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Sample records for early developmental cardiomyocytes

  1. Atrial natriuretic peptide regulates Ca channel in early developmental cardiomyocytes.

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    Lin Miao

    Full Text Available BACKGROUND: Cardiomyocytes derived from murine embryonic stem (ES cells possess various membrane currents and signaling cascades link to that of embryonic hearts. The role of atrial natriuretic peptide (ANP in regulation of membrane potentials and Ca(2+ currents has not been investigated in developmental cardiomyocytes. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the role of ANP in regulating L-type Ca(2+ channel current (I(CaL in different developmental stages of cardiomyocytes derived from ES cells. ANP decreased the frequency of action potentials (APs in early developmental stage (EDS cardiomyocytes, embryonic bodies (EB as well as whole embryo hearts. ANP exerted an inhibitory effect on basal I(CaL in about 70% EDS cardiomyocytes tested but only in about 30% late developmental stage (LDS cells. However, after stimulation of I(CaL by isoproterenol (ISO in LDS cells, ANP inhibited the response in about 70% cells. The depression of I(CaL induced by ANP was not affected by either Nomega, Nitro-L-Arginine methyl ester (L-NAME, a nitric oxide synthetase (NOS inhibitor, or KT5823, a cGMP-dependent protein kinase (PKG selective inhibitor, in either EDS and LDS cells; whereas depression of I(CaL by ANP was entirely abolished by erythro-9-(2-Hydroxy-3-nonyl adenine (EHNA, a selective inhibitor of type 2 phosphodiesterase(PDE2 in most cells tested. CONCLUSION/SIGNIFICANCES: Taken together, these results indicate that ANP induced depression of action potentials and I(CaL is due to activation of particulate guanylyl cyclase (GC, cGMP production and cGMP-activation of PDE2 mediated depression of adenosine 3', 5'-cyclic monophophate (cAMP-cAMP-dependent protein kinase (PKA in early cardiomyogenesis.

  2. The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation

    DEFF Research Database (Denmark)

    Clement, Christian A; Kristensen, Stine G; Møllgård, Kjeld

    2009-01-01

    Defects in the assembly or function of primary cilia, which are sensory organelles, are tightly coupled to developmental defects and diseases in mammals. Here, we investigated the function of the primary cilium in regulating hedgehog signaling and early cardiogenesis. We report that the pluripotent...... P19.CL6 mouse stem cell line, which can differentiate into beating cardiomyocytes, forms primary cilia that contain essential components of the hedgehog pathway, including Smoothened, Patched-1 and Gli2. Knockdown of the primary cilium by Ift88 and Ift20 siRNA or treatment with cyclopamine......, an inhibitor of Smoothened, blocks hedgehog signaling in P19.CL6 cells, as well as differentiation of the cells into beating cardiomyocytes. E11.5 embryos of the Ift88(tm1Rpw) (Ift88-null) mice, which form no cilia, have ventricular dilation, decreased myocardial trabeculation and abnormal outflow tract...

  3. Developmental regulation of intracellular calcium transients during cardiomyocyte differentiation of mouse embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    Ji-dong FU; Hui-mei YU; Rong WANG; Ji LIANG; Huang-tian YANG

    2006-01-01

    Aim: To investigate the developmental regulation of intracellular Ca2+ transients, an essential event in excitation-contraction coupling, during cardiomyocyte differentiation. Methods: Using the embryonic stem (ES) cell in vitro differentiation system and pharmacological intervention, we investigated the molecular and functional regulation of Ca2+ handling proteins on the Ca2+ transients at early, intermediate and later differentiation stages of ES cell-derived cardiomyocytes (ESCM). Results: Nifedipine, a selective antagonist of L-type Ca2+ channels, totally blocked Ca2+ transients even in the condition of field-electric stimulation in ESCM at three differentiation stages. The Ca2+ transients of ESCM were also inhibited by both ryanodine [an inhibitor of ryanodine receptors (RyRs)] and 2-aminoethoxydipheylborate [2-APB, an inhibitor of inositol-1,4,5-trisphosphate receptors (IP3Rs)]. The inhibitory effect of ryanodine increased with the time of differentiation, while the effect of 2-APB decreased with the differentiation. Thapsigargin, an inhibitor of SR Ca2+-pump ATPase, inhibited Ca2+ transients equally at three differentiation stages that matched the expression profile. Na+ free solution, which inhibits Na+-Ca2+ exchanger (NCX) to extrude Ca2+ from cytosol, did not affect the amplitude of Ca2+ transients of ESCM until the latter differentiation stage, but it significantly enhanced the basal Ca2+concentration. Conclusion: The Ca2+ transients in ESCM depend on both the sarcolemmal Ca2+ entry via L-type Ca2+ channels and the SR Ca2+ release from RyRs and IP3Rs even at the early differentiation stage; but NCX seems not to regulate the peak of Ca2+ transients until the latter differentiation stage.

  4. Early Writing: A Developmental Approach.

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    Goetz, Elizabeth; And Others

    This document consists of four papers on the acquisition of writing skills by young children. The first paper provides a historical and developmental perspective on early writing. Children's development of manual dexterity is briefly overviewed and aspects of the educational approaches of Pestalozzi, Montessori, Chomsky, Rogers and Ashton-Warner…

  5. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis.

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    Lin, Yan-Ren; Li, Chao-Jui; Syu, Shih-Han; Wen, Cheng-Hao; Buddhakosai, Waradee; Wu, Han-Ping; Hsu Chen, Cheng; Lu, Huai-En; Chen, Wen-Liang

    2016-01-01

    Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2) were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n = 20) and control (normal saline, n = 20) groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5) or to culture medium (control). Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p < 0.05). In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53) and apoptosis (caspase-3, Bcl-xL) markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR). L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5). More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells' beating function at a low pH level.

  6. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis

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    Yan-Ren Lin

    2016-01-01

    Full Text Available Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2 were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n=20 and control (normal saline, n=20 groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5 or to culture medium (control. Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p<0.05. In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53 and apoptosis (caspase-3, Bcl-xL markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR. L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5. More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells’ beating function at a low pH level.

  7. Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis.

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    Parra, Valentina; Eisner, Veronica; Chiong, Mario; Criollo, Alfredo; Moraga, Francisco; Garcia, Alejandra; Härtel, Steffen; Jaimovich, Enrique; Zorzano, Antonio; Hidalgo, Cecilia; Lavandero, Sergio

    2008-01-15

    In cells, mitochondria are organized as a network of interconnected organelles that fluctuate between fission and fusion events (mitochondrial dynamics). This process is associated with cell death. We investigated whether activation of apoptosis with ceramides affects mitochondrial dynamics and promotes mitochondrial fission in cardiomyocytes. Neonatal rat cardiomyocytes were incubated with C(2)-ceramide or the inactive analog dihydro-C(2)-ceramide for up to 6 h. Three-dimensional images of cells loaded with mitotracker green were obtained by confocal microscopy. Dynamin-related protein-1 (Drp-1) and mitochondrial fission protein 1 (Fis1) distribution and levels were studied by immunofluorescence and western blot. Mitochondrial membrane potential (DeltaPsi(m)) and cytochrome c (cyt c) distribution were used as indexes of early activation of apoptosis. Cell viability and DNA fragmentation were determined by propidium iodide staining/flow cytometry, whereas cytotoxicity was evaluated by lactic dehydrogenase activity. To decrease the levels of the mitochondrial fusion protein mitofusin 2, we used an antisense adenovirus (AsMfn2). C(2)-ceramide, but not dihydro-C(2)-ceramide, promoted rapid fragmentation of the mitochondrial network in a concentration- and time-dependent manner. C(2)-ceramide also increased mitochondrial Drp-1 and Fis1 content, Drp-1 colocalization with Fis1, and caused early activation of apoptosis. AsMfn2 accentuated the decrease in DeltaPsi(m) and cyt c redistribution induced by C(2)-ceramide. Doxorubicin, which induces cardiomyopathy and apoptosis through ceramide generation, also stimulated mitochondrial fragmentation. Ceramides stimulate mitochondrial fission and this event is associated with early activation of cardiomyocyte apoptosis.

  8. Segregation of Central Ventricular Conduction System Lineages in Early SMA+ Cardiomyocytes Occurs Prior to Heart Tube Formation

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    Caroline Choquet

    2016-01-01

    Full Text Available The cardiac conduction system (CCS transmits electrical activity from the atria to the ventricles to coordinate heartbeats. Atrioventricular conduction diseases are often associated with defects in the central ventricular conduction system comprising the atrioventricular bundle (AVB and right and left branches (BBs. Conducting and contractile working myocytes share common cardiomyogenic progenitors, however the time at which the CCS lineage becomes specified is unclear. In order to study the fate and the contribution to the CCS of cardiomyocytes during early heart tube formation, we performed a genetic lineage analysis using a Sma-CreERT2 mouse line. Lineage tracing experiments reveal a sequential contribution of early Sma expressing cardiomyocytes to different cardiac compartments, labeling at embryonic day (E 7.5 giving rise to the interventricular septum and apical left ventricular myocardium. Early Sma expressing cardiomyocytes contribute to the AVB, BBs and left ventricular Purkinje fibers. Clonal analysis using the R26-confetti reporter mouse crossed with Sma-CreERT2 demonstrates that early Sma expressing cardiomyocytes include cells exclusively fated to give rise to the AVB. In contrast, lineage segregation is still ongoing for the BBs at E7.5. Overall this study highlights the early segregation of the central ventricular conduction system lineage within cardiomyocytes at the onset of heart tube formation.

  9. Early Intervention in Children with Developmental Disabilities

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    Beena Johnson

    2016-01-01

    Full Text Available Developmental disabilities consist of conditions that delay or impair the physical, cognitive, and/or psychological development of children. If not intervened at the earliest, these disabilities will cause significant negative impact on multiple domains of functioning such as learning, language, self-care and capacity for independent living. Common developmental disabilities include autism spectrum disorders, intellectual disabilities, developmental delay and cerebral palsy. About one fourth of young children in developing countries are at risk for or have developmental delay or disabilities. Inadequate stimulation has significant negative impact on physical, socioemotional and cognitive development of children. Hence early scientific intervention programs are necessary in the management of children at risk for developmental delay.

  10. Practitioner Review: Early Adversity and Developmental Disorders

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    Taylor, Eric; Rogers, Jody Warner

    2005-01-01

    Background: Knowledge of genetic influences, on developmental disorders such as autism spectrum, attention deficit/hyperactivity disorder and learning disabilities, has increased the opportunities for understanding the influences of the early environment. Methods: This paper provides a selective, narrative review for clinicians of the effects of…

  11. Chromosomal Aneuploidies and Early Embryonic Developmental Arrest

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    Maria Maurer

    2015-07-01

    Full Text Available Background: Selecting the best embryo for transfer, with the highest chance of achieving a vital pregnancy, is a major goal in current in vitro fertilization (IVF technology. The high rate of embryonic developmental arrest during IVF treatment is one of the limitations in achieving this goal. Chromosomal abnormalities are possibly linked with chromosomal arrest and selection against abnormal fertilization products. The objective of this study was to evaluate the frequency and type of chromosomal abnormalities in preimplantation embryos with developmental arrest. Materials and Methods: This cohort study included blastomeres of embryos with early developmental arrest that were biopsied and analyzed by fluorescence in-situ hybridization (FISH with probes for chromosomes 13, 16, 18, 21 and 22. Forty-five couples undergoing IVF treatment were included, and 119 arrested embryos were biopsied. All probes were obtained from the Kinderwunsch Zentrum, Linz, Austria, between August 2009 and August 2011. Results: Of these embryos, 31.6% were normal for all chromosomes tested, and 68.4% were abnormal. Eleven embryos were uniformly aneuploid, 20 were polyploid, 3 were haploid, 11 displayed mosaicism and 22 embryos exhibited chaotic chromosomal complement. Conclusion: Nearly 70% of arrested embryos exhibit chromosomal errors, making chromosomal abnormalities a major cause of embryonic arrest and may be a further explanation for the high developmental failure rates during culture of the embryos in the IVF setting.

  12. EARLY DIAGNOSIS OF PERVASIVE DEVELOPMENTAL DISORDERS

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    Jelica ERCEG-DJURACIC

    1997-09-01

    Full Text Available Pervasive developmental disorders represent obviously a heterogeneous group of disorders, whose clinical expressions, courses and prospects differ significantly. Common to all these disorders, expect essential diagnostic characteristics, is the fact that they are life-long problems, thus, these are disorders without possibility of complete relief. Although measures of secondary prevention in these disorders do exert a limited effect, it is possible to achieve indubitable improvements in three fields:· well-timed application of adequate treatment may influence the essential characteristics of a disorder in the direction of adaptation to requirements of social environment, improvement of communication and enrichment of poor activity repertoire;· slowing down and delaying of unfavorable disorder evolution and· helping in understanding, accepting and adapting of child’s family to a pervasive developmental disorder.Value of early established diagnosis is not reflected only in foundation of organized adequate treatment. Early established diagnosis enables a well-timed giving of genetic advice to the family which is, as a rule, young, and without genetic load. On the other hand, well-timed diagnosis enables planning of life-long complete care for the patient with the disorder.

  13. Disruption of planar cell polarity signaling results in congenital heart defects and cardiomyopathy attributable to early cardiomyocyte disorganization.

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    Phillips, Helen M; Rhee, Hong Jun; Murdoch, Jennifer N; Hildreth, Victoria; Peat, Jonathan D; Anderson, Robert H; Copp, Andrew J; Chaudhry, Bill; Henderson, Deborah J

    2007-07-20

    The Drosophila scribble gene regulates apical-basal polarity and is implicated in control of cellular architecture and cell growth control. Mutations in mammalian Scrib (circletail; Crc mutant) also result in abnormalities suggestive of roles in planar cell polarity regulation. We show that Crc mutants develop heart malformations and cardiomyopathy attributable to abnormalities in cardiomyocyte organization within the early heart tube. N-Cadherin is lost from the cardiomyocyte cell membrane and cell-cell adhesion is disrupted. This results in abnormalities in heart looping and formation of both the trabeculae and compact myocardium, which ultimately results in cardiac misalignment defects and ventricular noncompaction. Thus, these late abnormalities arise from defects occurring at the earliest stages of heart development. Mislocalization of Vangl2 in Crc/Crc cardiomyocytes suggests Scrib is acting in the planar cell polarity pathway in this tissue. Moreover, double heterozygosity for mutations in both Scrib and Vangl2 can cause cardiac defects similar to those found in homozygous mutants for each gene but without other major defects. We propose that heterozygosity for mutations in different genes in the planar cell polarity pathway may be an important mechanism for congenital heart defects and cardiomyopathy in humans.

  14. Early Intervention in Children with Developmental Disabilities

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    Beena Johnson

    2016-01-01

    Developmental disabilities consist of conditions that delay or impair the physical, cognitive, and/or psychological development of children. If not intervened at the earliest, these disabilities will cause significant negative impact on multiple domains of functioning such as learning, language, self-care and capacity for independent living. Common developmental disabilities include autism spectrum disorders, intellectual disabilities, developmental delay and cerebral palsy. About one fourth...

  15. Relationship between Intrauterine Bacterial Infection and Early Embryonic Developmental Arrest

    Institute of Scientific and Technical Information of China (English)

    Shao-Fei Yan; Xin-Yan Liu; Yun-Fei Cheng; Zhi-Yi Li; Jie Ou; Wei Wang; Feng-Qin Li

    2016-01-01

    Background:Early embryonic developmental arrest is the most commonly understudied adverse outcome of pregnancy.The relevance of intrauterine infection to spontaneous embryonic death is rarely studied and remains unclear.This study aimed to investigate the relationship between intrauterine bacterial infection and early embryonic developmental arrest.Methods:Embryonic chorion tissue and uterine swabs for bacterial detection were obtained from 33 patients who underwent artificial abortion (control group) and from 45 patients who displayed early embryonic developmental arrest (trial group).Results:Intrauterine bacterial infection was discovered in both groups.The infection rate was 24.44% (11/45) in the early embryonic developmental arrest group and 9.09% (3/33) in the artificial abortion group.Classification analysis revealed that the highest detection rate for Micrococcus luteus in the early embryonic developmental arrest group was 13.33% (6/45),and none was detected in the artificial abortion group.M.luteus infection was significantly different between the groups (P < 0.05 as shown by Fisher's exact test).In addition,no correlation was found between intrauterine bacterial infection and history of early embryonic developmental arrest.Conclusions:M.luteus infection is related to early embryonic developmental arrest and might be one of its causative factors.

  16. Developmental Trajectories of Early Communication Skills

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    Maatta, Sira; Laakso, Marja-Leena; Tolvanen, Asko; Ahonen, Timo; Aro, Tuija

    2012-01-01

    Purpose: This study focused on developmental trajectories of prelinguistic communication skills and their connections to later parent-reported language difficulties. Method: The participants represent a subset of a community-based sample of 508 children. Data include parent reports of prelinguistic communication skills at 12, 15, 18, and 21 months…

  17. Developmental Trajectories of Early Communication Skills

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    Maatta, Sira; Laakso, Marja-Leena; Tolvanen, Asko; Ahonen, Timo; Aro, Tuija

    2012-01-01

    Purpose: This study focused on developmental trajectories of prelinguistic communication skills and their connections to later parent-reported language difficulties. Method: The participants represent a subset of a community-based sample of 508 children. Data include parent reports of prelinguistic communication skills at 12, 15, 18, and 21 months…

  18. Research on Children's Play: Analysis of Developmental and Early Education Journals from 2005 to 2007

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    Cheng, Mei-Fang; Johnson, James E.

    2010-01-01

    Our review examined four early childhood journals ("Early Child Development and Care," "Early Childhood Education Journal," "Journal of Research in Childhood Education," and "Early Childhood Research Quarterly") and four developmental science journals ("Child Development," "Developmental Psychology," "Journal of Applied Developmental…

  19. Research on Children's Play: Analysis of Developmental and Early Education Journals from 2005 to 2007

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    Cheng, Mei-Fang; Johnson, James E.

    2010-01-01

    Our review examined four early childhood journals ("Early Child Development and Care," "Early Childhood Education Journal," "Journal of Research in Childhood Education," and "Early Childhood Research Quarterly") and four developmental science journals ("Child Development," "Developmental Psychology," "Journal of Applied Developmental…

  20. Developmental and behavioral problems in pediatric primary care : Early identification

    NARCIS (Netherlands)

    van den Heuvel, Mathilda

    2016-01-01

    This thesis focuses on the early identification of developmental and behavioral problems in pediatric primary care. The social environment is considered a fundamental determinant of early child development. In our study countries with generous redistributive policies had a better organization of ear

  1. Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages.

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    Miwa, Keiko; Lee, Jong-Kook; Takagishi, Yoshiko; Opthof, Tobias; Fu, Xianming; Kodama, Itsuo

    2010-12-01

    Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal rat hearts and superior cervical ganglia, and were co-cultured, either in a random or localized way. Neurite growth from SNs toward CMs was assessed by immunohistochemistry for neurofilament M and α-actinin in response to neurotrophic factors-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) and a chemical repellent, semaphorin 3A. As a result, GDNF as well as NGF and BDNF stimulated neurite growth. GDNF enhanced neurite outgrowth even under the NGF-depleted culture condition, excluding an indirect effect of GDNF via NGF. Quantification of mRNA and protein by real-time PCR and immunohistochemistry at different developmental stages revealed that GDNF is abundantly expressed in the hearts of embryos and neonates, but not in adult hearts. GDNF plays an important role in inducing cardiac sympathetic innervation at the early developmental stages. A possible role in (re)innervation of injured or transplanted or cultured and transplanted myocardium may deserve investigation.

  2. Practice Guide to the Early Years Developmental Journal

    OpenAIRE

    Mengoni, Silvana; Oates, John

    2013-01-01

    The Early Years Developmental Journal is intended as a useful resource for practitioners when monitoring progress, supporting assessments and providing a basis for communicating with parents and other practitioners. In particular it can support the statutory early years progress assessment and child health monitoring when a child is around 2 years of age. It is closely linked with the Early Years Foundation Stage (EYFS) Development Matters and with the Personal Child Health Record (PCHR or ‘r...

  3. Sleep Problems and Early Developmental Delay: Implications for Early Intervention Programs

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    Bonuck, Karen; Grant, Roy

    2012-01-01

    Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common…

  4. Sleep Problems and Early Developmental Delay: Implications for Early Intervention Programs

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    Bonuck, Karen; Grant, Roy

    2012-01-01

    Sleep disorders negatively impact behavior, cognition, and growth--the same areas targeted by early intervention. Conversely, developmental delays and disabilities may themselves precipitate sleep disorders. Young children with developmental delays experience sleep disorders at a higher rate than do typically developing children; the most common…

  5. Early Risk Factors of Overweight Developmental Trajectories during Middle Childhood

    OpenAIRE

    Pryor, Laura E.; Mara Brendgen; Richard E Tremblay; Jean-Baptiste Pingault; Xuecheng Liu; Lise Dubois; Evelyne Touchette; Bruno Falissard; Michel Boivin; Sylvana M Côté

    2015-01-01

    Background Research is needed to identify early life risk factors associated with different developmental paths leading to overweight by adolescence. Objectives To model heterogeneity in overweight development during middle childhood and identify factors associated with differing overweight trajectories. Methods Data was drawn from the Quebec Longitudinal Study of Child Development (QLSCD; 1998-2010). Trained research assistants measured height and weight according to a standardized protocol ...

  6. Early Risk Factors of Overweight Developmental Trajectories during Middle Childhood.

    Directory of Open Access Journals (Sweden)

    Laura E Pryor

    Full Text Available Research is needed to identify early life risk factors associated with different developmental paths leading to overweight by adolescence.To model heterogeneity in overweight development during middle childhood and identify factors associated with differing overweight trajectories.Data was drawn from the Quebec Longitudinal Study of Child Development (QLSCD; 1998-2010. Trained research assistants measured height and weight according to a standardized protocol and conducted yearly home interviews with the child's caregiver (mother in 98% of cases. Information on several putative early life risk factors for the development of overweight were obtained, including factors related to the child's perinatal, early behavioral family and social environment. Group-based trajectories of the probability of overweight (6-12 years were identified with a semiparametric method (n=1678. Logistic regression analyses were used to identify early risk factors (5 months- 5 years associated with each trajectory.Three trajectories of overweight were identified: "early-onset overweight" (11.0 %, "late-onset overweight" (16.6% and "never overweight" (72.5%. Multinomial analyses indicated that children in the early and late-onset group, compared to the never overweight group, had 3 common types of risk factors: parental overweight, preschool overweight history, and large size for gestational age. Maternal overprotection (OR= 1.12, CI: 1.01-1.25, short nighttime sleep duration (OR=1.66, CI: 1.07-2.57, and immigrant status (OR=2.01, CI: 1.05-3.84 were factors specific to the early-onset group. Finally, family food insufficiency (OR=1.81, CI: 1.00-3.28 was weakly associated with membership in the late-onset trajectory group.The development of overweight in childhood follows two different trajectories, which have common and distinct risk factors that could be the target of early preventive interventions.

  7. [The Battelle developmental inventory screening test for early detection of developmental disorders in cerebral palsy].

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    Moraleda-Barreno, E; Romero-López, M; Cayetano-Menéndez, M J

    2011-12-01

    Cerebral palsy is usually associated with motor, cognitive, and language deficits, and with other disorders that cause disability in daily living skills, personal independence, social interaction and academic activities. Early detection of these deficits in the clinical setting is essential to anticipate and provide the child with the necessary support for adapting to the environment in all possible areas. The main objective of this study is to demonstrate that these deficits can be detected at an early age and comprehensively through the use of a brief development scale. We studied 100 children between 4 and 70 months old, half of them with cerebral palsy and the other half without any disorder. All subjects were evaluated using the Battelle Developmental Inventory screening test. We compared the developmental quotients in both groups and between the subjects with different motor impairments, using a simple prospective ex post facto design. The test detected statistically significant differences between the clinical group and the control group at all age levels. Statistically significant differences were also found between tetraplegia and other motor disorders. There were no differences by gender. The deficit in development associated with cerebral palsy can be quantified at early ages through the use of a brief development scale, thus we propose that the systematic implementation of protocols with this screening tool would be helpful for treatment and early intervention. This would also help in anticipating and establishing the means for the multidisciplinary actions required, and could provide guidance to other health professionals, to provide adequate school, social, and family support,. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  8. A unique chromatin signature uncovers early developmental enhancers in humans.

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    Rada-Iglesias, Alvaro; Bajpai, Ruchi; Swigut, Tomek; Brugmann, Samantha A; Flynn, Ryan A; Wysocka, Joanna

    2011-02-10

    Cell-fate transitions involve the integration of genomic information encoded by regulatory elements, such as enhancers, with the cellular environment. However, identification of genomic sequences that control human embryonic development represents a formidable challenge. Here we show that in human embryonic stem cells (hESCs), unique chromatin signatures identify two distinct classes of genomic elements, both of which are marked by the presence of chromatin regulators p300 and BRG1, monomethylation of histone H3 at lysine 4 (H3K4me1), and low nucleosomal density. In addition, elements of the first class are distinguished by the acetylation of histone H3 at lysine 27 (H3K27ac), overlap with previously characterized hESC enhancers, and are located proximally to genes expressed in hESCs and the epiblast. In contrast, elements of the second class, which we term 'poised enhancers', are distinguished by the absence of H3K27ac, enrichment of histone H3 lysine 27 trimethylation (H3K27me3), and are linked to genes inactive in hESCs and instead are involved in orchestrating early steps in embryogenesis, such as gastrulation, mesoderm formation and neurulation. Consistent with the poised identity, during differentiation of hESCs to neuroepithelium, a neuroectoderm-specific subset of poised enhancers acquires a chromatin signature associated with active enhancers. When assayed in zebrafish embryos, poised enhancers are able to direct cell-type and stage-specific expression characteristic of their proximal developmental gene, even in the absence of sequence conservation in the fish genome. Our data demonstrate that early developmental enhancers are epigenetically pre-marked in hESCs and indicate an unappreciated role of H3K27me3 at distal regulatory elements. Moreover, the wealth of new regulatory sequences identified here provides an invaluable resource for studies and isolation of transient, rare cell populations representing early stages of human embryogenesis.

  9. Precursors of adolescent substance use from early childhood and early adolescence: testing a developmental cascade model.

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    Sitnick, Stephanie L; Shaw, Daniel S; Hyde, Luke W

    2014-02-01

    This study examined developmentally salient risk and protective factors of adolescent substance use assessed during early childhood and early adolescence using a sample of 310 low-income boys. Child problem behavior and proximal family risk and protective factors (i.e., parenting and maternal depression) during early childhood, as well as child and family factors and peer deviant behavior during adolescence, were explored as potential precursors to later substance use during adolescence using structural equation modeling. Results revealed that early childhood risk and protective factors (i.e., child externalizing problems, mothers' depressive symptomatology, and nurturant parenting) were indirectly related to substance use at the age of 17 via risk and protective factors during early and middle adolescence (i.e., parental knowledge and externalizing problems). The implications of these findings for early prevention and intervention are discussed.

  10. Aconitase and Developmental End Points as Early Indicators of

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    Oleksandr Vasyliovuch Lozinsky

    2014-03-01

    Full Text Available Background: In this study, the toxicity of the different xenobiotics was tested on the fruit fly Drosophila melanogaster model system. Methods: Fly larvae were raised on food supplemented with xenobiotics at different concentrations (sodium nitroprusside (0.1-1.5 mM, S-nitrosoglutathione (0.5-4 mM, and potassium ferrocyanide (1 mM. Emergence of flies, food intake by larvae, and pupation height preference as well as aconitase activity (in 2-day old flies were measured. Results: Food supplementation with xenobiotics caused a developmental delay in the flies and decreased pupation height. Biochemical analyses of oxidative stress markers and activities of antioxidants and their associated enzymes were carried out on 2-day-old flies emerged from control larvae and larvae fed on food supplemented with chemicals. Larval exposure to chemicals resulted in lower activities of aconitase in flies of both sexes and perturbation in activities of antioxidant enzymes. Conclusions: The results of this study showed that among a variety of parameters tested, aconitase activity, developmental endpoints, and pupation height may be used as reliable early indicators of toxicity caused by different chemicals.

  11. [Developmental origins of cardiovascular disease and early intervention windows].

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    Mi, Jie

    2016-01-01

    Cardiovascular diseases are the major threat to human health and underlie almost half of all deaths in China. Even more serious, obesity and cardiometabolic risk factors have emerged to be prevalent in children and adolescents of some affluent regions. As scientific knowledge emerges on the role of nutritional factors and exposures to environmental risk factors in the developmental origins of health and disease, evidence suggests that it is imperative to create and implement early effective prevention strategies, including optimisation of nutrition at first 1 000 days in life course and reduction of risk factors of obesity exposures during whole childhood, to suppress the rising trend of cardiovascular disease, otherwise, the future costs of diagnosis and treatment are likely to be unaffordable.

  12. Early motor developmental milestones and level of neuroticism in young adulthood

    DEFF Research Database (Denmark)

    Flensborg-Madsen, T; Sørensen, H J; Revsbech, Rasmus

    2013-01-01

    Studies investigating early developmental factors in relation to psychopathology have mainly focused on schizophrenia. The personality dimension of neuroticism seems to be a general risk factor for psychopathology, but evidence on associations between early developmental precursors and personalit...... analysed by multiple linear regression adjusting for for sex, single-mother status, parity, mother's age, father's age, parental social status and birth weight....... traits is almost non-existent. This study is therefore the first to investigate associations between early motor developmental milestones and neuroticism in adulthood. Method Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first year...

  13. A patient with medulloblastoma in its early developmental stage.

    Science.gov (United States)

    Shinojima, Naoki; Nakamura, Hideo; Tasaki, Masayoshi; Kameno, Kouki; Anai, Shigeo; Iyama, Ken-ichi; Ando, Yukio; Seto, Hiroshi; Kuratsu, Jun-Ichi

    2014-12-01

    Medulloblastoma is the most frequent malignant brain tumor of the posterior fossa in children and is considered an embryonal tumor. It has been suggested that medulloblastomas be categorized into 4 distinct molecular subgroups- WNT (DKK1), SHH (SFRP1), Group 3 (NPR3), or Group 4 (KCNA1)-since each subgroup is distinct and there is no overlap. The authors report on a 13-year-old boy with medulloblastoma. He presented with sudden-onset nausea and vomiting due to intratumoral hemorrhage. The medulloblastoma was thought to be in an early developmental stage because the tumor volume was extremely small. Immunohistochemical analysis showed that the tumor was mainly composed of DKK1- and NPR3-positive areas. The individual areas of the tumor stained only for DKK1 or NPR3, with no overlap-that is, DKK1 and NPR3 expression were mutually exclusive. Samples obtained by laser microdissection of individual areas and subjected to mass spectrometry confirmed that the expression patterns of proteins were different. Fluorescence in situ hybridization for chromosome 6 showed there were 2 distinct types of cells that exhibited monosomy or disomy of chromosome 6. These results demonstrated that distinct subtypes of medulloblastoma may be present within a single tumor, an observation that has not been previously reported. Our findings in this case indicate that early-stage medulloblastoma may include more than 1 distinct subtype and hint at factors involved in the origin and development of medulloblastomas.

  14. Punishment Insensitivity in Early Childhood: A Developmental, Dimensional Approach.

    Science.gov (United States)

    Nichols, Sara R; Briggs-Gowan, Margaret J; Estabrook, Ryne; Burns, James L; Kestler, Jacqueline; Berman, Grace; Henry, David B; Wakschlag, Lauren S

    2015-08-01

    Impairment in learning from punishment ("punishment insensitivity") is an established feature of severe antisocial behavior in adults and youth but it has not been well studied as a developmental phenomenon. In early childhood, differentiating a normal: abnormal spectrum of punishment insensitivity is key for distinguishing normative misbehavior from atypical manifestations. This study employed a novel measure, the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB), to examine the distribution, dimensionality, and external validity of punishment insensitivity in a large, demographically diverse community sample of preschoolers (3-5 years) recruited from pediatric clinics (N = 1,855). Caregivers completed surveys from which a seven-item Punishment Insensitivity scale was derived. Findings indicated that Punishment Insensitivity behaviors are relatively common in young children, with at least 50 % of preschoolers exhibiting them sometimes. Item response theory analyses revealed a Punishment Insensitivity spectrum. Items varied along a severity continuum: most items needed to occur "Often" in order to be severe and behaviors that were qualitatively atypical or intense were more severe. Although there were item-level differences across sociodemographic groups, these were small. Construct, convergent, and divergent validity were demonstrated via association to low concern for others and noncompliance, motivational regulation, and a disruptive family context. Incremental clinical utility was demonstrated in relation to impairment. Early childhood punishment insensitivity varies along a severity continuum and is atypical when it predominates. Implications for understanding the phenomenology of emergent disruptive behavior are discussed.

  15. Children’s Early Helping in Action: Piagetian Developmental Theory and Early Prosocial Behavior

    OpenAIRE

    Stuart Ian Hammond

    2014-01-01

    After a brief overview of recent research on early helping, outlining some central problems, and issues, this paper examines children’s early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget’s “Moral Judgment of the Child” (Piaget, 1932/1997), “Play, Dreams, and Imitation in Childhood” (Piaget, 1945/1951), and the “Grasp of Consciousness” (Piaget, 1976). Piaget refers to a level of moral development in action that precedes heteronomous and autonomous mor...

  16. Developmentally Appropriate Practice in Early Elementary Grade Schools in Bangkok, Thailand

    Science.gov (United States)

    Saifah, Yotsawee

    2012-01-01

    The purposes of this study were (a) to examine early elementary grade teachers' developmentally appropriate beliefs and their teaching practices in public schools in Bangkok, (b) to explore the functioning of developmentally appropriate practice in the two chosen early elementary schools, and (c) to determine the factors that influence the…

  17. Olaparib protects cardiomyocytes against oxidative stress and improves graft contractility during the early phase after heart transplantation in rats.

    Science.gov (United States)

    Korkmaz-Icöz, Sevil; Szczesny, Bartosz; Marcatti, Michela; Li, Shiliang; Ruppert, Mihály; Lasitschka, Felix; Loganathan, Sivakkanan; Szabó, Csaba; Szabó, Gábor

    2017-08-14

    Olaparib, rucaparib and niraparib, potent inhibitors of poly(ADP-ribose) polymerase (PARP) are approved as anti-cancer drugs in humans. Considering the previously demonstrated role of PARP in various forms of acute and chronic myocardial injury, we tested the effects of olaparib in in-vitro models of oxidative stress in cardiomyocytes, and in an in vivo model of cardiac transplantation. H9c2-embryonic rat heart-derived myoblasts pretreated with vehicle or olaparib (10μM) were challenged with either hydrogen peroxide (H2 O2 ) or with glucose oxidase (GOx, which generates H2 O2 in the tissue culture medium). Cell viability assays (MTT, lactate dehydrogenase) and Western blotting for PARP and its product, PAR was performed. Heterotopic heart transplantation was performed in Lewis rats; recipients were treated either with vehicle or olaparib (10 mg kg(-1) ). Left ventricular function of transplanted hearts was monitored via a Millar catheter. Multiple gene expression in the graft was measured by qPCR. Olaparib blocked autoPARylation of PARP1 and attenuated the rapid onset of death in H9c2 cells, induced by H2 O2 , but did not affect cell death following chronic, prolonged oxidative stress induced by GOx. In rats, after transplantation, left ventricular systolic and diastolic function were improved by olaparib. In the transplanted hearts, olaparib also reduced gene expression for c-jun, caspase-12, catalase, and NADPH oxidase-2. Olaparib protected cardiomyocytes against oxidative stress and improved graft contractility in a rat model of heart transplantation. These findings raise the possibility of repurposing this clinically approved oncology drug, to be used in heart transplantation. © 2017 The British Pharmacological Society.

  18. Aetiological investigations in early developmental impairment: are they worth it?

    Science.gov (United States)

    Hart, Anthony Richard; Sharma, Ruchi; Atherton, Mark; Alabed, Samer; Simpson, Sally; Barfield, Stuart; Cohen, Judith; McGlashan, Nicholas; Ravi, Asha; Parker, Michael James; Connolly, Daniel Ja

    2017-07-22

    To study the frequency a diagnosis is made in children with early developmental impairment (EDI), and the contribution made to diagnosis by specific investigations. Retrospective case note review. Community, neurodisability and neurology department at a UK tertiary centre. Children referred to determine the aetiology of EDI where a cause was not evident on history and examination. Participants were divided into two groups: EDI and no additional features (EDI-) and EDI with additional features (EDI+). The frequency a cause was found for the child's EDI and which tests contributed to a diagnosis. 699 participants, 68.8% boys, median age at investigation 2 years 8 months (range 3 months to 11 years 5 months). 61 (8.7%) of participants had no investigations, and children with EDIâˆ' were less likely to be investigated (χ(2)=12.5, pdata. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Children's early helping in action: Piagetian developmental theory and early prosocial behavior.

    Science.gov (United States)

    Hammond, Stuart I

    2014-01-01

    After a brief overview of recent research on early helping, outlining some central problems, and issues, this paper examines children's early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget's "Moral Judgment of the Child" (Piaget, 1932/1997), "Play, Dreams, and Imitation in Childhood" (Piaget, 1945/1951), and the "Grasp of Consciousness" (Piaget, 1976). Piaget refers to a level of moral development in action that precedes heteronomous and autonomous moral reasoning. This action level allows children to begin to interact with people and objects. In his later work, Piaget explores the gradual construction of understanding from this activity level. Taken together, these elements of Piagetian theory provide a promising conceptual framework for understanding the development of early helping.

  20. Children’s Early Helping in Action: Piagetian Developmental Theory and Early Prosocial Behavior

    Directory of Open Access Journals (Sweden)

    Stuart Ian Hammond

    2014-07-01

    Full Text Available After a brief overview of recent research on early helping, outlining some central problems and issues, this paper examines children’s early helping through the lens of Piagetian moral and developmental theory, drawing on Piaget’s ‘Moral Judgment of the Child’ (1932/1997, ‘Play, Dreams, and Imitation in Childhood’ (1945/1951, and the ‘Grasp of Consciousness’ (1974. Piaget refers to a level of moral development in action that precedes heteronomous and autonomous moral reasoning. This action level allows children to begin to interact with people and objects. In his later work, Piaget explores the gradual construction of understanding from this activity level. Taken together, these elements of Piagetian theory provide a promising conceptual framework for understanding the development of early helping.

  1. Early motor developmental milestones and level of neuroticism in young adulthood

    DEFF Research Database (Denmark)

    Flensborg-Madsen, Trine; Sørensen, Holger Jelling; Revsbech, Rasmus

    2012-01-01

    intelligence. CONCLUSIONS: The findings are the first of their kind and suggest that delays in early motor development may not only characterize psychopathological disorders such as schizophrenia, but may also be associated with the personality dimension of neuroticism in adulthood.......BACKGROUND: Studies investigating early developmental factors in relation to psychopathology have mainly focused on schizophrenia. The personality dimension of neuroticism seems to be a general risk factor for psychopathology, but evidence on associations between early developmental precursors...... and personality traits is almost non-existent. This study is therefore the first to investigate associations between early motor developmental milestones and neuroticism in adulthood. Method Mothers of 9125 children of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first...

  2. Analysis of cardiomyocyte movement in the developing murine heart

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Hisayuki [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Tabata, Hidenori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Tohyama, Shugo; Seki, Tomohisa; Egashira, Toru; Hayashiji, Nozomi; Hattori, Fumiyuki; Kusumoto, Dai; Kunitomi, Akira; Takei, Makoto; Kashimura, Shin; Yozu, Gakuto; Shimojima, Masaya; Motoda, Chikaaki; Muraoka, Naoto [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan); Nakajima, Kazunori [Department of Anatomy, Keio University School of Medicine, Tokyo (Japan); Sakaue-Sawano, Asako; Miyawaki, Atsushi [Life Function and Dynamics, ERATO, JST, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198 (Japan); Fukuda, Keiichi [Department of Cardiology, Keio University School of Medicine, Tokyo (Japan)

    2015-09-04

    The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cell cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.

  3. Metabolites of Hypoxic Cardiomyocytes Induce the Migration of Cardiac Fibroblasts.

    Science.gov (United States)

    Shi, Huairui; Zhang, Xuehong; He, Zekun; Wu, Zhiyong; Rao, Liya; Li, Yushu

    2017-01-01

    The migration of cardiac fibroblasts to the infarct region plays a major role in the repair process after myocardial necrosis or damage. However, few studies investigated whether early hypoxia in cardiomyocytes induces the migration of cardiac fibroblasts. The purpose of this study was to assess the role of metabolites of early hypoxic cardiomyocytes in the induction of cardiac fibroblast migration. Neonatal rat heart tissue was digested with a mixture of trypsin and collagenase at an appropriate ratio. Cardiomyocytes and cardiac fibroblasts were cultured via differential adhesion. The cardiomyocyte cultures were subjected to hypoxia for 2, 4, 6, 8, 10, and 12 h. The supernatants of the cardiomyocyte cultures were collected to determine the differences in cardiac fibroblast migration induced by hypoxic cardiomyocyte metabolites at various time points using a Transwell apparatus. Meanwhile, ELISA was performed to measure TNF-α, IL-1β and TGF-β expression levels in the cardiomyocyte metabolites at various time points. The metabolites of hypoxic cardiomyocytes significantly induced the migration of cardiac fibroblasts. The induction of cardiac fibroblast migration was significantly enhanced by cardiomyocyte metabolites in comparison to the control after 2, 4, and 6 h of hypoxia, and the effect was most significant after 2 h. The expression levels of TNF-α, IL-1β, IL-6, and TGF-β were substantially increased in the metabolites of cardiomyocytes, and neutralization with anti-TNF-α and anti-IL-1β antibodies markedly reduced the induction of cardiac fibroblast migration by the metabolites of hypoxic cardiomyocytes. The metabolites of early hypoxic cardiomyocytes can induce the migration of cardiac fibroblasts, and TNF-α and IL-1β may act as the initial chemotactic inducers. © 2017 The Author(s) Published by S. Karger AG, Basel.

  4. Contractile properties of early human embryonic stem cell-derived cardiomyocytes: beta-adrenergic stimulation induces positive chronotropy and lusitropy but not inotropy.

    Science.gov (United States)

    Pillekamp, Frank; Haustein, Moritz; Khalil, Markus; Emmelheinz, Markus; Nazzal, Rewa; Adelmann, Roland; Nguemo, Filomain; Rubenchyk, Olga; Pfannkuche, Kurt; Matzkies, Matthias; Reppel, Michael; Bloch, Wilhelm; Brockmeier, Konrad; Hescheler, Juergen

    2012-08-10

    Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) provide the unique opportunity to study the very early development of the human heart. The aim of this study was to investigate the effect of calcium and beta-adrenergic stimulation on the contractile properties of early hESC-CMs. Beating clusters containing hESC-CMs were co-cultured in vitro with noncontractile slices of neonatal murine ventricles. After 5-7 days, when beating clusters had integrated morphologically into the damaged tissue, isometric force measurements were performed during spontaneous beating as well as during electrical field stimulation. Spontaneous beating stopped when extracellular calcium ([Ca²⁺](ec)) was removed or after administration of the Ca²⁺ channel blocker nifedipine. During field stimulation at a constant rate, the developed force increased with incremental concentrations of [Ca²⁺](ec). During spontaneous beating, rising [Ca²⁺](ec) increased beating rate and developed force up to a [Ca²⁺](ec) of 2.5 mM. When [Ca²⁺](ec) was increased further, spontaneous beating rate decreased, whereas the developed force continued to increase. The beta-adrenergic agonist isoproterenol induced a dose-dependent increase of the frequency of spontaneous beating; however, it did not significantly change the developed force during spontaneous contractions or during electrical stimulation at a constant rate. Force developed by early hESC-CMs depends on [Ca²⁺](ec) and on the L-type Ca²⁺ channel. The lack of an inotropic reaction despite a pronounced chronotropic response after beta-adrenergic stimulation most likely indicates immaturity of the sarcoplasmic reticulum. For cell-replacement strategies, further maturation of cardiac cells has to be achieved either in vitro before or in vivo after transplantation.

  5. Assessment of developmental cardiotoxic effects of some commonly used phytochemicals in mouse embryonic D3 stem cell differentiation and chick embryonic cardiomyocyte micromass culture models.

    Science.gov (United States)

    Mohammed, Omar J; McAlpine, Roseanna; Chiewhatpong, Phasawee; Latif, Muhammad Liaque; Pratten, Margaret K

    2016-09-01

    Pregnant women often use herbal medicines to alleviate symptoms of pregnancy. The active phytochemicals eugenol (from holy basil) and α-bisabolol (from chamomile) are recommended to promote calmness and reduce stress. There is evidence that both eugenol and α-bisabolol possess pro-apoptotic and anti-proliferative effects and induce reactive oxygen species. The potential effect was examined by monitoring cardiomyocyte contractile activity (differentiation), cell activity, protein content and ROS production for mouse D3 embryonic stem cell and ‎chick embryonic micromass culture. The results showed that eugenol (0.01-80μM) demonstrated effects on cell activity (both systems) and ROS production (stem cell system only), as well as decreasing the contractile activity and protein content at high concentrations in both systems. Additionally, α-bisabolol (0.01-80μM) at high concentrations decreased the contractile activity and cell activity and in the stem cell system induced ROS production and decreased protein content. The results suggest only low concentrations should be ingested in pregnancy.‎.

  6. Developmentally Appropriate Practice in Early Childhood Programs Serving Children from Birth through Age 8. Third Edition

    Science.gov (United States)

    Copple, Carol, Ed.; Bredekamp, Sue, Ed.

    2009-01-01

    Since the first edition in 1987, National Association for the Education of Young Children's book "Developmentally Appropriate Practice in Early Childhood Programs" has been an essential resource for the early child care field. Now fully revised and expanded, the 2009 version comes with a supplementary CD containing readings on key topics, plus…

  7. Using Survival Analysis to Describe Developmental Achievements of Early Intervention Recipients at Kindergarten

    Science.gov (United States)

    Scarborough, Anita A.; Hebbeler, Kathleen M.; Spiker, Donna; Simeonsson, Rune J.

    2011-01-01

    Survival analysis was used to document the developmental achievements of 2298 kindergarten children who participated in the National Early Intervention Longitudinal Study, a study that followed children from entry to Part C early intervention (EI) through kindergarten. Survival functions were produced depicting the percentage of children at…

  8. Developmental Dyslexia: Early Precursors, Neurobehavioral Markers, and Biological Substrates

    Science.gov (United States)

    Benasich, April A., Ed.; Fitch, R. Holly, Ed.

    2012-01-01

    Understanding the precursors and early indicators of dyslexia is key to early identification and effective intervention. Now there's a single research volume that brings together the very latest knowledge on the earliest stages of dyslexia and the diverse genetic, neurobiological, and cognitive factors that may contribute to it. Based on findings…

  9. Bringing a developmental perspective to early childhood and family interventionists: where to begin.

    Science.gov (United States)

    Hogan, Anne E; Quay, Herbert C

    2014-01-01

    There is a pressing need to share advances in developmental science with the large, multidisciplinary professional workforce that serves vulnerable infants and toddlers and their families. Foundational knowledge and conceptual frameworks that integrate material regarding the contents and processes of early development and promotion of their use can assist interventionists and the families they serve. This chapter describes an approach that has been developed over the past 10 years and summarizes key contents with sample practical applications. Topic areas include developmental theories, newborn capacities, a model for synthesizing information about early social competence (including self-regulation, early relationships, social skills, and social cognition), and key current topics in developmental psychopathology. Brief considerations of diversity and stigma for work with young children and families are also included.

  10. Traumatic Brain Injury in Early Childhood: Developmental Effects and Interventions.

    Science.gov (United States)

    Lowenthal, Barbara; Lowenthal, Barbara

    1998-01-01

    Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)

  11. Defining the Developmental Parameters of Temper Loss in Early Childhood: Implications for Developmental Psychopathology

    Science.gov (United States)

    Wakschlag, Lauren S.; Choi, Seung W.; Carter, Alice S.; Hullsiek, Heide; Burns, James; McCarthy, Kimberly; Leibenluft, Ellen; Briggs-Gowan, Margaret J.

    2012-01-01

    Background: Temper modulation problems are both a hallmark of early childhood and a common mental health concern. Thus, characterizing specific behavioral manifestations of temper loss along a dimension from normative misbehaviors to clinically significant problems is an important step toward identifying clinical thresholds. Methods:…

  12. Developmental rate and behavior of early life stages of bighead carp and silver carp

    Science.gov (United States)

    Chapman, Duane C.; George, Amy E.

    2011-01-01

    The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.

  13. Inducible effects of icariin, icaritin, and desmethylicaritin on directional differentiation of embryonic stem cells into cardiomyocytes in vitro

    Institute of Scientific and Technical Information of China (English)

    Dan-yan ZHU; Yi-jia LOU

    2005-01-01

    Aim: To investigate the possible inducible effects of icariin, icaritin, and desmethylicaritin on the directional differentiation of embryonic stem (ES) cells into cardiomyocytes in vitro. Methods: ES cells were cultivated as embryoid bodies (EBs) in hanging drops with icariin, icaritin, or desmethylicaritin. ES cells treated with retinoic acid and with solvent were used as positive and negative controls, respectively. The cardiomyocytes derived from the ES cells were veri fied using immunocytochemistry. The expression of cardiac developmental dependent genes was detected using the reverse transcription-polymerase chain reaction (RT-PCR) method. Cell cycle distribution and apoptosis were analyzed using flow cytometry to determine the partly inducible effect mechanisms involved.Results: The total percentage of beating EBs treated with 1 × 10-7 mol/L ic ariin,icaritin, or desmethylicaritin was 87% (P<0.01 ), 59% (P<0.01), and 49%, respectively.All the beating cardiomyocytes derived from the ES cells expressed cardiacspecific proteins for α-actinin and troponin T. Among them, 1 × 10-7 mol/L icariin treatment resulted in a significantly advanced and increased mRNA level of α-cardiac myosin heavy chain (MHC) and myosin light chain 2v (MLC-2v) in EBs in the early cardiac developmental stage. Before shifting to the cardiomyocyte phenotype, icariin could evoke the accumulation of ES cells in G0/G1 and accelerate apoptosis of the cell population (P<0.05). Conclusion: Icariin facilitated the directional differentiation of ES cells into cardiomyocytes at a concentration of 1 × 10-7 mol/L. The promoting effect of icariin on cardiac differentiation was related to increasing and accelerating gene expression of α-cardiac MHC and MLC-2v, as well as regulating the cell cycles and inducing apoptosis.

  14. Prenatal corticosteroid exposure alters early developmental seizures and behavior

    OpenAIRE

    Velíšek, Libor

    2011-01-01

    In humans, corticosteroids are often administered prenatally to improve lung development in preterm neonates. Studies in exposed children as well as in children, whose mothers experienced significant stress during pregnancy indicate behavioral problems and possible increased occurrence of epileptic spasms. This study investigated whether prenatal corticosteroid exposure alters early postnatal seizure susceptibility and behaviors. On gestational day 15, pregnant rats were injected i.p. with hy...

  15. Developmentally Appropriate Technology in Early Childhood (DATEC) in Botswana: In-Service Teachers’ Perspectives

    OpenAIRE

    BOSE, Kabita

    2009-01-01

    Developmentally Appropriate Technology in Early Childhood (DATEC) aims to identify themost appropriate applications of Information and Communication Technology to support thedevelopment of children under eight years of age. Botswana has a unique spread ofpopulation density and deep-rooted socio-cultural values. There is a need to address thecompatibility of these aspects with the application of Information and CommunicationTechnology in the proposed Early Childhood Education programmes throug...

  16. Persistence of Early Emerging Aberrant Behavior in Children with Developmental Disabilities

    Science.gov (United States)

    Green, Vanessa A.; O'Reilly, Mark; Itchon, Jonathan; Sigafoos, Jeff

    2005-01-01

    This study examined the persistence of early emerging aberrant behavior in 13 preschool children with developmental disabilities. The severity of aberrant behavior was assessed every 6 months over a 3-year period. Teachers completed the assessments using the Aberrant Behavior Checklist [Aman, M. G., & Singh, N. N. (1986). "Aberrant Behavior…

  17. The Effects of Developmental Placement and Early Retention on Children's Later Scores on Standardized Tests.

    Science.gov (United States)

    May, Deborah C.; Welch, Edward L.

    1984-01-01

    Examined the relationship between early school retention as a result of preschool and kindergarten developmental testing and children's later academic achievement (N=223). Results showed children who scored as immature on the Gesell Screening Test and who were retained a year had the lowest scores on all measures. (JAC)

  18. Developmentally Appropriate Technology Practice: Exploring Myths and Perceptions of Early Childhood and Instructional Technology Professionals

    Science.gov (United States)

    Blake, Sally; Winsor, Denise; Burkett, Candice; Allen, Lee

    2011-01-01

    The integration of technology in early childhood classrooms has become a controversial issue among professionals in this field. One issue which may influence technology in these classrooms may be perceptions of what is developmentally appropriate practice (DAP). This article explores perceptions about technology and age appropriate recommendations…

  19. Moving beyond Screen Time: Redefining Developmentally Appropriate Technology Use in Early Childhood Education. Policy Brief

    Science.gov (United States)

    Daugherty, Lindsay; Dossani, Rafiq; Johnson, Erin-Elizabeth; Wright, Cameron

    2014-01-01

    Conversations about what constitutes "developmentally appropriate" use of technology in early childhood education have, to date, focused largely on a single, blunt measure--screen time--that fails to capture important nuances, such as what type of media a child is accessing and whether technology use is taking place solo or with peers.…

  20. Parental divorce and offspring depressive symptoms : Dutch developmental trends during early adolescence

    NARCIS (Netherlands)

    Oldehinkel, A.J.; Ormel, J.; Veenstra, R.; De Winter, A.F.; Verhulst, F.C.

    2008-01-01

    In this study, we investigated if the association between parental divorce and depressive symptoms changes during early adolescence and if developmental patterns are similar for boys and girls. Data were collected in a prospective population cohort of Dutch adolescents (N = 2,149), aged 10 - 15 year

  1. Parental Divorce and Offspring Depressive Symptoms: Dutch Developmental Trends during Early Adolescence

    Science.gov (United States)

    Oldehinkel, Albertine J.; Ormel, Johan; Veenstra, Rene; De Winter, Andrea F.; Verhulst, Frank C.

    2008-01-01

    In this study, we investigated if the association between parental divorce and depressive symptoms changes during early adolescence and if developmental patterns are similar for boys and girls. Data were collected in a prospective population cohort of Dutch adolescents (N = 2,149), aged 10 - 15 years. Outcome variables were self-reported and…

  2. Correlations between Developmental Kindergarten Screenings and Early Reading Indicators One Year Later

    Science.gov (United States)

    Coughlan-Mainard, Kelly A.

    2012-01-01

    School districts in the U.S. are mandated to identify young children with disabilities. Developmental screeners are typically used to screen for such skill deficits. Academic tests are used in older students. A significant challenge is identifying children with potential learning disabilities early in their school career. This study identifies a…

  3. Caregiver Descriptions of the Developmental Skills of Infants and Toddlers Entering Early Intervention Services

    Science.gov (United States)

    Scarborough, Anita A.; Hebbeler, Kathleen M.; Simeonsson, Rune J.; Spiker, Donna

    2007-01-01

    The present study was conducted to describe the developmental skills of a national sample of infants and toddlers at entry into early intervention services. Caregivers were asked about their child's skills during a telephone interview. Summary values were derived from descriptions of motor, communication, independence, and cognitive skills. More…

  4. Developmental and Communication Disorders in Children with Intellectual Disability: The Place Early Intervention for Effective Inclusion

    Science.gov (United States)

    Jacob, Udeme Samuel; Olisaemeka, Angela Nneka; Edozie, Isioma Sitamalife

    2015-01-01

    The paper attempts to discuss the place of intervention in the developmental and communication disorders of children with intellectual disability for the purpose of providing effective inclusion programme. The definition of early intervention was stated, areas affected by children communication disorder such as language comprehension, fluency,…

  5. Transgenic zebrafish recapitulating tbx16 gene early developmental expression.

    Directory of Open Access Journals (Sweden)

    Simon Wells

    Full Text Available We describe the creation of a transgenic zebrafish expressing GFP driven by a 7.5 kb promoter region of the tbx16 gene. This promoter segment is sufficient to recapitulate early embryonic expression of endogenous tbx16 in the presomitic mesoderm, the polster and, subsequently, in the hatching gland. Expression of GFP in the transgenic lines later in development diverges to some extent from endogenous tbx16 expression with the serendipitous result that one line expresses GFP specifically in commissural primary ascending (CoPA interneurons of the developing spinal cord. Using this line we demonstrate that the gene mafba (valentino is expressed in CoPA interneurons.

  6. Methods for in vitro functional analysis of iPSC derived cardiomyocytes - Special focus on analyzing the mechanical beating behavior.

    Science.gov (United States)

    Laurila, Eeva; Ahola, Antti; Hyttinen, Jari; Aalto-Setälä, Katriina

    2016-07-01

    A rapidly increasing number of papers describing novel iPSC models for cardiac diseases are being published. To be able to understand the disease mechanisms in more detail, we should also take the full advantage of the various methods for analyzing these cell models. The traditionally and commonly used electrophysiological analysis methods have been recently accompanied by novel approaches for analyzing the mechanical beatingbehavior of the cardiomyocytes. In this review, we provide first a concise overview on the methodology for cardiomyocyte functional analysis and then concentrate on the video microscopy, which provides a promise for a new faster yet reliable method for cardiomyocyte functional analysis. We also show how analysis conditions may affect the results. Development of the methodology not only serves the basic research on the disease models, but could also provide the much needed efficient early phase screening method for cardiac safety toxicology. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  7. Endocrine and other physiologic modulators of perinatal cardiomyocyte endowment

    Science.gov (United States)

    Jonker, S S; Louey, S

    2015-01-01

    Immature contractile cardiomyocytes proliferate to rapidly increase cell number, establishing cardiomyocyte endowment in the perinatal period. Developmental changes in cellular maturation, size and attrition further contribute to cardiac anatomy. These physiological processes occur concomitant with a changing hormonal environment as the fetus prepares itself for the transition to extrauterine life. There are complex interactions between endocrine, hemodynamic and nutritional regulators of cardiac development. Birth has been long assumed to be the trigger for major differences between the fetal and postnatal cardiomyocyte growth patterns, but investigations in normally growing sheep and rodents suggest this may not be entirely true; in sheep, these differences are initiated before birth, while in rodents they occur after birth. The aim of this review is to draw together our understanding of the temporal regulation of these signals and cardiomyocyte responses relative to birth. Further, we consider how these dynamics are altered in stressed and suboptimal intrauterine environments. PMID:26432905

  8. Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

    Science.gov (United States)

    Tain, You-Lin; Hsu, Chien-Ning

    2017-01-01

    Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659

  9. Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

    Science.gov (United States)

    Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

    2016-04-01

    Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Integrin Based Isolation Enables Purification of Murine Lineage Committed Cardiomyocytes.

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    Laura Tarnawski

    Full Text Available In contrast to mature cardiomyocytes which have limited regenerative capacity, pluripotent stem cells represent a promising source for the generation of new cardiomyocytes. The tendency of pluripotent stem cells to form teratomas and the heterogeneity from various differentiation stages and cardiomyocyte cell sub-types, however, are major obstacles to overcome before this type of therapy could be applied in a clinical setting. Thus, the identification of extracellular markers for specific cardiomyocyte progenitors and mature subpopulations is of particular importance. The delineation of cardiomyocyte surface marker patterns not only serves as a means to derive homogeneous cell populations by FACS, but is also an essential tool to understand cardiac development. By using single-cell expression profiling in early mouse embryonic hearts, we found that a combination of integrin alpha-1, alpha-5, alpha-6 and N-cadherin enables isolation of lineage committed murine cardiomyocytes. Additionally, we were able to separate trabecular cardiomyocytes from solid ventricular myocardium and atrial murine cells. These cells exhibit expected subtype specific phenotype confirmed by electrophysiological analysis. We show that integrin expression can be used for the isolation of living, functional and lineage-specific murine cardiomyocytes.

  11. High throughput physiological screening of iPSC-derived cardiomyocytes for drug development.

    Science.gov (United States)

    Del Álamo, Juan C; Lemons, Derek; Serrano, Ricardo; Savchenko, Alex; Cerignoli, Fabio; Bodmer, Rolf; Mercola, Mark

    2016-07-01

    Cardiac drug discovery is hampered by the reliance on non-human animal and cellular models with inadequate throughput and physiological fidelity to accurately identify new targets and test novel therapeutic strategies. Similarly, adverse drug effects on the heart are challenging to model, contributing to costly failure of drugs during development and even after market launch. Human induced pluripotent stem cell derived cardiac tissue represents a potentially powerful means to model aspects of heart physiology relevant to disease and adverse drug effects, providing both the human context and throughput needed to improve the efficiency of drug development. Here we review emerging technologies for high throughput measurements of cardiomyocyte physiology, and comment on the promises and challenges of using iPSC-derived cardiomyocytes to model disease and introduce the human context into early stages of drug discovery. This article is part of a Special Issue entitled: Cardiomyocyte biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  12. DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

    Science.gov (United States)

    BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

    2017-01-01

    The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

  13. Fractalkine depresses cardiomyocyte contractility.

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    David Taube

    Full Text Available BACKGROUND: Our laboratory reported that male mice with cardiomyocyte-selective knockout of the prostaglandin E2 EP4 receptor sub-type (EP4 KO exhibit reduced cardiac function. Gene array on left ventricles (LV showed increased fractalkine, a chemokine implicated in heart failure. We therefore hypothesized that fractalkine is regulated by PGE2 and contributes to depressed contractility via alterations in intracellular calcium. METHODS: Fractalkine was measured in LV of 28-32 week old male EP4 KO and wild type controls (WT by ELISA and the effect of PGE2 on fractalkine secretion was measured in cultured neonatal cardiomyocytes and fibroblasts. The effect of fractalkine on contractility and intracellular calcium was determined in Fura-2 AM-loaded, electrical field-paced cardiomyocytes. Cardiomyocytes (AVM from male C57Bl/6 mice were treated with fractalkine and responses measured under basal conditions and after isoproterenol (Iso stimulation. RESULTS: LV fractalkine was increased in EP4 KO mice but surprisingly, PGE2 regulated fractalkine secretion only in fibroblasts. Fractalkine treatment of AVM decreased both the speed of contraction and relaxation under basal conditions and after Iso stimulation. Despite reducing contractility after Iso stimulation, fractalkine increased the Ca(2+ transient amplitude but decreased phosphorylation of cardiac troponin I, suggesting direct effects on the contractile machinery. CONCLUSIONS: Fractalkine depresses myocyte contractility by mechanisms downstream of intracellular calcium.

  14. [Relationship between developmental prognosis and changing picture of postural findings in early infancy among early treated children].

    Science.gov (United States)

    Yuge, M; Yamori, Y; Kanda, T; Ando, R

    1992-09-01

    We followed 93 infants prospectively who were treated because of moderate and severe grades of cerebral coordination disturbances since less than 6 months of age. They were divided into 3 groups according to developmental prognosis at 4 years of age; normal 44, mental retardation 18, and cerebral palsy 31. We compared the postural findings in supine and prone position, and 7 postural reactions at the first examination with those at discharge about 50 days after the first examination. We assessed the changing pictures of postural findings as improved, not changed or worsened. We analyzed the relationship between the changing pictures of postural findings during the short period in early infancy and the developmental prognosis among the 3 groups. The normal group showed improvement in a larger number of items than the other two groups. The findings of cerebral palsied children showed poor improvement, and more postural reactions changed to be more pathologic than those in the other two groups. Among the cerebral palsied children, ambulatory cases showed better improvement than those who could not crawl. But we found no significant difference between ambulatory and crawling children. This study demonstrated that assessment of changing pictures of postural findings in early infancy was helpful to predict developmental prognosis.

  15. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender

    OpenAIRE

    Xiaomei Cong; Wanli Xu; Susan Janton; Henderson, Wendy A.; Adam Matson; McGrath, Jacqueline M.; Kendra Maas; Joerg Graf

    2016-01-01

    Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of li...

  16. Developmentally Appropriate Technology in Early Childhood (DATEC in Botswana: In-Service Teachers’ Perspectives

    Directory of Open Access Journals (Sweden)

    Kabita BOSE

    2009-06-01

    Full Text Available Developmentally Appropriate Technology in Early Childhood (DATEC aims to identify themost appropriate applications of Information and Communication Technology to support thedevelopment of children under eight years of age. Botswana has a unique spread ofpopulation density and deep-rooted socio-cultural values. There is a need to address thecompatibility of these aspects with the application of Information and CommunicationTechnology in the proposed Early Childhood Education programmes throughout Botswana.The researcher felt that the views of the in-service teachers, (who are now students of theBachelor of Education Programme in the University of Botswana and have specialized inEarly Childhood Education, would be a valuable input towards an appropriate EarlyChildhood Education curriculum. Hence, a study was proposed to assess the views of theteachers, regarding DATEC in Botswana. Forty (40 fourth year students (Level 400 ofBachelor of Education (Primary Programme of University of Botswana, who specialised inearly years and have a good exposure to Information and Communication Technologyconstituted the sample. Their views were obtained from a semi-structured questionnaire.Both quantitative and qualitative approaches were used for analysis of data. The findings ofthe study showed that the respondents strongly believed that an integration of Informationand Communication Technology with the Early Childhood Education curriculum isnecessary to enhance an overall development of young children. Computers with relevantresources were thought to be the best Information and Communication Technologyapplications in Early Childhood Education for a developmentally appropriate programmethat would provide educational concepts, problem solving skills and creativity. However,they emphasised the need to make the technology socio-culturally compatible to citizens ofBotswana (Batswana to facilitate developmentally appropriate education of young children.The study

  17. An examination of the relationship between a child’s developmental age and early literacy learning

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    Christine E. Moran

    2016-12-01

    Full Text Available American students typically attend kindergarten at the chronological age (CA of five and currently with the implementation of Common Core State Standards, there are expectations that children learn how to read in order to meet these academic standards, despite whether or not they are developmentally ready. This mixed methods study examined age and environmental factors that relate to reading with 83 children from the ages of 4–6½ years. The relationship between developmental age (DA via the Gesell Developmental Observation-Revised and early literacy learning via Marie’s Clay observational tool, Concepts About Print (CAP, were explored. The purpose of the study was to highlight the need for better alignment of educational policies and practices as they relate to child development and to promote more effective synthesis between discoveries in the field of neuroscience about how children learn and what is known about child DAs and stages. The findings revealed a statistically significant relationship between a child’s DA and early literacy learning as measured by the CAP. The descriptive statistics revealed that the DA of the children in this study was younger than their CA. Furthermore, a child’s DA was found to be the strongest predictor of early literacy learning.

  18. Connecting Professional Development to Current Practices: An Examination of Implementation of Developmentally Appropriate Practices in Early Childhood Education

    Science.gov (United States)

    Sadlovsky, Kelly R.

    2013-01-01

    This study uses a basic qualitative research design to uncover and understand how early childhood teachers apply developmentally appropriate practices and what successes and barriers they encounter. The new knowledge produced might help professional development practitioners by increasing their understanding of how developmentally appropriate…

  19. Elucidation of a novel pathway through which HDAC1 controls cardiomyocyte differentiation through expression of SOX-17 and BMP2.

    Directory of Open Access Journals (Sweden)

    Eneda Hoxha

    Full Text Available Embryonic Stem Cells not only hold a lot of potential for use in regenerative medicine, but also provide an elegant and efficient way to study specific developmental processes and pathways in mammals when whole animal gene knock out experiments fail. We have investigated a pathway through which HDAC1 affects cardiovascular and more specifically cardiomyocyte differentiation in ES cells by controlling expression of SOX17 and BMP2 during early differentiation. This data explains current discrepancies in the role of HDAC1 in cardiovascular differentiation and sheds light into a new pathway through which ES cells determine cardiovascular cell fate.

  20. EARLY DETECTION OF CHILDREN WITH DEVELOPMENTAL DIFFICULTIES AS BASE FOR SUCCESSFUL REHABILITATION

    Directory of Open Access Journals (Sweden)

    Ivan DVOJAKOV

    1997-03-01

    Full Text Available In the composition of one well imagined axis, the approach towards the children with developmental difficulties, integrated rehabilitational system, the most important place takes the basic element, the early and adequate detection and evidence of these children, as essential condition for successful realization of the remained segments in the whole system i. e., building of the whole strategy of the children with developmental difficulties.The main goals of this presentation are:· the objective condition in the early detection, evidence and registration of children with developmental difficulties in the Republic, focusing on the present deficiency and partial solutions in this moment.· our professional and personnel possibilities as base for improvement of this segment;· the objective needs and organizational perspectives for a global system of detection of children with developmental difficulties;· the central evidence of these children, excluding the elements of improvisation and partial working.Absence of one unique methodology of detection, registration and central evidence of these children although there is a legislative regulation for their registration (in the centers for social affairs it puts us in a position only to predict the expected number of children with developmental difficulties ( according to WHO, about 5-7 % in pre-school population .The results of the commissions for categorization, as well as the number of persons with developmental difficulties, can’t be equal with the real position of early detected and evidenced, at this moment.Stressing the importance of the early detection and evidence, as a segment in the preventive health care, from one point of view, and pointing out the insufficient engagement of the health workers (doctors, from another point of view, automatically gives the conclusion, that this problem must be solved at health level, giving directions and education of the teaching staff, on the level of

  1. Increasing pre-kindergarten early literacy skills in children with developmental disabilities and delays.

    Science.gov (United States)

    Pears, Katherine C; Kim, Hyoun K; Fisher, Philip A; Yoerger, Karen

    2016-08-01

    Two hundred and nine children receiving early childhood special education services for developmental disabilities or delays who also had behavioral, social, or attentional difficulties were included in a study of an intervention to increase school readiness, including early literacy skills. Results showed that the intervention had a significant positive effect on children's literacy skills from baseline to the end of summer before the start of kindergarten (d=.14). The intervention also had significant indirect effects on teacher ratings of children's literacy skills during the fall of their kindergarten year (β=.09). Additionally, when scores were compared to standard benchmarks, a greater percentage of the children who received the intervention moved from being at risk for reading difficulties to having low risk. Overall, this study demonstrates that a school readiness intervention delivered prior to the start of kindergarten may help increase children's early literacy skills.

  2. [Early identification of children with developmental language disorders - when and how?].

    Science.gov (United States)

    von Suchodoletz, Waldemar

    2011-11-01

    Children with developmental language disorders have a high risk for their cognitive, social, and emotional development. Therefore, they should be identified and treated as early as possible. This paper reviews the possibilities and limits of methods for such early identification. Language screenings during the first 3 years of life are described and appraised with respect to their diagnostic accuracy. The overview indicates that the current stage of language development can be estimated with high reliability by means of parent questionnaires. The possibility of identifying children with developmental language disorders early on is limited. Precursors and first steps of language acquisition correlate with later language abilities, although the relationship is weak and predicting further language development in a individual child is not possible. At the end of the second year of life, however, late talkers can be identified; these children are at risk of language impairment. But not until the end of the third year can sufficient detection of language-impaired children succeed. Parent questionnaires are the most reliable screening instruments for evaluating language abilities during the first 3 years.

  3. Bacterial communities associated with white shrimp (Litopenaeus vannamei larvae at early developmental stages

    Directory of Open Access Journals (Sweden)

    ANTONIUS SUWANTO

    2010-04-01

    Full Text Available Bacterial communities associated with white shrimp (Litopenaeus vannamei larvae at early developmental stages. Biodiversitas 11 (2: 65-68.Terminal Restriction Fragment Length Polymorphism (T-RFLP was used to monitor the dynamics of the bacterial communities associated with early developmental stages of white shrimp (Litopenaeus vannamei larvae. Samples for analysis were egg, hatching nauplii, 24 hours old nauplii, and 48 hours old nauplii which were collected from one cycle of production at commercial hatchery. T-RFLP results indicated that the bacterial community associated with early stages of shrimp development might be transferred vertically from broodstock via egg. There was no significant difference between bacterial communities investigated, except the bacterial community of 48 hours old nauplii. Diversity analyses showed that the bacterial community of egg had the highest diversity and evenness, meanwhile the bacterial community of 48 hours old nauplii had the lowest diversity. Nine phylotypes were found at all stages with high abundance. Those TRFs were identified as γ- proteobacteria, α-proteobacteria, and bacteroidetes group.

  4. Early developmental conditions affect stress response in juvenile but not in adult house sparrows (Passer domesticus).

    Science.gov (United States)

    Lendvai, Adám Z; Loiseau, Claire; Sorci, Gabriele; Chastel, Olivier

    2009-01-01

    The short- and long-term consequences of developmental conditions on fitness have received growing attention because the environmental conditions during early life may influence growth, condition at independence, recruitment, reproductive success or survival. We tested here, in a natural house sparrow population, if early conditions during nestling stage affected the stress response of the birds (i) shortly after fledging and (ii) next year, during their first breeding. We experimentally manipulated brood size to mimic different rearing conditions, creating reduced (-2 chicks) and enlarged broods (+2 chicks), while in a third group brood size was not manipulated. Nestling nutrition state decreased with post-manipulation brood sizes as indicated by lower body mass. Fledglings with higher body mass at the age of ten days showed lower stress response than birds that were leaner at the same age. Fledglings reared in large broods showed a higher response to stress protocol than chicks from small broods, and this effect was in significant interaction with the age of fledglings at capture. This interaction indicates that the effects of the brood size became gradually smaller as the fledglings grew older and were further from their nestling period. The effects of early conditions vanished by the next year: the stress response of adult first time breeders was unrelated to the brood size they fledged from. These results suggest that stress response may reflect the actual state of an individual, rather than its developmental history.

  5. Early neural disruption and auditory processing outcomes in rodent models: Implications for developmental language disability

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    Roslyn Holly Fitch

    2013-10-01

    Full Text Available Most researchers in the field of neural plasticity are familiar with the Kennard Principle," which purports a positive relationship between age at brain injury and severity of subsequent deficits (plateauing in adulthood. As an example, a child with left hemispherectomy can recover seemingly normal language, while an adult with focal injury to sub-regions of left temporal and/or frontal cortex can suffer dramatic and permanent language loss. Here we present data regarding the impact of early brain injury in rat models as a function of type and timing, measuring long-term behavioral outcomes via auditory discrimination tasks varying in temporal demand. These tasks were created to model (in rodents aspects of human sensory processing that may correlate – both developmentally and functionally – with typical and atypical language. We found that bilateral focal lesions to the cortical plate in rats during active neuronal migration led to worse auditory outcomes than comparable lesions induced after cortical migration was complete. Conversely, unilateral hypoxic-ischemic injuries (similar to those seen in premature infants and term infants with birth complications led to permanent auditory processing deficits when induced at a neurodevelopmental point comparable to human "term," but only transient deficits (undetectable in adulthood when induced in a "preterm" window. Convergent evidence suggests that regardless of when or how disruption of early neural development occurs, the consequences may be particularly deleterious to rapid auditory processing outcomes when they trigger developmental alterations that extend into subcortical structures (i.e., lower sensory processing stations. Collective findings hold implications for the study of behavioral outcomes following early brain injury as well as genetic/environmental disruption, and are relevant to our understanding of the neurologic risk factors underlying developmental language disability in

  6. Developmental predictors of inattention-hyperactivity from pregnancy to early childhood.

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    Stéphanie Foulon

    Full Text Available The objective of the study was to characterize the developmental sequence of pre- and postnatal risk factors for inattention-hyperactivity symptoms in preschoolers.Longitudinal data came from a French population based birth cohort study (EDEN; N = 1311 mother-child pairs followed from the pregnancy onwards. Inattention-hyperactivity symptoms were assessed with the Strengths and Difficulties Questionnaire when participating children were 3 years of age. Potential risk factors were classified in four domains (fetal exposures and child somatic characteristics, child temperament, child neurodevelopmental status, psychosocial environment and four periods (before pregnancy, prenatal/birth, infancy, toddlerhood. Their role as potential moderator or mediator was tested with path analysis to determine the developmental sequence.A low family socioeconomic status before pregnancy was the main environmental risk factor for inattention-hyperactivity symptoms at 3 years, and its effect occurred via two pathways. The first was a risk pathway, where lower SES was associated with higher maternal depression and anxiety during pregnancy; then to higher maternal and child distress and dysregulation in infancy; and in turn to higher levels of inattention-hyperactivity at 3 years. The second was a protective pathway, where higher SES was associated with longer duration of breastfeeding during infancy; then to better child neurodevelopmental status in toddlerhood; and in turn to lower levels of inattention-hyperactivity at 3 years.This study identified psychosocial factors at several developmental periods that represent potential targets for preventing the emergence of inattention-hyperactivity symptoms in early childhood.

  7. Role of mother’s perceptions on their child development on early detection of developmental deviation

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    Pudji Andayani

    2006-10-01

    Full Text Available This report aimed to assess mothers’ perceptions on normal and deviation of development in their children. The study was done in underfive children and their mothers from May 1st 1999 to June 30th 1999 who visited the Nutrition, Growth & Development Clinic of the Child Health Department, Sanglah Hospital, Denpasar. A total of 76 children between 2 and 59 months of age and their mothers were enrolled. Data were collected by interview with mothers concerning the following items: perception of their children development, age of child, sex, mother’s education, mother’s job, number of sibling, and mother ability in making referral decisions. Denver II screening test was administered to each child to identify of development status as a gold standard. Sixteen (21% children was identified as having developmental deviation (by mother’s perception and 21 (28% by authors using Denver II screening test. The mother’s perception sensitivity was 67% and specificity was 97%. There were no significant differences of development status perception according to child’s age, mother’s education, mother’s job, and number of sibling. Most of mother’s perceptions about normal development were if the body weight increased and had no disability. Most of the sources of information about development was from the relatives. Thirteen of 21 children who had developmental deviation were referred by mothers. We conclude that mother’s perception can be used as early detection of developmental problems. Mother’s concerns of their children growth development had focused on again body weight, physical developmental and gross motor skill.

  8. Child Developmental Impact of Pittsburgh's Early Childhood Initiative (ECI) in High-Risk Communities: First-Phase Authentic Evaluation Research.

    Science.gov (United States)

    Bagnato, Stephen J.; Suen, Hoi K.; Brickley, Dale; Smith-Jones, Janell; Dettore, Ernie

    2002-01-01

    This study used an "enhanced constructed comparison group" statistical model to conduct longitudinal research on the child developmental impact of Pittsburgh's early childhood initiative (ECI), a partnership to provide high-quality early care and education for children in high-risk neighborhoods. First-phase findings indicate that…

  9. Stability of Developmental Problems after School Entry of Moderately-Late Preterm and Early Preterm-Born Children

    NARCIS (Netherlands)

    Hornman, Jorijn; de Winter, Andrea F.; Kerstjens, Jorien M.; Bos, Arend F.; Reijneveld, Sijmen A.

    Objective To assess the stability of developmental problems in moderately-late preterm-born children compared with early preterm and full term-born children before school entry at age 4 years and 1 year after school entry at age 5 years. Study design We included 376 early preterm, 688 born

  10. Stability of Developmental Problems after School Entry of Moderately-Late Preterm and Early Preterm-Born Children

    NARCIS (Netherlands)

    Hornman, Jorijn; de Winter, Andrea F; Kerstjens, Jorien M; Bos, Arend F; Reijneveld, Sijmen A

    OBJECTIVE: To assess the stability of developmental problems in moderately-late preterm-born children compared with early preterm and full term-born children before school entry at age 4 years and 1 year after school entry at age 5 years. STUDY DESIGN: We included 376 early preterm, 688 born

  11. Early developmental delay in children with autism: A study from a developing country.

    Science.gov (United States)

    Arabameri, Elahe; Sotoodeh, Mohammad Saber

    2015-05-01

    Early diagnosis is appropriate and important for developmental disorders such as autism spectrum disorder. In many less developed countries, unfortunately, diagnosis of this disorder is delayed. The aim of the present study is to determine whether this disorder can be screened using simple strategies such as comparison of the age of acquisition of motor skills. For this purpose, 124 children with autism were chosen to enter the study, and their parents were asked to retrospectively specify the age of achieving milestones of sitting without support, standing alone and walking alone. Information obtained from the parents was compared with World Health Organization standards. Results indicate that participants (male and female) have significantly delayed age of acquisition of all three skills. Based on this result, it can be suggested that existing standards, as a simple means with low cost and easy availability, can be used for early screening of the disease at a younger age so that treatment can be provided more quickly.

  12. Establishment of post-harvest early-developmental categories for viability maintenance of Araucaria angustifolia seeds

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    Cristhyane Garcia Araldi

    2015-12-01

    Full Text Available Araucaria angustifolia seeds are recalcitrant, and their metabolism remains high during storage. This research aimed to describe the initiation of germination in A. angustifolia seeds during storage in order to standardize the assessment of physiological quality and to promote seed conservation. Seeds were collected from two populations and stored for 270 days in the natural laboratory environment and cold chamber. Seeds were classified according to four early developmental stages: I - mature seeds; II - seeds with elongation along the embryonic axis; III - beginning of root protrusion; IV - advanced germination stage, with seedling shoots. After categorization, physical and physiological quality was assessed. In freshly collected seeds, only category I was observed. At 270 days, approximately 40% of seeds were in category III in laboratory conditions, while the maintenance in a cold chamber delayed germinative metabolism. Viability tests showed that seeds in categories III and IV were more susceptible to damage caused by storage. In conclusion, the percentage of viable A. angustifolia seeds depends on the development stage after collection. Seeds that have reached early developmental category III should be prioritized for propagation, while those remaining in categories I and II should be longer stored with periodic assessment for reduction in physiological quality.

  13. Developmental changes in mismatch responses to mandarin consonants and lexical tones from early to middle childhood.

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    Huei-Mei Liu

    Full Text Available The purpose of this study was to use mismatch responses (MMRs to explore the dynamic changes of Mandarin speech perception abilities from early to middle childhood. Twenty preschoolers, 18 school-aged children, and 26 adults participated in this study. Two sets of synthesized speech stimuli varying in Mandarin consonant (alveolo-palatal affricate vs. fricative and lexical tone features (rising vs. contour tone were used to examine the developmental course of speech perception abilities. The results indicated that only the adult group demonstrated typical early mismatch negativity (MMN responses, suggesting that the ability to discriminate specific speech cues in Mandarin consonant and lexical tone is a continuing process in preschool- and school-aged children. Additionally, distinct MMR patterns provided evidence indicating diverse developmental courses to different speech characteristics. By incorporating data from the two speech conditions, we propose using MMR profiles consisting of mismatch negativity (MMN, positive mismatch response (p-MMR, and late discriminative negativity (LDN as possible brain indices to investigate speech perception development.

  14. Early motor developmental milestones and schizophrenia: A systematic review and meta-analysis.

    Science.gov (United States)

    Filatova, S; Koivumaa-Honkanen, H; Hirvonen, N; Freeman, A; Ivandic, I; Hurtig, T; Khandaker, G M; Jones, P B; Moilanen, K; Miettunen, J

    2017-01-25

    The neurodevelopmental hypothesis of schizophrenia proposes that impaired brain development is a cause of the illness. Early motor developmental milestones, such as learning to walk, are predictors of later schizophrenia but studies have not been systematically reviewed. The aim of the present systematic review and meta-analysis was to explore the association between early motor developmental milestones and the risk of adult schizophrenia. In addition, we updated a systematic review on motor function and risk of schizophrenia. The PubMed, PsycINFO and Scopus databases were searched for original research articles published up to July 2015. Motor milestones were measured between ages 0 and 13years. Random effect meta-analysis calculated effect estimates (Hedges' g) for the association between individual motor milestones and schizophrenia risk. An electronic database and selected articles reference list search identified 5990 articles after removing duplicates. Sixty-nine full text articles were assessed for eligibility of which six were included in the review. Five studies provided sufficient data for meta-analyses. The following motor milestones were significantly associated with adult schizophrenia risk: walking unsupported (g=0.46; 95% CI 0.27-0.64; pmotor milestones in childhood and can contribute to the identification of individuals at risk of psychosis.

  15. The effects of early positive parenting and developmental delay status on child emotion dysregulation.

    Science.gov (United States)

    Norona, A N; Baker, B L

    2017-02-01

    Emotion regulation has been identified as a robust predictor of adaptive functioning across a variety of domains (Aldao et al. ). Furthermore, research examining early predictors of competence and deficits in ER suggests that factors internal to the individual (e.g. neuroregulatory reactivity, behavioural traits and cognitive ability) and external to the individual (e.g. caregiving styles and explicit ER training) contribute to the development of ER (Calkins ). Many studies have focused on internal sources or external sources; however, few have studied them simultaneously within one model, especially in studies examining children with developmental delays (DD). Here, we addressed this specific research gap and examined the contributions of one internal factor and one external factor on emotion dysregulation outcomes in middle childhood. Specifically, our current study used structural equation modelling (SEM) to examine prospective, predictive relationships between DD status, positive parenting at age 4 years and child emotion dysregulation at age 7 years. Participants were 151 families in the Collaborative Family Study, a longitudinal study of young children with and without DD. A positive parenting factor was composed of sensitivity and scaffolding scores from mother-child interactions at home and in the research centre at child age 4 years. A child dysregulation factor was composed of a dysregulation code from mother-child interactions and a parent-report measure of ER and lability/negativity at age 7 years. Finally, we tested the hypothesis that positive parenting would mediate the relationship between DD and child dysregulation. Mothers of children with DD exhibited fewer sensitive and scaffolding behaviours compared with mothers of typically developing children, and children with DD were more dysregulated on all measures of ER. SEM revealed that both DD status and early positive parenting predicted emotion dysregulation in middle childhood. Furthermore

  16. Sociodemographic risk, developmental competence, and PTSD symptoms in young children exposed to interpersonal trauma in early life.

    Science.gov (United States)

    Enlow, Michelle Bosquet; Blood, Emily; Egeland, Byron

    2013-12-01

    Young children are disproportionately exposed to interpersonal trauma (maltreatment, witnessing intimate partner violence [IPV]) and appear particularly susceptible to negative sequelae. Little is known about the factors influencing vulnerability to traumatic stress responses and other negative outcomes in early life. This study examined associations among interpersonal trauma exposure, sociodemographic risk, developmental competence, and posttraumatic stress disorder (PTSD) symptoms in 200 children assessed from birth to first grade via standardized observations, record reviews, and maternal and teacher interviews. More severe PTSD symptoms were predicted by greater trauma exposure (r = .43), greater sociodemographic risk (r = .22), and lower developmental competence (rs=−.31 and −.54 for preschool and school-age developmental competence, respectively). Developmental competence partially mediated the association between trauma exposure and symptoms. Trauma exposure fully mediated the association between sociodemographic risk and symptoms. Neither sociodemographic risk nor developmental competence moderated trauma exposure effects on symptoms. The findings suggest that (a)exposure to maltreatment and IPV has additive effects on posttraumatic stress risk in early life, (b) associations between sociodemographic adversity and poor mental health may be attributable to increased trauma exposure in disadvantaged populations, and (c) early exposures have a negative cascade effect on developmental competence and mental health.

  17. Novel developmental analyses identify longitudinal patterns of early gut microbiota that affect infant growth.

    Directory of Open Access Journals (Sweden)

    Richard A White

    Full Text Available It is acknowledged that some obesity trajectories are set early in life, and that rapid weight gain in infancy is a risk factor for later development of obesity. Identifying modifiable factors associated with early rapid weight gain is a prerequisite for curtailing the growing worldwide obesity epidemic. Recently, much attention has been given to findings indicating that gut microbiota may play a role in obesity development. We aim at identifying how the development of early gut microbiota is associated with expected infant growth. We developed a novel procedure that allows for the identification of longitudinal gut microbiota patterns (corresponding to the gut ecosystem developing, which are associated with an outcome of interest, while appropriately controlling for the false discovery rate. Our method identified developmental pathways of Staphylococcus species and Escherichia coli that were associated with expected growth, and traditional methods indicated that the detection of Bacteroides species at day 30 was associated with growth. Our method should have wide future applicability for studying gut microbiota, and is particularly important for translational considerations, as it is critical to understand the timing of microbiome transitions prior to attempting to manipulate gut microbiota in early life.

  18. Developmental trajectories of the fronto-temporal lobes from infancy to early adulthood in healthy individuals.

    Science.gov (United States)

    Tanaka, Chiaki; Matsui, Mie; Uematsu, Akiko; Noguchi, Kyo; Miyawaki, Toshio

    2012-01-01

    Brain development during early life in healthy individuals is rapid and dynamic, indicating that this period plays a very important role in neural and functional development. The frontal and temporal lobes are known to play a particularly important role in cognition. The study of healthy frontal and temporal lobe development in children is therefore of considerable importance. A better understanding of how these brain regions develop could also aid in the diagnosis and treatment of neurodevelopmental disorders. Some developmental studies have used magnetic resonance imaging (MRI) to examine infant brains, but it remains the case that relatively little is known about cortical brain development in the first few years of life. In the present study we examined whole brain, temporal lobe and frontal lobe developmental trajectories from infancy to early adulthood in healthy individuals, considering gender and brain hemisphere differences. We performed a cross-sectional, longitudinal morphometric MRI study of 114 healthy individuals (54 females and 60 males) aged 1 month to 25 years old (mean age ± SD 8.8 ± 6.9). We measured whole brain, temporal and frontal lobe gray matter (GM)/white matter (WM) volumes, following previously used protocols. There were significant non-linear age-related volume changes in all regions. Peak ages of whole brain, temporal lobe and frontal lobe development occurred around pre-adolescence (9-12 years old). GM volumes for all regions increased significantly as a function of age. Peak age was nevertheless lobe specific, with a pattern of earlier peak ages for females in both temporal and frontal lobes. Growth change in whole brain GM volume was larger in males than in females. However, GM volume growth changes for the temporal and frontal lobes showed a somewhat different pattern. GM volume for both temporal and frontal lobes showed a greater increase in females until around 5-6 years old, at which point this tendency reversed (GM volume

  19. The 'Early Developmental Stages of Psychopathology (EDSP) study': a 20-year review of methods and findings.

    Science.gov (United States)

    Beesdo-Baum, Katja; Knappe, Susanne; Asselmann, Eva; Zimmermann, Petra; Brückl, Tanja; Höfler, Michael; Behrendt, Silke; Lieb, Roselind; Wittchen, Hans-Ulrich

    2015-06-01

    The "Early Developmental Stages of Psychopathology (EDSP)" study is a prospective-longitudinal study program in a community sample (Munich, Germany) of adolescents and young adults. The program was launched in 1994 to study the prevalence and incidence of psychopathological syndromes and mental disorders, to describe the natural course and to identify vulnerability and risk factors for onset and progression as well as psychosocial consequences. This paper reviews methods and core outcomes of this study program. The EDSP is based on an age-stratified random community sample of originally N = 3021 subjects aged 14-24 years at baseline, followed up over 10 years with up to 3 follow-up waves. The program includes a family genetic supplement and nested cohorts with lab assessments including blood samples for genetic analyses. Psychopathology was assessed with the DSM-IV/M-CIDI; embedded dimensional scales and instruments assessed vulnerability and risk factors. Beyond the provision of age-specific prevalence and incidence rates for a wide range of mental disorders, analyses of their patterns of onset, course and interrelationships, the program identified common and diagnosis-specific distal and proximal vulnerability and risk factors including critical interactions. The EDSP study advanced our knowledge on the developmental pathways and trajectories, symptom progression and unfolding of disorder comorbidity, highlighting the dynamic nature of many disorders and their determinants. The results have been instrumental for defining more appropriate diagnostic thresholds, led to the derivation of symptom progression models and were helpful to identify promising targets for prevention and intervention.

  20. Developmental epidemiologically based preventive trials: baseline modeling of early target behaviors and depressive symptoms.

    Science.gov (United States)

    Kellam, S G; Werthamer-Larsson, L; Dolan, L J; Brown, C H; Mayer, L S; Rebok, G W; Anthony, J C; Laudolff, J; Edelsohn, G

    1991-08-01

    Describes a conceptual framework for identifying and targeting developmental antecedents in early childhood that have been shown in previous work to predict delinquency and violent behavior, heavy drug use, depression, and other psychiatric symptoms and possibly disorders in late adolescence and into adulthood. Criteria are described that guided choices of targets for two epidemiologically based, randomized preventive trials carried out in 19 elementary schools in the eastern half of Baltimore, involving more than 2,400 first-grade children over the course of first and second grades. Baseline models derived from the first of two cohorts show the evolving patterns of concurrence among the target antecedents. The central role of concentration problems emerged. From Fall to Spring in first grade, concentration problems led to shy and aggressive behavior and poor achievement in both genders and to depressive symptoms among girls. There was evidence for reciprocal relationships in girls. For example, depressive symptoms led to poor achievement in both girls and boys, whereas poor achievement led to depressive symptoms in girls but not boys, at least over the first-grade year. These results provide important epidemiological data relevant to the developmental paths leading to the problem outcomes and suggest preventive trials.

  1. DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5: SELECTIVE REVIEWS FROM A NEW NOSOLOGY FOR EARLY CHILDHOOD PSYCHOPATHOLOGY.

    Science.gov (United States)

    Zeanah, Charles H; Carter, Alice S; Cohen, Julie; Egger, Helen; Gleason, Mary Margaret; Keren, Miri; Lieberman, Alicia; Mulrooney, Kathleen; Oser, Cindy

    2016-09-01

    The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized. © 2016 Michigan Association for Infant Mental Health.

  2. Early life developmental effects of marine persistent organic pollutants on the sea urchin Psammechinus miliaris.

    Science.gov (United States)

    Anselmo, Henrique M R; Koerting, Lina; Devito, Sarah; van den Berg, Johannes H J; Dubbeldam, Marco; Kwadijk, Christiaan; Murk, Albertinka J

    2011-11-01

    A new 16-day echinoid early life stage (ELS) bioassay was developed to allow for prolonged observation of possible adverse effects during embryogenesis and larval development of the sea urchin Psammechinus miliaris. Subsequently, the newly developed bioassay was applied to study the effects of key marine persistent organic pollutants (POPs). Mortality, morphological abnormalities and larval development stages were quantified at specific time points during the 16-day experimental period. In contrast to amphibians and fish, P. miliaris early life development was not sensitive to dioxin-like toxicity in the prolonged early life stage test. Triclosan (TCS) levels higher than 500 nM were acutely toxic during embryo development. Morphological abnormalities were induced at concentrations higher than 50 nM hexabromocyclododecane (HBCD) and 1000 nM tetrabromobisphenol A (TBBPA). Larval development was delayed above 25 nM HBCD and 500 nM TBBPA. Heptadecafluorooctane sulfonic acid (PFOS) exposure slightly accelerated larval development at 9 days post-fertilization (dpf). However, the accelerated development was no longer observed at the end of the test period (16 dpf). The newly developed 16-day echinoid ELS bioassay proved to be sensitive to toxic effects of POPs that can be monitored for individual echinoid larvae. The most sensitive and dose related endpoint was the number of developmental penalty points. By manipulation of the housing conditions, the reproductive season could be extended from 3 to 9 months per year and the ELS experiments could be performed in artificial sea water as well.

  3. Long-term developmental outcome after early hemispherotomy for hemimegalencephaly in infants with epileptic encephalopathy.

    Science.gov (United States)

    Honda, Ryoko; Kaido, Takanobu; Sugai, Kenji; Takahashi, Akio; Kaneko, Yuu; Nakagwa, Eiji; Sasaki, Masayuki; Otsuki, Taisuke

    2013-10-01

    This study aimed to identify the effect of early hemispherotomy on development in a consecutive series of 12 infants with hemimegalencephaly (HME) demonstrating epileptic encephalopathy. Mean age at onset was 20.4 days (range, 1-140), mean age at surgery was 4.3 months (range, 2-9), and mean follow-up time was 78.8 months (range, 36-121). Eleven patients had a history of early infantile epileptic encephalopathy. Vertical parasagittal hemispherotomy was performed without mortality or severe morbidities. At follow-up, seizure freedom was obtained in 8 patients (66.7%), who showed significantly higher postoperative developmental quotient (DQ) (mean, 31.3; range, 7-61) than those with seizures (mean, 5.5; range, 3-8) (p=0.02). Within the seizure-free group, postoperative DQ correlated with preoperative seizure duration (r=-0.811, p=0.01). Our results showed that shorter seizure duration during early infancy could provide better postoperative DQ in infants with HME and epileptic encephalopathy. © 2013.

  4. Retinoic acid is enriched in Hensen's node and is developmentally regulated in the early chicken embryo.

    Science.gov (United States)

    Chen, Y; Huang, L; Russo, A F; Solursh, M

    1992-11-01

    Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring tissues. Furthermore, stage 6 Hensen's node contains approximately 3 times more retinoid than that of stage 4 embryos. These endogenous retinoids may establish a concentration gradient from Hensen's node to adjacent tissues and play a role in establishing the primary embryonic axis in the vertebrate. The results also suggest that the retinoid concentration in Hensen's node is developmentally regulated.

  5. Early developmental regression in autism spectrum disorder: evidence from an international multiplex sample.

    Science.gov (United States)

    Parr, Jeremy R; Le Couteur, Ann; Baird, Gillian; Rutter, Michael; Pickles, Andrew; Fombonne, Eric; Bailey, Anthony J

    2011-03-01

    The characteristics of early developmental regression (EDR) were investigated in individuals with ASD from affected relative pairs recruited to the International Molecular Genetic Study of Autism Consortium (IMGSAC). Four hundred and fifty-eight individuals with ASD were recruited from 226 IMGSAC families. Regression before age 36 months occurred in 23.9% of individuals. The observed concordance rate for EDR within sibling pairs (18.9%) was not significantly above the rate expected under independence (13.5%, p = 0.10). The rate of regression in individuals with ASD from multiplex families was similar to that reported in singleton and epidemiological samples. Regression concordance data were not supportive of a separate familial influence on EDR, other than as a part of autism itself.

  6. Toxic effects of magnesium oxide nanoparticles on early developmental and larval stages of zebrafish (Danio rerio).

    Science.gov (United States)

    Ghobadian, Mehdi; Nabiuni, Mohammad; Parivar, Kazem; Fathi, Mojtaba; Pazooki, Jamileh

    2015-12-01

    Magnesium oxide nanoparticles (MgONPs) are used in medicine, manufacturing and food industries. Because of their extensive application in our daily lives, environmental exposure to these nanoparticles is inevitable. The present study examined the effects of MgONPs on zebrafish (Danio rerio) early developmental stages. The results showed that, at different concentrations, MgONPs induced cellular apoptosis and intracellular reactive oxygen species. The hatching rate and survival of embryos decreased in a dose dependent manner. The 96-h LC50 value of MgONPs on zebrafish survival was 428 mg/l and the 48-h EC50 value of MgONPs on zebrafish embryo hatching rate was 175 mg/l. Moreover different types of malformation were observed in exposed embryos. The results demonstrate the toxic effects of MgONPs on zebrafish embryos and emphasize the need for further studies.

  7. EARLY DIAGNOSIS AS DETERMINATING FACTOR FOR PROFESSIONAL, RATIONAL AND EFFECTIVE TREATMENT OF CHILDREN WITH DEVELOPMENTAL DIFFICULTIES

    Directory of Open Access Journals (Sweden)

    Goran AJDINSKI

    1997-06-01

    Full Text Available Early diagnosis of children with developmental difficulties is one of the most important segments in the process of rehabilitation. It is not only an assessment and evaluation of the functional conditions, but also and detection of the possibilities for treatment and it’s improvement.In our presentation we give the first noticing for diagnostics of children with developmental difficulties in the Republic of Macedonia, the present capacities, possibilities, needs and suggestions for it’s improvement and advancement. Speaking about that we stress the need of multidisciplinary and complete professional team in the present institutions and solving out a number of problems that exist on that plan. It especially relates to the unique terminology, the procedure and involvement of defectologists in the diagnostic process.Having in mind the bio-psycho and social aspects of the personality of children with developmental difficulties, together with the need of a complex diagnostic procedure, we have tried to give the professional activities of all the profiles of professionals that take part in the diagnostic process. So, we give a review of the work of:· physician-pediatrician who is involved in the diagnostics of all children· audiologist who is involved in the diagnostics of children with damaged hearing from a medical point of view.· the clinical psychologist who works in the institute for medical rehabilitation and whose task is to prepare and realize all the necessary tests for the personality of the child with developmental difficulties.· physiologist for children with somatic damages.· neuropsychiatrist for children with psychological difficulties· specialist for eye diseases giving his report about the child’s damaged eyesight etc.We consider that we shouldn’t neglect the role of the defectologist, his examinations on psycho-motor status, speech, i. e. the functions of the individual in relation to the social aspect in a close

  8. Both Maternal and Pup Genotype Influence Ultrasonic Vocalizations and Early Developmental Milestones in Tsc2+/− Mice

    Directory of Open Access Journals (Sweden)

    Emily A. Greene-Colozzi

    2014-01-01

    Full Text Available Tuberous sclerosis complex (TSC is an autosomal dominant disorder characterized by tumor growth and neuropsychological symptoms such as autistic behavior, developmental delay, and epilepsy. While research has shed light on the biochemical and genetic etiology of TSC, the pathogenesis of the neurologic and behavioral manifestations remains poorly understood. TSC patients have a greatly increased risk of developmental delay and autism spectrum disorder, rendering the relationship between the two sets of symptoms an extremely pertinent issue for clinicians. We have expanded on previous observations of aberrant vocalizations in Tsc2+/− mice by testing vocalization output and developmental milestones systematically during the early postnatal period. In this study, we have demonstrated that Tsc2 haploinsufficiency in either dams or their pups results in a pattern of developmental delay in sensorimotor milestones and ultrasonic vocalizations.

  9. The human adult cardiomyocyte phenotype

    NARCIS (Netherlands)

    Bird, SD; Doevendans, PA; van Rooijen, MA; de la Riviere, AB; Hassink, RJ; Passier, R; Mummery, CL

    2003-01-01

    Aim: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. Methods: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured

  10. Developmental competence and ultrastructural changes of heat-stressed mouse early blastocysts produced in vitro

    Institute of Scientific and Technical Information of China (English)

    Pingping QU; Wenru TIAN; Tao LI; Zhongling JIANG; Shansong GAO; Zhongjie TIAN; Mingzhi WANG

    2009-01-01

    Mouse early blastocysts were exposed to temporatures of 39℃ and 41℃ for 2 h,respectively,to determine their developmental competence and uhrastructural changes. The results showed that heat stress at 41 ℃ for 2 h,significantly reduced the percentages of expanded and hatched blastocysts,but not at 39℃ for 2 h. The average cell numbers in expanded blastocysts,which developed from early blastocysts heat-stressed at temperatures of 39℃ and 41 ℃,were significantly reduced. The average cell numbers in hatched blastocysts subjected to heat stress were no different from those in the control group cultured at 37℃ . The mitochondria of the early blastocysts heat-stressed at 39T℃ for 2 h,were slightly swollen,but they had recovered after culturing at 37℃ for 2 h. However,the mitochondria in the blastocysts heat stressed at 41 ℃ for 2 h were severely swollen,and their number increased. The ribosomes shed from the rough endoplasmic reticulum,and the number of secondary lysosomes in the plasma increased. The integrity of desmosomes was disrupted. The space between the nuclear envelope and the perivitelline membrane enlarged. The fibre fraction and the particulate fraction of nucleoli were separated. The heterochromatin in nucleoli was also increased in its quantity. There were some lamellar-shape structures and heterogeneous dense materials exhibiting in the cytoplasm. The ultrastructural changes induced by heat shock at 41 ℃ for 2 h were not reversible. In conclusion,the damage of heat stress to mitochondria,lysosomes,ribosomes and cell nucleus,may be one of the most important factors that inhibit the normal development of mouse early blastocysts.

  11. A Framework for Early Literacy Instruction: Aligning Standards to Developmental Patterns and Student Behaviors. Pre-K through Kindergarten.

    Science.gov (United States)

    Bodrova, Elena; Leong, Deborah J.; Paynter, Diane E.; Semenov, Dmitri

    This document is designed to establish consistency in the definition and format to be used in developing early literacy standards and benchmarks. It articulates a set of standards and benchmarks that is based on current national and state standards documents and that reflects the foundational knowledge and developmental differences representative…

  12. Tackling the 'dyslexia paradox': reading brain and behavior for early markers of developmental dyslexiax.

    Science.gov (United States)

    Ozernov-Palchik, Ola; Gaab, Nadine

    2016-01-01

    Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5-17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in pre-reading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure.

  13. A developmental change of the visual behavior of the face recognition in the early infancy.

    Science.gov (United States)

    Konishi, Yukihiko; Okubo, Kensuke; Kato, Ikuko; Ijichi, Sonoko; Nishida, Tomoko; Kusaka, Takashi; Isobe, Kenichi; Itoh, Susumu; Kato, Masaharu; Konishi, Yukuo

    2012-10-01

    The purpose of this study was to examine developmental changes in visuocognitive function, particularly face recognition, in early infancy. In this study, we measured eye movement in healthy infants with a preference gaze problem, particularly eye movement between two face stimulations. We used the eye tracker system (Tobii1750, Tobii Technologies, Sweden) to measure eye movement in infants. Subjects were 17 3-month-old infants and 16 4-month-old infants. The subjects looked two types of face stimulation (upright face/scrambled face) at the same time and we measured their visual behavior (preference/looking/eye movement). Our results showed that 4-month-old infants looked at an upright face longer than 3-month infants, and exploratory behavior while comparing two face stimulations significantly increased. In this study, 4-month-old infants showed a preference towards an upright face. The numbers of eye movements between two face stimuli significantly increased in 4-month-old infants. These results suggest that eye movements may be an important index in face cognitive function during early infancy. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  14. Tackling the ‘dyslexia paradox’: reading brain and behavior for early markers of developmental dyslexia

    Science.gov (United States)

    Ozernov-Palchik, Ola; Gaab, Nadine

    2016-01-01

    Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5–17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in prereading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. PMID:26836227

  15. Icariin-mediated expression of cardiac genes and modulation of nitric oxide signaling pathway during differentiation of mouse embryonic stem cells into cardiomyocytes in vitro

    Institute of Scientific and Technical Information of China (English)

    Dan-yan ZHU; Yi-jia LOU

    2006-01-01

    Aim:To investigate effects of icariin on cardiac gene expression and the modulation of nitric oxide (NO)signal transduction during the differentiation of embryonic stem(ES)cells into cardiomyocytes in vitro.Methods:The expression levels of cardiac developmental-dependent genes were measured using reverse transcription-polymerase chain reaction(RT-PCR).The chronotropic responses of cardiomyocytes to β-adrenoceptor stimulation were determined.The levels of cAMP and cGMP in ES cells were measured using radioimmunoassay.Endogenous NO levels were measured by using the Griess reaction.Aminoguanidine (AG) was used to confirm the influence of icariin on the endogenous NO signal pathway.Results:Icariin significantly elevated mRNA levels of cardiac transcription factors GATA4 and Nkx2.5,and cardiac-specific α-MHC,MLC-2ν and β-AR genes in a concentration-and time-dependent manner (P<0.05).Cardiomyocytes derived from embryoid body (EB)treated with icariin were more sensitive to isoprenaline (P<0.01).Treatment of ES cells with icariin resulted in a continued elevation in the cAMP/cGMP ratio before a shift to the cardiomyocyte phenotype (P<0.05).AG decreased the NO level,and delayed and decreased the incidence of contracting EB to only approximately 35% on d 5+11,an effect that could be rescued by icariin.When cells were cocultured with icariin and AG,the percentage of beating EB reached a peak level of 73% on d 5+11(P<0.05).Conclusion:The inducible effects of icariin were partly related to increase in the expression of cardiac developmental-dependent genes,and elevation of the cAMP/cGMP ratio in ES cells,as well as upregulation of endogenous NO generation during the early stages of cardiac development.

  16. Early clinical characteristics according to developmental stage in children with definite moyamoya disease.

    Science.gov (United States)

    Kim, Young Ok; Joo, Sung-Pil; Seo, Bo-Ra; Rho, Young Il; Yoon, Woong; Woo, Young Jong

    2013-06-01

    The objective is to clarify the early clinical characteristics in childhood moyamoya disease (MD). Epidemiologic characteristics, symptoms and diagnostic rates were assessed in 64 children (0-18 years) with definite MD according to developmental stage: infancy (5; 0-1 years); toddlerhood/preschool age (22; 2-5 years); school age (29; 6-10 years); and adolescence (8; 11-18 years). The median ages at onset was 6.25 years and the female to male ratio was 1.9 (~2.5 in toddlerhood/preschool age and in adolescence, P=0.71). Previous headache was observed in 23% (14/64): frequently in school age (38%, P=0.02) and within 6 months before main symptoms (6/11). As an initial symptom, weakness was observed in 78% (50/64) mainly as transient ischemic attack (TIA, 61%) in limbs (90%) and unilaterally (82%). TIA was less frequent in infancy (40%, P=0.04). Seizure was observed in 27% (17/64): frequently in infancy (100%, Pchildren ~5 years (P<0.01). Severe headache associated with MD was observed in 14% (9/64). Provoking events were positive in 42% (27/64): in school age, frequently during eating (28%); and in toddlerhood/preschool age, during crying (27%). The diagnostic rates at 3 and 12 months from symptom-onset were 39% (80% during infancy vs. 28% in school age, P=0.14) and 67%, respectively. Symptomatic progression at diagnosis was observed in 38% (24/64). Initial clinical characteristics in childhood definite MD differed according to developmental stage and from at diagnosis.

  17. Differential Expression Levels of Integrin α6 Enable the Selective Identification and Isolation of Atrial and Ventricular Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Anne Maria Wiencierz

    Full Text Available Central questions such as cardiomyocyte subtype emergence during cardiogenesis or the availability of cardiomyocyte subtypes for cell replacement therapy require selective identification and purification of atrial and ventricular cardiomyocytes. However, current methodologies do not allow for a transgene-free selective isolation of atrial or ventricular cardiomyocytes due to the lack of subtype specific cell surface markers.In order to develop cell surface marker-based isolation procedures for cardiomyocyte subtypes, we performed an antibody-based screening on embryonic mouse hearts. Our data indicate that atrial and ventricular cardiomyocytes are characterized by differential expression of integrin α6 (ITGA6 throughout development and in the adult heart. We discovered that the expression level of this surface marker correlates with the intracellular subtype-specific expression of MLC-2a and MLC-2v on the single cell level and thereby enables the discrimination of cardiomyocyte subtypes by flow cytometry. Based on the differential expression of ITGA6 in atria and ventricles during cardiogenesis, we developed purification protocols for atrial and ventricular cardiomyocytes from mouse hearts. Atrial and ventricular identities of sorted cells were confirmed by expression profiling and patch clamp analysis.Here, we introduce a non-genetic, antibody-based approach to specifically isolate highly pure and viable atrial and ventricular cardiomyocytes from mouse hearts of various developmental stages. This will facilitate in-depth characterization of the individual cellular subsets and support translational research applications.

  18. Glial cell line-derived neurotrophic factor (GDNF) enhances sympathetic neurite growth in rat hearts at early developmental stages

    NARCIS (Netherlands)

    K. Miwa; J.K. Lee; Y. Takagishi; T. Opthof; X. Fu; I. Kodama

    2010-01-01

    Molecular signaling of sympathetic innervation of myocardium is an unresolved issue. The purpose of this study was to investigate the effect of neurotrophic factors on sympathetic neurite growth towards cardiomyocytes. Cardiomyocytes (CMs) and sympathetic neurons (SNs) were isolated from neonatal ra

  19. Essential role of Cdc42 in cardiomyocyte proliferation and cell-cell adhesion during heart development.

    Science.gov (United States)

    Li, Jieli; Liu, Yang; Jin, Yixin; Wang, Rui; Wang, Jian; Lu, Sarah; VanBuren, Vincent; Dostal, David E; Zhang, Shenyuan L; Peng, Xu

    2017-01-15

    Cdc42 is a member of the Rho GTPase family and functions as a molecular switch in regulating cell migration, proliferation, differentiation and survival. However, the role of Cdc42 in heart development remains largely unknown. To determine the function of Cdc42 in heart formation, we have generated a Cdc42 cardiomyocyte knockout (CCKO) mouse line by crossing Cdc42 flox mice with myosin light chain (MLC) 2a-Cre mice. The inactivation of Cdc42 in embryonic cardiomyocytes induced lethality after embryonic day 12.5. Histological analysis of CCKO embryos showed cardiac developmental defects that included thin ventricular walls and ventricular septum defects. Microarray and real-time PCR data also revealed that the expression level of p21 was significantly increased and cyclin B1 was dramatically decreased, suggesting that Cdc42 is required for cardiomyocyte proliferation. Phosphorylated Histone H3 staining confirmed that the inactivation of Cdc42 inhibited cardiomyocytes proliferation. In addition, transmission electron microscope studies showed disorganized sarcomere structure and disruption of cell-cell contact among cardiomyocytes in CCKO hearts. Accordingly, we found that the distribution of N-cadherin/β-Catenin in CCKO cardiomyocytes was impaired. Taken together, our data indicate that Cdc42 is essential for cardiomyocyte proliferation, sarcomere organization and cell-cell adhesion during heart development. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Effects of Substrate Mechanics on Contractility of Cardiomyocytes Generated from Human Pluripotent Stem Cells

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    Laurie B. Hazeltine

    2012-01-01

    Full Text Available Human pluripotent stem cell (hPSC- derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4–99.7 kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in substrate mechanics. Contraction stress was determined using traction force microscopy, and morphology was characterized by immunocytochemistry for α-actinin and subsequent image analysis. We found that contraction stress of all types of cardiomyocytes increased with substrate stiffness. This effect was not linked to beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte contractility responded appropriately to isoprenaline and remained stable in culture over a period of 2 months. This study demonstrates that hPSC-derived cardiomyocytes have appropriate functional responses to substrate stiffness and to a pharmaceutical agent, which motivates their use in further applications such as drug evaluation and cardiac therapies.

  1. Cell Competition Promotes Phenotypically Silent Cardiomyocyte Replacement in the Mammalian Heart

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    Cristina Villa del Campo

    2014-09-01

    Full Text Available Heterogeneous anabolic capacity in cell populations can trigger a phenomenon known as cell competition, through which less active cells are eliminated. Cell competition has been induced experimentally in stem/precursor cell populations in insects and mammals and takes place endogenously in early mouse embryonic cells. Here, we show that cell competition can be efficiently induced in mouse cardiomyocytes by mosaic overexpression of Myc during both gestation and adult life. The expansion of the Myc-overexpressing cardiomyocyte population is driven by the elimination of wild-type cardiomyocytes. Importantly, this cardiomyocyte replacement is phenotypically silent and does not affect heart anatomy or function. These results show that the capacity for cell competition in mammals is not restricted to stem cell populations and suggest that stimulated cell competition has potential as a cardiomyocyte-replacement strategy.

  2. The International Society for Developmental Psychobiology annual meeting symposium: Impact of early life experiences on brain and behavioral development.

    Science.gov (United States)

    Sullivan, Regina; Wilson, Donald A; Feldon, Joram; Yee, Benjamin K; Meyer, Urs; Richter-Levin, Gal; Avi, Avital; Michael, Tsoory; Gruss, Michael; Bock, Jörg; Helmeke, Carina; Braun, Katharina

    2006-11-01

    Decades of research in the area of developmental psychobiology have shown that early life experience alters behavioral and brain development, which canalizes development to suit different environments. Recent methodological advances have begun to identify the mechanisms by which early life experiences cause these diverse adult outcomes. Here we present four different research programs that demonstrate the intricacies of early environmental influences on behavioral and brain development in both pathological and normal development. First, an animal model of schizophrenia is presented that suggests prenatal immune stimulation influences the postpubertal emergence of psychosis-related behavior in mice. Second, we describe a research program on infant rats that demonstrates how early odor learning has unique characteristics due to the unique functioning of the infant limbic system. Third, we present work on the rodent Octodon degus, which shows that early paternal and/or maternal deprivation alters development of limbic system synaptic density that corresponds to heightened emotionality. Fourth, a juvenile model of stress is presented that suggests this developmental period is important in determining adulthood emotional well being. The approach of each research program is strikingly different, yet all succeed in delineating a specific aspect of early development and its effects on infant and adult outcome that expands our understanding of the developmental impact of infant experiences on emotional and limbic system development. Together, these research programs suggest that the developing organism's developmental trajectory is influenced by environmental factors beginning in the fetus and extending through adolescence, although the specific timing and nature of the environmental influence has unique impact on adult mental health.

  3. Adenosine improves cardiomyocyte respiratory efficiency.

    Science.gov (United States)

    Babsky, A M; Doliba, M M; Doliba, N M; Osbakken, M D

    1998-01-01

    The role of adenosine on the regulation of mitochondrial function has been studied. In order to evaluate this the following experiments were done in isolated rat cardiomyocites and mitochondria using polarographic techniques. Cardiomyocyte oxygen consumption (MVO2) and mitochondrial respiratory function (State 3 and State 4, respiratory control index, and ADP/O ratio) were evaluated after exposure to adenosine. Cardiomyocyte MVO2 was significantly lower in cells previously exposed to adenosine (10 microM, 15 min or 30 min cell incubation) than in cells not exposed to adenosine (control). Addition of dipyridamole (10 microM) or 8-(p-Sulfophenyl) theophylline (50 microM) to cardiomyocytes before adenosine incubation prevented the adenosine-induced changes in MVO2. Mitochondria obtained from isolated perfused beating heart previously perfused with adenosine (10 microM, 30 min heart perfusion) also resulted in significant increases in ADP/O and respiratory control index compared to matching control. Mitochondria isolated from cardiomyocytes previously exposed to adenosine (10 microM, 15 min or 30 min cell incubation) resulted in a significant increase in mitochondrial ADP/O ratio compared to control. Adenosine-induced decrease in cardiomyocyte MVO2 may be related to an increase in efficiency of mitochondrial oxidative phosphorylation, and more economical use of oxygen, which is necessary for survival under ischemic stress.

  4. Electrophysiological properties and calcium handling of embryonic stem cell-derived cardiomyocytes

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    Jae Boum Youm

    2016-03-01

    Full Text Available Embryonic stem cell-derived cardiomyocytes (ESC-CMs hold great interest in many fields of research including clinical applications such as stem cell and gene therapy for cardiac repair or regeneration. ESC-CMs are also used as a platform tool for pharmacological tests or for investigations of cardiac remodeling. ESC-CMs have many different aspects of morphology, electrophysiology, calcium handling, and bioenergetics compared with adult cardiomyocytes. They are immature in morphology, similar to sinus nodal-like in the electrophysiology, higher contribution of trans-sarcolemmal Ca2+ influx to Ca2+ handling, and higher dependence on anaerobic glycolysis. Here, I review a detailed electrophysiology and Ca2+ handling features of ESC-CMs during differentiation into adult cardiomyocytes to gain insights into how all the developmental changes are related to each other to display cardinal features of developing cardiomyocytes.

  5. The characteristics of action potential and nonselective cation current of cardiomyocytes in rabbit superior vena cava

    Institute of Scientific and Technical Information of China (English)

    WANG Pan; YANG XinChun; LIU XiuLan; BAO RongFeng; LIU TaiFeng

    2008-01-01

    As s special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cavs (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may increase or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can increase or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyocytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.

  6. Developmental and physiological challenges of octopus (Octopus vulgaris) early life stages under ocean warming.

    Science.gov (United States)

    Repolho, Tiago; Baptista, Miguel; Pimentel, Marta S; Dionísio, Gisela; Trübenbach, Katja; Lopes, Vanessa M; Lopes, Ana Rita; Calado, Ricardo; Diniz, Mário; Rosa, Rui

    2014-01-01

    The ability to understand and predict the effects of ocean warming (under realistic scenarios) on marine biota is of paramount importance, especially at the most vulnerable early life stages. Here we investigated the impact of predicted environmental warming (+3 °C) on the development, metabolism, heat shock response and antioxidant defense mechanisms of the early stages of the common octopus, Octopus vulgaris. As expected, warming shortened embryonic developmental time by 13 days, from 38 days at 18 °C to 25 days at 21 °C. Concomitantly, survival decreased significantly (~29.9 %). Size at hatching varied inversely with temperature, and the percentage of smaller premature paralarvae increased drastically, from 0 % at 18 °C to 17.8 % at 21 °C. The metabolic costs of the transition from an encapsulated embryo to a free planktonic form increased significantly with warming, and HSP70 concentrations and glutathione S-transferase activity levels were significantly magnified from late embryonic to paralarval stages. Yet, despite the presence of effective antioxidant defense mechanisms, ocean warming led to an augmentation of malondialdehyde levels (an indicative of enhanced ROS action), a process considered to be one of the most frequent cellular injury mechanisms. Thus, the present study provides clues about how the magnitude and rate of ocean warming will challenge the buffering capacities of octopus embryos and hatchlings' physiology. The prediction and understanding of the biochemical and physiological responses to warmer temperatures (under realistic scenarios) is crucial for the management of highly commercial and ecologically important species, such as O. vulgaris.

  7. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender.

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Janton, Susan; Henderson, Wendy A; Matson, Adam; McGrath, Jacqueline M; Maas, Kendra; Graf, Joerg

    2016-01-01

    Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, pgut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion, infant postnatal age, gender and feeding type significantly contribute to the dynamic development of the gut microbiome in preterm infants.

  8. Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

    Science.gov (United States)

    Murphy, M O; Cohn, D M; Loria, A S

    2017-03-01

    The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood.

  9. Developmental Trajectories of Disordered Eating from Early Adolescence to Young Adulthood: A Longitudinal Study

    Science.gov (United States)

    Slane, Jennifer D.; Klump, Kelly L.; McGue, Matthew; Iacono, William G.

    2014-01-01

    Objective Research examining changes in eating disorder symptoms across adolescence suggests an increase in disordered eating from early to late adolescence. However, relevant studies have largely been cross-sectional in nature and most have not examined the changes in the attitudinal symptoms of eating disorders (e.g., weight concerns). This longitudinal study aimed to address gaps in the available data by examining the developmental trajectories of disordered eating in females from preadolescence into young adulthood. Method Participants were 745 same-sex female twins from the Minnesota Twin Family Study. Disordered eating was assessed using the Total Score, Body Dissatisfaction subscale, Weight Preoccupation subscale, and a combined Binge Eating and Compensatory Behavior subscale from the Minnesota Eating Behavior Survey assessed at the ages of 11, 14, 18, 21, and 25. Several latent growth models were fit to the data to identify the trajectory that most accurately captures the changes in disordered eating symptoms from 11 to 25 years. Results The best-fitting models for overall levels of disordered eating, body dissatisfaction, and weight preoccupation showed an increase in from 11 through 25 years. In contrast, bulimic behaviors increased to age of 18 and then stabilized to age of 25. Discussion The findings expanded upon extant research by investigating longitudinal, symptom specific, within-person changes and showing an increase in cognitive symptoms into young adulthood and the stability of disordered eating behaviors past late adolescence. PMID:24995824

  10. Structure, expression, and developmental function of early divergent forms of metalloproteinases in Hydra

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Metalloproteinases have a critical role in a broad spectrum of cellular processes ranging from the break-down of extracellulax matrix to the processing of signal transduction-related proteins. These hydrolyticfunctions underlie a variety of mechanisms related to developmental processes as well as disease states.Structural analysis of metalloproteinases from both invertebrate and vertebrate species indicates that theseenzymes are highly conserved and arose early during metazoan evolution. In this regard, studies from vari-ous laboratories have reported that a number of classes of metalloproteinases are found in hydra, a memberof Cnidaria, the second oldest of existing animal phyla. These studies demonstrate that the hydra genomecontains at least three classes of metalloproteinases to include members of the 1) astacin class, 2) matrix met-alloproteinase class, and 3) neprilysin class. Functional studies indicate that these metalloproteinases playdiverse and important roles in hydra morphogenesis and cell differentiation as well as specialized functionsin adult polyps. This article will review the structure, expression, and function of these metalloproteinasesin hydra.

  11. Early maternal deprivation in rats: a proposed animal model for the study of developmental neuroimmunoendocrine interactions.

    Science.gov (United States)

    De la Fuente, M; Llorente, R; Baeza, I; De Castro, N M; Arranz, L; Cruces, J; Viveros, M P

    2009-02-01

    Adult animals that had been subjected to a single prolonged episode of maternal deprivation (MD) [24 h, postnatal day (PND) 9-10] show long-term behavioral alterations that resemble specific symptoms of schizophrenia. Moreover, at adolescence MD rats showed depressive-like behavior and altered motor responses. According to the neurodevelopmental hypothesis, certain behavioral abnormalities observed in MD animals may be related to altered neurodevelopmental processes triggered by MD-induced elevated glucocorticoids in relevant specific brain regions. We review here these neuroendocrine effects and show new data indicating that the MD procedure induces diverse detrimental effects on the immune system that are already revealed in the short term (PND 13) and persist into adulthood. These long-lasting effects might be related to altered hypothalamus-pituitary-adrenal axis activity and to social as well as nutrition-related factors. In fact, MD induces long-lasting decreases in body weight. In view of our findings we propose the present MD procedure as a potentially useful model to analyze developmental interactions between early psychophysiological stress and immunodeficient states.

  12. The early origins of human charity: Developmental changes in preschoolers’ sharing with poor and wealthy individuals

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    Markus ePaulus

    2014-06-01

    Full Text Available Recent studies have provided evidence that young children already engage in sharing behavior. The underlying social‐cognitive mechanisms, however, are still under debate. In particular, it is unclear whether or not young children’s sharing is motivated by an appreciation of others’ wealth. Manipulating the material needs of recipients in a sharing task (Experiment 1 and a resource allocation task (Experiment 2, we show that 5‐ but not 3‐year‐old children share more with poor than wealthy individuals. The 3-year-old children even showed a tendency to behave less selfishly towards the rich, yet not the poor recipient. This suggests that very early instances of sharing behavior are not motivated by a consideration of others’ material needs. Moreover, the results show that 5-year-old children were rather inclined to give more to the poor individual than distributing the resources equally, demonstrating that their wish to support the poor overruled the otherwise very prominent inclination to share resources equally. This indicates that charity has strong developmental roots in preschool children.

  13. Developmental trajectories of prejudice and tolerance toward immigrants from early to late adolescence.

    Science.gov (United States)

    van Zalk, Maarten Herman Walter; Kerr, Margaret

    2014-10-01

    Adolescence is an important period for the development of relationships between immigrants and non-immigrants, yet little is known about how problematic personality traits affect adolescents' relationships with and attitudes toward immigrants. This work identified the roles of intergroup relationships and one dimension of problematic personality traits, namely callous-unemotional traits, in the development of adolescents' tolerance and prejudice. Three annual measurements of a large community sample (N = 1,542) of non-immigrant adolescents (M age = 15.31 at first measurement; 50.2% girls) were used to show that tolerance and prejudice toward immigrants represent two dimensions with distinct developmental trajectories from early to late adolescence. Callous-unemotional traits predicted fewer decreases in prejudice toward immigrants, yet were not directly associated with tolerance. Intergroup friendships predicted stronger increases in tolerance, which, in turn, predicted decreases in prejudice toward immigrants. Thus, tolerance and prejudice toward immigrants seem to be differentially influenced by social experiences and problematic personality traits.

  14. Prenatal tobacco exposure and self-regulation in early childhood: Implications for developmental psychopathology.

    Science.gov (United States)

    Wiebe, Sandra A; Clark, Caron A C; De Jong, Desiree M; Chevalier, Nicolas; Espy, Kimberly Andrews; Wakschlag, Lauren

    2015-05-01

    Prenatal tobacco exposure (PTE) has a well-documented association with disruptive behavior in childhood, but the neurocognitive effects of exposure that underlie this link are not sufficiently understood. The present study was designed to address this gap, through longitudinal follow-up in early childhood of a prospectively enrolled cohort with well-characterized prenatal exposure. Three-year-old children (n = 151) were assessed using a developmentally sensitive battery capturing both cognitive and motivational aspects of self-regulation. PTE was related to motivational self-regulation, where children had to delay approach to attractive rewards, but not cognitive self-regulation, where children had to hold information in mind and inhibit prepotent motor responses. Furthermore, PTE predicted motivational self-regulation more strongly in boys than in girls, and when propensity scores were covaried to control for confounding risk factors, the effect of PTE on motivational self-regulation was significant only in boys. These findings suggest that PTE's impact on neurodevelopment may be greater in boys than in girls, perhaps reflecting vulnerability in neural circuits that subserve reward sensitivity and emotion regulation, and may also help to explain why PTE is more consistently related to disruptive behavior disorders than attention problems.

  15. Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

    Science.gov (United States)

    Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

    2014-12-01

    In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

  16. Skeletal Morphogenesis of Microbrachis and Hyloplesion (Tetrapoda: Lepospondyli, and Implications for the Developmental Patterns of Extinct, Early Tetrapods.

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    Jennifer C Olori

    Full Text Available The ontogeny of extant amphibians often is used as a model for that of extinct early tetrapods, despite evidence for a spectrum of developmental modes in temnospondyls and a paucity of ontogenetic data for lepospondyls. I describe the skeletal morphogenesis of the extinct lepospondyls Microbrachis pelikani and Hyloplesion longicostatum using the largest samples examined for either taxon. Nearly all known specimens were re-examined, allowing for substantial anatomical revisions that affect the scoring of characters commonly used in phylogenetic analyses of early tetrapods. The palate of H. longicostatum is re-interpreted and suggested to be more similar to that of M. pelikani, especially in the nature of the contact between the pterygoids. Both taxa possess lateral lines, and M. pelikani additionally exhibits branchial plates. However, early and rapid ossification of the postcranial skeleton, including a well-developed pubis and ossified epipodials, suggests that neither taxon metamorphosed nor were they neotenic in the sense of branchiosaurids and salamanders. Morphogenetic patterns in the foot suggest that digit 5 was developmentally delayed and the final digit to ossify in M. pelikani and H. longicostatum. Overall patterns of postcranial ossification may indicate postaxial dominance in limb and digit formation, but also more developmental variation in early tetrapods than has been appreciated. The phylogenetic position and developmental patterns of M. pelikani and H. longicostatum are congruent with the hypothesis that early tetrapods lacked metamorphosis ancestrally and that stem-amniotes exhibited derived features of development, such as rapid and complete ossification of the skeleton, potentially prior to the evolution of the amniotic egg.

  17. CstF-64 is necessary for endoderm differentiation resulting in cardiomyocyte defects

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    Bradford A. Youngblood

    2014-11-01

    Full Text Available Although adult cardiomyocytes have the capacity for cellular regeneration, they are unable to fully repair severely injured hearts. The use of embryonic stem cell (ESC-derived cardiomyocytes as transplantable heart muscle cells has been proposed as a solution, but is limited by the lack of understanding of the developmental pathways leading to specification of cardiac progenitors. Identification of these pathways will enhance the ability to differentiate cardiomyocytes into a clinical source of transplantable cells. Here, we show that the mRNA 3′ end processing protein, CstF-64, is essential for cardiomyocyte differentiation in mouse ESCs. Loss of CstF-64 in mouse ESCs results in loss of differentiation potential toward the endodermal lineage. However, CstF-64 knockout (Cstf2E6 cells were able to differentiate into neuronal progenitors, demonstrating that some differentiation pathways were still intact. Markers for mesodermal differentiation were also present, although Cstf2E6 cells were defective in forming beating cardiomyocytes and expressing cardiac specific markers. Since the extraembryonic endoderm is needed for cardiomyocyte differentiation and endodermal markers were decreased, we hypothesized that endodermal factors were required for efficient cardiomyocyte formation in the Cstf2E6 cells. Using conditioned medium from the extraembryonic endodermal (XEN stem cell line we were able to restore cardiomyocyte differentiation in Cstf2E6 cells, suggesting that CstF-64 has a role in regulating endoderm differentiation that is necessary for cardiac specification and that extraembryonic endoderm signaling is essential for cardiomyocyte development.

  18. Cardiomyocytic apoptosis and heart failure

    Institute of Scientific and Technical Information of China (English)

    Quanzhou Feng

    2008-01-01

    Heart failure is a major disease seriously threatening human health.Once left ventricular dysfunction develops,cardiac function usually deteriorates and progresses to congestive heart failure in several months or years even if no factors which accelerate the deterioration repeatedly exist.Mechanism through which cardiac function continually deteriorates is still unclear.Cardiomyocytic apoptosis can occur in acute stage of ischemic heart diseases and the compensated stage of cardiac dysfunction.In this review,we summarize recent advances in understanding the role of cardiomyocytic apoptosis in heart failure.

  19. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender.

    Directory of Open Access Journals (Sweden)

    Xiaomei Cong

    Full Text Available Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05-0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother's own breastmilk (MBM had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types

  20. Developmentally Universal Practice: Visioning Innovative Early Childhood Pedagogy for Meeting the Needs of Diverse Learners

    Science.gov (United States)

    Harris, Kathleen I.

    2015-01-01

    Although developmentally appropriate practice (DAP) has strong merits, there are considerations pertaining to its development and implementation which must be raised. In order for educators to include diverse voices of young children, the time has come for a new conversation to unfold introducing developmentally universal practice (DUP). With this…

  1. Explanations, mechanisms, and developmental models: Why the nativist account of early perceptual learning is not a proper mechanistic model

    Directory of Open Access Journals (Sweden)

    Radenović Ljiljana

    2013-01-01

    Full Text Available In the last several decades a number of studies on perceptual learning in early infancy have suggested that even infants seem to be sensitive to the way objects move and interact in the world. In order to explain the early emergence of infants’ sensitivity to causal patterns in the world some psychologists have proposed that core knowledge of objects and causal relations is innate (Leslie & Keeble 1987, Carey & Spelke, 1994; Keil, 1995; Spelke et al., 1994. The goal of this paper is to examine the nativist developmental model by investigating the criteria that a mechanistic model needs to fulfill if it is to be explanatory. Craver (2006 put forth a number of such criteria and developed a few very useful distinctions between explanation sketches and proper mechanistic explanations. By applying these criteria to the nativist developmental model I aim to show, firstly, that nativists only partially characterize the phenomenon at stake without giving us the details of when and under which conditions perception and attention in early infancy take place. Secondly, nativist start off with a description of the phenomena to be explained (even if it is only a partial description but import into it a particular theory of perception that requires further empirical evidence and further defense on its own. Furthermore, I argue that innate knowledge is a good candidate for a filler term (a term that is used to name the still unknown processes and parts of the mechanism and is likely to become redundant. Recent extensive research on early intermodal perception indicates that the mechanism enabling the perception of regularities and causal patterns in early infancy is grounded in our neurophysiology. However, this mechanism is fairly basic and does not involve highly sophisticated cognitive structures or innate core knowledge. I conclude with a remark that a closer examination of the mechanisms involved in early perceptual learning indicates that the nativism

  2. Determination of the human cardiomyocyte mRNA and miRNA differentiation network by fine-scale profiling.

    Science.gov (United States)

    Babiarz, Joshua E; Ravon, Morgane; Sridhar, Sriram; Ravindran, Palanikumar; Swanson, Brad; Bitter, Hans; Weiser, Thomas; Chiao, Eric; Certa, Ulrich; Kolaja, Kyle L

    2012-07-20

    To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR-208a/b) revealed an miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification.

  3. Isolation and culture of neonatal mouse cardiomyocytes.

    Science.gov (United States)

    Ehler, Elisabeth; Moore-Morris, Thomas; Lange, Stephan

    2013-09-06

    Cultured neonatal cardiomyocytes have long been used to study myofibrillogenesis and myofibrillar functions. Cultured cardiomyocytes allow for easy investigation and manipulation of biochemical pathways, and their effect on the biomechanical properties of spontaneously beating cardiomyocytes. The following 2-day protocol describes the isolation and culture of neonatal mouse cardiomyocytes. We show how to easily dissect hearts from neonates, dissociate the cardiac tissue and enrich cardiomyocytes from the cardiac cell-population. We discuss the usage of different enzyme mixes for cell-dissociation, and their effects on cell-viability. The isolated cardiomyocytes can be subsequently used for a variety of morphological, electrophysiological, biochemical, cell-biological or biomechanical assays. We optimized the protocol for robustness and reproducibility, by using only commercially available solutions and enzyme mixes that show little lot-to-lot variability. We also address common problems associated with the isolation and culture of cardiomyocytes, and offer a variety of options for the optimization of isolation and culture conditions.

  4. Developmental Links Between Children's Working Memory and their Social Relations with Teachers and Peers in the Early School Years.

    Science.gov (United States)

    de Wilde, Amber; Koot, Hans M; van Lier, Pol A C

    2016-01-01

    This study assessed the developmental links between children's working memory development and their relations with teachers and peers across 2 years of kindergarten and early elementary school. Kindergarten and first grade children, N = 1109, 50% boys, were followed across 2 school-years. Children were assessed across 3 waves, in the fall and spring of the first school-year (within school-year), and finally in the spring of the second school-year. Working memory was assessed using a visuo-spatial working memory task. The developmental links between working memory and child-reported teacher-child relationship quality (warmth and conflict) and peer-nominated likeability and friendedness were assessed using autoregressive cross-lagged models. Lower working memory scores were related to increases in teacher-child conflict and decreases in teacher-child warmth one school-year later, in addition to decreases in likeability by peers within the same school-year. Conversely, teacher-child conflict was negatively associated with the development of working memory across the studied period. Path estimates between working memory and social relational factors were similar for boys and girls. Findings show developmental links between working memory and social-relational factors and vice versa. These results suggest that children's working memory development can be fostered through pro-social relations with teachers in early elementary school children.

  5. Icariin, a Novel Blocker of Sodium and Calcium Channels, Eliminates Early and Delayed Afterdepolarizations, As Well As Triggered Activity, in Rabbit Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Wanzhen Jiang

    2017-05-01

    Full Text Available Icariin, a flavonoid monomer from Herba Epimedii, has confirmed pharmacological and biological effects. However, its effects on arrhythmias and cardiac electrophysiology remain unclear. Here we investigate the effects of icariin on ion currents and action potentials (APs in the rabbit myocardium. Furthermore, the effects of icariin on aconitine-induced arrhythmias were assessed in whole rabbits. Ion currents and APs were recorded in voltage-clamp and current-clamp mode in rabbit left ventricular myocytes (LVMs and left atrial myocytes (LAMs, respectively. Icariin significantly shortened action potential durations (APDs at 50 and 90% repolarization (APD50 and APD90 and reduced AP amplitude (APA and the maximum upstroke velocity (Vmax of APs in LAMs and LVMs; however, icariin had no effect on resting membrane potential (RMP in these cells. Icariin decreased the rate-dependence of the APD and completely abolished anemonia toxin II (ATX-II-induced early afterdepolarizations (EADs. Moreover, icariin significantly suppressed delayed afterdepolarizations (DADs and triggered activities (TAs elicited by isoproterenol (ISO, 1 μM and high extracellular calcium concentrations ([Ca2+]o, 3.6 mM in LVMs. Icariin also decreased INaT in a concentration-dependent manner in LAMs and LVMs, with IC50 values of 12.28 ± 0.29 μM (n = 8 cells/4 rabbits and 11.83 ± 0.92 μM (n = 10 cells/6 rabbits; p > 0.05 vs. LAMs, respectively, and reversed ATX-II-induced INaL in a concentration-dependent manner in LVMs. Furthermore, icariin attenuated ICaL in a dose-dependent manner in LVMs. The corresponding IC50 value was 4.78 ± 0.89 μM (n = 8 cells/4 rabbits, indicating that the aforementioned current in LVMs was 2.8-fold more sensitive to icariin than ICaL in LAMs (13.43 ± 2.73 μM; n = 9 cells/5 rabbits. Icariin induced leftward shifts in the steady-state inactivation curves of INaT and ICaL in LAMs and LVMs but did not have a significant effect on their activation

  6. Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

    Science.gov (United States)

    Garner, Andrew S; Shonkoff, Jack P

    2012-01-01

    Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.

  7. DEFINING RELATIONAL PATHOLOGY IN EARLY CHILDHOOD: THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5 APPROACH.

    Science.gov (United States)

    Zeanah, Charles H; Lieberman, Alicia

    2016-09-01

    Infant mental health is explicitly relational in its focus, and therefore a diagnostic classification system for early childhood disorders should include attention not only to within-the-child psychopathology but also between child and caregiver psychopathology. In this article, we begin by providing a review of previous efforts to introduce this approach that date back more than 30 years. Next, we introduce changes proposed in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-5 (ZERO TO THREE, in press). In a major change from previous attempts, the DC:0-5 includes an Axis I "Relationship Specific Disorder of Early Childhood." This disorder intends to capture disordered behavior that is limited to one caregiver relationship rather than cross contextually. An axial characterization is continued from the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood DC:0-3R (ZERO TO THREE, 2005), but two major changes are introduced. First, the DC:0-5 proposes to simplify ratings of relationship adaptation/maladaptation, and to expand what is rated so that in addition to characterizing the child's relationship with his or her primary caregiver, there also is a characterization of the network of family relationships in which the child develops. This includes coparenting relationships and the entire network of close relationships that impinge on the young child's development and adaptation. © 2016 Michigan Association for Infant Mental Health.

  8. Decay of antibody isotypes against early developmental stages of Schistosoma mansoni after treatment of schistosomiasis patients

    Directory of Open Access Journals (Sweden)

    Herminia Yohko KANAMURA

    1997-09-01

    Full Text Available Antibodies to a number of parasite antigens are found in schistosomiasis patients, and antibodies to early developmental stages were demonstrated to be efficient immunologic markers for the diagnosis of schistosomiasis. In the present study, decay patterns of IgM and IgG antibodies against cercariae and schistosomula were investigated, in comparison to antibodies against worms and eggs in schistosomiasis patients after chemotherapy, for an investigation of seroepidemiologic aspects. Data obtained in the study of 359 serum samples from patients with Schistosoma mansoni infection, noninfected individuals, and patients followed-up for a period of 12 to 15 months after treatment provided the basis to postulate a general pattern for the kinetics of antibody decay. Before treatment, the antibody pattern was represented by a unimodal curve, which shifted to a bimodal curve after treatment, and ended with a unimodal curve similar to that for the noninfected group. Different types of antibodies were classified into four categories according to their decay features, and anti-schistosomulum IgM was classified into the moderate-decay caterogy, whereas other antibodies to early parasite stages were classified into the slow-decay category. The present methodology permits the identification of the most suitable antibodies to be detected in field control programs for schistosomiasis or other parasitosesEm pacientes com esquistossomose, são encontrados anticorpos contra grande número de antígenos parasitários, e aqueles contra formas evolutivas jovens do parasita demonstraram que eram eficientes marcadores imunológicos para o diagnóstico da esquistossomose. Padrões de queda de anticorpos IgM e IgG contra cercária e esquistossômulo foram aqui estudados, comparativamente aos dos anticorpos contra verme e ovo, em pacientes esquistossomóticos após quimioterapia, abordando aspectos soroepidemiológicos. Dados obtidos no estudo de 359 amostras de soros

  9. Stability of Developmental Problems after School Entry of Moderately-Late Preterm and Early Preterm-Born Children.

    Science.gov (United States)

    Hornman, Jorijn; de Winter, Andrea F; Kerstjens, Jorien M; Bos, Arend F; Reijneveld, Sijmen A

    2017-08-01

    To assess the stability of developmental problems in moderately-late preterm-born children compared with early preterm and full term-born children before school entry at age 4 years and 1 year after school entry at age 5 years. We included 376 early preterm, 688 born moderately-late preterm, and 403 full term-born children from the Longitudinal Preterm Outcome Project (LOLLIPOP) cohort study. Developmental problems were assessed by the total score and the 5 domain scores of the Ages and Stages Questionnaire at ages 4 (ASQ-4) and 5 (ASQ-5). From the combinations of normal and abnormal ASQ-4 and ASQ-5 scores we constructed 4 categories: consistently normal, emerging, resolving, and persistent problems. The ASQ-4 total score was abnormal more frequently in moderately-late preterm (7.9%, P = .016) and early preterm-born children (13.0%, P preterm-born children had persistence and change comparable with full term-born children, and early preterm-born children had significantly greater rates than full term-born children of persistent (8.4% vs 2.2%, P preterm and moderately-late preterm-born children had mainly emerging motor problems and resolving communication problems, but the changing rates of moderately-late preterm-born children were lower. After school entry, the overall development of moderately-late preterm-born children had stability patterns comparable with full term-born children, whereas early preterm-born children had greater rates of persistent and emerging problems. On the underlying domains, moderately-late preterm-born children had patterns comparable with early preterm-born children but at lower rates. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Atypical perinatal sensory stimulation and early perceptual development: insights from developmental psychobiology.

    Science.gov (United States)

    Lickliter, R

    2000-12-01

    Comparative studies utilizing avian and mammalian embryos and neonates have proven particularly useful in exploring how alterations in sensory experience during the perinatal period can affect subsequent development. This article reviews research drawn from comparative developmental psychobiology and concludes that the effects of modified sensory stimulation on perceptual and behavioral development depend on several related factors, including the timing of stimulation relative to the developmental stage of the young organism, the overall amount of sensory stimulation provided or denied, and the type of sensory stimulation presented. Directions for future research on the care of the high-risk infant are discussed.

  11. The CASA Trauma and Attachment Group (TAG) Program for Children who have Attachment Issues Following Early Developmental Trauma.

    Science.gov (United States)

    Ashton, Chandra K; O'Brien-Langer, Anna; Silverstone, Peter H

    2016-01-01

    There is relatively little research about effective therapeutic approaches for children in middle childhood who have attachment related diagnoses as a result of experiencing significant, early developmental trauma. This study describes findings from an intensive, dyad-based intervention, aimed at stabilizing attachment relationships with primary caregivers, increasing caregiver reflective function skills, and reducing children's trauma-related behavioural sequelae. We analyzed retrospective data from 51 caregiver/child dyads who participated in the Trauma and Attachment Group (TAG) Program from September 2011-December 2014. This data included pre- and post-intervention scores retrieved from the Parenting Relationship Questionnaire (PRQ), the Parent Report of Post-Traumatic Stress Symptoms (PROPS), and the Parental Reflective Functioning Questionnaire (PRFQ-1). The preliminary findings show statistically significant improvements in attachment, communication, discipline practices, involvement, and relational frustration. Additionally there were statistically significant improvements in parental reflective functioning, and a trend towards a reduction in symptoms typical of post-traumatic stress disorder. Poor quality or inconsistent interactions with early caregivers can lead to life-long impairments in physical and mental health. This intensive program shows potential as a way to improve longer-term outcomes for children exposed to early developmental trauma. Longer-term research is required to further substantiate outcomes, appraise cost analysis, as well as to consider evaluation with appropriate comparison groups.

  12. Evaluation of stress and pain in young children with cerebral palsy during early developmental intervention programs: a descriptive study.

    Science.gov (United States)

    Zhao, Xiaoke; Chen, Mengying; Du, Senjie; Li, Hongying; Li, Xiaonan

    2015-03-01

    The aim of this study was to use the Face, Legs, Activity, Cry, Consolability Scale; salivary cortisol levels; and withdrawal reflex thresholds to assess pain, stress, and pain sensitivity in young children with cerebral palsy during early developmental intervention programs. A total of 40 children with cerebral palsy (age range, 1-4 yrs) participated in the early intervention programs, which included neurodevelopmental treatment, neuromuscular electrical stimulation, occupational therapy, head acupuncture, and Chinese traditional manipulation five times per week for 3 wks. The Face, Legs, Activity, Cry, Consolability Scale was applied during the course of each treatment, and salivary cortisol samples were obtained from each child 10 mins before and 10 mins after each treatment. Withdrawal reflex thresholds were assessed via mechanical stimulation of the foot with von Frey hairs. All treatment programs caused some degree of pain. In descending order, the extents of the pain caused by each treatment were head acupuncture, neurodevelopmental treatment, neuromuscular electrical stimulation, Chinese traditional manipulation, and occupational therapy. There were statistically significant increases in salivary cortisol levels after the head acupuncture (P treatment (P treatments. No significant changes were found in the withdrawal reflex thresholds during the study (P > 0.05). The results of this study demonstrate that early developmental intervention programs cause pain and stress in young children with cerebral palsy.

  13. Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1.

    Science.gov (United States)

    Champhekar, Ameya; Damle, Sagar S; Freedman, George; Carotta, Sebastian; Nutt, Stephen L; Rothenberg, Ellen V

    2015-04-15

    The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program.

  14. Early Childhood Predictors of Mothers' and Fathers' Relationships with Adolescents with Developmental Disabilities

    Science.gov (United States)

    Mitchell, D. B.; Hauser-Cram, P.

    2010-01-01

    Background: The importance of positive parent-adolescent relationships is stressed in research on adolescents, although very little is known about this relationship when a teen has developmental disabilities (DD). We investigated the relationships of adolescents with disabilities with their mothers and their fathers in order to answer a number of…

  15. The Role of Early Childhood Personality in the Developmental Course of Social Adjustment

    Science.gov (United States)

    Kavcic, Tina; Podlesek, Anja; Zupancic, Maja

    2012-01-01

    This study explored children, preschool, and family characteristics that contribute to individual differences in the developmental trajectories of social competence and internalizing and externalizing behavior. Teachers reported on personality and social adjustment of 304 children at ages 3, 4, 5, and 6 years. Predictors of social adjustment…

  16. Thinking about Feelings: Emotion Focus in the Parenting of Children with Early Developmental Risk

    Science.gov (United States)

    Baker, J. K.; Crnic, K. A.

    2009-01-01

    Background: Children with developmental delays exhibit more difficulty with certain emotional processes than their typically developing peers, which seems to partially account for the increased risk for the development of social problems in this population. Despite considerable study with typically developing populations, research on parental…

  17. Evaluating the Psychometric Integrity of Instruments Used in Early Intervention Research: The Battelle Developmental Inventory.

    Science.gov (United States)

    Snyder, Patricia; And Others

    1993-01-01

    This paper describes two measurement integrity analyses conducted using data on the Battelle Developmental Inventory, obtained from a sample of 78 children with severe disabilities. Procedures used to conduct internal reliability and construct validity analyses are discussed. Researchers are urged to evaluate a test's construct validity when their…

  18. Reinvention of early algebra : developmental research on the transition from arithmetic to algebra

    NARCIS (Netherlands)

    Amerom, B.A. van

    2002-01-01

    In chapter 1 we give our reasons for carrying out this developmental research project on the transition from arithmetic to algebra, which includes the design of an experimental learning strand on solving equations. Chapter 2 describes the theoretical background of the book: current views on the teac

  19. Child Maltreatment and Children's Developmental Trajectories in Early to Middle Childhood

    Science.gov (United States)

    Font, Sarah A.; Berger, Lawrence M.

    2015-01-01

    Associations between experiencing child maltreatment and adverse developmental outcomes are widely studied, yet conclusions regarding the extent to which effects are bidirectional, and whether they are likely causal, remain elusive. This study uses the Fragile Families and Child Wellbeing Study, a birth cohort of 4,898 children followed from birth…

  20. Early Childhood Predictors of Mothers' and Fathers' Relationships with Adolescents with Developmental Disabilities

    Science.gov (United States)

    Mitchell, D. B.; Hauser-Cram, P.

    2010-01-01

    Background: The importance of positive parent-adolescent relationships is stressed in research on adolescents, although very little is known about this relationship when a teen has developmental disabilities (DD). We investigated the relationships of adolescents with disabilities with their mothers and their fathers in order to answer a number of…

  1. Early developmental influences on self-esteem trajectories from adolescence through adulthood: Impact of birth weight and motor skills.

    Science.gov (United States)

    Poole, Kristie L; Schmidt, Louis A; Ferro, Mark A; Missiuna, Cheryl; Saigal, Saroj; Boyle, Michael H; Van Lieshout, Ryan J

    2017-04-20

    While the trajectory of self-esteem from adolescence to adulthood varies from person to person, little research has examined how differences in early developmental processes might affect these pathways. This study examined how early motor skill development interacted with preterm birth status to predict self-esteem from adolescence through the early 30s. We addressed this using the oldest known, prospectively followed cohort of extremely low birth weight (self-report, and self-esteem was reported during three follow-up periods (age 12-16, age 22-26, and age 29-36). We found that birth weight status moderated the association between early motor skills and self-esteem. Stable over three decades, the self-esteem of normal birth weight participants was sensitive to early motor skills such that those with poorer motor functioning manifested lower self-esteem, while those with better motor skills manifested higher self-esteem. Conversely, differences in motor skill development did not affect the self-esteem from adolescence to adulthood in individuals born at extremely low birth weight. Early motor skill development may exert differential effects on self-esteem, depending on whether one is born at term or prematurely.

  2. Human Stem Cell Derived Cardiomyocytes: An Alternative ...

    Science.gov (United States)

    Chemical spills and associated deaths in the US has increased 2.6-fold and 16-fold from 1983 to 2012, respectfully. In addition, the number of chemicals to which humans are exposed to in the environment has increased almost 10-fold from 2001 to 2013 within the US. Internationally, a WHO report on the global composite impact of chemicals on health reported that 16% of the total burden of cardiovascular disease was attributed to environmental chemical exposure with 2.5 million deaths per year. Clearly, the cardiovascular system, at all its various developmental and life stages, represents a critical target organ system that can be adversely affected by existing and emerging chemicals (e.g., engineered nanomaterials) in a variety of environmental media. The ability to assess chemical cardiac risk and safety is critically needed but extremely challenging due to the number and categories of chemicals in commerce, as indicated. This presentation\\session will evaluate the use of adult human stem cell derived cardiomyocytes, and existing platforms, as an alternative model to evaluate environmental chemical cardiac toxicity as well as provide key information for the development of predictive adverse outcomes pathways associated with environmental chemical exposures. (This abstract does not represent EPA policy) Rapid and translatable chemical safety screening models for cardiotoxicity current status for informing regulatory decisions, a workshop sponsored by the Society

  3. Early detection of parenting and developmental problems in toddlers : A randomized trial of home visits versus well-baby clinic visits in the Netherlands

    NARCIS (Netherlands)

    Staal, Ingrid I E; van Stel, Henk F.; Hermanns, Jo M A; Schrijvers, Augustinus J P

    2015-01-01

    Objective: The early detection of parenting and developmental problems by preventive child health care (CHC) services in the Netherlands takes place almost exclusively at the well-baby clinic. This study assesses whether, compared to a visit to the well-baby clinic, a home visit improves early detec

  4. Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis.

    Science.gov (United States)

    Ceballos-Picot, Irene; Mockel, Lionel; Potier, Marie-Claude; Dauphinot, Luce; Shirley, Thomas L; Torero-Ibad, Raoul; Fuchs, Julia; Jinnah, H A

    2009-07-01

    Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency results in Lesch-Nyhan disease (LND), where affected individuals exhibit a characteristic neurobehavioral disorder that has been linked with dysfunction of dopaminergic pathways of the basal ganglia. Since the functions of HPRT, a housekeeping enzyme responsible for recycling purines, have no direct relationships with the dopaminergic pathways, the mechanisms whereby HPRT deficiency affect them remain unknown. The current studies demonstrate that HPRT deficiency influences early developmental processes controlling the dopaminergic phenotype, using several different cell models for HPRT deficiency. Microarray methods and quantitative PCR were applied to 10 different HPRT-deficient (HPRT(-)) sublines derived from the MN9D cell line. Despite the variation inherent in such mutant sublines, several consistent abnormalities were evident. Most notable were increases in the mRNAs for engrailed 1 and 2, transcription factors known to play a key role in the specification and survival of dopamine neurons. The increases in mRNAs were accompanied by increases in engrailed proteins, and restoration of HPRT reverted engrailed expression towards normal levels, demonstrating a functional relationship between HPRT and engrailed. The functional relevance of the abnormal developmental molecular signature of the HPRT(-) MN9D cells was evident in impoverished neurite outgrowth when the cells were forced to differentiate chemically. To verify that these abnormalities were not idiosyncratic to the MN9D line, HPRT(-) sublines from the SK-N-BE(2) M17 human neuroblastoma line were evaluated and an increased expression of engrailed mRNAs was also seen. Over-expression of engrailed occurred even in primary fibroblasts from patients with LND in a manner that suggested a correlation with disease severity. These results provide novel evidence that HPRT deficiency may affect dopaminergic neurons by influencing early developmental

  5. Developmental Trajectories of Social Skills during Early Childhood and Links to Parenting Practices in a Japanese Sample.

    Science.gov (United States)

    Takahashi, Yusuke; Okada, Kensuke; Hoshino, Takahiro; Anme, Tokie

    2015-01-01

    This study used data from a nationwide survey in Japan to model the developmental course of social skills during early childhood. The goals of this study were to identify longitudinal profiles of social skills between 2 and 5 years of age using a group-based trajectory approach, and to investigate whether and to what extent parenting practices at 2 years of age predicted developmental trajectories of social skills during the preschool period. A relatively large sample of boys and girls (N > 1,000) was assessed on three social skill dimensions (Cooperation, Self-control, and Assertion) at four time points (ages 2, 3, 4, and 5), and on four parenting practices (cognitive and emotional involvement, avoidance of restriction and punishment, social stimulation, and social support for parenting) at age 2. The results indicated that for each social skill dimension, group-based trajectory models identified three distinct trajectories: low, moderate, and high. Multinomial regression analysis revealed that parenting practice variables showed differential contributions to development of child social skills. Specifically, Cooperation and Assertion were promoted by cognitive and emotional involvement, Self-control by social stimulation, and Assertion by avoidance of restriction and punishment. Abundant social support for parenting was not associated with higher child social skills trajectories. We found heterogeneity in developmental profiles of social skills during the preschool ages, and we identified parenting practices that contributed to different patterns of social skills development. We discussed the implications of higher-quality parenting practices on the improvement of child social skills across early childhood.

  6. Early life experience contributes to the developmental programming of depressive-like behaviour, neuroinflammation and oxidative stress.

    Science.gov (United States)

    Réus, Gislaine Z; Fernandes, Gabrielly C; de Moura, Airam B; Silva, Ritele H; Darabas, Ana Caroline; de Souza, Thays G; Abelaira, Helena M; Carneiro, Celso; Wendhausen, Diogo; Michels, Monique; Pescador, Bruna; Dal-Pizzol, Felipe; Macêdo, Danielle S; Quevedo, João

    2017-09-01

    This study used an animal model of depression induced by maternal care deprivation (MCD) to investigate whether depressive behaviour, neuroinflammation and oxidative stress were underlying factors in developmental programming after early life stress. At postnatal days (PND) 20, 30, 40, and 60, individual subsets of animals were evaluated in behavioural tests and then euthanized to assess cytokine levels and oxidative stress parameters in the prefrontal cortex (PFC), hippocampus and serum. The results showed that MCD did not induce behavioural changes at PND 30 and 40. However, at PND 20 and 60, the rats displayed a depressive-like behaviour in the forced swimming test, without changes in locomotor spontaneous activity. In the brain and serum, the levels of pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α)) were increased, and the anti-inflammatory cytokine (interleukin-10) level was reduced throughout developmental programming (PND 20, 30, 40 and 60). Protein carbonyl levels increased in the brain at PND 30, 40 and 60. Superoxide dismutase (SOD) activity was decreased during all developmental programming phases evaluated in the brain. Catalase (CAT) activity was decreased at PND 20, 40 and 60 in the brain. Our results revealed that "critical episodes" in early life stressful events are able to induce behavioural alterations that persist into adulthood and can stimulate inflammation and oxidative damage in both central and peripheral systems, which are required for distinct patterns of resilience against psychiatric disorders later in life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Developmental Trajectories of Social Skills during Early Childhood and Links to Parenting Practices in a Japanese Sample.

    Directory of Open Access Journals (Sweden)

    Yusuke Takahashi

    Full Text Available This study used data from a nationwide survey in Japan to model the developmental course of social skills during early childhood. The goals of this study were to identify longitudinal profiles of social skills between 2 and 5 years of age using a group-based trajectory approach, and to investigate whether and to what extent parenting practices at 2 years of age predicted developmental trajectories of social skills during the preschool period. A relatively large sample of boys and girls (N > 1,000 was assessed on three social skill dimensions (Cooperation, Self-control, and Assertion at four time points (ages 2, 3, 4, and 5, and on four parenting practices (cognitive and emotional involvement, avoidance of restriction and punishment, social stimulation, and social support for parenting at age 2. The results indicated that for each social skill dimension, group-based trajectory models identified three distinct trajectories: low, moderate, and high. Multinomial regression analysis revealed that parenting practice variables showed differential contributions to development of child social skills. Specifically, Cooperation and Assertion were promoted by cognitive and emotional involvement, Self-control by social stimulation, and Assertion by avoidance of restriction and punishment. Abundant social support for parenting was not associated with higher child social skills trajectories. We found heterogeneity in developmental profiles of social skills during the preschool ages, and we identified parenting practices that contributed to different patterns of social skills development. We discussed the implications of higher-quality parenting practices on the improvement of child social skills across early childhood.

  8. The characteristics of action potential and nonselec-tive cation current of cardiomyocytes in rabbit superior vena cava

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may in-crease or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can in-crease or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyo-cytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.

  9. Sex differences in the developmental trajectories of impulse control and sensation-seeking from early adolescence to early adulthood.

    Science.gov (United States)

    Shulman, Elizabeth P; Harden, K Paige; Chein, Jason M; Steinberg, Laurence

    2015-01-01

    It has been proposed that high rates of risk-taking in adolescence are partly attributable to patterns of neurobiological development that promote an increase in sensation-seeking tendencies at a time when impulse control is still developing. It is not known, however, whether this pattern is the same for males and females. The present study investigates sex differences in the developmental trajectories of self-reported impulse control and sensation-seeking between the ages of 10 and 25 using longitudinal data from the National Longitudinal Study of Youth 1979 Child and Young Adult Survey (N = 8,270; 49% female; 33% Black, 22% Hispanic, 45% Non-Black, Non-Hispanic). Prior work has found that, consistent with the dual-systems model of adolescent neurobiological development, sensation-seeking rises and falls across this age span, whereas impulse control increases into the 20s. In the present study, we find that this same general pattern holds for both males and females, but with some key differences. As expected, males exhibit higher levels of sensation-seeking and lower levels of impulse control than females. Differences also emerged in the shapes of the developmental trajectories. Females reach peak levels of sensation-seeking earlier than males (consistent with the idea that sensation-seeking is linked to pubertal development) and decline in sensation-seeking more rapidly thereafter. Also, males increase in impulse control more gradually than females. Consequently, sex differences in both impulse control and sensation-seeking increase with age. The findings suggest that the window of heightened vulnerability to risk-taking during adolescence may be greater in magnitude and more protracted for males than for females.

  10. Evidence for Cardiomyocyte Renewal in Humans

    Energy Technology Data Exchange (ETDEWEB)

    Bergmann, O; Bhardwaj, R D; Bernard, S; Zdunek, S; Barnabe-Heider, F; Walsh, S; Zupicich, J; Alkass, K; Buchholz, B A; Druid, H; Jovinge, S; Frisen, J

    2008-10-14

    It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of {sup 14}C, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 20 to 0.3% at the age of 75. Less than 50% of cardiomyocytes are exchanged during a normal lifespan. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work towards the development of therapeutic strategies aiming to stimulate this process in cardiac pathologies.

  11. The Developmental Relationship between Language and Low Early Numeracy Skills throughout Kindergarten

    Science.gov (United States)

    Toll, Sylke W. M.; Van Luit, Johannes E. H.

    2014-01-01

    The relationship between basic oral language and early numeracy has been studied extensively, but results hardly include kindergartners' math language, which might mediate this relationship. The aim of this study was to investigate the development of basic language skills--specifically, math language and low early numeracy. Dutch children (4-5…

  12. The Typical Developmental Trajectory of Social and Executive Functions in Late Adolescence and Early Adulthood

    Science.gov (United States)

    Taylor, Sophie Jane; Barker, Lynne Ann; Heavey, Lisa; McHale, Sue

    2013-01-01

    Executive functions and social cognition develop through childhood into adolescence and early adulthood and are important for adaptive goal-oriented behavior (Apperly, Samson, & Humphreys, 2009; Blakemore & Choudhury, 2006). These functions are attributed to frontal networks known to undergo protracted maturation into early adulthood…

  13. Applying Contemporary Developmental and Movement Science Theories and Evidence to Early Intervention Practice

    Science.gov (United States)

    Hickman, Robbin; McCoy, Sarah Westcott; Long, Toby M.; Rauh, Mitchell J.

    2011-01-01

    Changes in early childhood science, theory, and best practices for improving outcomes of children with motor delay or dysfunction and their families have evolved rapidly since EI began. Changes in daily early intervention (EI) practice have been more elusive. Closing the gap between knowledge and practice requires EI providers to piece together…

  14. Cardiomyocytes display low mitochondrial priming and are highly resistant toward cytotoxic T‐cell killing

    Science.gov (United States)

    Zheng, Xiang; Halle, Stephan; Yu, Kai; Mishra, Pooja; Scherr, Michaela; Pietzsch, Stefan; Willenzon, Stefanie; Janssen, Anika; Boelter, Jasmin; Hilfiker‐Kleiner, Denise; Eder, Matthias

    2016-01-01

    Following heart transplantation, alloimmune responses can cause graft rejection by damaging donor vascular and parenchymal cells. However, it remains unclear whether cardiomyocytes are also directly killed by immune cells. Here, we used two‐photon microscopy to investigate how graft‐specific effector CD8+ T cells interact with cardiomyocytes in a mouse heart transplantation model. Surprisingly, we observed that CD8+ T cells are completely impaired in killing cardiomyocytes. Even after virus‐mediated preactivation, antigen‐specific CD8+ T cells largely fail to lyse these cells although both cell types engage in dynamic interactions. Furthermore, we established a two‐photon microscopy‐based assay using intact myocardium to determine the susceptibility of cardiomyocytes to undergo apoptosis. This feature, also known as mitochondrial priming reveals an unexpected weak predisposition of cardiomyocytes to undergo apoptosis in situ. These observations together with the early exhaustion phenotype of graft‐infiltrating specific T cells provide an explanation why cardiomyocytes are largely protected from direct CD8+ T‐cell‐mediated killing. PMID:26970349

  15. Born early and born poor: An eco-bio-developmental model for poverty and preterm birth.

    Science.gov (United States)

    Brumberg, H L; Shah, S I

    2015-01-01

    Poverty is associated with adverse long-term cognitive outcomes in children. Poverty is also linked with preterm delivery which, in turn, is associated with adverse cognitive outcomes. However, the extent of the effect of poverty on preterm delivery, as well as proposed mechanisms by which they occur, have not been well described. Further, the impact of poverty on preterm school readiness has not been reviewed. As the childhood poverty level continues to increase in the U.S., we examine the evidence around physiological, neurological, cognitive and learning outcomes associated with prematurity in the context of poverty. We use the evidence gathered to suggest an Eco-Bio-Developmental model, emphasizing poverty as a toxic stress which predisposes preterm birth and which, via epigenetic forces, can continue into the next generation. Continued postnatal social disadvantage for these developmentally high-risk preterm infants is strongly linked with poor neurodevelopmental outcomes, decreased school readiness, and decreased educational attainment which can perpetuate the poverty cycle. We suggest social remedies aimed at decreasing the impact of poverty on mothers, fathers, and children which may be effective in reducing the burden of preterm birth.

  16. [Early detection of developmental disorders: the need for a new perspective].

    Science.gov (United States)

    de Winter, M

    1988-02-01

    Early detection of abnormality in young children (aged 0-7) in the Netherlands is to be organized on two levels. First, regional cooperation between child-health professionals and institutions will be stimulated in order to form a nationwide network of 'multidisciplinary teams', with the task of coordinating early detection in a specific area. These teams are to advise parents and professionals in those cases where a child's development is suspected of being 'at risk'. The second part of the program is a campaign to promote the idea of early detection among the population. The aim is to develop the 'signalizing' and diagnostic abilities of parents, teachers and child-health professionals through education and training. The subject of early detection seemed and still seems to be a focus of different interests, and of conflicts of competence between different groups and schools of professionals and different institutions. In this article some of the main conflicting issues are discussed. One of the important problems concerning early detection is the question of defining normality and abnormality. It is concluded that in the case of early detection of both somatic and psychosomatic disorder there can be no such thing as an absolute scientific rationality, as is often suggested. Theoretical frameworks underlying methods of early detection are influenced by social, cultural and historical factors, and thus form a social construction. Finally a protocol-approach is being suggested, a method that might clear some of the problems concerning the content and organizational procedures of the Dutch system for early detection.

  17. Hepcidin, Cathelicidin-1 and IL-8 as immunological markers of responsiveness in early developmental stages of rainbow trout.

    Science.gov (United States)

    Santana, Paula A; Guzmán, Fanny; Forero, Juan C; Luna, Omar F; Mercado, Luis

    2016-09-01

    During the early developmental stage of salmonids, high mortality occurs largely as a result of pathogens. These cause low immune competence in fry, producing disease, decreasing production and finally leading to economic losses. Therefore, the aim of this study was to characterise the developmental stages in which rainbow trout acquires immune response capability when challenged with LPS from Pseudomona aeruginosa for 8 h, studying the hepcidin, cathelicidin-1 and IL-8. Total RNA was extracted from fry at 34, 42, 56 and 66 days post hatching (dph). Hepcidin and cathelicidin-1 transcripts were detected only at days 34 and 42, whereas the IL-8 transcript was detected from day 34 to day 66. To analyse the protein expression in the fry, polyclonal anti-peptide antibodies were generated in rabbit. These three immune sera demonstrated the ability to recognise the whole molecule in biological samples. Immunofluorescence showed that skin, gills and intestine mainly responded to the LPS challenge, indicating that these portals of pathogen entry are capturing LPS. This study constitutes a valuable approach, since it has the potential to identify molecules with biological activity that can be used to evaluate the status of fry in culture.

  18. The validity and reliability of the System for Early Detection of Developmental Disorders: 3-36 months

    Directory of Open Access Journals (Sweden)

    Francisco Alcantud Marín

    2015-06-01

    Full Text Available This article introduces the System for Early Detection of Developmental Disorders (referred to as SDPTD for its abbreviation in Spanish, a system developed in previous papers. The SDPTD is a developmental screening test that includes seven questionnaires, one for each cutoff of age (3, 6, 9, 12, 18, 24 and 36 months. These questionnaires have been designed to be answered by parents. To study its validity, SDPTD was administered to a sample of 728 children (approximately 100 children in each of the seven cutoff age groups. A development scale known as Merrill-Palmer-Revised (MP-R was used as a criteria test. The development state of the children was tested again one year later. The results show a high level of agreement between parents and professionals. The concurrent validity is high although it varies by cutoff age. Regarding the diagnostic validity a year after the original evaluation, levels of sensitivity and specificity are high enough to consider the system reliable, valid and suitable for screening purposes.

  19. Developmental differences in early adolescent aggression: a gene × environment × intervention analysis.

    Science.gov (United States)

    Schlomer, Gabriel L; Cleveland, H Harrington; Vandenbergh, David J; Feinberg, Mark E; Neiderhiser, Jenae M; Greenberg, Mark T; Spoth, Richard; Redmond, Cleve

    2015-03-01

    Aggression-related problems such as assault and homicide among adolescents and young adults exact considerable social and economic costs. Although progress has been made, additional research is needed to help combat this persistent problem. Several lines of research indicate that parental hostility is an especially potent predictor of adolescent aggression, although most longitudinal research has focused on clarifying the direction of effects. In this study, we used longitudinal data from the PROSPER project (N = 580; 54.8% female), a primarily rural Caucasian preventative intervention sample, to examine developmental change in early- to mid-adolescent aggressive behavior problems (age 11-16 years). In addition, we examined maternal hostility as a predictor of developmental change in aggression and the PROSPER preventative intervention, designed to reduce substance use and aggression, as a potential influence on this association. Lastly, several studies indicate that variation in the DRD4 7-repeat gene moderates both parenting and intervention influences on externalizing behavior. Accordingly, we examined the potential moderating role of DRD4. As hypothesized, there was a significant maternal hostility by intervention interaction indicating that the intervention reduced the negative impact of maternal hostility on adolescent change in aggressive behavior problems. DRD4 7-repeat status (7+ vs. 7-) further conditioned this association whereby control group 7+ adolescents with hostile mothers showed increasing aggressive behavior problems. In contrast, aggression decreased for 7+ adolescents with similarly hostile mothers in the intervention. Implications for prevention are discussed as well as current perspectives in candidate gene-by-environment interaction research.

  20. Association of the use of bacterial cell wall synthesis Inhibitor drugs in early childhood with the Developmental Defects of Enamel

    Science.gov (United States)

    Tariq, Amna; Alam Ansari, Munawar; Owais Ismail, Muhammad; Memon, Zahida

    2014-01-01

    Objective: Our objective of the study was to determine the association between frequent use of Penicillins and Cephalosporins with developmental defects of enamel in pediatric age group. Methods: This is a cross sectional study, conducted at Ziauddin University. A total of 367 children, having the history of either Penicillin or Cephalosporin exposure were included. The parents of children were asked to complete a questionnaire related to disease and drug history. Dental examination was carried out to assess the hypomineralization in tooth enamel based on modified Developmental Defects of Enamel (DDE) index. Results: Out of 367 children, 124 (34%) were males and females were 243(66%). In the study group 22.6% (n= 83) of children were found to be hypomineralized. The maximum type of teeth defects were diffused opacities that was 12.0% (n=44). The statistically significant association (p-value hypomineralization for most teeth. Children who were exposed to either Penicillins or Cephalosporin in early childhood showed significant (p-value hypomineralized enamel. Conclusion: This study concludes that frequent use of antibiotics such as penicillins and cephalosporins has positive association with enamel hypomineralization in developing tooth structure. PMID:24772150

  1. Genome-wide identification and analysis of rice genes preferentially expressed in pollen at an early developmental stage.

    Science.gov (United States)

    Nguyen, Tien Dung; Moon, Sunok; Nguyen, Van Ngoc Tuyet; Gho, Yunsil; Chandran, Anil Kumar Nalini; Soh, Moon-Soo; Song, Jong Tae; An, Gynheung; Oh, Sung Aeong; Park, Soon Ki; Jung, Ki-Hong

    2016-09-01

    Microspore production using endogenous developmental programs has not been well studied. The main limitation is the difficulty in identifying genes preferentially expressed in pollen grains at early stages. To overcome this limitation, we collected transcriptome data from anthers and microspore/pollen and performed meta-expression analysis. Subsequently, we identified 410 genes showing preferential expression patterns in early developing pollen samples of both japonica and indica cultivars. The expression patterns of these genes are distinguishable from genes showing pollen mother cell or tapetum-preferred expression patterns. Gene Ontology enrichment and MapMan analyses indicated that microspores in rice are closely linked with protein degradation, nucleotide metabolism, and DNA biosynthesis and regulation, while the pollen mother cell or tapetum are strongly associated with cell wall metabolism, lipid metabolism, secondary metabolism, and RNA biosynthesis and regulation. We also generated transgenic lines under the control of the promoters of eight microspore-preferred genes and confirmed the preferred expression patterns in plants using the GUS reporting system. Furthermore, cis-regulatory element analysis revealed that pollen specific elements such as POLLEN1LELAT52, and 5659BOXLELAT5659 were commonly identified in the promoter regions of eight rice genes with more frequency than estimation. Our study will provide new sights on early pollen development in rice, a model crop plant.

  2. Developmental Trajectory of Audiovisual Speech Integration in Early Infancy. A Review of Studies Using the McGurk Paradigm

    Directory of Open Access Journals (Sweden)

    Tomalski Przemysław

    2015-10-01

    Full Text Available Apart from their remarkable phonological skills young infants prior to their first birthday show ability to match the mouth articulation they see with the speech sounds they hear. They are able to detect the audiovisual conflict of speech and to selectively attend to articulating mouth depending on audiovisual congruency. Early audiovisual speech processing is an important aspect of language development, related not only to phonological knowledge, but also to language production during subsequent years. Th is article reviews recent experimental work delineating the complex developmental trajectory of audiovisual mismatch detection. Th e central issue is the role of age-related changes in visual scanning of audiovisual speech and the corresponding changes in neural signatures of audiovisual speech processing in the second half of the first year of life. Th is phenomenon is discussed in the context of recent theories of perceptual development and existing data on the neural organisation of the infant ‘social brain’.

  3. Trait canalization analysis of water quality, temperature, and developmental associations with early life stages of two fish species.

    Science.gov (United States)

    Simon, Thomas P

    2015-06-01

    Evaluation of trait robustness based on environmental fluctuation in ontogenetic life stages are needed to evaluate stability and trait response during critical developmental events. Hardness, alkalinity, acidity, light intensity, and thermal differences were studied for trait canalization variation in morphometric, meristic, ontogenetic processes, and pigment characteristics. Trait canalization was observed with no statistical differences (p > 0.05) in mixed random two-way ANOVA comparisons between various block and treatment effects for hardness, alkalinity or acidity. Thermal block variation differences in six measures, including mandible length, yolk sac length, midpostanal depth, and head width, incubation, and hatching length, varied significantly (p ≤ 0.05) with declining temperatures. Water quality and thermal attributes exhibited trait canalization and did not increase character state variation in the early life stage morphological expression, which result in stable phenotypic inheritance rather than variable environmental conditions during embryonic and larval development.

  4. Developmental changes in the corpus callosum from infancy to early adulthood: a structural magnetic resonance imaging study.

    Science.gov (United States)

    Tanaka-Arakawa, Megumi M; Matsui, Mie; Tanaka, Chiaki; Uematsu, Akiko; Uda, Satoshi; Miura, Kayoko; Sakai, Tomoko; Noguchi, Kyo

    2015-01-01

    Previous research has reported on the development trajectory of the corpus callosum morphology. However, there have been only a few studies that have included data on infants. The goal of the present study was to examine the morphology of the corpus callosum in healthy participants of both sexes, from infancy to early adulthood. We sought to characterize normal development of the corpus callosum and possible sex differences in development. We performed a morphometric magnetic resonance imaging (MRI) study of 114 healthy individuals, aged 1 month to 25 years old, measuring the size of the corpus callosum. The corpus callosum was segmented into seven subareas of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus and splenium. Locally weighted regression analysis (LOESS) indicated significant non-linear age-related changes regardless of sex, particularly during the first few years of life. After this increase, curve slopes gradually became flat during adolescence and adulthood in both sexes. Age of local maximum for each subarea of the corpus callosum differed across the sexes. Ratios of total corpus callosum and genu, posterior midbody, as well as splenium to the whole brain were significantly higher in females compared with males. The present results demonstrate that the developmental trajectory of the corpus callosum during early life in healthy individuals is non-linear and dynamic. This pattern resembles that found for the cerebral cortex, further suggesting that this period plays a very important role in neural and functional development. In addition, developmental trajectories and changes in growth do show some sex differences.

  5. Regulation of cardiomyocyte autophagy by calcium.

    Science.gov (United States)

    Shaikh, Soni; Troncoso, Rodrigo; Criollo, Alfredo; Bravo-Sagua, Roberto; García, Lorena; Morselli, Eugenia; Cifuentes, Mariana; Quest, Andrew F G; Hill, Joseph A; Lavandero, Sergio

    2016-04-15

    Calcium signaling plays a crucial role in a multitude of events within the cardiomyocyte, including cell cycle control, growth, apoptosis, and autophagy. With respect to calcium-dependent regulation of autophagy, ion channels and exchangers, receptors, and intracellular mediators play fundamental roles. In this review, we discuss calcium-dependent regulation of cardiomyocyte autophagy, a lysosomal mechanism that is often cytoprotective, serving to defend against disease-related stress and nutrient insufficiency. We also highlight the importance of the subcellular distribution of calcium and related proteins, interorganelle communication, and other key signaling events that govern cardiomyocyte autophagy. Copyright © 2016 the American Physiological Society.

  6. Early Childhood Intervention in Portugal: An Overview Based on the Developmental Systems Model

    Science.gov (United States)

    Pinto, Ana Isabel; Grande, Catarina; Aguiar, Cecilia; de Almeida, Isabel Chaves; Felgueiras, Isabel; Pimentel, Julia Serpa; Serrano, Ana Maria; Carvalho, Leonor; Brandao, Maria Teresa; Boavida, Tania; Santos, Paula; Lopes-dos-Santos, Pedro

    2012-01-01

    Research studies on early childhood intervention (ECI) in Portugal are diffuse regarding both program components and the geographical area under scrutiny. Since the 1990s, a growing body of knowledge and evidence in ECI is being gathered, based on postgraduate teaching, in-service training, and research. This article draws on the systems theory…

  7. [Development and the developmental disorders of human brain. I. Early development of the cerebrum

    NARCIS (Netherlands)

    Donkelaar, H.J. ten; Wesseling, P.; Lammens, M.M.Y.; Renier, W.O.; Mullaart, R.A.; Thijssen, H.O.M.

    2001-01-01

    The recent discovery of many genes that regulate brain development is revolutionizing our knowledge of neuroembryology and, moreover, our understanding of how gene defects cause human birth defects. The first 8 weeks of the development of the cerebrum can be subdivided into 23 stages, with early

  8. Infants' Early Visual Attention and Social Engagement as Developmental Precursors to Joint Attention

    Science.gov (United States)

    Salley, Brenda; Sheinkopf, Stephen J.; Neal-Beevers, A. Rebecca; Tenenbaum, Elena J.; Miller-Loncar, Cynthia L.; Tronick, Ed; Lagasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles; Whitaker, Toni; Hammond, Jane; Lester, Barry M.

    2016-01-01

    This study examined infants' early visual attention (at 1 month of age) and social engagement (4 months) as predictors of their later joint attention (12 and 18 months). The sample (n = 325), drawn from the Maternal Lifestyle Study, a longitudinal multicenter project conducted at 4 centers of the National Institute of Child Health and Human…

  9. Developmental trajectories of cigarette smoking from adolescence to the early thirties: personality and behavioral risk factors.

    Science.gov (United States)

    Brook, David W; Brook, Judith S; Zhang, Chenshu; Whiteman, Martin; Cohen, Patricia; Finch, Stephen J

    2008-08-01

    The purpose of this study was to identify distinct trajectories of cigarette smoking from ages 14 to 32, and to examine adolescent personality factors that distinguish trajectories of smoking behavior. Participants (N = 975) were randomly selected and followed prospectively since 1975. Follow-up data on cigarette use and personality and behavioral attributes were collected at five points in time, using structured interviews given in private by trained interviewers. Of these subjects, 746 comprised the cohort used in this study. Growth mixture modeling identified five smoking trajectory groups: nonsmokers, occasional smokers, late starters, quitters, and heavy/continuous smokers. Adolescent personality and behavioral risk factors such as lower ego integration, more externalizing behavior, and lower educational aspirations distinguished the trajectory groups. No gender differences were noted. The findings supported the hypotheses indicating multiple distinct trajectory groups of smoking behavior. Smoking behavior appeared in early adolescence and most often continued into adulthood. Emotional difficulties (i.e., lower ego integration), externalizing behavior, and lower educational aspirations in early adolescence were associated both with smoking at an early age and with continuing to smoke into the thirties. To be more effective, smoking prevention programs should target personality and behavioral variations before smoking becomes habitual, particularly focused on characteristics reflecting behavioral problems as manifested in emotional difficulties, externalizing behavior, and low educational aspirations in early adolescence. The implications for research, prevention, and treatment are discussed.

  10. The Fate of Early Experience Following Developmental Change: Longitudinal Approaches to Individual Adaptation in Childhood.

    Science.gov (United States)

    Sroufe, L. Alan; And Others

    1990-01-01

    Examined Bowlby's proposition that early experiences and the adaptations to which they give rise influence later development, even beyond the influence of current circumstances or very recent adaptation. Groups whose adaptation were similar during preschool years but consistently different earlier were defined and compared. Results supported…

  11. Genetic Moderation of Early Child-Care Effects on Social Functioning Across Childhood: A Developmental Analysis

    Science.gov (United States)

    Belsky, Jay; Pluess, Michael

    2013-01-01

    Data from 508 Caucasian children in the NICHD Study of Early Child Care and Youth Development shows that the DRD4 (but not 5-HTTLPR) polymorphism moderates the effect of child-care quality (but not quantity or type) on caregiver-reported externalizing problems at 54 months and in kindergarten and teacher-reported social skills at kindergarten and…

  12. The Gift of Time: Enactments of Developmental Thought in Early Childhood Practice.

    Science.gov (United States)

    Graue, M. Elizabeth; Kroeger, Janice; Brown, Christopher

    This article explores the relationship between notions of development and practice in early education. Through an interpretive study of the experience of the "gift of time," the article follows small groups of children who delayed kindergarten entry, those who were relatively young but entered on time, and children retained in kindergarten to gain…

  13. Developmental Trends and L1 Effects in Early L2 Learners' Onset Cluster Production

    Science.gov (United States)

    Tessier, Anne-Michelle; Duncan, Tamara Sorenson; Paradis, Johanne

    2013-01-01

    This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04-6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2…

  14. Early Childhood Intervention in South Africa in Relation to the Developmental Systems Model

    Science.gov (United States)

    Samuels, Alecia M.; Slemming, Wiedaad; Balton, Sadna

    2012-01-01

    As highlighted in recent series in "The Lancet" (2007, 2011), children from low and middle income countries are more likely to be adversely affected by early biological and psychosocial experiences that have their origins in environments characterized by poverty, violence, nutritional deficiencies, HIV infections, substance abuse, and…

  15. Early Childhood Developmental Status in Low- and Middle-Income Countries: National, Regional, and Global Prevalence Estimates Using Predictive Modeling.

    Directory of Open Access Journals (Sweden)

    Dana Charles McCoy

    2016-06-01

    Full Text Available The development of cognitive and socioemotional skills early in life influences later health and well-being. Existing estimates of unmet developmental potential in low- and middle-income countries (LMICs are based on either measures of physical growth or proxy measures such as poverty. In this paper we aim to directly estimate the number of children in LMICs who would be reported by their caregivers to show low cognitive and/or socioemotional development.The present paper uses Early Childhood Development Index (ECDI data collected between 2005 and 2015 from 99,222 3- and 4-y-old children living in 35 LMICs as part of the Multiple Indicator Cluster Survey (MICS and Demographic and Health Surveys (DHS programs. First, we estimate the prevalence of low cognitive and/or socioemotional ECDI scores within our MICS/DHS sample. Next, we test a series of ordinary least squares regression models predicting low ECDI scores across our MICS/DHS sample countries based on country-level data from the Human Development Index (HDI and the Nutrition Impact Model Study. We use cross-validation to select the model with the best predictive validity. We then apply this model to all LMICs to generate country-level estimates of the prevalence of low ECDI scores globally, as well as confidence intervals around these estimates. In the pooled MICS and DHS sample, 14.6% of children had low ECDI scores in the cognitive domain, 26.2% had low socioemotional scores, and 36.8% performed poorly in either or both domains. Country-level prevalence of low cognitive and/or socioemotional scores on the ECDI was best represented by a model using the HDI as a predictor. Applying this model to all LMICs, we estimate that 80.8 million children ages 3 and 4 y (95% CI 48.1 million, 113.6 million in LMICs experienced low cognitive and/or socioemotional development in 2010, with the largest number of affected children in sub-Saharan Africa (29.4.1 million; 43.8% of children ages 3 and 4 y

  16. An early career in the military: A developmental-contextual perspective

    Directory of Open Access Journals (Sweden)

    M. E. Kotze

    1999-06-01

    Full Text Available Young professional military officers' experience of their internal career development was studied longitudinally from a life-span, life-space approach. Significant transitions between the life roles of worker, student and leisurite, with concomitant changes in their value system, away from traditional military values towards occupationalism, were confirmed. Gender differences were found for the work and community roles as well as in the developmental patterns of the need for authority, creativity, cultural identity, physical activities, social relationships and variety. Significant differences between the career development profiles of military and civilian students with regard to life roles were revealed. Opsomming Jong militere beroepsoffisiere se belewenis van hulle interne loopbaanontwikkeling is longitudinaal uit 'n lewenspan-Iewensruimte benadering bestudeer. Beduidende oorgange tussen die werk-, studie- en ontspanningsrolle met gepaardgaande veranderinge in hulle waardestelsel, weg van tradisionele militere waardes in die rigting van 'n beroepsgeoriënteerde waardestelsel, is bevestig. Geslagsverskille is gevind wat betref die werk- en gemeenskapsrolle sowel as in die volgende ontwikkelingspatrone: 'n behoefte aan outoriteit, kreatiwiteit, kulturele identiteit, fisiese aktiwiteite, sosiale verhoudings en verskeidenheid. Beduidende verskille met betrekking tot lewensrolle het in die loopbaanontwikkelingsprofiele van militere en burgerlike studente aan die lig gekom.

  17. Epigenetic changes caused by intrauterine malnutrition as potential disease mediator and early prevention in developmental stages.

    Science.gov (United States)

    Fukuoka, Hideoki

    2014-01-01

    Presently, the incidences of noncommunicable diseases (NCD) have been increasing in both low- and middle-income countries worldwidely. Effective long-term and multigeneration interventions to decrease the risk of NCD should be developed and introduced. The environment in utero alters phenotypes mainly through epigenetic mechanisms. The epigenetic changes induced in an unfavorable developmental environment have lifelong effects on cardiovascular and metabolic functions, susceptibility to cardiovascular disease, obesity, and other NCD. Although compared with animals, epigenetic analysis of human specimens is restricted except for peripheral blood, placental, or umbilical specimens, recently, important human studies have been reported concerning the epigenetic analysis of Line 1 gene from the umbilical blood, umbilical RXRα, or the peripheral nuclear cell IGF-2. The birth weight is an indirect marker of in-the-womb nutritional status. The incidence of low-birth-weight infants, weighing less than 2,500 g, has been increasing in Japan. Presently, it is higher than that in the latter half of the 20 s of the Showa era, and is the highest among the OECD countries. This trend suggests that in Japan the intrauterine nutritional status has been deteriorating. We have to change this trend and put much attention on the prepregnancy and pregnancy nutrition for the present and future generations.

  18. The microstructure and formation of biological soil crusts in their early developmental stage

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yuanming

    2005-01-01

    The biological soil crust serves as one of the biological factors contributing to the sand fixation in the Gurbantunggut Desert, the largest fixed and semi-fixed desert in China. This study was conducted to investigate the microstructure and formation of biological soil crusts which develop as a result of occurrence of cryptogams. One year after removal of biological soil crusts, the exposed surface could be fixed by bacteria, which make sand particles cohere by exopolysaccharides. The exopolysaccharides were mainly composed of glucose, mannitol, arabinose and galactose. The intension of pressure for this kind of crust is 13.42±1.38 Pa. After four-year recovery of the exposed sandy surface, the biological soil crust resulting from the colonization of soil surface by communities of filamentous cyanobacteria were mainly dominated by Microcoleus, which occurred as a cluster of filaments surrounded by a gelatinous sheath. At this developmental stage, the main contributors for sand fixation were changed from bacteria to filamentous cyanobacteria. Microscopic examination of this kind of crust revealed an intricate network of filamentous cyanobacteria and extracellular polymer secretions, which binds and entraps mineral particles and finer particles on the filament surface. These effects enhance soil cohesion and resistance to erosion. The intension of pressure for this kind of crust is 32.53±3.08 Pa.

  19. The Effects of Subchronic Exposure to Terbuthylazine on Early Developmental Stages of Common Carp

    Directory of Open Access Journals (Sweden)

    Stanislava Štěpánová

    2012-01-01

    Full Text Available The aim of this study was to assess the impact of terbuthylazine in surface waters on fish under experimental conditions. Subchronic toxic effects on embryos and larvae of common carp (Cyprinus carpio were investigated during a 30-day toxicity test. The exposure to terbuthylazin showed no effect on mortality, but significant differences (P<0.0001 were revealed on weight and growth parameters at concentrations of 520 and 820 μg/L. The inhibition of specific growth rate at concentrations of 520 and 820 μg/L was 14% compared to the control group. No significant negative effects on total body length and body weight were observed at lower concentrations (0.9 and 160 μg/L. The concentrations 520 and 820 μg/L were associated with a delay in development compared to other experimental groups and controls. On the basis of weight and growth rate evaluation and determination of developmental stages, the No Observed Effect Concentration (NOEC of terbuthylazine was estimated at 160 μg/L and the Lowest Observed Effect Concentration (LOEC was 520 μg/L. According to these results, the reported environmental concentration of terbuthylazine in Czech rivers does not impact growth, development, morphology, or histology of carp embryos and larvae.

  20. Early failure of Pavlik harness treatment for developmental hip dysplasia: clinical and ultrasound predictors.

    Science.gov (United States)

    Lerman, J A; Emans, J B; Millis, M B; Share, J; Zurakowski, D; Kasser, J R

    2001-01-01

    A cohort of 93 patients with developmental dysplasia of the hip (DDH) treated with a Pavlik harness were evaluated to determine predictors of treatment failure. Failure was defined as failure to achieve or maintain hip reduction in the Pavlik harness. Of 93 patients (137 hips), 17 (26 hips) failed Pavlik harness treatment. Univariate risk factors for failure included bilaterality, initial clinical exam, and initial ultrasound (US) percent coverage. Clinical exam and initial percent coverage were multivariate risk factors for failure. Among initially clinically dislocatable hips, a low initial US alpha angle correlated with an increased likelihood of failure. All (6/6) patients with an initially irreducible hip and an initial coverage of <20% by US eventually failed treatment. Gender, side of pathology, and age at diagnosis and initiation of treatment did not correlate with failure. Irreducibility by physical exam combined with US coverage of <20% identified a patient group that uniformly failed Pavlik harness treatment. These patients may be candidates for alternative bracing, traction, or closed or open reduction.

  1. Differential immune response of rainbow trout (Oncorhynchus mykiss) at early developmental stages (larvae and fry) against the bacterial pathogen Yersinia ruckeri

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar; Raida, Martin Kristian; Kania, Per Walter;

    2012-01-01

    Innate immune factors play a crucial role in survival of young fish especially during early stages of life when adaptive immunity is not fully developed. In the present study, we investigated the immune response of rainbow trout (Oncorhynchus mykiss) larvae and fry at an early stage of development...... trout fry with Y. ruckeri, in contrast, induced a cumulative mortality of 74%. A high expression of cytokines (IL-1b, TNF-a, IL-22, IL-8 and IL- 10), acute phase proteins (SAA, hepcidin, transferrin and precerebellin), complement factors (C3, C5 and factor B), antimicrobial peptide (cathelicidin-2...... at early developmental stages. A dense covering of surfaces of gill filaments by IgT antibody in the young fish suggest a role of this antibody as innate immune factor at early developmental stages....

  2. Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

    Science.gov (United States)

    Essex, Marilyn J.; Boyce, W. Thomas; Hertzman, Clyde; Lam, Lucia L.; Armstrong, Jeffrey M.; Neumann, Sarah M.A.; Kobor, Michael S.

    2011-01-01

    Fifteen-year-old adolescents (N=109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents’ infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide (CpG) sites within DNA derived from buccal epithelial cells showed differential methylation among adolescents whose parents reported high levels of stress during their children’s early lives. Maternal stressors in infancy and paternal stressors in the preschool years were most strongly predictive of differential methylation, and the patterning of such epigenetic marks varied by children’s gender. To the authors’ knowledge, this is the first report of prospective associations between adversities in early childhood and the epigenetic conformation of adolescents’ genomic DNA. PMID:21883162

  3. Retinoic acid is enriched in Hensen's node and is developmentally regulated in the early chicken embryo.

    OpenAIRE

    Chen, Y; Huang, L; Russo, A F; Solursh, M

    1992-01-01

    Retinoic acid (RA) has been considered as a potential morphogen in the chicken limb and has also been suggested to be involved in early embryonic development. On the basis of biological activity, previous reports suggest that Hensen's node, the anatomical equivalent in the chicken of the Spemann's organizer, may contain RA. Here, by using a molecular assay system, we demonstrate that Hensen's node contains retinoids in a concentration approximately 20 times more than that in the neighboring t...

  4. [Evaluating language acquisition using the Early Language Milestone (ELM) and Munich developmental scales].

    Science.gov (United States)

    Páez-Pineda, Oscar D; Valencia-Valencia, Doris; Ortiz Calderón, Martha Vanessa

    2014-01-01

    Evaluating language development by comparing the Munich Development method to the Early Language Milestone scale for identifying both diagnostic tests' agreement and enriching neurodevelopmental consultation. The clinical histories of a cohort of 129 children were evaluated, as prematurity is a risk factor for deviation in children's language development. The children had less than 40 weeks gestational age and 0 to 12 months corrected age. They were given both tests between 2008 and 2011. The results from both scales were compared regarding receptive and expressive language and visual response (Early Language Milestone scale) and evaluation of verbal response, vocal play, understanding and expression (Munich scale). Student's T-test was used for comparing means for paired samples. Results: A statistically significant correlation (p<0.05) was found between both tests and between them and corrected age. It was seen that the higher the corrected age, the greater correlation there was between tests. The Early Language Milestone and Munich Development scales, regarding their components dealing with language, both represent useful tools for following-up premature children's language development.

  5. Parent-Reported Attention Deficit/Hyperactivity Symptomatology in Preschool-Aged Children: Factor Structure, Developmental Change, and Early Risk Factors

    Science.gov (United States)

    Willoughby, Michael T.; Pek, Jolynn; Greenberg, Mark T.

    2012-01-01

    Although Attention Deficit/Hyperactivity Disorder (ADHD) has increasingly been studied in preschool-aged children, relatively few studies have provided a comprehensive evaluation of the factor structure and patterns of developmental changes in parent-reported ADHD symptomatology across the early childhood period. This study used confirmatory…

  6. The Study to Explore Early Development (SEED): A Multisite Epidemiologic Study of Autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network

    Science.gov (United States)

    Schendel, Diana E.; DiGuiseppi, Carolyn; Croen, Lisa A.; Fallin, M. Daniele; Reed, Philip L.; Schieve, Laura A.; Wiggins, Lisa D.; Daniels, Julie; Grether, Judith; Levy, Susan E.; Miller, Lisa; Newschaffer, Craig; Pinto-Martin, Jennifer; Robinson, Cordelia; Windham, Gayle C.; Alexander, Aimee; Aylsworth, Arthur S.; Bernal, Pilar; Bonner, Joseph D.; Blaskey, Lisa; Bradley, Chyrise; Collins, Jack; Ferretti, Casara J.; Farzadegan, Homayoon; Giarelli, Ellen; Harvey, Marques; Hepburn, Susan; Herr, Matthew; Kaparich, Kristina; Landa, Rebecca; Lee, Li-Ching; Levenseller, Brooke; Meyerer, Stacey; Rahbar, Mohammad H.; Ratchford, Andria; Reynolds, Ann; Rosenberg, Steven; Rusyniak, Julie; Shapira, Stuart K.; Smith, Karen; Souders, Margaret; Thompson, Patrick Aaron; Young, Lisa; Yeargin-Allsopp, Marshalyn

    2012-01-01

    The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal,…

  7. The Study to Explore Early Development (SEED): A Multisite Epidemiologic Study of Autism by the Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDRE) Network

    Science.gov (United States)

    Schendel, Diana E.; DiGuiseppi, Carolyn; Croen, Lisa A.; Fallin, M. Daniele; Reed, Philip L.; Schieve, Laura A.; Wiggins, Lisa D.; Daniels, Julie; Grether, Judith; Levy, Susan E.; Miller, Lisa; Newschaffer, Craig; Pinto-Martin, Jennifer; Robinson, Cordelia; Windham, Gayle C.; Alexander, Aimee; Aylsworth, Arthur S.; Bernal, Pilar; Bonner, Joseph D.; Blaskey, Lisa; Bradley, Chyrise; Collins, Jack; Ferretti, Casara J.; Farzadegan, Homayoon; Giarelli, Ellen; Harvey, Marques; Hepburn, Susan; Herr, Matthew; Kaparich, Kristina; Landa, Rebecca; Lee, Li-Ching; Levenseller, Brooke; Meyerer, Stacey; Rahbar, Mohammad H.; Ratchford, Andria; Reynolds, Ann; Rosenberg, Steven; Rusyniak, Julie; Shapira, Stuart K.; Smith, Karen; Souders, Margaret; Thompson, Patrick Aaron; Young, Lisa; Yeargin-Allsopp, Marshalyn

    2012-01-01

    The Study to Explore Early Development (SEED), a multisite investigation addressing knowledge gaps in autism phenotype and etiology, aims to: (1) characterize the autism behavioral phenotype and associated developmental, medical, and behavioral conditions and (2) investigate genetic and environmental risks with emphasis on immunologic, hormonal,…

  8. Risk Factors of Children Who Exited from an Early Intervention Program without an Identified Disability and Returned with a Developmental Disability

    Science.gov (United States)

    Giannoni, Peggy P.; Kass, Philip H.

    2010-01-01

    A retrospective cohort study was undertaken to identify risk factors for children at greatest risk of delayed diagnosis of developmental disability. Two thousand four hundred and thirty-nine children were selected for this study due to their participation in the California Early Start (ES) Program in 1998. Comparisons were made among children that…

  9. Social visual engagement in infants and toddlers with autism: early developmental transitions and a model of pathogenesis.

    Science.gov (United States)

    Klin, Ami; Shultz, Sarah; Jones, Warren

    2015-03-01

    Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism.

  10. Social visual engagement in infants and toddlers with autism: Early developmental transitions and a model of pathogenesis

    Science.gov (United States)

    Klin, Ami; Shultz, Sarah; Jones, Warren

    2014-01-01

    Efforts to determine and understand the causes of autism are currently hampered by a large disconnect between recent molecular genetics findings that are associated with the condition and the core behavioral symptoms that define the condition. In this perspective piece, we propose a systems biology framework to bridge that gap between genes and symptoms. The framework focuses on basic mechanisms of socialization that are highly-conserved in evolution and are early-emerging in development. By conceiving of these basic mechanisms of socialization as quantitative endophenotypes, we hope to connect genes and behavior in autism through integrative studies of neurodevelopmental, behavioral, and epigenetic changes. These changes both lead to and are led by the accomplishment of specific social adaptive tasks in a typical infant's life. However, based on recent research that indicates that infants later diagnosed with autism fail to accomplish at least some of these tasks, we suggest that a narrow developmental period, spanning critical transitions from reflexive, subcortically-controlled visual behavior to interactional, cortically-controlled and social visual behavior be prioritized for future study. Mapping epigenetic, neural, and behavioral changes that both drive and are driven by these early transitions may shed a bright light on the pathogenesis of autism. PMID:25445180

  11. Heavy alcohol use in early adulthood as a function of childhood ADHD: developmentally specific mediation by social impairment and delinquency.

    Science.gov (United States)

    Molina, Brooke S G; Walther, Christine A P; Cheong, Jeewon; Pedersen, Sarah L; Gnagy, Elizabeth M; Pelham, William E

    2014-04-01

    Frequent heavy drinking in early adulthood, particularly prior to age 21, is associated with multiple health and legal consequences including continued problems with drinking later into adulthood. Children with attention-deficit/hyperactivity disorder (ADHD) are at risk of alcohol use disorder in adulthood, but little is known about their frequency of underage drinking as young adults or about mediational pathways that might contribute to this risky outcome. The current study used data from the Pittsburgh ADHD Longitudinal Study to test social impairment and delinquency pathways from childhood ADHD to heavy drinking in early adulthood for individuals with (n = 148) and without (n = 117) childhood ADHD. Although ADHD did not predict heavy drinking, indirect mediating effects in opposing directions were found. A delinquency pathway from childhood ADHD to increased heavy drinking included adolescent and subsequently adult delinquent behavior. A social impairment pathway from childhood ADHD to decreased heavy drinking included adolescent, but not adult, social impairment. These findings help explain the heterogeneity of results for alcohol use among individuals with ADHD and suggest that common ADHD-related impairments may operate differently from each other and distinctly across developmental periods. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  12. Musicians' Enhanced Neural Differentiation of Speech Sounds Arises Early in Life: Developmental Evidence from Ages 3 to 30

    Science.gov (United States)

    Strait, Dana L.; O'Connell, Samantha; Parbery-Clark, Alexandra; Kraus, Nina

    2014-01-01

    The perception and neural representation of acoustically similar speech sounds underlie language development. Music training hones the perception of minute acoustic differences that distinguish sounds; this training may generalize to speech processing given that adult musicians have enhanced neural differentiation of similar speech syllables compared with nonmusicians. Here, we asked whether this neural advantage in musicians is present early in life by assessing musically trained and untrained children as young as age 3. We assessed auditory brainstem responses to the speech syllables /ba/ and /ga/ as well as auditory and visual cognitive abilities in musicians and nonmusicians across 3 developmental time-points: preschoolers, school-aged children, and adults. Cross-phase analyses objectively measured the degree to which subcortical responses differed to these speech syllables in musicians and nonmusicians for each age group. Results reveal that musicians exhibit enhanced neural differentiation of stop consonants early in life and with as little as a few years of training. Furthermore, the extent of subcortical stop consonant distinction correlates with auditory-specific cognitive abilities (i.e., auditory working memory and attention). Results are interpreted according to a corticofugal framework for auditory learning in which subcortical processing enhancements are engendered by strengthened cognitive control over auditory function in musicians. PMID:23599166

  13. Parent-child conflict and early childhood adjustment in two-parent low-income families: parallel developmental processes.

    Science.gov (United States)

    Weaver, Chelsea M; Shaw, Daniel S; Crossan, Jennifer L; Dishion, Thomas J; Wilson, Melvin N

    2015-02-01

    Parent-child conflict is central to most intervention models focused on reducing child problem behavior, yet few longitudinal studies have examined these processes during early childhood. The current study investigates (1) growth in mother-child and father figure (FF)-child conflict, (2) associations between trajectories of mother-child and FF-child conflict and children's adjustment; and (3) intervention effects in attenuating conflict. Participants are 195 ethnically diverse mother-FF-child triads drawn from a larger parenting intervention study for families with children at risk for developing conduct problems. Mother-child conflict decreased from ages 2 to 4, but decreases were unrelated to changes in children's adjustment problems. In contrast, the slope of FF-child conflict was positively related to the slope of child externalizing behaviors. Random assignment to a family-centered parenting intervention predicted rate of decline in mother-child conflict. Findings are discussed with respect to developmental patterns of parent-child conflict in early childhood and implications for prevention.

  14. Early reproductive developmental anatomy in Decaisnea (Lardizabalaceae) and its systematic implications.

    Science.gov (United States)

    Wang, Hua-Feng; Friedman, Cynthia Ross; Zhu, Zhi-Xin; Qin, Hai-Ning

    2009-11-01

    Decaisnea insignis, known as 'dead man's fingers' (Lardizabalaceae), is widely distributed in China and the Himalayan foothill countries. This economically important plant, which is the only species in the genus, has not been the subject of any embryological studies aside from one brief, older paper that lacks micrographs. Data on Decaisnea are also important because its systematic position has been unstable since the genus was established in 1855. Therefore, the objectives of this study were: (a) to use modern microscopy to document early reproductive anatomical development in Decaisnea; and (b) to compare qualitatively these early embryological characters with allied taxa in a systematic context. Decaisnea insignis floral buds and inflorescences were regularly collected from Shaanxi Province, China and prepared for light microscopy. The embryological characters studied were qualitatively compared with those of allied taxa via a thorough examination of the existing literature. Early reproductive anatomy in Decaisnea was documented and novel revelations made. It was discovered that the pollen is shed when three-celled (not two-celled, as previously reported), and that endosperm formation is nuclear (not cellular or helobial, as previously reported). These two newly revealed embryological characters are not found in any other members of Lardizabalaceae. Furthermore, neither are persistent antipodal cells, which we confirmed to be present in Decaisnea. Decaisnea and other Lardizabalaceae characteristically have tetrasporangiate anthers, a secretory tapetum, simultaneous microsporocyte cytokinesis, primarily bitegmic, crassinucellate ovules, and a Polygonum type embryo sac. However, in the family, persistent antipodals, nuclear endosperm, and pollen shed at the three-celled stage are only found in Decaisnea. These embryological data prompted the suggestion that Decaisnea needs elevation above the level of genus.

  15. Early interventions for youths at high risk for bipolar disorder: a developmental approach.

    Science.gov (United States)

    Benarous, Xavier; Consoli, Angèle; Milhiet, Vanessa; Cohen, David

    2016-03-01

    In recent decades, ongoing research programmes on primary prevention and early identification of bipolar disorder (BD) have been developed. The aim of this article is to review the principal forms of evidence that support preventive interventions for BD in children and adolescents and the main challenges associated with these programmes. We performed a literature review of the main computerised databases (MEDLINE, PUBMED) and a manual search of the literature relevant to prospective and retrospective studies of prodromal symptoms, premorbid stages, risk factors, and early intervention programmes for BD. Genetic and environmental risk factors of BD were identified. Most of the algorithms used to measure the risk of developing BD and the early interventions programmes focused on the familial risk. The prodromal signs varied greatly and were age dependent. During adolescence, depressive episodes associated with genetic or environmental risk factors predicted the onset of hypomanic/manic episodes over subsequent years. In prepubertal children, the lack of specificity of clinical markers and difficulties in mood assessment were seen as impeding preventive interventions at these ages. Despite encouraging results, biomarkers have not thus far been sufficiently validated in youth samples to serve as screening tools for prevention. Additional longitudinal studies in youths at high risk of developing BD should include repeated measures of putative biomarkers. Staging models have been developed as an integrative approach to specify the individual level of risk based on clinical (e.g. prodromal symptoms and familial history of BD) and non-clinical (e.g. biomarkers and neuroimaging) data. However, there is still a lack of empirically validated studies that measure the benefits of using these models to design preventive intervention programmes.

  16. Young Children With Autism Spectrum Disorders - Importance Of Early Developmental And Behavioural Interventions

    Directory of Open Access Journals (Sweden)

    Beena Johnson

    2015-04-01

    Full Text Available Children with autism spectrum disorders have impairment in reciprocal social interaction and impairment in communication skills. They also have repetitive behaviours and preoccupation with stereotyped patterns of behaviours. The most important therapy is early individualized intensive behavioural intervention. Intensive behavioural interventions should be provided to all young children at the onset of symptoms. If not, they will have lifelong difficulties in communication and social interaction. Parent mediated behavioural interventions are effective in the management of young children with autism spectrum disorders. Children with autistic symptoms who receive earlier referrals to specialists and obtain intensive behavioural intervention achieve optimal outcomes.

  17. Vanadate induces necrotic death in neonatal rat cardiomyocytes through mitochondrial membrane depolarization.

    Science.gov (United States)

    Soares, Sandra Sofia; Henao, Fernando; Aureliano, Manuel; Gutiérrez-Merino, Carlos

    2008-03-01

    Besides the well-known inotropic effects of vanadium in cardiac muscle, previous studies have shown that vanadate can stimulate cell growth or induce cell death. In this work, we studied the toxicity to neonatal rat ventricular myocytes (cardiomyocytes) of two vanadate solutions containing different oligovanadates distribution, decavanadate (containing decameric vanadate, V 10) and metavanadate (containing monomeric vanadate and also di-, tetra-, and pentavanadate). Incubation for 24 h with decavanadate or metavanadate induced necrotic cell death of cardiomyocytes, without significant caspase-3 activation. Only 10 microM total vanadium of either decavanadate (1 microM V 10) or metavanadate (10 microM total vanadium) was needed to produce 50% loss of cell viability after 24 h (assessed with MTT and propidium iodide assays). Atomic absorption spectroscopy showed that vanadium accumulation in cardiomyocytes after 24 h was the same when incubation was done with decavanadate or metavanadate. A decrease of 75% of the rate of mitochondrial superoxide anion generation, monitored with dihydroethidium, and a sustained rise of cytosolic calcium (monitored with Fura-2-loaded cardiomyocytes) was observed after 24 h of incubation of cardiomyocytes with decavanadate or metavanadate concentrations close to those inducing 50% loss of cell viability produced. In addition, mitochondrial membrane depolarization within cardiomyocytes, monitored with tetramethylrhodamine ethyl esther or with 3,3',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide, were observed after only 6 h of incubation with decavanadate or metavanadate. The concentration needed for 50% mitochondrial depolarization was 6.5 +/- 1 microM total vanadium for both decavanadate (0.65 microM V 10) and metavanadate. In conclusion, mitochondrial membrane depolarization was an early event in decavanadate- and monovanadate-induced necrotic cell death of cardiomyocytes.

  18. Intervening early to reduce developmentally harmful substance use among youth populations.

    Science.gov (United States)

    Lubman, Dan I; Hides, Leanne; Yücel, Murat; Toumbourou, John W

    2007-10-01

    Early-onset or frequent substance use during adolescence increases the risk of developing mental health problems, as well as a range of other adverse outcomes (eg, alcohol or drug dependence, educational underachievement, health problems, social difficulties) during late adolescence and early adulthood. Increases in rates of risky drinking among young people are particularly concerning, suggesting that an effective, evidence-based alcohol policy and preventive framework needs to be developed. Restricting the supply of licit and illicit substances to adolescents, delaying the age that licit substances can be legally purchased, reducing positive media portrayals of substance use, and banning targeted promotions, should be universal, public prevention priorities. Mass-media campaigns need to deliver coherent and credible evidence-based messages to young people, utilising a broad array of dissemination strategies. Clear policy and guidelines for parents regarding appropriate alcohol use for adolescents also need to be developed. Prevention programs should target children and adolescents in families with parents who use drugs, young people who have been suspended from school, or those with mental health problems. Preventive screening and targeted brief interventions can be effectively delivered in a variety of settings by a range of health professionals.

  19. The "early life" origins of obesity-related health disorders: new discoveries regarding the intergenerational transmission of developmentally programmed traits in the global cardiometabolic health crisis.

    Science.gov (United States)

    Benyshek, Daniel C

    2013-12-01

    Popular media reports concerning the causes of the current global obesity pandemic and its related sequelae-the cardiometabolic syndrome-are often couched in terms of dramatic changes in diet and lifestyle around the world; namely, drastically increasing dietary intakes of high energy foods and plummeting levels of daily physical activity-the hallmarks of the so called "nutrition transition." Far less attention is generally drawn to the important role phenotypic plasticity during early life (i.e., "developmental programming") plays in the cardiometabolic health crisis. Recently, however, researchers working within the field of the developmental origins of health and disease (DOHaD) and epigenetics have extended our understanding of the role played by these developmental processes and capacities in health and disease even further by investigating the transmissible nature of developmentally programmed cardiometabolic traits to subsequent generations. In this review, after briefly revisiting the fundamental discoveries of first-generation DOHaD research, I consider how recent discoveries regarding the transmissibility of developmentally acquired traits are providing new insights into the current global cardiometabolic pandemic, and how a better understanding of developmental programming-including transmissibility-are essential for the conceptualization and implementation of public health initiatives aimed at stemming this global health crisis.

  20. Early developmental stages of Ascaris lumbricoides featured by high-resolution mass spectrometry.

    Science.gov (United States)

    Melo, Carlos Fernando Odir Rodrigues; Esteves, Cibele Zanardi; de Oliveira, Rosimeire Nunes; Guerreiro, Tatiane Melina; de Oliveira, Diogo Noin; Lima, Estela de Oliveira; Miné, Júlio César; Allegretti, Silmara Marques; Catharino, Rodrigo Ramos

    2016-11-01

    Ascaris lumbricoides is responsible for a highly disseminated helminth parasitic disease, ascariosis, a relevant parasitosis that responds for great financial burden on the public health system of developing countries. In this work, metabolic fingerprinting using high-resolution mass spectrometry (HRMS) was employed to identify marker molecules from A. lumbricoides in different development stages. We have identified nine biomarkers, such as pheromones and steroidal prohormones in early stages, among other molecules in late development stages, making up four molecules for fertilized eggs, four marker molecules for first larvae (L1) and one marker molecule for third larvae (L3). Therefore, our findings indicate that this approach is suitable for biochemical characterization of A. lumbricoides development stages. Moreover, the straightforward analytical method employed, with almost no sample preparation from a complex matrix (feces) using high-resolution mass spectrometry, suggests that it is possible to seek for an easier and faster way to study animal molding processes.

  1. Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas.

    Directory of Open Access Journals (Sweden)

    Diane I Schroeder

    2015-08-01

    Full Text Available Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs and highly methylated domains (HMDs with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo.

  2. The response of the early developmental stages of Laminaria japonica to enhanced ultraviolet-B radiation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The responses of the early development of Laminaria japonica collected from Kiaochow Bay in China to enhanced ultraviolet-B radiation (UV-B, 280—320 nm) were studied in the laboratory. The low UV-B ra-diations (11.7—23.4 J·m-2·d-1) had no significant effects on zoospores attachment, but when the UV-B dose > 35.1 J·m-2·d-1 the attachment decreased significantly compared with the control. Germination of embryospores was >93% under the low (11.7—35.1 J·m-2·d-1) doses, and in the range of 78.5%—88.5% under the high (46.8—70.2 J·m-2·d-1) UV-B doses, indicating a significant radiation effect. Under the higher UV-B exposure (35.1—70.2 J·m-2·d-1), all of the few gametophytes formed from embryospores died 120 h post-release. After exposure to the low UV-B radiation (11.7—23.4 J·m-2·d-1), the formation of sporophytes decreased and the female gametophyte clones increased compared with the control. However, the sex ratio and the relative growth of female gametophytes/sporophytes had not signifi-cantly changed. According to the results, enhanced UV-B radiation has a significant effect on the early development of L. japonica under laboratory conditions, suggesting that the UV-B radiation could not be overlooked as one of the important environmental factors influencing the ontogeny of macroalgae living in marine ecosystems.

  3. The response of the early developmental stages of Laminaria japonica to enhanced ultraviolet-B radiation

    Institute of Scientific and Technical Information of China (English)

    LIU Su; ZHANG QuanSheng; WANG You; JU Qing; TANG XueXi

    2008-01-01

    The responses of the early development of Laminaria japonica collected from Kiaochow Bay in China to enhanced ultraviolet-B radiation (UV-B, 280-320 nm) were studied in the laboratory. The low UV-B radiations (11.7-23.4 J·m-2·d-) had no significant effects on zoospores attachment, but when the UV-B dose > 35.1 J·m-2·d-1 the attachment decreased significantly compared with the control. Germination of embryosperes was >93% under the low (11.7-35.1 J·m-2·d-1) doses, and in the range of 78.5%-88.5% under the high (46.8-70.2 J·m-2·d-1) UV-B doses, indicating a significant radiation effect. Under the higher UV-B exposure (35.1-70.2 J·m-2·d-1), all of the few gametophytes formed from embryospores died 120 h post-release. After exposure to the low UV-B radiation (11.7-23.4 J·m-2·d-1), the formation of sporophytes decreased and the female gametophyte clones increased compared with the control. However, the sex ratio and the relative growth of female gametophytes/sporophytes had not significantly changed. According to the results, enhanced UV-B radiation has a significant effect on the early development of L. japonica under laboratory conditions, suggesting that the UV-B radiation could not be overlooked as one of the important environmental factors influencing the ontogeny of macroalgae living in marine ecosystems.

  4. Closed Reduction for Developmental Dysplasia of the Hip: Early-term Results From a Prospective, Multicenter Cohort.

    Science.gov (United States)

    Sankar, Wudbhav N; Gornitzky, Alex L; Clarke, Nicholas M P; Herrera-Soto, José A; Kelley, Simon P; Matheney, Travis; Mulpuri, Kishore; Schaeffer, Emily K; Upasani, Vidyadhar V; Williams, Nicole; Price, Charles T

    2016-11-11

    Closed reduction (CR) is a common treatment for infantile developmental dysplasia of the hip. The purpose of this observational, prospective, multicenter study was to determine the early outcomes following CR. Prospectively collected data from an international multicenter study group was analyzed for patients treated from 2010 to 2014. Baseline demographics, clinical exam, radiographic/ultrasonographic data, and history of previous orthotic treatment were assessed. At minimum 1-year follow-up, failure was defined as an IHDI grade 3 or 4 hip and/or need for open reduction. The incidence of avascular necrosis (AVN), residual dysplasia, and need for further surgery was assessed. A total of 78 patients undergoing CR for 87 hips were evaluated with a median age at initial reduction of 8 months (range, 1 to 20 mo). Of these, 8 hips (9%) were unable to be closed reduced initially. At most recent follow-up (median 22 mo; range, 12 to 36 mo), 72/79 initially successful CRs (91%) remained stable. The likelihood of failure was unaffected by initial clinical reducibility of the hip (P=0.434), age at initial CR (P=0.897), or previous treatment in brace (P=0.222). Excluding those hips that failed initial CR, 18/72 hips (25%) developed AVN, and the risk of osteonecrosis was unaffected by prereduction reducibility of the hip (P=0.586), age at CR (P=0.745), presence of an ossific nucleus (P=0.496), or previous treatment in brace (P=0.662). Mean acetabular index on most recent radiographs was 25 degrees (±6 degrees), and was also unaffected by any of the above variables. During the follow-up period, 8/72 successfully closed reduced hips (11%) underwent acetabular and/or femoral osteotomy for residual dysplasia. Following an initially successful CR, 9% of hips failed reduction and 25% developed radiographic AVN at early-term follow-up. History of femoral head reducibility, previous orthotic bracing, and age at CR did not correlate with success or chances of developing AVN. Further

  5. Comparison of cardiomyocyte apoptosis and early postoperative recovery between propofol-and midazolam-combined anesthesia in patients undergoing cardiac valve replacement%异丙酚或咪达唑仑复合麻醉下心脏手术患者心肌细胞凋亡及术后早期恢复的比较

    Institute of Scientific and Technical Information of China (English)

    诸绍君; 周燕丰; 祝胜美

    2010-01-01

    Objective To compare the cardiomyocyte apoptosis and early postoperative recovery in patients undergoing cardiac valve replacement under propofol-or midazolam-combined anesthesia.Methods Forty NYHA class Ⅱ or Ⅲ patients (aged 48-64 yr and weighing 45-78 kg) undergoing cardiac valve replacement with cardiopulmonary bypass (CPB) were randomly divided into midazolam group (Group M) and propofol group (Group P) (n=20each). The patients were premedicated with morphine 0.1 mg/kg i.v. and scopolamine 0.3 mg i.v. Anesthesia was induced with midazolam 0.2 mg/kg (in Group M) or propofol 2 mg/kg (in Group P) combined with fentanyl 10 μg/kg and vecuronium 0.1 mg/kg, and maintained with propofol 5 mg. kg-1·h-1 (in Group P) or midazolam 0.1 mg·kg-1·h-1(in Group M) and intermittent i.v. boluses of fentanyl and vecuronium after tracheal intubation. The patients were mechanically ventilated with PETCO2 maintained at 35-45 mm Hg. Myocardial tissues were obtained from the right atrium before and after CPB for determination of apoptosis in cardiomyocytes (by TUNEL). The apoptotic index was calculated. The expression of caspase-3 and caspase-9 was determined by immunohistochemical avidin-biotin-peroxidase complex (ABC) technique staining. The mean airway pressure (MAP) and heart rate (HR) were monitored. Aortic cross-clamping time, surgical and CPB times, spontaneous recovery of normal heart beat, emergence from anesthesia, extubation time and duration of ICU stay were recorded and compared between the two groups.Results The percentage of spontaneous recovery of normal heart beat after release of aortic cross clamp was significantly higher and the need for dobutamine support was significantly less in Group P than in Group M ( P < 0.05). The emergence from anesthesia was significantly more rapid, the extubation time and the ICU stay were significantly shorter in Group P than in Group M (P<0.05). There were no significant differences in apoptosis index and expression of

  6. The impact of caffeine on connexin expression in the embryonic chick cardiomyocyte micromass culture system.

    Science.gov (United States)

    Ahir, Bhavesh K; Pratten, Margaret K

    2016-07-01

    Cardiomyocytes are electrically coupled by gap junctions, defined as clusters of low-resistance multisubunit transmembrane channels composed of connexins (Cxs). The expression of Cx40, Cx43 and Cx45, which are present in cardiomyocytes, is known to be developmentally regulated. This study investigates the premise that alterations in gap junction proteins are one of the mechanisms by which teratogens may act. Specifically, those molecules known to be teratogenic in humans could cause their effects via disruption of cell-to-cell communication pathways, resulting in an inability to co-ordinate tissue development. Caffeine significantly inhibited contractile activity at concentrations above and including 1500 μm (P caffeine on key cardiac gap junction protein (Cx40, Cx43 and Cx45) expression were analysed using immunocytochemistry and in-cell Western blotting. The results indicated that caffeine altered the expression pattern of Cx40, Cx43 and Cx45 at non-cytotoxic concentrations (≥2000 μm), i.e., at concentrations that did not affect total cell protein and cell viability. In addition the effects of caffeine on cardiomyocyte formation and function (contractile activity score) were correlated with modulation of Cxs (Cx40, Cx43 and Cx45) expression, at above and including 2000 μm caffeine concentrations (P < 0.05). These experiments provide evidence that embryonic chick cardiomyocyte micromass culture may be a useful in vitro method for mechanistic studies of perturbation of embryonic heart development. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    Science.gov (United States)

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Biochemical response to exposure to six textile dyes in early developmental stages of Xenopus laevis.

    Science.gov (United States)

    Güngördü, Abbas; Birhanli, Ayse; Ozmen, Murat

    2013-01-01

    The present study was undertaken to determine the toxic effect of a lethal concentration of six different commercially used textile dyes on the 46th stage of Xenopus laevis tadpoles. The tadpoles were exposed to Astrazon Red FBL, Astrazon Blue FGRL, Remazol Red RR, Remazol Turquoise Blue G-A, Cibacron Red FN-3G, and Cibacron Blue FN-R for 168 h in static test conditions, and thus, 168-h median lethal concentrations (LC(50)s) of each dye were determined to be 0.35, 0.13, 112, 7, 359, and 15.8 mg/L, respectively. Also, to evaluate the sublethal effects of each dye, tadpoles were exposed to different concentrations of dyes (with respect to 168-h LC(50)s) for 24 h. The alteration of selected enzyme activities was tested. For this aim, glutathione S-transferase (GST), carboxylesterase, and lactate dehydrogenase (LDH) were assayed. After dye exposure, the GST induction or inhibition and LDH induction indicated some possible mechanisms of oxidative stress and deterioration in aerobic respiration processes induced by the tested dyes. Findings of the study suggest that selected biomarker enzymes are useful in understanding the toxic mechanisms of these dyes in X. laevis tadpoles as early warning indicators. Therefore, these selected biomarkers may evaluate the effect of environmental factors, such as textile dye effluents and other industrial pollutants, on amphibians in biomonitoring studies.

  9. Temperature, paternity and asynchronous hatching influence early developmental characteristics of larval Atlantic cod, Gadus morhua

    DEFF Research Database (Denmark)

    Politis, Sebastian Nikitas; Dahlke, Flemming T.; Butts, Ian A.E.

    2014-01-01

    Offspring, especially during early development, are influenced by both intrinsic properties endowed to them by their parents, extrinsic environmental factors as well as the interplay between genes and the environment. We investigated the effects of paternity (P), temperature (T), and asynchronous...... hatching on larval traits of cod, Gadus morhua from the Atlantic Ocean and the Baltic Sea. Daily cohorts of 4 half-sib families of Atlantic larvae and 5 half-sib families of Baltic larvae were incubated and hatched at 5 temperatures (Atlantic 2.0-10.0°C, Baltic 6.5-12.5°C) and imaged for notochord length......, respectively. In Baltic larvae, size at peak hatch tended to decrease with increasing T and P × T explained 34.6% of the variance. In Atlantic larvae, growth, YUR and YUE were influenced by T while P alone explained 26.0% of the variance in YUE and up to 66.4% of variance in morphological traits at 4 DPH...

  10. Developmental trajectories of anxiety symptoms in early adolescence: the influence of anxiety sensitivity.

    Science.gov (United States)

    Allan, Nicholas P; Capron, Daniel W; Lejuez, Carl W; Reynolds, Elizabeth K; MacPherson, Laura; Schmidt, Norman B

    2014-05-01

    Children and adolescents seem to suffer from anxiety disorders at rates similar to adults. Interestingly, anxiety symptoms appear to generally decline over time within children as evidenced by lower rates in early and middle adolescence. There is some evidence that there may be heterogeneous subpopulations of adolescent children with different trajectories of anxiety symptoms, including a class of adolescents with elevated levels of anxiety that do not dissipate over time. Anxiety sensitivity has been identified as an important risk factor in the development of anxiety psychopathology. This study prospectively examined the development of anxiety symptoms in a sample of 277 adolescents (M age = 11.52; 44 % female, 56 % male) over a 3 year period including the influence of anxiety sensitivity on this development. Further, this study investigated whether there were distinct classes of adolescents based on their anxiety symptom trajectories and including anxiety sensitivity as a predictor. Consistent with other reports, findings indicated an overall decline in anxiety symptoms over time in the sample. However, three classes of adolescents were found with distinct anxiety symptom trajectories and anxiety sensitivity was an important predictor of class membership. Adolescents with elevated anxiety sensitivity scores were more likely to be classified as having high and increasing anxiety symptoms over time versus having moderate to low and decreasing anxiety symptoms over time. There are important implications for identification of adolescents and children who are at risk for the development of an anxiety disorder.

  11. Developmental trends in auditory processing can provide early predictions of language acquisition in young infants.

    Science.gov (United States)

    Chonchaiya, Weerasak; Tardif, Twila; Mai, Xiaoqin; Xu, Lin; Li, Mingyan; Kaciroti, Niko; Kileny, Paul R; Shao, Jie; Lozoff, Betsy

    2013-03-01

    Auditory processing capabilities at the subcortical level have been hypothesized to impact an individual's development of both language and reading abilities. The present study examined whether auditory processing capabilities relate to language development in healthy 9-month-old infants. Participants were 71 infants (31 boys and 40 girls) with both Auditory Brainstem Response (ABR) and language assessments. At 6 weeks and/or 9 months of age, the infants underwent ABR testing using both a standard hearing screening protocol with 30 dB clicks and a second protocol using click pairs separated by 8, 16, and 64-ms intervals presented at 80 dB. We evaluated the effects of interval duration on ABR latency and amplitude elicited by the second click. At 9 months, language development was assessed via parent report on the Chinese Communicative Development Inventory - Putonghua version (CCDI-P). Wave V latency z-scores of the 64-ms condition at 6 weeks showed strong direct relationships with Wave V latency in the same condition at 9 months. More importantly, shorter Wave V latencies at 9 months showed strong relationships with the CCDI-P composite consisting of phrases understood, gestures, and words produced. Likewise, infants who had greater decreases in Wave V latencies from 6 weeks to 9 months had higher CCDI-P composite scores. Females had higher language development scores and shorter Wave V latencies at both ages than males. Interestingly, when the ABR Wave V latencies at both ages were taken into account, the direct effects of gender on language disappeared. In conclusion, these results support the importance of low-level auditory processing capabilities for early language acquisition in a population of typically developing young infants. Moreover, the auditory brainstem response in this paradigm shows promise as an electrophysiological marker to predict individual differences in language development in young children. © 2012 Blackwell Publishing Ltd.

  12. Growth attenuation with developmental schedule progression in embryos and early larvae of Sterechinus neumayeri raised under elevated CO2.

    Directory of Open Access Journals (Sweden)

    Pauline C Yu

    Full Text Available The Southern Ocean, a region that will be an ocean acidification hotspot in the near future, is home to a uniquely adapted fauna that includes a diversity of lightly-calcified invertebrates. We exposed the larvae of the echinoid Sterechinus neumayeri to environmental levels of CO(2 in McMurdo Sound (control: 410 µatm, Ω = 1.35 and mildly elevated pCO(2 levels, both near the level of the aragonite saturation horizon (510 µatm pCO(2, Ω = 1.12, and to under-saturating conditions (730 µatm, Ω = 0.82. Early embryological development was normal under these conditions with the exception of the hatching process, which was slightly delayed. Appearance of the initial calcium carbonate (CaCO(3 spicule nuclei among the primary mesenchyme cells of the gastrulae was synchronous between control and elevated pCO(2 treatments. However, by prism (7 days after the initial appearance of the spicule nucleus, elongating arm rod spicules were already significantly shorter in the highest CO(2 treatment. Unfed larvae in the 730 µatm pCO(2 treatment remained significantly smaller than unfed control larvae at days 15-30, and larvae in the 510 µatm treatment were significantly smaller at day 20. At day 30, the arm lengths were more differentiated between 730 µatm and control CO(2 treatments than were body lengths as components of total length. Arm length is the most plastic morphological aspect of the echinopluteus, and appears to exhibit the greatest response to high pCO(2/low pH/low carbonate, even in the absence of food. Thus, while the effects of elevated pCO(2 representative of near future climate scenarios are proportionally minor on these early developmental stages, the longer term effects on these long-lived invertebrates is still unknown.

  13. Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio).

    Science.gov (United States)

    Dishaw, Laura V; Hunter, Deborah L; Padnos, Beth; Padilla, Stephanie; Stapleton, Heather M

    2014-12-01

    Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish.

  14. The Adipokine Chemerin Induces Apoptosis in Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Diego Rodríguez-Penas

    2015-08-01

    Full Text Available Background: The adipokine chemerin has been associated with cardiovascular disease. We investigated the effects of chemerin on viability and intracellular signalling in murine cardiomyocytes, and the effects of insulin and TNF-α on cardiomyocyte chemerin production. Methods: Hoechst dye vital staining and cell cycle analysis were used to analyse the viability of murine cardiac cells in culture. Western blot was used to explore the phosphorylation of AKT and caspase-9 activity in neonatal rat cardiomyocytes and HL-1 cells. Finally, RT-qPCR, ELISA and western blot were performed to examine chemerin and CMKLR1 expression after insulin and TNF-α treatment in cardiac cells. Results: Chemerin treatment increased apoptosis, reduced phosphorylation of AKT at Thr308 and increased caspase-9 activity in murine cardiomyocytes. Insulin treatment lowered chemerin and CMKLR1 mRNA and protein levels, and the amount of chemerin in the cell media, while TNF-α treatment increased chemerin mRNA and protein levels but decreased expression of the CMKLR1 gene. Conclusion: Chemerin induces apoptosis, reduces AKT phosphorylation and increases the cleavage of caspase-9 in murine cardiomyocytes. The expression of chemerin is regulated by important metabolic (insulin and inflammatory (TNF-α mediators at cardiac level. Our results suggest that chemerin could play a role in the physiopathology of cardiac diseases.

  15. Opposite Effects of Early-Life Competition and Developmental Telomere Attrition on Cognitive Biases in Juvenile European Starlings.

    Directory of Open Access Journals (Sweden)

    Melissa Bateson

    Full Text Available Moods are enduring affective states that we hypothesise should be affected by an individual's developmental experience and its current somatic state. We tested whether early-life adversity, induced by manipulating brood size, subsequently altered juvenile European starlings' (Sturnus vulgaris decisions in a judgment bias task designed to provide a cognitive measure of mood. We predicted that starlings from larger broods, specifically those that had experienced more nest competitors larger than themselves would exhibit reduced expectation of reward, indicative of a 'pessimistic', depression-like mood. We used a go/no-go task, in which 30 starlings were trained to probe a grey card disc associated with a palatable mealworm hidden underneath and avoid a different shade of grey card disc associated with a noxious quinine-injected mealworm hidden underneath. Birds' response latencies to the trained stimuli and also to novel, ambiguous stimuli intermediate between these were subsequently tested. Birds that had experienced greater competition in the nest were faster to probe trained stimuli, and it was therefore necessary to control statistically for this difference in subsequent analyses of the birds' responses to the ambiguous stimuli. As predicted, birds with more, larger nest competitors showed relatively longer latencies to probe ambiguous stimuli, suggesting reduced expectation of reward and a 'pessimistic', depression-like mood. However, birds with greater developmental telomere attrition--a measure of cellular aging associated with increased morbidity and reduced life-expectancy that we argue could be used as a measure of somatic state--showed shorter latencies to probe ambiguous stimuli. This would usually be interpreted as evidence for a more positive or 'optimistic' affective state. Thus, increased competition in the nest and poor current somatic state appear to have opposite effects on cognitive biases. Our results lead us to question

  16. Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life

    Science.gov (United States)

    Li, Minglan; Reynolds, Clare M.; Segovia, Stephanie A.; Vickers, Mark H.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention. PMID:26090409

  17. Parent-Reported Attention Deficit/Hyperactivity Symptomatology in Preschool-Aged Children: Factor Structure, Developmental Change, and Early Risk Factors

    OpenAIRE

    Willoughby, Michael T.; Pek, Jolynn; Greenberg, Mark T.

    2012-01-01

    Although Attention Deficit/Hyperactivity Disorder (ADHD) has increasingly been studied in preschool-aged children, relatively few studies have provided a comprehensive evaluation of the factor structure and patterns of developmental changes in parent-reported ADHD symptomatology across the early childhood period. This study used confirmatory factor analyses to test for longitudinal measurement invariance of ADHD symptoms and semi-parametric finite mixture models to identify prototypic pattern...

  18. Urotensin II Protects Cardiomyocytes from Apoptosis Induced by Oxidative Stress through the CSE/H2S Pathway

    Directory of Open Access Journals (Sweden)

    Hui Gong

    2015-06-01

    Full Text Available Plasma urotensin II (UII has been observed to be raised in patients with acute myocardial infarction; suggesting a possible cardiac protective role for this peptide. However, the molecular mechanism is unclear. Here, we treated cultured cardiomyocytes with H2O2 to induce oxidative stress; observed the effect of UII on H2O2-induced apoptosis and explored potential mechanisms. UII pretreatment significantly reduced the number of apoptotic cardiomyocytes induced by H2O2; and it partly abolished the increase of pro-apoptotic protein Bax and the decrease of anti-apoptotic protein Bcl-2 in cardiomyocytes induced by H2O2. SiRNA targeted to the urotensin II receptor (UT greatly inhibited these effects. Further analysis revealed that UII increased the production of hydrogen sulfide (H2S and the level of cystathionine-γ-lyase (CSE by activating the ERK signaling in H2O2-treated-cardiomyocytes. Si-CSE or ERK inhibitor not only greatly inhibited the increase in CSE level or the phosphorylation of ERK induced by UII but also reversed anti-apoptosis of UII in H2O2-treated-cadiomyocytes. In conclusion, UII rapidly promoted the phosphorylation of ERK and upregulated CSE level and H2S production, which in turn activated ERK signaling to protect cardiomyocytes from apoptosis under oxidative stress. These results suggest that increased plasma UII level may protect cardiomyocytes at the early-phase of acute myocardial infarction in patients.

  19. Developmental trajectory from early responses to transgressions to future antisocial behavior: evidence for the role of the parent-child relationship from two longitudinal studies.

    Science.gov (United States)

    Kim, Sanghag; Kochanska, Grazyna; Boldt, Lea J; Nordling, Jamie Koenig; O'Bleness, Jessica J

    2014-02-01

    Parent-child relationships are critical in development, but much remains to be learned about the mechanisms of their impact. We examined the early parent-child relationship as a moderator of the developmental trajectory from children's affective and behavioral responses to transgressions to future antisocial, externalizing behavior problems in the Family Study (102 community mothers, fathers, and infants, followed through age 8) and the Play Study (186 low-income, diverse mothers and toddlers, followed for 10 months). The relationship quality was indexed by attachment security in the Family Study and maternal responsiveness in the Play Study. Responses to transgressions (tense discomfort and reparation) were observed in laboratory mishaps wherein children believed they had damaged a valued object. Antisocial outcomes were rated by parents. In both studies, early relationships moderated the future developmental trajectory: diminished tense discomfort predicted more antisocial outcomes, but only in insecure or unresponsive relationships. That risk was defused in secure or responsive relationships. Moderated mediation analyses in the Family Study indicated that the links between diminished tense discomfort and future antisocial behavior in insecure parent-child dyads were mediated by stronger discipline pressure from parents. By indirectly influencing future developmental sequelae, early relationships may increase or decrease the probability that the parent-child dyad will embark on a path toward antisocial outcomes.

  20. Qualitative Reflections: CASA’s Trauma and Attachment Group (TAG) Program for Youth who have Experienced Early Developmental Trauma

    Science.gov (United States)

    Ashton, Chandra K.; O’Brien-Langer, Anna; Olson, Karin; Silverstone, Peter H.

    2017-01-01

    Objective We demonstrated previously that the Trauma and Attachment Group (TAG) program for youth in middle childhood significantly improved caregiver/child attachment relationships, reduced children’s symptoms of attachment trauma, and increased the caregiver’s ability for self-reflection. Here we examine the perspectives of both those administering and those taking part in this intensive dyad-based group intervention. Methods Utilizing an ethnographic design we collected and analyzed qualitative data obtained through a focus group and interviews with program facilitators, as well as interviews with participating caregivers. Data were collected from six TAG facilitators through a formal focus group interview (n=4), and informal interviews with TAG facilitators unable to attend the focus group (n=2). Four interviews were also carried out with caregivers (three females and one male). Thematic analysis of the focus group and interview transcripts was conducted. Results Three key themes were identified in the focus group and interview data: Relationship as locus of change, Group process, and Psychoeducation-based content. That the TAG program provides psychoeducation about the effects of trauma to caregiver/child dyads in a group setting appears important in supporting the effectiveness of the program. Structured parent-child play and sensory activities together (“kit-time”) were also highly valued. Conclusions This qualitative study suggests that establishment of a healthy and focused caregiver/child relationship may be the key mechanism to promoting change in relationships that have been challenged by adverse effects of early developmental trauma. Further evaluation may help to identify other components that contribute to the success of the program.

  1. Human Pluripotent Stem Cell-Derived Cardiomyocytes as Research and Therapeutic Tools

    Directory of Open Access Journals (Sweden)

    Ivana Acimovic

    2014-01-01

    Full Text Available Human pluripotent stem cells (hPSCs, namely, embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs, with their ability of indefinite self-renewal and capability to differentiate into cell types derivatives of all three germ layers, represent a powerful research tool in developmental biology, for drug screening, disease modelling, and potentially cell replacement therapy. Efficient differentiation protocols that would result in the cell type of our interest are needed for maximal exploitation of these cells. In the present work, we aim at focusing on the protocols for differentiation of hPSCs into functional cardiomyocytes in vitro as well as achievements in the heart disease modelling and drug testing on the patient-specific iPSC-derived cardiomyocytes (iPSC-CMs.

  2. Cardiomyocyte Marker Expression in Mouse Embryonic Fibroblasts by Cell-Free Cardiomyocyte Extract and Epigenetic Manipulation

    Directory of Open Access Journals (Sweden)

    Tahereh Talaei-Khozani

    2014-03-01

    Full Text Available Background: The regenerative capacity of the mammalian heart is quite limited. Recent reports have focused on reprogramming mesenchymal stem cells into cardiomyocytes. We investigated whether fibroblasts could transdifferentiate into myocardium. Methods: Mouse embryonic fibroblasts were treated with Trichostatin A (TSA and 5-Aza-2-Deoxycytidine (5-aza-dC. The treated cells were permeabilized with streptolysin O and exposed to the mouse cardiomyocyte extract and cultured for 1, 10, and 21 days. Cardiomyocyte markers were detected by immunohistochemistry. Alkaline phosphatase activity and OCT4 were also detected in cells treated by chromatin-modifying agents. Results: The cells exposed to a combination of 5-aza-dC and TSA and permeabilized in the presence of the cardiomyocyte extract showed morphological changes. The cells were unable to express cardiomyocyte markers after 24 h. Immunocytochemical assays showed a notable degree of myosin heavy chain and α-actinin expressions after 10 days. The expression of the natriuretic factor and troponin T occurred after 21 days in these cells. The cells exposed to chromatin-modifying agents also expressed cardiomyocyte markers; however, the proportion of reprogrammed cells was clearly smaller than that in the cultures exposed to 5-aza-dC , TSA, and extract. Conclusion: It seems that the fibroblasts were able to eliminate the previous epigenetic markers and form new ones according to the factors existing in the extract. Since no beating was observed, at least up to 21 days, the cells may need an appropriate extracellular matrix for their function.

  3. Highly efficient derivation of ventricular cardiomyocytes from induced pluripotent stem cells with a distinct epigenetic signature

    Institute of Scientific and Technical Information of China (English)

    Huansheng Xu; Ibrahim J Domian; Erding Hu; Robert Willette; John Lepore; Alexander Meissner; Zhong Wang; Kenneth R Chien; B Alexander Yi; Hao Wu; Christoph Bock; Hongcang Gu; Kathy O Lui; Joo-Hye C Park; Ying Shao; Alyssa K Riley

    2012-01-01

    Cardiomyocytes derived from pluripotent stem cells can be applied in drug testing,disease modeling and cellbased therapy.However,without procardiogenic growth factors,the efficiency of cardiomyogenesis from pluripotent stem cells is usually low and the resulting cardiomyocyte population is heterogeneous.Here,we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes (VMs),and consistent with other reports of iPSCs derived from various somatic cell types,VM-derived iPSCs (ViPSCs) exhibit a markedly higher propensity to spontaneously differentiate into beating cardiomyocytes as compared to genetically matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts.Strikingly,the majority of ViPSC-derived cardiomyocytes display a ventricular phenotype.The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation.In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs,we performed global gene expression and DNA methylation analysis,which revealed a distinct epigenetic signature that may be involved in specifying the VM fate in pluripotent stem cells.

  4. Abnormal Calcium "Sparks" in Cardiomyocytes of Post-myocardial Infarction Heart

    Institute of Scientific and Technical Information of China (English)

    Kai HUANG; Dan HUANG; Shengquan FU; Chongzhe YANG; Yuhua LIAO

    2008-01-01

    In ischemic hypertrophic myocardium, contractile dysfunction can be attributed to the decreased calcium induced calcium release (CICR) in cytoplasm. This study aimed to investigate the electrophysiological properties and the expression of L calcium channel subunits in post-MI myocardium. The ischemic heart remodeling model was established in SD rats. The expressions of calcium channel subunits were determined by realtime RT-PCR. Whole cell patch clamp was used to record the electrophysiological properties of L calcium channel. The results showed that the L calcium channel agonist Bayk 8644 induced the significantly decreased CICR in the rat cardiomyocyte 6weeks after myocardial infarction (MI). In the post-MI cardiomyocytes, the amplitude of ICaL decreased dramatically and the inactivation curve of the current shifted to more negative potential. At mRNA level, the expression of the calcium channel alphalc, beta2c subunits decreased dramatically in the ventricle of post-MI rats. The expression of alpha2/delta subunit, however, remained constant.It is concluded that the abnormal expression of the L calcium channel subunits in post-MI cardiomyocytes contributes to the ICaL decrease at early stage of the ischemic remodeling in cardiomyocytes,which leads to the decreased CICR in the cell and contractile dysfunction of myocardium.

  5. The impact of youth, family, peer and neighborhood risk factors on developmental trajectories of risk involvement from early through middle adolescence.

    Science.gov (United States)

    Wang, Bo; Deveaux, Lynette; Li, Xiaoming; Marshall, Sharon; Chen, Xinguang; Stanton, Bonita

    2014-04-01

    Few studies have analyzed the development course beginning in pre-/early adolescence of overall engagement in health-risk behaviors and associated social risk factors that place individuals in different health-risk trajectories through mid-adolescence. The current longitudinal study identified 1276 adolescents in grade six and followed them for three years to investigate their developmental trajectories of risk behaviors and to examine the association of personal and social risk factors with each trajectory. Group-based trajectory modeling was applied to identify distinctive trajectory patterns of risk behaviors. Multivariate multinomial logistic regression analyses were performed to examine the effects of the personal and social risk factors on adolescents' trajectories. Three gender-specific behavioral trajectories were identified for males (55.3% low-risk, 37.6% moderate-risk, increasing, and 7.1% high-risk, increasing) and females (41.4% no-risk, 53.4% low-risk, increasing and 5.2% moderate to high-risk, increasing). Sensation-seeking, family, peer, and neighborhood factors at baseline predicted following the moderate-risk, increasing trajectory and the high-risk, increasing trajectory in males; these risk factors predicted following the moderate to high-risk, increasing trajectory in females. The presence of all three social risk factors (high-risk neighborhood, high-risk peers and low parental monitoring) had a dramatic impact on increased probability of being in a high-risk trajectory group. These findings highlight the developmental significance of early personal and social risk factors on subsequent risk behaviors in early to middle adolescence. Future adolescent health behavior promotion interventions might consider offering additional prevention resources to pre- and early adolescent youth who are exposed to multiple contextual risk factors (even in the absence of risk behaviors) or youth who are early-starters of delinquency and substance use behaviors

  6. Developmental programming of somatic growth, behavior and endocannabinoid metabolism by variation of early postnatal nutrition in a cross-fostering mouse model.

    Science.gov (United States)

    Schreiner, Felix; Ackermann, Merle; Michalik, Michael; Hucklenbruch-Rother, Eva; Bilkei-Gorzo, Andras; Racz, Ildiko; Bindila, Laura; Lutz, Beat; Dötsch, Jörg; Zimmer, Andreas; Woelfle, Joachim

    2017-01-01

    Nutrient deprivation during early development has been associated with the predisposition to metabolic disorders in adulthood. Considering its interaction with metabolism, appetite and behavior, the endocannabinoid (eCB) system represents a promising target of developmental programming. By cross-fostering and variation of litter size, early postnatal nutrition of CB6F1-hybrid mice was controlled during the lactation period (3, 6, or 10 pups/mother). After weaning and redistribution at P21, all pups received standard chow ad libitum. Gene expression analyses (liver, visceral fat, hypothalamus) were performed at P50, eCB concentrations were determined in liver and visceral fat. Locomotor activity and social behavior were analyzed by means of computer-assisted videotracking. Body growth was permanently altered, with differences for length, weight, body mass index and fat mass persisting beyond P100 (all 3>6>10,peCB system were observed in fat (eCB-synthesis: 3>6>10 (DAGLα peCB-degradation: 3>6>10 (FAAH peCB-receptor transcripts (CB1R peCB system, with long-lasting impact of early postnatal nutrition. Developmental programming of the eCB system in metabolically active tissues, as shown here for liver and fat, may play a role in the formation of the adult cardiometabolic risk profile following perinatal malnutrition in humans.

  7. Effects of Multivitamins and Known Teratogens on Chick Cardiomyocytes Micromass Culture Assay

    Directory of Open Access Journals (Sweden)

    Samreen Memon

    2013-09-01

    Full Text Available   Objective(s: This study aimed to find out whether the chick cardiomyocyte micromass (MM system could be employed to predict the teratogenecity of common environmental factors. Different multivitamins and over the counter drugs were used in this study.   Materials and Methods: White Leghorn 5-day-old embryo hearts were dissected and trypsinized to produce a cardiomyocyte cell suspension in Dulbecco's Modified Eagle's Medium. The cultures were incubated at 370C in 5% CO2 in air, and observations were made at 24, 48 and 144 hr, for the detection of cell beating. Cellular viability was assessed using the resazurin assay and cell protein content was assessed by the kenacid blue assay. It was observed that while not affecting total cell number folic acid, vitamin C, sodium fluoride and ginseng did not significantly reduced cell activity and beating. However cadmium chloride significantly reduced the beating, cell viability and cell protein content in micromass cultures. Results: The results demonstrate the potential of the chick cardiomyocyte MM culture assay to identify teratogens/embryotoxins that alter morphology and function, which may result in either teratogenic outcome or cytotoxicity. Conclusion: This could form part of a screen for developmental toxicity related to cardiac function

  8. Mothers' Perceived Physical Health during Early and Middle Childhood: Relations with Child Developmental Delay and Behavior Problems

    Science.gov (United States)

    Eisenhower, Abbey; Blacher, Jan; Baker, Bruce L.

    2013-01-01

    The self-perceived physical health of mothers raising children with developmental delay (DD; N = 116) or typical development (TD; N = 129) was examined across child ages 3-9 years, revealing three main findings. First, mothers of children with DD experienced poorer self-rated physical health than mothers of children with TD at each age. Latent…

  9. Aggressive Behaviors in Social Interaction and Developmental Adaptation: A Narrative Analysis of Interpersonal Conflicts during Early Adolescence.

    Science.gov (United States)

    Xie, Hongling; Swift, Dylan J.; Cairns, Beverley D.; Cairns, Robert B.

    2002-01-01

    Investigated interactional properties and developmental functions of the following four types of aggressive behaviors in adolescents: social aggression, direct relational aggression, physical aggression, and verbal aggression. Found that the majority of conflict interactions involved more than a dyad, and that social aggression was an initiating…

  10. Early Developmental Assessment of Children with Major Non-Cardiac Congenital Anomalies Predicts Development at the Age of 5 Years

    Science.gov (United States)

    Mazer, Petra; Gischler, Saskia J.; van der Cammen-van Zijp, Monique H. M.; Tibboel, Dick; Bax, Nicolaas M. A.; Ijsselstijn, Hanneke; van Dijk, Monique; Duivenvoorden, Hugo J.

    2010-01-01

    Aim: The aim of this study was to evaluate cognitive and motor development in children with major congenital anomalies and the predictability of development at age 5 years. Method: A prospective, longitudinal follow-up study was undertaken. The Dutch version of the Bayley Scales of Infant Development--Mental Developmental Index (MDI) and…

  11. Teaching Early Reading Skills to Children with Intellectual and Developmental Disabilities Using Computer-Delivered Instruction: A Pilot Study

    Science.gov (United States)

    Tyler, Emily J.; Hughes, John C.; Wilson, Meadhbh M.; Beverley, Michael; Hastings, Richard P.; Williams, Bethan M.

    2015-01-01

    Many children with Intellectual and Developmental Disabilities (IDD) have considerable difficulty learning basic reading skills. Increasing evidence suggests individuals with IDD may benefit from instruction incorporating components of reading found to be effective for typically developing children. However, little research into reading…

  12. Elastic interactions synchronize beating in cardiomyocytes.

    Science.gov (United States)

    Cohen, Ohad; Safran, Samuel A

    2016-07-13

    Motivated by recent experimental results, we study theoretically the synchronization of the beating phase and frequency of two nearby cardiomyocyte cells. Each cell is represented as an oscillating force dipole in an infinite, viscoelastic medium and the propagation of the elastic signal within the medium is predicted. We examine the steady-state beating of two nearby cells, and show that elastic interactions result in forces that synchronize the phase and frequency of beating in a manner that depends on their mutual orientation. The theory predicts both in-phase and anti-phase steady-state beating depending on the relative cell orientations, as well as how synchronized beating varies with substrate elasticity and the inter-cell distance. These results suggest how mechanics plays a role in cardiac efficiency, and may be relevant for the design of cardiomyocyte based micro devices and other biomedical applications.

  13. Pulse splitter-based nonlinear microscopy for live-cardiomyocyte imaging

    OpenAIRE

    Wang, Zhonghai; Qin, Wan; Shao, Yonghong; Ma, Siyu; Borg, Thomas K.; GAO, BRUCE Z.

    2014-01-01

    Second harmonic generation (SHG) microscopy is a new imaging technique used in sarcomeric-addition studies. However, during the early stage of cell culture in which sarcomeric additions occur, the neonatal cardiomyocytes that we have been working with are very sensitive to photodamage, the resulting high rate of cell death prevents systematic study of sarcomeric addition using a conventional SHG system. To address this challenge, we introduced use of the pulse-splitter system developed by Na ...

  14. The international society for developmental psychobiology Sackler symposium: early adversity and the maturation of emotion circuits--a cross-species analysis.

    Science.gov (United States)

    Callaghan, Bridget L; Sullivan, Regina M; Howell, Brittany; Tottenham, Nim

    2014-12-01

    Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations.

  15. [The influence of fibroblast growth factor (FGF2) on cardiomyocytes differentiation of mesenchymal stem cells of bone marrow ex vivo].

    Science.gov (United States)

    Lobanok, E S; Kvacheva, Z B; Pinchuk, S V; Volk, M V; Mezhevkina, L M; Fesenko, E E; Volotovski, I D

    2014-01-01

    The influence of FGF2 on the efficiency of cardiomyocytes differentiation of mesenchymal stem cells (MSC) of bone marrow induced by 5-azacetidine (5-aza) was studied. The effect of FGF2 developing by the 14th day after the combined action of a differentiating agent and growth factor was manifested in an increase in Mef2A, Mef2D and gene transcription and a rise of ionized Ca2+ concentration in cytoplasm keeping cell viability and proliferation activity. In the presence of FGF2 this approach provided cardiomyogenesis and the increase in the formation of early precursors of cardiomyocytes.

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  11. Nkx2.5 homeoprotein regulates expression of gap junction protein connexin 43 and sarcomere organization in postnatal cardiomyocytes.

    Science.gov (United States)

    Kasahara, Hideko; Ueyama, Tomomi; Wakimoto, Hiroko; Liu, Margaret K; Maguire, Colin T; Converso, Kimber L; Kang, Peter M; Manning, Warren J; Lawitts, Joel; Paul, David L; Berul, Charles I; Izumo, Seigo

    2003-03-01

    Nkx2.5, an evolutionarily conserved homeodomain containing transcription factor, is one of the earliest cardiogenic markers. Although its expression continues through adulthood, its function in adult cardiomyocytes is not well understood. To examine the effect of Nkx2.5 in terminal differentiated postnatal cardiomyocytes, we generated transgenic mice expressing either wild-type Nkx2.5 (TG-wild), a putative transcriptionally active mutant (carboxyl-terminus deletion mutant: TG-DeltaC) or a DNA non-binding point mutant of Nkx2.5 (TG-I183P) under alpha-myosin heavy chain promoter. Most TG-wild and TG-DeltaC mice died before 4 months of age with heart failure associated with conduction abnormalities. Cardiomyocytes expressing wild-type Nkx2.5 or a putative transcriptionally active mutant (DeltaC) had dramatically reduced expression of connexin 43 and changed sarcomere structure. Wild-type Nkx2.5 adenovirus-infected adult cardiomyocytes demonstrated connexin 43 downregulation as early as 16 h after infection, indicating that connexin 43 downregulation is due to Nkx2.5 overexpression but not due to heart failure phenotype in vivo. These studies indicate that overexpression of Nkx2.5 in terminally differentiated cardiomyocytes dramatically alters cardiac cell structure and function.

  12. The use of the Battelle Developmental Inventory-Second Edition (BDI-2) as an early screener for autism spectrum disorders.

    Science.gov (United States)

    Sipes, Megan; Matson, Johnny L; Turygin, Nicole

    2011-01-01

    The purpose was to develop cut-off scores for a measure of developmental level (Battelle Developmental Inventory-Second Edition; BDI-2) which could be used as a screening tool to differentiate young children with possible autism spectrum disorders (ASD). Infants and toddlers with ASD (n = 604) and atypically-developing infants and toddlers (n = 1064) were administered the BDI-2. Cut-off scores were determined based on standard deviations from the mean of the ASD group. Using 1.5 standard deviations from the mean of the ASD group, a cut-off score of 96 was determined which had a sensitivity of 0.94 and a specificity of 0.31. With high sensitivity, these cut-off scores can be used to identify children who require further assessment. In addition, the measure can be used to determine treatment targets.

  13. Regulation of Insulin-Like Growth Factor Signaling by Yap Governs Cardiomyocyte Proliferation and Embryonic Heart Size

    Science.gov (United States)

    Xin, Mei; Kim, Yuri; Sutherland, Lillian B.; Qi, Xiaoxia; McAnally, John; Schwartz, Robert J.; Richardson, James A.; Bassel-Duby, Rhonda; Olson, Eric N.

    2012-01-01

    The Hippo signaling pathway regulates growth of the heart and other tissues. Hippo pathway kinases influence the activity of various targets, including the transcriptional coactivator Yap, but the specific role of Yap in heart growth has not been investigated. We show that Yap is necessary and sufficient for embryonic cardiac growth in mice. Deletion of Yap in the embryonic mouse heart impeded cardiomyocyte proliferation, causing myocardial hypoplasia and lethality at embryonic stage 10.5. Conversely, forced expression of a constitutively active form of Yap in the embryonic heart increased cardiomyocyte number and heart size. Yap activated the insulin-like growth factor (IGF) signaling pathway in cardiomyocytes, resulting in inactivation of glycogen synthase kinase 3β, which led to increased abundance of β-catenin, a positive regulator of cardiac growth. Our results point to Yap as a critical downstream effector of the Hippo pathway in the control of cardiomyocyte proliferation and a nexus for coupling the IGF, Wnt, and Hippo signaling pathways with the developmental program for heart growth. PMID:22028467

  14. An evaluation of a novel chick cardiomyocyte micromass culture assay with two teratogens/embryotoxins associated with heart defects.

    Science.gov (United States)

    Hurst, Helena S; Clothier, Richard H; Pratten, Margaret

    2007-10-01

    This study was aimed at determining whether the chick cardiomyocyte micromass (MM) system could be employed to predict the teratogenicity/embryotoxicity of exogenous chemicals. Two documented teratogens/embryotoxins, sodium valproate (the sodium salt of valproic acid; VPA) and all-trans retinoic acid (tRA), were used in the initial phase of the study. White Leghorn 5-day-old embryo hearts were dissociated to produce a cardiomyocyte suspension in Dulbecco's Modified Eagle's Medium. Cultures were incubated at 37 degrees C in 5% CO(2) in air, and observations were made every 24 hours over 5 days, for the detection of beating. Culture viability was assessed by using the resazurin reduction assay for determining culture activity and the kenacid blue assay for determining cell number. It was found that tRA significantly reduced cell activity and beating, whilst not affecting total cell number. VPA up to 500 microM induced no cytotoxicity in the MM cardiomyocyte cultures, whilst all the VPA concentrations tested reduced beating. The results demonstrate the potential of the chick cardiomyocyte MM culture assay to identify teratogens/embryotoxins that alter functionality, which may result in a teratogenic outcome, whilst not causing cytotoxicity (direct embryotoxicity). This could form part of a screen for developmental toxicity related to cardiac function, whilst limb cultures and brain cultures based on the same system could be relevant to teratogenic effects on those tissues.

  15. Endurance Exercise Mobilizes Developmentally Early Stem Cells into Peripheral Blood and Increases Their Number in Bone Marrow: Implications for Tissue Regeneration.

    Science.gov (United States)

    Marycz, Krzysztof; Mierzejewska, Katarzyna; Śmieszek, Agnieszka; Suszynska, Ewa; Malicka, Iwona; Kucia, Magda; Ratajczak, Mariusz Z

    2016-01-01

    Endurance exercise has been reported to increase the number of circulating hematopoietic stem/progenitor cells (HSPCs) in peripheral blood (PB) as well as in bone marrow (BM). We therefore became interested in whether endurance exercise has the same effect on very small embryonic-like stem cells (VSELs), which have been described as a population of developmentally early stem cells residing in BM. Mice were run daily for 1 hour on a treadmill for periods of 5 days or 5 weeks. Human volunteers had trained in long-distance running for one year, six times per week. FACS-based analyses and RT-PCR of murine and human VSELs and HSPCs from collected bone marrow and peripheral blood were performed. We observed that endurance exercise increased the number of VSELs circulating in PB and residing in BM. In parallel, we observed an increase in the number of HSPCs. These observations were subsequently confirmed in young athletes, who showed an increase in circulating VSELs and HSPCs after intensive running exercise. We provide for the first time evidence that endurance exercise may have beneficial effects on the expansion of developmentally early stem cells. We hypothesize that these circulating stem cells are involved in repairing minor exercise-related tissue and organ injuries.

  16. Unique metabolic features of stem cells, cardiomyocytes, and their progenitors.

    Science.gov (United States)

    Gaspar, John Antonydas; Doss, Michael Xavier; Hengstler, Jan Georg; Cadenas, Cristina; Hescheler, Jürgen; Sachinidis, Agapios

    2014-04-11

    Recently, growing attention has been directed toward stem cell metabolism, with the key observation that the plasticity of stem cells also reflects the plasticity of their energy substrate metabolism. There seems to be a clear link between the self-renewal state of stem cells, in which cells proliferate without differentiation, and the activity of specific metabolic pathways. Differentiation is accompanied by a shift from anaerobic glycolysis to mitochondrial respiration. This metabolic switch of differentiating stem cells is required to cover the energy demands of the different organ-specific cell types. Among other metabolic signatures, amino acid and carbohydrate metabolism is most prominent in undifferentiated embryonic stem cells, whereas the fatty acid metabolic signature is unique in cardiomyocytes derived from embryonic stem cells. Identifying the specific metabolic pathways involved in pluripotency and differentiation is critical for further progress in the field of developmental biology and regenerative medicine. The recently generated knowledge on metabolic key processes may help to generate mature stem cell-derived somatic cells for therapeutic applications without the requirement of genetic manipulation. In the present review, the literature about metabolic features of stem cells and their cardiovascular cell derivatives as well as the specific metabolic gene signatures differentiating between stem and differentiated cells are summarized and discussed.

  17. Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages

    Institute of Scientific and Technical Information of China (English)

    Hua-min LIANG; Su-yun LI; Ling-ling LAI; Juergen HESCHELER; Ming TANG; Chang-jin LIU; Hong-yan LUO; Yuan-long SONG; Xin-wu HU; Jiao-ya XI; Lin-lin GAO; Bin NIE

    2004-01-01

    AIM: To investigate the muscarinic regulation of L-type calcium current (ICa-L) during development. METHODS:The whole cell patch-clamp technique was used to record Ica- L in mice embryonic cardiomyocytes at different stages (the early developmental stage, EDS; the intermediate developmental stage, IDS; and the late developmental stage, LDS). Carbachol (CCh) was used to stimulate M-receptor in the embryonic cardiomyocytes of mice.RESULTS: The expression of Ica-L density did not change in different developmental stages (P>0.05). There was no difference in the sensitivity of ICa-L to CCh during development (P>0.05). This inhibitory action of CCh was mediated by inhibition of cyclic AMP since 8-bromo-cAMP completely reversed the muscarinic inhibitory action.IBMX, a non-selective inhibitor of phosphodiesterase (PDE), reversed the inhibitory action of M-receptor on ICa-Lcurrent by 71.2 %±9.2 % (n=8) and 11.3 %±2.5 % (n=9) in EDS and LDS respectively. However forskolin, an agonist of adenylyl cyclase (AC), reversed the action of CCh by 14.5 %±3.5 % (n=5) and 82.7 %±10.4 % (n=7) in EDS and LDS respectively. CONCLUSION: The inhibitory action of CCh on ICa-L current was mediated in different pathways: in EDS, the inhibitory action of M-receptor on ICa-L channel mainly depended on the stimulation of PDE. However, in LDS, the regulation by M-receptor on ICa-L channel mainly depended on the inactivation of AC.

  18. Muscarinic cholinergic regulation of L-type calcium channel in heart of embryonic mice at different developmental stages

    Institute of Scientific and Technical Information of China (English)

    Hua-minLIANG; MingTANG; Chang-jinLIU; Hong-yanLUO; Yuan-longSONG; Xin-wuHU; Jiao-yaXI; Lin-linGAO; BinNIE; Su-yunLI; Ling-lingLAI; JuergenHESCHELER

    2004-01-01

    AIM: To investigate the muscarinic regulation of L-type calcium current (ICa-L) during development. METHODS:The whole cell patch-clamp technique was used to record ICa-L in mice embryonic cardiomyocytes at different stages (the early developmental stage, EDS; the intermediate developmental stage, IDS; and the late developmental stage, LDS). Carbachol (CCh) was used to stimulate M-receptor in the embryonic cardiomyocytes of mice.RESULTS: The expression of lCa.L density did not change in different developmental stages (P>0.05). There was no difference in the sensitivity of ICa-L to CCh during development (P>0.05). This inhibitory action of CCh was mediated by inhibition of cyclic AMP since 8-bromo-cAMP completely reversed the muscarinic inhibitory action. IBMX, a non-selective inhibitor of phosphodiesterase (PDE), reversed the inhibitory action of M-receptor on ICa-L current by 71.2 %±9.2% (n=8) and 11.3%±2.5% (n=9) in EDS and LDS respectively. However forskolin, an agonist of adenylyl cyclase (AC), reversed the action of CCh by 14.5%±3.5% (n=5) and 82.7%± 10.4% (n=7) in EDS and LDS respectively. CONCLUSION: The inhibitory action of CCh on lca.L current was mediated in different pathways: in EDS, the inhibitory action of M-receptor on ICa-L channel mainly depended on the stimulation of PDE. However, in LDS, the regulation by M-receptor on lCa.L channel mainly depended on the inactivation of AC.

  19. Myc overexpression enhances of epicardial contribution to the developing heart and promotes extensive expansion of the cardiomyocyte population

    Science.gov (United States)

    Villa del Campo, Cristina; Lioux, Ghislaine; Carmona, Rita; Sierra, Rocío; Muñoz-Chápuli, Ramón; Clavería, Cristina; Torres, Miguel

    2016-01-01

    Myc is an essential regulator of cell growth and proliferation. Myc overexpression promotes the homeostatic expansion of cardiomyocyte populations by cell competition, however whether this applies to other cardiac lineages remains unknown. The epicardium contributes signals and cells to the developing and adult injured heart and exploring strategies for modulating its activity is of great interest. Using inducible genetic mosaics, we overexpressed Myc in the epicardium and determined the differential expansion of Myc-overexpressing cells with respect to their wild type counterparts. Myc-overexpressing cells overcolonized all epicardial-derived lineages and showed increased ability to invade the myocardium and populate the vasculature. We also found massive colonization of the myocardium by Wt1Cre-derived Myc-overexpressing cells, with preservation of cardiac development. Detailed analyses showed that this contribution is unlikely to derive from Cre activity in early cardiomyocytes but does not either derive from established epicardial cells, suggesting that early precursors expressing Wt1Cre originate the recombined cardiomyocytes. Myc overexpression does not modify the initial distribution of Wt1Cre-recombined cardiomyocytes, indicating that it does not stimulate the incorporation of early expressing Wt1Cre lineages to the myocardium, but differentially expands this initial population. We propose that strategies using epicardial lineages for heart repair may benefit from promoting cell competitive ability. PMID:27752085

  20. Manipulation of the Growth Hormone-Insulin-Like Growth Factor (GH-IGF) Axis: A Treatment Strategy to Reverse the Effects of Early Life Developmental Programming

    Science.gov (United States)

    Reynolds, Clare M.

    2017-01-01

    Evidence from human clinical, epidemiological, and experimental animal models has clearly highlighted a link between the early life environment and an increased risk for a range of cardiometabolic disorders in later life. In particular, altered maternal nutrition, including both undernutrition and overnutrition, spanning exposure windows that cover the period from preconception through to early infancy, clearly highlight an increased risk for a range of disorders in offspring in later life. This process, preferentially termed “developmental programming” as part of the developmental origins of health and disease (DOHaD) framework, leads to phenotypic outcomes in offspring that closely resemble those of individuals with untreated growth hormone (GH) deficiency, including increased adiposity and cardiovascular disorders. As such, the use of GH as a potential intervention strategy to mitigate the effects of developmental malprogramming has received some attention in the DOHaD field. In particular, experimental animal models have shown that early GH treatment in the setting of poor maternal nutrition can partially rescue the programmed phenotype, albeit in a sex-specific manner. Although the mechanisms remain poorly defined, they include changes to endothelial function, an altered inflammasome, changes in adipogenesis and cardiovascular function, neuroendocrine effects, and changes in the epigenetic regulation of gene expression. Similarly, GH treatment to adult offspring, where an adverse metabolic phenotype is already manifest, has shown efficacy in reversing some of the metabolic disorders arising from a poor early life environment. Components of the GH-insulin-like growth factor (IGF)-IGF binding protein (GH-IGF-IGFBP) system, including insulin-like growth factor 1 (IGF-1), have also shown promise in ameliorating programmed metabolic disorders, potentially acting via epigenetic processes including changes in miRNA profiles and altered DNA methylation. However

  1. Developmental links of very early phonological and language skills to second grade reading outcomes: strong to accuracy but only minor to fluency.

    Science.gov (United States)

    Puolakanaho, Anne; Ahonen, Timo; Aro, Mikko; Eklund, Kenneth; Leppänen, Paavo H T; Poikkeus, Anna-Maija; Tolvanen, Asko; Torppa, Minna; Lyytinen, Heikki

    2008-01-01

    The authors examined second grade reading accuracy and fluency and their associations via letter knowledge to phonological and language predictors assessed at 3.5, 4.5, and 5.5 years in children in the Jyväskylä Longitudinal Study of Dyslexia. Structural equation modeling showed that a developmentally highly stable factor (early phonological and language processing [EPLP]) behind key dyslexia predictors (i.e., phonological awareness, short-term memory, rapid naming, vocabulary, and pseudoword repetition) could already be identified at 3.5 years. EPLP was significantly associated with reading and spelling accuracy and by age with letter knowledge. However, EPLP had only a minor link with reading fluency, which was additionally explained by early letter knowledge. The results show that reading accuracy is well predicted by early phonological and language skills. Variation in fluent reading skills is not well explained by early skills, suggesting factors other than phonological core skills. Future research is suggested to explore the factors behind the development of fast and accurate decoding skills.

  2. Early developmental milestones and risk of schizophrenia: a 45-year follow-up of the Copenhagen Perinatal Cohort

    DEFF Research Database (Denmark)

    Sørensen, Holger J; Mortensen, Erik L; Schiffman, Jason

    2010-01-01

    disorders and in the 4982 cohort controls who were never admitted to a psychiatric department. Group comparisons were adjusted for gender, mother's age, father's age, parental social status, breadwinner's education, single mother status and parity. Individuals who developed schizophrenia reached all......The aim of the present study was to investigate the relationship between age of neuromotor milestone attainment and risk of adult schizophrenia. 5765 mothers of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the child's first year of life. Cohort members were followed...

  3. Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy

    Science.gov (United States)

    Putinski, Charis; Abdul-Ghani, Mohammad; Stiles, Rebecca; Brunette, Steve; Dick, Sarah A.; Fernando, Pasan; Megeney, Lynn A.

    2013-01-01

    Cardiomyocyte hypertrophy is the cellular response that mediates pathologic enlargement of the heart. This maladaptation is also characterized by cell behaviors that are typically associated with apoptosis, including cytoskeletal reorganization and disassembly, altered nuclear morphology, and enhanced protein synthesis/translation. Here, we investigated the requirement of apoptotic caspase pathways in mediating cardiomyocyte hypertrophy. Cardiomyocytes treated with hypertrophy agonists displayed rapid and transient activation of the intrinsic-mediated cell death pathway, characterized by elevated levels of caspase 9, followed by caspase 3 protease activity. Disruption of the intrinsic cell death pathway at multiple junctures led to a significant inhibition of cardiomyocyte hypertrophy during agonist stimulation, with a corresponding reduction in the expression of known hypertrophic markers (atrial natriuretic peptide) and transcription factor activity [myocyte enhancer factor-2, nuclear factor kappa B (NF-κB)]. Similarly, in vivo attenuation of caspase activity via adenoviral expression of the biologic effector caspase inhibitor p35 blunted cardiomyocyte hypertrophy in response to agonist stimulation. Treatment of cardiomyocytes with procaspase 3 activating compound 1, a small-molecule activator of caspase 3, resulted in a robust induction of the hypertrophy response in the absence of any agonist stimulation. These results suggest that caspase-dependent signaling is necessary and sufficient to promote cardiomyocyte hypertrophy. These results also confirm that cell death signal pathways behave as active remodeling agents in cardiomyocytes, independent of inducing an apoptosis response. PMID:24101493

  4. Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats

    Science.gov (United States)

    Albores-Garcia, Damaris; Hernandez, Alberto J.; Loera, Miriam J.

    2016-01-01

    Few studies have assessed the effects of developmental methylmercury (MeHg) exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1) control (vehicle), (2) 250 μg/kg/day MeHg, (3) 500 μg/kg/day MeHg, and (4) vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p.), an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined. PMID:26885512

  5. Early Developmental Low-Dose Methylmercury Exposure Alters Learning and Memory in Periadolescent but Not Young Adult Rats

    Directory of Open Access Journals (Sweden)

    Damaris Albores-Garcia

    2016-01-01

    Full Text Available Few studies have assessed the effects of developmental methylmercury (MeHg exposure on learning and memory at different ages. The possibility of the amelioration or worsening of the effects has not been sufficiently investigated. This study aimed to assess whether low-dose MeHg exposure in utero and during suckling induces differential disturbances in learning and memory of periadolescent and young adult rats. Four experimental groups of pregnant Sprague-Dawley rats were orally exposed to MeHg or vehicle from gestational day 5 to weaning: (1 control (vehicle, (2 250 μg/kg/day MeHg, (3 500 μg/kg/day MeHg, and (4 vehicle, and treated on the test day with MK-801 (0.15 mg/kg i.p., an antagonist of the N-methyl D-aspartate receptor. The effects were evaluated in male offspring through the open field test, object recognition test, Morris water maze, and conditioned taste aversion. For each test and stage assessed, different groups of animals were used. MeHg exposure, in a dose-dependent manner, disrupted exploratory behaviour, recognition memory, spatial learning, and acquisition of aversive memories in periadolescent rats, but alterations were not observed in littermates tested in young adulthood. These results suggest that developmental low-dose exposure to MeHg induces age-dependent detrimental effects. The relevance of decreasing exposure to MeHg in humans remains to be determined.

  6. Brief report: Assessing youth well-being in global emergency settings: Early results from the Emergency Developmental Assets Profile.

    Science.gov (United States)

    Scales, Peter C; Roehlkepartain, Eugene C; Wallace, Teresa; Inselman, Ashley; Stephenson, Paul; Rodriguez, Michael

    2015-12-01

    The 13-item Emergency Developmental Assets Profile measures the well-being of children and youth in emergency settings such as refugee camps and armed conflict zones, assessing whether young people are experiencing adequate positive relationships and opportunities, and developing positive values, skills, and self-perceptions, despite being in crisis circumstances. The instrument was found to have acceptable and nearly identical internal consistency reliability in 22 administrations in non-emergency samples in 15 countries (.75), and in 4 samples of youth ages 10-18 (n = 1550) in the emergency settings (war refugees and typhoon victims, .74) that are the measure's focus, and evidence of convergent validity. Confirmatory Factor Analysis showed acceptable model fit among those youth in emergency settings. Measures of model fit showed that the Em-DAP has configural and metric invariance across all emergency contexts and scalar invariance across some. The Em-DAP is a promising brief cross-cultural tool for assessing the developmental quality of life as reported by samples of youth in a current humanitarian crisis situation. The results can help to inform international relief program decisions about services and activities to be provided for children, youth, and families in emergency settings.

  7. On the nature of facultative and constitutive CAM: environmental and developmental control of CAM expression during early growth of Clusia, Kalanchöe, and Opuntia.

    Science.gov (United States)

    Winter, Klaus; Garcia, Milton; Holtum, Joseph A M

    2008-01-01

    The capacity to induce crassulacean acid metabolism developmentally (constitutive CAM) and to up-regulate CAM expression in response to drought stress (facultative CAM) was studied in whole shoots of seven species by measuring net CO(2) gas exchange for up to 120 day-night cycles during early growth. In Clusia rosea, CAM was largely induced developmentally. Well-watered seedlings began their life cycle as C(3) plants and developed net dark CO(2) fixation indicative of CAM after the initiation of the fourth leaf pair following the cotyledons. Thereafter, CAM activity increased progressively and drought stress led to only small additional, reversible increases in dark CO(2) fixation. In contrast, CAM expression was overwhelmingly under environmental control in seedlings and mature plants of Clusia pratensis. C(3)-type CO(2) exchange was maintained under well-watered conditions, but upon drought stress, CO(2) exchange shifted, in a fully reversible manner, to a CAM-type pattern. Clusia minor showed CO(2) exchange reponses intermediate to those of C. rosea and C. pratensis. Clusia cretosa operated in the C(3) mode at all times. Notably, reversible stress-induced increases of dark CO(2) fixation were also observed during the developmental progression to pronounced CAM in young Kalanchoë daigremontiana and Kalanchoë pinnata, two species considered constitutive CAM species. Drought-induced up-regulation of CAM was even detected in young cladodes of a cactus, Opuntia ficus-indica, an archetypal constitutive CAM species. Evidently, the defining characteristics of constitutive and facultative CAM are shared, to variable degrees, by all CAM species.

  8. Mechanical stretch induces mitochondria-dependent apoptosis in neonatal rat cardiomyocytes and G2/M accumulation in cardiac fibroblasts

    Institute of Scientific and Technical Information of China (English)

    Xu Dong LIAO; Xiao Hui WANG; Hai Jing JIN; Lan Ying CHEN; Quan CHEN

    2004-01-01

    Heart remodeling is associated with the loss of cardiomyocytes and increase of fibrous tissue owing to abnormal mechanical load in a number of heart disease conditions. In present study,a well-described in vitro sustained stretch model was employed to study mechanical stretch-induced responses in both neonatal cardiomyocytes and cardiac fibroblasts. Cardiomyocytes,but not cardiac fibroblasts,underwent mitochondria-dependent apoptosis as evidenced by cytochrome c (cyto c) and Smac/DIABLO release from mitochondria into cytosol accompanied by mitochondrial membrane potential (△ψm) reduction,indicative of mitochondrial permeability transition pore (PTP)opening. Cyclosporin A,an inhibitor of PTP,inhibited stretch-induced cyto c release,△ψm reduction and apoptosis,suggesting an important role of mitochondrial PTP in stretch-induced apoptosis. The stretch also resulted in increased expression of the pro-apoptotic Bcl-2 family proteins,including Bax and Bad,in cardiomyocytes,but not in fibroblasts. Bax was accumulated in mitochondria following stretch. Cell permeable Bid-BH3 peptide could induce and facilitate stretch-induced apoptosis and △ψm reduction in cardiomyocytes. These results suggest that Bcl-2 family proteins play an important role in coupling stretch signaling to mitochondrial death machinery,probably by targeting to PTP. Interestingly,the levels of p53 were increased at 12 h after stretch although we observed that Bax upregulation and apoptosis occurred as early as 1 h. Adenovirus delivered dominant negative p53 blocked Bax upregulation in cardiomyocytes but showed partial effect on preventing stretch-induced apoptosis,suggesting that p53 was only partially involved in mediating stretch-induced apoptosis. Furthermore,we showed that p21 was upregulated and cyclin B l was downregulated only in cardiac fibroblasts,which may be associated with G2/M accumulation in response to mechanical stretch.

  9. A new hynobiid-like salamander (Amphibia, Urodela from Inner Mongolia, China, provides a rare case study of developmental features in an Early Cretaceous fossil urodele

    Directory of Open Access Journals (Sweden)

    Jia Jia

    2016-10-01

    Full Text Available A new fossil salamander, Nuominerpeton aquilonaris (gen. et sp. nov., is named and described based on specimens from the Lower Cretaceous Guanghua Formation of Inner Mongolia, China. The new discovery documents a far northern occurrence of Early Cretaceous salamanders in China, extending the geographic distribution for the Mesozoic fossil record of the group from the Jehol area (40th–45th parallel north to near the 49th parallel north. The new salamander is characterized by having the orbitosphenoid semicircular in shape; coracoid plate of the scapulocoracoid greatly expanded with a convex ventral and posterior border; ossification of two centralia in carpus and tarsus; and first digit being about half the length of the second digit in both manus and pes. The new salamander appears to be closely related to hynobiids, although this inferred relationship awaits confirmation by research in progress by us on a morphological and molecular combined analysis of cryptobranchoid relationships. Comparison of adult with larval and postmetamorphic juvenile specimens provides insights into developmental patterns of cranial and postcranial skeletons in this fossil species, especially resorption of the palatine and anterior portions of the palatopterygoid in the palate and the coronoid in the mandible during metamorphosis, and postmetamorphic ossification of the mesopodium in both manus and pes. Thus, this study provides a rare case study of developmental features in a Mesozoic salamander.

  10. A role for Gcn5 in cardiomyocyte differentiation of rat mesenchymal stem cells.

    Science.gov (United States)

    Li, Li; Zhu, Jing; Tian, Jie; Liu, Xiaoyan; Feng, Chuan

    2010-12-01

    MSCs possess the capacity of self-renewal and potential of differentiation into various kinds of specialized tissue cells including myocardiocytes. From self-renewing to oriented differentiation, chromatin is remodeled into heritable states that allow activation or maintain the repression of regulatory genes, which means specific genes in self-renewing switched off and specific genes in oriented differentiation activated (Bernstein et al. Cell 125:315-326, 2006). These epigenetic states are established and controlled largely by specific patterns of histone posttranslational modifications, in particular, histone acetylation (Li Nat Rev Genet 3:662-673, 2002). In cardiomyocyte differentiation of rat MSCs, we focused on Gcn5, which linked a known transcriptional coactivator with catalytic histone acetyltransferase activity (Brownell et al. Cell 84:843-851, 1996). To clarify participatory in vivo role of Gcn5, using an RNA interference (RNAi) strategy employing shRNA to specifically knockdown Gcn5 expression in MSCs, we found that HAT activity altered dynamically depended on the inhibition of Gcn5 during MSCs differentiation. Chromatin immunoprecipitation (ChIP) assay showed the increased binding of acetyl histone H3 to the early cardiomyocyte-specific genes GATA4 and NKx2.5 promoters in cardiomyocyte differentiation of MSCs by 5-azacytidine inducing, whereas the decreased binding with lower Gcn5 expression. Cell ultrastructure analysis revealed that MSCs induced by 5-azacytidine possess morphological characteristics of cardiomyocyte cells. The shape of MSCs transfected by Gcn5 RNAi was similar to normal MSCs, but the chromatin showed heavy electron-density and a hard-packed structure. This intermediate state of chromatin may be an inactive part of MSCs differentiation. These results demonstrate that Gcn5, possessing acetyltransferase activity, is involved in regulating chromatin configuration around GATA4 and NKx2.5 in cardiomyocyte differentiation of rat MSCs by

  11. A Developmental Cascade Model of Behavioral Sleep Problems and Emotional and Attentional Self-Regulation Across Early Childhood.

    Science.gov (United States)

    Williams, Kate E; Berthelsen, Donna; Walker, Sue; Nicholson, Jan M

    2017-01-01

    This article documents the longitudinal and reciprocal relations among behavioral sleep problems and emotional and attentional self-regulation in a population sample of 4,109 children participating in Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC)-Infant Cohort. Maternal reports of children's sleep problems and self-regulation were collected at five time-points from infancy to 8-9 years of age. Longitudinal structural equation modeling supported a developmental cascade model in which sleep problems have a persistent negative effect on emotional regulation, which in turn contributes to ongoing sleep problems and poorer attentional regulation in children over time. Findings suggest that sleep behaviors are a key target for interventions that aim to improve children's self-regulatory capacities.

  12. Effect of synchronization of donor cells in early G1-phase using shake-off method on developmental potential of somatic cell nuclear transfer embryos in cattle.

    Science.gov (United States)

    Goto, Yuji; Hirayama, Muneyuki; Takeda, Kazuya; Tukamoto, Nobuyuki; Sakata, Osamu; Kaeriyama, Hiroshi; Geshi, Masaya

    2013-08-01

    In this study, we compared the developmental ability of somatic cell nuclear transfer (SCNT) embryos reconstructed with three bovine somatic cells that had been synchronized in G0-phase (G0-SCNT group) or early G1-phase (eG1-SCNT group). Furthermore, we investigated the production efficiency of cloned offspring for NT embryos derived from these donor cells. The G0-phase and eG1-phase cells were synchronized, respectively, using serum starvation and antimitotic reagent treatment combined with shaking of the plate containing the cells (shake-off method). The fusion rate in the G0-SCNT groups (64.2 ± 1.8%) was significantly higher than that of eG1-SCNT groups (39.2 ± 1.9%) (P cells in eG1-phase using the shake-off method improved the overall production efficiency of the clone offspring per transferred embryo.

  13. Intracellular diffusion restrictions in isolated cardiomyocytes from rainbow trout

    Directory of Open Access Journals (Sweden)

    Birkedal Rikke

    2009-12-01

    Full Text Available Abstract Background Restriction of intracellular diffusion of adenine nucleotides has been studied intensively on adult rat cardiomyocytes. However, their cause and role in vivo is still uncertain. Intracellular membrane structures have been suggested to play a role. We therefore chose to study cardiomyocytes from rainbow trout (Oncorhynchus mykiss, which are thinner and have fewer intracellular membrane structures than adult rat cardiomyocytes. Previous studies suggest that trout permeabilized cardiac fibers also have diffusion restrictions. However, results from fibers may be affected by incomplete separation of the cells. This is avoided when studying permeabilized, isolated cardiomyocytes. The aim of this study was to verify the existence of diffusion restrictions in trout cardiomyocytes by comparing ADP-kinetics of mitochondrial respiration in permeabilized fibers, permeabilized cardiomyocytes and isolated mitochondria from rainbow trout heart. Experiments were performed at 10, 15 and 20°C in the absence and presence of creatine. Results Trout cardiomyocytes hypercontracted in the solutions used for mammalian cardiomyocytes. We developed a new solution in which they retained their shape and showed stable steady state respiration rates throughout an experiment. The apparent ADP-affinity of permeabilized cardiomyocytes was different from that of fibers. It was higher, independent of temperature and not increased by creatine. However, it was still about ten times lower than in isolated mitochondria. Conclusions The differences between fibers and cardiomyocytes suggest that results from trout heart fibers were affected by incomplete separation of the cells. However, the lower ADP-affinity of cardiomyocytes compared to isolated mitochondria indicate that intracellular diffusion restrictions are still present in trout cardiomyocytes despite their lower density of intracellular membrane structures. The lack of a creatine effect indicates that

  14. Validity and reliability of a structured interview for early detection and risk assessment of parenting and developmental problems in young children: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    van Stel Henk F

    2012-06-01

    Full Text Available Abstract Background Preventive child health care is well suited for the early detection of parenting and developmental problems. However, as far as the younger age group is concerned, there are no validated early detection instruments which cover both the child and its environment. Therefore, we have developed a broad-scope structured interview which assesses parents’ concerns and their need for support, using both the parental perspective and the experience of the child health care nurse: the Structured Problem Analysis of Raising Kids (SPARK. This study reports the psychometric characteristics of the SPARK. Method A cross-sectional study of 2012 18-month-old children, living in Zeeland, a province of the Netherlands. Inter-rater reliability was assessed in 67 children. Convergent validity was assessed by comparing SPARK-domains with domains in self-report questionnaires on child development and parenting stress. Discriminative validity was assessed by comparing different outcomes of the SPARK between groups with different levels of socio-economic status and by performing an extreme-groups comparison. The user experience of both parents and nurses was assessed with the aid of an online survey. Results The response rate was 92.1% for the SPARK. Self-report questionnaires were returned in the case of 66.9% of the remaining 1721 children. There was selective non-reporting: 33.1% of the questionnaires were not returned, covering 65.2% of the children with a high-risk label according to the SPARK (p  Conclusion The SPARK discriminates between children with a high, increased and low risk of parenting and developmental problems. It does so in a reliable way, but more research is needed on aspects of validity and in other populations.

  15. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

    Science.gov (United States)

    Jonscher, Karen R; Stewart, Michael S; Alfonso-Garcia, Alba; DeFelice, Brian C; Wang, Xiaoxin X; Luo, Yuhuan; Levi, Moshe; Heerwagen, Margaret J R; Janssen, Rachel C; de la Houssaye, Becky A; Wiitala, Ellen; Florey, Garrett; Jonscher, Raleigh L; Potma, Eric O; Fiehn, Oliver; Friedman, Jacob E

    2016-12-22

    Nonalcoholic fatty liver disease (NAFLD) is widespread in adults and children. Early exposure to maternal obesity or Western-style diet (WD) increases steatosis and oxidative stress in fetal liver and is associated with lifetime disease risk in the offspring. Pyrroloquinoline quinone (PQQ) is a natural antioxidant found in soil, enriched in human breast milk, and essential for development in mammals. We investigated whether a supplemental dose of PQQ, provided prenatally in a mouse model of diet-induced obesity during pregnancy, could protect obese offspring from progression of NAFLD. PQQ treatment given pre- and postnatally in WD-fed offspring had no effect on weight gain but increased metabolic flexibility while reducing body fat and liver lipids compared with untreated obese offspring. Indices of NAFLD including hepatic ceramide levels, oxidative stress and expression of proinflammatory genes (Nos2, Nlrp3, Il6, and Ptgs2) were decreased in WD PQQ-fed mice, concomitant with increased expression of fatty acid oxidation genes and decreased Pparg expression. Notably, these changes persisted even after PQQ withdrawal at weaning. Our results suggest that supplementation with PQQ, particularly during pregnancy and lactation, protects offspring from WD-induced developmental programming of hepatic lipotoxicity and may help slow the advancing epidemic of NAFLD in the next generation.-Jonscher, K. R., Stewart, M. S., Alfonso-Garcia, A., DeFelice, B. C., Wang, X. X., Luo, Y., Levi, M., Heerwagen, M. J. R., Janssen, R. C., de la Houssaye, B. A., Wiitala, E., Florey, G., Jonscher, R. L., Potma, E. O., Fiehn, O. Friedman, J. E. Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice.

  16. Effects of Zn fertilization on hordein transcripts at early developmental stage of barley grain and correlation with increased Zn concentration in the mature grain.

    Directory of Open Access Journals (Sweden)

    Mohammad Nasir Uddin

    Full Text Available Zinc deficiency is causing malnutrition for nearly one third of world populations. It is especially relevant in cereal-based diets in which low amounts of mineral and protein are present. In biological systems, Zn is mainly associated with protein. Cereal grains contain the highest Zn concentration during early developmental stage. Although hordeins are the major storage proteins in the mature barley grain and suggested to be involved in Zn binding, very little information is available regarding the Zn fertilization effects of hordein transcripts at early developmental stage and possible incorporation of Zn with hordein protein of matured grain. Zinc fertilization experiments were conducted in a greenhouse with barley cv. Golden Promise. Zn concentration of the matured grain was measured and the results showed that the increasing Zn fertilization increased grain Zn concentration. Quantitative real time PCR showed increased level of total hordein transcripts upon increasing level of Zn fertilization at 10 days after pollination. Among the hordein transcripts the amount of B-hordeins was highly correlated with the Zn concentration of matured grain. In addition, protein content of the matured grain was analysed and a positive linear relationship was found between the percentage of B-hordein and total grain Zn concentration while C-hordein level decreased. Zn sensing dithizone assay was applied to localize Zn in the matured grain. The Zn distribution was not limited to the embryo and aleurone layer but was also present in the outer part of the endosperm (sub-aleurone layers which known to be rich in proteins including B-hordeins. Increased Zn fertilization enriched Zn even in the endosperm. Therefore, the increased amount of B-hordein and decreased C-hordein content suggested that B-hordein upregulation or difference between B and C hordein could be one of the key factors for Zn biofortification of cereal grains due to the Zn fertilization.

  17. SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0-5).

    Science.gov (United States)

    Soto, Timothy; Giserman Kiss, Ivy; Carter, Alice S

    2016-09-01

    Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development. © 2016 Michigan Association for Infant Mental Health.

  18. [Serological diagnosis of an infestation caused by the early developmental stages of botfly larvae (Oedemagena tarandi) in reindeer].

    Science.gov (United States)

    Solopov, N V; Kalinina, N G

    1984-01-01

    Undertaken investigations have shown that the antigen prepared from larvae of O. tarandi is diagnostically effective and stricktly specific only to this infection in the reaction of indirect hemagglutination (RIHA). The experiments have proved the possibility of practical use of RIHA as a principal method of early diagnosis of infection of reindeer caused by O. tarandi.

  19. Literacy and Language Outcomes of Comprehensive and Developmental-Constructivist Approaches to Early Childhood Education: A Systematic Review

    Science.gov (United States)

    Chambers, Bette; Cheung, Alan C. K.; Slavin, Robert E.

    2016-01-01

    This systematic review of research on early childhood programs seeks to identify effective approaches capable of improving literacy and language outcomes for preschoolers. It applies consistent standards to determine the strength of evidence supporting a variety of approaches, which fell into two main categories: "comprehensive…

  20. Exposure to parents’ negative emotions in early life as a developmental pathway in the intergenerational transmission of depression and anxiety

    NARCIS (Netherlands)

    Aktar, E.

    2016-01-01

    This thesis aims to examine the links between exposure to parents’ depression and anxiety in the early years of life, and infants’ socio-emotional development. The thesis first focuses on the associations between infants’ and parents’ emotional expressions, and between infants’ and parents’ reaction

  1. Implications of a neural network model of early sensori-motor development for the field of developmental neurology

    NARCIS (Netherlands)

    van Heijst, JJ; Touwen, BCL; Vos, JE

    1999-01-01

    This paper reports on a neural network model for early sensori-motor development and on the possible implications of this research for our understanding and, eventually, treatment of motor disorders like cerebral palsy. We recapitulate the results we published in detail in a series of papers [1-4].

  2. Mapping Early Speech: Prescriptive Developmental Profiles for Very Remote Aboriginal Students in the First Two Years of School

    Science.gov (United States)

    Kenny, Lawrence

    2011-01-01

    This article examines the issues surrounding the mapping of the oral language development of Standard Australian English (SAE) in the early school years of remote and very remote Aboriginal education in the Northern Territory (NT). Currently, teachers in this context have 2 mandated documents as guides that chart the development of SAE oracy.…

  3. Potential Developmental and Early Life Health Effects of Nanomaterials: Data Gaps and Research Needs for Risk Assessment

    Science.gov (United States)

    Although research examining the toxicology of nanomaterials has been ongoing for many years, early studies largely focus on respiratory effects, and are limited by lack of appropriate dose metrics and a limited understanding of the role of the physicochemical properties of nanoma...

  4. In vitro differentiation of rat embryonic stem cells into functional cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    Nan Cao; Jing Liao; Zumei Liu; Wen min Zhu; Jia Wang; Lijun Liu; Lili Yu

    2011-01-01

    The recent breakthrough in the generation of rat embryonic stem cells (rESCs) opens the door to application of gene targeting to create models for the study of human diseases.In addition,the in vitro differentiation system from rESCs into derivatives of three germ layers will serve as a powerful tool and resource for the investigation of mammalian development,cell function,tissue repair,and drug discovery.However,these uses have been limited by the difficulty of in vitro differentiation.The aims of this study were to establish an in vitro differentiation system from rESCs and to investigate whether rESCs are capable of forming terminal-differentiated cardiomyocytes.Using newly established rESCs,we found that embryoid body (EB)-based method used in mouse ESC (mESC) differentiation failed to work for the serum-free cultivated rESCs.We then developed a protocol by combination of three chemical inhibitors and feeder-conditioned medium.Under this condition,rESCs formed EBs,propagated and differentiated into three embryonic germ layers.Moreover,rESC-formed EBs could differentiate into spontaneously beating cardiomyocytes after plating.Analyses of molecular,structural,and functional properties revealed that rESC-derived cardiomyocytes were similar to those derived from fetal rat hearts and mESCs.In conclusion,we successfully developed an in vitro differentiation system for rESCs through which functional myocytes were generated and displayed phenotypes of rat fetal cardiomyocytes.This unique cellular system will provide a new approach to study the early development and cardiac function,and serve as an important tool in pharmacological testing and cell therapy.

  5. Regulation of myoglobin in hypertrophied rat cardiomyocytes in experimental pulmonary hypertension.

    Science.gov (United States)

    Peters, E L; Offringa, C; Kos, D; Van der Laarse, W J; Jaspers, R T

    2016-10-01

    A major problem in chronic heart failure is the inability of hypertrophied cardiomyocytes to maintain the required power output. A Hill-type oxygen diffusion model predicts that oxygen supply is limiting in hypertrophied cardiomyocytes at maximal rates of oxygen consumption and that this limitation can be reduced by increasing the myoglobin (Mb) concentration. We explored how cardiac hypertrophy, oxidative capacity, and Mb expression in right ventricular cardiomyocytes are regulated at the transcriptional and translational levels in an early stage of experimental pulmonary hypertension, in order to identify targets to improve the oxygen supply/demand ratio. Male Wistar rats were injected with monocrotaline to induce pulmonary hypertension (PH) and right ventricular heart failure. The messenger RNA (mRNA) expression levels per nucleus of growth factors insulin-like growth factor-1Ea (IGF-1Ea) and mechano growth factor (MGF) were higher in PH than in healthy controls, consistent with a doubling in cardiomyocyte cross-sectional area (CSA). Succinate dehydrogenase (SDH) activity was unaltered, indicating that oxidative capacity per cell increased. Although the Mb protein concentration was unchanged, Mb mRNA concentration was reduced. However, total RNA per nucleus was about threefold higher in PH rats versus controls, and Mb mRNA content expressed per nucleus was similar in the two groups. The increase in oxidative capacity without an increase in oxygen supply via Mb-facilitated diffusion caused a doubling of the critical extracellular oxygen tension required to prevent hypoxia (PO2crit). We conclude that Mb mRNA expression is not increased during pressure overload-induced right ventricular hypertrophy and that the increase in myoglobin content per myocyte is likely due to increased translation. We conclude that increasing Mb mRNA expression may be beneficial in the treatment of experimental PH.

  6. Lack of long-term behavioral alterations after early postnatal treatment with tropisetron: implications for developmental psychobiology.

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    Inta, Dragos; Vogt, Miriam A; Lima-Ojeda, Juan M; Pfeiffer, Natascha; Schneider, Miriam; Gass, Peter

    2011-07-01

    The early postnatal period represents a critical time window for brain development. Transient Cajal-Retzius cells in layer I of the cortex play an important role in cortical lamination by modulating neuronal migration and maturation. Recent data have demonstrated that the 5-HT(3) receptor antagonist and alpha7 nicotinic receptor partial agonist tropisetron, acting via 5-HT(3) receptors expressed on Cajal-Retzius cells, can disturb the formation of cortical columns at perinatal stages. This process is thought to be involved in several neuropsychiatric disorders. Here we investigated the possible long-term behavioral effects of exposure to tropisetron at early postnatal stages in mice. We found that the administration of 1mg/kg, intraperitoneal (i.p.) tropisetron from postnatal days 2-12 (P2-P12) did not induce significant cognitive, schizophrenia-like or emotional alterations in tropisetron-treated animals as compared to controls, when tested in multiple behavioral assays. These results may be of relevance regarding the possible protracted deleterious neuropsychiatric effects of tropisetron during early life.

  7. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    Science.gov (United States)

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.

  8. Toxicity of road deicing salt (NaCl) and copper (Cu) to fertilization and early developmental stages of Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Mahrosh, Urma; Kleiven, Merethe; Meland, Sondre; Rosseland, Bjørn Olav; Salbu, Brit; Teien, Hans-Christian

    2014-09-15

    In many countries, salting of ice or snow covered roads may affect aquatic organisms in the catchment directly or indirectly by mobilization of toxic metals. We studied the toxicity of road deicing salt and copper (Cu) on the vulnerable early life stages of Atlantic salmon (Salmo salar), from fertilization till hatching. Controlled episodic exposure to road salt (≥ 5,000 mg/L) during fertilization resulted in reduced swelling and less percent egg survival. Exposure to Cu both during and post fertilization caused delayed hatching. Larval deformities were, however found as an additional effect, when eggs were exposed to high salt concentration (≥ 5,000 mg/L) mixed with Cu (10 μg Cu/L) during fertilization. Thus, it appears that the sensitivity of early developmental stages of Atlantic salmon increased when exposed to these stressors, and road salt application during spawning can pose threat to Atlantic salmon in water bodies receiving road runoff. The study gives insight on assessment and management of risks on Atlantic salmon population posed by road related hazardous chemicals.

  9. Newborn hypoxia/anoxia inhibits cardiomyocyte proliferation and decreases cardiomyocyte endowment in the developing heart: role of endothelin-1.

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    Alexandra N Paradis

    Full Text Available In the developing heart, cardiomyocytes undergo terminal differentiation during a critical window around birth. Hypoxia is a major stress to preterm infants, yet its effect on the development and maturation of the heart remains unknown. We tested the hypothesis in a rat model that newborn anoxia accelerates cardiomyocyte terminal differentiation and results in reduced cardiomyocyte endowment in the developing heart via an endothelin-1-dependent mechanism. Newborn rats were exposed to anoxia twice daily from postnatal day 1 to 3, and hearts were isolated and studied at postnatal day 4 (P4, 7 (P7, and 14 (P14. Anoxia significantly increased HIF-1α protein expression and pre-proET-1 mRNA abundance in P4 neonatal hearts. Cardiomyocyte proliferation was significantly decreased by anoxia in P4 and P7, resulting in a significant reduction of cardiomyocyte number per heart weight in the P14 neonates. Furthermore, the expression of cyclin D2 was significantly decreased due to anoxia, while p27 expression was increased. Anoxia has no significant effect on cardiomyocyte binucleation or myocyte size. Consistently, prenatal hypoxia significantly decreased cardiomyocyte proliferation but had no effect on binucleation in the fetal heart. Newborn administration of PD156707, an ETA-receptor antagonist, significantly increased cardiomyocyte proliferation at P4 and cell size at P7, resulting in an increase in the heart to body weight ratio in P7 neonates. In addition, PD156707 abrogated the anoxia-mediated effects. The results suggest that hypoxia and anoxia via activation of endothelin-1 at the critical window of heart development inhibits cardiomyocyte proliferation and decreases myocyte endowment in the developing heart, which may negatively impact cardiac function later in life.

  10. Anti-aging effects of vitamin C on human pluripotent stem cell-derived cardiomyocytes.

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    Kim, Yoon Young; Ku, Seung-Yup; Huh, Yul; Liu, Hung-Ching; Kim, Seok Hyun; Choi, Young Min; Moon, Shin Yong

    2013-10-01

    Human pluripotent stem cells (hPSCs) have arisen as a source of cells for biomedical research due to their developmental potential. Stem cells possess the promise of providing clinicians with novel treatments for disease as well as allowing researchers to generate human-specific cellular metabolism models. Aging is a natural process of living organisms, yet aging in human heart cells is difficult to study due to the ethical considerations regarding human experimentation as well as a current lack of alternative experimental models. hPSC-derived cardiomyocytes (CMs) bear a resemblance to human cardiac cells and thus hPSC-derived CMs are considered to be a viable alternative model to study human heart cell aging. In this study, we used hPSC-derived CMs as an in vitro aging model. We generated cardiomyocytes from hPSCs and demonstrated the process of aging in both human embryonic stem cell (hESC)- and induced pluripotent stem cell (hiPSC)-derived CMs. Aging in hESC-derived CMs correlated with reduced membrane potential in mitochondria, the accumulation of lipofuscin, a slower beating pattern, and the downregulation of human telomerase RNA (hTR) and cell cycle regulating genes. Interestingly, the expression of hTR in hiPSC-derived CMs was not significantly downregulated, unlike in hESC-derived CMs. In order to delay aging, vitamin C was added to the cultured CMs. When cells were treated with 100 μM of vitamin C for 48 h, anti-aging effects, specifically on the expression of telomere-related genes and their functionality in aging cells, were observed. Taken together, these results suggest that hPSC-derived CMs can be used as a unique human cardiomyocyte aging model in vitro and that vitamin C shows anti-aging effects in this model.

  11. Stroma cell-derived factor-1α signaling enhances calcium transients and beating frequency in rat neonatal cardiomyocytes.

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    Ielham Hadad

    Full Text Available Stroma cell-derived factor-1α (SDF-1α is a cardioprotective chemokine, acting through its G-protein coupled receptor CXCR4. In experimental acute myocardial infarction, administration of SDF-1α induces an early improvement of systolic function which is difficult to explain solely by an anti-apoptotic and angiogenic effect. We wondered whether SDF-1α signaling might have direct effects on calcium transients and beating frequency.Primary rat neonatal cardiomyocytes were culture-expanded and characterized by immunofluorescence staining. Calcium sparks were studied by fluorescence microscopy after calcium loading with the Fluo-4 acetoxymethyl ester sensor. The cardiomyocyte enriched cellular suspension expressed troponin I and CXCR4 but was vimentin negative. Addition of SDF-1α in the medium increased cytoplasmic calcium release. The calcium response was completely abolished by using a neutralizing anti-CXCR4 antibody and partially suppressed and delayed by preincubation with an inositol triphosphate receptor (IP3R blocker, but not with a ryanodine receptor (RyR antagonist. Calcium fluxes induced by caffeine, a RyR agonist, were decreased by an IP3R blocker. Treatment with forskolin or SDF-1α increased cardiomyocyte beating frequency and their effects were additive. In vivo, treatment with SDF-1α increased left ventricular dP/dtmax.These results suggest that in rat neonatal cardiomyocytes, the SDF-1α/CXCR4 signaling increases calcium transients in an IP3-gated fashion leading to a positive chronotropic and inotropic effect.

  12. Developmental trajectories of preschool early literacy skills: a comparison of language-minority and monolingual-English children.

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    Lonigan, Christopher J; Farver, Joann M; Nakamoto, Jonathan; Eppe, Stefanie

    2013-10-01

    This study utilized latent growth-curve analyses to determine if the early literacy skills of children who were Spanish-speaking language-minority (LM) followed a similar quantitative growth profile over a preschool year as that of a group of children from a comparable socioeconomic (SES) background but who were not LM. Participants, who ranged in age from 37 to 60 months (M = 50.73; SD = 5.04), included 540 Spanish-speaking LM and 408 non-LM children (47% girls) who were enrolled in 30 Head Start classrooms. Scores on a measure of oral language and measures of code-related skills (i.e., phonological awareness, print knowledge) were lower for LM children than for non-LM children. LM children experienced significantly faster growth in oral language skills than did non-LM children. Growth for print knowledge and blending was similar for LM and non-LM children, whereas LM children experienced slightly less growth than non-LM children on elision. The inclusion of child (i.e., initial language scores, age, nonverbal cognitive ability) and family (i.e., maternal/paternal education, 2-parent household, father employment) variables eliminated initial differences between LM and non-LM children on the code-related variables, and the effect was due primarily to children's initial oral language skills. These results indicate that the early risk for reading-related problems experienced by Spanish-speaking LM children is due both to low SES and to their LM status, and they highlight the critical need for the development, evaluation, and deployment of early instructional programs for LM children with limited English oral language proficiency.

  13. Calcium and mitochondrial metabolism in ceramide-induced cardiomyocyte death.

    Science.gov (United States)

    Parra, Valentina; Moraga, Francisco; Kuzmicic, Jovan; López-Crisosto, Camila; Troncoso, Rodrigo; Torrealba, Natalia; Criollo, Alfredo; Díaz-Elizondo, Jessica; Rothermel, Beverly A; Quest, Andrew F G; Lavandero, Sergio

    2013-08-01

    Ceramides are important intermediates in the biosynthesis and degradation of sphingolipids that regulate numerous cellular processes, including cell cycle progression, cell growth, differentiation and death. In cardiomyocytes, ceramides induce apoptosis by decreasing mitochondrial membrane potential and promoting cytochrome-c release. Ca(2+) overload is a common feature of all types of cell death. The aim of this study was to determine the effect of ceramides on cytoplasmic Ca(2+) levels, mitochondrial function and cardiomyocyte death. Our data show that C2-ceramide induces apoptosis and necrosis in cultured cardiomyocytes by a mechanism involving increased Ca(2+) influx, mitochondrial network fragmentation and loss of the mitochondrial Ca(2+) buffer capacity. These biochemical events increase cytosolic Ca(2+) levels and trigger cardiomyocyte death via the activation of calpains. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Developmental effects of imatinib mesylate on follicle assembly and early activation of primordial follicle pool in postnatal rat ovary.

    Science.gov (United States)

    Asadi-Azarbaijani, Babak; Santos, Regiane R; Jahnukainen, Kirsi; Braber, Saskia; van Duursen, Majorie B M; Toppari, Jorma; Saugstad, Ola D; Nurmio, Mirja; Oskam, Irma C

    2017-03-01

    Imatinib mesylate is an anti-cancer agent that competitively inhibits several receptor tyrosine kinases (RTKs). RTKs play important roles in the regulation of primordial follicle formation, the recruitment of primordial follicles into the pool of growing follicles and maturation of the follicles. In the present study, we investigated the effects of the tyrosine kinase inhibitor imatinib on primordial follicle assembly and early folliculogenesis in postnatal rats. Female Sprague-Dawley rats were treated with either imatinib (150mg/kg) or placebo (water) on postnatal days 2-4. Bilateral ovariectomy was performed on postnatal day 2 and 5. Histology, immunohistochemistry, and mRNA analysis were performed. Imatinib treatment was associated with increased density of the multi-oocyte follicles (Pprimordial follicles, increased expression of c-Kit and AMH, and decreased protein expression of Kit-ligand and GDF9 when compared to age-matched controls. In conclusion, imatinib affects folliculogenesis in postnatal rat ovaries by delaying the cluster breakdown, follicular assembly and early activation of the primordial follicle pool. Copyright © 2016 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  15. Chronic intermittent hypoxia aggravates cardiomyocyte apoptosis in rat ovariectomized model

    Institute of Scientific and Technical Information of China (English)

    GAO Ying-hui; CHEN Lin; MA Yan-liang; HE Quan-ying

    2012-01-01

    group,but the ratio of bax/bcl-2was significantly increased in the OC group (P <0.05); this was associated with severe cardiomycyte apoptosis in the OC group.TUNEL confirmed this observation.Conclusions This study found that CIH may induce oxidative stress in OVX rats but not in CIH rats,and cause more severe cardiomyocyte apoptosis in OVX rats compared with CIH rats.This means that OVX rats exposed to CIH suffered more severe cardiac injury compared with CIH rats due to reduced antioxidation.These findings may partly explain the reason why OSA has a worse cardiovascular impact on menopausal women,and emphasize the importance of detection and early treatment of OSA in menopausal patients.

  16. Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform.

    Science.gov (United States)

    Denning, Chris; Borgdorff, Viola; Crutchley, James; Firth, Karl S A; George, Vinoj; Kalra, Spandan; Kondrashov, Alexander; Hoang, Minh Duc; Mosqueira, Diogo; Patel, Asha; Prodanov, Ljupcho; Rajamohan, Divya; Skarnes, William C; Smith, James G W; Young, Lorraine E

    2016-07-01

    Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

  17. Developmental relations between sympathy, moral emotion attributions, moral reasoning, and social justice values from childhood to early adolescence.

    Science.gov (United States)

    Daniel, Ella; Dys, Sebastian P; Buchmann, Marlis; Malti, Tina

    2014-10-01

    This study examined the development of sympathy, moral emotion attributions (MEA), moral reasoning, and social justice values in a representative sample of Swiss children (N = 1273) at 6 years of age (Time 1), 9 years of age (Time 2), and 12 years of age (Time 3). Cross-lagged panel analyses revealed that sympathy predicted subsequent increases in MEA and moral reasoning, but not vice versa. In addition, sympathy and moral reasoning at 6 and 9 years of age were associated with social justice values at 12 years of age. The results point to increased integration of affect and cognition in children's morality from middle childhood to early adolescence, as well as to the role of moral development in the emergence of social justice values.

  18. Basal autophagy protects cardiomyocytes from doxorubicin-induced toxicity.

    Science.gov (United States)

    Pizarro, Marcela; Troncoso, Rodrigo; Martínez, Gonzalo J; Chiong, Mario; Castro, Pablo F; Lavandero, Sergio

    2016-08-31

    Doxorubicin (Doxo) is one of the most effective anti-neoplastic agents but its cardiotoxicity has been an important clinical limitation. The major mechanism of Doxo-induced cardiotoxicity is associated to its oxidative capacity. However, other processes are also involved with significant consequences for the cardiomyocyte. In recent years, a number of studies have investigated the role of autophagy on Doxo-induced cardiotoxicity but to date it is not clear how Doxo alters that process and its consequence on cardiomyocytes viability. Here we investigated the effect of Doxo 1uM for 24h of stimulation on cultured neonatal rat cardiomyocytes. We showed that Doxo inhibits basal autophagy. This inhibition is due to both Akt/mTOR signaling pathway activation and Beclin 1 level decrease. To assess the role of autophagy on Doxo-induced cardiomyocyte death, we evaluated the effects 3-methyladenine (3-MA), bafilomycin A1 (BafA), siRNA Beclin 1 (siBeclin 1) and rapamycin (Rapa) on cell viability. Inhibition of autophagy with 3-MA, BafA and siBeclin 1 increased lactate dehydrogenase (LDH) release but, when autophagy was induced by Rapa, Doxo-induced cardiomyocyte death was decreased. These results suggest that Doxo inhibits basal autophagy and contributes to cardiomyocyte death. Activation of autophagy could be used as a strategy to protect the heart against Doxo toxicity.

  19. The Developing, Aging Neocortex: How genetics and epigenetics influence early developmental patterning and age-related change.

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    Kelly J. Huffman

    2012-10-01

    Full Text Available A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging

  20. Metabolic induction and early responses of mouse blastocyst developmental programming following maternal low protein diet affecting life-long health.

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    Judith J Eckert

    Full Text Available Previously, we have shown that a maternal low protein diet, fed exclusively during the preimplantation period of mouse development (Emb-LPD, is sufficient to induce by the blastocyst stage a compensatory growth phenotype in late gestation and postnatally, correlating with increased risk of adult onset cardiovascular disease and behavioural dysfunction. Here, we examine mechanisms of induction of maternal Emb-LPD programming and early compensatory responses by the embryo. Emb-LPD induced changes in maternal serum metabolites at the time of blastocyst formation (E3.5, notably reduced insulin and increased glucose, together with reduced levels of free amino acids (AAs including branched chain AAs leucine, isoleucine and valine. Emb-LPD also caused reduction in the branched chain AAs within uterine fluid at the blastocyst stage. These maternal changes coincided with an altered content of blastocyst AAs and reduced mTORC1 signalling within blastocysts evident in reduced phosphorylation of effector S6 ribosomal protein and its ratio to total S6 protein but no change in effector 4E-BP1 phosphorylated and total pools. These changes were accompanied by increased proliferation of blastocyst trophectoderm and total cells and subsequent increased spreading of trophoblast cells in blastocyst outgrowths. We propose that induction of metabolic programming following Emb-LPD is achieved through mTORC1signalling which acts as a sensor for preimplantation embryos to detect maternal nutrient levels via branched chain AAs and/or insulin availability. Moreover, this induction step associates with changes in extra-embryonic trophectoderm behaviour occurring as early compensatory responses leading to later nutrient recovery.

  1. Structure of a shark IgNAR antibody variable domain and modeling of an early-developmental isotype.

    Science.gov (United States)

    Streltsov, Victor A; Carmichael, Jennifer A; Nuttall, Stewart D

    2005-11-01

    The new antigen receptor (IgNAR) antibodies from sharks are disulphide bonded dimers of two protein chains, each containing one variable and five constant domains. Three types of IgNAR variable domains have been discovered, with Type 3 appearing early in shark development and being overtaken by the antigen-driven affinity-matured Type 1 and 2 response. Here, we have determined the first structure of a naturally occurring Type 2 IgNAR variable domain, and identified the disulphide bond that links and stabilizes the CDR1 and CDR3 loops. This disulphide bridge locks the CDR3 loop in an "upright" conformation in contrast to other shark antibody structures, where a more lateral configuration is observed. Further, we sought to model the Type 3 isotype based on the crystallographic structure reported here. This modeling indicates (1) that internal Type 3-specific residues combine to pack into a compact immunoglobulin core that supports the CDR loop regions, and (2) that despite apparent low-sequence variability, there is sufficient plasticity in the CDR3 loop to form a conformationally diverse antigen-binding surface.

  2. Mapping Human Pluripotent-to-Cardiomyocyte Differentiation: Methylomes, Transcriptomes, and Exon DNA Methylation “Memories”

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    Joshua D. Tompkins

    2016-02-01

    Full Text Available The directed differentiation of human cardiomyocytes (CMs from pluripotent cells provides an invaluable model for understanding mechanisms of cell fate determination and offers considerable promise in cardiac regenerative medicine. Here, we utilize a human embryonic stem cell suspension bank, produced according to a good manufacturing practice, to generate CMs using a fully defined and small molecule-based differentiation strategy. Primitive and cardiac mesoderm purification was used to remove non-committing and multi-lineage populations and this significantly aided the identification of key transcription factors, lncRNAs, and essential signaling pathways that define cardiomyogenesis. Global methylation profiles reflect CM development and we report on CM exon DNA methylation “memories” persisting beyond transcription repression and marking the expression history of numerous developmentally regulated genes, especially transcription factors.

  3. Reverse engineering life: physical and chemical mimetics for controlled stem cell differentiation into cardiomyocytes.

    Science.gov (United States)

    Skuse, Gary R; Lamkin-Kennard, Kathleen A

    2013-01-01

    Our ability to manipulate stem cells in order to induce differentiation along a desired developmental pathway has improved immeasurably in recent years. That is in part because we have a better understanding of the intracellular and extracellular signals that regulate differentiation. However, there has also been a realization that stem cell differentiation is not regulated only by chemical signals but also by the physical milieu in which a particular stem cell exists. In this regard we are challenged to mimic both chemical and physical environments. Herein we describe a method to induce stem cell differentiation into cardiomyocytes using a combination of chemical and physical cues. This method can be applied to produce differentiated cells for research and potentially for cell-based therapy of cardiomyopathies.

  4. Does routine child health surveillance contribute to the early detection of children with pervasive developmental disorders? – An epidemiological study in Kent, U.K.

    Directory of Open Access Journals (Sweden)

    Ritchie Jane

    2004-03-01

    Full Text Available Abstract Background Recently changed guidelines for child health surveillance in the United Kingdom (U.K. suggest targeted checks only, instead of the previously conducted routine or universal screening at 2 years and 3.5 years. There are concerns that these changes could lead to a delay in the detection of children with autism and other pervasive developmental disorders (PDD. Recent U.K. studies have suggested that the prevalence of PDD is much higher than previously estimated. This study establishes to which extent the routine checks contributed to the early detection and assessment of cases of PDD. Simultaneously we have evaluated the process involved and estimate the prevalence of PDD in our district. Methods Retrospective study design utilising community medical files. Headteachers of schools (n = 75 within Maidstone district (Kent were asked to report all children with an established diagnosis of autism or PDD attending year 4 (born '91 and '92 / n = 2536 in October 2000 based on educational records. Results 59 schools (78.7% took part in the study. A total of 33 children were reported. 21 fulfilled the inclusion criteria (12 falsely reported. The prevalences were (per 10,000: PDD 82.8 (male to female ratio 6:1, childhood autism 23.7, Asperger's syndrome 11.8 and autistic spectrum disorder 47.3. Co-existing medical conditions were noted in 14.3%; 52.4% were attending mainstream schools. In 63.2% of cases concerns – mainly in the area of speech and language development (SLD – had been documented at the 2 year check. At the 3.5 year check concerns were noted in 94.1% – the main area was again SLD (76.5%, although behavioural abnormalities were becoming more frequent (47.1%. A total of 13 children (68.4% were referred for further assessment as a direct result of the checks. Conclusions The prevalences for different types of PDD were similar to figures published recently, but much higher than reported a few years ago. Analysis of our

  5. Exposure time to caffeine affects heartbeat and cell damage-related gene expression of zebrafish Danio rerio embryos at early developmental stages.

    Science.gov (United States)

    Abdelkader, Tamer Said; Chang, Seo-Na; Kim, Tae-Hyun; Song, Juha; Kim, Dong Su; Park, Jae-Hak

    2013-11-01

    Caffeine is white crystalline xanthine alkaloid that is naturally found in some plants and can be produced synthetically. It has various biological effects, especially during pregnancy and lactation. We studied the effect of caffeine on heartbeat, survival and the expression of cell damage related genes, including oxidative stress (HSP70), mitochondrial metabolism (Cyclin G1) and apoptosis (Bax and Bcl2), at early developmental stages of zebrafish embryos. We used 100 µm concentration based on the absence of locomotor effects. Neither significant mortality nor morphological changes were detected. We monitored hatching at 48 h post-fertilization (hpf) to 96 hpf. At 60 and 72 hpf, hatching decreased significantly (P caffeine treatment with no significant difference (P > 0.05). Heartbeats per minute were 110, 110 and 112 in control at 48, 72 and 96 hpf, respectively. Caffeine significantly increased heartbeat - 122 and 136 at 72 and 96 hpf, respectively. Quantitative RT-PCR showed significant up-regulation after caffeine exposure in HSP70 at 72 hpf; in Cyclin G1 at 24, 48 and 72 hpf; and in Bax at 48 and 72 hpf. Significant down-regulation was found in Bcl2 at 48 and 72 hpf. The Bax/Bcl2 ratio increased significantly at 48 and 72 hpf. We conclude that increasing exposure time to caffeine stimulates oxidative stress and may trigger apoptosis via a mitochondrial-dependent pathway. Also caffeine increases heartbeat from early phases of development without affecting the morphology and survival but delays hatching. Use of caffeine during pregnancy and lactation may harm the fetus by affecting the expression of cell-damage related genes.

  6. Denver developmental screening test II for early identification of the infants who will develop major neurological deficit as a sequalea of hypoxic-ischemic encephalopathy.

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    Hallioglu, O; Topaloglu, A K; Zenciroglu, A; Duzovali, O; Yilgor, E; Saribas, S

    2001-08-01

    The primary aim of this study was to find widely available, inexpensive, and non-invasive parameters for early identification or prediction of the infants with hypoxic-ischemic encephalopathy (HIE) who will have a severe adverse outcome (classified as death or a major neurological deficit). Fifty-seven full-term or near-term newborn infants with a diagnosis of HIE were consecutively admitted to the neonatal intensive care unit and studied. Occurrence of seizures during the first 24 h, cranial ultrasonography (US) findings within the first 5 days of life, and Denver developmental screening test II (DDST II) at 6 months of age, were analyzed in relation to mortality and neurological status at 2 years of age. Of the 57 infants, 10 were lost to follow-up. Twenty of the remaining 47 infants had a severe adverse outcome. Among the predictors of severe adverse outcome, occurrence of seizures was found to have a poor predictive accuracy. Cranial US had 100% sensitivity, however with a rather low specificity (55%). However, DDST II at 6 months of age, yielded a very high predictive accuracy (sensitivity=100%, specificity=95%). We conclude that DDST II at 6 months of age could be used in predicting severe neurological outcome in infants with HIE.

  7. (Positive) power to the child: The role of children's willing stance toward parents in developmental cascades from toddler age to early preadolescence.

    Science.gov (United States)

    Kochanska, Grazyna; Kim, Sanghag; Boldt, Lea J

    2015-11-01

    In a change from the once-dominant view of children as passive in the parent-led process of socialization, children are now seen as active agents who can considerably influence that process. However, these newer perspectives typically focus on the child's antagonistic influence, due either to a difficult temperament or aversive, resistant, negative behaviors that elicit adversarial responses from the parent and lead to future coercive cascades in the relationship. Children's capacity to act as receptive, willing, even enthusiastic, active socialization agents is largely overlooked. Informed by attachment theory and other relational perspectives, we depict children as able to adopt an active willing stance and to exert robust positive influence in the mutually cooperative socialization enterprise. A longitudinal study of 100 community families (mothers, fathers, and children) demonstrates that willing stance (a) is a latent construct, observable in diverse parent-child contexts, parallel at 38, 52, and 67 months and longitudinally stable; (b) originates within an early secure parent-child relationship at 25 months; and (c) promotes a positive future cascade toward adaptive outcomes at age 10. The outcomes include the parent's observed and child-reported positive, responsive behavior, as well as child-reported internal obligation to obey the parent and parent-reported low level of child behavior problems. The construct of willing stance has implications for basic research in typical socialization and in developmental psychopathology as well as for prevention and intervention.

  8. Adolescent motherhood and developmental outcomes of children in early head start: the influence of maternal parenting behaviors, well-being, and risk factors within the family setting.

    Science.gov (United States)

    Rafferty, Yvonne; Griffin, Kenneth W; Lodise, Michelle

    2011-04-01

    This longitudinal study examined the influence of parenting behaviors, well-being, and risk factors of low-income adolescent mothers on the cognitive and language abilities of children from infancy to age 3. Participants consisted of 1,240 mother-child dyads enrolled in the Early Head Start Research and Evaluation Project. Data were collected using structured interviews with the mothers and from videotaped mother-child interactions during play activities when children were approximately 14 months old and again at 36 months of age. Positive parenting behaviors exhibited toward the 14-month-old children predicted gains in both cognitive and language abilities more so than did maternal well-being, risk factors within the family setting, and demographic risk factors. Gains in cognitive abilities from infancy to age 3 were predicted by supportive parenting, higher family resources, and lower family conflict when children were infants. Gains in language abilities were predicted by supportive parenting, support for language and learning in the home environment, and higher family resources when children were infants. Finally, path analyses showed that maternal age had an indirect effect on child cognitive and language abilities at age 3 through effects on parenting behaviors. Older mothers were more likely to be supportive during play at age 14 months, which in turn promoted enhanced developmental outcomes at age 3. Implications for intervention and future research are discussed.

  9. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

    Directory of Open Access Journals (Sweden)

    Ioannis Kokkinopoulos

    Full Text Available In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

  10. Single-Cell Expression Profiling Reveals a Dynamic State of Cardiac Precursor Cells in the Early Mouse Embryo.

    Science.gov (United States)

    Kokkinopoulos, Ioannis; Ishida, Hidekazu; Saba, Rie; Ruchaya, Prashant; Cabrera, Claudia; Struebig, Monika; Barnes, Michael; Terry, Anna; Kaneko, Masahiro; Shintani, Yasunori; Coppen, Steven; Shiratori, Hidetaka; Ameen, Torath; Mein, Charles; Hamada, Hiroshi; Suzuki, Ken; Yashiro, Kenta

    2015-01-01

    In the early vertebrate embryo, cardiac progenitor/precursor cells (CPs) give rise to cardiac structures. Better understanding their biological character is critical to understand the heart development and to apply CPs for the clinical arena. However, our knowledge remains incomplete. With the use of single-cell expression profiling, we have now revealed rapid and dynamic changes in gene expression profiles of the embryonic CPs during the early phase after their segregation from the cardiac mesoderm. Progressively, the nascent mesodermal gene Mesp1 terminated, and Nkx2-5+/Tbx5+ population rapidly replaced the Tbx5low+ population as the expression of the cardiac genes Tbx5 and Nkx2-5 increased. At the Early Headfold stage, Tbx5-expressing CPs gradually showed a unique molecular signature with signs of cardiomyocyte differentiation. Lineage-tracing revealed a developmentally distinct characteristic of this population. They underwent progressive differentiation only towards the cardiomyocyte lineage corresponding to the first heart field rather than being maintained as a progenitor pool. More importantly, Tbx5 likely plays an important role in a transcriptional network to regulate the distinct character of the FHF via a positive feedback loop to activate the robust expression of Tbx5 in CPs. These data expands our knowledge on the behavior of CPs during the early phase of cardiac development, subsequently providing a platform for further study.

  11. Mechanical unloading activates FoxO3 to trigger Bnip3-dependent cardiomyocyte atrophy.

    Science.gov (United States)

    Cao, Dian J; Jiang, Nan; Blagg, Andrew; Johnstone, Janet L; Gondalia, Raj; Oh, Misook; Luo, Xiang; Yang, Kai-Chun; Shelton, John M; Rothermel, Beverly A; Gillette, Thomas G; Dorn, Gerald W; Hill, Joseph A

    2013-04-08

    Mechanical assist device therapy has emerged recently as an important and rapidly expanding therapy in advanced heart failure, triggering in some patients a beneficial reverse remodeling response. However, mechanisms underlying this benefit are unclear. In a model of mechanical unloading of the left ventricle, we observed progressive myocyte atrophy, autophagy, and robust activation of the transcription factor FoxO3, an established regulator of catabolic processes in other cell types. Evidence for FoxO3 activation was similarly detected in unloaded failing human myocardium. To determine the role of FoxO3 activation in cardiac muscle in vivo, we engineered transgenic mice harboring a cardiomyocyte-specific constitutively active FoxO3 mutant (caFoxO3(flox);αMHC-Mer-Cre-Mer). Expression of caFoxO3 triggered dramatic and progressive loss of cardiac mass, robust increases in cardiomyocyte autophagy, declines in mitochondrial biomass and function, and early mortality. Whereas increases in cardiomyocyte apoptosis were not apparent, we detected robust increases in Bnip3 (Bcl2/adenovirus E1B 19-kDa interacting protein 3), an established downstream target of FoxO3. To test the role of Bnip3, we crossed the caFoxO3(flox);αMHC-Mer-Cre-Mer mice with Bnip3-null animals. Remarkably, the atrophy and autophagy phenotypes were significantly blunted, yet the early mortality triggered by FoxO3 activation persisted. Rather, declines in cardiac performance were attenuated by proteasome inhibitors. Consistent with involvement of FoxO3-driven activation of the ubiquitin-proteasome system, we detected time-dependent activation of the atrogenes program and sarcomere protein breakdown. In aggregate, these data point to FoxO3, a protein activated by mechanical unloading, as a master regulator that governs both the autophagy-lysosomal and ubiquitin-proteasomal pathways to orchestrate cardiac muscle atrophy.

  12. Early developmental exposure to high fructose intake in rats with NaCl stimulation causes cardiac damage.

    Science.gov (United States)

    Araujo, I C; Andrade, R P; Santos, F; Soares, E S; Yokota, R; Mostarda, C; Fiorino, P; De Angelis, K; Irigoyen, M C; Morris, M; Farah, V

    2016-02-01

    comparison with other groups. However, there was a uniform increase in plasma ACE activity in all treated groups compared with the C group. Data suggest that early exposure to high fructose intake produced marked alterations in metabolic and cardiovascular function. When stimulated by NaCl, the fructose-fed subjects showed further impairment in cardiac function.

  13. Dioxin exposure disrupts the differentiation of mouse embryonic stem cells into cardiomyocytes.

    Science.gov (United States)

    Wang, Ying; Fan, Yunxia; Puga, Alvaro

    2010-05-01

    Experimental exposure of fish, birds, and rodents to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) causes multiple Ah receptor-mediated developmental abnormalities, an observation consistent with compelling evidence in human populations that TCDD exposure is responsible for a significant incidence of birth defects. To characterize molecular mechanisms that might explain the developmental effects of dioxin, we have studied the consequences of TCDD exposure on the differentiation of mouse embryonic stem (ES) cells in culture and on the expression of genes, including those coding for homeodomain containing transcription factors, with a role in progression of tissue differentiation and embryonic identity during development. We find that TCDD treatment causes expression changes in a number of homeobox genes concomitant with Ah receptor recruitment to the promoters of many of these genes, whether under naïve or dioxin-activated conditions. TCDD exposure also derails temporal expression trajectories of developmentally regulated genes in a wide diversity of differentiation pathways, including genes with functions in neural and cardiovascular development, self-renewal, hematopoiesis and mesenchymal lineage specification, and Notch and Wnt pathways. Among these, we find that TCDD represses the expression of the cardiac development-specific Nkx2.5 homeobox transcription factor, of cardiac troponin-T and of alpha- and beta-myosin heavy chains, inhibiting the formation of beating cardiomyocytes, a characteristic phenotype of differentiating mouse ES cells in culture. These data identify potential pathways for dioxin to act as a developmental teratogen, possibly critical to cardiovascular development and disease, and provide molecular targets that may help us understand the molecular basis of Ah receptor-mediated developmental toxicity.

  14. 大菱鲆早期发育过程中免疫器官的发生%Ontogeny of immune organs during early developmental stages of turbot

    Institute of Scientific and Technical Information of China (English)

    佟雪红; 徐世宏; 刘清华; 李军; 肖志忠; 马道远

    2011-01-01

    应用组织切片研究了大菱鲆(Scophthalmus maximus)初孵仔鱼至60日龄幼鱼免疫器官的发育过程。结果表明,免疫器官原基出现的先后顺序是头肾、脾脏和胸腺。1日龄仔鱼可以观察到头肾原基,包含未分化的造血干细胞。5日龄时,脾脏原基出现,其淋巴化开始于27日龄且发育速度较慢。13日龄时,大菱鲆仔鱼胸腺原基出现,且发育速度较快,分为外区和内区。在大菱鲆早期发育过程中,胸腺和头肾之间出现细胞迁移现象。免疫器官淋巴化的顺序是胸腺、头肾和脾脏。在免疫器官发育后期,脾脏和头,肾中均发现了黑色素-巨噬细胞中心(%A histological study was performed to investigate the development of immune organs in turbot Scophthalmus maximus from hatching to 60 days after hatching (DAH). The temporal sequence of the appearance of immune organ anlages was head kidney, spleen, and thymus. At 1 DAH, head kidney anlage and primordial stem cells were observed. Spleen anlage was present at 5 DAH, became lymphoid at 27 DAH, and developed slowly. Progenitor thymus appeared at 13 DAH, and grew quickly. An outer zone and an inner zone in the thymus were observed. Cell migration occurred between thymus and head kidney. The first functional lymphoid organ was thymus, being followed by head kidney and spleen. During the posterior developmental period of the immune organs, the melano-macrophage centers (MMCs) were not found in thymus, but was found in spleen and head kidney, with higher abundance in spleen. During the early developmental stages of turbot larvae, before the maturity of immune organs, non-specific systems might play an important role in the immunocompetence mechanisms.

  15. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  16. σK of Clostridium acetobutylicum is the first known sporulation-specific sigma factor with two developmentally separated roles, one early and one late in sporulation.

    Science.gov (United States)

    Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T

    2014-01-01

    Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σ(H) (early), σ(F), σ(E), σ(G), and σ(K) (late). Here we show that the Clostridium acetobutylicum σ(K) acts both early, prior to Spo0A expression, and late, past σ(G) activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σ(G) proteins were not detectable by Western analysis, while σ(F) protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σ(K) is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σ(F), σ(E), and σ(G), but not sporulation, which was blocked past the σ(G) stage of development, thus demonstrating that σ(K) is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles.

  17. Developmental Evaluation.

    Science.gov (United States)

    Patton, Michael Quinn

    1994-01-01

    Developmental evaluation is proposed as a term to describe certain long-term partnering relationships with clients who are, themselves, engaged in ongoing program development. Rather than a model, developmental evaluation is a relationship founded on a shared purpose and is a way of being useful in innovative settings. (SLD)

  18. AMPK and substrate availability regulate creatine transport in cultured cardiomyocytes.

    Science.gov (United States)

    Darrabie, Marcus D; Arciniegas, Antonio Jose Luis; Mishra, Rajashree; Bowles, Dawn E; Jacobs, Danny O; Santacruz, Lucia

    2011-05-01

    Profound alterations in myocellular creatine and phosphocreatine levels are observed during human heart failure. To maintain its intracellular creatine stores, cardiomyocytes depend upon a cell membrane creatine transporter whose regulation is not clearly understood. Creatine transport capacity in the intact heart is modulated by substrate availability, and it is reduced in the failing myocardium, likely adding to the energy imbalance that characterizes heart failure. AMPK, a key regulator of cellular energy homeostasis, acts by switching off energy-consuming pathways in favor of processes that generate energy. Our objective was to determine the effects of substrate availability and AMPK activation on creatine transport in cardiomyocytes. We studied creatine transport in rat neonatal cardiomyocytes and HL-1 cardiac cells expressing the human creatine transporter cultured in the presence of varying creatine concentrations and the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribonucleoside (AICAR). Transport was enhanced in cardiomyocytes following incubation in creatine-depleted medium or AICAR. The changes in transport were due to alterations in V(max) that correlated with changes in total and cell surface creatine transporter protein content. Our results suggest a positive role for AMPK in creatine transport modulation for cardiomyocytes in culture.

  19. Glucocorticoid Induced Leucine Zipper inhibits apoptosis of cardiomyocytes by doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar, David; Strom, Joshua; Chen, Qin M., E-mail: qchen@email.arizona.edu

    2014-04-01

    Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. - Highlights: • Corticosteroids act as a cytoprotective agent in cardiomyocytes • Corticosteroids induce GILZ expression in cardiomyocytes • Elevated GILZ results in resistance against apoptosis induced by doxorubicin • GILZ induces Bcl-xL protein without inducing Bcl-xL mRNA.

  20. Comparison of osteoblast and cardiomyocyte differentiation in the embryonic stem cell test for predicting embryotoxicity in vivo.

    Science.gov (United States)

    de Jong, Esther; van Beek, Lianne; Piersma, Aldert H

    2014-09-01

    One of the most studied alternative embryotoxicity assays is the embryonic stem cell test, in which the effect of compounds on cardiomyocyte differentiation is evaluated (subsequently termed the ESTc). This single differentiation endpoint may limit the predictive value of the assay. We recently published a novel embryonic stem cell based osteoblast differentiation assay (subsequently termed the ESTo), in which we studied the effect of six embryotoxic compounds. Differentiation is monitored via the differential expression of three genes related to osteogenesis (Runx2, SPARC and collagen type I). In the current study, we evaluated the effect of 14 additional compounds in the ESTo, to assess its added value as compared to the ESTc. To this end, we compared the effects of the compounds in the ESTo to their effects in the ESTc and to their published in vivo developmental toxicity profiles. The results show that there is a high overall correlation between compound potencies as regards inhibition of osteoblast and cardiomyocyte differentiation. Moreover, the results in both the ESTo and ESTc showed a significant correlation to in vivo developmental toxicity potency ranking of compounds tested. Interestingly, the embryotoxic effect of TCDD could only be detected using the ESTo, which can be explained based on its mechanism of action and its known inhibitory effect on osteogenesis. The results of TCDD suggest that incorporating the ESTo into a testing battery together with the ESTc could improve the overall predictive value of the battery.

  1. Deletion of exon 20 of the Familial Dysautonomia gene Ikbkap in mice causes developmental delay, cardiovascular defects, and early embryonic lethality.

    Directory of Open Access Journals (Sweden)

    Paula Dietrich

    Full Text Available Familial Dysautonomia (FD is an autosomal recessive disorder that affects 1/3,600 live births in the Ashkenazi Jewish population, and leads to death before the age of 40. The disease is characterized by abnormal development and progressive degeneration of the sensory and autonomic nervous system. A single base pair substitution in intron 20 of the Ikbkap gene accounts for 98% of FD cases, and results in the expression of low levels of the full-length mRNA with simultaneous expression of an aberrantly spliced mRNA in which exon 20 is missing. To date, there is no animal model for the disease, and the essential cellular functions of IKAP--the protein encoded by Ikbkap--remain unknown. To better understand the normal function of IKAP and in an effort to generate a mouse model for FD, we have targeted the mouse Ikbkap gene by homologous recombination. We created two distinct alleles that result in either loss of Ikbkap expression, or expression of an mRNA lacking only exon 20. Homozygosity for either mutation leads to developmental delay, cardiovascular and brain malformations, accompanied with early embryonic lethality. Our analyses indicate that IKAP is essential for expression of specific genes involved in cardiac morphogenesis, and that cardiac failure is the likely cause of abnormal vascular development and embryonic lethality. Our results also indicate that deletion of exon 20 abolishes gene function. This implies that the truncated IKAP protein expressed in FD patients does not retain any significant biological function.

  2. Co-parenting and feeding in early childhood: Reflections of parent dyads on how they manage the developmental stages of feeding over the first three years.

    Science.gov (United States)

    Thullen, Matthew; Majee, Wilson; Davis, Alexandra N

    2016-10-01

    Family-level influences on the development of healthy eating behaviors start in infancy and toddlerhood with how families manage developmental stages of feeding. Little research on home feeding environments for young children has examined how mothers and fathers collaborate around feeding issues or contribute jointly to feeding. The purpose of this qualitative study is to examine co-parenting with regard to infant/toddler feeding practices. Twenty-four sets of co-resident, biological parents with a child between 6 months and 3 years were interviewed together about their feeding practices and how they discussed and collaborated on feeding during the main stages of feeding development in the first three years. Analyses illuminate themes related to how specific domains of co-parenting (satisfaction with labor, support, agreement, conflict) factor into infant and toddler feeding as well as how additional factors such as having older children and employment schedules shape how both food parenting practices and co-parenting are managed in relation to feeding. Mothers were the primary managers of feeding labor. Fathers participated in feeding in different ways and levels starting in infancy and increased involvement in feeding over the first few years requiring an ongoing negotiation around co-parenting related to feeding. Overall, this study develops insights into how multiple caregivers construct a family environment specifically related to early feeding - a perspective missing from current conceptualizations of home feeding environment. Attention to the concept of co-parenting within home feeding environments should help inform more effective approaches to intervene with families on issues around childhood obesity and family health.

  3. Dietary levels of acrylamide affect rat cardiomyocyte properties.

    Science.gov (United States)

    Walters, Brandan; Hariharan, Venkatesh; Huang, Hayden

    2014-09-01

    The toxic effects of acrylamide on cytoskeletal integrity and ion channel balance is well-established in many cell types, but there has been little examination regarding the effects of acrylamide on primary cardiomyocytes, despite the importance of such components in their function. Furthermore, acrylamide toxicity is generally examined using concentrations higher than those found in vivo under starch-rich diets. Accordingly, we sought to characterize the dose-dependent effects of acrylamide on various properties, including cell morphology, contraction patterns, and junctional connexin 43 staining, in primary cardiomyocytes. We show that several days exposure to 1-100 μM acrylamide resulted in altered morphology, irregular contraction patterns, and an increase in the amount of immunoreactive signal for connexin 43 at cell junctions. We conclude that dietary levels of acrylamide may alter cellular function with prolonged exposure, in primary cardiomyocytes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Functional Differences in Engineered Myocardium from Embryonic Stem Cell-Derived versus Neonatal Cardiomyocytes

    NARCIS (Netherlands)

    Feinberg, Adam W.; Ripplinger, Crystal M.; van der Meer, Peter; Sheehy, Sean P.; Domian, Ibrahim; Chien, Kenneth R.; Parker, Kevin Kit

    2013-01-01

    Stem cell-derived cardiomyocytes represent unique tools for cell-and tissue-based regenerative therapies, drug discovery and safety, and studies of fundamental heart-failure mechanisms. However, the degree to which stem cell-derived cardiomyocytes compare to mature cardiomyocytes is often debated.

  5. File list: His.CDV.05.AllAg.Cardiomyocytes [Chip-atlas[Archive

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  12. EARLY DISTANCE INTERVENTION AND FOLLOW-UP FOR FAMILIES OF INFANTS AND TODDLERS AT RISK FOR DEVELOPMENTAL DISABILITIES AND SEVERE BEHAVIOR PROBLEMS IN PERU

    Directory of Open Access Journals (Sweden)

    Rosa Oyama-Ganiko

    2013-11-01

    Full Text Available http://dx.doi.org/10.5902/1984686X9946A major barrier to meeting the needs of low-income children and families with disabilities is distance from a center providing the diagnostics and treatment. In the U.S. several innovative ways of overcoming this difficulty have emerged, e.g. Call-In, Come-In Services in a Pediatric Psychology Practice, diagnostics and consultation via telemedicine, use of the Internet for webcasting conferences, library resources over the Internet, etc. These services are not yet available in many developing countries or in rural areas of the U.S., however.  We report below an inexpensive and effective method of early distance intervention using workshops every two months and monthly telephone follow-up at the Centro Ann Sullivan del Peru in Lima, Peru. While many poor families may not have regular access to radio, television, or the Internet, we and others (Bigelow, Carta, & LeFever, 2008 have found that almost all have cell phones, and they can be followed regularly. In our project on early prevention of severe aggression, self-injury, and stereotyped behavior among infants and toddlers at risk for developmental disabilities, monthly telephone follow-up attendance remained high throughout the one-year follow-up period (92%, while family attendance at the six bi-monthly workshops dropped off (75% to 28%. Mean BPI frequency scores decreased significantly over the year. BPI scores were significantly higher, and they decreased more in the high-attendance group than in the low-attendance group.  Family stress was reduced by 65%. Consumer satisfaction was 98%.A very similar workshop package has been given to many orphanages and to remote areas in Peru, where there is not any kind of education about disabilities and where parents have to be the best teachers. Having such tools gives them knowledge of what their children can achieve, so they would not relinquish them to government orphanages.  

  13. Icariin promotes expression of PGC-1α, PPARα, and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Ling DING; Xing-guang LIANG; Dan-yan ZHU; Yi-jia LOU

    2007-01-01

    Aim: To investigate the effect of icariin on the expression of peroxisome proliferator-activated receptor γ coactivator- 1 alpha (PGC- 1 α), peroxisome proliferator-activated receptor alpha (PPARα), and nuclear respiratory factor 1 (NRF-1) on cardiomyocyte differentiation of murine embryonic stem (ES) cells in vitro.Methods: The cardiomyocytes derived from murine ES cells were verified by immunocytochemistry using confocal laser scanning microscopy. Cardiacspecific sarcomeric proteins (ie α-actinin, troponin T) were evaluated when embryoid bodies (EB) were treated with icariin or retinoid acid. The expression of PGC-1α, PPARα, and NRF-1 were analyzed using both semiquantitative RT-PCR and Western blotting in cardiomyocyte differentiation. The phosphorylation of the p38 mitogen-activated protein kinase (MAPK) was studied in the differentiation process, and its specific inhibitor SB203580 was employed to confirm the function of the p38 MAPK on icariin-induced cardiac differentiation. Results:The application of icariin significantly induced the cardiomyocyte differentiation of EB as indicated by the promoted expression of α-actinin and troponin T. The expression of PGC-1α, PPARα and NRF-1 increased coincidently in early differentiation and the increase was dose-dependently upregulated by icariin treatment.The phosphorylation of the p38 MAPK peaked on d 6 and decreased after d 8, andthe activation was further enhanced and prolonged when the EB were subjected to icariin, which was concurrent with the elevation of PGC-1α, PPARα, and NRF-1. Moreover, the inhibition of the p38 MAPK pathway by SB203580 efficiently abolished icariin-stimulated cardiomyocyte differentiation and resulted in the capture of the upregulation of PGC-lα, PPARα, and NRF-1. Conclusion: Taken together, icariin promoted the expression of PGC-1 α, PPARα, and NRF-1 during cardiomyocyte differentiation ofmurine ES cells in vitro and the effect was partly responsible for the activation of

  14. Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is independent of myosin isoform

    Directory of Open Access Journals (Sweden)

    Yi Ting

    2012-11-01

    Full Text Available Abstract It has been reported previously that diabetic cardiomyopathy can be inhibited or reverted with chronic zinc supplementation. In the current study, we hypothesized that total cardiac calcium and zinc content is altered in early onset diabetes mellitus characterized in part as hyperglycemia (HG and that exposure of zinc ion (Zn2+ to isolated cardiomyocytes would enhance contraction-relaxation function in HG more so than in nonHG controls. To better control for differential cardiac myosin isoform expression as occurs in rodents after β-islet cell necrosis, hypothyroidism was induced in 16 rats resulting in 100% β-myosin heavy chain expression in the heart. β-Islet cell necrosis was induced in half of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG controls rats demonstrated similar myofilament performance measured as thin filament calcium sensitivity, native thin filament velocity in the myosin motility assay and contractile velocity and power. Extracellular Zn2+ reduced cardiomyocyte contractile function in both groups, but enhanced relaxation function significantly in the HG group compared to controls. Most notably, a reduction in diastolic sarcomere length with increasing pacing frequencies, i.e., incomplete relaxation, was more pronounced in the HG compared to controls, but was normalized with extracellular Zn2+ application. This is a novel finding implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation can be amelioration by Zn2+. Among the many post-translational modifications examined, only phosphorylation of ryanodine receptor (RyR at S-2808 was significantly higher in HG compared to nonHG. We did not find in our hypothyroid rats any differentiating effects of HG on myofibrillar protein phosphorylation, lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end-products, which are often implicated as complicating factors in cardiac performance due to HG. Our

  15. Zinc-induced cardiomyocyte relaxation in a rat model of hyperglycemia is independent of myosin isoform.

    Science.gov (United States)

    Yi, Ting; Cheema, Yaser; Tremble, Sarah M; Bell, Stephen P; Chen, Zengyi; Subramanian, Meenakumari; LeWinter, Martin M; VanBuren, Peter; Palmer, Bradley M

    2012-11-02

    It has been reported previously that diabetic cardiomyopathy can be inhibited or reverted with chronic zinc supplementation. In the current study, we hypothesized that total cardiac calcium and zinc content is altered in early onset diabetes mellitus characterized in part as hyperglycemia (HG) and that exposure of zinc ion (Zn2+) to isolated cardiomyocytes would enhance contraction-relaxation function in HG more so than in nonHG controls. To better control for differential cardiac myosin isoform expression as occurs in rodents after β-islet cell necrosis, hypothyroidism was induced in 16 rats resulting in 100% β-myosin heavy chain expression in the heart. β-Islet cell necrosis was induced in half of the rats by streptozocin administration. After 6 wks of HG, both HG and nonHG controls rats demonstrated similar myofilament performance measured as thin filament calcium sensitivity, native thin filament velocity in the myosin motility assay and contractile velocity and power. Extracellular Zn2+ reduced cardiomyocyte contractile function in both groups, but enhanced relaxation function significantly in the HG group compared to controls. Most notably, a reduction in diastolic sarcomere length with increasing pacing frequencies, i.e., incomplete relaxation, was more pronounced in the HG compared to controls, but was normalized with extracellular Zn2+ application. This is a novel finding implicating that the detrimental effect of HG on cardiomyocyte Ca2+ regulation can be amelioration by Zn2+. Among the many post-translational modifications examined, only phosphorylation of ryanodine receptor (RyR) at S-2808 was significantly higher in HG compared to nonHG. We did not find in our hypothyroid rats any differentiating effects of HG on myofibrillar protein phosphorylation, lysine acetylation, O-linked N-acetylglucosamine and advanced glycated end-products, which are often implicated as complicating factors in cardiac performance due to HG. Our results suggest that the

  16. The GH/IGF-1 axis in a critical period early in life determines cellular DNA repair capacity by altering transcriptional regulation of DNA repair-related genes: implications for the developmental origins of cancer.

    Science.gov (United States)

    Podlutsky, Andrej; Valcarcel-Ares, Marta Noa; Yancey, Krysta; Podlutskaya, Viktorija; Nagykaldi, Eszter; Gautam, Tripti; Miller, Richard A; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2017-02-23

    Experimental, clinical, and epidemiological findings support the concept of developmental origins of health and disease (DOHAD), suggesting that early-life hormonal influences during a sensitive period around adolescence have a powerful impact on cancer morbidity later in life. The endocrine changes that occur during puberty are highly conserved across mammalian species and include dramatic increases in circulating GH and IGF-1 levels. Importantly, patients with developmental IGF-1 deficiency due to GH insensitivity (Laron syndrome) do not develop cancer during aging. Rodents with developmental GH/IGF-1 deficiency also exhibit significantly decreased cancer incidence at old age, marked resistance to chemically induced carcinogenesis, and cellular resistance to genotoxic stressors. Early-life treatment of GH/IGF-1-deficient mice and rats with GH reverses the cancer resistance phenotype; however, the underlying molecular mechanisms remain elusive. The present study was designed to test the hypothesis that developmental GH/IGF-1 status impacts cellular DNA repair mechanisms. To achieve that goal, we assessed repair of γ-irradiation-induced DNA damage (single-cell gel electrophoresis/comet assay) and basal and post-irradiation expression of DNA repair-related genes (qPCR) in primary fibroblasts derived from control rats, Lewis dwarf rats (a model of developmental GH/IGF-1 deficiency), and GH-replete dwarf rats (GH administered beginning at 5 weeks of age, for 30 days). We found that developmental GH/IGF-1 deficiency resulted in persisting increases in cellular DNA repair capacity and upregulation of several DNA repair-related genes (e.g., Gadd45a, Bbc3). Peripubertal GH treatment reversed the radiation resistance phenotype. Fibroblasts of GH/IGF-1-deficient Snell dwarf mice also exhibited improved DNA repair capacity, showing that the persisting influence of peripubertal GH/IGF-1 status is not species-dependent. Collectively, GH/IGF-1 levels during a critical period

  17. Transgenerational developmental programming.

    Science.gov (United States)

    Aiken, Catherine E; Ozanne, Susan E

    2014-01-01

    The concept of developmental programming suggests that the early life environment influences offspring characteristics in later life, including the propensity to develop diseases such as the metabolic syndrome. There is now growing evidence that the effects of developmental programming may also manifest in further generations without further suboptimal exposure. This review considers the evidence, primarily from rodent models, for effects persisting to subsequent generations, and evaluates the mechanisms by which developmental programming may be transmitted to further generations. In particular, we focus on the potential role of the intrauterine environment in contributing to a developmentally programmed phenotype in subsequent generations. The literature was systematically searched at http://pubmed.org and http://scholar.google.com to identify published findings regarding transgenerational (F2 and beyond) developmental programming effects in human populations and animal models. Transmission of programming effects is often viewed as a form of epigenetic inheritance, either via the maternal or paternal line. Evidence exists for both germline and somatic inheritance of epigenetic modifications which may be responsible for phenotypic changes in further generations. However, there is increasing evidence for the role of both extra-genomic components of the zygote and the interaction of the developing conceptus with the intrauterine environment in propagating programming effects. The contribution of a suboptimal reproductive tract environment or maternal adaptations to pregnancy may be critical to inheritance of programming effects via the maternal line. As the effects of age exacerbate the programmed metabolic phenotype, advancing maternal age may increase the likelihood of developmental programming effects being transmitted to further generations. We suggest that developmental programming effects could be propagated through the maternal line de novo in generations

  18. Dynamic Alterations to α-Actinin Accompanying Sarcomere Disassembly and Reassembly during Cardiomyocyte Mitosis.

    Science.gov (United States)

    Fan, Xiaohu; Hughes, Bryan G; Ali, Mohammad A M; Cho, Woo Jung; Lopez, Waleska; Schulz, Richard

    2015-01-01

    Although mammals are thought to lose their capacity to regenerate heart muscle shortly after birth, embryonic and neonatal cardiomyocytes in mammals are hyperplastic. During proliferation these cells need to selectively disassemble their myofibrils for successful cytokinesis. The mechanism of sarcomere disassembly is, however, not understood. To study this, we performed a series of immunofluorescence studies of multiple sarcomeric proteins in proliferating neonatal rat ventricular myocytes and correlated these observations with biochemical changes at different cell cycle stages. During myocyte mitosis, α-actinin and titin were disassembled as early as prometaphase. α-actinin (representing the sarcomeric Z-disk) disassembly precedes that of titin (M-line), suggesting that titin disassembly occurs secondary to the collapse of the Z-disk. Sarcomere disassembly was concurrent with the dissolution of the nuclear envelope. Inhibitors of several intracellular proteases could not block the disassembly of α-actinin or titin. There was a dramatic increase in both cytosolic (soluble) and sarcomeric α-actinin during mitosis, and cytosolic α-actinin exhibited decreased phosphorylation compared to sarcomeric α-actinin. Inhibition of cyclin-dependent kinase 1 (CDK1) induced the quick reassembly of the sarcomere. Sarcomere dis- and re-assembly in cardiomyocyte mitosis is CDK1-dependent and features dynamic differential post-translational modifications of sarcomeric and cytosolic α-actinin.

  19. Alendronate affects calcium dynamics in cardiomyocytes in vitro.

    Science.gov (United States)

    Kemeny-Suss, Naomi; Kasneci, Amanda; Rivas, Daniel; Afilalo, Jonathan; Komarova, Svetlana V; Chalifour, Lorraine E; Duque, Gustavo

    2009-01-01

    Therapy with bisphosphonates, including alendronate (ALN), is considered a safe and effective treatment for osteoporosis. However, recent studies have reported an unexpected increase in serious atrial fibrillation (AF) in patients treated with bisphosphonates. The mechanism that explains this side effect remains unknown. Since AF is associated with an altered sarcoendoplasmic reticulum calcium load, we studied how ALN affects cardiomyocyte calcium homeostasis and protein isoprenylation in vitro. Acute and long-term (48h) treatment of atrial and ventricular cardiomyocytes with ALN (10(-8)-10(-6)M) was performed. Changes in calcium dynamics were determined by both fluorescence measurement of cytosolic free Ca(2+) concentration and western blot analysis of calcium-regulating proteins. Finally, effect of ALN on protein farnesylation was also identified. In both atrial and ventricular cardiomyocytes, ALN treatment delayed and diminished calcium responses to caffeine. Only in atrial cells, long-term exposure to ALN-induced transitory calcium oscillations and led to the development of oscillatory component in calcium responses to caffeine. Changes in calcium dynamics were accompanied by changes in expression of proteins controlling sarcoendoplasmic reticulum calcium. In contrast, ALN minimally affected protein isoprenylation in these cells. In summary, treatment of atrial cardiomyocytes with ALN-induced abnormalities in calcium dynamics consistent with induction of a self-stimulatory, pacemaker-like behavior, which may contribute to the development of cardiac side effects associated with these drugs.

  20. Excitation model of pacemaker cardiomyocytes of cardiac conduction system

    Science.gov (United States)

    Grigoriev, M.; Babich, L.

    2015-11-01

    Myocardium includes typical and atypical cardiomyocytes - pacemakers, which form the cardiac conduction system. Excitation from the atrioventricular node in normal conditions is possible only in one direction. Retrograde direction of pulses is impossible. The most important prerequisite for the work of cardiomyocytes is the anatomical integrity of the conduction system. Changes in contractile force of the cardiomyocytes, which appear periodically, are due to two mechanisms of self-regulation - heterometric and homeometric. Graphic course of the excitation pulse propagation along the heart muscle more accurately reveals the understanding of the arrhythmia mechanism. These models have the ability to visualize the essence of excitation dynamics. However, they do not have the proper forecasting function for result estimation. Integrative mathematical model enables further investigation of general laws of the myocardium active behavior, allows for determination of the violation mechanism of electrical and contractile function of cardiomyocytes. Currently, there is no full understanding of the topography of pacemakers and ionic mechanisms. There is a need for the development of direction of mathematical modeling and comparative studies of the electrophysiological arrangement of cells of atrioventricular connection and ventricular conduction system.

  1. Doxorubicin Blocks Cardiomyocyte Autophagic Flux by Inhibiting Lysosome Acidification.

    Science.gov (United States)

    Li, Dan L; Wang, Zhao V; Ding, Guanqiao; Tan, Wei; Luo, Xiang; Criollo, Alfredo; Xie, Min; Jiang, Nan; May, Herman; Kyrychenko, Viktoriia; Schneider, Jay W; Gillette, Thomas G; Hill, Joseph A

    2016-04-26

    The clinical use of doxorubicin is limited by cardiotoxicity. Histopathological changes include interstitial myocardial fibrosis and the appearance of vacuolated cardiomyocytes. Whereas dysregulation of autophagy in the myocardium has been implicated in a variety of cardiovascular diseases, the role of autophagy in doxorubicin cardiomyopathy remains poorly defined. Most models of doxorubicin cardiotoxicity involve intraperitoneal injection of high-dose drug, which elicits lethargy, anorexia, weight loss, and peritoneal fibrosis, all of which confound the interpretation of autophagy. Given this, we first established a model that provokes modest and progressive cardiotoxicity without constitutional symptoms, reminiscent of the effects seen in patients. We report that doxorubicin blocks cardiomyocyte autophagic flux in vivo and in cardiomyocytes in culture. This block was accompanied by robust accumulation of undegraded autolysosomes. We go on to localize the site of block as a defect in lysosome acidification. To test the functional relevance of doxorubicin-triggered autolysosome accumulation, we studied animals with diminished autophagic activity resulting from haploinsufficiency for Beclin 1. Beclin 1(+/-) mice exposed to doxorubicin were protected in terms of structural and functional changes within the myocardium. Conversely, animals overexpressing Beclin 1 manifested an amplified cardiotoxic response. Doxorubicin blocks autophagic flux in cardiomyocytes by impairing lysosome acidification and lysosomal function. Reducing autophagy initiation protects against doxorubicin cardiotoxicity. © 2016 American Heart Association, Inc.

  2. Role of nuclear Lamin A/C in cardiomyocyte functions.

    Science.gov (United States)

    Carmosino, Monica; Torretta, Silvia; Procino, Giuseppe; Gerbino, Andrea; Forleo, Cinzia; Favale, Stefano; Svelto, Maria

    2014-10-01

    Lamin A/C is a structural protein of the nuclear envelope (NE) and cardiac involvement in Lamin A/C mutations was one of the first phenotypes to be reported in humans, suggesting a crucial role of this protein in the cardiomyocytes function. Mutations in LMNA gene cause a class of pathologies generically named 'Lamanopathies' mainly involving heart and skeletal muscles. Moreover, the well-known disease called Hutchinson-Gilford Progeria Syndrome due to extensive mutations in LMNA gene, in addition to the systemic phenotype of premature aging, is characterised by the death of patients at around 13 typically for a heart attack or stroke, suggesting again the heart as the main site sensitive to Lamin A/C disfunction. Indeed, the identification of the roles of the Lamin A/C in cardiomyocytes function is a key area of exploration. One of the primary biological roles recently conferred to Lamin A/C is to affect contractile cells lineage determination and senescence. Then, in differentiated adult cardiomyocytes both the 'structural' and 'gene expression hypothesis' could explain the role of Lamin A in the function of cardiomyocytes. In fact, recent advances in the field propose that the structural weakness/stiffness of the NE, regulated by Lamin A/C amount in NE, can 'consequently' alter gene expression. © 2014 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.

  3. Reduced function and disassembled microtubules of cultured cardiomyocytes in spaceflight

    Institute of Scientific and Technical Information of China (English)

    YANG Fen; DAI ZhongQuan; TAN YingJun; WAN YuMin; LI YingHui; DING Bai; NIE JieLin; WANG HongHui; ZHANG XiaoYou; WANG ChunYan; LING ShuKuan; NI ChengZhi

    2008-01-01

    Lack of gravity during spaceflight has profound effects on cardiovascular system, but little is known about how the cardiomyocytes respond to microgravity. In the present study, the effects of spaceflight on the structure and function of cultured cardiomyocytes were reported. The primary cultures of neo-natal rat cardiomyocytes were carried on Shenzhou-6 spacecraft and activated at 4 h in orbit. 8 samples were fixed respectively at 4, 48 and 96 h after launching for immunofluorescence of cytoskeleton, and 2 samples remained unfixed to analyze contractile and secretory functions of the cultures. Ground sam-ples were treated in our laboratory in parallel. After 115 h spaceflight, video recordings displayed that the number of spontaneous beating sites in flown samples decreased significantly, and the cells in the beating aggregate contracted in fast frequency without synchrony. Radioimmunoassay of the medium showed that the atrial natriuretic peptide secreted from flown cells reduced by 59.6%. Confocal images demonstrated the time-dependant disassembly of mirotubules versus unchanged distribution and or-ganization of microfilaments. In conclusion, above results indicate reduced function and disorganized cytoskeleton of cardiomyocytes in spaceflight, which might provide some cellular basis for further investigations to probe into the mechanisms underlying space cardiovascular dysfunction.

  4. Data on calcium increases depending on stretch in dystrophic cardiomyocytes

    Directory of Open Access Journals (Sweden)

    E. Aguettaz

    2016-09-01

    Here, the Ca2+ dye fluo-8 was used for [Ca2+]i measurement, in both resting and stretching conditions, using a perfusion protocol starting initially with a calcium free Tyrode solution followed by the perfusion of 1.8 mM Ca2+ Tyrode solution. The variation of [Ca2+]i was found higher in mdx cardiomyocytes.

  5. Combinatorial MicroRNAs Suppress Hypoxia-Induced Cardiomyocytes Apoptosis

    Directory of Open Access Journals (Sweden)

    Yingqi Xu

    2015-09-01

    Full Text Available Background/Aims: Our previous in silico analysis revealed potential synergy in the activities of micro(miRNAs in myocardial infarction. The present study investigated whether miR-1 and -21 act synergistically to protect against cardiomyocytes apoptosis. Methods: Cell survival was analyzed with cell viability assay; apoptosis was detected by flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling, and the caspase-3 activity assay; and protein expression level was determined by western blotting. Results: MiR-1:miR-21 and several other miRNA pairs were evaluated for their potentially synergistic effects against myocardial hypoxia in neonatal rat ventricular cardiomyocytes. Lower combination indices suggested that miRNA pairs acted synergistically to inhibit apoptosis; miR-1 and -21 jointly blocked hypoxia-induced cardiomyocytes apoptosis. Moreover, combined application of miR-1 and -21 activated Akt and blocked hypoxia-induced upregulation of p53 in these cells. Conclusion: MiR-1 and -21 exert synergistic effects against hypoxia-induced cardiomyocytes apoptosis. These results provide a basis for the development of combined miRNA-based therapeutics to treat cardiovascular diseases.

  6. Enhancement of cardiomyocyte differentiation from human embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Several approaches have been used to encourage the differentiation of cardiomyocytes from human embryonic stem cells.However,the differentiation efficiency is low,and appropriate culture protocols are needed to produce adequate numbers of cardiomyocytes for therapeutic cell transplantation.This study investigated the effects of serum on cardiomyocyte differentiation in suspension culture medium during embryoid body(EB) formation by human embryonic stem cells.The addition of ascorbic acid,dimethylsulfoxide and 5-aza-2’-deoxycytidine during days 5-7 at the EB-forming stage resulted in an increase in the numbers of rhythmically contracting clusters of derived cardiomyocytes.Treatment with 0.1 mmol L-1 ascorbic acid alone,or more notably in combination with 10 μmol L-1 5-aza-2’-deoxycytidine,induced the formation of beating cells within EBs.Most of the beating clusters had spontaneous contraction rates similar to those found in human adults,and their contractile ac-tivity lasted for up to 194 days.

  7. In Situ Single Photon Confocal Imaging of Cardiomyocyte T-tubule System from Langendorff-Perfused Hearts

    Directory of Open Access Journals (Sweden)

    Biyi eChen

    2015-05-01

    Full Text Available Transverse tubules (T-tubules are orderly invaginations of the sarcolemma in mammalian cardiomyocytes. The integrity of T-tubule architecture is critical for cardiac excitation-contraction coupling function. T-tubule remodeling is recognized as a key player in cardiac dysfunction. Early studies on T-tubule structure were based on electron microscopy, which uncovered important information about the T-tubule architecture. The advent of fluorescent membrane probes allowed the application of confocal microscopy to investigations of T-tubule structure. Studies have now been extended beyond single cardiomyocytes to examine the T-tubule network in intact hearts through in situ confocal imaging of Langendorff-perfused hearts. This technique has allowed visualization of T-tubule organization in their natural habitat, avoiding the damage induced by isolation of cardiomyocytes. Additionally, it is possible to obtain T-tubule images in different subepicardial regions in a single intact heart. We review how this state-of-the-art imaging technique has provided important mechanistic insights into maturation of T-tubules in developing hearts and defined the role of T-tubule remodeling in development and progression of heart failure.

  8. Wnt/β-catenin signaling directs the regional expansion of first and second heart field-derived ventricular cardiomyocytes.

    Science.gov (United States)

    Buikema, Jan Willem; Mady, Ahmed S; Mittal, Nikhil V; Atmanli, Ayhan; Caron, Leslie; Doevendans, Pieter A; Sluijter, Joost P G; Domian, Ibrahim J

    2013-10-01

    In mammals, cardiac development proceeds from the formation of the linear heart tube, through complex looping and septation, all the while increasing in mass to provide the oxygen delivery demands of embryonic growth. The developing heart must orchestrate regional differences in cardiomyocyte proliferation to control cardiac morphogenesis. During ventricular wall formation, the compact myocardium proliferates more vigorously than the trabecular myocardium, but the mechanisms controlling such regional differences among cardiomyocyte populations are not understood. Control of definitive cardiomyocyte proliferation is of great importance for application to regenerative cell-based therapies. We have used murine and human pluripotent stem cell systems to demonstrate that, during in vitro cellular differentiation, early ventricular cardiac myocytes display a robust proliferative response to β-catenin-mediated signaling and conversely accelerate differentiation in response to inhibition of this pathway. Using gain- and loss-of-function murine genetic models, we show that β-catenin controls ventricular myocyte proliferation during development and the perinatal period. We further demonstrate that the differential activation of the Wnt/β-catenin signaling pathway accounts for the observed differences in the proliferation rates of the compact versus the trabecular myocardium during normal cardiac development. Collectively, these results provide a mechanistic explanation for the differences in localized proliferation rates of cardiac myocytes and point to a practical method for the generation of the large numbers of stem cell-derived cardiac myocytes necessary for clinical applications.

  9. Coordinating cardiomyocyte interactions to direct ventricular chamber morphogenesis.

    Science.gov (United States)

    Han, Peidong; Bloomekatz, Joshua; Ren, Jie; Zhang, Ruilin; Grinstein, Jonathan D; Zhao, Long; Burns, C Geoffrey; Burns, Caroline E; Anderson, Ryan M; Chi, Neil C

    2016-06-29

    Many organs are composed of complex tissue walls that are structurally organized to optimize organ function. In particular, the ventricular myocardial wall of the heart comprises an outer compact layer that concentrically encircles the ridge-like inner trabecular layer. Although disruption in the morphogenesis of this myocardial wall can lead to various forms of congenital heart disease and non-compaction cardiomyopathies, it remains unclear how embryonic cardiomyocytes assemble to form ventricular wall layers of appropriate spatial dimensions and myocardial mass. Here we use advanced genetic and imaging tools in zebrafish to reveal an interplay between myocardial Notch and Erbb2 signalling that directs the spatial allocation of myocardial cells to their proper morphological positions in the ventricular wall. Although previous studies have shown that endocardial Notch signalling non-cell-autonomously promotes myocardial trabeculation through Erbb2 and bone morphogenetic protein (BMP) signalling, we discover that distinct ventricular cardiomyocyte clusters exhibit myocardial Notch activity that cell-autonomously inhibits Erbb2 signalling and prevents cardiomyocyte sprouting and trabeculation. Myocardial-specific Notch inactivation leads to ventricles of reduced size and increased wall thickness because of excessive trabeculae, whereas widespread myocardial Notch activity results in ventricles of increased size with a single-cell-thick wall but no trabeculae. Notably, this myocardial Notch signalling is activated non-cell-autonomously by neighbouring Erbb2-activated cardiomyocytes that sprout and form nascent trabeculae. Thus, these findings support an interactive cellular feedback process that guides the assembly of cardiomyocytes to morphologically create the ventricular myocardial wall and more broadly provide insight into the cellular dynamics of how diverse cell lineages organize to create form.

  10. Hypoxia reoxygenation induces premature senescence in neonatal SD rat cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    Feng-xiang ZHANG; Ming-long CHEN; Qi-jun SHAN; Jian-gang ZOU; Chun CHEN; Bing YANG; Dong-jie XU; Yu JIN; Ke-jiang CAO

    2007-01-01

    Aim: To investigate whether hypoxia reoxygenation induces premature senes-cence in neonatal Sprague-Dawley (SD) rat cardiomyocytes. Methods: Cardio-myocytes were isolated from neonatal SD rat heart and identified by immunohisto-chemistry. The control cultures were incubated at 37 ℃ in a humidified atmo-sphere of 5% CO and 95% air. The hypoxic cultures were incubated in a modular incubator chamber filled with 1% O2, 5% CO2, and balance N2 for 6 h. The reoxygen-ated cultures were subjected to 1% O2 and 5% CO2 for 6 h, then 21% oxygen for 4,8, 12, 24, and 48 h, respectively. Cell proliferation was determined using bromo-deoxyuridine labeling. The ultrastructure of cardiomyocytes was observed by using an electron microscope. Β-Galactosidase activity was determined by using a senescence β-galactosidase Staining Kit. P16INK4a and telomerase reverse tran-scriptase (TERT) mRNA levels were measured by real time quantitative PCR. TERT protein expression was determined by immunohistochemistry. Telomerase activi-ties were assayed by using the Telo TAGGG Telomerase PCR ELISApplus kit. Results:The initial cultures consisted of pure cardiomyocytes identified by immunohisto-chemistry. The proportion of BrdU positive cells was reduced significantly in the hypoxia reoxygenation-treated group (P<0.01). Under the condition of hypoxia reoxygenation, mitochondrial dehydration appeared; p16'INK4a and TERT mRNA levels, β-galactosidase activity, TERT protein expression and telomerase activi-ties were all significantly increased (P<0.01 or P<0.05). Conclusion: These data indicate that premature senescence could be induced in neonatal SD rat cardiomyo-cytes exposed to hypoxia reoxygenation. Although TERT significantly increased,it could not block senescence.

  11. Developmental Scaffolding

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio

    2015-01-01

    . Within the developmental hierarchy, each module yields an inter-level relationship that makes it possible for the scaffolding to mediate the production of selectable variations. Awide range of genetic, cellular and morphological mechanisms allows the scaffolding to integrate these modular variations...... is eventually attained when the embryo acquires the capacity to impose a number of developmental constraints on its constituting parts in a top-down direction. The acquisition of this capacity allows a semiotic threshold to emerge between the living cellular world and the underlying nonliving molecular world...... to the complexity of sign recognition proper of a cellular community. In this semiotic perspective, the apparent goal directness of any developmental strategy should no longer be accounted for by a predetermined genetic program, but by the gradual definition of the relationships selected amongst the ones...

  12. EXPERIMENT STUDY OF CARDIOMYOCYTE APOPTOSIS AND CARDIOMYOCYTE PROLIFERATION DURING THE DEVELOPMENT OF CARDIAC HYPERTROPHY IN SPONTANEOUSLY HYPERTENSIVE RATS

    Institute of Scientific and Technical Information of China (English)

    江立生; 方宁远; 高天; 孟超

    2005-01-01

    Objective To investigate the effect and significance of cardiomyocyte apoptosis and cardiomyocyte proliferation on cardiac hypertrophy by observing the dynamic changes of them during the development of cardiac hypertrophy in spontaneously hypertensive rats (SHR). Methods Hearts were excised from SHR and Wistar-Kyoto rats(WKY) at different ages. Cardiac hypertrophic index (CHI) was calculated as the radio of heart weight to body weight; Cardiomyocyte apoptosis was identified by in situ TDT-mediated dUTP nick end labeling (TUNEL); Localization and expression of proliferating cell nuclear antigen (PCNA) were examined by immunohistochemistry. Results Compared with age-matched WKY, CHI in SHR was significantly increased at 12 weeks old and 24 weeks old (3. 604 ± 0. 089 vs 2. 997 ± 0. 166, P<0.01; 4. 156 ± 0. 385 vs 3. 119 ± 0. 208, P < 0. 01 ) ,and CHI in SHR was increased little by little with the age increasing and attained plaiform since 20 weeks old. In contrast with age-matched WKY, cardiomyocyte apoptotic index (APOI) in SHR at 12 weeks was not increased significantly (4. 248 ± 1. 592 vs 3. 678 ± 0. 856, P > 0. 05 ), but decreased markedly when their age were 24 weeks (3. 207 ± 1. 794 vs 5. 494 ± 1. 372, P <0. 05); APOI in SHR at 12 weeks old, 16 weeks old, 20 weeks old and 24weeks old were 4. 248 ± 1. 592, 5. 707 ± 1. 322, 7. 436 ± 1. 128, 3. 207 ± 1. 794, respectively. On the other hand,APOI in SHR from 12 weeks old to 20 weeks old increased gradually, and attained peak at 20 weeks old, but decreased markedly after 20 weeks old ( P <0. 01 ). Compared with age-matched WKY, the rate of cardiomyocyte PCNA positive labeling (PCNAR) in SHR at 12 weeks old and 24 weeks old didn' t have obvious difference. Conclusion Imbalance of cardiomyocyte apoptosis and cardiomyocyte proliferation existed during the development of cardiac hypertrophy in spontaneously hypertensive rats.

  13. Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation.

    Science.gov (United States)

    Kobayashi, Soushi; Nakamura, Tomoe Y; Wakabayashi, Shigeo

    2015-07-01

    Cardiac hypertrophy is a leading cause of serious heart diseases. Although many signaling molecules are involved in hypertrophy, the functions of some proteins in this process are still unknown. Calcineurin B homologous protein 3 (CHP3)/tescalcin is an EF-hand Ca(2+)-binding protein that is abundantly expressed in the heart; however, the function of CHP3 is unclear. Here, we aimed to identify the cardiac functions of CHP3. CHP3 was expressed in hearts at a wide range of developmental stages and was specifically detected in neonatal rat ventricular myocytes (NRVMs) but not in cardiac fibroblasts in culture. Moreover, knockdown of CHP3 expression using adenoviral-based RNA interference in NRVMs resulted in enlargement of cardiomyocyte size, concomitant with increased expression of a pathological hypertrophy marker ANP. This same treatment elevated glycogen synthase kinase (GSK3α/β) phosphorylation, which is known to inhibit GSK3 function. In contrast, CHP3 overexpression blocked the insulin-induced phosphorylation of GSK3α/β without affecting the phosphorylation of Akt, which is an upstream kinase of GSK3α/β, in HEK293 cells, and it inhibited both IGF-1-induced phosphorylation of GSK3β and cardiomyocyte hypertrophy in NRVMs. Co-immunoprecipitation experiments revealed that GSK3β interacted with CHP3. However, a Ca(2+)-binding-defective mutation of CHP3 (CHP3-D123A) also interacted with GSK3β and had the same inhibitory effect on GSK3α/β phosphorylation, suggesting that the action of CHP3 was independent of Ca(2+). These findings suggest that CHP3 functions as a novel negative regulator of cardiomyocyte hypertrophy via inhibition of GSK3α/β phosphorylation and subsequent enzymatic activation of GSK3α/β. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard

    2003-01-01

    Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work...

  15. Developmental Work

    DEFF Research Database (Denmark)

    Møller, Niels; Hvid, Helge; Kristensen, Tage Søndergaard;

    2003-01-01

    Human Deveoplment and Working Life - Work for Welfare explores whether the development of human resources at company level can improve individuals' quality of life, companies' possibilities of development, and welfare and democracy in society. Chapter two discuss the concept "developmental work...

  16. The Debate over the Young "Disadvantaged Child": Preschool Intervention, Developmental Psychology, and Compensatory Education in the 1960s and Early 1970s

    Science.gov (United States)

    Beatty, Barbara

    2012-01-01

    I focus on the role of preschool intervention and developmental psychology researchers in defining the concept of the "disadvantaged child" and in designing and evaluating remedies to alleviate educational "disadvantages" in young children. I argue that preschool interventions concentrated especially on compensating for…

  17. Associations of maternal fish intake during pregnancy and breastfeeding duration with attainment of developmental milestones in early childhood : a study from the Danish National Birth Cohort

    NARCIS (Netherlands)

    Oken, Emily; Osterdal, Marie Louise; Gillman, Matthew W.; Knudsen, Vibeke K.; Halldorsson, Thorhallur I.; Strom, Marin; Bellinger, David C.; Hadders-Algra, Mijna; Michaelsen, Kim Fleischer; Olsen, Sjurdur F.

    2008-01-01

    Background: Few studies have examined the overall effect of maternal fish intake during pregnancy on child development or examined whether the developmental benefits of maternal fish intake are greater in infants breastfed for a shorter duration. Objective: We aimed to study associations of maternal

  18. Mitigating the Effects of Poverty and Crime: The Long-Term Effects of an Early Intervention Programme for Children Who Were Developmentally Delayed and Prenatally Exposed to Cocaine

    Science.gov (United States)

    Ullery, Mary Anne; Gonzalez, Antonio; Katz, Lynne

    2016-01-01

    This study explores the long-term impact on participation in the Linda Ray Intervention Program (LRIP) for children (n = 54) who were developmentally delayed and prenatally exposed to cocaine. By identifying a group of programme graduates from a high crime/high poverty neighbourhood in Miami-Dade County using ArcGIS 10.2 software, a…

  19. Maturity-associated variation in change of direction and dribbling speed in early pubertal years and 5-year developmental changes in young soccer players

    NARCIS (Netherlands)

    Valente-Dos-Santos, J.; Coelho-E-Silva, M. J.; Vaz, V.; Figueiredo, A. J.; Capranica, L.; Sherar, L. B.; Elferink-Gemser, M. T.; Malina, R. M.

    2014-01-01

    Aim. The purpose of the current study was to assess the developmental changes in change of direction and dribbling speed in youth soccer players taking into account skeletal age (SA), maturity status, body size, estimated fat mass, aerobic endurance, lower limb explosive strength and annual volume o

  20. The Debate over the Young "Disadvantaged Child": Preschool Intervention, Developmental Psychology, and Compensatory Education in the 1960s and Early 1970s

    Science.gov (United States)

    Beatty, Barbara

    2012-01-01

    I focus on the role of preschool intervention and developmental psychology researchers in defining the concept of the "disadvantaged child" and in designing and evaluating remedies to alleviate educational "disadvantages" in young children. I argue that preschool interventions concentrated especially on compensating for supposedly deficient…

  1. Two inhibitory systems and CKIs regulate cell cycle exit of mammalian cardiomyocytes after birth

    Energy Technology Data Exchange (ETDEWEB)

    Tane, Shoji; Okayama, Hitomi; Ikenishi, Aiko; Amemiya, Yuki [School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503 (Japan); Nakayama, Keiichi I. [Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582 (Japan); Takeuchi, Takashi, E-mail: takeuchi@med.tottori-u.ac.jp [School of Life Sciences, Faculty of Medicine, Tottori University, Yonago 683-8503 (Japan)

    2015-10-16

    Mammalian cardiomyocytes actively proliferate during embryonic stages, following which they exit their cell cycle after birth, and the exit is maintained. Previously, we showed that two inhibitory systems (the G1-phase inhibitory system: repression of cyclin D1 expression; the M-phase inhibitory system: inhibition of CDK1 activation) maintain the cell cycle exit of mouse adult cardiomyocytes. We also showed that two CDK inhibitors (CKIs), p21{sup Cip1} and p27{sup Kip1}, regulate the cell cycle exit in a portion of postnatal cardiomyocytes. It remains unknown whether the two inhibitory systems are involved in the cell cycle exit of postnatal cardiomyocytes and whether p21{sup Cip1} and p27{sup Kip1} also inhibit entry to M-phase. Here, we showed that more than 40% of cardiomyocytes entered an additional cell cycle by induction of cyclin D1 expression at postnatal stages, but M-phase entry was inhibited in the majority of cardiomyocytes. Marked cell cycle progression and endoreplication were observed in cardiomyocytes of p21{sup Cip1} knockout mice at 4 weeks of age. In addition, tri- and tetranucleated cardiomyocytes increased significantly in p21{sup Cip1} knockout mice. These data showed that the G1-phase inhibitory system and two CKIs (p21{sup Cip1} and p27{sup Kip1}) inhibit entry to an additional cell cycle in postnatal cardiomyocytes, and that the M-phase inhibitory system and p21{sup Cip1} inhibit M-phase entry of cardiomyocytes which have entered the additional cell cycle. - Highlights: • Many postnatal cardiomyocytes entered an additional cell cycle by cyclin D1 induction. • The majority of cardiomyocytes could not enter M-phase after cyclin D1 induction. • Cell cycle progressed markedly in p21{sup Cip1} knockout mice after postnatal day 14. • Tri- and tetranucleated cardiomyocytes increased in p21{sup Cip1} knockout mice.

  2. Early developmental characteristics of external apparatus of bluefin leatherjacket Thamnaconus modestus%绿鳍马面鲀外部器官的早期发育

    Institute of Scientific and Technical Information of China (English)

    关健; 刘洪军; 郑永允; 李祥东; 于道德; 陈海滨; 官曙光

    2012-01-01

    This study described the developmental characteristics of external apparatus during early life stages of bluefin leatherjacket, Thamnaconus modestus. The developmental morphological characteristics of 11 external apparatus were recorded and described in detail. 1) Mouth; opened at 2-3 dph(days post hatching), then grew continuously except at the stagnation stage (24-28 dph). 2) Eyes: pigment appeared at 1 dph, choroids formed and the pupil was black at 3 dph, sclera formed at 4 dph, rim of the eye appeared at 14 dph, and the eye form was same with adults at 40 dph basically. 3) First dorsal fin spine: anlage appeared at 3 dph, fin spine formed initially at 7-8 dph, protruded out of body at 10 dph, development finished roughly at 14 dph, and the shape was the same with adult at 60dph basically. 4) Girdles and pelvic fin spine: Girdles appeared at 5 dph, pelvic fin spine grew fast at 5-7 dph, and shunk from l0dph, all pelvic fin spine off at 30 dph. The shape of girdles was the same with adult at 60 dph. 5) Pectoral fin: fin membrane thickened and the fin ray formed at 15dph, developed completely at 30 dph. 6) Dorsal fin and anal fin: fin suspensorium and fin ray appeared at 14 dph, fin ray developed completely at 24dph, and the shape at 60 dph was the same with adult's. 7) Caudal peduncle: caudal vertebra was straight until 14dph, some fin ray anlage appeared under the tail end of notochord at 16 dph. The tail end of notochord up-curved, fin ray developed completely and sub-section at 16-24 dph. Caudal fin turned into rotundity at 50 dph. 8) Scales and skin: epidermis thickened at 8dph, the compact epidermis appeared first at head, full body covered by scales at 40dph, turned into withy leathery epidermis. 9) Abdomen and splanchnic zone: yolk-sac was absorbed, anus and the first intestinal loop formed at 2 dph, oil ball disappeared and the fish larvae fed on the oyster larvae. The anlages of liver, kidney and swim bladder appeared at 8-12 dph, and the three organ

  3. Arguments from Developmental Order.

    Science.gov (United States)

    Stöckle-Schobel, Richard

    2016-01-01

    In this article, I investigate a special type of argument regarding the role of development in theorizing about psychological processes and cognitive capacities. Among the issues that developmental psychologists study, discovering the ontogenetic trajectory of mechanisms or capacities underpinning our cognitive functions ranks highly. The order in which functions are developed or capacities are acquired is a matter of debate between competing psychological theories, and also philosophical conceptions of the mind - getting the role and the significance of the different steps in this order right could be seen as an important virtue of such theories. Thus, a special kind of strategy in arguments between competing philosophical or psychological theories is using developmental order in arguing for or against a given psychological claim. In this article, I will introduce an analysis of arguments from developmental order, which come in two general types: arguments emphasizing the importance of the early cognitive processes and arguments emphasizing the late cognitive processes. I will discuss their role in one of the central tools for evaluating scientific theories, namely in making inferences to the best explanation. I will argue that appeal to developmental order is, by itself, an insufficient criterion for theory choice and has to be part of an argument based on other core explanatory or empirical virtues. I will end by proposing a more concerted study of philosophical issues concerning (cognitive) development, and I will present some topics that also pertain to a full-fledged 'philosophy of development.'

  4. Geometry-dependent functional changes in iPSC-derived cardiomyocytes probed by functional imaging and RNA sequencing

    Science.gov (United States)

    Gaublomme, Jellert; Shekhar, Karthik; Butty, Vincent; Yi, B. Alexander; Kralj, Joel M.; Bloxham, William; Boyer, Laurie A.; Regev, Aviv

    2017-01-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly for tissue repair in humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, and electrophysiology similar to that of embryonic cardiomyocytes. We grew hiPSC-CM in patterned islands of different sizes and shapes, and measured the effect of island geometry on action potential waveform and calcium dynamics using optical recordings of voltage and calcium from 970 islands of different sizes. hiPSC-CM in larger islands showed electrical and calcium dynamics indicative of greater functional maturity. We then compared transcriptional signatures of the small and large islands against a developmental time course of cardiac differentiation. Although island size had little effect on expression of most genes whose levels differed between hiPSC-CM and adult primary CM, we identified a subset of genes for which island size drove the majority (58%) of the changes associated with functional maturation. Finally, we patterned hiPSC-CM on islands with a variety of shapes to probe the relative contributions of soluble factors, electrical coupling, and direct cell-cell contacts to the functional maturation. Collectively, our data show that optical electrophysiology is a powerful tool for assaying hiPSC-CM maturation, and that island size powerfully drives activation of a subset of genes involved in cardiac maturation. PMID:28333933

  5. Mechanical Unloading Activates FoxO3 to Trigger Bnip3‐Dependent Cardiomyocyte Atrophy

    Science.gov (United States)

    Cao, Dian J.; Jiang, Nan; Blagg, Andrew; Johnstone, Janet L.; Gondalia, Raj; Oh, Misook; Luo, Xiang; Yang, Kai‐Chun; Shelton, John M.; Rothermel, Beverly A.; Gillette, Thomas G.; Dorn, Gerald W.; Hill, Joseph A.

    2013-01-01

    Background Mechanical assist device therapy has emerged recently as an important and rapidly expanding therapy in advanced heart failure, triggering in some patients a beneficial reverse remodeling response. However, mechanisms underlying this benefit are unclear. Methods and Results In a model of mechanical unloading of the left ventricle, we observed progressive myocyte atrophy, autophagy, and robust activation of the transcription factor FoxO3, an established regulator of catabolic processes in other cell types. Evidence for FoxO3 activation was similarly detected in unloaded failing human myocardium. To determine the role of FoxO3 activation in cardiac muscle in vivo, we engineered transgenic mice harboring a cardiomyocyte‐specific constitutively active FoxO3 mutant (caFoxO3flox;αMHC‐Mer‐Cre‐Mer). Expression of caFoxO3 triggered dramatic and progressive loss of cardiac mass, robust increases in cardiomyocyte autophagy, declines in mitochondrial biomass and function, and early mortality. Whereas increases in cardiomyocyte apoptosis were not apparent, we detected robust increases in Bnip3 (Bcl2/adenovirus E1B 19‐kDa interacting protein 3), an established downstream target of FoxO3. To test the role of Bnip3, we crossed the caFoxO3flox;αMHC‐Mer‐Cre‐Mer mice with Bnip3‐null animals. Remarkably, the atrophy and autophagy phenotypes were significantly blunted, yet the early mortality triggered by FoxO3 activation persisted. Rather, declines in cardiac performance were attenuated by proteasome inhibitors. Consistent with involvement of FoxO3‐driven activation of the ubiquitin‐proteasome system, we detected time‐dependent activation of the atrogenes program and sarcomere protein breakdown. Conclusions In aggregate, these data point to FoxO3, a protein activated by mechanical unloading, as a master regulator that governs both the autophagy‐lysosomal and ubiquitin‐proteasomal pathways to orchestrate cardiac muscle atrophy. PMID:23568341

  6. Impact of mitochondria on nitrite metabolism in HL-1 cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Peter eDungel

    2013-05-01

    Full Text Available Apart from ATP synthesis mitochondria have many other functions, one being nitrite reductase activity. NO released from nitrite has been shown to protect the heart from ischemia/reperfusion injury in a cGMP-dependent manner. However, the exact impact of mitochondria on the release of NO from nitrite in cardiomyocytes is not completely understood. Besides mitochondria, a number of non-mitochondrial metalloproteins have been suggested to facilitate this process. The aim of this study was to investigate the impact of mitochondria on the bioactivation of nitrite in HL-1 cardiomyocytes.The levels of nitrosyl complexes of hemoglobin (NO-Hb and cGMP levels were measured by electron spin resonance spectroscopy and enzyme immunoassay. In addition the formation of free NO was determined by confocal microscopy as well as intracellular nitrite and S-nitrosothiols by chemoluminescence analysis. NO was released from nitrite in cell culture in an oxygen dependent manner. Application of specific inhibitors of the respiratory chain, p450, NO synthases and xanthine oxidoreductase showed that all four enzymatic systems are involved in the release of NO, but more than 50% of NO is released via the mitochondrial pathway. Only NO released by mitochondria activated cGMP synthesis. Cardiomyocytes co-cultured with red blood cells (RBC competed with RBC for nitrite, but free NO was detected only in HL-1 cells suggesting that RBC are not a source of NO in this model. Apart from activation of cGMP synthesis, NO formed in HL-1 cells diffused out of the cells and formed NO-Hb complexes. In addition nitrite was converted by HL-1 cells to S-nitrosyl complexes. In HL-1 cardiomyocytes, several enzymatic systems are involved in nitrite reduction to NO but only the mitochondrial pathway of NO release activates cGMP synthesis. Our data suggest that this pathway may be a key regulator of myocardial contractility especially under hypoxic conditions.

  7. Endothelin-1 downregulates Mas receptor expression in human cardiomyocytes.

    Science.gov (United States)

    Chen, Zhiheng; Tang, Yamei; Yang, Zuocheng; Liu, Shaojun; Liu, Yong; Li, Yan; He, Wei

    2013-09-01

    Endothelin-1 (ET-1) and the renin-angiotensin system (RAS) are involved in the pathogenesis of cardiac dysfunction. The Mas receptor is a functional binding site for angiotensin (Ang)‑(1-7), which is now considered a critical component of the RAS and exerts cardioprotective effects. To the best of our knowledge, the present study aimed to examine, for the first time, the effects of ET-1 on Mas expression in cultured human cardiomyocytes. Human cardiomyocytes were treated with ET-1 at different concentrations (1, 5, 10, 20 and 30 nM) for varied time periods (0.5, 1.5, 3, 4.5 or 6 h) with or without the transcription inhibitor actinomycin D, endothelin A (ETA) receptor blocker BQ123 and ETB receptor blocker BQ788, or different kinase inhibitors. ET-1 decreased the Mas mRNA level in a statistically significant dose- and time-dependent manner within 4.5 h, which was reflected in the dose-dependent downregulation of Mas promoter activity, Mas protein levels and Ang-(1-7) binding on the cell membrane. Actinomycin D (1 mg/ml), BQ123 (1 µM), p38 mitogen-activated protein kinase (MAPK) siRNA and inhibitor PD169316 (25 µM), completely eliminated the inhibitory effects of ET-1 on Mas expression in human cardiomyocytes. In conclusion, the present study demonstrated that ET-1 downregulates Mas expression at the transcription level in human cardiomyocytes via the ETA receptor by a p38 MAPK‑dependent mechanism. This study provides novel insights into the function of ET-1 and the Ang‑(1-7)/Mas axis in cardiac pathophysiology.

  8. Modeling Fatty Acid Transfer from Artery to Cardiomyocyte.

    Science.gov (United States)

    Arts, Theo; Reneman, Robert S; Bassingthwaighte, James B; van der Vusse, Ger J

    2015-12-01

    Despite the importance of oxidation of blood-borne long-chain fatty acids (Fa) in the cardiomyocytes for contractile energy of the heart, the mechanisms underlying the transfer of Fa from the coronary plasma to the cardiomyocyte is still incompletely understood. To obtain detailed insight into this transfer process, we designed a novel model of Fa transfer dynamics from coronary plasma through the endothelial cells and interstitium to the cardiomyocyte, applying standard physicochemical principles on diffusion and on the chemical equilibrium of Fa binding to carrier proteins Cp, like albumin in plasma and interstitium and Fatty Acid-Binding Proteins within endothelium and cardiomyocytes. Applying these principles, the present model strongly suggests that in the heart, binding and release of Fa to and from Cp in the aqueous border zones on both sides of the cell membranes form the major hindrance to Fa transfer. Although often considered, the membrane itself appears not to be a significant hindrance to diffusion of Fa. Proteins, residing in the cellular membrane, may facilitate transfer of Fa between Cp and membrane. The model is suited to simulate multiple tracer dilution experiments performed on isolated rabbit hearts administrating albumin and Fa as tracer substances into the coronary arterial perfusion line. Using parameter values on myocardial ultrastructure and physicochemical properties of Fa and Cp as reported in literature, simulated washout curves appear to be similar to the experimentally determined ones. We conclude therefore that the model is realistic and, hence, can be considered as a useful tool to better understand Fa transfer by evaluation of experimentally determined tracer washout curves.

  9. Modeling Fatty Acid Transfer from Artery to Cardiomyocyte.

    Directory of Open Access Journals (Sweden)

    Theo Arts

    2015-12-01

    Full Text Available Despite the importance of oxidation of blood-borne long-chain fatty acids (Fa in the cardiomyocytes for contractile energy of the heart, the mechanisms underlying the transfer of Fa from the coronary plasma to the cardiomyocyte is still incompletely understood. To obtain detailed insight into this transfer process, we designed a novel model of Fa transfer dynamics from coronary plasma through the endothelial cells and interstitium to the cardiomyocyte, applying standard physicochemical principles on diffusion and on the chemical equilibrium of Fa binding to carrier proteins Cp, like albumin in plasma and interstitium and Fatty Acid-Binding Proteins within endothelium and cardiomyocytes. Applying these principles, the present model strongly suggests that in the heart, binding and release of Fa to and from Cp in the aqueous border zones on both sides of the cell membranes form the major hindrance to Fa transfer. Although often considered, the membrane itself appears not to be a significant hindrance to diffusion of Fa. Proteins, residing in the cellular membrane, may facilitate transfer of Fa between Cp and membrane. The model is suited to simulate multiple tracer dilution experiments performed on isolated rabbit hearts administrating albumin and Fa as tracer substances into the coronary arterial perfusion line. Using parameter values on myocardial ultrastructure and physicochemical properties of Fa and Cp as reported in literature, simulated washout curves appear to be similar to the experimentally determined ones. We conclude therefore that the model is realistic and, hence, can be considered as a useful tool to better understand Fa transfer by evaluation of experimentally determined tracer washout curves.

  10. Ghrelin promotes differentiation of human embryonic stem cells into cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    Jin YANG; Guo-qiang LIU; Rui WEI; Wen-fang HOU; Mei-juan GAO; Ming-xia ZHU; Hai-ning WANG; Gui-an CHEN; Tian-pei HONG

    2011-01-01

    Aim:Ghrelin is involved in regulating the differentiation of mesoderm-derived precursor cells.The aim of this study was to investigate whether ghrelin modulated the differentiation of human embryonic stem (hES) cells into cardiomyocytes and,if so,whether the effect was mediated by growth hormone secretagogue receptor 1α (GHS-R1α).Methods:Cardiomyocyte differentiation from hES cells was performed according to an embryoid body (EB)-based protocol.The cumulative percentage of beating EBs was calculated.The expression of cardiac-specific markers including cardiac troponin Ⅰ (cTnl) and α-myosin heavy chain (α-MHC) was detected using RT-PCR,real-time PCR and Western blot.The dispersed beating EBs were examined using immunofluorescent staining.Results:The percentage of beating EBs and the expression of cTnl were significantly increased after ghrelin (0.1 and 1 nmol/L) added into the differentiation medium.From 6 to 18 d of differentiation,the increased expression of cTnl and α-MHC by ghrelin (1 nmol/L)was time-dependent,and in line with the alteration of the percentages of beating EBs.Furthermore,the dispersed beating EBs were double-positively immunostained with antibodies against cTnl and α-actinin.However,blockage of GHS-R1α with its specific antagonist D-[lys3]-GHRP-6 (1 μmol/L) did not alter the effects of ghrelin on cardiomyocyte differentiation.Conclusion:Our data show that ghrelin enhances the generation of cardiomyocytes from hES cells,which is not mediated via GHS-R1α.

  11. Shock Wave Therapy Promotes Cardiomyocyte Autophagy and Survival during Hypoxia

    Directory of Open Access Journals (Sweden)

    Ling Du

    2017-06-01

    Full Text Available Background: Autophagy plays an important role in cardiovascular disease. Controversy still exists regarding the effect of autophagy on ischemic/hypoxic myocardium. Cardiac shock wave therapy (CSWT is an effective alternative treatment for refractory ischemic heart disease. Whether CSWT can regulate cardiomyocyte autophagy under hypoxic conditions is not clear. We established a myocardial hypoxia model using the H9c2 cell line and performed shock waves (SWs treatment to evaluate the effect of SW on autophagy. Methods: The H9c2 cells were incubated under hypoxic conditions, and SW treatment was then performed at energies of 0.02, 0.05, or 0.10 mJ/mm2. The cell viability and intracellular ATP level were examined. Western blot analysis was used to assess the expression of LC3B, AMPK, mTOR, Beclin-1, Sirt1, and HIF-1α. Autophagic vacuoles were visualized by monodansylcadaverine staining. Results: After the 24-hour hypoxic period, cardiomyocyte viability and ATP levels were decreased and autophagy was significantly increased in H9c2 cells. SW treatment with an energy of 0.05 mJ/mm2 significantly increased the cellular viability, ATP level, LC3B-II/I, and number of autophagic vacuoles. In addition, phosphorylated AMPK and Sirt1 were increased and phosphorylated mTOR and HIF-1α were decreased after SW treatment. Conclusion: SW treatment can potentially promote cardiomyocyte autophagy during hypoxia and protect cardiomyocyte function by regulating the AMPK/mTOR pathway.

  12. Caffeine exposure alters cardiac gene expression in embryonic cardiomyocytes

    Science.gov (United States)

    Fang, Xiefan; Mei, Wenbin; Barbazuk, William B.; Rivkees, Scott A.

    2014-01-01

    Previous studies demonstrated that in utero caffeine treatment at embryonic day (E) 8.5 alters DNA methylation patterns, gene expression, and cardiac function in adult mice. To provide insight into the mechanisms, we examined cardiac gene and microRNA (miRNA) expression in cardiomyocytes shortly after exposure to physiologically relevant doses of caffeine. In HL-1 and primary embryonic cardiomyocytes, caffeine treatment for 48 h significantly altered the expression of cardiac structural genes (Myh6, Myh7, Myh7b, Tnni3), hormonal genes (Anp and BnP), cardiac transcription factors (Gata4, Mef2c, Mef2d, Nfatc1), and microRNAs (miRNAs; miR208a, miR208b, miR499). In addition, expressions of these genes were significantly altered in embryonic hearts exposed to in utero caffeine. For in utero experiments, pregnant CD-1 dams were treated with 20–60 mg/kg of caffeine, which resulted in maternal circulation levels of 37.3–65.3 μM 2 h after treatment. RNA sequencing was performed on embryonic ventricles treated with vehicle or 20 mg/kg of caffeine daily from E6.5-9.5. Differential expression (DE) analysis revealed that 124 genes and 849 transcripts were significantly altered, and differential exon usage (DEU) analysis identified 597 exons that were changed in response to prenatal caffeine exposure. Among the DE genes identified by RNA sequencing were several cardiac structural genes and genes that control DNA methylation and histone modification. Pathway analysis revealed that pathways related to cardiovascular development and diseases were significantly affected by caffeine. In addition, global cardiac DNA methylation was reduced in caffeine-treated cardiomyocytes. Collectively, these data demonstrate that caffeine exposure alters gene expression and DNA methylation in embryonic cardiomyocytes. PMID:25354728

  13. Modeling Fatty Acid Transfer from Artery to Cardiomyocyte

    Science.gov (United States)

    Arts, Theo; Reneman, Robert S.; Bassingthwaighte, James B.; van der Vusse, Ger J.

    2015-01-01

    Despite the importance of oxidation of blood-borne long-chain fatty acids (Fa) in the cardiomyocytes for contractile energy of the heart, the mechanisms underlying the transfer of Fa from the coronary plasma to the cardiomyocyte is still incompletely understood. To obtain detailed insight into this transfer process, we designed a novel model of Fa transfer dynamics from coronary plasma through the endothelial cells and interstitium to the cardiomyocyte, applying standard physicochemical principles on diffusion and on the chemical equilibrium of Fa binding to carrier proteins Cp, like albumin in plasma and interstitium and Fatty Acid-Binding Proteins within endothelium and cardiomyocytes. Applying these principles, the present model strongly suggests that in the heart, binding and release of Fa to and from Cp in the aqueous border zones on both sides of the cell membranes form the major hindrance to Fa transfer. Although often considered, the membrane itself appears not to be a significant hindrance to diffusion of Fa. Proteins, residing in the cellular membrane, may facilitate transfer of Fa between Cp and membrane. The model is suited to simulate multiple tracer dilution experiments performed on isolated rabbit hearts administrating albumin and Fa as tracer substances into the coronary arterial perfusion line. Using parameter values on myocardial ultrastructure and physicochemical properties of Fa and Cp as reported in literature, simulated washout curves appear to be similar to the experimentally determined ones. We conclude therefore that the model is realistic and, hence, can be considered as a useful tool to better understand Fa transfer by evaluation of experimentally determined tracer washout curves. PMID:26675003

  14. Rac1 modulates cardiomyocyte adhesion during mouse embryonic development

    Energy Technology Data Exchange (ETDEWEB)

    Abu-Issa, Radwan, E-mail: rabuissa@umich.edu

    2015-01-24

    Highlights: • Conditional knockout of Rac1 using Nkx2.5 Cre line is lethal at E13.5. • The myocardium of the mutant is thin and disorganized. • The phenotype is not due to cardiomyocyte low proliferation or apoptosis. • The phenotype is due to specific defect in cardiomyocyte adhesion. - Abstract: Rac1, a member of the Rho subfamily of small GTPases, is involved in morphogenesis and differentiation of many cell types. Here we define a role of Rac1 in cardiac development by specifically deleting Rac1 in the pre-cardiac mesoderm using the Nkx2.5-Cre transgenic driver line. Rac1-conditional knockout embryos initiate heart development normally until embryonic day 11.5 (E11.5); their cardiac mesoderm is specified, and the heart tube is formed and looped. However, by E12.5-E13.5 the mutant hearts start failing and embryos develop edema and hemorrhage which is probably the cause for the lethality observed soon after. The hearts of Rac1-cKO embryos exhibit disorganized and thin myocardial walls and defects in outflow tract alignment. No significant differences of cardiomyocyte death or proliferation were found between developing control and mutant embryos. To uncover the role of Rac1 in the heart, E11.5 primary heart cells were cultured and analyzed in vitro. Rac1-deficient cardiomyocytes were less spread, round and loosely attached to the substrate and to each other implying that Rac1-mediated signaling is required for appropriate cell–cell and/or cellmatrix adhesion during cardiac development.

  15. Mapping of Redox State of Mitochondrial Cytochromes in Live Cardiomyocytes Using Raman Microspectroscopy

    Science.gov (United States)

    Brazhe, Nadezda A.; Treiman, Marek; Brazhe, Alexey R.; Find, Ninett L.; Maksimov, Georgy V.; Sosnovtseva, Olga V.

    2012-01-01

    This paper presents a nonivasive approach to study redox state of reduced cytochromes , and of complexes II and III in mitochondria of live cardiomyocytes by means of Raman microspectroscopy. For the first time with the proposed approach we perform studies of rod- and round-shaped cardiomyocytes, representing different morphological and functional states. Raman mapping and cluster analysis reveal that these cardiomyocytes differ in the amounts of reduced cytochromes , and . The rod-shaped cardiomyocytes possess uneven distribution of reduced cytochromes , and in cell center and periphery. Moreover, by means of Raman spectroscopy we demonstrated the decrease in the relative amounts of reduced cytochromes , and in the rod-shaped cardiomyocytes caused by H2O2-induced oxidative stress before any visible changes. Results of Raman mapping and time-dependent study of reduced cytochromes of complexes II and III and cytochrome in cardiomyocytes are in a good agreement with our fluorescence indicator studies and other published data. PMID:22957018

  16. Simple non-invasive analysis of embryonic stem cell-derived cardiomyocytes beating in vitro

    Science.gov (United States)

    Radaszkiewicz, Katarzyna Anna; Sýkorová, Dominika; Karas, Pavel; Kudová, Jana; Kohút, Lukáš; Binó, Lucia; Večeřa, Josef; Víteček, Jan; Kubala, Lukáš; Pacherník, Jiří

    2016-02-01

    The analysis of digital video output enables the non-invasive screening of various active biological processes. For the monitoring and computing of the beating parameters of cardiomyocytes in vitro, CB Analyser (cardiomyocyte beating analyser) software was developed. This software is based on image analysis of the video recording of beating cardiomyocytes. CB Analyser was tested using cardiomyocytes derived from mouse embryonic stem cells at different stages of cardiomyogenesis. We observed that during differentiation (from day 18), the beat peak width decreased, which corresponded to the increased speed of an individual pulse. However, the beating frequency did not change. Further, the effects of epinephrine modulating mature cardiomyocyte functions were tested to validate the CB Analyser analysis. In conclusion, data show that CB Analyser is a useful tool for evaluating the functions of both developing and mature cardiomyocytes under various conditions in vitro.

  17. Atrial Fibrillation and Fibrosis: Beyond the Cardiomyocyte Centric View

    Science.gov (United States)

    Miragoli, Michele; Glukhov, Alexey V.

    2015-01-01

    Atrial fibrillation (AF) associated with fibrosis is characterized by the appearance of interstitial myofibroblasts. These cells are responsible for the uncontrolled deposition of the extracellular matrix, which pathologically separate cardiomyocyte bundles. The enhanced fibrosis is thought to contribute to arrhythmias “indirectly” because a collagenous septum is a passive substrate for propagation, resulting in impulse conduction block and/or zigzag conduction. However, the emerging results demonstrate that myofibroblasts in vitro also promote arrhythmogenesis due to direct implications upon cardiomyocyte electrophysiology. This electrical interference may be considered beneficial as it resolves any conduction blocks; however, the passive properties of myofibroblasts might cause a delay in impulse propagation, thus promoting AF due to discontinuous slow conduction. Moreover, low-polarized myofibroblasts reduce, via cell-density dependence, the fast driving inward current for cardiac impulse conduction, therefore resulting in arrhythmogenic uniformly slow propagation. Critically, the subsequent reduction in cardiomyocytes resting membrane potential in vitro significantly increases the likelihood of ectopic activity. Myofibroblast densities and the degree of coupling at cellular border zones also impact upon this likelihood. By considering future in vivo studies, which identify myofibroblasts “per se” as a novel targets for cardiac arrhythmias, this review aims to describe the implications of noncardiomyocyte view in the context of AF. PMID:26229964

  18. Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited

    Science.gov (United States)

    Borkowski, Brian J.; Cheema, Yaser; Shahbaz, Atta U.; Bhattacharya, Syamal K.; Weber, Karl T.

    2011-01-01

    An ongoing loss of cardiomyocytes to apoptotic and necrotic cell death pathways contributes to the progressive nature of heart failure. The pathophysiological origins of necrotic cell loss relate to the neurohormonal activation that accompanies acute and chronic stressor states and which includes effector hormones of the adrenergic nervous system. Fifty years ago, Albrecht Fleckenstein and coworkers hypothesized the hyperadrenergic state, which accompanies such stressors, causes cardiomyocyte necrosis based on catecholamine-initiated excessive intracellular Ca2+ accumulation (EICA), and mitochondrial Ca2+ overloading in particular, in which the ensuing dysfunction and structural degeneration of these organelles leads to necrosis. In recent years, two downstream factors have been identified which, together with EICA, constitute a signal–transducer–effector pathway: (i) mitochondria-based induction of oxidative stress, in which the rate of reactive oxygen metabolite generation exceeds their rate of detoxification by endogenous antioxidant defences; and (ii) the opening of the mitochondrial inner membrane permeability transition pore (mPTP) followed by organellar swelling and degeneration. The pathogenesis of stress-related cardiomyopathy syndromes is likely related to this pathway. Other factors which can account for cytotoxicity in stressor states include: hypokalaemia; ionized hypocalcaemia and hypomagnesaemia with resultant elevations in parathyroid hormone serving as a potent mediator of EICA; and hypozincaemia with hyposelenaemia, which compromise antioxidant defences. Herein, we revisit the Fleckenstein hypothesis of EICA in leading to cardiomyocyte necrosis and the central role played by mitochondria. PMID:21398641

  19. Role of Histone Demethylases in Cardiomyocytes Induced to Hypertrophy

    Directory of Open Access Journals (Sweden)

    Wendy Rosales

    2016-01-01

    Full Text Available Epigenetic changes induced by histone demethylases play an important role in differentiation and pathological changes in cardiac cells. However, the role of the jumonji family of demethylases in the development of cardiac hypertrophy remains elusive. In this study, the presence of different histone demethylases in cardiac cells was evaluated after hypertrophy was induced with neurohormones. A cell line from rat cardiomyocytes was used as a biological model. The phenotypic profiles of the cells, as well as the expression of histone demethylases, were studied through immunofluorescence, transient transfection, western blot, and qRT-PCR analysis after inducing hypertrophy by angiotensin II and endothelin-1. An increase in fetal gene expression (ANP, BNP, and β-MHC was observed in cardiomyocytes after treatment with angiotensin II and endothelin-1. A significant increase in JMJD2A expression, but not in UTX or JMJD2C expression, was observed. When JMJD2A was overexpressed in cardiomyocytes through transient transfection, the effect of neurohormones on fetal cardiac gene expression was increased. We conclude that JMJD2A plays a principal role in the regulation of fetal cardiac genes, which increase in expression during the pathological hypertrophic process.

  20. Effect of biophysical cues on reprogramming to cardiomyocytes.

    Science.gov (United States)

    Sia, Junren; Yu, Pengzhi; Srivastava, Deepak; Li, Song

    2016-10-01

    Reprogramming of fibroblasts to cardiomyocytes offers exciting potential in cell therapy and regenerative medicine, but has low efficiency. We hypothesize that physical cues may positively affect the reprogramming process, and studied the effects of periodic mechanical stretch, substrate stiffness and microgrooved substrate on reprogramming yield. Subjecting reprogramming fibroblasts to periodic mechanical stretch and different substrate stiffness did not improve reprogramming yield. On the other hand, culturing the cells on microgrooved substrate enhanced the expression of cardiomyocyte genes by day 2 and improved the yield of partially reprogrammed cells at day 10. By combining microgrooved substrate with an existing optimized culture protocol, yield of reprogrammed cardiomyocytes with striated cardiac troponin T staining and spontaneous contractile activity was increased. We identified the regulation of Mkl1 activity as a new mechanism by which microgroove can affect reprogramming. Biochemical approach could only partially recapitulate the effect of microgroove. Microgroove demonstrated an additional effect of enhancing organization of sarcomeric structure, which could not be recapitulated by biochemical approach. This study provides insights into new mechanisms by which topographical cues can affect cellular reprogramming.

  1. Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct Reprogramming

    OpenAIRE

    Burridge, Paul W.; Keller, Gordon; Gold, Joseph D.; Wu, Joseph C

    2012-01-01

    Cardiovascular disease is a leading cause of death worldwide. The limited capability of heart tissue to regenerate has prompted method developments for creating de novo cardiomyocytes, both in vitro and in vivo. Beyond uses in cell replacement therapy, patient-specific cardiomyocytes may find applications in drug testing, drug discovery, and disease modeling. Recently, approaches for generating cardiomyocytes have expanded to encompass three major sources of starting cells: human pluripotent ...

  2. Cardiac protein kinases: the cardiomyocyte kinome and differential kinase expression in human failing hearts

    OpenAIRE

    Fuller, Stephen J.; Osborne, Sally A.; Leonard, Sam J.; Hardyman, Michelle A.; Vaniotis, George; Allen, Bruce G.; Sugden, Peter H.; Clerk, Angela

    2015-01-01

    Aims. Protein kinases are potential therapeutic targets for heart failure, but most studies of cardiac protein kinases derive from other systems, an approach that fails to account for specific kinases expressed in the heart and the contractile cardiomyocytes. We aimed to define the cardiomyocyte kinome (i.e. the protein kinases expressed in cardiomyocytes) and identify kinases with altered expression in human failing hearts. Methods and Results. Expression profiling (Affymetrix microarrays) d...

  3. BASIC SUPPOSITIONS FOR ORGANIZING AND ESTABLISHING A COHERENT SYSTEM OF EARLY TREATMENT AND PRE-SCHOOL UPBRINGING OF CHILDREN WITH DEVELOPMENTAL DIFFICULTIES IN CONDITIONS OF TRANSITION (situation, problems and needs

    Directory of Open Access Journals (Sweden)

    Ljupco Ajdinski

    1997-03-01

    Full Text Available The author of this paper wants to pay attention to the utmost problems of treatment and pre-school upbringing, from several points of view ( health, social, educational, economic, normative etc., that are related to the establishment of the primary conditions and suppositions for successful organization of protection and rehabilitation of these children.Children with developmental difficulties are quite a complex problem of the family, society and professional problem. The complexity and the burden of this problem are seen through the type and level of impairment, through the number of such children, as in providing financial, personnel and other conditions that are needed for successful protection and treatment.Taking into consideration the number of these children, in the paper is given the prognosis according to some percentages used for the whole population by ON and WHO. It is considered that 5-7 % are children with developmental difficulties at pre-school period. because the main topic at this Symposium is early treatment and pre- school upbringing, the early age is taken for the mentioned percentage. According to this, in our country there are about 19.000 children from 0-9 years of age, if this percentage of 6 % is applied from the total number of children at that age, that shows in the latest census of the population in the R. of Macedonia in 1994 , that there are 313.908 children. This number shows the gravity of the problem that is elaborated in this paper. The author stresses that the complexity of this problem increases if we take into consideration the present conditions according to the range of these children with early treatment and preschool upbringing, as apart of the whole system of rehabilitation.The complete treatment, i.e. the rehabilitation of children with developmental difficulties presents the unity of all the provisions and proceedings that are necessary to be undertaken to eliminate or reduce to the minimum

  4. Analysis of Calcium Transients and Uniaxial Contraction Force in Single Human Embryonic Stem Cell-Derived Cardiomyocytes on Microstructured Elastic Substrate with Spatially Controlled Surface Chemistries.

    Science.gov (United States)

    Grespan, Eleonora; Martewicz, Sebastian; Serena, Elena; Le Houerou, Vincent; Rühe, Jürgen; Elvassore, Nicola

    2016-11-22

    The mechanical activity of cardiomyocytes is the result of a process called excitation-contraction coupling (ECC). A membrane depolarization wave induces a transient cytosolic calcium concentration increase that triggers activation of calcium-sensitive contractile proteins, leading to cell contraction and force generation. An experimental setup capable of acquiring simultaneously all ECC features would have an enormous impact on cardiac drug development and disease study. In this work, we develop a microengineered elastomeric substrate with tailor-made surface chemistry to measure simultaneously the uniaxial contraction force and the calcium transients generated by single human cardiomyocytes in vitro. Microreplication followed by photocuring is used to generate an array consisting of elastomeric micropillars. A second photochemical process is employed to spatially control the surface chemistry of the elastomeric pillar. As result, human embryonic stem cell-derived cardiomyocytes (hESC-CMs) can be confined in rectangular cell-adhesive areas, which induce cell elongation and promote suspended cell anchoring between two adjacent micropillars. In this end-to-end conformation, confocal fluorescence microscopy allows simultaneous detection of calcium transients and micropillar deflection induced by a single-cell uniaxial contraction force. Computational finite elements modeling (FEM) and 3D reconstruction of the cell-pillar interface allow force quantification. The platform is used to follow calcium dynamics and contraction force evolution in hESC-CMs cultures over the course of several weeks. Our results show how a biomaterial-based platform can be a versatile tool for in vitro assaying of cardiac functional properties of single-cell human cardiomyocytes, with applications in both in vitro developmental studies and drug screening on cardiac cultures.

  5. EGCG inhibits cardiomyocyte apoptosis in pressure overload-induced cardiac hypertrophy and protects cardiomyocytes from oxidative stress in rats

    Institute of Scientific and Technical Information of China (English)

    Rui SHENG; Zhen-lun GU; Mei-lin XIE; Wen-xuan ZHOU; Ci-yi GUO

    2007-01-01

    Aim: To investigate the effects of epigallocatechin gallate (EGCG) on pressure overload and hydrogen peroxide (H2O2) induced cardiac myocyte apoptosis. Methods: Cardiac hypertrophy was established in rats by abdominal aortic constriction. EGCG 25, 50 and 100 mg/kg were administered intragastrically (ig). Cultured newborn rat cardiomyocytes were preincubated with EGCG, and oxidative stress injury was induced by H2O2. Results: In cardiac hypertrophy induced by AC in rats, relative to the model group, EGCG 25, 50 and 100 mg/kg ig for 6weeks dose-dependently reduced systolic blood pressure (SBP) and heart weight indices, decreased malondialdehyde (MDA) content, and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, both in serum and in the myocardium. Also, treatment with EGCG 50 and 100 mg/kg markedly improved cardiac structure and inhibited fibrosis in HE and van Gieson (VG) stain, and reduced apoptotic myocytes in the hypertrophic myocardium detected by terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Inthe Western blot analysis, EGCG significantly inhibited pressure overload-inducedp53 increase and bcl-2 decrease. In H2O2-induced cardiomyocyte injury, when preincubated with myocytes for 6-48 h, EGCG 12.5-200 mg/L increased cell viability determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. EGCG also attenuated H2O2-induced lactate dehydrogenase (LDH) release and MDA formation. Meanwhile, EGCG 50 and 100 mg/L significantly inhibited the cardiomyocyte apoptotic rate in flow cytometry. Conclusion: EGCG inhibits cardiac myocyte apoptosis and oxidative stress in pressure overload in-duced cardiac hypertrophy. Also, EGCG prevented cardiomyocyte apoptosis from oxidative stress in vitro. The mechanism might be related to the inhibitory effects of EGCG on p53 induction and bcl-2 decrease.

  6. Dedifferentiated fat cells convert to cardiomyocyte phenotype and repair infarcted cardiac tissue in rats.

    Science.gov (United States)

    Jumabay, Medet; Matsumoto, Taro; Yokoyama, Shin-ichiro; Kano, Koichiro; Kusumi, Yoshiaki; Masuko, Takayuki; Mitsumata, Masako; Saito, Satoshi; Hirayama, Atsushi; Mugishima, Hideo; Fukuda, Noboru

    2009-11-01

    Adipose tissue-derived stem cells have been demonstrated to differentiate into cardiomyocytes and vascular endothelial cells. Here we investigate whether mature adipocyte-derived dedifferentiated fat (DFAT) cells can differentiate to cardiomyocytes in vitro and in vivo by establishing DFAT cell lines via ceiling culture of mature adipocytes. DFAT cells were obtained by dedifferentiation of mature adipocytes from GFP-transgenic rats. We evaluated the differentiating ability of DFAT cells into cardiomyocytes by detection of the cardiac phenotype markers in immunocytochemical and RT-PCR analyses in vitro. We also examined effects of the transplantation of DFAT cells into the infarcted heart of rats on cardiomyocytes regeneration and angiogenesis. DFAT cells expressed cardiac phenotype markers when cocultured with cardiomyocytes and also when grown in MethoCult medium in the absence of cardiomyocytes, indicating that DFAT cells have the potential to differentiate to cardiomyocyte lineage. In a rat acute myocardial infarction model, transplanted DFAT cells were efficiently accumulated in infarcted myocardium and expressed cardiac sarcomeric actin at 8 weeks after the cell transplantation. The transplantation of DFAT cells significantly (pDFAT cells have the ability to differentiate to cardiomyocyte-like cells in vitro and in vivo. In addition, transplantation of DFAT cells led to neovascuralization in rats with myocardial infarction. We propose that DFAT cells represent a promising candidate cell source for cardiomyocyte regeneration in severe ischemic heart disease.

  7. Multi-parameter in vitro toxicity testing of crizotinib, sunitinib, erlotinib, and nilotinib in human cardiomyocytes

    Energy Technology Data Exchange (ETDEWEB)

    Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com [Quintiles, 777 Oakmont Lane Suite 100, Westmont, IL 60559 (United States); Wappel, Robert L.; Talbert, Dominique R.; Trusk, Patricia B.; Moran, Diarmuid M. [Quintiles, 777 Oakmont Lane Suite 100, Westmont, IL 60559 (United States); Kramer, James W.; Brown, Arthur M. [ChanTest Corporation, 14656 Neo Parkway, Cleveland, OH 44128 (United States); Shell, Scott A.; Bacus, Sarah [Quintiles, 777 Oakmont Lane Suite 100, Westmont, IL 60559 (United States)

    2013-10-01

    Tyrosine kinase inhibitors (TKi) have greatly improved the treatment and prognosis of multiple cancer types. However, unexpected cardiotoxicity has arisen in a subset of patients treated with these agents that was not wholly predicted by pre-clinical testing, which centers around animal toxicity studies and inhibition of the human Ether-à-go-go-Related Gene (hERG) channel. Therefore, we sought to determine whether a multi-parameter test panel assessing the effect of drug treatment on cellular, molecular, and electrophysiological endpoints could accurately predict cardiotoxicity. We examined how 4 FDA-approved TKi agents impacted cell viability, apoptosis, reactive oxygen species (ROS) generation, metabolic status, impedance, and ion channel function in human cardiomyocytes. The 3 drugs clinically associated with severe cardiac adverse events (crizotinib, sunitinib, nilotinib) all proved to be cardiotoxic in our in vitro tests while the relatively cardiac-safe drug erlotinib showed only minor changes in cardiac cell health. Crizotinib, an ALK/MET inhibitor, led to increased ROS production, caspase activation, cholesterol accumulation, disruption in cardiac cell beat rate, and blockage of ion channels. The multi-targeted TKi sunitinib showed decreased cardiomyocyte viability, AMPK inhibition, increased lipid accumulation, disrupted beat pattern, and hERG block. Nilotinib, a second generation Bcr-Abl inhibitor, led to increased ROS generation, caspase activation, hERG block, and an arrhythmic beat pattern. Thus, each drug showed a unique toxicity profile that may reflect the multiple mechanisms leading to cardiotoxicity. This study demonstrates that a multi-parameter approach can provide a robust characterization of drug-induced cardiomyocyte damage that can be leveraged to improve drug safety during early phase development. - Highlights: • TKi with known adverse effects show unique cardiotoxicity profiles in this panel. • Crizotinib increases ROS, apoptosis, and

  8. iPSC-derived cardiomyocytes reveal abnormal TGFβ signaling in left ventricular non-compaction cardiomyopathy

    Science.gov (United States)

    Kodo, Kazuki; Ong, Sang-Ging; Jahanbani, Fereshteh; Termglinchan, Vittavat; Hirono, Keiichi; InanlooRahatloo, Kolsoum; Ebert, Antje D.; Shukla, Praveen; Abilez, Oscar J.; Churko, Jared M.; Karakikes, Ioannis; Jung, Gwanghyun; Ichida, Fukiko; Wu, Sean M.; Snyder, Michael P.; Bernstein, Daniel; Wu, Joseph C.

    2016-01-01

    Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and was associated with perturbed transforming growth factor beta (TGFβ) signaling. LVNC iPSC-CMs have decreased proliferative capacity due to abnormal activation of TGFβ signaling. TBX20 regulates the expression of TGFβ signaling modifiers including a known genetic cause of LVNC, PRDM16, and genome editing of PRDM16 caused proliferation defects in iPSC-CMs. Inhibition of TGFβ signaling and genome correction of the TBX20 mutation were sufficient to reverse the disease phenotype. Our study demonstrates that iPSC-CMs are a useful tool for the exploration of pathological mechanisms underlying poorly understood cardiomyopathies including LVNC. PMID:27642787

  9. Ischaemia-induced autophagy leads to degradation of gap junction protein connexin43 in cardiomyocytes.

    Science.gov (United States)

    Martins-Marques, Tania; Catarino, Steve; Zuzarte, Monica; Marques, Carla; Matafome, Paulo; Pereira, Paulo; Girão, Henrique

    2015-04-15

    GJIC (gap junction intercellular communication) between cardiomyocytes is essential for synchronous heart contraction and relies on Cx (connexin)-containing channels. Increased breakdown of Cx43 has been often associated with various cardiac diseases. However, the mechanisms whereby Cx43 is degraded in ischaemic heart remain unknown. The results obtained in the present study, using both HL-1 cells and organotypic heart cultures, show that simulated ischaemia induces degradation of Cx43 that can be prevented by chemical or genetic inhibitors of autophagy. Additionally, ischaemia-induced degradation of Cx43 results in GJIC impairment in HL-1 cells, which can be restored by autophagy inhibition. In cardiomyocytes, ubiquitin signals Cx43 for autophagic degradation, through the recruitment of the ubiquitin-binding proteins Eps15 (epidermal growth factor receptor substrate 15) and p62, that assist in Cx43 internalization and targeting to autophagic vesicles, via LC3 (light chain 3). Moreover, we establish that degradation of Cx43 in ischaemia or I/R (ischaemia/reperfusion) relies upon different molecular players. Indeed, degradation of Cx43 during early periods of ischaemia depends on AMPK (AMP-activated protein kinase), whereas in late periods of ischaemia and I/R Beclin 1 is required. In the Langendorff-perfused heart, Cx43 is dephosphorylated in ischaemia and degraded during I/R, where Cx43 degradation correlates with autophagy activation. In summary, the results of the present study provide new evidence regarding the molecular mechanisms whereby Cx43 is degraded in ischaemia, which may contribute to the development of new strategies that aim to preserve GJIC and cardiac function in ischaemic heart.

  10. Mothers' power assertion; children's negative, adversarial orientation; and future behavior problems in low-income families: early maternal responsiveness as a moderator of the developmental cascade.

    Science.gov (United States)

    Kim, Sanghag; Kochanska, Grazyna

    2015-02-01

    Parental power assertion, a key dimension of family environment, generally sets in motion detrimental developmental cascades; however, evidence suggests that other qualities of parenting, such as responsiveness, can significantly moderate those processes. Mechanisms that account for such moderating effects are not fully understood. We propose a conceptual model of processes linking parental power assertion, parental responsiveness, children's negative, adversarial, rejecting orientation toward the parent, and behavior problems. We test that model in a short-term longitudinal design involving 186 low-income, ethnically diverse mothers and their toddlers. When children were 30 months, the dyads were observed in multiple, lengthy, naturalistic laboratory interactions to assess behaviorally mothers' responsiveness and their power-assertive control style. At 33 months, we observed behavioral indicators of children's negative, adversarial, rejecting orientation toward the mothers in several naturalistic and standardized paradigms. At 40 months, mothers rated children's behavior problems. The proposed moderated mediation sequence, tested using a new approach, PROCESS (Hayes, 2013), was supported. The indirect effect from maternal power assertion to children's negative, adversarial orientation to future behavior problems was present when mothers' responsiveness was either low or average but absent when mothers were highly responsive. This study elucidates a potential process that may link parental power assertion with behavior problems and highlights how positive aspects of parenting can moderate this process and defuse maladaptive developmental cascades. It also suggests possible targets for parenting intervention and prevention efforts.

  11. Evolutionary developmental psychology.

    Science.gov (United States)

    King, Ashley C; Bjorklund, David F

    2010-02-01

    The field of evolutionary developmental psychology can potentially broaden the horizons of mainstream evolutionary psychology by combining the principles of Darwinian evolution by natural selection with the study of human development, focusing on the epigenetic effects that occur between humans and their environment in a way that attempts to explain how evolved psychological mechanisms become expressed in the phenotypes of adults. An evolutionary developmental perspective includes an appreciation of comparative research and we, among others, argue that contrasting the cognition of humans with that of nonhuman primates can provide a framework with which to understand how human cognitive abilities and intelligence evolved. Furthermore, we argue that several aspects of childhood (e.g., play and immature cognition) serve both as deferred adaptations as well as imparting immediate benefits. Intense selection pressure was surely exerted on childhood over human evolutionary history and, as a result, neglecting to consider the early developmental period of children when studying their later adulthood produces an incomplete picture of the evolved adaptations expressed through human behavior and cognition.

  12. 早期作业治疗对全面性发育迟缓患儿认知发育的影响%Effect of early cognitive occupational therapy on children with global developmental delay

    Institute of Scientific and Technical Information of China (English)

    胡继红; 郭春光; 周平秋; 刘丽君; 陈建树; 张惠佳

    2016-01-01

    目的:探讨早期作业疗法对全面性发育迟缓患儿智力发育的影响。方法:将62例全面性发育迟缓患儿分为观察组38例和对照组24例,对照组患儿接受运动训练、慢性小脑电刺激、水疗等康复训练治疗,观察组在此基础上进行早期作业治疗。2组治疗前和治疗12周后分别进行 Gesell 智力测试评估检查(GDS)和 Peabody 运动发育量表(PDMS)测试。结果:治疗12周后,2组 GDS 及 PDMS 各项评分均较治疗前明显提高(P <0.05),且观察组更高于对照组(P <0.05)。在不同年龄段,治疗前后观察组患儿的 GDS 各项评分差值有统计学差异(P <0.05),1岁以内的患儿治疗前后发育商差值最大。结论:早期作业训练治疗可有效的提高全面性发育迟缓患儿的智力各能区的发育水平,越早干预效果越好,值得临床推广。%Objective:To evaluate the effect of early occupational therapy on cognitive development of children withglobal developmental delay.Methods:Sixty-two children with global developmental delay were divided into observationgroup (n=38)and control group (n=24).Observation group accepted early occupational therapy and generalcomprehensive rehabilitation therapies,such as exercise training,low-frequency cerebellum electrical stimulation,hydrotherapy and so on,while the control group only accepted the comprehensive rehabilitation therapy.Each groupwas assessed with Gesell developmental scale (GDS)and Peabody developmental motor scale (PDMS)before and 12weeks after treatment.Results:The scores of GDS and PDMS in the observation group and the control group weresignificantly increased after 12-week treatment (P <0.05),more significantly in the observation group than in thecontrol group (P <0.05).At different age states,and before and after treatment,the GDS scores showed significantdifferences in the observation group (P <0.05).The difference in GDS scores was

  13. Myeloperoxidase impairs the contractile function in isolated human cardiomyocytes.

    Science.gov (United States)

    Kalász, Judit; Pásztor, Enikő T; Fagyas, Miklós; Balogh, Ágnes; Tóth, Attila; Csató, Viktória; Édes, István; Papp, Zoltán; Borbély, Attila

    2015-07-01

    We set out to characterize the mechanical effects of myeloperoxidase (MPO) in isolated left-ventricular human cardiomyocytes. Oxidative myofilament protein modifications (sulfhydryl (SH)-group oxidation and carbonylation) induced by the peroxidase and chlorinating activities of MPO were additionally identified. The specificity of the MPO-evoked functional alterations was tested with an MPO inhibitor (MPO-I) and the antioxidant amino acid Met. The combined application of MPO and its substrate, hydrogen peroxide (H2O2), largely reduced the active force (Factive), increased the passive force (Fpassive), and decreased the Ca(2+) sensitivity of force production (pCa50) in permeabilized cardiomyocytes. H2O2 alone had significantly smaller effects on Factive and Fpassive and did not alter pCa50. The MPO-I blocked both the peroxidase and the chlorinating activities, whereas Met selectively inhibited the chlorinating activity of MPO. All of the MPO-induced functional effects could be prevented by the MPO-I and Met. Both H2O2 alone and MPO + H2O2 reduced the SH content of actin and increased the carbonylation of actin and myosin-binding protein C to the same extent. Neither the SH oxidation nor the carbonylation of the giant sarcomeric protein titin was affected by these treatments. MPO activation induces a cardiomyocyte dysfunction by affecting Ca(2+)-regulated active and Ca(2+)-independent passive force production and myofilament Ca(2+) sensitivity, independent of protein SH oxidation and carbonylation. The MPO-induced deleterious functional alterations can be prevented by the MPO-I and Met. Inhibition of MPO may be a promising therapeutic target to limit myocardial contractile dysfunction during inflammation.

  14. Rat Cardiomyocytes Express a Classical Epithelial Beta-Defensin

    Directory of Open Access Journals (Sweden)

    Annika Linde

    2008-01-01

    Full Text Available Beta-defensins (BDs are classical epithelial antimicrobial peptides of immediate importance in innate host defense. Since recent studies have suggested that certain BDs are also expressed in non-traditional tissues, including whole heart homogenate and because effector molecules of innate immunity and inflammation can influence the development of certain cardiovascular disease processes, we hypothesized that BDs are produced by cardiomyocytes as a local measure of cardioprotection against danger signals. Here we report that at least one rat beta-defensin, rBD1, is expressed constitutively in cardiomyocytes specifically isolated using position-ablation-laser-microdissection (P.A.L.M. Microlaser Technologies. RT-PCR analysis showed expression of a single 318 bp transcript in adult rat heart (laser-excised cardiomyocytes and H9c2 cells (neonatal rat heart myoblasts. Moreover, the full length cDNA of rBD1 was established and translated into a putative peptide with 69 amino acid residues. The predicted amino acid sequence of the adult rat cardiac BD-1 peptide displayed 99% identity with the previously reported renal rBD1 and 88, 53, 53 and 50% identity with mouse, human, gorilla and rhesus monkey BD1 respectively. Furthermore, structural analysis of the cardiac rBD1 showed the classical six-cysteine conserved motif of the BD family with an alpha-helix and three beta-sheets. Additionally, rBD1 displayed a significantly greater number of amphoteric residues than any of the human analogs, indicating a strong pH functional dependence in the rat. We suggest that rBD1, which was initially believed to be a specific epithelium-derived peptide, may be also involved in local cardiac innate immune defense mechanisms.

  15. ADAM10 modulates calcitriol-regulated RAGE in cardiomyocytes.

    Science.gov (United States)

    Lee, Ting-Wei; Kao, Yu-Hsun; Lee, Ting-I; Chen, Yi-Jen

    2017-09-01

    Receptor for advanced glycation end products (RAGE) signalling plays a critical role in the pathogenesis of cardiovascular disease. Calcitriol modulates cardiac RAGE expression. This study explored the mechanisms underlying the effect of calcitriol on RAGE and soluble RAGE (sRAGE) expression in cardiomyocytes. Western blot, ELISA, fluorometric assay and PCR analyses were used to evaluate the RAGE, sRAGE, endogenous secretory RAGE (esRAGE), Jun N-terminal kinase (JNK), and a disintegrin and metalloprotease 10 (ADAM10) expression and enzyme activity in HL-1 atrial myocytes without and with calcitriol (10 and 100 nM), nuclear factor-κB (NF-κB) inhibitor (50 μg/mL), or ADAM10 inhibitor (5 μM) incubation for 48 h. Calcitriol (10 nM) significantly reduced RAGE protein expression and increased sRAGE concentrations in HL-1 cardiomyocytes compared with control cells. These changes were associated with increased protein expression and enzyme activity of ADAM10 and higher mRNA expression of esRAGE. In the presence of ADAM10 inhibitor, however, the suppressive effect of calcitriol on RAGE was diminished. Methylglyoxal (500 μM for 10 min)-mediated JNK phosphorylation was attenuated in the presence of calcitriol (10 nM). Moreover, control and NF-κB inhibitor-treated HL-1 cells had similar RAGE and sRAGE expression, suggesting that calcitriol-mediated RAGE modulation was independent of NF-κB signalling. We showed that RAGE downregulation and increased sRAGE production by calcitriol were mediated through ADAM10 activation in cardiomyocytes. The results suggest that calcitriol has therapeutic potential in treating RAGE-mediated cardiovascular complications. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  16. Dystrophin-deficient cardiomyocytes derived from human urine: New biologic reagents for drug discovery

    Directory of Open Access Journals (Sweden)

    Xuan Guan

    2014-03-01

    Full Text Available The ability to extract somatic cells from a patient and reprogram them to pluripotency opens up new possibilities for personalized medicine. Induced pluripotent stem cells (iPSCs have been employed to generate beating cardiomyocytes from a patient's skin or blood cells. Here, iPSC methods were used to generate cardiomyocytes starting from the urine of a patient with Duchenne muscular dystrophy (DMD. Urine was chosen as a starting material because it contains adult stem cells called urine-derived stem cells (USCs. USCs express the canonical reprogramming factors c-myc and klf4, and possess high telomerase activity. Pluripotency of urine-derived iPSC clones was confirmed by immunocytochemistry, RT-PCR and teratoma formation. Urine-derived iPSC clones generated from healthy volunteers and a DMD patient were differentiated into beating cardiomyocytes using a series of small molecules in monolayer culture. Results indicate that cardiomyocytes retain the DMD patient's dystrophin mutation. Physiological assays suggest that dystrophin-deficient cardiomyocytes possess phenotypic differences from normal cardiomyocytes. These results demonstrate the feasibility of generating cardiomyocytes from a urine sample and that urine-derived cardiomyocytes retain characteristic features that might be further exploited for mechanistic studies and drug discovery.

  17. From fetus towards adult : maturation and functional analysis of pluripotent stem cell-derived cardiomyocytes

    NARCIS (Netherlands)

    Catarino, Ribeiro M.

    2016-01-01

    This thesis describes research about the differentiation of human stem cells into cardiomyocytes (heart cells). During the differentiation process the stem cells become contractile myocytes that resemble the native heart cells. Nevertheless, the phenotype of these cardiomyocytes is comparable to a s

  18. KCNQ channels are involved in the regulatory volume decrease response in primary neonatal rat cardiomyocytes

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Nielsen, Morten Schak; Grunnet, Morten;

    2007-01-01

    Cardiomyocytes may experience significant cell swelling during ischemia and reperfusion. Such changes in cardiomyocyte volume have been shown to affect the electrical properties of the heart, possibly leading to cardiac arrhythmia. In the present study the regulatory volume decrease (RVD) response...

  19. Inhibition of Receptor Interacting Protein Kinases Attenuates Cardiomyocyte Hypertrophy Induced by Palmitic Acid.

    Science.gov (United States)

    Zhao, Mingyue; Lu, Lihui; Lei, Song; Chai, Hua; Wu, Siyuan; Tang, Xiaoju; Bao, Qinxue; Chen, Li; Wu, Wenchao; Liu, Xiaojing

    2016-01-01

    Palmitic acid (PA) is known to cause cardiomyocyte dysfunction. Cardiac hypertrophy is one of the important pathological features of PA-induced lipotoxicity, but the mechanism by which PA induces cardiomyocyte hypertrophy is still unclear. Therefore, our study was to test whether necroptosis, a receptor interacting protein kinase 1 and 3 (RIPK1 and RIPK3-) dependent programmed necrosis, was involved in the PA-induced cardiomyocyte hypertrophy. We used the PA-treated primary neonatal rat cardiac myocytes (NCMs) or H9c2 cells to study lipotoxicity. Our results demonstrated that cardiomyocyte hypertrophy was induced by PA treatment, determined by upregulation of hypertrophic marker genes and cell surface area enlargement. Upon PA treatment, the expression of RIPK1 and RIPK3 was increased. Pretreatment with the RIPK1 inhibitor necrostatin-1 (Nec-1), the PA-induced cardiomyocyte hypertrophy, was attenuated. Knockdown of RIPK1 or RIPK3 by siRNA suppressed the PA-induced myocardial hypertrophy. Moreover, a crosstalk between necroptosis and endoplasmic reticulum (ER) stress was observed in PA-treated cardiomyocytes. Inhibition of RIPK1 with Nec-1, phosphorylation level of AKT (Ser473), and mTOR (Ser2481) was significantly reduced in PA-treated cardiomyocytes. In conclusion, RIPKs-dependent necroptosis might be crucial in PA-induced myocardial hypertrophy. Activation of mTOR may mediate the effect of necroptosis in cardiomyocyte hypertrophy induced by PA.

  20. NIDCAP and developmental care

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    Dominique Haumont

    2014-06-01

    Full Text Available Perinatal mortality in very low birth weight infants has dramatically decreased during the last decades. However, 15-25% of these infants will show neurodevelopmental impairment later on. The aim of implementing early developmental care (EDC, emerged as a new field in neonatology, is to create an intervention program designed to provide support for optimal neurobehavioral development during this highly vulnerable period of brain growth. The theoretical framework, which underlies the approach, is supported by research in different scientific fields, including neuroscience, psychology, medicine and nursing. EDC utilizes a range of medical and nursing interventions that aim to decrease the stress of preterm neonates in neonatal intensive care units (NICUs. The Neonatal Individualized Developmental Care Assessment Program (NIDCAP is an integrated and holistic form of family-centered developmental care. Changing the traditional NICU towards an EDC-NICU includes training nursing and medical staff, investing in their quality and most importantly keeping parents in proximity to the infants. The new challenge of modern neonatology is to restore the mother-infant dyad applying “couplet care” starting at birth until discharge. Most of the European NICUs apply some elements of EDC, but it is more consistent in northern Europe. The development of NIDCAP training centers in Europe demonstrates the evolution of care. It is likely that future research and intervention programs will optimize our practices. Developmental care could prove to be an important recent step in improving outcome in extremely preterm neonates. Proceedings of the 10th International Workshop on Neonatology · Cagliari (Italy · October 22nd-25th, 2014 · The last ten years, the next ten years in Neonatology Guest Editors: Vassilios Fanos, Michele Mussap, Gavino Faa, Apostolos Papageorgiou

  1. Imaging alterations of cardiomyocyte cAMP microdomains in disease

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    Alexander eFroese

    2015-08-01

    Full Text Available 3’,5’-cyclic adenosine monophosphate (cAMP is an important second messenger which regulates heart function by acting in distinct subcellular microdomains. Recent years have provided deeper mechanistic insights into compartmentalized cAMP signaling and its link to cardiac disease. In this mini review, we summarize newest developments in this field achieved by cutting-edge biochemical and biophysical techniques. We further compile the data from different studies into a bigger picture of so far uncovered alterations in cardiomyocyte cAMP microdomains which occur in compensated cardiac hypertrophy and chronic heart failure. Finally, future research directions and translational perspectives are briefly discussed.

  2. Effects of leptin on in vitro maturation, fertilization and embryonic cleavage after ICSI and early developmental expression of leptin (Ob and leptin receptor (ObR proteins in the horse

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    Arrighi Silvana

    2009-10-01

    Full Text Available Abstract Background The identification of the adipocyte-derived obesity gene product, leptin (Ob, and subsequently its association with reproduction in rodents and humans led to speculations that leptin may be involved in the regulation of oocyte and preimplantation embryo development. In mice and pigs, in vitro leptin addition significantly increased meiotic resumption and promoted preimplantation embryo development in a dose-dependent manner. This study was conducted to determine whether leptin supplementation during in vitro maturation (IVM to horse oocytes could have effects on their developmental capacity after fertilization by IntraCytoplasmic Sperm Injection (ICSI. Methods Compact and expanded-cumulus horse oocytes were matured in medium containing different concentrations (1, 10, 100, 1000 ng/ml of recombinant human leptin and the effects on maturation, fertilization and embryo cleavage were evaluated. Furthermore, early developmental expression of Ob and leptin receptor (Ob-R was investigated by immunocytochemical staining. Results In expanded-cumulus oocytes, the addition of leptin in IVM medium improved maturation (74% vs 44%, for 100 ng/ml leptin-treated and control groups, respectively; P Conclusion Leptin plays a cumulus cell-mediated role in the regulation of oocyte maturation in the mare. Species-specific differences may exist in oocyte sensitivity to leptin.

  3. Cardiomyocyte death induced by ischaemic/hypoxic stress is differentially affected by distinct purinergic P2 receptors.

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    Cosentino, Simona; Banfi, Cristina; Burbiel, Joachim C; Luo, Haijian; Tremoli, Elena; Abbracchio, Maria P

    2012-05-01

    Blood levels of extracellular nucleotides (e.g. ATP) are greatly increased during heart ischaemia, but, despite the presence of their specific receptors on cardiomyocytes (both P2X and P2Y subtypes), their effects on the subsequent myocardial damage are still unknown. In this study, we aimed at investigating the role of ATP and specific P2 receptors in the appearance of cell injury in a cardiac model of ischaemic/hypoxic stress. Cells were maintained in a modular incubator chamber in a controlled humidified atmosphere of 95% N(2) for 16 hrs in a glucose-free medium. In this condition, we detected an early increase in the release of ATP in the culture medium, which was followed by a massive increase in the release of cytoplasmic histone-associated-DNA-fragments, a marker of apoptosis. Addition of either apyrase, which degrades extracellular ATP, or various inhibitors of ATP release via connexin hemichannels fully abolished ischaemic/hypoxic stress-associated apoptosis. To dissect the role of specific P2 receptor subtypes, we used a combined approach: (i) non-selective and, when available, subtype-selective P2 antagonists, were added to cardiomyocytes before ischaemic/hypoxic stress; (ii) selected P2 receptors genes were silenced via specific small interfering RNAs. Both approaches indicated that the P2Y(2) and P2χ(7) receptor subtypes are directly involved in the induction of cell death during ischaemic/hypoxic stress, whereas the P2Y(4) receptor has a protective effect. Overall, these findings indicate a role for ATP and its receptors in modulating cardiomyocyte damage during ischaemic/hypoxic stress.

  4. Developmental dyslexia.

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    Peterson, Robin L; Pennington, Bruce F

    2015-01-01

    This review uses a levels-of-analysis framework to summarize the current understanding of developmental dyslexia's etiology, brain bases, neuropsychology, and social context. Dyslexia is caused by multiple genetic and environmental risk factors as well as their interplay. Several candidate genes have been identified in the past decade. At the brain level, dyslexia is associated with aberrant structure and function, particularly in left hemisphere reading/language networks. The neurocognitive influences on dyslexia are also multifactorial and involve phonological processing deficits as well as weaknesses in other oral language skills and processing speed. We address contextual issues such as how dyslexia manifests across languages and social classes as well as what treatments are best supported. Throughout the review, we highlight exciting new research that cuts across levels of analysis. Such work promises eventually to provide a comprehensive explanation of the disorder as well as its prevention and remediation.

  5. Generation and characterization of functional cardiomyocytes derived from human T cell-derived induced pluripotent stem cells.

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    Tomohisa Seki

    Full Text Available Induced pluripotent stem cells (iPSCs have been proposed as novel cell sources for genetic disease models and revolutionary clinical therapies. Accordingly, human iPSC-derived cardiomyocytes are potential cell sources for cardiomyocyte transplantation therapy. We previously developed a novel generation method for human peripheral T cell-derived iPSCs (TiPSCs that uses a minimally invasive approach to obtain patient cells. However, it remained unknown whether TiPSCs with genomic rearrangements in the T cell receptor (TCR gene could differentiate into functional cardiomyocyte in vitro. To address this issue, we investigated the morphology, gene expression pattern, and electrophysiological properties of TiPSC-derived cardiomyocytes differentiated by floating culture. RT-PCR analysis and immunohistochemistry showed that the TiPSC-derived cardiomyocytes properly express cardiomyocyte markers and ion channels, and show the typical cardiomyocyte morphology. Multiple electrode arrays with application of ion channel inhibitors also revealed normal electrophysiological responses in the TiPSC-derived cardiomyocytes in terms of beating rate and the field potential waveform. In this report, we showed that TiPSCs successfully differentiated into cardiomyocytes with morphology, gene expression patterns, and electrophysiological features typical of native cardiomyocytes. TiPSCs-derived cardiomyocytes obtained from patients by a minimally invasive technique could therefore become disease models for understanding the mechanisms of cardiac disease and cell sources for revolutionary cardiomyocyte therapies.

  6. Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context.

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    Sungur, A Özge; Schwarting, Rainer K W; Wöhr, Markus

    2016-06-01

    Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1(-/-) null mutant, Shank1(+/-) heterozygous, and Shank1(+/+) wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1(-/-) pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696-709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley

  7. Global expression profile of highly enriched cardiomyocytes derived from human embryonic stem cells.

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    Xu, Xiu Qin; Soo, Set Yen; Sun, William; Zweigerdt, Robert

    2009-09-01

    Human embryonic stem cells (hESC), with their ability to differentiate into cardiomyocytes in culture, hold great potential for cell replacement therapies and provide an in vitro model of human heart development. A genomewide characterization of the molecular phenotype of hESC-derived cardiomyocytes is important for their envisioned applications. We have employed a lineage selection strategy to generate a pure population of cardiomyocytes (>99%) from transgenic hESC lines. Global gene expression profiling showed that these cardiomyocytes are distinct from pluripotent and differentiated hESC cultures. Pure cardiomyocytes displayed similarities with heart tissue, but in many aspects presented an individual transcriptome pattern. A subset of 1,311 cardiac-enriched transcripts was identified, which were significantly overpresented (p human heart development.

  8. Homologs of the Xenopus developmental gene DG42 are present in zebrafish and mouse and are involved in the synthesis of Nod-like chitin oligosaccharides during early embryogenesis.

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    Semino, C E; Specht, C A; Raimondi, A; Robbins, P W

    1996-05-14

    The Xenopus developmental gene DG42 is expressed during early embryonic development, between the midblastula and neurulation stages. The deduced protein sequence of Xenopus DG42 shows similarity to Rhizobium Nod C, Streptococcus Has A, and fungal chitin synthases. Previously, we found that the DG42 protein made in an in vitro transcription/translation system catalyzed synthesis of an array of chitin oligosaccharides. Here we show that cell extracts from early Xenopus and zebrafish embryos also synthesize chitooligosaccharides. cDNA fragments homologous to DG42 from zebrafish and mouse were also cloned and sequenced. Expression of these homologs was similar to that described for Xenopus based on Northern and Western blot analysis. The Xenopus anti-DG42 antibody recognized a 63-kDa protein in extracts from zebrafish embryos that followed a similar developmental expression pattern to that previously described for Xenopus. The chitin oligosaccharide synthase activity found in extracts was inactivated by a specific DG42 antibody; synthesis of hyaluronic acid (HA) was not affected under the conditions tested. Other experiments demonstrate that expression of DG42 under plasmid control in mouse 3T3 cells gives rise to chitooligosaccharide synthase activity without an increase in HA synthase level. A possible relationship between our results and those of other investigators, which show stimulation of HA synthesis by DG42 in mammalian cell culture systems, is provided by structural analyses to be published elsewhere that suggest that chitin oligosaccharides are present at the reducing ends of HA chains. Since in at least one vertebrate system hyaluronic acid formation can be inhibited by a pure chitinase, it seems possible that chitin oligosaccharides serve as primers for hyaluronic acid synthesis.

  9. Understanding greater cardiomyocyte functions on aligned compared to random carbon nanofibers in PLGA

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    Asiri AM

    2014-12-01

    Full Text Available Abdullah M Asiri,1 Hadi M Marwani,1 Sher Bahadar Khan,1 Thomas J Webster1,2 1Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Chemical Engineering, Northeastern University, Boston, MA, USA Abstract: Previous studies have demonstrated greater cardiomyocyte density on carbon nanofibers (CNFs aligned (compared to randomly oriented in poly(lactic-co-glycolic acid (PLGA composites. Although such studies demonstrated a closer mimicking of anisotropic electrical and mechanical properties for such aligned (compared to randomly oriented CNFs in PLGA composites, the objective of the present in vitro study was to elucidate a deeper mechanistic understanding of how cardiomyocyte densities recognize such materials to respond more favorably. Results showed lower wettability (greater hydrophobicity of CNFs embedded in PLGA compared to pure PLGA, thus providing evidence of selectively lower wettability in aligned CNF regions. Furthermore, the results correlated these changes in hydrophobicity with increased adsorption of fibronectin, laminin, and vitronectin (all proteins known to increase cardiomyocyte adhesion and functions on CNFs in PLGA compared to pure PLGA, thus providing evidence of selective initial protein adsorption cues on such CNF regions to promote cardiomyocyte adhesion and growth. Lastly, results of the present in vitro study further confirmed increased cardiomyocyte functions by demonstrating greater expression of important cardiomyocyte biomarkers (such as Troponin-T, Connexin-43, and α-sarcomeric actin when CNFs were aligned compared to randomly oriented in PLGA. In summary, this study provided evidence that cardiomyocyte functions are improved on CNFs aligned in PLGA compared to randomly oriented in PLGA since CNFs are more hydrophobic than PLGA and attract the adsorption of key proteins (fibronectin, laminin, and vironectin that are known to promote cardiomyocyte adhesion

  10. The role of mAKAPβ in the process of cardiomyocyte hypertrophy induced by angiotensin II.

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    Guo, Huixin; Liu, Baoxin; Hou, Lei; The, Erlinda; Li, Gang; Wang, Dongzhi; Jie, Qiqiang; Che, Wenliang; Wei, Yidong

    2015-05-01

    Angiotensin II (AngII) is the central product of the renin-angiotensin system (RAS) and this octapeptide contributes to the pathophysiology of cardiac hypertrophy and remodeling. mAKAPβ is an A-kinase anchoring protein (AKAP) that has the function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. In this study, we aimed to investigate the role of mAKAPβ in AngII‑induced cardiomyocyte hypertrophy and the possible mechanisms involved. Cultured cardiomyocytes from neonatal rats were treated with AngII. Subsequently, the morphology of the cardiomyocytes was observed and the expression of mAKAPβ and cardiomyocyte hypertrophic markers was measured. mAKAPβ‑shRNA was constructed for RNA interference; the expression of mAKAPβ and hypertrophic markers, the cell surface area and the [3H]Leucine incorporation rate in the AngII‑treated rat cardiomyocytes were detected following RNA interference. Simultaneously, changes in the expression levels of phosphorylated extracellular signal-regulated kinase (p-ERK)2 in the cardiomyocytes were assessed. The cell size of the AngII-treated cardiaomyocytes was significantly larger than that of the untreated cardiomyocytes. The expression of hypertrophic markers and p-ERK2, the cell surface area and the [3H]Leucine incorporation rate were all significantly increased in the AngII‑treated cells. However, the expression of mAKAPβ remained unaltered in this process. RNA interference simultaneously inhibited the protein expression of mAKAPβ and p‑ERK2, and the hypertrophy of the cardiomyocytes induced by AngII was attenuated. These results demonstrate that AngII induces hypertrophy in cardiomyocytes, and mAKAPβ is possibly involved in this process. The effects of mAKAPβ on AngII‑induced cardiomyocyte hypertrophy may be associated with p-ERK2 expression.

  11. Negative elongation factor controls energy homeostasis in cardiomyocytes.

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    Pan, Haihui; Qin, Kunhua; Guo, Zhanyong; Ma, Yonggang; April, Craig; Gao, Xiaoli; Andrews, Thomas G; Bokov, Alex; Zhang, Jianhua; Chen, Yidong; Weintraub, Susan T; Fan, Jian-Bing; Wang, Degeng; Hu, Yanfen; Aune, Gregory J; Lindsey, Merry L; Li, Rong

    2014-04-10

    Negative elongation factor (NELF) is known to enforce promoter-proximal pausing of RNA polymerase II (Pol II), a pervasive phenomenon observed across multicellular genomes. However, the physiological impact of NELF on tissue homeostasis remains unclear. Here, we show that whole-body conditional deletion of the B subunit of NELF (NELF-B) in adult mice results in cardiomyopathy and impaired response to cardiac stress. Tissue-specific knockout of NELF-B confirms its cell-autonomous function in cardiomyocytes. NELF directly supports transcription of those genes encoding rate-limiting enzymes in fatty acid oxidation (FAO) and the tricarboxylic acid (TCA) cycle. NELF also shares extensively transcriptional target genes with peroxisome proliferator-activated receptor α (PPARα), a master regulator of energy metabolism in the myocardium. Mechanistically, NELF helps stabilize the transcription initiation complex at the metabolism-related genes. Our findings strongly indicate that NELF is part of the PPARα-mediated transcription regulatory network that maintains metabolic homeostasis in cardiomyocytes.

  12. Cardiomyocyte regeneration from circulating bone marrow cells in mice.

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    Kuramochi, Yukio; Fukazawa, Ryuji; Migita, Makoto; Hayakawa, Jun; Hayashida, Mari; Uchikoba, Yohko; Fukumi, Daichi; Shimada, Takashi; Ogawa, Shunichi

    2003-09-01

    We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for GFP-positive cells confirmed reconstitution of transplanted bone marrow. Bone marrow transplant mice subsequently underwent left coronary artery ligation (myocardial infarction) or sham-operation, and were killed at 1 mo or 3 mo after operation. Infarct size was similar in bone marrow transplant mice at 1 mo (47.1 +/- 5.9%) and at 3 mo (45.3 +/- 7.8%), and echocardiography at 2 and 8 wk revealed decreasing left ventricular function. In infarcted heart, GFP-positive cells that expressed desmin and troponin T-C were identified by confocal microscopy. GFP and troponin T-C double-positive cells were predominantly in the peri-infarcted region (1 mo, 365 +/- 45 cells/50 sections; 3 mo: 458 +/- 100 cells/50 sections; p infarct, and sham-operated regions). Furthermore, BMC mobilization and differentiation into cardiomyocytes was found to be complete within 1 mo after myocardial infarction. These results demonstrate that circulating BMC undergo mobilization and differentiation in cardiac cells after myocardial infarction. Future studies are required to determine the molecular signaling mechanisms responsible for this phenomenon.

  13. Exogenous HGF Prevents Cardiomyocytes from Apoptosis after Hypoxia via Up-Regulating Cell Autophagy

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    Yunle Wang

    2016-06-01

    Full Text Available Background: Hepatocyte growth factor (HGF is widely known as a protective factor in ischemic myocardium, however HGF sensitive cellular mechanism remained ill-defined. Autophagy at early stage of hypoxia has been demonstrated to play a role in protecting myocardium both in vivo and vitro. We performed this study to investigate the association between the protective effect of HGF and autophagy. Methods: Ventricular myocytes were isolated from neonatal rat heart (NRVMs. We evaluated cardiomyocytes apoptosis by Hoechst staining and flow cytometry. Autophagy was assessed by transmission electron microscope and mRFP-GFP-LC3 adenovirus infection. Mitochondrial membrane potential was estimated by JC-1 staining. Western blotting and ELISA assay were used to quantify protein concentrations. Results: We found that autophagy in NRVMs increased at early stage after hypoxia and HGF release was consistent with the change of autophagy. Exogenous HGF enhanced autophagy and decreased apoptosis, while neutralizing HGF yielded opposite effects. Besides, inhibition of autophagy increased apoptosis of myocytes. Furthermore, exogenous HGF induced Parkin, the marker of mitochondrial autophagy, indicating increased clearance of injured mitochondria. Conclusions: Our results revealed a potential mechanism in which exogenous HGF prevented NRVMs from apoptosis after hypoxia. Upregulation of Parkin through administration of exogenous HGF may be a potential therapeutic strategy ptotecting myocytes during ischemia.

  14. Developmental Screening

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    ... the Signs. Act Early. Aprenda más sobre el desarrollo de su niño: Control y Evaluación del Desarrollo Dar un primer paso, decir “adiós” con la ... y señalar algo interesante son todos indicadores del desarrollo o cosas que la mayoría de los niños ...

  15. Early Writing among Ancient Vikings and Today's Pre-Schoolers: A Cognitive Developmental Perspective on Reading Acquisition and Alphabets as Effective Artefacts

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    Olofsson, Ake

    2008-01-01

    The present paper reports some observations on pre-school children's spontaneous as well as adult-supported spelling behaviour and makes comparisons between aspects of these early literacy activities and some features of spellings from mostly twelfth- to fourteenth-century Norwegian runic inscriptions. The runic inscriptions originate from a…

  16. Developmental Dynamics between Children's Externalizing Problems, Task-Avoidant Behavior, and Academic Performance in Early School Years: A 4-Year Follow-Up

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    Metsäpelto, Riitta-Leena; Pakarinen, Eija; Kiuru, Noona; Poikkeus, Anna-Maija; Lerkkanen, Marja-Kristiina; Nurmi, Jari-Erik

    2015-01-01

    This longitudinal study investigated the associations among children's externalizing problems, task-avoidant behavior, and academic performance in early school years. The participants were 586 children (43% girls, 57% boys). Data pertaining to externalizing problems (teacher ratings) and task-avoidant behaviors (mother and teacher ratings) were…

  17. Suppression of Wnt1-induced mammary tumor growth and lower serum insulin in offspring exposed to maternal blueberry diet suggest early dietary influence on developmental programming

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    Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. Here, we investigated whether earl...

  18. Annual Research Review: New Frontiers in Developmental Neuropharmacology--Can Long-Term Therapeutic Effects of Drugs Be Optimized through Carefully Timed Early Intervention?

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    Andersen, Susan L.; Navalta, Carryl P.

    2011-01-01

    Our aim is to present a working model that may serve as a valuable heuristic to predict enduring effects of drugs when administered during development. Our primary tenet is that a greater understanding of neurodevelopment can lead to improved treatment that intervenes early in the progression of a given disorder and prevents symptoms from…

  19. 早期综合干预对发育临界儿神经心理发育的影响%Effects of Early Systematical Intervention on Neuropsychological Development of Developmental Borderline Children

    Institute of Scientific and Technical Information of China (English)

    刘小英; 杨梅凤; 寇海燕; 刘文龙

    2014-01-01

    Objective: To explore effects of early systematical intervention on neuropsychological development of developmental borderline children (DBC).Method: 100 DBC aged from 0 to 6, whose developmental quotient(DQ) were from 70 to 85, were randomly grouped. There were 50 children in intervention group and control group respectively. Children from control group accepted only routine early education guidance while children from intervention group were educated by early systematical intervention training besides routine early education guidance. Their DQ were assessed after 6 months and were compared with DQ before intervention to evaluate educational training results.Result: The scores of DQ, gross motor, fine motor, adaptation, language and social behavior of children from intervention group were higher than those of children from control group and the difference was significant (P<0.01). The interventional effective rate of the intervention group was 92%, while that of the control group was 60%, and the difference was significant (P<0.01). Conclusion:Early systematical intervention can improve neuropsychological development of developmental borderline children (DBC).%目的:探究早期综合干预对发育临界儿神经心理发育的影响。方法:筛查出的总发育商为70~85分的0~6岁发育临界儿100例随机数字表法分为干预组和对照组,每组50例。对照组接受传统以体检为主的保健的基础上的常规早期教育指导,干预组在常规早期教育指导基础上,还进行了早期综合干预,采用0~6岁小儿神经心理发育检查表对两组患者分别在干预前和干预6个月后进行测查,比较两组发育临界儿干预效果。结果:干预6个月后干预组的发育商数、大运动、精细运动、适应能力、语言和社交行为的得分较对照组均有明显提高,差异有统计学意义(P<0.01);干预组总有效率达92%,明显高于对照组的总有效率60%,比较

  20. Do we need to follow up an early normal ultrasound with a later plain radiograph in children with a family history of developmental dysplasia of the hip?

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    Tafazal, Suhayl; Flowers, Mark J

    2015-10-01

    We routinely perform a pelvic radiograph between 6 and 12 months of age for children with a family history of developmental dysplasia of hip (DDH). We conducted this study to determine whether children with a family history of DDH and a normal hip ultrasound after birth require any further radiological follow-up. We identified all children referred to our hip-screening clinic in a 3-year period between August 2008 and August 2011 with a family history of DDH and a normal hip ultrasound after birth. A total of 119 patients with a normal hip ultrasound after birth had a pelvic radiograph at a median age of 6.6 months. Six patients had residual dysplasia (acetabular index >30°) on the initial radiograph; five of these had resolved spontaneously by age 12 months, and the remaining patient had a normal radiograph at 21 months of age and was discharged. We have found no cases of residual hip dysplasia requiring treatment in children with a family history of DDH and a normal hip ultrasound after birth. We have therefore changed our practice accordingly and no longer routinely followed up such cases. Diagnostic study, Level II.

  1. Histamine deficiency exacerbates myocardial injury in acute myocardial infarction through impaired macrophage infiltration and increased cardiomyocyte apoptosis.

    Science.gov (United States)

    Deng, Long; Hong, Tao; Lin, Jinyi; Ding, Suling; Huang, Zheyong; Chen, Jinmiao; Jia, Jianguo; Zou, Yunzeng; Wang, Timothy C; Yang, Xiangdong; Ge, Junbo

    2015-08-17

    Histamine is a biogenic amine that is widely distributed and has multiple functions, but the role it plays in acute myocardial infarction (AMI) remains unclear. In this study, we investigated the origin and contribution of endogenous histamine to AMI. Histidine decarboxylase (HDC) is the unique enzyme responsible for histamine generation. Using HDC-EGFP bacterial artificial chromosome (BAC) transgenic mice in which EGFP expression is controlled by the HDC promoter, we identified HDC expression primarily in CD11b(+)Gr-1(+) immature myeloid cells (IMCs) that markedly increase in the early stages of AMI. Deficiency of histamine in HDC knockout mice (HDC(-/-)) reduced cardiac function and exacerbated the injury of infarcted heart. Furthermore, administering either an H1 receptor antagonist (pyrilamine) or an H2 receptor antagonist (cimetidine) demonstrated a protective effect of histamine against myocardial injury. The results of in vivo and in vitro assays showed that histamine deficiency promotes the apoptosis of cardiomyocytes and inhibits macrophage infiltration. In conclusion, CD11b(+)Gr-1(+) IMCs are the predominant HDC-expressing sites in AMI, and histamine plays a protective role in the process of AMI through inhibition of cardiomyocyte apoptosis and facilitation of macrophage infiltration.

  2. Developmental dyspraxia and developmental coordination disorder.

    Science.gov (United States)

    Miyahara, M; Möbs, I

    1995-12-01

    This article discusses the role developmental dyspraxia plays in developmental coordination disorder (DCD), based upon a review of literature on apraxia, developmental dyspraxia, and DCD. Apraxia and dyspraxia have often been equated with DCD. However, it is argued that apraxia and dyspraxia primarily refer to the problems of motor sequencing and selection, which not all children with DCD exhibit. The author proposes to distinguish developmental dyspraxia from DCD. Other issues discussed include the assessment, etiology, and treatment of developmental dyspraxia and DCD, and the relationship between DCD and learning disabilities. A research agenda is offered regarding future directions to overcome current limitation.

  3. ANG II promotes IGF-IIR expression and cardiomyocyte apoptosis by inhibiting HSF1 via JNK activation and SIRT1 degradation.

    Science.gov (United States)

    Huang, C-Y; Kuo, W-W; Yeh, Y-L; Ho, T-J; Lin, J-Y; Lin, D-Y; Chu, C-H; Tsai, F-J; Tsai, C-H; Huang, C-Y

    2014-08-01

    Hypertension-induced cardiac hypertrophy and apoptosis are major characteristics of early-stage heart failure. Our previous studies found that the activation of insulin-like growth factor receptor II (IGF-IIR) signaling was critical for hypertensive angiotensin II (ANG II)-induced cardiomyocyte apoptosis. However, the detailed mechanism by which ANG II regulates IGF-IIR in heart cells remains elusive. In this study, we found that ANG II activated its downstream kinase JNK to increase IGF-IIR expression through the ANG II receptor angiotensin type 1 receptor. JNK activation subsequently led to sirtuin 1 (SIRT1) degradation via the proteasome, thus preventing SIRT1 from deacetylating heat-shock transcription factor 1 (HSF1). The resulting increase in the acetylation of HSF1 impaired its ability to bind to the IGF-IIR promoter region (nt -748 to -585). HSF1 protected cardiomyocytes by acting as a repressor of IGF-IIR gene expression, and ANG II diminished this HSF1-mediated repression through enhanced acetylation, thus activating the IGF-IIR apoptosis pathway. Taken together, these results suggest that HSF1 represses IGF-IIR gene expression to protect cardiomyocytes. ANG II activates JNK to degrade SIRT1, resulting in HSF1 acetylation, which induces IGF-IIR expression and eventually results in cardiac hypertrophy and apoptosis. HSF1 could be a valuable target for developing treatments for cardiac diseases in hypertensive patients.

  4. The origin of novel features by changes in developmental mechanisms: ontogeny and three-dimensional microanatomy of polyodontode scales of two early osteichthyans.

    Science.gov (United States)

    Qu, Qingming; Sanchez, Sophie; Zhu, Min; Blom, Henning; Ahlberg, Per Erik

    2017-05-01

    Recent advances in synchrotron imaging allow us to study the three-dimensional (3D) histology of vertebrate fossils, including microfossils (e.g. teeth and scales) of early jawed vertebrates. These microfossils can often be scanned at submicron resolution (propagation phase-contrast synchrotron X-ray microtomography (PPC-SRµCT), and 3D models of internal canal systems and buried odontodes were created from the scans. Based on these new data, we review the evolutionary origin of cosmine and its associated pore-canal system, which has been long recognized as a synapomorphy of sarcopterygians. The first odontode that appeared during growth shows almost identical morphology in the two scales, but the second odontode of the Psarolepis scale shows a distinctive morphology with several pores on the surface. It is suggested that a shift from ridge-like odontode to pore-bearing odontode was the key step in the origin of cosmine, which was then elaborated further in more-derived sarcopterygians. We perform a detailed comparison between the two scales and propose a primary homology framework to generate microanatomical characters, which can be used in the phylogenetic analysis of early osteichthyans when more 3D data become available. Our results highlight the importance of 3D data for the study of histology and ontogeny of the dermal skeleton of early jawed vertebrates, especially scales of the polyodontode type. The traditional microvertebrate collection is not only useful for biostratigraphic studies, but also preserves invaluable biological information about the growth of vertebrate hard tissues. Today, we are only beginning to understand the biological meaning of the new 3D data. The increasing availability of such data will enable, and indeed require, a complete revision of traditional palaeohistological studies on early vertebrates. © 2016 Cambridge Philosophical Society.

  5. [In vitro experimental study of rat cardiomyocyte injury with targeting of perfluorocarbon lipid particles].

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    He, Baiyong; Li, Zhaohuan; Tang, Hong; Li, Guohua; Chen, Song; Wang, Lian; Song, Haibo; Fang, Hua; Zeng, Jun

    2011-12-01

    The present study was to investigate in vitro the rat cardiomyocyte injury with targeting of home-made perfluorocarbon lipid particles with avidin-biotin interaction. Neonatal rat cardiomyocytes were cultured in vitro and divided into two groups: TNF-alpha activated group and non-activated group. Those in the TNF-alpha activated group were exposed to 200 ng/ml TNF-alpha solution for 6 hours and then cardiomyocytes in both groups were pretargeted with biotinylated ICAM-1 monoclonal antibodies, and were exposed to streptavidin, and then to homemade green fluorescently-labeled biotinylated perfluorocarbon lipid particles. Cardiomyocytes nucleus stained with Hoechst. The results were detected with fluorescence microscope. As a result, in TNF-alpha activated group, around blue fluorescent cardiomyocytes nucleus, a great amount of green fluorescent particles were found, while there were few green fluorescent particles in non-TNF activated group. It has been shown that ICAM-1 is expressed in the surface of cardiomyocytes when they are stimulated by TNF-alpha. Perfluorocarbon lipid particles associated with ICAM-1 monoclonal antibodies can be targeted to injured cardiomyocytes by avidin-biotin interaction.

  6. Role of TRPV1 in the Differentiation of Mouse Embryonic Stem Cells into Cardiomyocytes.

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    Yan Qi

    Full Text Available Cytosolic Ca2+ ([Ca2+]i is an important signal that regulates cardiomyocyte differentiation during cardiogenesis. TRPV1 is a Ca2+-permeable channel that is expressed in cardiomyocytes. In the present study, we utilized mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs as a model to investigate the functional role of TRPV1 in cardiomyocyte differentiation. Induction of embryonic stem cells into cardiomyocytes was achieved using embryoid body (EB-based differentiation method. Quantitative PCRs showed an increased TRPV1 expression during the differentiation process. In [Ca2+]i measurement study, application of TRPV1 agonists, capsaicin and camphor, elicited a [Ca2+]i rise in mESC-CMs, the effect of which was abolished by TRPV1-shRNA. In functional study, treatment of EBs with TRPV1 antagonists (capsazepine and SB366791 and TRPV1-shRNA reduced the size of the EBs and decreased the percentage of spontaneously beating EBs. TRPV1 antagonists and TRPV1-shRNA also suppressed the expression of cardiomyocyte marker genes, including cardiac actin, c-TnT, c-TnI, and α-MHC. Taken together, this study demonstrated an important functional role of TRPV1 channels in the differentiation of mESCs into cardiomyocytes.

  7. Involvement of PIKE in icariin induced cardiomyocyte differentiation from murine embryonic stem cells.

    Science.gov (United States)

    Zhou, Limin; Zheng, Bei; Tang, Leilei; Huang, Yujie; Zhu, Danyan

    2014-03-01

    Icariin (ICA) has demonstrated to induce cardiomyocyte differentiation from murine embryonic stem (ES) cells in vitro, however, the mechanisms have not been fully elucidated. In the present study, we investigated whether phosphatidylinositol 3-kinase enhancer (PIKE) was involved in ICA induced cardiomyocyte differentiation of ES cells. Small interfering RNA (siRNA) of PIKE was applied to investigate the role of PIKE in ICA induced cardiomyocyte differentiation. The cardiomyocytes derived from ES cells were verified using immunofluorescence. The expressions of Troponin T, PIKE, phosphatidylinositol 3-kinase (PI3K), and nuclear factor-kappaB (NF-kappaB) were detected by western blot. The change of reactive oxygen species (ROS) generation was estimated using the fluorescent dye 2', 7' - dichlorodihydrofluorescein diacetate. The results showed that PIKE expression increased during cardiomyocyte differentiation. ICA markedly enhanced PIKE and PI3K expression in a time-dependent manner. Knockdown of PIKE by siRNAs blocked the differentiation of ES cells into cardiomyocytes expressing alpha-actinin for cardiac sarcomeric structures. Moreover, reduced ROS generation and NF-kappaB nuclear translocation were responsible for the inhibitory effect of si-PIKE. In conclusion, PIKE was involved in ICA induced cardiomyocyte differentiation, and ROS generation and NF-kappaB nuclear translocation were associated with PIKE activation.

  8. Expression of Foxm1 transcription factor in cardiomyocytes is required for myocardial development.

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    Craig Bolte

    Full Text Available Forkhead Box M1 (Foxm1 is a transcription factor essential for organ morphogenesis and development of various cancers. Although complete deletion of Foxm1 in Foxm1(-/- mice caused embryonic lethality due to severe abnormalities in multiple organ systems, requirements for Foxm1 in cardiomyocytes remain to be determined. This study was designed to elucidate the cardiomyocyte-autonomous role of Foxm1 signaling in heart development. We generated a new mouse model in which Foxm1 was specifically deleted from cardiomyocytes (Nkx2.5-Cre/Foxm1(fl/f mice. Deletion of Foxm1 from cardiomyocytes was sufficient to disrupt heart morphogenesis and induce embryonic lethality in late gestation. Nkx2.5-Cre/Foxm1(fl/fl hearts were dilated with thinning of the ventricular walls and interventricular septum, as well as disorganization of the myocardium which culminated in cardiac fibrosis and decreased capillary density. Cardiomyocyte proliferation was diminished in Nkx2.5-Cre/Foxm1(fl/fl hearts owing to altered expression of multiple cell cycle regulatory genes, such as Cdc25B, Cyclin B(1, Plk-1, nMyc and p21(cip1. In addition, Foxm1 deficient hearts displayed reduced expression of CaMKIIδ, Hey2 and myocardin, which are critical mediators of cardiac function and myocardial growth. Our results indicate that Foxm1 expression in cardiomyocytes is critical for proper heart development and required for cardiomyocyte proliferation and myocardial growth.

  9. Cardiomyocyte proliferation in cardiac development and regeneration: a guide to methodologies and interpretations.

    Science.gov (United States)

    Leone, Marina; Magadum, Ajit; Engel, Felix B

    2015-10-01

    The newt and the zebrafish have the ability to regenerate many of their tissues and organs including the heart. Thus, a major goal in experimental medicine is to elucidate the molecular mechanisms underlying the regenerative capacity of these species. A wide variety of experiments have demonstrated that naturally occurring heart regeneration relies on cardiomyocyte proliferation. Thus, major efforts have been invested to induce proliferation of mammalian cardiomyocytes in order to improve cardiac function after injury or to protect the heart from further functional deterioration. In this review, we describe and analyze methods currently used to evaluate cardiomyocyte proliferation. In addition, we summarize the literature on naturally occurring heart regeneration. Our analysis highlights that newt and zebrafish heart regeneration relies on factors that are also utilized in cardiomyocyte proliferation during mammalian fetal development. Most of these factors have, however, failed to induce adult mammalian cardiomyocyte proliferation. Finally, our analysis of mammalian neonatal heart regeneration indicates experiments that could resolve conflicting results in the literature, such as binucleation assays and clonal analysis. Collectively, cardiac regeneration based on cardiomyocyte proliferation is a promising approach for improving adult human cardiac function after injury, but it is important to elucidate the mechanisms arresting mammalian cardiomyocyte proliferation after birth and to utilize better assays to determine formation of new muscle mass.

  10. Stable, covalent attachment of laminin to microposts improves the contractility of mouse neonatal cardiomyocytes.

    Science.gov (United States)

    Ribeiro, Alexandre J S; Zaleta-Rivera, Kathia; Ashley, Euan A; Pruitt, Beth L

    2014-09-10

    The mechanical output of contracting cardiomyocytes, the muscle cells of the heart, relates to healthy and disease states of the heart. Culturing cardiomyocytes on arrays of elastomeric microposts can enable inexpensive and high-throughput studies of heart disease at the single-cell level. However, cardiomyocytes weakly adhere to these microposts, which limits the possibility of using biomechanical assays of single cardiomyocytes to study heart disease. We hypothesized that a stable covalent attachment of laminin to the surface of microposts improves cardiomyocyte contractility. We cultured cells on polydimethylsiloxane microposts with laminin covalently bonded with the organosilanes 3-glycidoxypropyltrimethoxysilane and 3-aminopropyltriethoxysilane with glutaraldehyde. We measured displacement of microposts induced by the contractility of mouse neonatal cardiomyocytes, which attach better than mature cardiomyocytes to substrates. We observed time-dependent changes in contractile parameters such as micropost deformation, contractility rates, contraction and relaxation speeds, and the times of contractions. These parameters were affected by the density of laminin on microposts and by the stability of laminin binding to micropost surfaces. Organosilane-mediated binding resulted in higher laminin surface density and laminin binding stability. 3-glycidoxypropyltrimethoxysilane provided the highest laminin density but did not provide stable protein binding with time. Higher surface protein binding stability and strength were observed with 3-aminopropyltriethoxysilane with glutaraldehyde. In cultured cardiomyocytes, contractility rate, contraction speeds, and contraction time increased with higher laminin stability. Given these variations in contractile function, we conclude that binding of laminin to microposts via 3-aminopropyltriethoxysilane with glutaraldehyde improves contractility observed by an increase in beating rate and contraction speed as it occurs during the

  11. Growth factor PDGF-BB stimulates cultured cardiomyocytes to synthesize the extracellular matrix component hyaluronan.

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    Urban Hellman

    Full Text Available BACKGROUND: Hyaluronan (HA is a glycosaminoglycan located in the interstitial space which is essential for both structural and cell regulatory functions in connective tissue. We have previously shown that HA synthesis is up-regulated in a rat model of experimental cardiac hypertrophy and that cardiac tissue utilizes two different HA synthases in the hypertrophic process. Cardiomyocytes and fibroblasts are two major cell types in heart tissue. The fibroblasts are known to produce HA, but it has been unclear if cardiomyocytes share the same feature, and whether or not the different HA synthases are activated in the different cell types. METHODOLOGY/PRINCIPAL FINDINGS: This study shows, for the first time that cardiomyocytes can produce HA. Cardiomyocytes (HL-1 and fibroblasts (NIH 3T3 were cultivated in absence or presence of the growth factors FGF2, PDGF-BB and TGFB2. HA concentration was quantified by ELISA, and the size of HA was estimated using dynamic light scattering. Cardiomyocytes synthesized HA but only when stimulated by PDGF-BB, whereas fibroblasts synthesized HA without addition of growth factors as well as when stimulated by any of the three growth factors. When fibroblasts were stimulated by the growth factors, reverse dose dependence was observed, where the highest dose induced the least amount of HA. With the exception of TGFB2, a trend of reverse dose dependence of HA size was also observed. CONCLUSIONS/SIGNIFICANCE: Co-cultivation of cardiomyocytes and fibroblasts (80%/20% increased HA concentration far more that can be explained by HA synthesis by the two cell types separately, revealing a crosstalk between cardiomyocytes and fibroblasts that induces HA synthesis. We conclude that dynamic changes of the myocardium, such as in cardiac hypertrophy, do not depend on the cardiomyocyte alone, but are achieved when both cardiomyocytes and fibroblasts are present.

  12. BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2.

    Science.gov (United States)

    Aguado, Fernando; Carmona, Maria A; Pozas, Esther; Aguiló, Agustín; Martínez-Guijarro, Francisco J; Alcantara, Soledad; Borrell, Victor; Yuste, Rafael; Ibañez, Carlos F; Soriano, Eduardo

    2003-04-01

    Spontaneous neural activity is a basic property of the developing brain, which regulates key developmental processes, including migration, neural differentiation and formation and refinement of connections. The mechanisms regulating spontaneous activity are not known. By using transgenic embryos that overexpress BDNF under the control of the nestin promoter, we show here that BDNF controls the emergence and robustness of spontaneous activity in embryonic hippocampal slices. Further, BDNF dramatically increases spontaneous co-active network activity, which is believed to synchronize gene expression and synaptogenesis in vast numbers of neurons. In fact, BDNF raises the spontaneous activity of E18 hippocampal neurons to levels that are typical of postnatal slices. We also show that BDNF overexpression increases the number of synapses at much earlier stages (E18) than those reported previously. Most of these synapses were GABAergic, and GABAergic interneurons showed hypertrophy and a 3-fold increase in GAD expression. Interestingly, whereas BDNF does not alter the expression of GABA and glutamate ionotropic receptors, it does raise the expression of the recently cloned K(+)/Cl(-) KCC2 co-transporter, which is responsible for the conversion of GABA responses from depolarizing to inhibitory, through the control of the Cl(-) potential. Together, results indicate that both the presynaptic and postsynaptic machineries of GABAergic circuits may be essential targets of BDNF actions to control spontaneous activity. The data indicate that BDNF is a potent regulator of spontaneous activity and co-active networks, which is a new level of regulation of neurotrophins. Given that BDNF itself is regulated by neuronal activity, we suggest that BDNF acts as a homeostatic factor controlling the emergence, complexity and networking properties of spontaneous networks.

  13. Gene expression of selenoproteins can be regulated by thioredoxin(Txn) silence in chicken cardiomyocytes.

    Science.gov (United States)

    Yang, Jie; Hamid, Sattar; Liu, Qi; Cai, Jingzeng; Xu, Shiwen; Zhang, Ziwei

    2017-09-04

    Thioredoxin (Txn) system is the most crucial antioxidant defense mechanism in myocardium. The aim of this study was to clarify the effect of Txn low expression on 25 selenoproteins in chicken cardiomyocytes. We developed a Se-deficient model (0.033mg/kg) and Txn knock down cardiomyocytes model (siRNA) studies. Western Blot, Quantitative Real-time PCR (qPCR) were performed, and correlation analysis, heat map were used for further analysis. Both low expression of Txn models are significantly decreased (Psilence of Txn in chicken cardiomyocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless 'Frank-Starling Gain' index.

    Science.gov (United States)

    Bollensdorff, Christian; Lookin, Oleg; Kohl, Peter

    2011-07-01

    This paper briefly recapitulates the Frank-Starling law of the heart, reviews approaches to establishing diastolic and systolic force-length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called 'Frank-Starling Gain', calculated as the ratio of slopes of end-systolic and end-diastolic force-length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank-Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties.

  15. Developmental dyslexia.

    Science.gov (United States)

    Grizzle, Kenneth L

    2007-06-01

    Reading skills progress in a stage-like manner. There is no evidence that reading, unlike language, develops without direct instruction. Failing to develop preceding skills has a dramatic impact on development of more sophisticated cognitive skills. For example, children who have poor phonemic sensitivity struggle to develop phonetic decoding; poor word recognition and word decoding skills have a negative impact on reading comprehension. Primary care physicians need to be aware of reading problems and frequent comorbid conditions. Recognition of risk factors can help physicians direct children early to badly needed resources, which, at the least, decreases the risk for and minimize the impact of one additional challenge for these children.

  16. Developmental changes in hepatic glucose metabolism in a newborn piglet model: A comparative analysis for suckling period and early weaning period.

    Science.gov (United States)

    Xie, Chunyan; Wang, Qinhua; Wang, Jing; Tan, Bie; Fan, Zhiyong; Deng, Ze-yuan; Wu, Xin; Yin, Yulong

    2016-02-19

    The liver glucose metabolism, supplying sufficient energy for glucose-dependent tissues, is important in suckling or weaned animals, although there are few studies with piglet model. To better understand the development of glucose metabolism in the piglets during suckling period and early weaning period, we determined the hepatic glycogen content, and investigated the relative protein expression of key enzymes of glucogenesis (GNG) and mRNA levels of some glucose metabolism-related genes. During suckling period, the protein level of G6Pase in the liver of suckling piglets progressively declined with day of age compared with that of newborn piglets (at 1 day of age), whereas the PEPCK level stabilized until day 21 of age, indicating that hepatic GNG capacity gradually weakened in suckling piglets. The synthesis of hepatic glycogen, which was consistent with the fluctuation of glycolytic key genes PFKL and PKLR that gradually decreased after birth and was more or less steady during latter suckling period, although both the mRNA levels of GCK and key glucose transporter GLUT2 presented uptrend in suckling piglets. However, early weaning significantly suppressed the hepatic GNG in the weaned piglets, especially at d 3-5 of weaning period, then gradually recovered at d 7 of weaning period. Meanwhile, PFKL, PKLR and GLUT2 showed the similar trend during weaning period. On the contrast, the hepatic glycogen reached the maximum value when the G6Pase and PEPCK protein expression were at the lowest level, although the GCK level maintained increasing through 7 days of weaning period. Altogether, our study provides evidence that hepatic GNG and glycolysis in newborn piglets were more active than other days during suckling period, and early weaning could significantly suppressed glucose metabolism in liver, but this inhibition would progressively recover at day 7 after weaning.

  17. Pharmacoelectrophysiology of viral-free induced pluripotent stem cell-derived human cardiomyocytes.

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    Mehta, Ashish; Chung, YingYing; Sequiera, Glen Lester; Wong, Philip; Liew, Reginald; Shim, Winston

    2013-02-01

    Development of pharmaceutical agents for cardiac indication demands elaborate safety screening in which assessing repolarization of cardiac cells remains a critical path in risk evaluations. An efficient platform for evaluating cardiac repolarization in vitro significantly facilitates drug developmental programs. In a proof of principle study, we examined the effect of antiarrhythmogenic drugs (Vaughan Williams class I-IV) and noncardiac active drugs (terfenadine and cisapride) on the repolarization profile of viral-free human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Extracellular field potential (FP) recording using microelectrode arrays demonstrated significant delayed repolarization as prolonged corrected FP durations (cFPDs) by class I (quinidine and flecainide), class III (sotalol and amiodarone), and class IV (verapamil), whereas class II drugs (propranolol and nadolol) had no effects. Consistent with their sodium channel-blocking ability, class I drugs also significantly reduced FPmin and conduction velocity. Although lidocaine (class IB) had no effects on cFPDs, verapamil shortened cFPD and FPmin by 25 and 50%, respectively. Furthermore, verapamil reduced beating frequencies drastically. Importantly, the examined drugs exhibited dose-response curve on prolongation of cFPDs at an effective range that correlated significantly with therapeutic plasma concentrations achieved clinically. Consistent with clinical outcomes, drug-induced arrhythmia of tachycardia and bigeminy-like waveforms by quinidine, flecainide, and sotalol was demonstrated at supraphysiological concentrations. Furthermore, off-target effects of terfenadine and cisapride on cFPD and Na( + ) channel blockage were similarly revealed. These results suggest that hiPSC-CMs may be useful for safety evaluation of cardioactive and noncardiac acting drugs for personalized medicine.

  18. Effects of in vitro growth culture duration and prematuration culture on maturational and developmental competences of bovine oocytes derived from early antral follicles.

    Science.gov (United States)

    Huang, Weiping; Nagano, Masashi; Kang, Sung-Sik; Yanagawa, Yojiro; Takahashi, Yoshiyuki

    2013-10-15

    Bovine ovaries offer a large pool of oocytes that could be used for in vitro production of embryos of genetically valuable animals. The effects of in vitro growth (IVG) culture duration (10, 12, and 14 days) on the viability and growth of bovine oocytes derived from early antral follicles (0.5-1 mm diameter) in this study. In addition, the effect of pre-IVM culture with phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine) on nuclear maturation of IVG oocytes was also evaluated. In experiment 1, oocyte viability observed after 10 or 12 days of IVG culture was greater (P culture. Oocyte diameters and proportions of oocytes at metaphase II stage were greater (P culture where used when compared with 10 days culture. In addition, the proportion of oocytes at metaphase II stage was greater (P culture was performed for oocytes derived from 12 and 14 days of IVG culture. When 12 and 14 days of IVG culture followed by pre-IVM culture were compared in experiment 2, cumulus cell membrane integrity was greater (P culture (24.5%) was greater (P culture was considered the optimal processing system for bovine oocytes derived from early antral follicles when oocyte viability, diameter, maturation, and development competences were considered.

  19. Effect of provision of an integrated neonatal survival kit and early cognitive stimulation package by community health workers on developmental outcomes of infants in Kwale County, Kenya: study protocol for a cluster randomized trial.

    Science.gov (United States)

    Pell, Lisa G; Bassani, Diego G; Nyaga, Lucy; Njagi, Isaac; Wanjiku, Catherine; Thiruchselvam, Thulasi; Macharia, William; Minhas, Ripudaman S; Kitsao-Wekulo, Patricia; Lakhani, Amyn; Bhutta, Zulfiqar A; Armstrong, Robert; Morris, Shaun K

    2016-09-08

    Each year, more than 200 million children under the age of 5 years, almost all in low- and middle-income countries (LMICs), fail to achieve their developmental potential. Risk factors for compromised development often coexist and include inadequate cognitive stimulation, poverty, nutritional deficiencies, infection and complications of being born low birthweight and/or premature. Moreover, many of these risk factors are closely associated with newborn morbidity and mortality. As compromised development has significant implications on human capital, inexpensive and scalable interventions are urgently needed to promote neurodevelopment and reduce risk factors for impaired development. This cluster randomized trial aims at evaluating the impact of volunteer community health workers delivering either an integrated neonatal survival kit, an early stimulation package, or a combination of both interventions, to pregnant women during their third trimester of pregnancy, compared to the current standard of care in Kwale County, Kenya. The neonatal survival kit comprises a clean delivery kit (sterile blade, cord clamp, clean plastic sheet, surgical gloves and hand soap), sunflower oil emollient, chlorhexidine, ThermoSpot(TM), Mylar infant sleeve, and a reusable instant heater. Community health workers are also equipped with a portable hand-held electric scale. The early cognitive stimulation package focuses on enhancing caregiver practices by teaching caregivers three key messages that comprise combining a gentle touch with making eye contact and talking to children, responsive feeding and caregiving, and singing. The primary outcome measure is child development at 12 months of age assessed with the Protocol for Child Monitoring (Infant and Toddler version). The main secondary outcome is newborn mortality. This study will provide evidence on effectiveness of delivering an innovative neonatal survival kit and/or early stimulation package to pregnant women in Kwale County

  20. The location of energetic compartments affects energetic communication in cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Rikke eBirkedal

    2014-09-01

    Full Text Available The heart relies on accurate regulation of mitochondrial energy supply to match energy demand. The main regulators are Ca2+ and feedback of ADP and Pi. Regulation via feedback has intrigued for decades. First, the heart exhibits a remarkable metabolic stability. Second, diffusion of ADP and other molecules is restricted specifically in heart and red muscle, where a fast feedback is needed the most. To explain the regulation by feedback, compartmentalization must be taken into account. Experiments and theoretical approaches suggest that cardiomyocyte energetic compartmentalization is elaborate with barriers obstructing diffusion in the cytosol and at the level of the mitochondrial outer membrane (MOM. A recent study suggests the barriers are organized in a lattice with dimensions in agreement with those of intracellular structures. Here, we discuss the possible location of these barriers. The more plausible scenario includes a barrier at the level of MOM. Much research has focused on how the permeability of MOM itself is regulated, and the importance of the creatine kinase system to facilitate energetic communication. We hypothesize that at least part of the diffusion restriction at the MOM level is not by MOM itself, but due to the close physical association between the sarcoplasmic reticulum (SR and mitochondria. This will explain why animals with a disabled creatine kinase system exhibit rather mild phenotype modifications. Mitochondria are hubs of energetics, but also ROS production and signaling. The close association between SR and mitochondria may form a diffusion barrier to ADP added outside a permeabilised cardiomyocyte. But in vivo, it is the structural basis for the mitochondrial-SR coupling that is crucial for the regulation of mitochondrial Ca2+-transients to regulate energetics, and for avoiding Ca2+-overload and irreversible opening of the mitochondrial permeability transition pore.

  1. Hydrogel-coated microfluidic channels for cardiomyocyte culture

    Science.gov (United States)

    Annabi, Nasim; Selimović, Šeila; Cox, Juan Pablo Acevedo; Ribas, João; Bakooshli, Mohsen Afshar; Heintze, Déborah; Weiss, Anthony S.; Cropek, Donald; Khademhosseini, Ali

    2013-01-01

    The research areas of tissue engineering and drug development have displayed increased interest in organ-on-a-chip studies, in which physiologically or pathologically relevant tissues can be engineered to test pharmaceutical candidates. Microfluidic technologies enable the control of the cellular microenvironment for these applications through the topography, size, and elastic properties of the microscale cell culture environment, while delivering nutrients and chemical cues to the cells through continuous media perfusion. Traditional materials used in the fabrication of microfluidic devices, such as poly(dimethylsiloxane) (PDMS), offer high fidelity and high feature resolution, but do not facilitate cell attachment. To overcome this challenge, we have developed a method for coating microfluidic channels inside a closed PDMS device with a cell-compatible hydrogel layer. We have synthesized photocrosslinkable gelatin and tropoelastin-based hydrogel solutions that were used to coat the surfaces under continuous flow inside 50 μm wide, straight microfluidic channels to generate a hydrogel layer on the channel walls. Our observation of primary cardiomyocytes seeded on these hydrogel layers showed preferred attachment as well as higher spontaneous beating rates on tropoelastin coatings compared to gelatin. In addition, cellular attachment, alignment and beating were stronger on 5 % (w/v) hydrogel-coated devices than on 10 % (w/v) gel-coated channels. Our results demonstrate that cardiomyocytes respond favorably to the elastic, soft tropoelastin culture substrates, indicating that tropoelastin-based hydrogels may be a suitable coating choice for some organ-on-a-chip applications. We anticipate that the proposed hydrogel coating method and tropoelastin as a cell culture substrate may be useful for the generation of elastic tissues, e.g. blood vessels, using microfluidic approaches. PMID:23728018

  2. Study on the early intervention in developmental dysplasia of hip%发育性髋关节异常的早期干预及结果分析

    Institute of Scientific and Technical Information of China (English)

    李琳; 赵虹; 王风梅; 梁香丽

    2012-01-01

    [Objective] To explore the effects of early intervention in developmental dysplasia of hip. [Methods] For those,infants under six months who were diagnosed with developmental dysplasia of hip by Color Ultrasonic Doppler, according to the hyper acoustic results and their ages,we enacted different intervening strategies and therapeutic schedules, and also advised their parents conduct early intervention and regular follow-up interview. [Results] After these 73 of 122 hip joints of Graflla were reexamined and found that 71 of them had return to normal,and the other 2 of no avail also returned to normal after Pavlik hammock treat. 8 of 10 of Grafllb returned to normal after Pavlik hammock treat,and the other 2 also had return to normal after treat in children orthopedics department. 2 of 3 hip joints of Grafllc-IV had return to normal after receiving treat in children orthopedics department,and the other 1 took in an operation after non-effected traditional treat. 23 of 41 hip joints without reexamination received X-ray check after six months. 2 of them were diagnosed as DDH and back to normal after treat in children orthopedics department. The left 18 refused to take reexamination and another 8 lost contact. [Conclusion] Therefore it is concluded that the early intervention in developmental dysplasia of hip will help them progress towards normal hip joint structure.%[目的]分析早期干预对发育性髋关节异常转归的影响及结果,为早期干预提供科学依据. [方法]对在本院经超声确诊的髋关节发育异常的0~6月儿童,根据超声分型结果及患儿年龄制定不同的干预方法和治疗方案,并指导家长进行早期干预和定期随访. [结果]通过早期干预及随访,诊断为GrafⅡa的122个髋关节有73个髋关节进行了复查,71个髋关节通过髋关节外展操转为正常,2个髋关节经髋关节外展操治疗无效,通过Pavlik吊带治疗后转为正常.诊断为GrafⅡb的10

  3. Fetal and early-postnatal developmental patterns of obese-genotype piglets exposed to prenatal programming by maternal over- and undernutrition.

    Science.gov (United States)

    Gonzalez-Bulnes, Antonio; Ovilo, Cristina; Lopez-Bote, Clemente J; Astiz, Susana; Ayuso, Miriam; Perez-Solana, Maria L; Sanchez-Sanchez, Raul; Torres-Rovira, Laura

    2013-09-01

    The present study evaluated the effect of nutritional imbalances during pregnancy, either by excess or deficiency, on fertility and conceptus development in obese-genotype swine (Iberian pig). Twenty-five multiparous sows were fed, from mating to farrowing, with a standard diet fulfilling either 1.6 folds their daily maintenance requirements for pregnancy (overfed group, n = 12) or only the 50% of such requirements (underfed group, n = 13). Ten out of 12 overfed but only two out of 13 underfed sows became pregnant (Pdevelopmental patterns of fetuses. Thus, weight and size of the offspring from both nutritional treatments were finally similar at delivery; the same was found at weaning. There was thereafter a sex-related effect on the growth during the early-postnatal period, with male piglets of both nutritional origins being significantly heavier and more corpulent at weaning that their sisters (Porigin, with male piglets growing faster than females.

  4. Effects of elevated carbon dioxide (CO2) concentrations on early developmental stages of the marine copepod Calanus finmarchicus Gunnerus (Copepoda: Calanoidae).

    Science.gov (United States)

    Pedersen, Sindre Andre; Våge, Vegard Thorset; Olsen, Anders Johny; Hammer, Karen Marie; Altin, Dag

    2014-01-01

    Ocean acidification poses an ongoing threat to marine organisms, and early life stages are believed to be particularly sensitive. The boreal calanoid copepod Calanus finmarchicus seasonally dominates the standing stock of zooplankton in the northern North Sea and North Atlantic, and due to its size and abundance is considered an ecological key species linking energy from primary producers to higher trophic levels. To examine whether the early stages of C. finmarchicus are particularly vulnerable to elevated levels of CO2, eggs and nauplii were subjected to different levels of CO2-acidified seawater for 1 wk. The first experiment, with eggs as the starting point, revealed no marked effect on hatching success, but a significant reduction in nauplii survival during incubation at 8800 ppm CO2. In addition, a significant decrease in ontogenetic development rate during incubation at 8800 ppm CO2 was observed in this experiment. In the second experiment, where third-stage nauplii represented the starting point, no significant effects on ontogenetic development and survival following exposure to pCO2 ≥ 7700 ppm were observed. Data suggest that the two first nauplii stages, which are fed endogenously, may be more vulnerable and therefore likely to represent the "bottleneck" for this species in a more acidic ocean. However, the absence of significant effects in the most sensitive stages during exposure to 2800 ppm CO2, a level that is well above worst-case scenario predictions for year 2300 (approximately 2000 ppm CO2), suggests that this species may be generally robust to direct effects of ocean acidification.

  5. Early and sustained increase in the expression of hippocampal IGF-1, but not EPO, in a developmental rodent model of traumatic brain injury.

    Science.gov (United States)

    Schober, Michelle E; Block, Benjamin; Beachy, Joanna C; Statler, Kimberly D; Giza, Christopher C; Lane, Robert H

    2010-11-01

    Pediatric traumatic brain injury (pTBI) is the leading cause of traumatic death and disability in children in the United States. Impaired learning and memory in these young survivors imposes a heavy toll on society. In adult TBI (aTBI) models, cognitive outcome improved after administration of erythropoietin (EPO) or insulin-like growth factor-1 (IGF-1). Little is known about the production of these agents in the hippocampus, a brain region critical for learning and memory, after pTBI. Our objective was to describe hippocampal expression of EPO and IGF-1, together with their receptors (EPOR and IGF-1R, respectively), over time after pTBI in 17-day-old rats. We used the controlled cortical impact (CCI) model and measured hippocampal mRNA levels of EPO, IGF-1, EPOR, IGF-1R, and markers of caspase-dependent apoptosis (bcl2, bax, and p53) at post-injury days (PID) 1, 2, 3, 7, and 14. CCI rats performed poorly on Morris water maze testing of spatial working memory, a hippocampally-based cognitive function. Apoptotic markers were present early and persisted for the duration of the study. EPO in our pTBI model increased much later (PID7) than in aTBI models (12 h), while EPOR and IGF-1 increased at PID1 and PID2, respectively, similar to data from aTBI models. Our data indicate that EPO expression showed a delayed upregulation post-pTBI, while EPOR increased early. We speculate that administration of EPO in the first 1-2 days after pTBI would increase hippocampal neuronal survival and function.

  6. Peroxisome Proliferator-Activated Receptor γ Activity is Required for Appropriate Cardiomyocyte Differentiation

    Directory of Open Access Journals (Sweden)

    Maryam Peymani

    2016-07-01

    Full Text Available Objective Peroxisome proliferator-activated receptor γ (PPARγ is a member of the PPAR nuclear receptor superfamily. Although PPARγ acts as a master transcription factor in adipocyte differentiation, it is also associated with a variety of cell functions including carbohydrate and lipid metabolism, glucose homeostasis, cell proliferation and cell differentiation. This study aimed to assess the expression level of PPARγ in order to address its role in cardiac cell differentiation of mouse embryonic stem cells (mESCs. Materials and Methods In this an intervening study, mESCs were subjected to cardiac differentiation. Total RNA was extracted from the cells and quantitative real time polymerase chain reaction (qPCR was carried out to estimate level of gene expression. Furthermore, the requirement of PPARγ in cardiac differentiation of mESCs, during cardiac progenitor cells (CPCs formation, was examined by applying the respective agonist and antagonist. Results The obtained data revealed an elevation in the expression level of PPARγ during spontaneous formation of CPCs and cardiomyocytes. Our results indicated that during CPC formation, PPARγ inactivation via treatment with GW9662 (GW reduced expression of CPC and cardiac markers. Conclusion We conclude that PPARγ modulation has an effective role on cardiac differentiation of mESCs at the early stage of cardiomyogenesis.

  7. Functional cardiomyocytes derived from Isl1 cardiac progenitors via Bmp4 stimulation.

    Directory of Open Access Journals (Sweden)

    Esra Cagavi

    Full Text Available As heart failure due to myocardial infarction remains a leading cause of morbidity worldwide, cell-based cardiac regenerative therapy using cardiac progenitor cells (CPCs could provide a potential treatment for the repair of injured myocardium. As adult CPCs may have limitations regarding tissue accessibility and proliferative ability, CPCs derived from embryonic stem cells (ESCs could serve as an unlimited source of cells with high proliferative ability. As one of the CPCs that can be derived from embryonic stem cells, Isl1 expressing cardiac progenitor cells (Isl1-CPCs may serve as a valuable source of cells for cardiac repair due to their high cardiac differentiation potential and authentic cardiac origin. In order to generate an unlimited number of Isl1-CPCs, we used a previously established an ESC line that allows for isolation of Isl1-CPCs by green fluorescent protein (GFP expression that is directed by the mef2c gene, specifically expressed in the Isl1 domain of the anterior heart field. To improve the efficiency of cardiac differentiation of Isl1-CPCs, we studied the role of Bmp4 in cardiogenesis of Isl1-CPCs. We show an inductive role of Bmp directly on cardiac progenitors and its enhancement on early cardiac differentiation of CPCs. Upon induction of Bmp4 to Isl1-CPCs during differentiation, the cTnT+ cardiomyocyte population was enhanced 2.8±0.4 fold for Bmp4 treated CPC cultures compared to that detected for vehicle treated cultures. Both Bmp4 treated and untreated cardiomyocytes exhibit proper electrophysiological and calcium signaling properties. In addition, we observed a significant increase in Tbx5 and Tbx20 expression in differentiation cultures treated with Bmp4 compared to the untreated control, suggesting a link between Bmp4 and Tbx genes which may contribute to the enhanced cardiac differentiation in Bmp4 treated cultures. Collectively these findings suggest a cardiomyogenic role for Bmp4 directly on a pure population of

  8. Characterization of the regulatory mechanisms of activating transcription factor 3 by hypertrophic stimuli in rat cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Elina Koivisto

    Full Text Available AIMS: Activating transcription factor 3 (ATF3 is a stress-activated immediate early gene suggested to have both detrimental and cardioprotective role in the heart. Here we studied the mechanisms of ATF3 activation by hypertrophic stimuli and ATF3 downstream targets in rat cardiomyocytes. METHODS AND RESULTS: When neonatal rat cardiomyocytes were exposed to endothelin-1 (ET-1, 100 nM and mechanical stretching in vitro, maximal increase in ATF3 expression occurred at 1 hour. Inhibition of extracellular signal-regulated kinase (ERK by PD98059 decreased ET-1- and stretch-induced increase of ATF3 protein but not ATF3 mRNA levels, whereas protein kinase A (PKA inhibitor H89 attenuated both ATF3 mRNA transcription and protein expression in response to ET-1 and stretch. To characterize further the regulatory mechanisms upstream of ATF3, p38 mitogen-activated protein kinase (MAPK signaling was investigated using a gain-of-function approach. Adenoviral overexpression of p38α, but not p38β, increased ATF3 mRNA and protein levels as well as DNA binding activity. To investigate the role of ATF3 in hypertrophic process, we overexpressed ATF3 by adenovirus-mediated gene transfer. In vitro, ATF3 gene delivery attenuated the mRNA transcription of interleukin-6 (IL-6 and plasminogen activator inhibitor-1 (PAI-1, and enhanced nuclear factor-κB (NF-κB and Nkx-2.5 DNA binding activities. Reduced PAI-1 expression was also detected in vivo in adult rat heart by direct intramyocardial adenovirus-mediated ATF3 gene delivery. CONCLUSIONS: These data demonstrate that ATF3 activation by ET-1 and mechanical stretch is partly mediated through ERK and cAMP-PKA pathways, whereas p38 MAPK pathway is involved in ATF3 activation exclusively through p38α isoform. ATF3 activation caused induction of modulators of the inflammatory response NF-κB and Nkx-2.5, as well as attenuation of pro-fibrotic and pro-inflammatory proteins IL-6 and PAI-1, suggesting cardioprotective role

  9. Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using Raman microspectroscopy

    DEFF Research Database (Denmark)

    Brazhe, Nadezda A; Treiman, Marek; Brazhe, Alexey R

    2012-01-01

    This paper presents a nonivasive approach to study redox state of reduced cytochromes [Formula: see text], [Formula: see text] and [Formula: see text] of complexes II and III in mitochondria of live cardiomyocytes by means of Raman microspectroscopy. For the first time with the proposed approach we...... perform studies of rod- and round-shaped cardiomyocytes, representing different morphological and functional states. Raman mapping and cluster analysis reveal that these cardiomyocytes differ in the amounts of reduced cytochromes [Formula: see text], [Formula: see text] and [Formula: see text]. The rod......-shaped cardiomyocytes possess uneven distribution of reduced cytochromes [Formula: see text], [Formula: see text] and [Formula: see text] in cell center and periphery. Moreover, by means of Raman spectroscopy we demonstrated the decrease in the relative amounts of reduced cytochromes [Formula: see text], [Formula: see...

  10. In vitro simulation of spiral waves in cardiomyocyte networks using multi-electrode array technology

    OpenAIRE

    Jacquir, Sabir; Laurent, Gabriel; Vandroux, David; Binczak, Stéphane; Bilbault, Jean-Marie; Athias, Pierre

    2009-01-01

    International audience; We aimed thus to provide new insights into the cellular origin of the fibrillation phenomenon by exploring the impulse propagation between cardiac myocytes in confluent monolayers of cultured cardiomyocytes (CM),

  11. Cardiac injury of the newborn mammalian heart accelerates cardiomyocyte terminal differentiation

    DEFF Research Database (Denmark)

    Zebrowski, David C.; Jensen, Charlotte H.; Becker, Robert

    2017-01-01

    After birth cardiomyocytes undergo terminal differentiation, characterized by binucleation and centrosome disassembly, rendering the heart unable to regenerate. Yet, it has been suggested that newborn mammals regenerate their hearts after apical resection by cardiomyocyte proliferation. Thus, we...... tested the hypothesis that apical resection either inhibits, delays, or reverses cardiomyocyte centrosome disassembly and binucleation. Our data show that apical resection rather transiently accelerates centrosome disassembly as well as the rate of binucleation. Consistent with the nearly 2-fold...... exhibited midbody formation consistent with successful abscission, whereas those from 3 day-old cardiomyocytes after apical resection exhibited midbody formation consistent with abscission failure. Lastly, injured hearts failed to fully regenerate as evidenced by persistent scarring and reduced wall motion...

  12. Modeling Cardiovascular Diseases with Patient-Specific Human Pluripotent Stem Cell-Derived Cardiomyocytes

    Science.gov (United States)

    Burridge, Paul W.; Diecke, Sebastian; Matsa, Elena; Sharma, Arun; Wu, Haodi; Wu, Joseph C.

    2016-01-01

    The generation of cardiomyocytes from human induced pluripotent stem cells (hiPSCs) provides a source of cells that accurately recapitulate the human cardiac pathophysiology. The application of these cells allows for modeling of cardiovascular diseases, providing a novel understanding of human disease mechanisms and assessment of therapies. Here, we describe a stepwise protocol developed in our laboratory for the generation of hiPSCs from patients with a specific disease phenotype, long-term hiPSC culture and cryopreservation, differentiation of hiPSCs to cardiomyocytes, and assessment of disease phenotypes. Our protocol combines a number of innovative tools that include a codon-optimized mini intronic plasmid (CoMiP), chemically defined culture conditions to achieve high efficiencies of reprogramming and differentiation, and calcium imaging for assessment of cardiomyocyte phenotypes. Thus, this protocol provides a complete guide to use a patient cohort on a testable cardiomyocyte platform for pharmacological drug assessment. PMID:25690476

  13. An improved protocol for primary culture of cardiomyocyte from neonatal mice.

    Science.gov (United States)

    Sreejit, P; Kumar, Suresh; Verma, Rama S

    2008-01-01

    The primary culture of neonatal mice cardiomyocyte model enables researchers to study and understand the morphological, biochemical, and electrophysiological characteristics of the heart, besides being a valuable tool for pharmacological and toxicological studies. Because cardiomyocytes do not proliferate after birth, primary myocardial culture is recalcitrant. The present study describes an improved method for rapid isolation of cardiomyocytes from neonatal mice, as well as the maintenance and propagation of such cultures for the long term. Immunocytochemical and gene expression data also confirmed the presence of several cardiac markers in the beating cells during the long-term culture condition used in this protocol. The whole culture process can be effectively shortened by reducing the enzyme digestion period and the cardiomyocyte enrichment step.

  14. The antiapoptotic effect of insulin against anoxia/reoxygenation injury in cultured cardiomyocyte of neonatal rat

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective: To study protective effect of insulin against cardiomyocyte apoptosis in anoxia/reoxygenation (A/R)injury of neonatal rat. Methods: The model of A/R injury was finished through receiving anoxia for 2 h and reoxygenation for 4 h in cultured cardiomyocytes of neonatal rat. The cardiomyocytes were divided randomly into 3 groups: control group (CON), anoxia/reoxygenation group (A/R) and insulin-treated group (INS). At the end of reoxygenation of 4 hours, activities of lactate dehydrogenase (LDH),contents of malondialdehyde (MDA) were assessed through spectrophotometric procedures, myocyte apoptosis were detected through TUNEL and DNA Ladder. Results: MDA, LDH, and Apoptosis Index were significantly decreased in INS group compared with A/R group (P<0.01). Conclusion: Insulin has a protective effect against A/R injury in cultured cardiomyocyte of neonatal rat; the protective mechanism may contribute to antiapoptosis of insulin.

  15. [Adult resident cardiomyocytes wake up: new axis for cardiac tissue regeneration].

    Science.gov (United States)

    Mias, Céline; Genet, Gaël; Pathak, Atul; Sénard, Jean-Michel; Galés, Céline

    2012-12-01

    All cardiomyopathies and more specifically myocardial infarction always evolve to cardiomyocytes death and the ensuing heart failure setting. So far, cardiac regenerative medicine has focused on the use of stem cells and completely ignored the resident cardiomyocytes, assumed in a postmitotic state. However, recent findings in zebrafish and mammalians challenge this view and suggest that these cells have some capacity to proliferate and can contribute to heart regeneration. In this review, we propose an overall synthesis about knowledge of the proliferative and regenerative capacities of resident cardiomyocytes, dealing with some mechanistic aspects. In the future, the accurate identification of molecular mechanisms allowing wake-up of resident cardiomyocyte proliferation will certainly open new therapeutic avenues in cardiac regeneration. © 2012 médecine/sciences – Inserm / SRMS.

  16. Group B streptococcal beta-hemolysin/cytolysin directly impairs cardiomyocyte viability and function.

    Directory of Open Access Journals (Sweden)

    Mary E Hensler

    Full Text Available BACKGROUND: Group B Streptococcus (GBS is a leading cause of neonatal sepsis where myocardial dysfunction is an important contributor to poor outcome. Here we study the effects of the GBS pore-forming beta-hemolysin/cytolysin (Bh/c exotoxin on cardiomyocyte viability, contractility, and calcium transients. METHODOLOGY/PRINCIPAL FINDINGS: HL-1 cardiomyocytes exposed to intact wild-type (WT or isogenic Deltabeta h/c mutant GBS, or to cell-free extracts from either strain, were assessed for viability by trypan blue exclusion and for apoptosis by TUNEL staining. Functionality of exposed cardiomyocytes was analyzed by visual quantitation of the rate and extent of contractility. Mitochondrial membrane polarization was measured in TMRE-loaded cells exposed to GBS beta h/c. Effects of GBS beta h/c on calcium transients were studied in fura-2AM-loaded primary rat ventricular cardiomyocytes. Exposure of HL-1 cardiomyocytes to either WT GBS or beta h/c extracts significantly reduced both rate and extent of contractility and later induced necrotic and apoptotic cell death. No effects on cardiomyocyte viability or function were observed after treatment with Deltabeta h/c mutant bacteria or extracts. The beta h/c toxin was associated with complete and rapid loss of detectable calcium transients in primary neonatal rat ventricular cardiomyocytes and induced a loss of mitochondrial membrane polarization. These effects on viability and function were abrogated by the beta h/c inhibitor, dipalmitoyl phosphatidylcholine (DPPC. CONCLUSIONS/SIGNIFICANCE: Our data show a rapid loss of cardiomyocyte viability and function induced by GBS beta h/c, and these deleterious effects are inhibited by DPPC, a normal constituent of human pulmonary surfactant.. These findings have clinical implications for the cardiac dysfunction observed in neonatal GBS infections.

  17. Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications.

    Directory of Open Access Journals (Sweden)

    Maresha S Gay

    Full Text Available The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1, 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner.

  18. Muscle-on-chip: An in vitro model for donor–host cardiomyocyte coupling

    Science.gov (United States)

    Dierickx, Pieterjan

    2016-01-01

    A key aspect of cardiac cell–based therapy is the proper integration of newly formed cardiomyocytes into the remnant myocardium after injury. In this issue, Aratyn-Schaus et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508026) describe an in vitro model for heterogeneous cardiomyocyte coupling in which force transmission between cells can be measured. PMID:26858264

  19. Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila

    Science.gov (United States)

    Ishikawa, Zachary

    2017-01-01

    The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body. In a Drosophila genetic screen, we discovered that when haplo-insufficient, microsomal triglyceride transfer protein (mtp), required for the biosynthesis of apoB-lipoproteins, suppressed the development of diet-induced obesity. Tissue-specific inhibition of Mtp revealed that whereas knockdown of mtp only in the fat body decreases systemic triglyceride (TG) content on normal food diet (NFD) as expected, knockdown of mtp only in the cardiomyocytes also equally decreases systemic TG content on NFD, suggesting that the cardiomyocyte- and fat body-derived apoB-lipoproteins serve similarly important roles in regulating whole-body lipid metabolism. Unexpectedly, on high fat diet (HFD), knockdown of mtp in the cardiomyocytes, but not in fat body, protects against the gain in systemic TG levels. We further showed that inhibition of the Drosophila apoB homologue, apolipophorin or apoLpp, another gene essential for apoB-lipoprotein biosynthesis, affects systemic TG levels similarly to that of Mtp inhibition in the cardiomyocytes on NFD or HFD. Finally, we determined that HFD differentially alters Mtp and apoLpp expression in the cardiomyocytes versus the fat body, culminating in higher Mtp and apoLpp levels in the cardiomyocytes than in fat body and possibly underlying the predominant role of cardiomyocyte-derived apoB-lipoproteins in lipid metabolic regulation. Our findings reveal a novel and significant function of heart-mediated apoB-lipoproteins in controlling lipid homeostasis. PMID:28095410

  20. Developmental appearance of dentin matrix protein 1 during the early dentinogenesis in rat molars as identified by high-resolution immunocytochemistry.

    Science.gov (United States)

    Massa, Luciana F; Ramachandran, Amsaveni; George, Anne; Arana-Chavez, Victor E

    2005-09-01

    Dentin matrix protein 1 (DMP 1) is an acidic phosphoprotein that has been postulated to play an important role in mineralized tissue formation. We have examined rat molar tooth germs by applying a high-resolution immunocytochemical approach with the purpose to identify the temporal and spatial localization of DMP 1 at the onset of dentinogenesis. Upper molar tooth germs of 2- to 3-day-old Wistar rats were fixed in a cacodylate-buffered 0.1% glutaraldehyde + 4% formaldehyde fixative, left unosmicated and embedded in LR White resin. The sections were incubated with a polyclonal DMP 1 antibody for postembedding colloidal gold immunolabeling and examined in a Jeol 1010 transmission electron microscope. The earliest localization of DMP 1 was in the Golgi region as well as in the nucleus of differentiating odontoblasts. When mineralization spread from matrix vesicles to the surrounding matrix, DMP 1 was extracellularly detected around the mineralizing globules. In the regions of fully mineralized mantle dentin, it was present in the mineralized regions, mainly around the peritubular dentin. The appearance of DMP 1 during early dentinogenesis implies a direct role for this protein in both odontoblast differentiation and matrix mineralization.

  1. Gene coexpression patterns during early development of the native Arabidopsis reproductive meristem: novel candidate developmental regulators and patterns of functional redundancy.

    Science.gov (United States)

    Mantegazza, Otho; Gregis, Veronica; Chiara, Matteo; Selva, Caterina; Leo, Giulia; Horner, David S; Kater, Martin M

    2014-09-01

    During very early stages of flower development in Arabidopsis thaliana, a series of key decisions are taken. Indeed, the position and the basic patterning of new flowers are determined in less than 4 days. Given that the scientific literature provides hard evidence for the function of only 10% of A. thaliana genes, we hypothesized that although many essential genes have already been identified, many poorly characterized genes are likely to be involved in floral patterning. In the current study, we use high-throughput sequencing to describe the transcriptome of the native inflorescence meristem, the floral meristem and the new flower immediately after the start of organ differentiation. We provide evidence that our experimental system is reliable and less affected by experimental artefacts than a widely used floral induction system. Furthermore, we show how these data can be used to identify candidate genes for functional studies, and to generate hypotheses of functional redundancies and regulatory interactions. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  2. Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using Raman microspectroscopy.

    Science.gov (United States)

    Brazhe, Nadezda A; Treiman, Marek; Brazhe, Alexey R; Find, Ninett L; Maksimov, Georgy V; Sosnovtseva, Olga V

    2012-01-01

    This paper presents a nonivasive approach to study redox state of reduced cytochromes c, c1 and b of complexes II and III in mitochondria of live cardiomyocytes by means of Raman microspectroscopy. For the first time with the proposed approach we perform studies of rod- and round-shaped cardiomyocytes, representing different morphological and functional states. Raman mapping and cluster analysis reveal that these cardiomyocytes differ in the amounts of reduced cytochromes c, c1 and b. The rod-shaped cardiomyocytes possess uneven distribution of reduced cytochromes c, c1 and b in cell center and periphery. Moreover, by means of Raman spectroscopy we demonstrated the decrease in the relative amounts of reduced cytochromes c, c1 and b in the rod-shaped cardiomyocytes caused by H2O2-induced oxidative stress before any visible changes. Results of Raman mapping and time-dependent study of reduced cytochromes of complexes II and III and cytochrome c in cardiomyocytes are in a good agreement with our fluorescence indicator studies and other published data.

  3. Three-dimensional direct measurement of cardiomyocyte volume, nuclearity, and ploidy in thick histological sections.

    Science.gov (United States)

    Bensley, Jonathan Guy; De Matteo, Robert; Harding, Richard; Black, Mary Jane

    2016-01-01

    Quantitative assessment of myocardial development and disease requires accurate measurement of cardiomyocyte volume, nuclearity (nuclei per cell), and ploidy (genome copies per cell). Current methods require enzymatically isolating cells, which excludes the use of archived tissue, or serial sectioning. We describe a method of analysis that permits the direct simultaneous measurement of cardiomyocyte volume, nuclearity, and ploidy in thick histological sections. To demonstrate the utility of our technique, heart tissue was obtained from four species (rat, mouse, rabbit, sheep) at up to three life stages: prenatal, weaning and adulthood. Thick (40 μm) paraffin sections were stained with Wheat Germ Agglutinin-Alexa Fluor 488 to visualise cell membranes, and DAPI (4',6-diamidino-2-phenylindole) to visualise nuclei and measure ploidy. Previous methods have been restricted to thin sections (2-10 μm) and offer an incomplete picture of cardiomyocytes. Using confocal microscopy and three-dimensional image analysis software (Imaris Version 8.2, Bitplane AG, Switzerland), cardiomyocyte volume, nuclearity, and ploidy were measured. This method of staining and analysis of cardiomyocytes enables accurate morphometric measurements in thick histological sections, thus unlocking the potential of archived tissue. Our novel time-efficient method permits the entire cardiomyocyte to be visualised directly in 3D, eliminating the need for precise alignment of serial sections.

  4. The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response.

    Science.gov (United States)

    Puente, Bao N; Kimura, Wataru; Muralidhar, Shalini A; Moon, Jesung; Amatruda, James F; Phelps, Kate L; Grinsfelder, David; Rothermel, Beverly A; Chen, Rui; Garcia, Joseph A; Santos, Celio X; Thet, SuWannee; Mori, Eiichiro; Kinter, Michael T; Rindler, Paul M; Zacchigna, Serena; Mukherjee, Shibani; Chen, David J; Mahmoud, Ahmed I; Giacca, Mauro; Rabinovitch, Peter S; Aroumougame, Asaithamby; Shah, Ajay M; Szweda, Luke I; Sadek, Hesham A

    2014-04-24

    The mammalian heart has a remarkable regenerative capacity for a short period of time after birth, after which the majority of cardiomyocytes permanently exit cell cycle. We sought to determine the primary postnatal event that results in cardiomyocyte cell-cycle arrest. We hypothesized that transition to the oxygen-rich postnatal environment is the upstream signal that results in cell-cycle arrest of cardiomyocytes. Here, we show that reactive oxygen species (ROS), oxidative DNA damage, and DNA damage response (DDR) markers significantly increase in the heart during the first postnatal week. Intriguingly, postnatal hypoxemia, ROS scavenging, or inhibition of DDR all prolong the postnatal proliferative window of cardiomyocytes, whereas hyperoxemia and ROS generators shorten it. These findings uncover a protective mechanism that mediates cardiomyocyte cell-cycle arrest in exchange for utilization of oxygen-dependent aerobic metabolism. Reduction of mitochondrial-dependent oxidative stress should be an important component of cardiomyocyte proliferation-based therapeutic approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Three-dimensional direct measurement of cardiomyocyte volume, nuclearity, and ploidy in thick histological sections

    Science.gov (United States)

    Bensley, Jonathan Guy; de Matteo, Robert; Harding, Richard; Black, Mary Jane

    2016-04-01

    Quantitative assessment of myocardial development and disease requires accurate measurement of cardiomyocyte volume, nuclearity (nuclei per cell), and ploidy (genome copies per cell). Current methods require enzymatically isolating cells, which excludes the use of archived tissue, or serial sectioning. We describe a method of analysis that permits the direct simultaneous measurement of cardiomyocyte volume, nuclearity, and ploidy in thick histological sections. To demonstrate the utility of our technique, heart tissue was obtained from four species (rat, mouse, rabbit, sheep) at up to three life stages: prenatal, weaning and adulthood. Thick (40 μm) paraffin sections were stained with Wheat Germ Agglutinin-Alexa Fluor 488 to visualise cell membranes, and DAPI (4‧,6-diamidino-2-phenylindole) to visualise nuclei and measure ploidy. Previous methods have been restricted to thin sections (2–10 μm) and offer an incomplete picture of cardiomyocytes. Using confocal microscopy and three-dimensional image analysis software (Imaris Version 8.2, Bitplane AG, Switzerland), cardiomyocyte volume, nuclearity, and ploidy were measured. This method of staining and analysis of cardiomyocytes enables accurate morphometric measurements in thick histological sections, thus unlocking the potential of archived tissue. Our novel time-efficient method permits the entire cardiomyocyte to be visualised directly in 3D, eliminating the need for precise alignment of serial sections.

  6. Role of Nodal-PITX2C signaling pathway in glucose-induced cardiomyocyte hypertrophy.

    Science.gov (United States)

    Su, Dongmei; Jing, Sun; Guan, Lina; Li, Qian; Zhang, Huiling; Gao, Xiaobo; Ma, Xu

    2014-06-01

    Pathological cardiac hypertrophy is a major cause of morbidity and mortality in cardiovascular disease. Recent studies have shown that cardiomyocytes, in response to high glucose (HG) stimuli, undergo hypertrophic growth. While much work still needs to be done to elucidate this important mechanism of hypertrophy, previous works have showed that some pathways or genes play important roles in hypertrophy. In this study, we showed that sublethal concentrations of glucose (25 mmol/L) could induce cardiomyocyte hypertrophy with an increase in the cellular surface area and the upregulation of the atrial natriuretic peptide (ANP) gene, a hypertrophic marker. High glucose (HG) treatments resulted in the upregulation of the Nodal gene, which is under-expressed in cardiomyocytes. We also determined that the knockdown of the Nodal gene resisted HG-induced cardiomyocyte hypertrophy. The overexpression of Nodal was able to induce hypertrophy in cardiomyocytes, which was associated with the upregulation of the PITX2C gene. We also showed that increases in the PITX2C expression, in response to Nodal, were mediated by the Smad4 signaling pathway. This study is highly relevant to the understanding of the effects of the Nodal-PITX2C pathway on HG-induced cardiomyocyte hypertrophy, as well as the related molecular mechanisms.

  7. Autophagy protects cardiomyocytes from the myocardial ischaemia-reperfusion injury through the clearance of CLP36

    Science.gov (United States)

    Li, Shiguo; Liu, Chao; Gu, Lei; Wang, Lina; Shang, Yongliang; Liu, Qiong; Wan, Junyi; Shi, Jian; Wang, Fang; Xu, Zhiliang; Ji, Guangju

    2016-01-01

    Cardiovascular disease (CVD) is the leading cause of the death worldwide. An increasing number of studies have found that autophagy is involved in the progression or prevention of CVD. However, the precise mechanism of autophagy in CVD, especially the myocardial ischaemia-reperfusion injury (MI/R injury), is unclear and controversial. Here, we show that the cardiomyocyte-specific disruption of autophagy by conditional knockout of Atg7 leads to severe contractile dysfunction, myofibrillar disarray and vacuolar cardiomyocytes. A negative cytoskeleton organization regulator, CLP36, was found to be accumulated in Atg7-deficient cardiomyocytes. The cardiomyocyte-specific knockout of Atg7 aggravates the MI/R injury with cardiac hypertrophy, contractile dysfunction, myofibrillar disarray and severe cardiac fibrosis, most probably due to CLP36 accumulation in cardiomyocytes. Altogether, this work reveals autophagy may protect cardiomyocytes from the MI/R injury through the clearance of CLP36, and these findings define a novel relationship between autophagy and the regulation of stress fibre in heart. PMID:27512143

  8. Hawthorn (Crataegus monogyna Jacq.) extract exhibits atropine-sensitive activity in a cultured cardiomyocyte assay.

    Science.gov (United States)

    Salehi, Satin; Long, Shannon R; Proteau, Philip J; Filtz, Theresa M

    2009-01-01

    Hawthorn (Crataegus spp.) plant extract is used as a herbal alternative medicine for the prevention and treatment of various cardiovascular diseases. Recently, it was shown that hawthorn extract preparations caused negative chronotropic effects in a cultured neonatal murine cardiomyocyte assay, independent of beta-adrenergic receptor blockade. The aim of this study was to further characterize the effect of hawthorn extract to decrease the contraction rate of cultured cardiomyocytes. To test the hypothesis that hawthorn is acting via muscarinic receptors, the effect of hawthorn extract on atrial versus ventricular cardiomyocytes in culture was evaluated. As would be expected for activation of muscarinic receptors, hawthorn extract had a greater effect in atrial cells. Atrial and/or ventricular cardiomyocytes were then treated with hawthorn extract in the presence of atropine or himbacine. Changes in the contraction rate of cultured cardiomyocytes revealed that both muscarinic antagonists significantly attenuated the negative chronotropic activity of hawthorn extract. Using quinuclidinyl benzilate, L-[benzylic-4,4'-(3)H] ([(3)H]-QNB) as a radioligand antagonist, the effect of a partially purified hawthorn extract fraction to inhibit muscarinic receptor binding was quantified. Hawthorn extract fraction 3 dose-dependently inhibited [(3)H]-QNB binding to mouse heart membranes. Taken together, these findings suggest that decreased contraction frequency by hawthorn extracts in neonatal murine cardiomyocytes may be mediated via muscarinic receptor activation.

  9. A p53-based genetic tracing system to follow postnatal cardiomyocyte expansion in heart regeneration.

    Science.gov (United States)

    Xiao, Qi; Zhang, Guoxin; Wang, Huijuan; Chen, Lai; Lu, Shuangshuang; Pan, Dejing; Liu, Geng; Yang, Zhongzhou

    2017-02-15

    In the field of heart regeneration, the proliferative potential of cardiomyocytes in postnatal mice is under intense investigation. However, solely relying on immunostaining of proliferation markers, the long-term proliferation dynamics and potential of the cardiomyocytes cannot be readily addressed. Previously, we found that a p53 promoter-driving reporter predominantly marked the proliferating lineages in mice. Here, we established a p53-based genetic tracing system to investigate postnatal cardiomyocyte proliferation and heart regeneration. By selectively tracing proliferative cardiomyocytes, a differential pattern of clonal expansion in p53(+) cardiac myocytes was revealed in neonatal, adolescent and adult stages. In addition, the percentage of p53(+) lineage cardiomyocytes increased continuously in the first month. Furthermore, these cells rapidly responded to heart injury and greatly contributed to the replenished myocardium. Therefore, this study reveals complex proliferating dynamics in postnatal cardiomyocytes and heart repair, and provides a novel genetic tracing strategy for studying postnatal cardiac turnover and regeneration. © 2017. Published by The Company of Biologists Ltd.

  10. MiR-25 protects cardiomyocytes against oxidative damage by targeting the mitochondrial calcium uniporter.

    Science.gov (United States)

    Pan, Lei; Huang, Bi-Jun; Ma, Xiu-E; Wang, Shi-Yi; Feng, Jing; Lv, Fei; Liu, Yuan; Liu, Yi; Li, Chang-Ming; Liang, Dan-Dan; Li, Jun; Xu, Liang; Chen, Yi-Han

    2015-03-10

    MicroRNAs (miRNAs) are a class of small non-coding RNAs, whose expression levels vary in different cell types and tissues. Emerging evidence indicates that tissue-specific and -enriched miRNAs are closely associated with cellular development and stress responses in their tissues. MiR-25 has been documented to be abundant in cardiomyocytes, but its function in the heart remains unknown. Here, we report that miR-25 can protect cardiomyocytes against oxidative damage by down-regulating mitochondrial calcium uniporter (MCU). MiR-25 was markedly elevated in response to oxidative stimulation in cardiomyocytes. Further overexpression of miR-25 protected cardiomyocytes against oxidative damage by inactivating the mitochondrial apoptosis pathway. MCU was identified as a potential target of miR-25 by bioinformatical analysis. MCU mRNA level was reversely correlated with miR-25 under the exposure of H2O2, and MCU protein level was largely decreased by miR-25 overexpression. The luciferase reporter assay confirmed that miR-25 bound directly to the 3' untranslated region (UTR) of MCU mRNA. MiR-25 significantly decreased H2O2-induced elevation of mitochondrial Ca2+ concentration, which is likely to be the result of decreased activity of MCU. We conclude that miR-25 targets MCU to protect cardiomyocytes against oxidative damages. This finding provides novel insights into the involvement of miRNAs in oxidative stress in cardiomyocytes.

  11. MicroRNA-1 and-16 inhibit cardiomyocyte hypertrophy by targeting cyclins/Rb pathway

    Institute of Scientific and Technical Information of China (English)

    SHAN Zhi-xin; ZHU Jie-ning; TANG Chun-mei; ZHU Wen-si; LIN Qiu-xiong; HU Zhi-qin; FU Yong-heng; ZHANG Meng-zhen

    2016-01-01

    AIM:MicroRNAs ( miRNAs) were recognized to play significant roles in cardiac hypertrophy .But, it remains unknown whether cyclin/Rb pathway is modulated by miRNAs during cardiac hypertrophy .This study investigates the potential roles of microRNA-1 (miR-1) and microRNA-16 (miR-16) in modulating cyclin/Rb pathway during cardiomyocyte hypertrophy .METHODS:An animal model of hypertrophy was established in a rat with abdominal aortic constriction (AAC).In addition, a cell model of hypertrophy was also achieved based on PE-promoted neonatal rat ventricular cardiomyocyte .RESULTS:miR-1 and-16 expression were markedly de-creased in hypertrophic myocardium and hypertrophic cardiomyocytes in rats .Overexpression of miR-1 and -16 suppressed rat cardiac hypertrophy and hypertrophic phenotype of cultured cardiomyocytes .Expression of cyclins D1, D2 and E1, CDK6 and phosphorylated pRb was increased in hypertrophic myocardium and hypertrophic cardiomyocytes , but could be reversed by enforced expression of miR-1 and -16.CDK6 was validated to be modulated post-transcriptionally by miR-1, and cyclins D1, D2 and E1 were further validated to be modulated post-transcriptionally by miR-16.CONCLUSION: Attenuations of miR-1 and -16 provoke cardiomyocyte hypertrophy via derepressing the cyclins D1, D2, E1 and CDK6, and activating cyclin/Rb pathway.

  12. Antioxidant Effect of Selenium-containing Glutathione S-Transferase in Rat Cardiomyocytes

    Institute of Scientific and Technical Information of China (English)

    YIN Li; HAN Xiao; YU Yang; GUO Xiao; REN Li-qun; FANG Jing-qi; LIU Zhi-yi; YAN Gang-lin; WEI Jing-yan

    2012-01-01

    As one of the most important antioxidant enzymes,glutathione peroxidase(GPX) protects cells and tissues from oxidative damage,and plays an important role in cardiovascular and cerebrovascular injuries induced by oxidative stress.The antioxidant effect of selenium-containing glutathione S-transferase(Se-GST),a mimic of GPX was investigated on rat cardiomyocytes.To explore the protection function of Se-GST in hydrogen peroxide(H2O2) challenged rat cardiomyocytes,we examined malondialdehyde(MDA),lactate dehydrogenase(LDH),superoxide dismutase(SOD) and cell apoptosis.The results demonstrate exposure of rat cardiomyocytes to H2O2 for 6 and 12 h induced the significant increases of MDA,LDH and apoptosis rate of cardiomyocytes,but pretreatment of rat cardiomyocytes with Se-GST at 0.0005 or 0.001 unit/mL prevents oxidative stress induced by H2O2 with the decreases of cell apoptosis.All the results him Se-GST has antioxidant activity for oxidative stress challenged rat cardiomyocytes.

  13. Effect of Early Cognitive and Speech Intervention on Developmental Delay%早期认知语言康复训练对发育迟缓患儿各发育能区的影响

    Institute of Scientific and Technical Information of China (English)

    胡继红; 周平秋; 郭春光; 刘丽君; 陈建树; 张惠佳

    2016-01-01

    目的:探讨早期认知语言康复训练对发育迟缓患儿各项发育能区的影响。方法2014年6月~2015年6月住院和门诊治疗的发育迟缓患儿58例,根据诊疗情况分为观察组(n=32)和对照组(n=26)。观察组接受早期认知语言康复训练和常规康复,对照组仅接受常规康复。两组患儿在治疗前和治疗3个月后,分别采用Gesell发育量表进行评定。结果两组治疗后,大运动、精细动作、语言、个人-社交能区发育商均有显著改善(t>2.90, P2.84, P36.52, P2.90, P2.84, P36.52, P<0.01). Conclusion Early cognitive and speech intervention may improve development of many dimensions in children with developmental delay. The earlier the intervention, the better the outcome.

  14. Inhibition of aldehyde dehydrogenase 2 activity enhances antimycin-induced rat cardiomyocytes apoptosis through activation of MAPK signaling pathway.

    Science.gov (United States)

    Zhang, Peng; Xu, Danling; Wang, Shijun; Fu, Han; Wang, Keqiang; Zou, Yunzeng; Sun, Aijun; Ge, Junbo

    2011-12-01

    Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial-specific enzyme, has been proved to be involved in oxidative stress-induced cell apoptosis, while little is known in cardiomyocytes. This study was aimed at investigating the role of ALDH2 in antimycin A-induced cardiomyocytes apoptosis by suppressing ALDH2 activity with a specific ALDH2 inhibitor Daidzin. Antimycin A (40μg/ml) was used to induce neonatal cardiomyocytes apoptosis. Daidzin (60μM) effectively inhibited ALDH2 activity by 50% without own effect on cell apoptosis, and significantly enhanced antimycin A-induced cardiomyocytes apoptosis from 33.5±4.4 to 56.5±6.4% (Hochest method, pdaidzin treated cardiomyocytes compared to the cells treated with antimycin A alone. These findings indicated that modifying mitochondrial ALDH2 activity/expression might be a potential therapeutic option on reducing oxidative insults induced cardiomyocytes apoptosis.

  15. A piezoelectric electrospun platform for in situ cardiomyocyte contraction analysis

    Science.gov (United States)

    Beringer, Laura Toth

    hyperpolarized state, proving their potential use as contractile analysis microdevices. The third and final aim of this dissertation was to be able to measure contraction events from both cultured cardiomyocytes and whole tissues in situ. Rat neonatal cardiomyocytes grew on the prepared collagen/PVDF-TrFe nanogenerators and yielded a distinct signal after 8 days of growth. These contractions were verified with live cell imaging and video recording. In addition, cardiomyocyte exposure to the drug isoproterenol increased contraction strength and frequency, which was reflected in the nanogenerator recordings. Frog whole heart and heart tissue slices also were interfaced with the fabricated nanogenerators and signals were recorded. The same held true for heart slices from male Sprague-Dawley rats. These signals were determined to be statistically different compared to the control baseline nanogenerator recordings in media in the absence of cell culture. Overall the fabricated nanogenerators have demonstrated their potential to be used as in situ analysis tools for contractile events and have potential in the field of personalized medicine and drug diagnostic assays. The facile fabrication and ease of setup to obtain the electrical voltage signal corresponding to the contractile events are what sets the nanogenerator apart from any polymer based sensor available today.

  16. Developmental coordination disorder

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/001533.htm Developmental coordination disorder To use the sharing features on this page, please enable JavaScript. Developmental coordination disorder is a childhood disorder. It leads to ...

  17. Developmental and functional outcomes at school age of preschool children with global developmental delay.

    Science.gov (United States)

    Shevell, Michael; Majnemer, Annette; Platt, Robert W; Webster, Richard; Birnbaum, Rena

    2005-08-01

    The later developmental trajectory of young children diagnosed early with global developmental delay was determined. Using a prospective study, preschool children diagnosed with global developmental delay were systematically reassessed during the early school years with standardized developmental and functional outcome measures (Battelle Developmental Inventory and Vineland Adaptive Behavior Scale). Of an original cohort of 99 children assessed and diagnosed at a mean age of 3.4 +/- 1.1 years, 48 were reassessed at a mean age of 7.3 +/- 0.9 years. Group performance on the Battelle Developmental Inventory overall was 66.4 +/- 4.3 (mean 100 +/- 15). Between 75% and 100% of the cohort performed at least 1.5 SD below the normative mean on the individual domains of the Battelle Developmental Inventory. Similarly, the group mean on the Vineland Adaptive Behavior Scale overall was 63.5 +/- 20.8 (mean 100 +/- 15), with between 61% and 76% of the cohort scoring more than 1.5 SD below the mean on each of the domains. Univariate and multivariate analyses on potential predictor variables identified a lack of an underlying etiology as predictive of poorer performance on the Battelle Developmental Inventory fine motor and motor domains and increasing severity of initial delay as predictive of poorer performance on the Vineland Adaptive Behavior Scale communication domain and overall score. Similarly, maternal employment and paternal postsecondary education improved Vineland Adaptive Behavior Scale communication scores, whereas paternal postsecondary education alone predicted better socialization and total scores on the Vineland Adaptive Behavior Scale. Children with early global developmental delay demonstrate persistent and consistently poor performance across all developmental and functional domains. Few variables are apparent at intake to predict later performance.

  18. Developmental screening and detection of developmental delays in infants and toddlers with fragile X syndrome.

    Science.gov (United States)

    Mirrett, Penny L; Bailey, Donald B; Roberts, Jane E; Hatton, Deborah D

    2004-02-01

    Three developmental screening tests (the Denver-II, Battelle Developmental Inventory Screening Test, and Early Language Milestone Scale-2) were administered to 18 infants and toddlers (13 boys and 5 girls) with confirmed diagnoses of fragile X syndrome as part of a comprehensive developmental assessment at 9, 12, and 18 months of age. The Denver-II identified delays for 10 of 11 boys at 9 months of age and the Denver-II and the Early Language Milestone Scale-2 identified delays in 100% of the boys at 12 and 18 months. The Battelle Developmental Inventory Screening Test identified delays in 75% of the children at 12 and 18 months. When compared with more comprehensive developmental tests (Mullen Scales of Early Learning and Receptive-Expressive Emergent Language Scale-2), the screening tests concurred at least 76% of the time at the 12- and 18-month assessments. These results indicate that developmental delays could be detected in most children with fragile X syndrome through routine developmental screening by the age of 9 to 12 months.

  19. The Domain of Developmental Psychopathology.

    Science.gov (United States)

    Sroufe, L. Alan; Rutter, Michael

    1984-01-01

    Describes how developmental psychopathology differs from related disciplines, including abnormal psychology, psychiatry, clinical child psychology, and developmental psychology. Points out propositions underlying a developmental perspective and discusses implications for research in developmental psychopathology. (Author/RH)

  20. Structural differentiation, proliferation, and association of human embryonic stem cell-derived cardiomyocytes in vitro and in their extracardiac tissues.

    Science.gov (United States)

    Cui, Li; Johkura, Kohei; Takei, Shunsuke; Ogiwara, Naoko; Sasaki, Katsunori

    2007-06-01

    The proliferation, structural differentiation, and capacity of association of human ES cell-derived cardiomyocytes were assessed in culture and in extracardiac graft tissues. Embryoid body (EB) outgrowths having cardiomyocytes, and their transplants in mice retroperitoneum or renal subcapsular region were analyz