor-vehicle crash systems' ability to capture crashes involving drug impaired driving (DUID) is a critical first step for identifying frequency and risk factors for crashes related to DUID. Published by Elsevier Ltd.

Best Bang for the Buck: Part 2 – Choosing Between Different Sized Designs

DOE PAGES

Anderson-Cook, Christine Michaela; Lu, Lu

2016-11-01

Last month, we considered four potential designs of varying sizes and a variety of their attributes for an engineering problem involving a screening design with seven factors. The engineer’s original request was to find a design with 14 runs that could estimate all of the main effects, as well as have some potential for finding important two-factor interactions and possibly curvature in the underlying surface. This assessment was that the proposed size of design was potentially a bit too ambitious for the experiment’s goals, so we explored three other competing designs that had slightly larger sizes but were able tomore » improve several aspects of the design.« less

The role of colonic metabolism in lactose intolerance.

PubMed

He, T; Venema, K; Priebe, M G; Welling, G W; Brummer, R-J M; Vonk, R J

2008-08-01

Lactose maldigestion and intolerance affect a large part of the world population. The underlying factors of lactose intolerance are not fully understood. In this review, the role of colonic metabolism is discussed, i.e. fermentation of lactose by the colonic microbiota, colonic processing of the fermentation metabolites and how these processes would play a role in the pathophysiology of lactose intolerance. We suggest that the balance between the removal and production rate of osmotic-active components (lactose, and intermediate metabolites, e.g. lactate, succinate, etc.) in the colon is a key factor in the development of symptoms. The involvement of the colon may provide the basis for designing new targeted strategies for dietary and clinical management of lactose intolerance.

Comparison of mixed-mode stress-intensity factors obtained through displacement correlation, J-integral formulation, and modified crack-closure integral

NASA Astrophysics Data System (ADS)

Bittencourt, Tulio N.; Barry, Ahmabou; Ingraffea, Anthony R.

This paper presents a comparison among stress-intensity factors for mixed-mode two-dimensional problems obtained through three different approaches: displacement correlation, J-integral, and modified crack-closure integral. All mentioned procedures involve only one analysis step and are incorporated in the post-processor page of a finite element computer code for fracture mechanics analysis (FRANC). Results are presented for a closed-form solution problem under mixed-mode conditions. The accuracy of these described methods then is discussed and analyzed in the framework of their numerical results. The influence of the differences among the three methods on the predicted crack trajectory of general problems is also discussed.

Best Bang for the Buck: Part 2 – Choosing Between Different Sized Designs

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

Anderson-Cook, Christine Michaela; Lu, Lu

Last month, we considered four potential designs of varying sizes and a variety of their attributes for an engineering problem involving a screening design with seven factors. The engineer’s original request was to find a design with 14 runs that could estimate all of the main effects, as well as have some potential for finding important two-factor interactions and possibly curvature in the underlying surface. This assessment was that the proposed size of design was potentially a bit too ambitious for the experiment’s goals, so we explored three other competing designs that had slightly larger sizes but were able tomore » improve several aspects of the design.« less

Neural basis of social status hierarchy across species.

PubMed

Chiao, Joan Y

2010-12-01

Social status hierarchy is a ubiquitous principle of social organization across the animal kingdom. Recent findings in social neuroscience reveal distinct neural networks associated with the recognition and experience of social hierarchy in humans, as well as modulation of these networks by personality and culture. Additionally, allelic variation in the serotonin transporter gene is associated with prevalence of social hierarchy across species and cultures, suggesting the importance of the study of genetic factors underlying social hierarchy. Future studies are needed to determine how genetic and environmental factors shape neural systems involved in the production and maintenance of social hierarchy across ontogeny and phylogeny. Copyright © 2010 Elsevier Ltd. All rights reserved.

Regulation of theta-antigen expression by agents altering cyclic AMP level and by thymic factor.

PubMed

Bach, M A; Fournier, C; Bach, J F

1975-02-28

Thymic factor, cyclic AMP, and products increasing its cellular level, such as Prostaglandin E1, induce the appearance of the theta-antigen on T-cell precursors whether assessed by a rossette-inhibition assay or a cytotoxic assay after cell fractionation on BSA discontinuous gradiet. Synergism has been demonstrated between cyclic AMPT and TF for that effect. Conversely, decrease of theta expression has been obtained by altering cyclic AMP level in theta-positive cells either increasing it by dibutyryl cAMP treatment or decreasing it by indomethacin treatment. Finally, these data suggest the involvement of cyclic AMP in the regulation of theta expression under thymic hormone control.

Insights into the etiology-associated gene regulatory networks in hepatocellular carcinoma from The Cancer Genome Atlas.

PubMed

Seshachalam, Veerabrahma Pratap; Sekar, Karthik; Hui, Kam M

2018-04-19

Hepatitis B virus, hepatitis C virus, alcoholic consumption and non-alcoholic fatty liver are the major known risk factors for Hepatocellular carcinoma (HCC). There have been very few studies comparing the underlying biological mechanisms associated with the different etiologies of HCC. In this study, we hypothesized the existence of different regulatory networks associated with different liver disease etiologies involved in hepatocarcinogenesis. Using upstream regulatory analysis tool in ingenuity pathway analysis software, URs were predicted using differential expressed genes for HCC to facilitate the interrogation of global gene regulation. Analysis of regulatory networks for HBV HCC revealed E2F1 as activated UR, regulating genes involved in cell cycle and DNA replication and HNF4A and HNF1A as inhibited UR. In HCV HCC, IFNG, involved in cellular movement and signaling was activated while IL1RN, MAPK1 involved in IL-22 signaling and immune response was inhibited. In Alcoholic-consumption HCC, ERBB2 involved in inflammatory response and cellular movement was activated, whereas HNF4A, NUPR1 were inhibited. For HCC derived from Non-alcoholic fatty liver disease, miR-1249-5p was activated and NUPR1 involved in cell cycle and apoptosis was inhibited. The prognostic value of representative genes identified in the regulatory networks for HBV HCC can be further validated by an independent HBV HCC dataset established in our laboratory with survival data. Our study identified functionally distinct candidate URs for HCC developed from different etiologic risk factors. Further functional validation studies of these regulatory networks could facilitate the management of HCC towards personalized medicine. This article is protected by copyright. All rights reserved.

Consumer involvement in mental health education for health professionals: feasibility and support for the role.

PubMed

Happell, Brenda; Bennetts, Wanda; Platania-Phung, Chris; Tohotoa, Jenny

2015-12-01

To explore factors impacting on the feasibility of academic and educator roles for consumers of mental health services. The supports required to facilitate these roles from the perspectives of mental health nurse academics and consumer educators/academics will also be explored. Involving consumers in the education of health professionals is becoming more common. Frequently this strategy is viewed as important to influence the attitudes of health professionals towards consumer participation in mental health services. There remains a paucity of research about these roles and the factors which promote and support their feasibility. Qualitative exploratory. In-depth telephone interviews were undertaken with 34 nurse academics and 12 consumer educators or academics. Participants included nurse academics coordinating undergraduate and postgraduate mental health subjects, and consumer academics and educators involved in teaching mental health nursing components. Interviews were 20-45 minutes in duration. Data were analysed thematically. Four subthemes were identified under the broad theme of feasibility and support: Reliability, support, vulnerability and seen to be griping. Significant barriers were identified by nurses and consumers to effective consumer involvement, largely reflecting the impact of mental health challenges. Despite this, there was little evidence of structured support being available to enhance the viability of these positions. Involving consumers in the education of health professionals through teaching, curriculum development, assessment and evaluation, is likely to enhance consumer participation in mental health services and ultimately improve service delivery. This involvement needs to be genuine to be effective. Consumers are often viewed as unreliable, vulnerable and using education to voice their own negative experiences. These issues and lack of support provided pose major barriers to successful roles, strategies to overcome barriers and maximise the effectiveness of roles require investigation and implementation. © 2015 John Wiley & Sons Ltd.

The Role of Hospital Inpatients in Supporting Medication Safety: A Qualitative Study.

PubMed

Garfield, Sara; Jheeta, Seetal; Husson, Fran; Lloyd, Jill; Taylor, Alex; Boucher, Charles; Jacklin, Ann; Bischler, Anna; Norton, Christine; Hayles, Rob; Franklin, Bryony Dean

2016-01-01

Inpatient medication errors are a significant concern. An approach not yet widely studied is to facilitate greater involvement of inpatients with their medication. At the same time, electronic prescribing is becoming increasingly prevalent in the hospital setting. In this study we aimed to explore hospital inpatients' involvement with medication safety-related behaviours, facilitators and barriers to this involvement, and the impact of electronic prescribing. We conducted ethnographic observations and interviews in two UK hospital organisations, one with established electronic prescribing and one that changed from paper to electronic prescribing during our study. Researchers and lay volunteers observed nurses' medication administration rounds, pharmacists' ward rounds, doctor-led ward rounds and drug history taking. We also conducted interviews with healthcare professionals, patients and carers. Interviews were audio-recorded and transcribed. Observation notes and transcripts were coded thematically. Paper or electronic medication records were shown to patients in only 4 (2%) of 247 cases. However, where they were available during patient-healthcare professional interactions, healthcare professionals often viewed them in order to inform patients about their medicines and answer any questions. Interprofessional discussions about medicines seemed more likely to happen in front of the patient where paper or electronic drug charts were available near the bedside. Patients and carers had more access to paper-based drug charts than electronic equivalents. However, interviews and observations suggest there are potentially more significant factors that affect patient involvement with their inpatient medication. These include patient and healthcare professional beliefs concerning patient involvement, the way in which healthcare professionals operate as a team, and the underlying culture. Patients appear to have more access to paper-based records than electronic equivalents. However, to develop interventions to increase patient involvement with medication safety behaviours, a wider range of factors needs to be considered.

Genetic causes of male infertility.

PubMed

Stouffs, Katrien; Seneca, Sara; Lissens, Willy

2014-05-01

Male infertility, affecting around half of the couples with a problem to get pregnant, is a very heterogeneous condition. Part of patients are having a defect in spermatogenesis of which the underlying causes (including genetic ones) remain largely unknown. The only genetic tests routinely used in the diagnosis of male infertility are the analyses for the presence of Yq microdeletions and/or chromosomal abnormalities. Various other single gene or polygenic defects have been proposed to be involved in male fertility. Yet, their causative effect often remains to be proven. The recent evolution in the development of whole genome-based techniques may help in clarifying the role of genes and other genetic factors involved in spermatogenesis and spermatogenesis defects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Adult bacterial meningitis: aetiology, penicillin susceptibility, risk factors, prognostic factors and guidelines for empirical antibiotic treatment.

PubMed

Meyer, C N; Samuelsson, I S; Galle, M; Bangsborg, J M

2004-08-01

Episodes of adult bacterial meningitis (ABM) at a Danish hospital in 1991-2000 were identified from the databases of the Department of Clinical Microbiology, and compared with data from the Danish National Patient Register and the Danish National Notification System. Reduced penicillin susceptibility occurred in 21 (23%) of 92 cases of known aetiology, compared to an estimated 6% in nationally notified cases (p < 0.001). Ceftriaxone plus penicillin as empirical treatment was appropriate in 97% of ABM cases in the study population, and in 99.6% of nationally notified cases. The notification rate was 75% for penicillin-susceptible episodes, and 24% for penicillin-non-susceptible episodes (p < 0.001). Cases involving staphylococci, Pseudomonas spp. and Enterobacteriaceae were under-reported. Among 51 ABM cases with no identified risk factors, nine of 11 cases with penicillin-non-susceptible bacteria were community-acquired. Severe sequelae correlated independently with age, penicillin non-susceptibility, mechanical ventilation and non-transferral to a tertiary hospital (p < 0.05; logistic regression). Other factors that correlated with severe sequelae by univariate analysis only were inappropriate clinical handling, abnormal consciousness, convulsions and nosocomial infection. Overall, the data indicated that neither age alone, community-acquired infection nor absence of identified risk factors can predict susceptibility to penicillin accurately. Recommendations for empirical antibiotic treatment for ABM should not be based exclusively on clinical notification systems with possible unbalanced under-reporting.

Types of social participation and psychological distress in Japanese older adults: A five-year cohort study.

PubMed

Amagasa, Shiho; Fukushima, Noritoshi; Kikuchi, Hiroyuki; Oka, Koichiro; Takamiya, Tomoko; Odagiri, Yuko; Inoue, Shigeru

2017-01-01

The most effective type of social participation against psychological distress in older adults is not well documented. The aim of this study was to examine whether different types of social participation are associated with changes in psychological distress level in older men and women in Japan. Two thousand seven hundred community-dwelling older adults (aged 65-74 years, 50% women) were randomly selected from the resident registry of three cities. Of these, participants who reported social participation and psychological distress level in the baseline survey in 2010 were followed up. Psychological distress was evaluated based on K6 scales at baseline and follow-up (in 2015). Social participation level was examined using question items from the National Health and Nutrition Survey in Japan. Exploratory factor analysis was used to derive the underlying factor structure. Multiple linear regression analysis was used to examine the association between social participation and changes in psychological distress level after adjusting for covariates stratified by both gender and age group or living arrangement. Data from 825 community-dwelling older adults (45.3% women) were analyzed. Social participation was categorized into two types using factor analysis: community involvement (volunteer activities, community events, clubs for the elderly) and individual relationship (friendship, communication with family and friends, hobbies). During the 5-year follow-up, 29.5% of participants reported a deterioration in psychological distress. Higher community involvement was independently associated with lower risk of psychological distress for older women (β = 0.099, p = 0.047), whereas there were no associations with individual relationship for either gender. Furthermore, in older women living with others, higher community involvement was also associated with lower risk of psychological distress (β = 0.110, p = 0.048). Community involvement provides older women with mental health benefits regardless of individual relationship level. Promoting community involvement may be an effective strategy for healthy mental aging.

Life cycle assessment of potential biojet fuel production in the United States.

PubMed

Agusdinata, Datu B; Zhao, Fu; Ileleji, Klein; DeLaurentis, Dan

2011-11-01

The objective of this paper is to reveal to what degree biobased jet fuels (biojet) can reduce greenhouse gas (GHG) emissions from the U.S. aviation sector. A model of the supply and demand chain of biojet involving farmers, biorefineries, airlines, and policymakers is developed by considering factors that drive the decisions of actors (i.e., decision-makers and stakeholders) in the life cycle stages. Two kinds of feedstock are considered: oil-producing feedstock (i.e., camelina and algae) and lignocellulosic biomass (i.e., corn stover, switchgrass, and short rotation woody crops). By factoring in farmer/feedstock producer and biorefinery profitability requirements and risk attitudes, land availability and suitability, as well as a time delay and technological learning factor, a more realistic estimate of the level of biojet supply and emissions reduction can be developed under different oil price assumptions. Factors that drive biojet GHG emissions and unit production costs from each feedstock are identified and quantified. Overall, this study finds that at likely adoption rates biojet alone would not be sufficient to achieve the aviation emissions reduction target. In 2050, under high oil price scenario assumption, GHG emissions can be reduced to a level ranging from 55 to 92%, with a median value of 74%, compared to the 2005 baseline level.

ABA signaling in stress-response and seed development.

PubMed

Nakashima, Kazuo; Yamaguchi-Shinozaki, Kazuko

2013-07-01

KEY MESSAGE : We review the recent progress on ABA signaling, especially ABA signaling for ABA-dependent gene expression, including the AREB/ABF regulon, SnRK2 protein kinase, 2C-type protein phosphatases and ABA receptors. Drought negatively impacts plant growth and the productivity of crops. Drought causes osmotic stress to organisms, and the osmotic stress causes dehydration in plant cells. Abscisic acid (ABA) is produced under osmotic stress conditions, and it plays an important role in the stress response and tolerance of plants. ABA regulates many genes under osmotic stress conditions. It also regulates gene expression during seed development and germination. The ABA-responsive element (ABRE) is the major cis-element for ABA-responsive gene expression. ABRE-binding protein (AREB)/ABRE-binding factor (ABF) transcription factors (TFs) regulate ABRE-dependent gene expression. Other TFs are also involved in ABA-responsive gene expression. SNF1-related protein kinases 2 are the key regulators of ABA signaling including the AREB/ABF regulon. Recently, ABA receptors and group A 2C-type protein phosphatases were shown to govern the ABA signaling pathway. Moreover, recent studies have suggested that there are interactions between the major ABA signaling pathway and other signaling factors in stress-response and seed development. The control of the expression of ABA signaling factors may improve tolerance to environmental stresses.

Individual neurophysiological profile in external effects investigation

NASA Astrophysics Data System (ADS)

Schastlivtseva, Daria; Tatiana Kotrovskaya, D..

Cortex biopotentials are the significant elements in human psychophysiological individuality. Considered that cortical biopotentials are diverse and individually stable, therefore there is the existence of certain dependence between the basic properties of higher nervous activity and cerebral bioelectric activity. The main purpose of the study was to reveal the individual neurophysiological profile and CNS initial functional state manifestation in human electroencephalogram (EEG) under effect of inert gases (argon, xenon, helium), hypoxia, pressure changes (0.02 and 0.2 MPa). We obtained 5-minute eyes closed background EEG on 19 scalp positions using Ag/AgCl electrodes mounted in an electrode cap. All EEG signals were re-referenced to average earlobes; Fast Furies Transformation analysis was used to calculate the relative power spectrum of delta-, theta-, alpha- and beta frequency band in artifact-free EEG. The study involved 26 healthy men who provided written informed consent, aged 20 to 35 years. Data obtained depend as individual EEG type and initial central nervous functional state as intensity, duration and mix of factors. Pronounced alpha rhythm in the raw EEG correlated with their adaptive capacity under studied factor exposure. Representation change and zonal distribution perversion of EEG alpha rhythm were accompanied by emotional instability, increased anxiety and difficulty adapting subjects. High power factor or combination factor with psychological and emotional or physical exertion minimizes individual EEG pattern.

A WRKY Transcription Factor Regulates Fe Translocation under Fe Deficiency.

PubMed

Yan, Jing Ying; Li, Chun Xiao; Sun, Li; Ren, Jiang Yuan; Li, Gui Xin; Ding, Zhong Jie; Zheng, Shao Jian

2016-07-01

Iron (Fe) deficiency affects plant growth and development, leading to reduction of crop yields and quality. Although the regulation of Fe uptake under Fe deficiency has been well studied in the past decade, the regulatory mechanism of Fe translocation inside the plants remains unknown. Here, we show that a WRKY transcription factor WRKY46 is involved in response to Fe deficiency. Lack of WRKY46 (wrky46-1 and wrky46-2 loss-of-function mutants) significantly affects Fe translocation from root to shoot and thus causes obvious chlorosis on the new leaves under Fe deficiency. Gene expression analysis reveals that expression of a nodulin-like gene (VACUOLAR IRON TRANSPORTER1-LIKE1 [VITL1]) is dramatically increased in wrky46-1 mutant. VITL1 expression is inhibited by Fe deficiency, while the expression of WRKY46 is induced in the root stele. Moreover, down-regulation of VITL1 expression can restore the chlorosis phenotype on wrky46-1 under Fe deficiency. Further yeast one-hybrid and chromatin immunoprecipitation experiments indicate that WRKY46 is capable of binding to the specific W-boxes present in the VITL1 promoter. In summary, our results demonstrate that WRKY46 plays an important role in the control of root-to-shoot Fe translocation under Fe deficiency condition via direct regulation of VITL1 transcript levels. © 2016 American Society of Plant Biologists. All Rights Reserved.

Cell type-selective disease-association of genes under high regulatory load.

PubMed

Galhardo, Mafalda; Berninger, Philipp; Nguyen, Thanh-Phuong; Sauter, Thomas; Sinkkonen, Lasse

2015-10-15

We previously showed that disease-linked metabolic genes are often under combinatorial regulation. Using the genome-wide ChIP-Seq binding profiles for 93 transcription factors in nine different cell lines, we show that genes under high regulatory load are significantly enriched for disease-association across cell types. We find that transcription factor load correlates with the enhancer load of the genes and thereby allows the identification of genes under high regulatory load by epigenomic mapping of active enhancers. Identification of the high enhancer load genes across 139 samples from 96 different cell and tissue types reveals a consistent enrichment for disease-associated genes in a cell type-selective manner. The underlying genes are not limited to super-enhancer genes and show several types of disease-association evidence beyond genetic variation (such as biomarkers). Interestingly, the high regulatory load genes are involved in more KEGG pathways than expected by chance, exhibit increased betweenness centrality in the interaction network of liver disease genes, and carry longer 3' UTRs with more microRNA (miRNA) binding sites than genes on average, suggesting a role as hubs integrating signals within regulatory networks. In summary, epigenetic mapping of active enhancers presents a promising and unbiased approach for identification of novel disease genes in a cell type-selective manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cycles of Ubiquitination and Deubiquitination Critically Regulate Growth Factor-Mediated Activation of Akt Signaling

PubMed Central

Yang, Wei-Lei; Jin, Guoxiang; Li, Chien-Feng; Jeong, Yun Seong; Moten, Asad; Xu, Dazhi; Feng, Zizhen; Chen, Wei; Cai, Zhen; Darnay, Bryant; Gu, Wei; Lin, Hui-Kuan

2013-01-01

K63-linked ubiquitination of Akt is a posttranslational modification that plays a critical role in growth factor-mediated membrane recruitment and activation of Akt. Although E3 ligases involved in growth factor-induced Akt ubiquitination have been defined, the deubiquitinating enzyme (DUB) that triggers deubiquitination of Akt and the function of Akt deubiquitination remain largely unclear. Here, we showed that CYLD was a DUB for Akt and suppressed growth factor-mediated Akt ubiquitination and activation. CYLD directly removed ubiquitin moieties on Akt under serum-starved conditions. CYLD dissociated from Akt upon growth factor stimulation, thereby allowing E3 ligases to induce ubiquitination and activation of Akt. CYLD deficiency also promoted cancer cell proliferation, survival, glucose uptake and growth of prostate tumors. Our findings reveal the crucial role of cycles of ubiquitination and deubiquitination of Akt in its membrane recruitment and activation, and further identifies CYLD as a molecular switch for these processes. PMID:23300340

Scheffersomyces stipitis: a comparative systems biology study with the Crabtree positive yeast Saccharomyces cerevisiae

PubMed Central

2012-01-01

Background Scheffersomyces stipitis is a Crabtree negative yeast, commonly known for its capacity to ferment pentose sugars. Differently from Crabtree positive yeasts such as Saccharomyces cerevisiae, the onset of fermentation in S. stipitis is not dependent on the sugar concentration, but is regulated by a decrease in oxygen levels. Even though S. stipitis has been extensively studied due to its potential application in pentoses fermentation, a limited amount of information is available about its metabolism during aerobic growth on glucose. Here, we provide a systems biology based comparison between the two yeasts, uncovering the metabolism of S. stipitis during aerobic growth on glucose under batch and chemostat cultivations. Results Starting from the analysis of physiological data, we confirmed through 13C-based flux analysis the fully respiratory metabolism of S. stipitis when growing both under glucose limited or glucose excess conditions. The patterns observed showed similarity to the fully respiratory metabolism observed for S. cerevisiae under chemostat cultivations however, intracellular metabolome analysis uncovered the presence of several differences in metabolite patterns. To describe gene expression levels under the two conditions, we performed RNA sequencing and the results were used to quantify transcript abundances of genes from the central carbon metabolism and compared with those obtained with S. cerevisiae. Interestingly, genes involved in central pathways showed different patterns of expression, suggesting different regulatory networks between the two yeasts. Efforts were focused on identifying shared and unique families of transcription factors between the two yeasts through in silico transcription factors analysis, suggesting a different regulation of glycolytic and glucoenogenic pathways. Conclusions The work presented addresses the impact of high-throughput methods in describing and comparing the physiology of Crabtree positive and Crabtree negative yeasts. Based on physiological data and flux analysis we identified the presence of one metabolic condition for S. stipitis under aerobic batch and chemostat cultivations, which shows similarities to the oxidative metabolism observed for S. cerevisiae under chemostat cultivations. Through metabolome analysis and genome-wide transcriptomic analysis several differences were identified. Interestingly, in silico analysis of transciption factors was useful to address a different regulation of mRNAs of genes involved in the central carbon metabolism. To our knowledge, this is the first time that the metabolism of S. stiptis is investigated in details and is compared to S. cerevisiae. Our study provides useful results and allows for the possibility to incorporate these data into recently developed genome-scaled metabolic, thus contributing to improve future industrial applications of S. stipitis as cell factory. PMID:23043429

Investigation of pajama properties on skin under mild cold conditions: the interaction between skin and clothing.

PubMed

Yao, Lei; Gohel, Mayur D I; Li, Yi; Chung, Waiyee J

2011-07-01

Clothing is considered the second skin of the human body. The aim of this study was to determine clothing-wearer interaction on skin physiology under mild cold conditions. Skin physiological parameters, subjective sensory response, stress level, and physical properties of clothing fabric from two longitude parallel-designed wear trials were studied. The wear trials involved four kinds of pajamas made from cotton or polyester material that had hydrophilic or hydrophobic treatment, conducted for three weeks under mild cold conditions. Statistical tools, factor analysis, hierarchical linear regression, and logistic regression were applied to analyze the strong predictors of skin physiological parameters, stress level, and sensory response. A framework was established to illustrate clothing-wearer interactions with clothing fabric properties, skin physiology, stress level, and sensory response under mild cold conditions. Fabric has various effects on the human body under mild cold conditions. A fabric's properties influence skin physiology, sensation, and psychological response. © 2011 The International Society of Dermatology.

Potential involvement of drought-induced Ran GTPase CLRan1 in root growth enhancement in a xerophyte wild watermelon.

PubMed

Akashi, Kinya; Yoshimura, Kazuya; Kajikawa, Masataka; Hanada, Kouhei; Kosaka, Rina; Kato, Atsushi; Katoh, Akira; Nanasato, Yoshihiko; Tsujimoto, Hisashi; Yokota, Akiho

2016-10-01

Enhanced root growth is known as the survival strategy of plants under drought. Previous proteome analysis in drought-resistant wild watermelon has shown that Ran GTPase, an essential regulator of cell division and proliferation, was induced in the roots under drought. In this study, two cDNAs were isolated from wild watermelon, CLRan1 and CLRan2, which showed a high degree of structural similarity with those of other plant Ran GTPases. Quantitative RT-PCR and promoter-GUS assays suggested that CLRan1 was expressed mainly in the root apex and lateral root primordia, whereas CLRan2 was more broadly expressed in other part of the roots. Immunoblotting analysis confirmed that the abundance of CLRan proteins was elevated in the root apex region under drought stress. Transgenic Arabidopsis overexpressing CLRan1 showed enhanced primary root growth, and the growth was maintained under osmotic stress, indicating that CLRan1 functions as a positive factor for maintaining root growth under stress conditions.

Comparison of motives underlying food choice and barriers to healthy eating among low medium income consumers in Uruguay.

PubMed

Ares, Gastón; Machín, Leandro; Girona, Alejandra; Curutchet, María Rosa; Giménez, Ana

2017-05-18

Interventions aimed at changing dietary patterns should be designed based on the main motives underlying the food choices of specific target populations. The aim of the present study was to identify motives underlying food choice and barriers to healthy eating among consumers in two socioeconomic levels in Uruguay. Eleven focus groups were carried out with a total of 76 participants. Six of the groups involved low income participants and the others were conducted with middle income participants. Discussions were held around frequently consumed products, motives underlying food choices and barriers to healthy eating. Results confirmed the strong influence of income level on motives underlying food choice and barriers to the adoption of healthy eating. Low income participants described their choices as mainly driven by economic factors and satiety, whereas convenience was the main determinant of food selection for middle income participants. Implications for the design of public policies targeted at each group are discussed.

Regulation of the reserve carbohydrate metabolism by alkaline pH and calcium in Neurospora crassa reveals a possible cross-regulation of both signaling pathways.

PubMed

Virgilio, Stela; Cupertino, Fernanda Barbosa; Ambrosio, Daniela Luz; Bertolini, Maria Célia

2017-06-09

Glycogen and trehalose are storage carbohydrates and their levels in microorganisms vary according to environmental conditions. In Neurospora crassa, alkaline pH stress highly influences glycogen levels, and in Saccharomyces cerevisiae, the response to pH stress also involves the calcineurin signaling pathway mediated by the Crz1 transcription factor. Recently, in yeast, pH stress response genes were identified as targets of Crz1 including genes involved in glycogen and trehalose metabolism. In this work, we present evidence that in N. crassa the glycogen and trehalose metabolism is modulated by alkaline pH and calcium stresses. We demonstrated that the pH signaling pathway in N. crassa controls the accumulation of the reserve carbohydrates glycogen and trehalose via the PAC-3 transcription factor, which is the central regulator of the signaling pathway. The protein binds to the promoters of most of the genes encoding enzymes of glycogen and trehalose metabolism and regulates their expression. We also demonstrated that the reserve carbohydrate levels and gene expression are both modulated under calcium stress and that the response to calcium stress may involve the concerted action of PAC-3. Calcium activates growth of the Δpac-3 strain and influences its glycogen and trehalose accumulation. In addition, calcium stress differently regulates glycogen and trehalose metabolism in the mutant strain compared to the wild-type strain. While glycogen levels are decreased in both strains, the trehalose levels are significantly increased in the wild-type strain and not affected by calcium in the mutant strain when compared to mycelium not exposed to calcium. We previously reported the role of PAC-3 as a transcription factor involved in glycogen metabolism regulation by controlling the expression of the gsn gene, which encodes an enzyme of glycogen synthesis. In this work, we extended the investigation by studying in greater detail the effects of pH on the metabolism of the reserve carbohydrate glycogen and trehalose. We also demonstrated that calcium stress affects the reserve carbohydrate levels and the response to calcium stress may require PAC-3. Considering that the reserve carbohydrate metabolism may be subjected to different signaling pathways control, our data contribute to the understanding of the N. crassa responses under pH and calcium stresses.

A new mutant of Arabidopsis disturbed in its roots, right-handed slanting, and gravitropism defines a gene that encodes a heat-shock factor.

PubMed

Fortunati, A; Piconese, S; Tassone, P; Ferrari, S; Migliaccio, F

2008-01-01

A new mutant of Arabidopsis named rha1 is characterized and the gene involved cloned. In roots, the mutant shows minimal right-handed slanting, reduced gravitropic response, notable resistance to 2,4-D, but scarce resistance to IAA and NAA. The roots also show a clear resistance to the auxin transport inhibitors TIBA and NPA, and to ethylene. Other characteristics are a reduced number of lateral roots and reduced size of shoot and root in the seedlings. The gene, cloned through TAIL-PCR, was found to be a heat-shock factor that maps on chromosome 5, close to and above the RFLP marker m61. The rha1 structure, mRNA, and translation product are reported. Since, so far, no other gravitropic mutant has been described as mutated in a heat-shock factor, rha1 belongs to a new group of mutants disturbed in slanting, gravitropism, and auxin physiology. As shown through the RT-PCR analyses of its expression, the gene retains the function connected with heat shock. If the characteristics connected with auxin physiology are considered, however, it is also likely that the gene, as a transcription factor, could be involved in root circumnutation, gravitropic response, and hormonal control of differentiation. Since GUS staining under the gene promoter was localized mainly in the mature tissues, rha1 does not seem to be involved in the first steps of gravitropism, but is rather related to the general response to auxin. The alterations in slanting (mainly due to reduced chiral circumnutation) and gravitropism lead to the supposition that the two processes may have, at least in part, common origins.

Implementing family involvement in the treatment of patients with psychosis: a systematic review of facilitating and hindering factors.

PubMed

Eassom, Erica; Giacco, Domenico; Dirik, Aysegul; Priebe, Stefan

2014-10-03

To synthesise the evidence on implementing family involvement in the treatment of patients with psychosis with a focus on barriers, problems and facilitating factors. Systematic review of studies evaluating the involvement of families in tripartite communication between health professionals, 'families' (or other unpaid carers) and adult patients, in a single-family context. A theoretical thematic analysis approach and thematic synthesis were used. A systematic electronic search was carried out in seven databases, using database-specific search strategies and controlled vocabulary. A secondary manual search of grey literature was performed as well as using forwards and backwards snowballing techniques. A total of 43 studies were included. The majority featured qualitative data (n=42), focused solely on staff perspectives (n=32) and were carried out in the UK (n=23). Facilitating the training and ongoing supervision needs of staff are necessary but not sufficient conditions for a consistent involvement of families. Organisational cultures and paradigms can work to limit family involvement, and effective implementation appears to operate via a whole team coordinated effort at every level of the organisation, supported by strong leadership. Reservations about family involvement regarding power relations, fear of negative outcomes and the need for an exclusive patient-professional relationship may be explored and addressed through mutually trusting relationships. Implementing family involvement carries additional challenges beyond those generally associated with translating research to practice. Implementation may require a cultural and organisational shift towards working with families. Family work can only be implemented if this is considered a shared goal of all members of a clinical team and/or mental health service, including the leaders of the organisation. This may imply a change in the ethos and practices of clinical teams, as well as the establishment of working routines that facilitate family involvement approaches. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Spatial distribution and cognitive correlates of gamma noise power in schizophrenia.

PubMed

Díez, A; Suazo, V; Casado, P; Martín-Loeches, M; Molina, V

2013-06-01

Brain activity is less organized in patients with schizophrenia than in healthy controls (HC). Noise power (scalp-recorded electroencephalographic activity unlocked to stimuli) may be of use for studying this disorganization. Method Fifty-four patients with schizophrenia (29 minimally treated and 25 stable treated), 23 first-degree relatives and 27 HC underwent clinical and cognitive assessments and an electroencephalographic recording during an oddball P300 paradigm to calculate noise power magnitude in the gamma band. We used a principal component analysis (PCA) to determine the factor structure of gamma noise power values across electrodes and the clinical and cognitive correlates of the resulting factors. The PCA revealed three noise power factors, roughly corresponding to the default mode network (DMN), frontal and occipital regions respectively. Patients showed higher gamma noise power loadings in the first factor when compared to HC and first-degree relatives. In the patients, frontal gamma noise factor scores related significantly and inversely to working memory and problem-solving performance. There were no associations with symptoms. There is an elevated gamma activity unrelated to task processing over regions coherent with the DMN topography in patients with schizophrenia. The same type of gamma activity over frontal regions is inversely related to performance in tasks with high involvement in these frontal areas. The idea of gamma noise as a possible biological marker for schizophrenia seems promising. Gamma noise might be of use in the study of underlying neurophysiological mechanisms involved in this disease.

Identification of basic/helix-loop-helix transcription factors reveals candidate genes involved in anthocyanin biosynthesis from the strawberry white-flesh mutant.

PubMed

Zhao, Fengli; Li, Gang; Hu, Panpan; Zhao, Xia; Li, Liangjie; Wei, Wei; Feng, Jiayue; Zhou, Houcheng

2018-02-09

As the second largest transcription factor family in plant, the basic helix-loop-helix (bHLH) transcription factor family, characterized by the conserved bHLH domain, plays a central regulatory role in many biological process. However, the bHLH transcription factor family of strawberry has not been systematically identified, especially for the anthocyanin biosynthesis. Here, we identified a total of 113 bHLH transcription factors and described their chromosomal distribution and bioinformatics for the diploid woodland strawberry Fragaria vesca. In addition, transcription profiles of 113 orthologous bHLH genes from various tissues were analyzed for the cultivar 'Benihoppe', its white-flesh mutant 'Xiaobai', and the 'Snow Princess' from their fruit development to the ripening, as well as those under either the ABA or Eth treatment. Both the RT-PCR and qRT-PCR results show that seven selected FabHLH genes (FabHLH17, FabHLH25, FabHLH27, FabHLH29, FabHLH40, FabHLH80, FabHLH98) are responsive to the fruit anthocyanin biosynthesis and hormone signaling according to transcript profiles where three color modes are observed for strawberry's fruit skin and flesh. Further, prediction for the protein interaction network reveals that four bHLHs (FabHLH25, FabHLH29, FabHLH80, FabHLH98) are involved in the fruit anthocyanin biosynthesis and hormone signaling transduction. These bioinformatics and expression profiles provide a good basis for a further investigation of strawberry bHLH genes.

Gemfibrozil pretreatment resulted in a sexually dimorphic outcome in the rat models of global cerebral ischemia-reperfusion via modulation of mitochondrial pro-survival and apoptotic cell death factors as well as MAPKs.

PubMed

Mohagheghi, Fatemeh; Ahmadiani, Abolhassan; Rahmani, Behrouz; Moradi, Fatemeh; Romond, Nathalie; Khalaj, Leila

2013-07-01

Inducers of mitochondrial biogenesis are widely under investigation for use in a novel therapeutic approach in neurodegenerative disorders. The ability of Gemfibrozil, a fibrate, is investigated for the first time to modulate mitochondrial pro-survival factors involved in the mitochondrial biogenesis signaling pathway, including peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF-1), and mitochondrial transcription factor A (TFAM) in the brain. Gemfibozil is clinically administered to control hyperlipidemia. It secondarily prevents cardiovascular events such as cardiac arrest in susceptible patients. In this study, pretreatment of animals with gemfibrozil prior to ischemia-reperfusion (I/R) resulted in a sexually dimorphic outcome. While the expression of NRF-1 and TFAM were induced in gemfibrozil-pretreated met-estrous females, they were suppressed in males. Gemfibrozil also proved to be neuroprotective in met-estrous females, as it inhibited caspase-dependent apoptosis while in males it led to hippocampal neurodegeneration via activation of both the caspase-dependent and caspase-independent apoptosis. In the mitogen-activated protein kinase (MAPKs) pathway, gemfibrozil pretreatment induced the expression of extracellular signal-regulated kinases (ERK1/2) in met-estrous females and reduced it in males. These findings correlatively point to the sexual-dimorphic effects of gemfibrozil in global cerebral I/R context by affecting important factors involved in the mitochondrial biogenesis, MAPKs, and apoptotic cell death pathways.

Cell-Nonautonomous Mechanisms Underlying Cellular and Organismal Aging.

PubMed

Medkour, Younes; Svistkova, Veronika; Titorenko, Vladimir I

2016-01-01

Cell-autonomous mechanisms underlying cellular and organismal aging in evolutionarily distant eukaryotes have been established; these mechanisms regulate longevity-defining processes within a single eukaryotic cell. Recent findings have provided valuable insight into cell-nonautonomous mechanisms modulating cellular and organismal aging in eukaryotes across phyla; these mechanisms involve a transmission of various longevity factors between different cells, tissues, and organisms. Herein, we review such cell-nonautonomous mechanisms of aging in eukaryotes. We discuss the following: (1) how low molecular weight transmissible longevity factors modulate aging and define longevity of cells in yeast populations cultured in liquid media or on solid surfaces, (2) how communications between proteostasis stress networks operating in neurons and nonneuronal somatic tissues define longevity of the nematode Caenorhabditis elegans by modulating the rates of aging in different tissues, and (3) how different bacterial species colonizing the gut lumen of C. elegans define nematode longevity by modulating the rate of organismal aging. Copyright © 2016. Published by Elsevier Inc.

Phytoextraction potential of poplar (Populus alba L. var. pyramidalis Bunge) from calcareous agricultural soils contaminated by cadmium.

PubMed

Hu, Yahu; Nan, Zhongren; Jin, Cheng; Wang, Ning; Luo, Huanzhang

2014-01-01

To investigate the phytoextraction potential of Populus alba L. var. pyramidalis Bunge for cadmium (Cd) contaminated calcareous soils, a concentration gradient experiment and a field sampling experiment (involving poplars of different ages) were conducted. The translocation factors for all experiments and treatments were greater than 1. The bioconcentration factor decreased from 2.37 to 0.25 with increasing soil Cd concentration in the concentration gradient experiment and generally decreased with stand age under field conditions. The Cd concentrations in P. pyramidalis organs decreased in the order of leaves > stems > roots. The shoot biomass production in the concentration gradient experiment was not significantly reduced with soil Cd concentrations up to or slightly over 50 mg kg(-1). The results show that the phytoextraction efficiency of P. pyramidalis depends on both the soil Cd concentration and the tree age. Populus pyramidalis is most suitable for remediation of slightly Cd contaminated calcareous soils through the combined harvest of stems and leaves under actual field conditions.

Inconclusive quantum measurements and decisions under uncertainty

NASA Astrophysics Data System (ADS)

Yukalov, Vyacheslav; Sornette, Didier

2016-04-01

We give a mathematical definition for the notion of inconclusive quantum measurements. In physics, such measurements occur at intermediate stages of a complex measurement procedure, with the final measurement result being operationally testable. Since the mathematical structure of Quantum Decision Theory has been developed in analogy with the theory of quantum measurements, the inconclusive quantum measurements correspond, in Quantum Decision Theory, to intermediate stages of decision making in the process of taking decisions under uncertainty. The general form of the quantum probability for a composite event is the sum of a utility factor, describing a rational evaluation of the considered prospect, and of an attraction factor, characterizing irrational, subconscious attitudes of the decision maker. Despite the involved irrationality, the probability of prospects can be evaluated. This is equivalent to the possibility of calculating quantum probabilities without specifying hidden variables. We formulate a general way of evaluation, based on the use of non-informative priors. As an example, we suggest the explanation of the decoy effect. Our quantitative predictions are in very good agreement with experimental data.

Emotional regulation of fertility decision making: what is the nature and structure of "baby fever"?

PubMed

Brase, Gary L; Brase, Sandra L

2012-10-01

Baby fever-a visceral physical and emotional desire to have a baby-is well known in popular culture, but has not been empirically studied in psychology. Different theoretical perspectives suggest that desire for a baby is either superfluous to biological sex drives and maternal instincts, a sociocultural phenomenon unrelated to biological or evolutionary forces, or an evolved adpatation for regulating birth timing, proceptive behavior, and life history trajectories. A series of studies (involving 337 undergraduate participants and 853 participants from a general population Internet sample) found that: (a) a simple scale measure could elicit ratings of desire frequency; (b) these ratings exhibited significant sex differences; (c) this sex difference was distinct from a general desire for sexual activity; and (d) these findings generalize to a more diverse online population. Factor analyses of ratings for desire elicitors/inhibitors identified three primary factors underlying baby fever. Baby fever appears to be a real phenomenon, with an underlying multifactorial structure.

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

Wang, Huan, E-mail: wanghuan7@126.com; Institute for Liver Diseases of Anhui Medical University; Wang, Ying-hong

Metabolic syndrome characterized by hyperglycemia contributes to nonalcoholic steatohepatitis-associated liver fibrosis. This study was to investigate the effects of Acid-sensing ion Channel 1a (ASIC1a) on the process of liver fibrosis under hyperglycemia. Results showed that high glucose significantly worsen the pathology of liver fibrosis in vivo. In vitro, high glucose stimulated proliferation, activation and extracellular matrix (ECM) production in HSCs, and enhanced the effect of PDGF-BB on the activation and proliferation of HSCs. These effects could be attenuated by ASIC1a specific inhibitor Psalmotoxin-1(PcTx1) or specific ShRNA for ASIC1a through Notch1/Hes-1 pathways. These data indicate that ASIC1a plays an important role in diabetesmore » complication liver fibrosis. - Highlights: • Hyperglycemia is a risk factor for the process of liver fibrosis. • ASIC1a may be a key factor linking between high glucose and liver fibrosis. • Notch1/Hes-1 may involve to the process of liver fibrosis under hyperglycemia.« less

Direct evidence for tumor necrosis factor-induced mitochondrial reactive oxygen intermediates and their involvement in cytotoxicity.

PubMed Central

Goossens, V; Grooten, J; De Vos, K; Fiers, W

1995-01-01

Tumor necrosis factor (TNF) is selectively cytotoxic to some types of tumor cells in vitro and exerts antitumor activity in vivo. Reactive oxygen intermediates (ROIs) have been implicated in the direct cytotoxic activity of TNF. By using confocal microscopy, flow cytometry, and the ROI-specific probe dihydrorhodamine 123, we directly demonstrate that intracellular ROIs are formed after TNF stimulation. These ROIs are observed exclusively under conditions where cells are sensitive to the cytotoxic activity of TNF, suggesting a direct link between both phenomena. ROI scavengers, such as butylated hydroxyanisole, effectively blocked the formation of free radicals and arrested the cytotoxic response, confirming that the observed ROIs are cytocidal. The mitochondrial glutathione system scavenges the major part of the produced ROIs, an activity that could be blocked by diethyl maleate; under these conditions, TNF-induced ROIs detectable by dihydrorhodamine 123 oxidation were 5- to 20-fold higher. Images Fig. 1 Fig. 4 PMID:7667254

Phytochrome-imposed oscillations in PIF3 protein abundance regulate hypocotyl growth under diurnal light/dark conditions in Arabidopsis.

PubMed

Soy, Judit; Leivar, Pablo; González-Schain, Nahuel; Sentandreu, Maria; Prat, Salomé; Quail, Peter H; Monte, Elena

2012-08-01

Arabidopsis seedlings display rhythmic growth when grown under diurnal conditions, with maximal elongation rates occurring at the end of the night under short-day photoperiods. Current evidence indicates that this behavior involves the action of the growth-promoting bHLH factors PHYTOCHROME-INTERACTING FACTOR 4 (PIF4) and PHYTOCHROME-INTERACTING FACTOR 5 (PIF5) at the end of the night, through a coincidence mechanism that combines their transcriptional regulation by the circadian clock with control of protein accumulation by light. To assess the possible role of PIF3 in this process, we have analyzed hypocotyl responses and marker gene expression in pif single- and higher-order mutants. The data show that PIF3 plays a prominent role as a promoter of seedling growth under diurnal light/dark conditions, in conjunction with PIF4 and PIF5. In addition, we provide evidence that PIF3 functions in this process through its intrinsic transcriptional regulatory activity, at least in part by directly targeting growth-related genes, and independently of its ability to regulate phytochrome B (phyB) levels. Furthermore, in sharp contrast to PIF4 and PIF5, our data show that the PIF3 gene is not subject to transcriptional regulation by the clock, but that PIF3 protein abundance oscillates under diurnal conditions as a result of a progressive decline in PIF3 protein degradation mediated by photoactivated phyB, and consequent accumulation of the bHLH factor during the dark period. Collectively, the data suggest that phyB-mediated, post-translational regulation allows PIF3 accumulation to peak just before dawn, at which time it accelerates hypocotyl growth, together with PIF4 and PIF5, by directly regulating the induction of growth-related genes. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

When underadditivity of factor effects in the Psychological Refractory Period paradigm implies a bottleneck: evidence from psycholinguistics.

PubMed

Besner, Derek; Reynolds, Mike; O'Malley, Shannon

2009-11-01

The Psychological Refractory Period (PRP) paradigm is a dual-task procedure that can be used to examine the resource demands of specific cognitive processes. Inferences about the underlying processes are typically based on performance in the second of two speeded tasks. If the effect of a factor manipulated in Task 2 decreases as the stimulus onset asynchrony (SOA) between tasks decreases (underadditivity), the normative inference is that the effect of this factor occurs prior to a limited-capacity central processing mechanism. In contrast, if the effect of a factor is additive with SOA then the inference is that this indexes a process that either uses a limited-capacity central processing mechanism or occurs after some process that uses this mechanism. A heretofore unidentified exception to this logic arises when Task 2 involves two separate processes that operate in parallel, but compete. Interference with one process in Task 2 because of work on Task 1 will eliminate or reduce competition within Task 2 and is hence manifest as an underadditive interaction with decreasing SOA. This is illustrated here by reference to a PRP experiment in which the ubiquitous effect of spelling-to-sound regularity on reading aloud time is eliminated at a short SOA and by consideration of three converging lines of investigation in the PRP paradigm when Task 2 involves reading aloud.

Factors Affecting the Latitudinal Location of the Intertropical Convergence Zone in a GCM

NASA Technical Reports Server (NTRS)

Chao, Winston C.; Chen, Baode

2002-01-01

The dominant role of the latitudinal peak of the sea surface temperature (SST) in determining the latitudinal location of the intertropical convergence zone (ITCZ) is well-known. However, the roles of the other factors are less well-known and are the topic of this study. These other factors include the inertial stability, the interaction between convection and surface fluxes and the interaction between convection and radiation. Since these interactions involve convection, in a model they involve the cumulus parameterization scheme. These factors are studied with a general circulation model with uniform SST and solar angle. Under the aforementioned model settings, the latitudinal location of the ITCZ is the latitude where the balance of two types of attraction on the ITCZ, both due to earth's rotation, exists. Directly related to the Coriolis parameter, the first type pulls the ITCZ toward the equator and is not sensitive to model design changes. Related to the convective circulation, the second type pulls the ITCZ poleward and is sensitive to model design changes. Due to the shape and the magnitude of the attractors, the balance of the two types of attractions is reached either at the equator or more than 10 degrees away from the equator. The former case results in a single ITCZ over the equator and the latter case a double ITCZ straddling the equator.

The genetics of pre-eclampsia and other hypertensive disorders of pregnancy

PubMed Central

Williams, Paula J.; Broughton Pipkin, Fiona

2011-01-01

Hypertension is the most frequent medical complication occurring during pregnancy. In this chapter, we aim to address the genetic contribution to these disorders, with specific focus on pre-eclampsia. The pathogenic mechanisms underlying pre-eclampsia remain to be elucidated; however, immune maladaptation, inadequate placental development and trophoblast invasion, placental ischaemia, oxidative stress and thrombosis are all thought to represent key factors in the development of disease. Furthermore, all of these components have genetic factors that may be involved in the pathogenic changes occurring. The familial nature of pre-eclampsia has been known for many years and, as such, extensive genetic research has been carried out in this area using strategies that include candidate gene studies and linkage analysis. Interactions between fetal and maternal genotypes, the effect of environmental factors, and epistasis will also be considered. PMID:21429808

Aspergillosis and stem cell transplantation: An overview of experimental pathogenesis studies.

PubMed

Al-Bader, Nadia; Sheppard, Donald C

2016-11-16

Invasive aspergillosis is a life-threatening infection caused by the opportunistic filamentous fungus Aspergillus fumigatus. Patients undergoing haematopoietic stem cell transplant (HSCT) for the treatment of hematological malignancy are at particularly high risk of developing this fatal infection. The susceptibility of HSCT patients to infection with A. fumigatus is a consequence of a complex interplay of both fungal and host factors. Here we review our understanding of the host-pathogen interactions underlying the susceptibility of the immunocompromised host to infection with A. fumigatus with a focus on the experimental validation of fungal and host factors relevant to HSCT patients. These include fungal factors such as secondary metabolites, cell wall constituents, and metabolic adaptations that facilitate immune evasion and survival within the host microenvironment, as well as the innate and adaptive immune responses involved in host defense against A. fumigatus.

Proteomic Analysis of Differentially Expressed Proteins Involved in Peel Senescence in Harvested Mandarin Fruit

PubMed Central

Li, Taotao; Zhang, Jingying; Zhu, Hong; Qu, Hongxia; You, Shulin; Duan, Xuewu; Jiang, Yueming

2016-01-01

Mandarin (Citrus reticulata), a non-climacteric fruit, is an economically important fruit worldwide. The mechanism underlying senescence of non-climacteric fruit is poorly understood. In this study, a gel-based proteomic study followed by LC-ESI-MS/MS analysis was carried out to investigate the proteomic changes involved in peel senescence in harvested mandarin “Shatangju” fruit stored for 18 days. Over the course of the storage period, the fruit gradually senesced, accompanied by a decreased respiration rate and increased chlorophyll degradation and disruption of membrane integrity. Sixty-three proteins spots that showed significant differences in abundance were identified. The up-regulated proteins were mainly associated with cell wall degradation, lipid degradation, protein degradation, senescence-related transcription factors, and transcription-related proteins. In contrast, most proteins associated with ATP synthesis and scavenging of reactive oxygen species were significantly down-regulated during peel senescence. Three thioredoxin proteins and three Ca2+ signaling-related proteins were significantly up-regulated during peel senescence. It is suggested that mandarin peel senescence is associated with energy supply efficiency, decreased antioxidant capability, and increased protein and lipid degradation. In addition, activation of Ca2+ signaling and transcription factors might be involved in cell wall degradation and primary or secondary metabolism. PMID:27303420

The C2H2-type transcription factor, FlbC, is involved in the transcriptional regulation of Aspergillus oryzae glucoamylase and protease genes specifically expressed in solid-state culture.

PubMed

Tanaka, Mizuki; Yoshimura, Midori; Ogawa, Masahiro; Koyama, Yasuji; Shintani, Takahiro; Gomi, Katsuya

2016-07-01

Aspergillus oryzae produces a large amount of secreted proteins in solid-state culture, and some proteins such as glucoamylase (GlaB) and acid protease (PepA) are specifically produced in solid-state culture, but rarely in submerged culture. From the disruption mutant library of A. oryzae transcriptional regulators, we successfully identified a disruption mutant showing an extremely low production level of GlaB but a normal level of α-amylase production. This strain was a disruption mutant of the C2H2-type transcription factor, FlbC, which is reported to be involved in the regulation of conidiospore development. Disruption mutants of other upstream regulators comprising a conidiation regulatory network had no apparent effect on GlaB production in solid-state culture. In addition to GlaB, the production of acid protease in solid-state culture was also markedly decreased by flbC disruption. Northern blot analyses revealed that transcripts of glaB and pepA were significantly decreased in the flbC disruption strain. These results suggested that FlbC is involved in the transcriptional regulation of genes specifically expressed under solid-state cultivation conditions, possibly independent of the conidiation regulatory network.

Psychological predictors of mobile phone use while crossing the street among college students: An application of the theory of planned behavior.

PubMed

Jiang, Kang; Ling, Feiyang; Feng, Zhongxiang; Wang, Kun; Guo, Lei

2017-02-17

As the prevalence of mobile phone use has increased globally, experts have verified the effects of mobile phone distraction on traffic safety. However, the psychological factors underlying pedestrians' decisions to use their mobile phones while crossing the street have received little attention. The present study employed the theory of planned behavior (TPB) to investigate the psychological factors that influence pedestrians' intentions to use a mobile phone while crossing the street. The additional predictors of descriptive norms, moral norms, risk perception, mobile phone involvement, and perceived ability to compensate are included. Approximately 40% of participants reported having used a mobile phone while crossing during the previous week and 5.4% had been involved in crossing accidents due to mobile phone distractions. Hierarchical multiple regression analyses revealed overall support for the predictive utility of the TPB. The standard TPB variables accounted for 13.3% of variance in intentions after demographic variables were controlled, and the extended predictors contributed an additional 7.6% beyond the standard constructs. The current study revealed that attitude, perceived behavior control, descriptive norms, mobile phone involvement, and perceived ability to compensate all emerged as significant predictors of intentions. The findings could support the design of more effective safety campaigns and interventions to reduce pedestrians' distracted crossing behaviors.

Relation between age and carotid artery intima-medial thickness: a systematic review.

PubMed

van den Munckhof, Inge C L; Jones, Helen; Hopman, Maria T E; de Graaf, Jacqueline; Nyakayiru, Jean; van Dijk, Bart; Eijsvogels, Thijs M H; Thijssen, Dick H J

2018-05-12

Carotid artery intima-medial thickness (cIMT) represents a popular measure of atherosclerosis and is predictive of future cardiovascular and cerebrovascular events. Although older age is associated with a higher cIMT, little is known about whether this increase in cIMT follows a linear relationship with age or it is affected under influence of cardiovascular diseases (CVD) or CVD risk factors. We hypothesize that the relationship between cIMT and age is nonlinear and is affected by CVD or risk factors. A systematic review of studies that examined cIMT in the general population and human populations free from CVD/risk factors was undertaken. The literature search was conducted in PubMed, Scopus, and Web of Science. Seventeen studies with 32 unique study populations, involving 10,124 healthy individuals free from CVD risk factors, were included. Furthermore, 58 studies with 115 unique study populations were included, involving 65,774 individuals from the general population (with and without CVD risk factors). A strong positive association was evident between age and cIMT in the healthy population, demonstrating a gradual, linear increase in cIMT that did not differ between age decades (r = 0.91, P < 0.001). Although populations with individuals with CVD demonstrated a higher cIMT compared to populations free of CVD, a linear relation between age and cIMT was also present in this population. Our data suggest that cIMT is strongly and linearly related to age. This linear relationship was not affected by CVD or risk factors. © 2018 Wiley Periodicals, Inc.

Process factors facilitating and inhibiting medical ethics teaching in small groups.

PubMed

Bentwich, Miriam Ethel; Bokek-Cohen, Ya'arit

2017-11-01

To examine process factors that either facilitate or inhibit learning medical ethics during case-based learning. A qualitative research approach using microanalysis of transcribed videotaped discussions of three consecutive small-group learning (SGL) sessions on medical ethics teaching (MET) for three groups, each with 10 students. This research effort revealed 12 themes of learning strategies, divided into 6 coping and 6 evasive strategies. Cognitive-based strategies were found to relate to Kamin's model of critical thinking in medical education, thereby supporting our distinction between the themes of coping and evasive strategies. The findings also showed that cognitive efforts as well as emotional strategies are involved in discussions of ethical dilemmas. Based on Kamin's model and the constructivist learning theory, an examination of the different themes within the two learning strategies-coping and evasive-revealed that these strategies may be understood as corresponding to process factors either facilitating or inhibiting MET in SGL, respectively. Our classification offers a more nuanced observation, specifically geared to pinpointing the desired and less desired process factors in the learning involved in MET in the SGL environment. Two key advantages of this observation are: (1) it brings to the forefront process factors that may inhibit and not merely facilitate MET in SGL and (2) it acknowledges the existence of emotional and not just cognitive process factors. Further enhancement of MET in SGL may thus be achieved based on these observations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The Neurogenetic Correlates of Consciousness

NASA Astrophysics Data System (ADS)

Grandy, John K.

2013-09-01

The neurogenetic correlates of consciousness (NgCC) is a new field of consciousness studies that focuses on genes that have an effect on or are involved in the continuum of neuron-based consciousness. A framework of consciousness based on the neural correlates of consciousness (NCC) has already been established by Francis Crick and Christof Kock. In this work I propose that there are NgCC underlying the NCC which are both active during the conscious experience. So how are genes involved? There are two significant connections between DNA and neurons that are involved in the conscious experience. First, any brain system can be adversely affected by underlying genetic abnormalities which can be expressed in an individual at birth, in adulthood, or later in life. Second, the DNA molecule does not lay dormant while the neuron runs on autopilot. DNA is active in translating and transcribing RNA and protein products that are utilized during neuron functioning. Without these products being continuously produced by the DNA during a conscious experience the neurons would cease to function correctly and be rendered unable to provide a continuum of human consciousness. Consequently, in addition to NCC, NgCC must be factored in when appreciating a conscious event. In this work I will discuss and explain some NgCC citing several examples.

The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity.

PubMed

Raivio, Tracy L; Leblanc, Shannon K D; Price, Nancy L

2013-06-01

The Cpx envelope stress response mediates adaptation to stresses that cause envelope protein misfolding. Adaptation is partly conferred through increased expression of protein folding and degradation factors. The Cpx response also plays a conserved role in the regulation of virulence determinant expression and impacts antibiotic resistance. We sought to identify adaptive mechanisms that may be involved in these important functions by characterizing changes in the transcriptome of two different Escherichia coli strains when the Cpx response is induced. We show that, while there is considerable strain- and condition-specific variability in the Cpx response, the regulon is enriched for proteins and functions that are inner membrane associated under all conditions. Genes that were changed by Cpx pathway induction under all conditions were involved in a number of cellular functions and included several intergenic regions, suggesting that posttranscriptional regulation is important during Cpx-mediated adaptation. Some Cpx-regulated genes are centrally involved in energetics and play a role in antibiotic resistance. We show that a number of small, uncharacterized envelope proteins are Cpx regulated and at least two of these affect phenotypes associated with membrane integrity. Altogether, our work suggests new mechanisms of Cpx-mediated envelope stress adaptation and antibiotic resistance.

Proteome analysis to assess physiological changes in Escherichia coli grown under glucose-limited fed-batch conditions.

PubMed

Raman, Babu; Nandakumar, M P; Muthuvijayan, Vignesh; Marten, Mark R

2005-11-05

Proteome analysis was used to compare global protein expression changes in Escherichia coli fermentation between exponential and glucose-limited fed-batch phase. Two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry were used to separate and identify 49 proteins showing >2-fold difference in expression. Proteins upregulated during exponential phase include ribonucleotide biosynthesis enzymes and ribosomal recycling factor. Proteins upregulated during fed-batch phase include those involved in high-affinity glucose uptake, transport and degradation of alternate carbon sources and TCA cycle, suggesting an enhanced role of the cycle under glucose- and energy-limited conditions. We report the upregulation of several putative proteins (ytfQ, ygiS, ynaF, yggX, yfeX), not identified in any previous study under carbon-limited conditions. Copyright (c) 2005 Wiley Periodicals, Inc.

Carcinogen-induced trans activation of gene expression.

PubMed Central

Kleinberger, T; Flint, Y B; Blank, M; Etkin, S; Lavi, S

1988-01-01

We report a new mechanism of carcinogen action by which the expression of several genes was concomitantly enhanced. This mechanism involved the altered activity of cellular factors which modulate the expression of genes under their control. The increased expression was regulated at least in part on the transcriptional level and did not require amplification of the overexpressed genes. This phenomenon was transient; it was apparent as early as 24 h after carcinogen treatment and declined a few days later. Images PMID:2835673

Scientific experiments in the flight of the 1977 biological satellite (draft plan)

NASA Technical Reports Server (NTRS)

1977-01-01

The physiological, biological, radiobiological and radiophysical experiments planned for the 1977 biological satellite are described. The biological experiments will involve rats, higher and lower plants, insects and other biological specimens carried on the biosatellite. The responses of these organisms to weightlessness, artificial gravity, cosmic radiation particles and general flight factors will be studied. The radiophysical experiments will investigate certain properties of cosmic radiation as well as the possibility of creating electrostatic and dielectric radiation shields under actual space-flight conditions.

Novel Humanized mice to test Therapeutics for Human Type 1 Diabetes

DTIC Science & Technology

2014-01-06

performed in non- obese diabetic (NOD) mice, the closest animal model for human T1D, have identified different immune cells involved in pancreatic β-cell...periphery. Each MHC class II chain contributes to the formation of a groove where the peptide is embedded (78). 17 The polygenetic factor underlying...diabetes mellitus in non- obese diabetic mice by transgenes encoding modified I-A beta-chain or normal I-E alpha-chain. Nature 345:727-9 63. Marek

Mechanisms Underlying Testicular Damage and Dysfunction in Mice With Partial IGF-1 Deficiency and the Effectiveness of IGF-1 Replacement Therapy.

PubMed

Castilla-Cortázar, Inma; Gago, Alberto; Muñoz, Úrsula; Ávila-Gallego, Elena; Guerra-Menéndez, Lucía; Sádaba, María Cruz; García-Magariño, Mariano; Olleros Santos-Ruiz, María; Aguirre, G A; Puche, Juan Enrique

2015-12-01

To determine whether insulin-like growth factor (IGF-1) deficiency can cause testicular damage and to examine changes of the testicular morphology and testicular function-related gene expression caused by IGF-1 deficiency. Therefore, this study aims to determine the benefits of low doses of IGF-1 and to explore the mechanisms underlying the IGF-1 replacement therapy. A murine model of IGF-1 deficiency was used to avoid any factor that could contribute to testicular damage. Testicular weight, score of histopathological damage, and gene expressions were studied in 3 experimental groups of mice: controls (wild-type Igf1(+/+)), heterozygous Igf1(+/-) with partial IGF-1 deficiency, and heterozygous Igf1(+/-) treated with IGF-1. Results show that the partial IGF-1 deficiency induced testicular damage and altered expression of genes involved in IGF-1 and growth hormone signaling and regulation, testicular hormonal function, extracellular matrix establishment and its regulation, angiogenesis, fibrogenesis, inflammation, and cytoprotection. In addition, proteins involved in tight junction expression were found to be reduced. However, low doses of IGF-1 restored the testicular damage and most of these parameters. IGF-1 deficiency caused the damage of the blood-testis barrier and testicular structure and induced the abnormal testicular function-related gene expressions. However, low doses of IGF-1 constitute an effective replacement therapy that restores the described testicular damage. Data herein show that (1) cytoprotective activities of IGF-1 seem to be mediated by heat shock proteins and that (2) connective tissue growth factor could play a relevant role together with IGF-1 in the extracellular matrix establishment. Copyright © 2015 Elsevier Inc. All rights reserved.

The SigF Regulon in Mycobacterium smegmatis Reveals Roles in Adaptation to Stationary Phase, Heat, and Oxidative Stress▿ ‡

PubMed Central

Hümpel, Anja; Gebhard, Susanne; Cook, Gregory M.; Berney, Michael

2010-01-01

SigF is an alternative sigma factor that is highly conserved among species of the genus Mycobacterium. In this study we identified the SigF regulon in Mycobacterium smegmatis using whole-genome microarray and promoter consensus analyses. In total, 64 genes in exponential phase and 124 genes in stationary phase are SigF dependent (P < 0.01, >2-fold expression change). Our experimental data reveal the SigF-dependent promoter consensus GTTT-N(15-17)-GGGTA for M. smegmatis, and we propose 130 potential genes under direct control of SigF, of which more than 50% exhibited reduced expression in a ΔsigF strain. We previously reported an increased susceptibility of the ΔsigF strain to heat and oxidative stress, and our expression data indicate a molecular basis for these phenotypes. We observed SigF-dependent expression of several genes purportedly involved in oxidative stress defense, namely, a heme-containing catalase, a manganese-containing catalase, a superoxide dismutase, the starvation-induced DNA-protecting protein MsDps1, and the biosynthesis genes for the carotenoid isorenieratene. Our data suggest that SigF regulates the biosynthesis of the thermoprotectant trehalose, as well as an uptake system for osmoregulatory compounds, and this may explain the increased heat susceptibility of the ΔsigF strain. We identified the regulatory proteins SigH3, PhoP, WhiB1, and WhiB4 as possible genes under direct control of SigF and propose four novel anti-sigma factor antagonists that could be involved in the posttranslational regulation of SigF in M. smegmatis. This study emphasizes the importance of this sigma factor for stationary-phase adaptation and stress response in mycobacteria. PMID:20233930

Factors impacting same-day cancellation of outpatient pediatric magnetic resonance imaging under anesthesia.

PubMed

Hoffman, Andrea S; Matlow, Anne; Shroff, Manohar; Cohen, Eyal

2015-01-01

Studies of elective surgical procedures indicate that cancellation is common and preventable. Little is known about cancellation of anesthesia-supported elective diagnostic imaging. To describe the reasons for same-day cancellation of MRI studies performed under sedation or anesthesia and identify patient characteristics associated with cancellations. This case-control study was carried out in a university-affiliated tertiary care children's hospital. Cases were defined as elective outpatient MRI studies booked under anesthesia that were cancelled after the patient had arrived in the radiology department in 2009. Matched controls were identified by selecting the same day and time 1 week before or after the cancelled case. Main outcome measures included demographics, MRI study characteristics, and social and medical factors. There were 111 outpatient anesthesia-supported MRI studies cancelled on the same day as the assessment (cancellation rate: 4.5%), of which 74.6% were related to family and patient factors, while 22% were related to system factors. Cancelled cases involved patients who lived in lower median income quintile neighborhoods compared to controls (2 vs. 3; P = 0.0007; odds ratio [OR] 3.81; 95% confidence interval [CI] 1.18-12.34). Those who traveled a greater median distance (in kilometers) were less likely to be cancelled (18.8 vs. 27.1, P = 0.0035). Although cancelled patients had a lower mean number of total medical services (2.5 vs. 3.0; P = 0.03; OR = 0.78; 95% CI 0.62-0.98), current medical factors (past 12 months) did not impact cancellations. Same-day cancellations of anesthesia-supported MRI studies are not uncommon, and the main predictor of cancellation seems to be socioeconomic rather than medical.

[Relationship between high-sensitivity C-reactive protein and obesity/metabolic syndrome in children].

PubMed

Chen, Fangfang; Wang, Wenpeng; Teng, Yue; Hou, Dongqing; Zhao, Xiaoyuan; Yang, Ping; Yan, Yinkun; Mi, Jie

2014-06-01

To explore the relationship between high-sensitivity C-reactive protein (hsCRP) and obesity/metabolic syndrome (MetS) related factors in children. 403 children aged 10-14 and born in Beijing were involved in this study. Height, weight, waist circumference, fat mass percentage (Fat%), blood pressure (BP), hsCRP, triglyceride (TG), total cholesterol (TC), fasting plasma glucose (FPG), high and low density lipoprotein cholesterol (HDL-C, LDL-C) were observed among these children. hsCRP was transformed with base 10 logarithm (lgCRP). MetS was defined according to the International Diabetes Federation 2007 definition. Associations between MetS related components and hsCRP were tested using partial correlation analysis, analysis of covariance and linear regression models. 1) lgCRP was positively correlated with BMI, waist circumference, Fat%,BP, FPG, LDL-C and TC while negatively correlated with HDL-C. With BMI under control, the relationships disappeared, but LDL-C (r = 0.102). 2) The distributions of lgCRP showed obvious differences in all the metabolic indices, in most groups, respectively. With BMI under control, close relationships between lgCRP and high blood pressure/high TG disappeared and the relationship with MetS weakened. 3) Through linear regression models, factors as waist circumference, BMI, Fat% were the strongest factors related to hsCRP, followed by systolic BP, HDL-C, diastolic BP, TG and LDL-C. With BMI under control, the relationships disappeared, but LDL-C(β = 0.045). hsCRP was correlated with child obesity, lipid metabolism and MetS. Waist circumference was the strongest factors related with hsCRP. Obesity was the strongest and the independent influencing factor of hsCRP.

Activating transcription factor 3 promotes loss of the acinar cell phenotype in response to cerulein-induced pancreatitis in mice.

PubMed

Fazio, Elena N; Young, Claire C; Toma, Jelena; Levy, Michael; Berger, Kurt R; Johnson, Charis L; Mehmood, Rashid; Swan, Patrick; Chu, Alphonse; Cregan, Sean P; Dilworth, F Jeffrey; Howlett, Christopher J; Pin, Christopher L

2017-09-01

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. Of importance, ATF3-dependent regulation of these genes was observed only upon induction of pancreatitis, with pathways involved in inflammation, acinar cell differentiation, and cell junctions being specifically targeted. Characterizing expression of transcription factors that affect acinar cell differentiation suggested that acinar cells lacking ATF3 maintain a mature cell phenotype during pancreatitis, a finding supported by maintenance of junctional proteins and polarity markers. As a result, Atf3 -/- pancreatic tissue displayed increased tissue damage and inflammatory cell infiltration at early time points during injury but, at later time points, showed reduced acinar-to-duct cell metaplasia. Thus our results reveal a critical role for ATF3 as a key regulator of the acinar cell transcriptional response during injury and may provide a link between chronic pancreatitis and PDAC. © 2017 Fazio et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The Yfe and Feo transporters are involved in microaerobic growth and virulence of Yersinia pestis in bubonic plague.

PubMed

Fetherston, Jacqueline D; Mier, Ildefonso; Truszczynska, Helena; Perry, Robert D

2012-11-01

The Yfe/Sit and Feo transport systems are important for the growth of a variety of bacteria. In Yersinia pestis, single mutations in either yfe or feo result in reduced growth under static (limited aeration), iron-chelated conditions, while a yfe feo double mutant has a more severe growth defect. These growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (Ybt) and the putative ferrous transporter FetMP. Both fetP and a downstream locus (flp for fet linked phenotype) were required for growth of a yfe feo ybt mutant under static, iron-limiting conditions. An feoB mutation alone had no effect on the virulence of Y. pestis in either bubonic or pneumonic plague models. An feo yfe double mutant was still fully virulent in a pneumonic plague model but had an ∼90-fold increase in the 50% lethal dose (LD(50)) relative to the Yfe(+) Feo(+) parent strain in a bubonic plague model. Thus, Yfe and Feo, in addition to Ybt, play an important role in the progression of bubonic plague. Finally, we examined the factors affecting the expression of the feo operon in Y. pestis. Under static growth conditions, the Y. pestis feo::lacZ fusion was repressed by iron in a Fur-dependent manner but not in cells grown aerobically. Mutations in feoC, fnr, arcA, oxyR, or rstAB had no significant effect on transcription of the Y. pestis feo promoter. Thus, the factor(s) that prevents repression by Fur under aerobic growth conditions remains to be identified.

The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague

PubMed Central

Fetherston, Jacqueline D.; Mier, Ildefonso; Truszczynska, Helena

2012-01-01

The Yfe/Sit and Feo transport systems are important for the growth of a variety of bacteria. In Yersinia pestis, single mutations in either yfe or feo result in reduced growth under static (limited aeration), iron-chelated conditions, while a yfe feo double mutant has a more severe growth defect. These growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (Ybt) and the putative ferrous transporter FetMP. Both fetP and a downstream locus (flp for fet linked phenotype) were required for growth of a yfe feo ybt mutant under static, iron-limiting conditions. An feoB mutation alone had no effect on the virulence of Y. pestis in either bubonic or pneumonic plague models. An feo yfe double mutant was still fully virulent in a pneumonic plague model but had an ∼90-fold increase in the 50% lethal dose (LD50) relative to the Yfe+ Feo+ parent strain in a bubonic plague model. Thus, Yfe and Feo, in addition to Ybt, play an important role in the progression of bubonic plague. Finally, we examined the factors affecting the expression of the feo operon in Y. pestis. Under static growth conditions, the Y. pestis feo::lacZ fusion was repressed by iron in a Fur-dependent manner but not in cells grown aerobically. Mutations in feoC, fnr, arcA, oxyR, or rstAB had no significant effect on transcription of the Y. pestis feo promoter. Thus, the factor(s) that prevents repression by Fur under aerobic growth conditions remains to be identified. PMID:22927049

An ABRE promoter sequence is involved in osmotic stress-responsive expression of the DREB2A gene, which encodes a transcription factor regulating drought-inducible genes in Arabidopsis.

PubMed

Kim, June-Sik; Mizoi, Junya; Yoshida, Takuya; Fujita, Yasunari; Nakajima, Jun; Ohori, Teppei; Todaka, Daisuke; Nakashima, Kazuo; Hirayama, Takashi; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2011-12-01

In plants, osmotic stress-responsive transcriptional regulation depends mainly on two major classes of cis-acting elements found in the promoter regions of stress-inducible genes: ABA-responsive elements (ABREs) and dehydration-responsive elements (DREs). ABRE has been shown to perceive ABA-mediated osmotic stress signals, whereas DRE is known to be involved in an ABA-independent pathway. Previously, we reported that the transcription factor DRE-BINDING PROTEIN 2A (DREB2A) regulates DRE-mediated transcription of target genes under osmotic stress conditions in Arabidopsis (Arabidopsis thaliana). However, the transcriptional regulation of DREB2A itself remains largely uncharacterized. To elucidate the transcriptional mechanism associated with the DREB2A gene under osmotic stress conditions, we generated a series of truncated and base-substituted variants of the DREB2A promoter and evaluated their transcriptional activities individually. We found that both ABRE and coupling element 3 (CE3)-like sequences located approximately -100 bp from the transcriptional initiation site are necessary for the dehydration-responsive expression of DREB2A. Coupling our transient expression analyses with yeast one-hybrid and chromatin immunoprecipitation (ChIP) assays indicated that the ABRE-BINDING PROTEIN 1 (AREB1), AREB2 and ABRE-BINDING FACTOR 3 (ABF3) bZIP transcription factors can bind to and activate the DREB2A promoter in an ABRE-dependent manner. Exogenous ABA application induced only a modest accumulation of the DREB2A transcript when compared with the osmotic stress treatment. However, the osmotic stress-induced DREB2A expression was found to be markedly impaired in several ABA-deficient and ABA-insensitive mutants. These results suggest that in addition to an ABA-independent pathway, the ABA-dependent pathway plays a positive role in the osmotic stress-responsive expression of DREB2A.

Genetic pleiotropy explains associations between musical auditory discrimination and intelligence.

PubMed

Mosing, Miriam A; Pedersen, Nancy L; Madison, Guy; Ullén, Fredrik

2014-01-01

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions.

Genetic Pleiotropy Explains Associations between Musical Auditory Discrimination and Intelligence

PubMed Central

Mosing, Miriam A.; Pedersen, Nancy L.; Madison, Guy; Ullén, Fredrik

2014-01-01

Musical aptitude is commonly measured using tasks that involve discrimination of different types of musical auditory stimuli. Performance on such different discrimination tasks correlates positively with each other and with intelligence. However, no study to date has explored these associations using a genetically informative sample to estimate underlying genetic and environmental influences. In the present study, a large sample of Swedish twins (N = 10,500) was used to investigate the genetic architecture of the associations between intelligence and performance on three musical auditory discrimination tasks (rhythm, melody and pitch). Phenotypic correlations between the tasks ranged between 0.23 and 0.42 (Pearson r values). Genetic modelling showed that the covariation between the variables could be explained by shared genetic influences. Neither shared, nor non-shared environment had a significant effect on the associations. Good fit was obtained with a two-factor model where one underlying shared genetic factor explained all the covariation between the musical discrimination tasks and IQ, and a second genetic factor explained variance exclusively shared among the discrimination tasks. The results suggest that positive correlations among musical aptitudes result from both genes with broad effects on cognition, and genes with potentially more specific influences on auditory functions. PMID:25419664

Rising youth suicide and the changing cultural context in South Korea.

PubMed

Park, B C Ben; Soo Im, Jeong; Strother Ratcliff, Kathryn

2014-01-01

South Korean society faces a serious challenge in the increasing rates of youth suicidal behavior. There is a need both to gain a better understanding of the causes of this behavior and to develop strategies for responding to this critical public health issue. This article analyzes how psychological, sociopsychological, and subcultural factors influence suicidal proneness among Korean youth as well as makes suggestions for developing social policies that could reduce Korean youth suicidal behaviors. Correlation and multivariate regression analyses on suicide proneness and depression were employed using a sample of 172 South Korean youths (aged 18-24) selected from the 2009 General Social Survey collected through face-to-face interviews. Young people's suicidal proneness is associated with depression, a tolerant attitude toward suicide, strained family relations, living in rural areas, being female, and being closely related to survivors of suicide or potential suicides. The findings from this study reveal the significance of social and cultural factors as influences on recent youth suicidal behavior in Korea. The analysis suggests that the underlying risk factors of suicidal behavior are embedded in the changing social and cultural context of Korean society. Thus, suicide prevention efforts should involve more than merely treating any underlying psychiatric disorders.

Role of platelet-activating factor in long-term potentiation of the rat medial vestibular nuclei.

PubMed

Grassi, S; Francescangeli, E; Goracci, G; Pettorossi, V E

1998-06-01

In rat brain stem slices, we investigated the role of platelet activating factor (PAF) in long-term potentiation (LTP) induced in the ventral part of the medial vestibular nuclei (MVN) by high-frequency stimulation (HFS) of the primary vestibular afferent. The synaptosomal PAF receptor antagonist, BN-52021 was administered before and after HFS. BN-52021 did not modify the vestibular potentials under basal conditions, but it reduced the magnitude of potentiation induced by HFS, which completely developed after the drug wash-out. The same effect was obtained by using CV-62091, a more potent PAF antagonist at microsomal binding sites, but with concentrations higher than those of BN-52021. By contrast both BN-52021 and CV-6209 had no effect on the potentiation once induced. This demonstrates that PAF is involved in the induction but not in the maintenance of vestibular long-term effect through activation of synaptosomal PAF receptors. In addition, we analyzed the effect of the PAF analogue, 1-O-hexadecyl-2-O- (methylcarbamyl)-sn-glycero-3-phosphocoline (MC-PAF) and the inactive PAF metabolite, 1-O-hexadecyl-sn-glycero-3-phosphocoline (Lyso-PAF) on vestibular responses. Our results show that MC-PAF, but not Lyso-PAF induced potentiation. This potentiation was prevented by D,L-2-amino 5-phosphonopentanoic acid, suggesting an involvement of N-methyl-D-aspartate receptors. Furthermore, under BN-52021 and CV-6209, the MC-PAF potentiation was reduced or abolished. The dose-effect curve of MC-PAF showed a shift to the right greater under BN-52021 than under CV-6209, confirming the main dependence of MC-PAF potentiation on the activation of synaptosomal PAF receptors. Our results suggest that PAF can be released in the MVN after the activation of postsynaptic mechanisms triggering LTP, and it may act as a retrograde messenger which activates the presynaptic mechanisms facilitating synaptic plasticity.

Cold shock protein YB-1 is involved in hypoxia-dependent gene transcription.

PubMed

Rauen, Thomas; Frye, Bjoern C; Wang, Jialin; Raffetseder, Ute; Alidousty, Christina; En-Nia, Abdelaziz; Floege, Jürgen; Mertens, Peter R

2016-09-16

Hypoxia-dependent gene regulation is largely orchestrated by hypoxia-inducible factors (HIFs), which associate with defined nucleotide sequences of hypoxia-responsive elements (HREs). Comparison of the regulatory HRE within the 3' enhancer of the human erythropoietin (EPO) gene with known binding motifs for cold shock protein Y-box (YB) protein-1 yielded strong similarities within the Y-box element and 3' adjacent sequences. DNA binding assays confirmed YB-1 binding to both, single- and double-stranded HRE templates. Under hypoxia, we observed nuclear shuttling of YB-1 and co-immunoprecipitation assays demonstrated that YB-1 and HIF-1α physically interact with each other. Cellular YB-1 depletion using siRNA significantly induced hypoxia-dependent EPO production at both, promoter and mRNA level. Vice versa, overexpressed YB-1 significantly reduced EPO-HRE-dependent gene transcription, whereas this effect was minor under normoxia. HIF-1α overexpression induced hypoxia-dependent gene transcription through the same element and accordingly, co-expression with YB-1 reduced HIF-1α-mediated EPO induction under hypoxic conditions. Taken together, we identified YB-1 as a novel binding factor for HREs that participates in fine-tuning of the hypoxia transcriptome. Copyright © 2016 Elsevier Inc. All rights reserved.

Periodontal abscess during supportive periodontal therapy: a review of the literature.

PubMed

Silva, Geraldo L M; Soares, Rodrigo V; Zenóbio, Elton G

2008-09-01

The aim of this review is to present the current status of the occurrence and management of a periodontal abscess during supportive periodontal therapy (SPT). A periodontal abscess depicts typical features and has been described in patients under SPT in clinical trials. Common periodontal pathogens have been observed in this lesion and some etiologic factors may be responsible for its recurrence. This condition can be isolated or associated with factors that can change the prognosis of affected teeth. Although it has been frequently noticed in untreated periodontitis, the periodontal abscess can also occur in patients under SPT and has been regarded as one of the possible complications of SPT. Patients with a high susceptibility to periodontal disease lost more teeth than those with a healthy periodontium. Early diagnosis and appropriate intervention for periodontal abscesses in patients under SPT are extremely important for the management of the periodontal abscess since this condition can lead to loss of the involved tooth. A single case of a tooth diagnosed with periodontal abscess that responds favorably to adequate treatment does not seem to affect its longevity. An accurate diagnosis and adequate treatment can preserve the longevity of affected teeth.

Facilitating Factors and Barriers to the Use of Emerging Technologies for Suicide Prevention in Europe: Multicountry Exploratory Study.

PubMed

Muñoz-Sánchez, Juan-Luis; Delgado, Carmen; Parra-Vidales, Esther; Franco-Martín, Manuel

2018-01-24

This study provides an analysis on the use of emerging technologies for the prevention of suicide in 8 different European countries. The objective of this study was to analyze the potentiality of using emerging technologies in the area of suicide prevention based on the opinion of different professionals involved in suicide prevention. Opinions of 3 groups of stakeholders (ie, relevant professionals in suicide field) were gathered using a specifically designed questionnaire to explore dimensions underlying perceptions of facilitating factors and barriers in relation to the use of emerging technologies for suicide prevention. Goal 1 involved facilitating factors for the use of emerging technologies in suicide prevention. Northern European countries, except for Belgium, attach greater relevance to those that optimize implementation and benefits. On the other hand, Southern European countries attach greater importance to professionally oriented and user-centered facilitating factors. According to different stakeholders, the analysis of these facilitating factors suggest that professionals in the field of social work attach greater relevance to those that optimize implementation and benefits. However, professionals involved in the area of mental health, policy makers, and political decision makers give greater importance to professionally oriented and user-centered facilitating factors. Goal 2 was related to barriers to the usability of emerging technologies for suicide prevention. Both countries and stakeholders attach greater importance to barriers associated with resource constraints than to those centered on personal limitations. There are no differences between countries or between stakeholders. Nevertheless, there is a certain stakeholders-countries interaction that indicates that the opinions on resource constraints expressed by different stakeholders do not follow a uniform pattern in different countries, but they differ depending on the country. Although all countries and stakeholders agree in identifying resource constraints as the main barrier to the use of emerging technologies, factors facilitating their use in suicide prevention differ among countries and among stakeholders. ©Juan-Luis Muñoz-Sánchez, Carmen Delgado, Esther Parra-Vidales, Manuel Franco-Martín. Originally published in JMIR Mental Health (http://mental.jmir.org), 24.01.2018.

Enhanced actions of insulin-like growth factor-I and interferon-alpha co-administration in experimental cirrhosis.

PubMed

Tutau, Federico; Rodríguez-Ortigosa, Carlos; Puche, Juan Enrique; Juanarena, Nerea; Monreal, Iñigo; García Fernández, María; Clavijo, Encarna; Castilla, Alberto; Castilla-Cortázar, Inma

2009-01-01

Cirrhosis is a diffuse process of hepatic fibrosis and regenerative nodule formation. The liver is the major source of circulating insulin-like growth factor-I (IGF-I) whose plasma levels are diminished in cirrhosis. IGF-I supplementation has been shown to induce beneficial effects in cirrhosis, including antifibrogenic and hepatoprotective effects. On other hand, interferon-alpha (IFN-alpha) therapy seems to suppress the progression of hepatic fibrosis. The aim of this study was to investigate the effect of the co-administration of IGF-I+IFN-alpha to Wistar rats with CCl(4)-induced cirrhosis, exploring liver function tests, hepatic lipid peroxidation and histopathology. The mechanisms underlying the effects of these agents were studied by reverse transcription-polymerase chain reaction, determining the expression of some factors [hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta), alpha-smooth muscle actin, collagen, tissular inhibitor of metalloproteinases-1 and pregnane X receptor (PXR)] involved in fibrogenesis, fibrolysis and/or hepatoprotection. Both IGF-I and IFN-alpha exerted significant effects on fibrogenesis. IGF-I significantly increased serum albumin and HGF whereas IFN-alpha-therapy did not. The inhibition of TGF-beta expression was only observed by the effect of IFN-alpha-therapy. In addition, only the co-administration of IGF-I and IFN-alpha was able to increase the PXR. The combined therapy with both factors improved liver function tests, hepatic lipid peroxidation and reduced fibrosis, inducing a relevant histological improvement, reducing fibrosis and recovering hepatic architecture. The co-administration IGF-I+IFN enhanced all the beneficial effects observed with each factor separately, showing an additive action on histopathology and PXR expression, which is involved in the inhibition of fibrogenesis.

RNA-Seq revealed the impairment of immune defence of tilapia against the infection of Streptococcus agalactiae with simulated climate warming.

PubMed

Wang, Le; Liu, Peng; Wan, Zi Yi; Huang, Shu Qing; Wen, Yan Fei; Lin, Grace; Yue, Gen Hua

2016-08-01

Global warming is one of the causes of disease outbreaks in fishes. Understanding its mechanisms is critical in aquaculture and fisheries. We used tilapia to study the effects of a high temperature on the infection of a bacterial pathogen Streptococcus agalactiae using RNA-Seq. We found that the dissolved oxygen level in water at 32 °C is lower than at 22 °C, and tilapia infected with the pathogen died more rapidly at 32 °C. The gene expression profiles showed significant differences in fish raised under different conditions. We identified 126 and 576 differentially expressed genes (DEGs) at 4 and 24 h post infection at 22 °C, respectively, whereas at 32 °C, the data were 312 and 1670, respectively. Almost all responding pathways at 22 °C were involved in the immune responses, whereas at 32 °C, the enriched pathways were not only involved in immune responses but also involved in oxygen and energy metabolisms. We identified significant signals of immunosuppression of immune responses at 32 °C. In addition, many of the enriched transcription factors and DEGs under positive selection were involved in immune responses, oxygen and/or energy metabolisms. Our results suggest that global warming could reduce the oxygen level in water and impair the defence of tilapia against bacterial infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mothers in methadone treatment and their involvement with the child protection system: a replication and extension study.

PubMed

Taplin, Stephanie; Mattick, Richard P

2013-08-01

Although a high level of involvement with the child protection system has been identified in families where parental substance use is a feature, not all such parents abuse or neglect their children or have contact with the child protection system. Identifying parents with substance-use histories who are able to care for their children without intervention by the child protection system, and being able to target interventions to the families who need them the most is important. This study interviewed a relatively large sample of mothers about their histories, their children and their involvement with the child protection system. We hypothesized that mothers in opioid pharmacological treatment who are involved with child protection services are different in characteristics to those mothers who are not involved. One hundred and seventy-one women, with at least one child aged under 16 years, were interviewed at nine treatment clinics providing pharmacological treatment for opioid dependence across Sydney, Australia. Just over one-third of the women were involved with child protection services at the time of interview, mostly with children in out-of-home care. Logistic regression analyses revealed that factors which significantly increased the likelihood of the mother being involved with the child protection system were: (1) having a greater number of children, (2) being on psychiatric medication, and (3) having less than daily contact with her own parents. This study replicates and extends the work of Grella, Hser, and Huang (2006) and the limited literature published to date examining the factors which contribute to some substance-using mothers becoming involved with the child protection system while others do not. The finding that mental health problems and parental supports (along with the number of children) were significantly associated with child protection system involvement in this study, indicates a need for improved interventions and the provision of treatment and support services if we are to reduce the involvement of the child protection system with these families. Copyright © 2013 Elsevier Ltd. All rights reserved.

24 CFR 1000.501 - Who is involved in monitoring activities under NAHASDA?

Code of Federal Regulations, 2011 CFR

2011-04-01

..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient Monitoring, Oversight and Accountability § 1000.501 Who is involved in monitoring activities under NAHASDA? The recipient, the grant beneficiary and HUD are involved in monitoring activities under NAHASDA. ...

24 CFR 1000.501 - Who is involved in monitoring activities under NAHASDA?

Code of Federal Regulations, 2010 CFR

2010-04-01

..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient Monitoring, Oversight and Accountability § 1000.501 Who is involved in monitoring activities under NAHASDA? The recipient, the grant beneficiary and HUD are involved in monitoring activities under NAHASDA. ...

24 CFR 1000.501 - Who is involved in monitoring activities under NAHASDA?

Code of Federal Regulations, 2014 CFR

2014-04-01

..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient Monitoring, Oversight and Accountability § 1000.501 Who is involved in monitoring activities under NAHASDA? The recipient, the grant beneficiary and HUD are involved in monitoring activities under NAHASDA. ...

24 CFR 1000.501 - Who is involved in monitoring activities under NAHASDA?

Code of Federal Regulations, 2012 CFR

2012-04-01

..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient Monitoring, Oversight and Accountability § 1000.501 Who is involved in monitoring activities under NAHASDA? The recipient, the grant beneficiary and HUD are involved in monitoring activities under NAHASDA. ...

24 CFR 1000.501 - Who is involved in monitoring activities under NAHASDA?

Code of Federal Regulations, 2013 CFR

2013-04-01

..., DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT NATIVE AMERICAN HOUSING ACTIVITIES Recipient Monitoring, Oversight and Accountability § 1000.501 Who is involved in monitoring activities under NAHASDA? The recipient, the grant beneficiary and HUD are involved in monitoring activities under NAHASDA. ...

Contributing factors to vehicle to vehicle crash frequency and severity under rainfall.

PubMed

Jung, Soyoung; Jang, Kitae; Yoon, Yoonjin; Kang, Sanghyeok

2014-09-01

This study combined vehicle to vehicle crash frequency and severity estimations to examine factor impacts on Wisconsin highway safety in rainy weather. Because of data deficiency, the real-time water film depth, the car-following distance, and the vertical curve grade were estimated with available data sources and a GIS analysis to capture rainy weather conditions at the crash location and time. Using a negative binomial regression for crash frequency estimation, the average annual daily traffic per lane, the interaction between the posted speed limit change and the existence of an off-ramp, and the interaction between the travel lane number change and the pavement surface material change were found to increase the likelihood of vehicle to vehicle crashes under rainfall. However, more average daily rainfall per month and a wider left shoulder were identified as factors that decrease the likelihood of vehicle to vehicle crashes. In the crash severity estimation using the multinomial logit model that outperformed the ordered logit model, the travel lane number, the interaction between the travel lane number and the slow grade, the deep water film, and the rear-end collision type were more likely to increase the likelihood of injury crashes under rainfall compared with crashes involving only property damage. As an exploratory data analysis, this study provides insight into potential strategies for rainy weather highway safety improvement, specifically, the following weather-sensitive strategies: road design and ITS implementation for drivers' safety awareness under rainfall. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

[ASSESSMENT OF EXTREME FACTORS OF SHIFT WORK IN ARCTIC CONDITIONS BY WORKERS WITH DIFFERENT REGULATORY PROCESSES].

PubMed

Korneeva, Ya A; Simonova, N N

2016-01-01

A man working on a shift basis in the Arctic, every day is under the influence of various extreme factors which are inevitable for oil and gas indudtry. To adapt to shift work employees use various resources of the individual. The purpose of research is the determination of personal resources of shift workers to overcome the adverse factors of the environment in the Arctic. The study involved 191 builder of main gas pipelines, working in shifts in the Tyumen region (the length of the shift 52 days of arrival) at the age of 23 to 59 (mean age 34.9 ± 8.1) years. Methods: psychological testing, questioning, observation, descriptive statistics, discriminant step by step analysis. There was revealed the correlation between the subjective assessment of the majority of adverse climatic factors in the regulatory process "assessment of results"; production factors--regulatory processes such as flexibility, autonomy, simulation, and the general level of self-regulation; social factors are more associated with the severity of such regulatory processes, flexibility and evaluation of results.

Risk and Protective Factors of Suicidal Ideation and Attempt among Adolescents with Different Types of School Bullying Involvement.

PubMed

Yen, Cheng-Fang; Liu, Tai-Ling; Yang, Pinchen; Hu, Huei-Fan

2015-01-01

Suicide has been found to be prevalent among adolescents involved in bullying; however, there has been a lack of research examining whether the risk and protective factors of suicidal ideation and attempt are different among adolescents with different types of bullying involvement. The aims of this study were to examine the risk and protective factors of suicidal ideation and attempt among adolescents with different experiences of bullying involvement, victimization, and perpetration. A total of 4,533 adolescents participated in this study. Different groups of bullying involvement, victimization, and perpetration were determined through use of the Chinese version of the School Bullying Experience Questionnaire. The associations of suicidal ideation and attempt with possible risk factors (domestic violence, overweight, depression, anxiety, and alcohol abuse) and protective factors (family support and self-esteem) were examined using logistic regression analysis. Pure victims, pure perpetrators, and victim-perpetrators were more likely to report suicidal ideation and attempt than the neutral group. The risk and protective factors of suicidal ideation and attempt were different across adolescents with different experiences of bullying involvement, victimization, and perpetrators. The risk of suicide should be monitored among adolescents who are involved in any type of bullying. The risk and protective factors of suicide identified in this study should be taken into consideration in prevention and intervention programs for suicide in adolescents involved in bullying.

Force sensor characterization under sinusoidal excitations.

PubMed

Medina, Nieves; de Vicente, Jesús

2014-10-06

The aim in the current work is the development of a method to characterize force sensors under sinusoidal excitations using a primary standard as the source of traceability. During this work the influence factors have been studied and a method to minimise their contributions, as well as the corrections to be performed under dynamic conditions have been established. These results will allow the realization of an adequate characterization of force sensors under sinusoidal excitations, which will be essential for its further proper use under dynamic conditions. The traceability of the sensor characterization is based in the direct definition of force as mass multiplied by acceleration. To do so, the sensor is loaded with different calibrated loads and is maintained under different sinusoidal accelerations by means of a vibration shaker system that is able to generate accelerations up to 100 m/s2 with frequencies from 5 Hz up to 2400 Hz. The acceleration is measured by means of a laser vibrometer with traceability to the units of time and length. A multiple channel data acquisition system is also required to simultaneously acquire the electrical output signals of the involved instrument in real time.

Word Naming in the L1 and L2: A Dynamic Perspective on Automatization and the Degree of Semantic Involvement in Naming

PubMed Central

Plat, Rika; Lowie, Wander; de Bot, Kees

2018-01-01

Reaction time data have long been collected in order to gain insight into the underlying mechanisms involved in language processing. Means analyses often attempt to break down what factors relate to what portion of the total reaction time. From a dynamic systems theory perspective or an interaction dominant view of language processing, it is impossible to isolate discrete factors contributing to language processing, since these continually and interactively play a role. Non-linear analyses offer the tools to investigate the underlying process of language use in time, without having to isolate discrete factors. Patterns of variability in reaction time data may disclose the relative contribution of automatic (grapheme-to-phoneme conversion) processing and attention-demanding (semantic) processing. The presence of a fractal structure in the variability of a reaction time series indicates automaticity in the mental structures contributing to a task. A decorrelated pattern of variability will indicate a higher degree of attention-demanding processing. A focus on variability patterns allows us to examine the relative contribution of automatic and attention-demanding processing when a speaker is using the mother tongue (L1) or a second language (L2). A word naming task conducted in the L1 (Dutch) and L2 (English) shows L1 word processing to rely more on automatic spelling-to-sound conversion than L2 word processing. A word naming task with a semantic categorization subtask showed more reliance on attention-demanding semantic processing when using the L2. A comparison to L1 English data shows this was not only due to the amount of language use or language dominance, but also to the difference in orthographic depth between Dutch and English. An important implication of this finding is that when the same task is used to test and compare different languages, one cannot straightforwardly assume the same cognitive sub processes are involved to an equal degree using the same task in different languages. PMID:29403404

Piper betle Induced Cytoprotective Genes and Proteins via the Nrf2/ARE Pathway in Aging Mice.

PubMed

Aliahmat, Nor Syahida; Abdul Sani, Nur Fathiah; Wan Hasan, Wan Nuraini; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

2016-01-01

The objective of this study was to elucidate the underlying antioxidant mechanism of aqueous extract of Piper betle (PB) in aging rats. The nuclear factor erythroid 2-related factor 2 (Nrf2)/ARE pathway involving phase II detoxifying and antioxidant enzymes plays an important role in the antioxidant system by reducing electrophiles and reactive oxygen species through induction of phase II enzymes and proteins. Genes and proteins of phase II detoxifying antioxidant enzymes were analyzed by QuantiGenePlex 2.0 Assay and Western blot analysis. PB significantly induced genes and proteins of phase II and antioxidant enzymes, NAD(P)H quinone oxidoreductase 1, and catalase in aging mice (p < 0.05). The expression of these enzymes were stimulated via translocation of Nrf2 into the nucleus, indicating the involvement of ARE, a cis-acting motif located in the promoter region of nearly all phase II genes. PB was testified for the first time to induce cytoprotective genes through the Nrf2/ARE signaling pathway, thus unraveling the antioxidant mechanism of PB during the aging process. © 2016 S. Karger AG, Basel.

A study of carburetor/induction system icing in general aviation accidents

NASA Technical Reports Server (NTRS)

Obermayer, R. W.; Roe, W. T.

1975-01-01

An assessment of the frequency and severity of carburetor/induction icing in general-aviation accidents was performed. The available literature and accident data from the National Transportation Safety Board were collected. A computer analysis of the accident data was performed. Between 65 and 90 accidents each year involve carburetor/induction system icing as a probable cause/factor. Under conditions conducive to carburetor/induction icing, between 50 and 70 percent of engine malfunction/failure accidents (exclusive of those due to fuel exhaustion) are due to carburetor/induction system icing. Since the evidence of such icing may not remain long after an accident, it is probable that the frequency of occurrence of such accidents is underestimated; therefore, some extrapolation of the data was conducted. The problem of carburetor/induction system icing is particularly acute for pilots with less than 1000 hours of total flying time. The severity of such accidents is about the same as any accident resulting from a forced landing or precautionary landing. About 144 persons, on the average, are exposed to death and injury each year in accidents involving carburetor/induction icing as a probable cause/factor.

Molecular Basis of Virulence in Staphylococcus aureus Mastitis

PubMed Central

Le Maréchal, Caroline; Seyffert, Nubia; Jardin, Julien; Hernandez, David; Jan, Gwenaël; Rault, Lucie; Azevedo, Vasco; François, Patrice; Schrenzel, Jacques; van de Guchte, Maarten; Even, Sergine; Berkova, Nadia; Thiéry, Richard; Fitzgerald, J. Ross

2011-01-01

Background S. aureus is one of the main pathogens involved in ruminant mastitis worldwide. The severity of staphylococcal infection is highly variable, ranging from subclinical to gangrenous mastitis. This work represents an in-depth characterization of S. aureus mastitis isolates to identify bacterial factors involved in severity of mastitis infection. Methodology/Principal Findings We employed genomic, transcriptomic and proteomic approaches to comprehensively compare two clonally related S. aureus strains that reproducibly induce severe (strain O11) and milder (strain O46) mastitis in ewes. Variation in the content of mobile genetic elements, iron acquisition and metabolism, transcriptional regulation and exoprotein production was observed. In particular, O11 produced relatively high levels of exoproteins, including toxins and proteases known to be important in virulence. A characteristic we observed in other S. aureus strains isolated from clinical mastitis cases. Conclusions/Significance Our data are consistent with a dose-dependant role of some staphylococcal factors in the hypervirulence of strains isolated from severe mastitis. Mobile genetic elements, transcriptional regulators, exoproteins and iron acquisition pathways constitute good targets for further research to define the underlying mechanisms of mastitis severity. PMID:22096559

Differential Involvement of Brain-Derived Neurotrophic Factor in Reconsolidation and Consolidation of Conditioned Taste Aversion Memory

PubMed Central

Wang, Yue; Zhang, Tian-Yi; Xin, Jian; Li, Ting; Yu, Hui; Li, Na; Chen, Zhe-Yu

2012-01-01

Consolidated memory can re-enter states of transient instability following reactivation, which is referred to as reconsolidation, and the exact molecular mechanisms underlying this process remain unexplored. Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic plasticity and memory processes. We have recently observed that BDNF signaling in the central nuclei of the amygdala (CeA) and insular cortex (IC) was involved in the consolidation of conditioned taste aversion (CTA) memory. However, whether BDNF in the CeA or IC is required for memory reconsolidation is still unclear. In the present study, using a CTA memory paradigm, we observed increased BDNF expression in the IC but not in the CeA during CTA reconsolidation. We further determined that BDNF synthesis and signaling in the IC but not in the CeA was required for memory reconsolidation. The differential, spatial-specific roles of BDNF in memory consolidation and reconsolidation suggest that dissociative molecular mechanisms underlie reconsolidation and consolidation, which might provide novel targets for manipulating newly encoded and reactivated memories without causing universal amnesia. PMID:23185492

The Role of Online Communication in Long-Term Cyberbullying Involvement Among Girls and Boys.

PubMed

Festl, Ruth; Quandt, Thorsten

2016-09-01

Digital media, especially mobile communication technologies, enable adolescents to explore and experiment with each other with only limited adult control. Conflicts between peers can be easily staged since nearly everybody can be reached at any time under the radar of authorities. Therefore, involvement in conflicts and bullying might depend on how adolescents use and behave online. In the present study, we provide a comprehensive picture of the role aspects of online communication play in long-term involvement in cyberbullying. We focused on a gender-specific perspective, as girls and boys were found to differ not only according to their online communication but also in their cyberbullying involvement. Using a two-wave panel survey of 1817 adolescents between 13 and 17 years (56 % female), we found that girls' cyberbullying involvement (perpetration and victimization) could be traced back to more intensive online social activities and a higher amount of online contact with strangers. In contrast, for boys, only higher exposure to antisocial media content predicted higher levels of victimization over time. The findings indicate that certain patterns of online communication increase the cyberbullying risk over time. However, it needs to be noted that these risk factors vary between girls and boys.

Enhancing the placebo response: fMRI Evidence of Memory and Semantic Processing in Placebo Analgesia

PubMed Central

Craggs, Jason G.; Price, Donald D.; Robinson, Michael E.

2014-01-01

Two groups of patients with irritable bowel syndrome (IBS) rated pain and underwent fMRI brain scanning during experimentally induced rectal distension (20 sec, 7 stimuli). Group #1 was tested under baseline (natural history) and a verbally induced placebo condition, whereas Group #2 was tested under baseline, and standard placebo (no verbal suggestion for pain reduction) and intrarectal lidocaine conditions. As hypothesized, intrarectal lidocaine reduced evoked pain and pain-related brain activity within Group #2Between-group comparisons showed that adding a verbal suggestion to a placebo condition increased neural activity involved in memory and semantic processing, areas that process the placebo suggestions. These areas, in turn, are likely to influence brain areas involved in emotions and analgesia and consequently the placebo effect. These placebo suggestions also added significant decreases in activity of brain areas that process pain. The test stimulus itself seems to cue these effects and is consistent with previous explanations that somatic focus and sensory feedback reinforce expectations and other factors that mediate placebo analgesic effects. PMID:24412799

Oligonucleotide microarray analysis reveals dysregulation of energy-related metabolism in insulin-sensitive tissues of type 2 diabetes patients.

PubMed

Wang, M; Wang, X C; Zhao, L; Zhang, Y; Yao, L L; Lin, Y; Peng, Y D; Hu, R M

2014-06-17

Impaired insulin action within skeletal muscle, adipose tissue, and the liver is an important characteristic of type 2 diabetes (T2D). In order to identify common underlying defects in insulin-sensitive tissues that may be involved in the pathogenesis of T2D, the gene expression profiles of skeletal muscle, visceral adipose tissue, and liver from autopsy donors with or without T2D were examined using oligonucleotide microarrays and quantitative reverse transcriptase-PCR. Compared with controls, 691 genes were commonly dysregulated in these three insulin-sensitive tissues of humans with T2D. These co-expressed genes were enriched within the mitochondrion, with suggested involvement in energy metabolic processes such as glycolysis and gluconeogenesis, fatty acid beta oxidative, tricarboxylic acid cycle, and electron transport. Genes related to energy metabolism were mostly downregulated in diabetic skeletal muscle and visceral adipose tissue, while they were upregulated in the diabetic liver. This observed dysregulation in energy-related metabolism may be the underlying factor leading to the molecular mechanisms responsible for the insulin resistance of patients with T2D.

Strychnine inhibits inflammatory angiogenesis in mice via down regulation of VEGF, TNF-α and TGF-β.

PubMed

Saraswati, Sarita; Agarwal, S S

2013-05-01

Strychnine is known to possess anti-inflammatory and antitumour activity, but its roles in tumour angiogenesis, the key step involved in tumour growth and metastasis, and the involved molecular mechanism are still unknown. We aimed to investigate the effects of strychnine on key components of inflammatory angiogenesis in the murine cannulated sponge implant angiogenesis model. Polyester-polyurethane sponges, used as a framework for fibrovascular tissue growth, were implanted in Swiss albino mice and strychnine (0.25, and 0.5 mg/kg/day) was given through installed cannulas for 9 days. The implants collected at day 9 postimplantation were processed for the assessment of haemoglobin (Hb), myeloperoxidase (MPO), N-acetylglucosaminidase (NAG) and collagen used as indexes for angiogenesis, neutrophil and macrophage accumulation and extracellular matrix deposition, respectively. Relevant inflammatory, angiogenic and fibrogenic cytokines were also determined. Strychnine treatment attenuated the main components of the fibrovascular tissue, wet weight, vascularization (Hb content), macrophage recruitment (NAG activity), collagen deposition and the levels of vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-α and transforming growth factor (TGF-β). A regulatory function of strychnine on multiple parameters of main components of inflammatory angiogenesis has been revealed giving insight into the potential therapeutic underlying the actions of strychnine. Copyright © 2013 Elsevier Inc. All rights reserved.

Redox-Dependent Modulation of Anthocyanin Biosynthesis by the TCP Transcription Factor TCP15 during Exposure to High Light Intensity Conditions in Arabidopsis.

PubMed

Viola, Ivana L; Camoirano, Alejandra; Gonzalez, Daniel H

2016-01-01

TCP proteins integrate a family of transcription factors involved in the regulation of developmental processes and hormone responses. It has been shown that most members of class I, one of the two classes in which the TCP family is divided, contain a conserved Cys that leads to inhibition of DNA binding when oxidized. In this work, we describe that the class-I TCP protein TCP15 inhibits anthocyanin accumulation during exposure of plants to high light intensity by modulating the expression of transcription factors involved in the induction of anthocyanin biosynthesis genes, as suggested by the study of plants that express TCP15 from the 35SCaMV promoter and mutants in TCP15 and the related gene TCP14. In addition, the effect of TCP15 on anthocyanin accumulation is lost after prolonged incubation under high light intensity conditions. We provide evidence that this is due to inactivation of TCP15 by oxidation of Cys-20 of the TCP domain. Thus, redox modulation of TCP15 activity in vivo by high light intensity may serve to adjust anthocyanin accumulation to the duration of exposure to high irradiation conditions. © 2016 American Society of Plant Biologists. All Rights Reserved.

Enhanced visual awareness for morality and pajamas? Perception vs. memory in 'top-down' effects.

PubMed

Firestone, Chaz; Scholl, Brian J

2015-03-01

A raft of prominent findings has revived the notion that higher-level cognitive factors such as desire, meaning, and moral relevance can directly affect what we see. For example, under conditions of brief presentation, morally relevant words reportedly "pop out" and are easier to identify than morally irrelevant words. Though such results purport to show that perception itself is sensitive to such factors, much of this research instead demonstrates effects on visual recognition--which necessarily involves not only visual processing per se, but also memory retrieval. Here we report three experiments which suggest that many alleged top-down effects of this sort are actually effects on 'back-end' memory rather than 'front-end' perception. In particular, the same methods used to demonstrate popout effects for supposedly privileged stimuli (such as morality-related words, e.g. "punishment" and "victim") also yield popout effects for unmotivated, superficial categories (such as fashion-related words, e.g. "pajamas" and "stiletto"). We conclude that such effects reduce to well-known memory processes (in this case, semantic priming) that do not involve morality, and have no implications for debates about whether higher-level factors influence perception. These case studies illustrate how it is critical to distinguish perception from memory in alleged 'top-down' effects. Copyright © 2014 Elsevier B.V. All rights reserved.

Long term betaine supplementation regulates genes involved in lipid and cholesterol metabolism of two muscles from an obese pig breed.

PubMed

Albuquerque, A; Neves, José A; Redondeiro, M; Laranjo, M; Félix, M R; Freitas, Amadeu; Tirapicos, José L; Martins, José M

2017-02-01

This study evaluates the effects of betaine supplementation (1gkg -1 for 20weeks) on the regulation of genes involved in lipid and cholesterol metabolism of Longissimus lumborum and Biceps femoris from obese Alentejano pigs. Betaine supplementation led to an increase in total cholesterol in both muscles, complementing results previously published indicating a significant increase on the intramuscular lipid content. The expression of twelve genes involved in lipogenesis, lipolysis/FA oxidation, FA transport, and cholesterol metabolism, as well as two transcription factors were also evaluated. Genes related to lipid and cholesterol synthesis plus FA transport were consistently up-regulated in both muscles of betaine fed pigs. On the other hand, genes related to lipolysis/FA oxidation were not affected or down-regulated by betaine supplementation. Our data suggest that the underlying mechanism regulating IMF and cholesterol accumulation in Alentejano pigs supplemented with betaine is associated with the up-regulation of genes involved in lipid synthesis, FA transport, and cholesterol synthesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

PDGF activates K-Cl cotransport through phosphoinositide 3-kinase and protein phosphatase-1 in primary cultures of vascular smooth muscle cells.

PubMed

Zhang, Jing; Lauf, Peter K; Adragna, Norma C

2005-07-15

K-Cl cotransport (K-Cl COT, KCC) is an electroneutrally coupled movement of K and Cl present in most cells. In this work, we studied the pathways of regulation of K-Cl COT by platelet-derived growth factor (PDGF) in primary cultures of vascular smooth muscle cells (VSMCs). Wortmannin and LY 294002 blocked the PDGF-induced K-Cl COT activation, indicating that the phosphoinositide 3-kinase (PI 3-K) pathway is involved. However, PD 98059 had no effect on K-Cl COT activation by PDGF, suggesting that the mitogen-activated protein kinase pathway is not involved under the experimental conditions tested. Involvement of phosphatases was also examined. Sodium orthovanadate, cyclosporin A and okadaic acid had no effect on PDGF-stimulated K-Cl COT. Calyculin A blocked the PDGF-stimulated K-Cl COT by 60%, suggesting that protein phosphatase-1 (PP-1) is a mediator in the PDGF signaling pathway/s. In conclusion, our results indicate that the PDGF-mediated pathways of K-Cl COT regulation involve the signaling molecules PI 3-K and PP-1.

Hyperhomocysteinemia impairs regional blood flow: involvements of endothelial and neuronal nitric oxide.

PubMed

Toda, Noboru; Okamura, Tomio

2016-09-01

Increasing evidence support the idea that hyperhomocysteinemia (HHcy) is responsible for pathogenesis underlying cerebral, coronary, renal, and other vascular circulatory disorders and for hypertension. Impaired synthesis of nitric oxide (NO) in the endothelium or increased production of asymmetric dimethylarginine and activated oxygen species are involved in the impairment of vasodilator effects of NO. Impaired circulation in the brain derived from reduced synthesis and actions of NO would be an important triggering factor to dementia and Alzheimer's disease. Reduced actions of NO and brain hypoperfusion trigger increased production of amyloid-β that inhibits endothelial function, thus establishing a vicious cycle for impairing brain circulation. HHcy is involved in the genesis of anginal attack and coronary myocardial infarction. HHcy is also involved in renal circulatory diseases. The homocysteine (Hcy)-induced circulatory failure is promoted by methionine and is prevented by increased folic acid and vitamin B6/B12. Eliminating poor life styles, such as smoking and being sedentary; keeping favorable dietary habits; and early treatment maintaining constitutive NOS functions healthy, reducing oxidative stresses would be beneficial in protecting HHcy-induced circulatory failures.

{open_quotes}Horizontal{close_quotes} gene transfer from a transgenic potato line to a bacterial pathogen (Erwinia chrysanthemi) occurs - if at all - at an extremely low frequency

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

Schlueter, K.; Fuetterer, J.; Potrykus, I.

1995-10-01

The frequency of possible {open_quotes}horizontal{close_quotes} gene transfer between a plant and a tightly associated bacterial pathogen was studied in a model system consisting of transgenic Solanum tuberosum, containing a {beta}-lactamase gene linked to a pBR322 origin of replication, and Erwinia chrysanthemi. This experimental system offers optimal conditions for the detection of possible horizontal gene transfer events, even when they occur at very low frequency. Horizontal gene transfer was not detected under conditions mimicking a {open_quotes}natural{close_quotes} infection. The gradual, stepwise alteration of artificial, positive control conditions to idealized natural conditions, however, allowed the characterization of factors that affected gene transfer, andmore » revealed a gradual decrease of the gene transfer frequency from 6.3 x 10{sup -2} under optimal control conditions to a calculated 2.0 x 10{sub -17} under idealized natural conditions. These data, in combination with other published studies, argue that horizontal gene transfer is so rare as to be essentially irrelevant to any realistic assessment of the risk involved in release experiments involving transgenic plants. 22 refs., 3 figs., 2 tabs.« less

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins.

PubMed

González-Guerra, José Luis; Castilla-Cortazar, Inma; Aguirre, Gabriel A; Muñoz, Úrsula; Martín-Estal, Irene; Ávila-Gallego, Elena; Granado, Miriam; Puche, Juan E; García-Villalón, Ángel Luis

2017-01-01

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions.

Partial IGF-1 deficiency is sufficient to reduce heart contractibility, angiotensin II sensibility, and alter gene expression of structural and functional cardiac proteins

PubMed Central

Aguirre, Gabriel A.; Muñoz, Úrsula; Martín-Estal, Irene; Ávila-Gallego, Elena; Granado, Miriam; Puche, Juan E.; García-Villalón, Ángel Luis

2017-01-01

Circulating levels of IGF-1 may decrease under several circumstances like ageing, metabolic syndrome, and advanced cirrhosis. This reduction is associated with insulin resistance, dyslipidemia, progression to type 2 diabetes, and increased risk for cardiovascular diseases. However, underlying mechanisms between IGF-1 deficiency and cardiovascular disease remain elusive. The specific aim of the present work was to study whether the partial IGF-1 deficiency influences heart and/or coronary circulation, comparing vasoactive factors before and after of ischemia-reperfusion (I/R). In addition, histology of the heart was performed together with cardiac gene expression for proteins involved in structure and function (extracellular matrix, contractile proteins, active peptides); carried out using microarrays, followed by RT-qPCR confirmation of the three experimental groups. IGF-1 partial deficiency is associated to a reduction in contractility and angiotensin II sensitivity, interstitial fibrosis as well as altered expression pattern of genes involved in extracellular matrix proteins, calcium dynamics, and cardiac structure and function. Although this work is descriptive, it provides a clear insight of the impact that partial IGF-1 deficiency on the heart and establishes this experimental model as suitable for studying cardiac disease mechanisms and exploring therapeutic options for patients under IGF-1 deficiency conditions. PMID:28806738

The influence of patient factors on patient-reported outcomes of orthopedic surgery involving implantable devices: a systematic review.

PubMed

Waheeb, Androu; Zywiel, Michael G; Palaganas, Marvilyn; Venkataramanan, Viji; Davis, Aileen M

2015-02-01

Recent evidence suggests that patient factors can influence response to medical and surgical treatment and may play an under-recognized role in predicting treatment outcomes. However, the current state of knowledge concerning potential associations following orthopedic surgery in particular is unclear. The purpose of the present study was to systematically review current literature to investigate the currently known associations between pre-operative patient factors and patient-reported outcomes following orthopedic surgery. A systematic review was performed of the PubMed database to identify original studies that investigated the relationships between one or more patient factors and patient-reported outcomes of primary orthopedic surgical procedures involving implantation of a medical device. A total of 10,174 records were identified, with 83 studies included in the final review. The most commonly assessed patient factors included age, sex, and body mass index (BMI), reported in 63%, 55%, and 48% of studies, respectively. The only other patient factors identified were socioeconomic status and race, both of which were assessed in a single study. Considerable heterogeneity was observed in the methods used to stratify subjects by patient factors, patient-reported outcome constructs assessed, and follow-up intervals. Only 10% of studies performed appropriate sample size or power calculations, only 51% used methodologies to control for potentially confounding factors, and 6% assessed responder status. Overall, variable and conflicting findings were seen. While female sex and increasing BMI did appear to be associated with worse absolute outcomes, these differences did not appear to be maintained when differences in baseline status were considered. No clear associations between age and outcomes were identified. The present understanding of these relationships between patient factors and patient-reported outcomes following orthopedic surgery is limited. There is a need for further studies using high-quality methodology, consistent stratification of participants based on patient factors, accepted patient-reported outcome constructs, and appropriate assessment of responder status. Copyright © 2014 Elsevier Inc. All rights reserved.

Diabetes, cardiac disorders and asthma as risk factors for severe organ involvement among adult dengue patients: A matched case-control study.

PubMed

Pang, Junxiong; Hsu, Jung Pu; Yeo, Tsin Wen; Leo, Yee Sin; Lye, David C

2017-01-03

Progression to severe organ involvement due to dengue infection has been associated with severe dengue disease, intensive care treatment, and mortality. However, there is a lack of understanding of the impact of pre-existing comorbidities and other risk factors of severe organ involvement among dengue adults. The aim of this retrospective case-control study is to characterize and identify risk factors that predispose dengue adults at risk of progression with severe organ involvement. This study involved 174 dengue patients who had progressed with severe organ involvement and 865 dengue patients without severe organ involvement, matched by the year of presentation of the cases, who were admitted to Tan Tock Seng Hospital between year 2005 and 2008. Age group of 60 years or older, diabetes, cardiac disorders, asthma, and having two or more pre-existing comorbidities were independent risk factors of severe organ involvement. Abdominal pain, clinical fluid accumulation, and hematocrit rise and rapid platelet count drop at presentation were significantly associated with severe organ involvement. These risk factors, when validated in a larger study, will be useful for triage by clinicians for prompt monitoring and clinical management at first presentation, to minimize the risk of severe organ involvement and hence, disease severity.

Neurobiology of Inflammation-Associated Anorexia

PubMed Central

Gautron, Laurent; Layé, Sophie

2009-01-01

Compelling data demonstrate that inflammation-associated anorexia directly results from the action of pro-inflammatory factors, primarily cytokines and prostaglandins E2, on the nervous system. For instance, the aforementioned pro-inflammatory factors can stimulate the activity of peripheral sensory neurons, and induce their own de novo synthesis and release into the brain parenchyma and cerebrospinal fluid. Ultimately, it results in the mobilization of a specific neural circuit that shuts down appetite. The present article describes the different cell groups and neurotransmitters involved in inflammation-associated anorexia and examines how they interact with neural systems regulating feeding such as the melanocortin system. A better understanding of the neurobiological mechanisms underlying inflammation-associated anorexia will help to develop appetite stimulants for cancer and AIDS patients. PMID:20582290

Organizational stress and individual strain: A social-psychological study of risk factors in coronary heart disease among administrators, engineers, and scientists

NASA Technical Reports Server (NTRS)

Caplan, R. D.

1971-01-01

It is hypothesized that organizational stresses, such as high quantitative work load, responsibility for persons, poor relations with role senders, and contact with alien organizational territories, may be associated with high levels of psychological and physiological strain which are risk factors in coronary heart disease. It is further hypothesized that persons with coronary-prone Type A personality characteristics are most likely to exhibit strain under conditions of organizational stress. Measures of these stresses, personality traits, and strains were obtained from 205 male NASA administrators, engineers, and scientists. Type A personality measures included sense of time urgency, persistence, involved striving, leadership, and preference for competitive and environmentally overburdening situations.

Lempel-Ziv complexity analysis of one dimensional cellular automata.

PubMed

Estevez-Rams, E; Lora-Serrano, R; Nunes, C A J; Aragón-Fernández, B

2015-12-01

Lempel-Ziv complexity measure has been used to estimate the entropy density of a string. It is defined as the number of factors in a production factorization of a string. In this contribution, we show that its use can be extended, by using the normalized information distance, to study the spatiotemporal evolution of random initial configurations under cellular automata rules. In particular, the transfer information from time consecutive configurations is studied, as well as the sensitivity to perturbed initial conditions. The behavior of the cellular automata rules can be grouped in different classes, but no single grouping captures the whole nature of the involved rules. The analysis carried out is particularly appropriate for studying the computational processing capabilities of cellular automata rules.

Long-term effects of bullying.

PubMed

Wolke, Dieter; Lereya, Suzet Tanya

2015-09-01

Bullying is the systematic abuse of power and is defined as aggressive behaviour or intentional harm-doing by peers that is carried out repeatedly and involves an imbalance of power. Being bullied is still often wrongly considered as a 'normal rite of passage'. This review considers the importance of bullying as a major risk factor for poor physical and mental health and reduced adaptation to adult roles including forming lasting relationships, integrating into work and being economically independent. Bullying by peers has been mostly ignored by health professionals but should be considered as a significant risk factor and safeguarding issue. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Lempel-Ziv complexity analysis of one dimensional cellular automata

NASA Astrophysics Data System (ADS)

Estevez-Rams, E.; Lora-Serrano, R.; Nunes, C. A. J.; Aragón-Fernández, B.

2015-12-01

Lempel-Ziv complexity measure has been used to estimate the entropy density of a string. It is defined as the number of factors in a production factorization of a string. In this contribution, we show that its use can be extended, by using the normalized information distance, to study the spatiotemporal evolution of random initial configurations under cellular automata rules. In particular, the transfer information from time consecutive configurations is studied, as well as the sensitivity to perturbed initial conditions. The behavior of the cellular automata rules can be grouped in different classes, but no single grouping captures the whole nature of the involved rules. The analysis carried out is particularly appropriate for studying the computational processing capabilities of cellular automata rules.

A UV-B-specific signaling component orchestrates plant UV protection

PubMed Central

Brown, Bobby A.; Cloix, Catherine; Jiang, Guang Huai; Kaiserli, Eirini; Herzyk, Pawel; Kliebenstein, Daniel J.; Jenkins, Gareth I.

2005-01-01

UV-B radiation in sunlight has diverse effects on humans, animals, plants, and microorganisms. UV-B can cause damage to molecules and cells, and consequently organisms need to protect against and repair UV damage to survive in sunlight. In plants, low nondamaging levels of UV-B stimulate transcription of genes involved in UV-protective responses. However, remarkably little is known about the underlying mechanisms of UV-B perception and signal transduction. Here we report that Arabidopsis UV RESISTANCE LOCUS 8 (UVR8) is a UV-B-specific signaling component that orchestrates expression of a range of genes with vital UV-protective functions. Moreover, we show that UVR8 regulates expression of the transcription factor HY5 specifically when the plant is exposed to UV-B. We demonstrate that HY5 is a key effector of the UVR8 pathway, and that it is required for survival under UV-B radiation. UVR8 has sequence similarity to the eukaryotic guanine nucleotide exchange factor RCC1, but we found that it has little exchange activity. However, UVR8, like RCC1, is located principally in the nucleus and associates with chromatin via histones. Chromatin immunoprecipitation showed that UVR8 associates with chromatin in the HY5 promoter region, providing a mechanistic basis for its involvement in regulating transcription. We conclude that UVR8 defines a UV-B-specific signaling pathway in plants that orchestrates the protective gene expression responses to UV-B required for plant survival in sunlight. PMID:16330762

The sunflower transcription factor HaHB11 confers tolerance to water deficit and salinity to transgenic Arabidopsis and alfalfa plants.

PubMed

Cabello, Julieta V; Giacomelli, Jorge I; Gómez, María C; Chan, Raquel L

2017-09-10

Homeodomain-leucine zipper (HD-Zip) transcription factors are unique to the plant kingdom; members of subfamily I are known to be involved in abiotic stress responses. HaHB11 belongs to this subfamily and it was previously shown that it is able to confer improved yield and tolerance to flooding via a quiescent strategy. Here we show that HaHB11 expression is induced by ABA, NaCl and water deficit in sunflower seedlings and leaves. Arabidopsis transgenic plants expressing HaHB11, controlled either by its own promoter or by the constitutive 35S CaMV, presented rolled leaves and longer roots than WT when grown under standard conditions. In addition, these plants showed wider stems and more vascular bundles. To deal with drought, HaHB11 transgenic plants closed their stomata faster and lost less water than controls, triggering an enhanced tolerance to such stress condition and also to salinity stress. Concomitantly, ABA-synthesis and sensing related genes were differentially regulated in HaHB11 transgenic plants. Either under long-term salinity stress or mild drought stress, HaHB11 transgenic plants did not exhibit yield penalties. Moreover, alfalfa transgenic plants were generated which also showed enhanced drought tolerance. Altogether, the results indicated that HaHB11 was able to confer drought and salinity tolerance via a complex mechanism which involves morphological, physiological and molecular changes. Copyright © 2016 Elsevier B.V. All rights reserved.

Influences on final year medical students' attitudes to general practice as a career.

PubMed

Parker, Johanna E; Hudson, Ben; Wilkinson, Tim J

2014-03-01

General practice is under-represented in student career choices. This study aimed to identify and explore factors that influence the attitudes of final year medical students to general practice as a career. This qualitative study used semi-structured interviews of focus groups of final year undergraduate medical students at the University of Otago, Christchurch, New Zealand. Thematic analysis and grounded theory were used to interpret the data. General practitioners (GPs) play a key role in influencing medical students' attitudes to general practice as a career. Students identified their general practice placement during medical school training and personal contact with their own GP as principal factors. The media portrayal of general practice and the attitudes of friends and family were also influential. Students were positively influenced when they were made to feel part of the team, involved with consultations, allowed to carry out practical procedures under supervision, and witnessed what they perceived as good medical practice during clinical placements. Positive experiences often occurred later in training, when students felt more confident of their clinical abilities. While students reported occasional negative comments about general practice by some hospital doctors, these had a lesser role in influencing their perceptions of general practice compared with their own experiences, both as students and patients. GPs have a strong influence, positively and negatively, on the attitudes of medical students to general practice as a career. Effective influences include being made to feel welcome, involved, valued, and given legitimate roles during clinical placements.

Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1beta and nerve growth factor in cultured hippocampal neuronal cells.

PubMed

Di Loreto, Silvia; Caracciolo, Valentina; Colafarina, Sabrina; Sebastiani, Pierluigi; Gasbarri, Antonella; Amicarelli, Fernanda

2004-05-01

Methylglyoxal (MG) is one of the most powerful glycating agents of proteins and other important cellular components and has been shown to be toxic to cultured cells. Under hyperglycaemic conditions, an increase in the concentration of MG has been observed in human body fluids and tissues that seems to be responsible for diabetic complications. Recent data suggest that diabetes may cause impairment of cognitive processes, according to a mechanism involving both oxidative stress and advanced glycation end product (AGE) formation. In this work, we explored the molecular mechanism underlying MG toxicity in neural cells, by investigating the effect of MG on both the interleukin-1beta (IL-1beta), as the major inducer of the acute phase response, and the nervous growth factor (NGF) expression. Experiments were performed on cultured neural cells from rat hippocampus, being this brain region mostly involved in cognitive processes and, therefore, possible target of diabetes-mediated impairment of cognitive abilities. Results show that MG treatment causes in hippocampal neural cells extensive, oxidative stress-mediated cell death, in consequence of a strong catalase enzymatic activity and protein inhibition. MG also causes a very significant increase in both transcript and protein expression of the NGF as well as of the pro-inflammatory cytokine IL-1beta. MG co-treatment with the antioxidant N-acetylcysteine (NAC) completely abrogates the observed effects. Taken together, these data demonstrate that hippocampal neurons are strongly susceptible to MG-mediated oxidative stress.

Psoriasis as a cardiovascular risk factor: updates and algorithmic approach.

PubMed

Cozzani, Emanuele; Rosa, Gianmarco; Burlando, Martina; Parodi, Aurora

2018-04-19

Although psoriasis is predominantly a chronic inflammatory skin disorder, it has been known to be associated with cardiovascular disease. Patients with psoriasis, particularly with moderate to severe forms, present an increased rate of cardiovascular mortality, myocardial infarction and stroke. However the pathophysiology of the relationship between psoriasis and cardiovascular risk and comorbidities has not yet completely known. Chronic inflammation may be considered a solid link between psoriasis and related cardiovascular events. Several cytokines and inflammatory cells play a pivotal role in the development of psoriatic lesions, resulting in angiogenesis and endothelial dysfunction. Furthermore, the imbalance between oxidative stress and anti-oxidant mechanisms in psoriatic patients may contribute to explain the pathogenesis of increased reactive oxygen species and the formation of atherosclerotic plaque. Other mechanistic pathways which may be involved in this relationship include cardiovascular effects of medications, a common genetic background and a higher prevalence of cardiovascular risk factors, which are often under-diagnosed and under-treated in psoriatic patients. Indeed, the early detection of specific markers of cardiovascular impairment, such as N-terminal pro B-type natriuretic peptide, homocysteine and YKL-40, may enable psoriatic patients at higher cardiovascular risk to be identified as soon as possible. This review examines the increased cardiovascular risk profile and high prevalence of cardiovascular disease associated with psoriasis, focusing on pathogenic links between psoriasis and atherosclerosis, serological markers of cardiovascular involvement and the implications of anti-psoriatic therapies on cardiovascular risk and proposes a flow chart, that every dermatologist should follow to screen psoriatic patients.

IL-13 may be involved in the development of CAD via different mechanisms under different conditions in a Chinese Han population.

PubMed

Zha, Ling-Feng; Nie, Shao-Fang; Chen, Qian-Wen; Liao, Yu-Hua; Zhang, Hong-Song; Dong, Jiang-Tao; Xie, Tian; Wang, Fan; Tang, Ting-Ting; Xia, Ni; Xu, Cheng-Qi; Zhou, Ying-Chao; Zeng, Zhi-Peng; Jiao, Jiao; Wang, Peng-Yun; Wang, Qing K; Tu, Xin; Cheng, Xiang

2018-04-18

Interleukin-13 (IL-13) has important functions in atherosclerosis, but its role in coronary artery disease (CAD) is unclear. Here, we studied the genetic role of IL-13 in CAD in a Chinese Han population using tag SNPs covering the whole IL13 gene (i.e., rs1881457, rs2069744 and rs20541) and a two-stage cohort containing 1863 CAD cases and 1841 controls. Traditional risk factors for CAD, such as age, BMI, and other factors, were used as covariates in logistic regression analysis. In the total population, we found that two haplotypes of IL13 (ATG and ATA, ordered rs1881457 C -rs2069744 T -rs20541 A ) significantly contributed to the risk of CAD with adjusted p values less than 0.05 (p adj  = 0.019 and p adj  = 0.042, respectively). In subgroup population analyses, the variant rs1881457 C was found to significantly contribute to a nearly two fold increase in the risk of CAD in men (p adj  = 0.023, OR = 1.91, 95% CI: 1.09-3.33). The variant rs1881457 C also significantly contributed to a nearly twofold risk of late-onset CAD (p adj  = 0.024, OR = 1.93, 95% CI: 1.09-3.42). In conclusion, IL13 might be involved in CAD via different mechanisms under different conditions in the Chinese Han population.

The Circadian Clock Coordinates Ribosome Biogenesis

PubMed Central

Symul, Laura; Martin, Eva; Atger, Florian; Naef, Felix; Gachon, Frédéric

2013-01-01

Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis. PMID:23300384

Distinct functions of human RecQ helicases during DNA replication.

PubMed

Urban, Vaclav; Dobrovolna, Jana; Janscak, Pavel

2017-06-01

DNA replication is the most vulnerable process of DNA metabolism in proliferating cells and therefore it is tightly controlled and coordinated with processes that maintain genomic stability. Human RecQ helicases are among the most important factors involved in the maintenance of replication fork integrity, especially under conditions of replication stress. RecQ helicases promote recovery of replication forks being stalled due to different replication roadblocks of either exogenous or endogenous source. They prevent generation of aberrant replication fork structures and replication fork collapse, and are involved in proper checkpoint signaling. The essential role of human RecQ helicases in the genome maintenance during DNA replication is underlined by association of defects in their function with cancer predisposition. Copyright © 2016 Elsevier B.V. All rights reserved.

Process feasibility study in support of silicon material, task 1

NASA Technical Reports Server (NTRS)

Li, K. Y.; Hansen, K. C.; Yaws, C. L.

1979-01-01

Analyses of process system properties were continued for materials involved in the alternate processes under consideration for semiconductor silicon. Primary efforts centered on physical and thermodynamic property data for dichlorosilane. The following property data are reported for dichlorosilane which is involved in processing operations for solar cell grade silicon: critical temperature, critical pressure, critical volume, critical density, acentric factor, vapor pressure, heat of vaporization, gas heat capacity, liquid heat capacity and density. Work was initiated on the assembly of a system to prepare binary gas mixtures of known proportions and to measure the thermal conductivity of these mixtures between 30 and 350 C. The binary gas mixtures include silicon source material such as silanes and halogenated silanes which are used in the production of semiconductor silicon.

Gene expression analysis in hypoplastic lungs in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Burgos, Carmen Mesas; Uggla, Andreas Ringman; Fagerström-Billai, Fredrik; Eklöf, Ann-Christine; Frenckner, Björn; Nord, Magnus

2010-07-01

Pulmonary hypoplasia and persistent pulmonary hypertension are the main causes of mortality and morbidity in newborns with congenital diaphragmatic hernia (CDH). Nitrofen is well known to induce CDH and lung hypoplasia in a rat model, but the mechanism remains unknown. To increase the understanding of the underlying pathogenesis of CDH, we performed a global gene expression analysis using microarray technology. Pregnant rats were given 100 mg nitrofen on gestational day 9.5 to create CDH. On day 21, fetuses after nitrofen administration and control fetuses were removed; and lungs were harvested. Global gene expression analysis was performed using Affymetrix Platform and the RAE 230 set arrays. For validation of microarray data, we performed real-time polymerase chain reaction and Western blot analysis. Significantly decreased genes after nitrofen administration included several growth factors and growth factors receptors involved in lung development, transcription factors, water and ion channels, and genes involved in angiogenesis and extracellular matrix. These results could be confirmed with real-time polymerase chain reaction and protein expression studies. The pathogenesis of lung hypoplasia and CDH in the nitrofen model includes alteration at a molecular level of several pathways involved in lung development. The complexity of the nitrofen mechanism of action reminds of human CDH; and the picture is consistent with lung hypoplasia and vascular disease, both important contributors to the high mortality and morbidity in CDH. Increased understanding of the molecular mechanisms that control lung growth may be the key to develop novel therapeutic techniques to stimulate pre- and postnatal lung growth. Copyright 2010 Elsevier Inc. All rights reserved.

Underlying risk factors for prescribing errors in long-term aged care: a qualitative study.

PubMed

Tariq, Amina; Georgiou, Andrew; Raban, Magdalena; Baysari, Melissa Therese; Westbrook, Johanna

2016-09-01

To identify system-related risk factors perceived to contribute to prescribing errors in Australian long-term care settings, that is, residential aged care facilities (RACFs). The study used qualitative methods to explore factors that contribute to unsafe prescribing in RACFs. Data were collected at three RACFs in metropolitan Sydney, Australia between May and November 2011. Participants included RACF managers, doctors, pharmacists and RACF staff actively involved in prescribing-related processes. Methods included non-participant observations (74 h), in-depth semistructured interviews (n=25) and artefact analysis. Detailed process activity models were developed for observed prescribing episodes supplemented by triangulated analysis using content analysis methods. System-related factors perceived to increase the risk of prescribing errors in RACFs were classified into three overarching themes: communication systems, team coordination and staff management. Factors associated with communication systems included limited point-of-care access to information, inadequate handovers, information storage across different media (paper, electronic and memory), poor legibility of charts, information double handling, multiple faxing of medication charts and reliance on manual chart reviews. Team factors included lack of established lines of responsibility, inadequate team communication and limited participation of doctors in multidisciplinary initiatives like medication advisory committee meetings. Factors related to staff management and workload included doctors' time constraints and their accessibility, lack of trained RACF staff and high RACF staff turnover. The study highlights several system-related factors including laborious methods for exchanging medication information, which often act together to contribute to prescribing errors. Multiple interventions (eg, technology systems, team communication protocols) are required to support the collaborative nature of RACF prescribing. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Influence of Postnatal Psychiatric Disorder on Child Development

PubMed Central

Stein, Alan; Lehtonen, Annukka; Harvey, Allison G.; Nicol-Harper, Rosie; Craske, Michelle

2009-01-01

There is considerable evidence that maternal postnatal psychiatric disorder has an adverse influence on infant development. In attempting to examine the pathways of intergenerational transmission, most research has concentrated on genetic factors or on maternal behaviours during mother-child interaction and attachment. However, researchers have largely ignored the possible role of maternal cognition underlying behaviour, especially the thought and attentional processes involved in psychiatric disorders. This paper argues that a particular form of maternal cognition, namely ‘preoccupation’, is one key, but under-recognised, mechanism in the transmission of psychiatric disturbance. We propose that preoccupation interferes with specific aspects of mental functioning, especially attention and responsivity to the environment. This impairs the mother's parenting capacities and adversely affects mother-child interaction and child development. PMID:19023230

An exploratory analysis of task-interspersal procedures while teaching object labels to children with autism.

PubMed

Volkert, Valerie M; Lerman, Dorothea C; Trosclair, Nicole; Addison, Laura; Kodak, Tiffany

2008-01-01

Research has demonstrated that interspersing mastered tasks with new tasks facilitates learning under certain conditions; however, little is known about factors that influence the effectiveness of this treatment strategy. The initial purpose of the current investigation was to evaluate the effects of similar versus dissimilar interspersed tasks while teaching object labels to children diagnosed with autism or developmental delays. We then conducted a series of exploratory analyses involving the type of reinforcer delivered for correct responses on trials with unknown or known object labels. Performance was enhanced under the interspersal condition only when either brief praise was delivered for all correct responses or presumably more preferred reinforcers were provided for performance on known trials rather than on unknown trials.

Recurrent symptomatic ischemic stroke in a 46-year-old African male revealing Angio-Behçet with severe cardiovascular involvement.

PubMed

Marie, Ba Djibril; Aminata, Diack; Cherif, Mboup Mouhamed; Daouda, Fall Moussa

2017-03-01

Behçet'sdisease (BD) is a chronic, multisystem vasculitis. It is categorized under variable vessel vasculitis in the new Chapel Hill nomenclature as it involves blood vessels of any type and size. It is characterized by relapsing aphthous ulcers commonly occurring in the oral mucosa and genitalia with ocular involvement. Other organ systems may be involved any time throughout the course of the disease. The exact cause is unknown. However, combination of genetic and environmental factors is likely to play a role. Cardiac involvement may occur in the form of intracardiac thrombus, endocarditis, myocarditis, pericarditis, endomyocardial fibrosis, coronary arteritis, myocardial infarction, and valvular disease. We present a case of Angio-Behçet in a 46-year-old African male with severe cardiovascular involvement including pulmonary artery hypertension (PAH), right ventricular failure and left ventricular diastolic dysfunction diagnosed after 2 episodes of symptomatic ischemic stroke resulting from complete occlusion of the right internal carotid artery (ICA) up to its intracranial portion. Immunosuppressive and anticoagulant therapies have induced improvement in cardiac manifestations. Nevertheless, prompt recognition of the primarily vascular manifestation of BD without mucocutaneous manifestations was responsible for considerable delay that did not afford surgical therapy for the carotid occlusion.

[Various pathways leading to the progression of chronic liver diseases].

PubMed

Egresi, Anna; Lengyel, Gabriella; Somogyi, Anikó; Blázovics, Anna; Hagymási, Krisztina

2016-02-21

As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

SP and KLF Transcription Factors in Digestive Physiology and Diseases.

PubMed

Kim, Chang-Kyung; He, Ping; Bialkowska, Agnieszka B; Yang, Vincent W

2017-06-01

Specificity proteins (SPs) and Krüppel-like factors (KLFs) belong to the family of transcription factors that contain conserved zinc finger domains involved in binding to target DNA sequences. Many of these proteins are expressed in different tissues and have distinct tissue-specific activities and functions. Studies have shown that SPs and KLFs regulate not only physiological processes such as growth, development, differentiation, proliferation, and embryogenesis, but pathogenesis of many diseases, including cancer and inflammatory disorders. Consistently, these proteins have been shown to regulate normal functions and pathobiology in the digestive system. We review recent findings on the tissue- and organ-specific functions of SPs and KLFs in the digestive system including the oral cavity, esophagus, stomach, small and large intestines, pancreas, and liver. We provide a list of agents under development to target these proteins. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

The origin of Behçet's disease geoepidemiology: possible role of a dual microbial-driven genetic selection.

PubMed

Piga, Matteo; Mathieu, Alessandro

2014-01-01

It is recognised that the genetic profiles that give rise to chronic inflammatory diseases, under the influence of environmental agents, might have been implicated in the host defence mechanism against lethal infections in the past. Behçet's disease (BD) is an immune-mediated inflammatory disease, expressed as vasculitis, triggered by environmental factors in genetically susceptible individuals. We carried out a review of published data to draw up an evolutionary adaptation model, as Author's perspective, for genetic susceptibility factors and inflammatory immune response involved in BD pathogenesis. Two lethal infectious agents, Plasmodium Falciparum and Yersinia Pestis, are proposed as the putative driving forces that favoured the fixing of the major genetic susceptibility factors to BD, thus determining its geoepidemiology. Further studies are needed to confirm the validity of this evolutionary model which includes and integrates the key insights of previous hypotheses.

Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome.

PubMed

O'Malley, Dervla

2016-11-01

Irritable bowel syndrome (IBS) is a common disorder characterized by recurrent abdominal pain, bloating, and disturbed bowel habit, symptoms that impact the quality of life of sufferers. The pathophysiological changes underlying this multifactorial condition are complex and include increased sensitivity to luminal and mucosal factors, resulting in altered colonic transit and visceral pain. Moreover, dysfunctional communication in the bidirectional signaling axis between the brain and the gut, which involves efferent and afferent branches of the peripheral nervous system, circulating endocrine hormones, and local paracrine and neurocrine factors, including immune and perhaps even microbial signaling molecules, has a role to play in this disorder. This minireview will examine recent advances in our understanding of the pathophysiology of IBS and assess how cross talk between hormones, immune, and microbe-derived factors and their neuromodulatory effects on peripheral nerves may underlie IBS symptomatology. Copyright © 2016 the American Physiological Society.

Development and validation of the coping with terror scale.

PubMed

Stein, Nathan R; Schorr, Yonit; Litz, Brett T; King, Lynda A; King, Daniel W; Solomon, Zahava; Horesh, Danny

2013-10-01

Terrorism creates lingering anxiety about future attacks. In prior terror research, the conceptualization and measurement of coping behaviors were constrained by the use of existing coping scales that index reactions to daily hassles and demands. The authors created and validated the Coping with Terror Scale to fill the measurement gap. The authors emphasized content validity, leveraging the knowledge of terror experts and groups of Israelis. A multistep approach involved construct definition and item generation, trimming and refining the measure, exploring the factor structure underlying item responses, and garnering evidence for reliability and validity. The final scale comprised six factors that were generally consistent with the authors' original construct specifications. Scores on items linked to these factors demonstrate good reliability and validity. Future studies using the Coping with Terror Scale with other populations facing terrorist threats are needed to test its ability to predict resilience, functional impairment, and psychological distress.

L1 track triggers for ATLAS in the HL-LHC

DOE PAGES

Lipeles, E.

2012-01-01

The HL-LHC, the planned high luminosity upgrade for the LHC, will increase the collision rate in the ATLAS detector approximately a factor of 5 beyond the luminosity for which the detectors were designed, while also increasing the number of pile-up collisions in each event by a similar factor. This means that the level-1 trigger must achieve a higher rejection factor in a more difficult environment. This presentation discusses the challenges that arise in this environment and strategies being considered by ATLAS to include information from the tracking systems in the level-1 decision. The main challenges involve reducing the data volumemore » exported from the tracking system for which two options are under consideration: a region of interest based system and an intelligent sensor method which filters on hits likely to come from higher transverse momentum tracks.« less

The effects of environmental and socioeconomic factors on land-use changes: a study of Alberta, Canada.

PubMed

Ruan, Xiaofeng; Qiu, Feng; Dyck, Miles

2016-08-01

Various environmental and socioeconomic issues have been attributed to land-use changes, and therefore, the underlying mechanisms merit investigation and quantification. This study assesses a comprehensive series of land-use conversions that were implemented over a recent 12-year period in the province of Alberta, Canada, where rapid economic and population growth has occurred. Spatial autocorrelation models are applied to identify the comprehensive effects of environmental and socioeconomic factors in each conversion case. The empirical results show that the impacts of key environmental and socioeconomic factors varied in intensity depending on the type of land-use conversion involved. Overall, land suitability for agricultural uses, road density, elevation, and population growth were found to be significant predictors of land-use changes. High land suitability, low elevation, and moderate road density were associated with land conversion for agricultural purposes.

Community acquired pneumonia: genetic variants influencing systemic inflammation.

PubMed

Ferrer Agüero, J M; Millán, S; Rodríguez de Castro, F; Martín-Loeches, I; Solé Violán, J

2014-01-01

The inflammatory response depends on several factors, including pathogenicity and duration of the stimulus, and also on the balance between inflammatory and antiinflammatory response. Several studies have presented evidence of the importance of genetic factors in severe infections. The innate immune response prevents the invasion and spread of pathogens during the first hours after infection. Each of the different processes involved in innate immunity may be affected by genetic polymorphisms, which can result in susceptibility or resistance to infection. The results obtained in the different studies do not irrefutably prove the role or function of a gene in the pathogenesis of respiratory infections. However, they can generate new hypotheses, suggest new candidate genes based on their role in the inflammatory response, and constitute a first step in understanding the underlying genetic factors. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Motivations for sexual risk behavior across commercial and casual partners among male urban drug users: contextual features and clinical correlates.

PubMed

Bornovalova, Marina A; Daughters, Stacey B; Lejuez, Carl W

2010-05-01

The current study aimed to develop a measure for assessing the various motivations for sexual risk behavior (SRB) across commercial (involving the exchange of sex for money or drugs) and casual (nonregular) partners in a sample of inner-city, primarily African American drug users, and to examine the relationship of these motivations with a history of childhood trauma, as well as current symptoms of depression, posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). Exploratory factor analysis indicated a 5-factor solution for commercial partner type, and a 4-factor solution for casual partner type, including the motivations of sexual sensation-seeking, intimacy seeking, reassurance-seeking, emotional avoidance, and emotional expressivity. Emotional avoidance and emotional expressivity were strongly related to childhood trauma and PTSD and BPD symptoms. These results provide initial results for mechanisms underlying the relationship between SRB and a history of trauma and psychopathology.

Murder-suicide: a review of the recent literature.

PubMed

Eliason, Scott

2009-01-01

There has been recent widespread media coverage of events that involve murder-suicide. In this paper, the author does an extensive literature review of studies about murder-suicide. The purpose is to determine whether the incidence of murder-suicide is increasing and what its risk factors are. The results of this review show that the incidence of murder-suicide remains at under 0.001%. Risk factors for murder-suicide are based on relationship between perpetrator and victims, history of domestic violence, sex or perpetrator and victim, age of perpetrator, presence of divorce/separation, use of weapon, and history of mental illness. This paper shows that the incidence of murder-suicide is low, stable, and similar to what has been reported in the past. There are, however, some distinct risk factors for murder-suicide including: substance abuse (not as common), mostly male perpetrators, depression (more common), and older male caregivers are at risk.

[In utero thrombosis of neonates: inherited thrombophilia?].

PubMed

Nagy, Andrea; Mogyorósy, Gábor; Kiss, Csongor; Pataki, István; Amir Houshang, Shemirani; Oláh, Eva

2009-04-19

Thromboembolic events are relatively uncommon in childhood. It involves mainly children under one year of age and adolescents, with an incidence is 5.1/10000 live births. Authors present a course of disease of seven cases with neonatal thromboembolic events (2.5/admissions), diagnosed and treated at the Neonatal Division of Department of Pediatrics. In three of seven cases thrombosis proved to be of intrauterine origin. In each of the latter cases, inherited thrombophilia of the mothers was detected. Additional risk factors including infection could be revealed only in one case. Using in vivo and post mortem DNA analysis, mother-like-thrombophilia could not be confirmed in any of the newborns. Based on their experiences, authors suppose that undetected predisposing factors added to maternal thrombophilia can be considered as etiological factor. Authors suggest the intensive follow-up of pregnant women with thrombophilia and also their fetuses.

Nrf2: bane or blessing in cancer?

PubMed

Xiang, MingJun; Namani, Akhileshwar; Wu, ShiJun; Wang, XiaoLi

2014-08-01

The Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element pathway serves a major function in endogenous cytoprotection in normal cells. Nrf2 is a transcription factor that mainly regulates the expression of a wide array of genes that produce the antioxidants and other proteins responsible for the detoxification of xenobiotics and reactive oxygen species. Nrf2 mediates the chemoprevention of cancer in normal cells. Growing body of evidence suggests that Nrf2 is not only involved in the chemoprevention of normal cells but also promotes the growth of cancer cells. However, the mechanism underlying the function of Nrf2 in oncogenesis and tumor protection in cancer cells remains unclear and thus requires further study. This review aims to rationalize the existing functions of Nrf2 in chemoprevention and tumorigenesis, as well as the somatic mutations of Nrf2 and Keap1 in cancer and Nrf2 cross talk with miRNAs. This review also discusses the future challenges in Nrf2 research.

Role of the plasma membrane H+-ATPase in the regulation of organic acid exudation under aluminum toxicity and phosphorus deficiency

PubMed Central

Yu, Wenqian; Kan, Qi; Zhang, Jiarong; Zeng, Bingjie; Chen, Qi

2016-01-01

Aluminum (Al) toxicity and phosphorus (P) deficiency are 2 major limiting factors for plant growth and crop production in acidic soils. Organic acids exuded from roots have been generally regarded as a major resistance mechanism to Al toxicity and P deficiency. The exudation of organic acids is mediated by membrane-localized OA transporters, such as ALMT (Al-activated malate transporter) and MATE (multidrug and toxic compound extrusion). Beside on up-regulation expression of organic acids transporter gene, transcriptional, translational and post-translational regulation of the plasma membrane H+-ATPase are also involved in organic acid release process under Al toxicity and P deficiency. This mini-review summarizes the current knowledge about this field of study on the role of the plasma membrane H+-ATPase in organic acid exudation under Al toxicity and P deficiency conditions. PMID:26713714

Role of the plasma membrane H(+)-ATPase in the regulation of organic acid exudation under aluminum toxicity and phosphorus deficiency.

PubMed

Yu, Wenqian; Kan, Qi; Zhang, Jiarong; Zeng, Bingjie; Chen, Qi

2016-01-01

Aluminum (Al) toxicity and phosphorus (P) deficiency are 2 major limiting factors for plant growth and crop production in acidic soils. Organic acids exuded from roots have been generally regarded as a major resistance mechanism to Al toxicity and P deficiency. The exudation of organic acids is mediated by membrane-localized OA transporters, such as ALMT (Al-activated malate transporter) and MATE (multidrug and toxic compound extrusion). Beside on up-regulation expression of organic acids transporter gene, transcriptional, translational and post-translational regulation of the plasma membrane H(+)-ATPase are also involved in organic acid release process under Al toxicity and P deficiency. This mini-review summarizes the current knowledge about this field of study on the role of the plasma membrane H(+)-ATPase in organic acid exudation under Al toxicity and P deficiency conditions.

The influence of attention toward facial expressions on size perception.

PubMed

Choi, Jeong-Won; Kim, Kiho; Lee, Jang-Han

2016-01-01

According to the New Look theory, size perception is affected by emotional factors. Although previous studies have attempted to explain the effects of both emotion and motivation on size perception, they have failed to identify the underlying mechanisms. This study aimed to investigate the underlying mechanisms of size perception by applying attention toward facial expressions using the Ebbinghaus illusion as a measurement tool. The participants, female university students, were asked to judge the size of a target stimulus relative to the size of facial expressions (i.e., happy, angry, and neutral) surrounding the target. The results revealed that the participants perceived angry and neutral faces to be larger than happy faces. This finding indicates that individuals pay closer attention to neutral and angry faces than happy ones. These results suggest that the mechanisms underlying size perception involve cognitive processes that focus attention toward relevant stimuli and block out irrelevant stimuli.

Trends and ethnic disparities in oral and oro-pharyngeal cancers in South Africa, 1992-2001.

PubMed

Ayo-Yusuf, O A; Lalloo, R; Johnson, N W

2013-05-01

To describe trends in the epidemiology of oral and of oro-pharyngeal (OAP) cancers in South Africa for the atest period available. Data were obtained from the South African pathology-based National Cancer Registry. All new cases of OAP cancers diagnosed and confirmed histologically from 1992 to 2001 are included for the ICD-10 sites C00 to C14, excluding those involving the major salivary glands (C07-C08) and the nasopharynx (C11). OAP cancer incidence is reported by demographics (gender, age, race/ethnicity) and the anatomical sites involved. The analysis on anatomical sites was restricted to squamous cell carcinomas. Overall, males had a much higher OAP cancer incidence rate (world age-Standardised incidence rate [ASIR] = 7.01/100 000 per year) than females (ASIR = 1.99). However, among Asian/Indian South Africans, OAP cancer incidence was higher among females (ASIR = 4.60) than among males (ASIR = 3.80). OAP cancer, excluding those involving the lip, was highest among Coloureds (ASIR = 5.72) and lowest among Blacks (ASIR = 3.16). OAP cancer incidence was stable overall, but incidence rates increased significantly among Coloured South Africans over the period under review (p < 0.05). Cancer specifically involving the oro-pharyngeal was most common among Coloureds and showed an increasing trend during the period under review. Variations in the incidence of OAP cancers by gender, race/ethnicity and anatomic site indicate a need for culturally-targeted reductions in major risk factors, including promoting tobacco cessation and prevention of risky alcohol use. The implications of the role of the human papillomavirus (HPV) in the prevention of squamous cell carcinomas involving the oro-pharyngeal in South Africa require further investigation.

Feeding Problems and Their Underlying Mechanisms in the Esophageal Atresia–Tracheoesophageal Fistula Patient

PubMed Central

Mahoney, Lisa; Rosen, Rachel

2017-01-01

Feeding difficulties such as dysphagia, coughing, choking, or vomiting during meals, slow eating, oral aversion, food refusal, and stressful mealtimes are common in children with repaired esophageal atresia (EA) and the reasons for this are often multifactorial. The aim of this review is to describe the possible underlying mechanisms contributing to feeding difficulties in patients with EA and approaches to management. Underlying mechanisms for these feeding difficulties include esophageal dysphagia, oropharyngeal dysphagia and aspiration, and aversions related to prolonged gastrostomy tube feeding. The initial diagnostic evaluation for feeding difficulties in a patient with EA may involve an esophagram, videofluoroscopic imaging or fiberoptic endoscopic evaluation during swallowing, upper endoscopy with biopsies, pH-impedance testing, and/or esophageal motility studies. The main goal of management is to reduce the factors contributing to feeding difficulties and may include reducing esophageal stasis, maximizing reflux therapies, treating underlying lung disease, dilating strictures, and altering feeding methods, routes, or schedules. PMID:28620597

Predicting Alcohol-Impaired Driving among Spanish Youth with the Theory of Reasoned Action.

PubMed

Espada, José P; Griffin, Kenneth W; Gonzálvez, María T; Orgilés, Mireia

2015-06-19

Alcohol consumption is a risk factor for motor vehicle accidents in young drivers. Crashes associated with alcohol consumption typically have greater severity. This study examines the prevalence of driving under the influence among Spanish youth and tests the theory of reasoned action as a model for predicting driving under the influence. Participants included 478 Spanish university students aged 17-26 years. Findings indicated that alcohol was the substance most associated with impaired driving, and was involved in more traffic crashes. Men engage in higher levels of alcohol and other drug use, and perceived less risk in drunk driving (p < .01). The study confirms that alcohol use and driving under the influence of alcohol are highly prevalent in Spanish young people, and some gender differences exist in these behaviors (p < .01). Furthermore, the study confirms the validity of theory of reasoned action as a predictive model of driving under the influence of alcohol among youth in Spain (p < .001) and can help in the design of prevention programs.

Epigenetic Mechanisms in Bone Biology and Osteoporosis: Can They Drive Therapeutic Choices?

PubMed Central

Marini, Francesca; Cianferotti, Luisella; Brandi, Maria Luisa

2016-01-01

Osteoporosis is a complex multifactorial disorder of the skeleton. Genetic factors are important in determining peak bone mass and structure, as well as the predisposition to bone deterioration and fragility fractures. Nonetheless, genetic factors alone are not sufficient to explain osteoporosis development and fragility fracture occurrence. Indeed, epigenetic factors, representing a link between individual genetic aspects and environmental influences, are also strongly suspected to be involved in bone biology and osteoporosis. Recently, alterations in epigenetic mechanisms and their activity have been associated with aging. Also, bone metabolism has been demonstrated to be under the control of epigenetic mechanisms. Runt-related transcription factor 2 (RUNX2), the master transcription factor of osteoblast differentiation, has been shown to be regulated by histone deacetylases and microRNAs (miRNAs). Some miRNAs were also proven to have key roles in the regulation of Wnt signalling in osteoblastogenesis, and to be important for the positive or negative regulation of both osteoblast and osteoclast differentiation. Exogenous and environmental stimuli, influencing the functionality of epigenetic mechanisms involved in the regulation of bone metabolism, may contribute to the development of osteoporosis and other bone disorders, in synergy with genetic determinants. The progressive understanding of roles of epigenetic mechanisms in normal bone metabolism and in multifactorial bone disorders will be very helpful for a better comprehension of disease pathogenesis and translation of this information into clinical practice. A deep understanding of these mechanisms could help in the future tailoring of proper individual treatments, according to precision medicine’s principles. PMID:27529237

Determinants of sickness absence duration after an occupational back injury in the Belgian population.

PubMed

Mazina, D; Donneau, A-F; Mairiaux, Ph

2012-03-01

This study aimed at assessing factors associated to the duration of sickness absence after a back injury in the Belgian working population, with a special emphasis on cultural factors. The data were retrieved from the Belgian Fund for Work Accidents database over a 3-year period (2001-2003). The population source involved all Belgian workers under a job contract in the private sector registered as compensated cases for an accident that occurred at the workplace (n = 558,276). From that database, all back injury cases involving a complete data set and registered during the first 6 months of each year (n = 11,262) were selected and eight factors (gender, age, seniority in the current job, job category, accident regional location, enterprise size, sector of activity, and accident circumstances) were analyzed in relation to the outcome variable, sick leave duration recorded as ordered time intervals between 0 and 183-366 days. Sick leave duration was strongly associated in a multivariate model to age (≥40 years: OR = 2.18), blue-collar job (1.55), work in building industry (1.32), and enterprise size (>100: 0.85), and to a less extent to seniority (>10y: 0.88), and circumstance of accident (falls: 1.26). Injuries occurring in the French-speaking part of the country were associated to a longer sick leave (1.07; P = 0.034). This study shows that besides well-known risk factors, subtle cultural language-linked factors and/or regional differences in economic climate may significantly influence the length of disability period after a back injury. Copyright © 2012 Wiley Periodicals, Inc.

A wheat WRKY transcription factor TaWRKY10 confers tolerance to multiple abiotic stresses in transgenic tobacco.

PubMed

Wang, Chen; Deng, Pengyi; Chen, Liulin; Wang, Xiatian; Ma, Hui; Hu, Wei; Yao, Ningcong; Feng, Ying; Chai, Ruihong; Yang, Guangxiao; He, Guangyuan

2013-01-01

WRKY transcription factors are reported to be involved in defense regulation, stress response and plant growth and development. However, the precise role of WRKY transcription factors in abiotic stress tolerance is not completely understood, especially in crops. In this study, we identified and cloned 10 WRKY genes from genome of wheat (Triticum aestivum L.). TaWRKY10, a gene induced by multiple stresses, was selected for further investigation. TaWRKY10 was upregulated by treatment with polyethylene glycol, NaCl, cold and H2O2. Result of Southern blot indicates that the wheat genome contains three copies of TaWRKY10. The TaWRKY10 protein is localized in the nucleus and functions as a transcriptional activator. Overexpression of TaWRKY10 in tobacco (Nicotiana tabacum L.) resulted in enhanced drought and salt stress tolerance, mainly demonstrated by the transgenic plants exhibiting of increased germination rate, root length, survival rate, and relative water content under these stress conditions. Further investigation showed that transgenic plants also retained higher proline and soluble sugar contents, and lower reactive oxygen species and malonaldehyde contents. Moreover, overexpression of the TaWRKY10 regulated the expression of a series of stress related genes. Taken together, our results indicate that TaWRKY10 functions as a positive factor under drought and salt stresses by regulating the osmotic balance, ROS scavenging and transcription of stress related genes.

Critical management practices influencing on-site waste minimization in construction projects.

PubMed

Ajayi, Saheed O; Oyedele, Lukumon O; Bilal, Muhammad; Akinade, Olugbenga O; Alaka, Hafiz A; Owolabi, Hakeem A

2017-01-01

As a result of increasing recognition of effective site management as the strategic approach for achieving the required performance in construction projects, this study seeks to identify the key site management practices that are requisite for construction waste minimization. A mixed methods approach, involving field study and survey research were used as means of data collection. After confirmation of construct validity and reliability of scale, data analysis was carried out through a combination of Kruskal-Wallis test, descriptive statistics and exploratory factor analysis. The study suggests that site management functions could significantly reduce waste generation through strict adherence to project drawings, and by ensuring fewer or no design changes during construction process. Provision of waste skips for specific materials and maximisation of on-site reuse of materials are also found to be among the key factors for engendering waste minimization. The result of factor analysis suggests four factors underlying on-site waste management practices with 96.093% of total variance. These measures include contractual provisions for waste minimization, waste segregation, maximisation of materials reuse and effective logistic management. Strategies through which each of the underlying measures could be achieved are further discussed in the paper. Findings of this study would assist construction site managers and other site operatives in reducing waste generated by construction activities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Integration of light and circadian signals that regulate chloroplast transcription by a nuclear-encoded sigma factor.

PubMed

Belbin, Fiona E; Noordally, Zeenat B; Wetherill, Sarah J; Atkins, Kelly A; Franklin, Keara A; Dodd, Antony N

2017-01-01

We investigated the signalling pathways that regulate chloroplast transcription in response to environmental signals. One mechanism controlling plastid transcription involves nuclear-encoded sigma subunits of plastid-encoded plastid RNA polymerase. Transcripts encoding the sigma factor SIG5 are regulated by light and the circadian clock. However, the extent to which a chloroplast target of SIG5 is regulated by light-induced changes in SIG5 expression is unknown. Moreover, the photoreceptor signalling pathways underlying the circadian regulation of chloroplast transcription by SIG5 are unidentified. We monitored the regulation of chloroplast transcription in photoreceptor and sigma factor mutants under controlled light regimes in Arabidopsis thaliana. We established that a chloroplast transcriptional response to light intensity was mediated by SIG5; a chloroplast transcriptional response to the relative proportions of red and far red light was regulated by SIG5 through phytochrome and photosynthetic signals; and the circadian regulation of chloroplast transcription by SIG5 was predominantly dependent on blue light and cryptochrome. Our experiments reveal the extensive integration of signals concerning the light environment by a single sigma factor to regulate chloroplast transcription. This may originate from an evolutionarily ancient mechanism that protects photosynthetic bacteria from high light stress, which subsequently became integrated with higher plant phototransduction networks. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

In silico evolution of the Drosophila gap gene regulatory sequence under elevated mutational pressure.

PubMed

Chertkova, Aleksandra A; Schiffman, Joshua S; Nuzhdin, Sergey V; Kozlov, Konstantin N; Samsonova, Maria G; Gursky, Vitaly V

2017-02-07

Cis-regulatory sequences are often composed of many low-affinity transcription factor binding sites (TFBSs). Determining the evolutionary and functional importance of regulatory sequence composition is impeded without a detailed knowledge of the genotype-phenotype map. We simulate the evolution of regulatory sequences involved in Drosophila melanogaster embryo segmentation during early development. Natural selection evaluates gene expression dynamics produced by a computational model of the developmental network. We observe a dramatic decrease in the total number of transcription factor binding sites through the course of evolution. Despite a decrease in average sequence binding energies through time, the regulatory sequences tend towards organisations containing increased high affinity transcription factor binding sites. Additionally, the binding energies of separate sequence segments demonstrate ubiquitous mutual correlations through time. Fewer than 10% of initial TFBSs are maintained throughout the entire simulation, deemed 'core' sites. These sites have increased functional importance as assessed under wild-type conditions and their binding energy distributions are highly conserved. Furthermore, TFBSs within close proximity of core sites exhibit increased longevity, reflecting functional regulatory interactions with core sites. In response to elevated mutational pressure, evolution tends to sample regulatory sequence organisations with fewer, albeit on average, stronger functional transcription factor binding sites. These organisations are also shaped by the regulatory interactions among core binding sites with sites in their local vicinity.

The bHLH transcription factor GmPIB1 facilitates resistance to Phytophthora sojae in Glycine max

PubMed Central

Cheng, Qun; Dong, Lidong; Gao, Tianjiao; Liu, Tengfei; Li, Ninghui; Wang, Le; Chang, Xin; Wu, Junjiang; Xu, Pengfei

2018-01-01

Abstract Phytophthora sojae Kaufmann and Gerdemann causes Phytophthora root rot, a destructive soybean disease worldwide. A basic helix–loop–helix (bHLH) transcription factor is thought to be involved in the response to P. sojae infection in soybean, as revealed by RNA sequencing (RNA-seq). However, the molecular mechanism underlying this response is currently unclear. Here, we explored the function and underlying mechanisms of a bHLH transcription factor in soybean, designated GmPIB1 (P. sojae-inducible bHLH transcription factor), during host responses to P. sojae. GmPIB1 was significantly induced by P. sojae in the resistant soybean cultivar ‘L77-1863’. Analysis of transgenic soybean hairy roots with elevated or reduced expression of GmPIB1 demonstrated that GmPIB1 enhances resistance to P. sojae and reduces reactive oxygen species (ROS) accumulation. Quantitative reverse transcription PCR and chromatin immunoprecipitation–quantitative PCR assays revealed that GmPIB1 binds directly to the promoter of GmSPOD1 and represses its expression; this gene encodes a key enzyme in ROS production. Moreover, transgenic soybean hairy roots with GmSPOD1 silencing through RNA interference exhibited improved resistance to P. sojae and reduced ROS generation. These findings suggest that GmPIB1 enhances resistance to P. sojae by repressing the expression of GmSPOD1. PMID:29579245

Reactive Oxygen Species/Hypoxia-Inducible Factor-1α/Platelet-Derived Growth Factor-BB Autocrine Loop Contributes to Cocaine-Mediated Alveolar Epithelial Barrier Damage

PubMed Central

Yang, Lu; Chen, Xufeng; Simet, Samantha M.; Hu, Guoku; Cai, Yu; Niu, Fang; Kook, Yeonhee

2016-01-01

Abuse of psychostimulants, such as cocaine, has been shown to be closely associated with complications of the lung, such as pulmonary hypertension, edema, increased inflammation, and infection. However, the mechanism by which cocaine mediates impairment of alveolar epithelial barrier integrity that underlies various pulmonary complications has not been well determined. Herein, we investigate the role of cocaine in disrupting the alveolar epithelial barrier function and the associated signaling cascade. Using the combinatorial electric cell–substrate impedance sensing and FITC-dextran permeability assays, we demonstrated cocaine-mediated disruption of the alveolar epithelial barrier, as evidenced by increased epithelial monolayer permeability with a concomitant loss of the tight junction protein zonula occludens-1 (Zo-1) in both mouse primary alveolar epithelial cells and the alveolar epithelial cell line, L2 cells. To dissect the signaling pathways involved in this process, we demonstrated that cocaine-mediated induction of permeability factors, platelet-derived growth factor (PDGF-BB) and vascular endothelial growth factor, involved reactive oxygen species (ROS)-dependent induction of hypoxia-inducible factor (HIF)-1α. Interestingly, we demonstrated that ROS-dependent induction of another transcription factor, nuclear factor erythroid-2–related factor-2, that did not play a role in cocaine-mediated barrier dysfunction. Importantly, this study identifies, for the first time, that ROS/HIF-1α/PDGF-BB autocrine loop contributes to cocaine-mediated barrier disruption via amplification of oxidative stress and downstream signaling. Corroboration of these cell culture findings in vivo demonstrated increased permeability of the alveolar epithelial barrier, loss of expression of Zo-1, and a concomitantly increased expression of both HIF-1α and PDGF-BB. Pharmacological blocking of HIF-1α significantly abrogated cocaine-mediated loss of Zo-1. Understanding the mechanism(s) by which cocaine mediates barrier dysfunction could provide insights into the development of potential therapeutic targets for cocaine-mediated pulmonary hypertension. PMID:27391108

Allocation trade-off under climate warming in experimental amphibian populations

PubMed Central

Gao, Xu; Jin, Changnan; Camargo, Arley

2015-01-01

Climate change could either directly or indirectly cause population declines via altered temperature, rainfall regimes, food availability or phenological responses. However few studies have focused on allocation trade-offs between growth and reproduction under marginal resources, such as food scarce that may be caused by climate warming. Such critical changes may have an unpredicted impact on amphibian life-history parameters and even population dynamics. Here, we report an allocation strategy of adult anuran individuals involving a reproductive stage under experimental warming. Using outdoor mesocosm experiments we simulated a warming scenario likely to occur at the end of this century. We examined the effects of temperature (ambient vs. pre-/post-hibernation warming) and food availability (normal vs. low) on reproduction and growth parameters of pond frogs (Pelophylax nigromaculatus). We found that temperature was the major factor influencing reproductive time of female pond frogs, which showed a significant advancing under post-hibernation warming treatment. While feeding rate was the major factor influencing reproductive status of females, clutch size, and variation of body size for females, showed significant positive correlations between feeding rate and reproductive status, clutch size, or variation of body size. Our results suggested that reproduction and body size of amphibians might be modulated by climate warming or food availability variation. We believe this study provides some new evidence on allocation strategies suggesting that amphibians could adjust their reproductive output to cope with climate warming. PMID:26500832

A fuzzy-theory-based method for studying the effect of information transmission on nonlinear crowd dispersion dynamics

NASA Astrophysics Data System (ADS)

Fu, Libi; Song, Weiguo; Lo, Siuming

2017-01-01

Emergencies involved in mass events are related to a variety of factors and processes. An important factor is the transmission of information on danger that has an influence on nonlinear crowd dynamics during the process of crowd dispersion. Due to much uncertainty in this process, there is an urgent need to propose a method to investigate the influence. In this paper, a novel fuzzy-theory-based method is presented to study crowd dynamics under the influence of information transmission. Fuzzy functions and rules are designed for the ambiguous description of human states. Reasonable inference is employed to decide the output values of decision making such as pedestrian movement speed and directions. Through simulation under four-way pedestrian situations, good crowd dispersion phenomena are achieved. Simulation results under different conditions demonstrate that information transmission cannot always induce successful crowd dispersion in all situations. This depends on whether decision strategies in response to information on danger are unified and effective, especially in dense crowds. Results also suggest that an increase in drift strength at low density and the percentage of pedestrians, who choose one of the furthest unoccupied Von Neumann neighbors from the dangerous source as the drift direction at high density, is helpful in crowd dispersion. Compared with previous work, our comprehensive study improves an in-depth understanding of nonlinear crowd dynamics under the effect of information on danger.

Salicylic acid and nitric oxide alleviate high temperature induced oxidative damage in Lablab purpureus L plants by regulating bio-physical processes and DNA methylation.

PubMed

Rai, Krishna Kumar; Rai, Nagendra; Rai, Shashi Pandey

2018-07-01

Salicylic acid (SA) and sodium nitroprusside (SNP, NO donor) modulates plant growth and development processes and recent findings have also revealed their involvement in the regulation of epigenetic factors under stress condition. In the present study, some of these factors were comparatively studied in hyacinth bean plants subjected to high temperature (HT) environment (40-42 °C) with and without exogenous application of SA and SNP under field condition. Exogenous application of SA and SNP substantially modulated the growth and biophysical process of hyacinth bean plants under HT environment. Exogenous application of SA and SNP also remarkably regulated the activities of antioxidant enzymes, modulated mRNA level of certain enzymes, improves plant water relation, enhance photosynthesis and thereby increasing plant defence under HT. Coupled restriction enzyme digestion-random amplification (CRED-RA) technique revealed that many methylation changes were "dose dependent" and HT significantly increased DNA damages as evidenced by both increase and decrease in bands profiles, methylation and de-methylation pattern. Thus, the result of the present study clearly shows that exogenous SA and SNP regulates DNA methylation pattern, modulates stress-responsive genes and can impart transient HT tolerance by synchronizing growth and physiological acclimatization of plants, thus narrowing the gaps between physio-biochemical and molecular events in addressing HT tolerance. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A moso bamboo WRKY gene PeWRKY83 confers salinity tolerance in transgenic Arabidopsis plants.

PubMed

Wu, Min; Liu, Huanlong; Han, Guomin; Cai, Ronghao; Pan, Feng; Xiang, Yan

2017-09-15

The WRKY family are transcription factors, involved in plant development, and response to biotic and abiotic stresses. Moso bamboo is an important bamboo that has high ecological, economic and cultural value and is widely distributed in the south of China. In this study, we performed a genome-wide identification of WRKY members in moso bamboo and identified 89 members. By comparative analysis in six grass genomes, we found the WRKY gene family may have experienced or be experiencing purifying selection. Based on relative expression levels among WRKY IIc members under three abiotic stresses, PeWRKY83 functioned as a transcription factor and was selected for detailed analysis. The transgenic Arabidopsis of PeWRKY83 showed superior physiological properties compared with the WT under salt stress. Overexpression plants were less sensitive to ABA at both germination and postgermination stages and accumulated more endogenous ABA under salt stress conditions. Further studies demonstrated that overexpression of PeWRKY83 could regulate the expression of some ABA biosynthesis genes (AtAAO3, AtNCED2, AtNCED3), signaling genes (AtABI1, AtPP2CA) and responsive genes (AtRD29A, AtRD29B, AtABF1) under salt stress. Together, these results suggested that PeWRKY83 functions as a novel WRKY-related TF which plays a positive role in salt tolerance by regulating stress-induced ABA synthesis.

Gender inequality and bio-social factors in nutritional status among under five children attending anganwadis in an urban slum of a town in Western Maharashtra, India.

PubMed

Patel, Kriti A; Langare, Sanjivani D; Naik, J D; Rajderkar, S S

2013-04-01

Nutrition for under-5 children is of great importance as the foundation for life-time health, strength, and intellectual vitality is laid during this period. Globally, more than one-third of the child deaths are attributable to under-nutrition. The discriminatory attitudes against female children vary from being implicit to those that are quite explicit. So, the present cross-sectional study aims to assess the nutritional status (gender differences) of 146 under-5 children attending Anganwadis and also to study the bio-socio-demographic factors associated with malnutrition attending three Anganwadis of Adopted Urban slum area, involving anthropometric examination using standardized techniques and interview using predesigned semi-structured questionnaire for the mothers in September-October 2011. Nutritional status grading was done based on weight for age as per Indian Academy of Pediatrics (IAP) Classification and using height for age as per Vishveshwara Rao's Classification. 51.4% were males, majority in age group of 2-3 years. 63% children were malnourished, majority in Grade I malnutrition. Out of the total females, 72% were stunted and 43% were severely malnourished having mid arm circumference <12.5 cm. Birth order (P < 0.05), education status of the mother (P < 0.001), socio-economic status (P < 0.05) and type of family (P < 0.05) were found to be significantly associated with malnutrition.

The Public Health Service guidelines. Governing research involving human subjects: An analysis of the policy-making process

NASA Technical Reports Server (NTRS)

Frankel, M. S.

1972-01-01

The policy making process which led to development of the Public Health Service Guidelines governing research involving human subjects is outlined. Part 1 examines the evolution of PHS Guidelines, tracing (1) evolution of thought and legal interpretation regarding research using human subjects; (2) initial involvement of the Federal government; (3) development of the government's research program; (4) the social-political environment in which formal government policy was developed; and (5) various policy statements issued by the government. Part 2 analyzes the process by which PHS Guidelines were developed and examines the values and other underlying factors which contributed to their development. It was concluded that the evolution of the Guidelines is best understood within the context of a mixed-scanning strategy. In such a strategy, policy makers make fundamental decisions regarding the basic direction of policy and subsequent decisions are made incrementally and within the contexts set by the original fundamental decisions.

Magnetic Field Generation Processes Involving Gravity and Differential Rotation. Solitary Plasma Rings Formation around Black Holes

NASA Astrophysics Data System (ADS)

Coppi, Bruno

2012-10-01

A clear theoretical framework to describe how magnetic fields are generated and amplified is provided by the magneto-gravitational modes that involve both differential rotation and gravity and for which other factors such as temperature gradients can contribute to their excitation. These modes are shown to be important for the evolution of plasma disks surrounding black holes.footnotetextB. Coppi, Phys. Plasmas 18, 032901 (2011) Non-linear and axi-symmetric plasmas and associated field configurations are found under stationary conditions that do not involve the presence of a pre-existing ``seed'' magnetic field unlike other configurations found previously.footnotetextIbid. The relevant magnetic energy density is of the order of the gravitationally confined plasma pressure. The solitary plasma rings that characterize these configurations are localized radially over regions with vanishing differential rotation and can be envisioned as the saturated state of magneto-gravitational modes. The ``source'' of these configurations is the combination of the gravitational force and of the plasma density gradient orthogonal to it.

Involvement of pterygoid venous plexus in patulous eustachian tube symptoms.

PubMed

Oshima, Takeshi; Ogura, Masaki; Kikuchi, Toshiaki; Hori, Yoko; Mugikura, Shunji; Higano, Shuichi; Takahashi, Shoki; Kawase, Tetsuaki; Kobayashi, Toshimitsu

2007-07-01

The pterygoid venous plexus (PVP) is an important factor in the mechanism of eustachian tube (ET) closure under conditions that can cause increased venous pressure in the head, such as during neck compression and postural change from the sitting/standing to the recumbent position. The symptoms of patulous ET are usually improved by neck compression or postural change (from sitting/standing to recumbent position). Venous congestion around the ET and/or gravitational change may be involved in the changing degree of symptoms, but its mechanism is not understood. This study investigated whether the PVP is involved. The dimensions of soft tissues surrounding ET were measured on magnetic resonance images before and after neck compression. The lateral pterygoid muscle became enlarged after neck compression. Simultaneously, the volume of venous plexus observed between the medial pterygoid muscle and tensor veli palatini muscle was increased. Such enlargement was probably due to blood pooling in the PVP, resulting in protrusion of the ET anterior wall to the luminal side, and decreased ET patency.

Evaluation of motorcycle safety strategies using the severity of injuries.

PubMed

Jung, Soyoung; Xiao, Qin; Yoon, Yoonjin

2013-10-01

The growth of motorcycle fatalities in California has been especially prominent, specifically with regard to the 24 and under age group and those aged 45-54. This research quantitatively examined factors associated with motorcyclist fatalities and assessed strategies that could improve motorcyclist safety, specifically focusing on the two age groups mentioned above. Severity of injury was estimated separately for both age groups with multinomial logit models and pseudo-elasticity using motorcycle-related collision data that was collected between 2005 and 2009. The results were compared with motorcyclists aged 35-44, a group that shows a consistent trend of fatalities. This research found that lack or improper use of helmets, victim ejection, alcohol/drug effects, collisions (head-on, broadside, hit-object), and truck involvement were more likely to result in fatal injuries regardless of age group. Weekend and non-peak hour activity was found to have a strong effect in both the younger and older age groups. Two factors, movement of running off the road preceding a collision and multi-vehicle involvement, were found to be statistically significant factors in increasing older motorcyclist fatalities. Use of street lights in the dark was found to decrease the probability of severe injury for older motorcyclists. Driver type of victim, at-fault driver, local road, and speed violation were significant factors in increasing the fatalities of younger motorcyclists. Road conditions and collision location factors were not found to be statistically significant to motorcyclist fatalities. Based on the statistically significant factors identified in this research, the following safety strategies appear to be effective methods of reducing motorcyclist fatalities: public education of alcohol use, promoting helmet use, enforcing heavy vehicle and speed violations, improving roadway facilities, clearer roadway guidance and street lighting systems, and motorcyclist training. Copyright © 2013 Elsevier Ltd. All rights reserved.

Modeling pedestrian violation behavior at signalized crosswalks in China: a hazards-based duration approach.

PubMed

Guo, Hongwei; Gao, Ziyou; Yang, Xiaobao; Jiang, Xiaobei

2011-02-01

Pedestrian violation is a major cause of traffic accidents involving pedestrians. The research objectives were to investigate the relationship between waiting duration and pedestrian violation and to provide a qualitative and quantitative analysis of the effects of human factors and external environmental factors on street-crossing behavior. Pedestrians' street-crossing behavior was examined by modeling the waiting duration at signalized crosswalk. Pedestrian waiting duration was collected by video cameras and it was assigned as censored and uncensored data to distinguish between normal crossing and violating crossing. A nonparametric baseline duration model was introduced, and variables revealing personal characteristics, traffic conditions, and trip features were defined as covariates to describe the effects of internal and external factors. Pedestrians' crossing behaviors represented positive duration dependence that the longer the waiting time elapsed the more likely pedestrians would end the wait soon. The violation inclination of most pedestrians increased with the increasing waiting duration, but about 10 percent of pedestrians were at high risk of violation to cross the street. About half of pedestrians would still obey the traffic rules even after waiting for 50 s by the street. Human factors and the external environment played an important role in street-crossing behavior, especially for factors that involved pedestrians' subjective willingness. The street-crossing behavior of pedestrians was time dependent. Pedestrians behave differently under the effects of various factors. Pedestrian safety interventions that aim at reducing pedestrian injuries may need to consider these effects. The pedestrians' behavioral modifications, such as enhancing the safety awareness, might be the most efficient means to reducing the likelihood of pedestrian violation, though environmental modifications also worked well in improving pedestrian safety.

Geo-spatial and log-linear analysis of pedestrian and bicyclist crashes involving school-aged children.

PubMed

Abdel-Aty, Mohamed; Chundi, Sai Srinivas; Lee, Chris

2007-01-01

There is a growing concern with the safety of school-aged children. This study identifies the locations of pedestrian/bicyclist crashes involving school-aged children and examines the conditions when these crashes are more likely to occur. The 5-year records of crashes in Orange County, Florida where school-aged children were involved were used. The spatial distribution of these crashes was investigated using the Geographic Information Systems (GIS) and the likelihoods of crash occurrence under different conditions were estimated using log-linear models. A majority of school-aged children crashes occurred in the areas near schools. Although elementary school children were generally very involved, middle and high school children were more involved in crashes, particularly on high-speed multi-lane roadways. Driver's age, gender, and alcohol use, pedestrian's/bicyclist's age, number of lanes, median type, speed limits, and speed ratio were also found to be correlated with the frequency of crashes. The result confirms that school-aged children are exposed to high crash risk near schools. High crash involvement of middle and high school children reflects that middle and high schools tend to be located near multi-lane high-speed roads. The pedestrian's/bicyclist's demographic factors and geometric characteristics of the roads adjacent to schools associated with school children's crash involvement are of interest to school districts.

The tomato mutant ars1 (altered response to salt stress 1) identifies an R1-type MYB transcription factor involved in stomatal closure under salt acclimation.

PubMed

Campos, Juan F; Cara, Beatriz; Pérez-Martín, Fernando; Pineda, Benito; Egea, Isabel; Flores, Francisco B; Fernandez-Garcia, Nieves; Capel, Juan; Moreno, Vicente; Angosto, Trinidad; Lozano, Rafael; Bolarin, Maria C

2016-06-01

A screening under salt stress conditions of a T-DNA mutant collection of tomato (Solanum lycopersicum L.) led to the identification of the altered response to salt stress 1 (ars1) mutant, which showed a salt-sensitive phenotype. Genetic analysis of the ars1 mutation revealed that a single T-DNA insertion in the ARS1 gene was responsible of the mutant phenotype. ARS1 coded for an R1-MYB type transcription factor and its expression was induced by salinity in leaves. The mutant reduced fruit yield under salt acclimation while in the absence of stress the disruption of ARS1 did not affect this agronomic trait. The stomatal behaviour of ars1 mutant leaves induced higher Na(+) accumulation via the transpiration stream, as the decreases of stomatal conductance and transpiration rate induced by salt stress were markedly lower in the mutant plants. Moreover, the mutation affected stomatal closure in a response mediated by abscisic acid (ABA). The characterization of tomato transgenic lines silencing and overexpressing ARS1 corroborates the role of the gene in regulating the water loss via transpiration under salinity. Together, our results show that ARS1 tomato gene contributes to reduce transpirational water loss under salt stress. Finally, this gene could be interesting for tomato molecular breeding, because its manipulation could lead to improved stress tolerance without yield penalty under optimal culture conditions. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Strategic and non-strategic problem gamblers differ on decision-making under risk and ambiguity.

PubMed

Lorains, Felicity K; Dowling, Nicki A; Enticott, Peter G; Bradshaw, John L; Trueblood, Jennifer S; Stout, Julie C

2014-07-01

To analyse problem gamblers' decision-making under conditions of risk and ambiguity, investigate underlying psychological factors associated with their choice behaviour and examine whether decision-making differed in strategic (e.g., sports betting) and non-strategic (e.g., electronic gaming machine) problem gamblers. Cross-sectional study. Out-patient treatment centres and university testing facilities in Victoria, Australia. Thirty-nine problem gamblers and 41 age, gender and estimated IQ-matched controls. Decision-making tasks included the Iowa Gambling Task (IGT) and a loss aversion task. The Prospect Valence Learning (PVL) model was used to provide an explanation of cognitive, motivational and response style factors involved in IGT performance. Overall, problem gamblers performed more poorly than controls on both the IGT (P = 0.04) and the loss aversion task (P = 0.01), and their IGT decisions were associated with heightened attention to gains (P = 0.003) and less consistency (P = 0.002). Strategic problem gamblers did not differ from matched controls on either decision-making task, but non-strategic problem gamblers performed worse on both the IGT (P = 0.006) and the loss aversion task (P = 0.02). Furthermore, we found differences in the PVL model parameters underlying strategic and non-strategic problem gamblers' choices on the IGT. Problem gamblers demonstrated poor decision-making under conditions of risk and ambiguity. Strategic (e.g. sports betting, poker) and non-strategic (e.g. electronic gaming machines) problem gamblers differed in decision-making and the underlying psychological processes associated with their decisions. © 2014 Society for the Study of Addiction.

Facilitation influences patterns of perennial species abundance and richness in a subtropical dune system

PubMed Central

Dalotto, Cecilia E S; Sühs, Rafael B; Dechoum, Michele S; Pugnaire, Francisco I; Peroni, Nivaldo; Castellani, Tânia T

2018-01-01

Abstract Positive interactions in plant communities are under-reported in subtropical systems most likely because they are not identified as stressful environments. However, environmental factors or disturbance can limit plant growth in any system and lead to stressful conditions. For instance, salinity and low nutrient and water availability generate a gradient of stressful conditions in coastal systems depending on distance to shore. In a tropical coastal system in SE Brazil, we aimed to assess whether Guapira opposita, a shrub common in restinga environments, acted as nurse involved in ecological succession and which factors influenced its facilitation process. We sampled perennial species above 10 cm in height under the canopy of 35 G. opposita individuals and in neighbouring open areas. Shrub height, canopy area and distance to freshwater bodies were measured in the field, and distance to the ocean was obtained from aerial images. In addition, we measured the distance to the closest forest patch as a potential source of seeds. Plant abundance and species richness were higher under the canopy of G. opposita than in open areas. Facilitation by G. opposita was mainly determined by shrub height, which had a positive relationship with woody and bromeliads abundance and species richness while there was no relationship with the other factors. Overall, our data evidence that tropical environments may be highly stressful for plants and that nurse species play a key role in the regeneration of restinga environments, where their presence is critical to maintain ecosystem diversity and function. PMID:29644027

The Yeast Forkhead Transcription Factors Fkh1 and Fkh2 Regulate Lifespan and Stress Response Together with the Anaphase-Promoting Complex

PubMed Central

Postnikoff, Spike D. L.; Malo, Mackenzie E.; Wong, Berchman; Harkness, Troy A. A.

2012-01-01

Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan. A key function in this process involves the regulation of the cell cycle and stress responses including free radical scavenging. We employed yeast chronological and replicative lifespan assays, as well as oxidative stress assays, to explore the potential evolutionary conservation of function between the FOXOs and the yeast forkhead box transcription factors FKH1 and FKH2. We report that the deletion of both FKH genes impedes normal lifespan and stress resistance, particularly in stationary phase cells, which are non-responsive to caloric restriction. Conversely, increased expression of the FKHs leads to extended lifespan and improved stress response. Here we show the Anaphase-Promoting Complex (APC) genetically interacts with the Fkh pathway, likely working in a linear pathway under normal conditions, as fkh1Δ fkh2Δ post-mitotic survival is epistatic to that observed in apc5CA mutants. However, under stress conditions, post-mitotic survival is dramatically impaired in apc5CA fkh1Δ fkh2Δ, while increased expression of either FKH rescues APC mutant growth defects. This study establishes the FKHs role as evolutionarily conserved regulators of lifespan in yeast and identifies the APC as a novel component of this mechanism under certain conditions, likely through combined regulation of stress response, genomic stability, and cell cycle regulation. PMID:22438832

Energy Modeling of IoT Mobile Terminals on WiFi Environmental Impacts †.

PubMed

Sun, Yuxia; Chen, Junxian; Tang, Yong; Chen, Yanjia

2018-05-28

With the popularity of various IoT mobile terminals such as mobile phones and sensors, the energy problems of IoT mobile terminals have attracted increasingly more attention. In this paper, we explore the impacts of some important factors of WiFi environments on the energy consumption of mobile phones, which are typical IoT end devices. The factors involve the WiFi signal strength under good signal conditions, the type and the amount of protocol packets that are initiated by WiFi APs (Access Points) to maintain basic network communication with the phones. Controlled experiments are conducted to quantitatively study the phone energy impacts by the above WiFi environmental factors. To describe such impacts, we construct a time-based signal strength-aware energy model and packet type/amount-aware energy models. The models constructed in the paper corroborate the following user experience on phone energy consumption: (1) a phone's energy is drawn faster under higher WiFi signal strengths than under lower ones even in normal signal conditions; (2) phones consume energy faster in a public WiFi network than in a private one even in the basic phone state. The energy modeling methods proposed in the paper enable ordinary developers to analyze phone energy draw conveniently by utilizing inexpensive power meters as measurement tools. The modeling methods are general and are able to be used for phones of any type and any platform.

Interacting TCP and NLP transcription factors control plant responses to nitrate availability.

PubMed

Guan, Peizhu; Ripoll, Juan-José; Wang, Renhou; Vuong, Lam; Bailey-Steinitz, Lindsay J; Ye, Dening; Crawford, Nigel M

2017-02-28

Plants have evolved adaptive strategies that involve transcriptional networks to cope with and survive environmental challenges. Key transcriptional regulators that mediate responses to environmental fluctuations in nitrate have been identified; however, little is known about how these regulators interact to orchestrate nitrogen (N) responses and cell-cycle regulation. Here we report that teosinte branched1/cycloidea/proliferating cell factor1-20 (TCP20) and NIN-like protein (NLP) transcription factors NLP6 and NLP7, which act as activators of nitrate assimilatory genes, bind to adjacent sites in the upstream promoter region of the nitrate reductase gene, NIA1 , and physically interact under continuous nitrate and N-starvation conditions. Regions of these proteins necessary for these interactions were found to include the type I/II Phox and Bem1p (PB1) domains of NLP6&7, a protein-interaction module conserved in animals for nutrient signaling, and the histidine- and glutamine-rich domain of TCP20, which is conserved across plant species. Under N starvation, TCP20-NLP6&7 heterodimers accumulate in the nucleus, and this coincides with TCP20 and NLP6&7-dependent up-regulation of nitrate assimilation and signaling genes and down-regulation of the G 2 /M cell-cycle marker gene, CYCB1;1 TCP20 and NLP6&7 also support root meristem growth under N starvation. These findings provide insights into how plants coordinate responses to nitrate availability, linking nitrate assimilation and signaling with cell-cycle progression.