bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis
Authors: Kawata Koji , Shimazaki Ryuhei , Okabe Satoshi 
Published: November 2008

AbstractCarcinogenesis is an important chronic toxicity of metals and metalloids, although their mechanisms of action are still unclear. Comparison of gene expression patterns induced by carcinogenic metals, metalloids, and model carcinogens would give an insight into understanding of their carcinogenic mechanisms. In this study, we examined the gene expression alteration in human hepatoma cell line, HepG2, after exposing to two metals (cadmium and nickel), a metalloid (arsenic), and three model carcinogenic chemicalsN‐dimethylnitrosoamine (DMN), 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), and tetrachloroethylene (TCE) using DNA microarrays with 8,795 human genes. Of the genes altered by As, Cd, and Ni exposures, 31–55% were overlapped with those altered by three model carcinogenic chemical exposures in our experiments. In particular, the metals and metalloid shared certain characteristics with TPA and TCE in remarkable upregulations of the genes associated with progression of cell cycle, which might play a central role in As, Cd, and Ni carcinogenesis. This characteristic of gene expression alteration was partially counteracted by intracellular accumulation of vitamin C in As‐exposed cells, whereas the number of cell‐cycle associated genes was increased in Cd‐ and Ni‐exposed cells. In our experimental conditions, ROS might have an accelerative effect on the cell proliferation mechanisms of As, but have an inhibitory effect on those of other two heavy metals. Furthermore, based on the results of Q‐PCR, the oncogenePTTG1, which was upregulated by all carcinogenic chemical exposures in the array experiments, might be a useful biomarker for evaluation of the carcinogenesis of inorganic carcinogens. Environ. Mol. Mutagen., 2009. © 2008 Wiley‐Liss, Inc.
Bone morphogenetic protein 4 inhibits TGF‐β2 stimulation of extracellular matrix proteins in optic nerve head cells: Role of gremlin in ECM modulation
Authors: Zode Gulab S. , Clark Abbot F. , Wordinger Robert J. 
Published: November 2008

AbstractThe characteristic cupping of the optic nerve head (ONH) in glaucoma is associated with elevated TGF‐β2 and increased synthesis and deposition of extracellular matrix (ECM) proteins. In addition to TGF‐β2, the human ONH also expresses bone morphogenetic proteins (BMPs) and BMP receptors, which are members of the TGF‐β superfamily. We examined the potential effects of BMP4 and the BMP antagonist gremlin on TGF‐β2 induction of ECM proteins in ONH cells. BMP‐4 dose dependently inhibited TGF‐β2‐induced fibronectin (FN) and PAI‐1 expression in ONH astrocytes and lamina cribrosa (LC) cells and also reduced TGF‐β2 stimulation of collagen I, collagen VI, and elastin. Addition of gremlin blocked this BMP‐4 response, increasing cellular and secreted FN as well as PAI‐1 levels in both cell types. Gremlin was expressed in ONH tissues and ONH cells, and gremlin protein levels were significantly increased in the LC region of human glaucomatous ONH tissues. Interestingly, recombinant gremlin dose dependently increased ECM protein expression in cultured ONH astrocytes and LC cells. Gremlin stimulation of ECM required activation of TGF‐β receptor and R‐Smad3. TGF‐β2 increased gremlin mRNA expression and protein levels in ONH cells. Inhibition of either the type I TGF‐β receptor or Smad3 phosphorylation blocked TGF‐β2‐induced gremlin expression. In conclusion, BMP4 blocked the TGF‐β2 induction of ECM proteins in ONH cells. The BMP antagonist gremlin reversed this inhibition, allowing TGF‐β2 stimulation of ECM synthesis. Increased expression of gremlin in the glaucomatous ONH may further exacerbate TGF‐β2 effects on ONH ECM metabolism by inhibiting BMP‐4 antagonism of TGF‐β2 signaling. Modulation of the ECM via gremlin provides a novel therapeutic target for glaucoma. © 2008 Wiley‐Liss, Inc.
The endocannabinoid anandamide inhibits potassium conductance in rat cortical astrocytes
Authors: Vignali M. , Benfenati V. , Caprini M. , Anderova M. , Nobile M. , Ferroni S. 
Published: November 2008

AbstractEndocannabinoids are a family of endogenous signaling molecules that modulate neuronal excitability in the central nervous system (CNS) by interacting with cannabinoid (CB) receptors. In spite of the evidence that astroglial cells also possess CB receptors, there is no information on the role of endocannabinoids in regulating CNS function through the modulation of ion channel‐mediated homeostatic mechanisms in astroglial cells. We provide electrophysiological evidence that the two brain endocannabinoids anandamide (AEA) and 2‐arachidonylglycerol (2‐AG) markedly depress outward conductance mediated by delayed outward rectifier potassium current (IKDR) in primary cultured rat cortical astrocytes. Pharmacological experiments suggest that the effect of AEA does not result from the activation of known CB receptors. Moreover, neither the production of AEA metabolites nor variations in free cytosolic calcium are involved in the negative modulation of IKDR. We show that the action of AEA is mediated by its interaction with the extracellular leaflet of the plasma membrane. Similar experiments performedin situin cortical slices indicate that AEA downregulates IKDRin complex and passive astroglial cells. Moreover, IKDRis also inhibited by AEA in NG2 glia. Collectively, these results support the notion that endocannabinoids may exert their modulation of CNS function via the regulation of homeostatic function of the astroglial syncytium mediated by ion channel activity. © 2008 Wiley‐Liss, Inc.
Effect of corticosterone on developing hippocampus: Short‐term and long‐term outcomes
Authors: He Wen‐Bin , Zhao Ming , Machida Takeo , Chen Nai‐Hong 
Published: November 2008

AbstractMany documents implicate that corticosterone plays a negative role in brain function, especially in learning and memory. However, less evidence confirms its direct actions on hippocampal development. In the work reported here, pro treatment, minimum corticosterone administration in infant mice, and con treatment, corticosterone deprivation by adrenalectomy, were used to examine the effects imposed by corticosterone on the structure and function of developing hippocampus. Our study shows that adrenalectomy induces decrease of plasma corticosterone levels and results in the impairment of learning performance and the degenerative changes not in CA regions of hippocampus but in dentate gyrus. Noteworthily, this damage effect is severer in 5‐week‐old mice than that in 10‐week‐old mice. In addition, the short‐term effect of minimum corticosterone administration may accelerate the development of dentate gyrus of 10‐day‐old mice. Moreover, minimum corticosterone administration during infancy contributed to the learning performance and the structural integrity of hippocampal CA regions in different developing stages, while this phenomenon was not observed in dentate gyrus. In conclusion, corticosterone is necessary for the development of dentate gyrus, especially in relatively young individuals, and administration with minimum corticosterone in infancy has a long‐term positive influence on the hippocampal structure and function in different developing stages. © 2008 Wiley‐Liss, Inc.
Low social inclusion in childhood: adjustment and early predictors
Authors: Nyberg Lilianne , Henricsson Lisbeth , Rydell Ann‐Margret 
Published: November 2008

AbstractThe principal aim of the present study was to obtain a deeper understanding than hitherto of the concurrent correlates and prospective predictors of loneliness and poor peer acceptance, both falling under the umbrella term low social inclusion. Problematic and socially competent behaviours were investigated as possible predictors of low social inclusion in grade 6, as defined by self‐rated loneliness and degree of peer non‐acceptance, respectively. In grade 6 808 children participated whereof 323 were followed longitudinally from first grade. Loneliness in grade 6 was distinctively associated with high levels of internalizing problems, concurrently as well as prospectively. Peer acceptance, on the other hand, emerged as a complex, multifaceted aspect, with concurrent, independent predictions from both externalizing and internalizing problem behaviours as well as social competence, although prospective analyses found early externalizing problems to be the strongest predictor of peer acceptance. Moderating effects of social competence were sparse, although peer nominated social competence buffered peer acceptance for children with high levels of aggression in the concurrent analyses and social competence boosted peer acceptance for children with low problem levels in the predictive analyses. Social competence did not appear to buffer the negative impact of early problem behaviours on peer relations. Copyright © 2008 John Wiley & Sons, Ltd.
Who knows best? Preschoolers sometimes prefer child informants over adult informants
Authors: VanderBorght Mieke , Jaswal Vikram K. 
Published: November 2008

AbstractDo preschoolers think adults know more about everything than children? Or do they recognize that there are some things that children might know more about than adults? Three‐, four‐, and five‐year olds (N=65) were asked to decide whether an adult or child informant would better be able to answer a variety of questions about the nutritional value of foods and about toys. Children at all ages chose to direct the food questions to the adult and the toy questions to the child. Thus, there are some kinds of information for which preschoolers expect that a child would be a better informant than an adult. Copyright © 2008 John Wiley & Sons, Ltd.
Israeli kindergarten children's gender constancy for others' counter‐stereotypic toy play and appearance: the role of sibling gender and relative age
Authors: Karniol Rachel 
Published: November 2008

AbstractTo test divergent theoretical predictions as to the impact of having a younger or older, same‐sex sibling or opposite‐sex sibling on other gender constancy, Israeli kindergarten children in two‐child families responded to a gender constancy task in which a male and female picture target engaged in counter‐stereotypic toy play and adopted counter‐stereotypic appearance. Children were also asked whether the target child could change sex at will and to explain the difference between boys and girls. Relative age of sibling, both independently and in interaction with participant sex, was associated with greater gender constancy in the face of counter‐stereotypic toy play. Relative age of sibling and sibling sex was independently associated with greater gender constancy in the face of counter‐stereotypic appearance. In both cases, children with a younger sibling evidenced greater gender constancy. Boys, especially ones with a male sibling, referred most explicitly to target's birth sex in accounting for his or her being unable to change sex at will. Genital and anatomical differences between boys and girls were cited more often by children who referred explicitly to target's birth sex and had a younger sibling. The results were discussed in the context of theories of gender development and the socialization of gender within the family. Copyright © 2008 John Wiley & Sons, Ltd.
Infant‐holding biases in mothers and affective symptoms during pregnancy and after delivery
Authors: Vauclair Jacques , Scola Céline 
Published: November 2008

AbstractSeveral authors have reported that participants have a leftward bias when holding a newborn or young infant. Our study of mothers met before and after their infant's birth sought to ascertain whether particular combinations of affective symptoms (depression, anxiety) and holding positions (horizontal versus vertical) were related to holding‐side biases. Our results showed that (a) mothers displayed a significant leftward (71%) holding bias, (b) mothers with affective symptoms held their newborn on the right side and more frequently in the vertical position, and (c) hemispheric specialization for perceiving visual emotions had no significant effect on the holding‐side biases of new mothers. These results suggest that maternal affective symptoms have a dominant effect on the determination of holding‐side preferences, when associated with a particular holding position. Copyright © 2008 John Wiley & Sons, Ltd.
Predicting developmental deficiencies at the age of four based on data from the first seven months of life
Authors: Rostad Anne Margrethe , Nyberg Per , Sivberg Bengt 
Published: November 2008

AbstractThe study examines very young children with the aim of identifying precursors of developmental problems during the first 7 months of age. Information from screening and observations in the birth clinic, in the first level of health care, and from parents was collected on five different occasions. The information that was included concerning the child and family was defined as either optimal or nonoptimal. At the age of 4 years, a clinical group was identified (11.1% of the total population). Logistic regression analyses were performed to detect risk factors. Twenty‐one precursors were used to create a screening questionnaire that provided useful information (sensitivity = 56.1%, specificity = 98.8%) for predicting developmental problems of the children. The contribution of sociodemographic data was significant; medical information was less significant. The highest prediction rate surprisingly was found in the moderate clinical subgroup (62.1%), compared to the group with more severe problems that had a slightly lower rate (46.7%). The conclusion of the study is that it is possible to detect infants in need of early intervention using a continuous process of observation and screening.
Parents' attachment styles, mental representations, and institutionalization of children in Bulgaria
Authors: Markova Galina , Shilkret Robert , Djalev Liubomir 
Published: November 2008

AbstractWe first summarize the history, extent, and characteristics of institutionalization of non‐orphan children in Bulgaria. Then we describe a study of certain psychological characteristics of mothers who use institutionalization compared with mothers similar in ethnicity and close‐to‐poverty circumstances, those using state daycare programs, and those using weekly care programs for their children. Institutionalizing mothers had been institutionalized themselves far more often than had the other mothers. On two attachment measures, as expected, institutionalizing mothers were less secure and more insecure than daycare mothers, with weekly care mothers intermediate. On a parental representation task, results were somewhat more equivocal. Results suggest that psychological characteristics, especially attachment style, are important in decisions to use institutionalization as a means of child care.
Posttraumatic stress symptoms following childbirth and mothers' perceptions of their infants
Authors: Davies John , Slade Pauline , Wright Ingram , Stewart Peter 
Published: November 2008

AbstractPostpartum psychological distress can adversely affect the early mother–infant relationship; however, this has not been investigated in relation to posttraumatic stress disorder (PTSD) following childbirth. This article explores whether PTSD symptoms relating to labor and delivery are associated with mothers' early perceptions of their infant. Using labor and childbirth as the stressor criterion, 211 women were assessed at 6 weeks' postpartum for symptoms of intrusions, avoidance, and hyperarousal. Their perceptions of their infants, of mother‐to‐infant attachment, and infant behavioral characteristics also were evaluated. In sum, 3.8% of the women fulfilled full diagnostic criteria, and a further 21.3% reported clinically significant symptoms on at least one dimension of PTSD. Those meeting full or partial criteria perceived their attachment relationships to be significantly less optimal and reported more negative maternal representations in terms of their infants being less warm and more invasive. They also rated them as being temperamentally more difficult, prone to distress, and less easy to soothe. However, when the effects of depression were partialled, only the effect for perceived warmth remained. Posttraumatic stress symptoms relating to labor and delivery may adversely influence maternal perceptions of infants, with potentially adverse implications for the developing mother–infant relationship. The overlap with depressive symptoms requires further exploration.
Attachment in foster children associated with caregivers' sensitivity and behavioral problems
Authors: Oosterman Mirjam , Schuengel Carlo 
Published: November 2008

AbstractThis study focused on attachment of foster children by examining factors associated with attachment relationships of children raised from birth by the same parents. The sample included 61 children between 26 to 88 months of age and their foster caregivers. Attachment security and caregiver sensitivity were coded on the basis of, respectively, a home‐observation (Attachment Q‐Set) and a laboratory procedure (Three boxes). Other measures included caregiver reports of child externalizing and internalizing behavior problems and symptoms of attachment disorder, including inhibited and disinhibited attachment as well as secure base distortions. For a subsample of children, teacher ratings of behavior problems also were available. Foster parent sensitivity was positively associated with attachment security, but only if symptoms of disordered attachment were partialled out. Symptoms of inhibited and disinhibited attachment as well as secure base distortions were positively related to parent reports of externalizing and internalizing behavior problems whereas attachment security was negatively related to teacher reports of externalizing behavior problems. Attachment theoretical tenets appeared valid with foster parent–child relationships, except for children with symptoms of attachment disorder.
Influences of maternal postpartum depression on fathers and on father–infant interaction
Authors: Goodman Janice H. 
Published: November 2008

AbstractMaternal postpartum depression (PPD) has been shown to negatively influence mother–infant interaction; however, little research has explored how fathers and father–infant interaction are affected when a mother is depressed. This study examined the influence of maternal PPD on fathers and identified maternal and paternal factors associated with father–infant interaction in families with depressed as compared with nondepressed mothers. A convenience sample of 128 mother–father–infant triads, approximately half of which included women with significant symptoms of PPD at screening, were recruited from a screening sample of 790 postpartum women. Mothers and fathers completed measures of depression, marital satisfaction, and parenting stress at 2 to 3 months' postpartum and were each videotaped interacting with their infants. Results indicate that maternal PPD is associated with increased paternal depression and higher paternal parenting stress. Partners of depressed women demonstrated less optimal interaction with their infants, indicating that fathers do not compensate for the negative effects of maternal depression on the child. Although mother–infant interaction did not influence father–infant interaction, how the mother felt about her relationship with the infant did, even more so than maternal depression. The links between maternal PPD, fathers, and father–infant interaction indicate a need for further understanding of the reciprocal influences between mothers, fathers, and infants.
The p38 mitogen‐activated protein kinase pathway is involved in the regulation of heme oxygenase‐1 by acidic extracellular pH in aortic smooth muscle cells
Authors: Guan Jason , Wu Xinqi , Arons Elena , Christou Helen 
Published: November 2008

AbstractExtracellular acidosis (EA) regulates Heme Oxygenase‐1 (HO‐1) expression in vascular smooth muscle cells via transcriptional and posttranscriptional mechanisms but the signaling pathways involved are not known. We examined the role of Mitogen‐Activated Protein Kinase (MAPK) pathways in HO‐1 regulation by EA. Primary rat aortic smooth muscle cells were exposed to EA or physiologic pH. Levels of the total and phosphorylated forms of p38, extracellular signal‐regulated protein kinases1/2 (ERK1/2), c‐Jun N‐terminal kinases/stress‐activated protein kinases (JNK1/2), and HO‐1 protein were assessed by Western analysis and HO‐1 mRNA levels were assessed by quantitative PCR. Inhibition of p38 MAPK was achieved with the chemical inhibitor SB203580, or adenoviral infection of a dominant‐negative form of p38α. Phospho p38 MAPK activity was evaluated with an in vitro kinase activity assay. Binding of Activator Protein‐1 (AP‐1), a known target of MAPK pathways, was assessed by Electromobility shift assay (EMSA). EA induced phosphorylation of p38 MAPK in a biphasic manner while total p38 was unchanged. EA did not alter levels of phospho ERK 1/2 and phospho JNK 1/2. There was increased phospho p38 MAPK activity in the setting of EA which preceded the induction of HO‐1. Inhibition of phospho p38 activity with either SB20358 or a dominant negative p38α oligonucleotide abrogated the induction of HO‐1 by EA. Increased specific binding of AP‐1 in the setting of EA was shown by EMSA. Increased phospho p38 activity precedes and likely mediates HO‐1 induction by EA. Increased AP‐1 binding may underlie the transcriptional regulation of HO‐1 by EA. J. Cell. Biochem. 105: 1298–1306, 2008. © 2008 Wiley‐Liss, Inc.
A new method for the gradient‐based optimization of molecular complexes
Authors: Fuhrmann Jan , Rurainski Alexander , Lenhof Hans‐Peter , Neumann Dirk 
Published: November 2008

AbstractWe present a novel method for the local optimization of molecular complexes. This new approach is especially suited for usage in molecular docking. In molecular modeling, molecules are often described employing a compact representation to reduce the number of degrees of freedom. This compact representation is realized by fixing bond lengths and angles while permitting changes in translation, orientation, and selected dihedral angles. Gradient‐based energy minimization of molecular complexes using this representation suffers from well‐known singularities arising during the optimization process. We suggest an approach new in the field of structure optimization that allows to employ gradient‐based optimization algorithms for such a compact representation. We propose to use exponential mapping to define the molecular orientation which facilitates calculating the orientational gradient. To avoid singularities of this parametrization, the local minimization algorithm is modified to change efficiently the orientational parameters while preserving the molecular orientation, i.e. we perform well‐defined jumps on the objective function. Our approach is applicable to continuous, but not necessarily differentiable objective functions. We evaluated our new method by optimizing several ligands with an increasing number of internal degrees of freedom in the presence of large receptors. In comparison to the method of Solis and Wets in the challenging case of a non‐differentiable scoring function, our proposed method leads to substantially improved results in all test cases, i.e. we obtain better scores in fewer steps for all complexes. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009