Arf6 Guanine Nucleotide Exchange Factor Cytohesin-2 Binds to CCDC120 and Is Transported Along Neurites to Mediate Neurite Growth*

PubMed Central

Torii, Tomohiro; Miyamoto, Yuki; Tago, Kenji; Sango, Kazunori; Nakamura, Kazuaki; Sanbe, Atsushi; Tanoue, Akito; Yamauchi, Junji

2014-01-01

The mechanism of neurite growth is complicated, involving continuous cytoskeletal rearrangement and vesicular trafficking. Cytohesin-2 is a guanine nucleotide exchange factor for Arf6, an Arf family molecular switch protein, controlling cell morphological changes such as neuritogenesis. Here, we show that cytohesin-2 binds to a protein with a previously unknown function, CCDC120, which contains three coiled-coil domains, and is transported along neurites in differentiating N1E-115 cells. Transfection of the small interfering RNA (siRNA) specific for CCDC120 into cells inhibits neurite growth and Arf6 activation. When neurites start to extend, vesicles containing CCDC120 and cytohesin-2 are transported in an anterograde manner rather than a retrograde one. As neurites continue extension, anterograde vesicle transport decreases. CCDC120 knockdown inhibits cytohesin-2 localization into vesicles containing CCDC120 and diffuses cytohesin-2 in cytoplasmic regions, illustrating that CCDC120 determines cytohesin-2 localization in growing neurites. Reintroduction of the wild type CCDC120 construct into cells transfected with CCDC120 siRNA reverses blunted neurite growth and Arf6 activity, whereas the cytohesin-2-binding CC1 region-deficient CCDC120 construct does not. Thus, cytohesin-2 is transported along neurites by vesicles containing CCDC120, and it mediates neurite growth. These results suggest a mechanism by which guanine nucleotide exchange factor for Arf6 is transported to mediate neurite growth. PMID:25326380

ARF1 and SAR1 GTPases in Endomembrane Trafficking in Plants

PubMed Central

Cevher-Keskin, Birsen

2013-01-01

Small GTPases largely control membrane traffic, which is essential for the survival of all eukaryotes. Among the small GTP-binding proteins, ARF1 (ADP-ribosylation factor 1) and SAR1 (Secretion-Associated RAS super family 1) are commonly conserved among all eukaryotes with respect to both their functional and sequential characteristics. The ARF1 and SAR1 GTP-binding proteins are involved in the formation and budding of vesicles throughout plant endomembrane systems. ARF1 has been shown to play a critical role in COPI (Coat Protein Complex I)-mediated retrograde trafficking in eukaryotic systems, whereas SAR1 GTPases are involved in intracellular COPII-mediated protein trafficking from the ER to the Golgi apparatus. This review offers a summary of vesicular trafficking with an emphasis on the ARF1 and SAR1 expression patterns at early growth stages and in the de-etiolation process. PMID:24013371

An Arf-GAP promotes endocytosis and hyphal growth of Ashbya gossypii.

PubMed

Oscarsson, Therese; Walther, Andrea; Lengeler, Klaus B; Wendland, Jürgen

2017-12-29

The ADP-ribosylation factor (ARF) family of GTPases are highly conserved from yeast to human and regulate vesicle budding. Sec7 domain containing proteins stimulate the guanine nucleotide exchange on Arf proteins, while ARF-GTPase activating proteins stimulate the hydrolysis of GTP. Since vesicle trafficking is important for hyphal growth, we studied the Ashbya gossypii homolog of Saccharomyces cerevisiae ARF3 along with its putative GEF and GTPase-activating protein (GAP) encoded by YEL1 and GTS1, respectively. Deletion of YEL1 had no discernible phenotype and deletion of ARF3 had only a minor defect in vacuolar fusion. In contrast, deletion of GTS1 severely impaired hyphal growth, and mutants showed defects in the maintenance of polarity and the localization of cortical actin patches. The uptake of the lipophilic dye FM4-64 was delayed in gts1 hyphae, indicating a defect in endocytosis. Gts1 has several protein domains, of which the Arf-GAP domain is required for complementation of the gts1 mutant phenotype. GFP-tagged GTS1 under control of its endogenous promoter localized to the plasma membrane but was enriched at hyphal tips and septal sites corresponding to a role in polarized vesicle trafficking. Our results indicate that this ARF-GTPase module plays an important role for filamentous hyphal growth. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Internalization of exogenous ADP-ribosylation factor 6 (Arf6) proteins into cells.

PubMed

Afroze, Syeda H; Uddin, M Nasir; Cao, Xiaobo; Asea, Alexzander; Gizachew, Dawit

2011-08-01

Endogenous Arf6 is a myristoylated protein mainly involved in endosomal membrane traffic and structural organization at the plasma membrane. It has been shown that Arf6 mediates cancer cell invasion and shedding of plasma membrane microvesicles derived from tumor cells. In this article, we determined that Arf6 proteins both in the GDP and GTPγS bound forms can enter cells when simply added in the cell culture medium without requiring the myristoyl group. The GTPγS bound can enter cells at a faster rate than the GDP-bound Arf6. Despite the role of the endogenous Arf6 in endocytosis and membrane trafficking, the internalization of exogenous Arf6 may involve non-endocytic processes. As protein therapeutics is becoming important in medicine, we examined the effect of the uptake of Arf6 proteins on cellular functions and determined that exogenous Arf6 inhibits proliferation, invasion, and migration of cells. Future studies of the internalization of Arf6 mutants will reveal key residues that play a role in the internalization of Arf6 and its interaction and possible structural conformations bound to the plasma membrane.

Auxin-dependent compositional change in Mediator in ARF7- and ARF19-mediated transcription.

PubMed

Ito, Jun; Fukaki, Hidehiro; Onoda, Makoto; Li, Lin; Li, Chuanyou; Tasaka, Masao; Furutani, Masahiko

2016-06-07

Mediator is a multiprotein complex that integrates the signals from transcription factors binding to the promoter and transmits them to achieve gene transcription. The subunits of Mediator complex reside in four modules: the head, middle, tail, and dissociable CDK8 kinase module (CKM). The head, middle, and tail modules form the core Mediator complex, and the association of CKM can modify the function of Mediator in transcription. Here, we show genetic and biochemical evidence that CKM-associated Mediator transmits auxin-dependent transcriptional repression in lateral root (LR) formation. The AUXIN/INDOLE 3-ACETIC ACID 14 (Aux/IAA14) transcriptional repressor inhibits the transcriptional activity of its binding partners AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 by making a complex with the CKM-associated Mediator. In addition, TOPLESS (TPL), a transcriptional corepressor, forms a bridge between IAA14 and the CKM component MED13 through the physical interaction. ChIP assays show that auxin induces the dissociation of MED13 but not the tail module component MED25 from the ARF7 binding region upstream of its target gene. These findings indicate that auxin-induced degradation of IAA14 changes the module composition of Mediator interacting with ARF7 and ARF19 in the upstream region of their target genes involved in LR formation. We suggest that this regulation leads to a quick switch of signal transmission from ARFs to target gene expression in response to auxin.

Aspergillus nidulans ArfB Plays a Role in Endocytosis and Polarized Growth ▿ †

PubMed Central

Lee, Soo Chan; Schmidtke, Sabrina N.; Dangott, Lawrence J.; Shaw, Brian D.

2008-01-01

Filamentous fungi undergo polarized growth throughout most of their life cycles. The Spitzenkörper is an apical organelle composed primarily of vesicles that is unique to filamentous fungi and is likely to act as a vesicle supply center for tip growth. Vesicle assembly and trafficking are therefore important for hyphal growth. ADP ribosylation factors (Arfs), a group of small GTPase proteins, play an important role in nucleating vesicle assembly. Little is known about the role of Arfs in filamentous hyphal growth. We found that Aspergillus nidulans is predicted to encode six Arf family proteins. Analysis of protein sequence alignments suggests that A. nidulans ArfB shares similarity with ARF6 of Homo sapiens and Arf3p of Saccharomyces cerevisiae. An arfB null allele (arfB disrupted by a transposon [arfB::Tn]) was characterized by extended isotropic growth of germinating conidia followed by cell lysis or multiple, random germ tube emergence, consistent with a failure to establish polarity. The mutant germ tubes and hyphae that do form initially meander abnormally off of the axis of polarity and frequently exhibit dichotomous branching at cell apices, consistent with a defect in polarity maintenance. FM4-64 staining of the arfB::Tn strain revealed that another phenotypic characteristic seen for arfB::Tn is a reduction and delay in endocytosis. ArfB is myristoylated at its N terminus. Green fluorescent protein-tagged ArfB (ArfB::GFP) localizes to the plasma membrane and endomembranes and mutation (ArfBG2A::GFP) of the N-terminal myristoylation motif disperses the protein to the cytoplasm rather than to the membranes. These results demonstrate that ArfB functions in endocytosis to play important roles in polarity establishment during isotropic growth and polarity maintenance during hyphal extension. PMID:18539885

Arf6 negatively controls the rapid recycling of the β2 adrenergic receptor.

PubMed

Macia, Eric; Partisani, Mariagrazia; Paleotti, Olivia; Luton, Frederic; Franco, Michel

2012-09-01

β2-adrenergic receptor (β2AR), a member of the GPCR (G-protein coupled receptor) family, is internalized in a ligand- and β-arrestin-dependent manner into early endosomes, and subsequently recycled back to the plasma membrane. Here, we report that β-arrestin promotes the activation of the small G protein Arf6, which regulates the recycling and degradation of β2AR. We demonstrate in vitro that the C-terminal region of β-arrestin1 interacts directly and simultaneously with Arf6GDP and its specific exchange factor EFA6, to promote Arf6 activation. Similarly, the ligand-mediated activation of β2AR leads to the formation of Arf6GTP in vivo in a β-arrestin-dependent manner. Expression of either EFA6 or an activated Arf6 mutant caused accumulation of β2AR in the degradation pathway. This phenotype could be rescued by the expression of an activated mutant of Rab4, suggesting that Arf6 acts upstream of Rab4. We propose a model in which Arf6 plays an essential role in β2AR desensitization. The ligand-mediated stimulation of β2AR relocates β-arrestin to the plasma membrane, and triggers the activation of Arf6 by EFA6. The activation of Arf6 leads to accumulation of β2AR in the degradation pathway, and negatively controls Rab4-dependent fast recycling to prevent the re-sensitization of β2AR.

A role for POR1, a Rac1-interacting protein, in ARF6-mediated cytoskeletal rearrangements.

PubMed Central

D'Souza-Schorey, C; Boshans, R L; McDonough, M; Stahl, P D; Van Aelst, L

1997-01-01

The ARF6 GTPase, the least conserved member of the ADP ribosylation factor (ARF) family, associates with the plasma membrane and intracellular endosome vesicles. Mutants of ARF6 defective in GTP binding and hydrolysis have a marked effect on endocytic trafficking and the gross morphology of the peripheral membrane system. Here we report that expression of the GTPase-defective mutant of ARF6, ARF6(Q67L), remodels the actin cytoskeleton by inducing actin polymerization at the cell periphery. This cytoskeletal rearrangement was inhibited by co-expression of ARF6(Q67L) with deletion mutants of POR1, a Rac1-interacting protein involved in membrane ruffling, but not with the dominant-negative mutant of Rac1, Rac1(S17N). A synergistic effect between POR1 and ARF6 for the induction of actin polymerization was detected. Furthermore, we observed that ARF6 interacts directly with POR1 and that this interaction was GTP dependent. These findings indicate that ARF6 and Rac1 function on distinct signaling pathways to mediate cytoskeletal reorganization, and suggest a role for POR1 as an important regulatory element in orchestrating cytoskeletal rearrangements at the cell periphery induced by ARF6 and Rac1. PMID:9312003

TBC1D24, an ARF6-interacting protein, is mutated in familial infantile myoclonic epilepsy.

PubMed

Falace, Antonio; Filipello, Fabia; La Padula, Veronica; Vanni, Nicola; Madia, Francesca; De Pietri Tonelli, Davide; de Falco, Fabrizio A; Striano, Pasquale; Dagna Bricarelli, Franca; Minetti, Carlo; Benfenati, Fabio; Fassio, Anna; Zara, Federico

2010-09-10

Idiopathic epilepsies (IEs) are a group of disorders characterized by recurrent seizures in the absence of detectable brain lesions or metabolic abnormalities. IEs include common disorders with a complex mode of inheritance and rare Mendelian traits suggesting the occurrence of several alleles with variable penetrance. We previously described a large family with a recessive form of idiopathic epilepsy, named familial infantile myoclonic epilepsy (FIME), and mapped the disease locus on chromosome 16p13.3 by linkage analysis. In the present study, we found that two compound heterozygous missense mutations (D147H and A509V) in TBC1D24, a gene of unknown function, are responsible for FIME. In situ hybridization analysis revealed that Tbc1d24 is mainly expressed at the level of the cerebral cortex and the hippocampus. By coimmunoprecipitation assay we found that TBC1D24 binds ARF6, a Ras-related family of small GTPases regulating exo-endocytosis dynamics. The main recognized function of ARF6 in the nervous system is the regulation of dendritic branching, spine formation, and axonal extension. TBC1D24 overexpression resulted in a significant increase in neurite length and arborization and the FIME mutations significantly reverted this phenotype. In this study we identified a gene mutation involved in autosomal-recessive idiopathic epilepsy, unveiled the involvement of ARF6-dependent molecular pathway in brain hyperexcitability and seizures, and confirmed the emerging role of subtle cytoarchitectural alterations in the etiology of this group of common epileptic disorders. 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genome-Wide Identification, Phylogeny, and Expression Analysis of ARF Genes Involved in Vegetative Organs Development in Switchgrass.

PubMed

Wang, Jianli; Wu, Zhenying; Shen, Zhongbao; Bai, Zetao; Zhong, Peng; Ma, Lichao; Pan, Duofeng; Zhang, Ruibo; Li, Daoming; Zhang, Hailing; Fu, Chunxiang; Han, Guiqing; Guo, Changhong

2018-01-01

Auxin response factors (ARFs) have been reported to play vital roles during plant growth and development. In order to reveal specific functions related to vegetative organs in grasses, an in-depth study of the ARF gene family was carried out in switchgrass ( Panicum virgatum L.), a warm-season C4 perennial grass that is mostly used as bioenergy and animal feedstock. A total of 47 putative ARF genes ( PvARFs ) were identified in the switchgrass genome (2n = 4x = 36), 42 of which were anchored to the seven pairs of chromosomes and found to be unevenly distributed. Sixteen PvARFs were predicted to be potential targets of small RNAs (microRNA160 and 167). Phylogenetically speaking, PvARFs were divided into seven distinct subgroups based on the phylogeny, exon/intron arrangement, and conserved motif distribution. Moreover, 15 pairs of PvARFs have different temporal-spatial expression profiles in vegetative organs (2nd, 3rd, and 4th internode and leaves), which implies that different PvARFs have specific functions in switchgrass growth and development. In addition, at least 14 pairs of PvARFs respond to naphthylacetic acid (NAA) treatment, which might be helpful for us to study on auxin response in switchgrass. The comprehensive analysis, described here, will facilitate the future functional analysis of ARF genes in grasses.

Dynamics of ARF regulation that control senescence and cancer.

PubMed

Ko, Aram; Han, Su Yeon; Song, Jaewhan

2016-11-01

ARF is an alternative reading frame product of the INK4a/ARF locus, inactivated in numerous human cancers. ARF is a key regulator of cellular senescence, an irreversible cell growth arrest that suppresses tumor cell growth. It functions by sequestering MDM2 (a p53 E3 ligase) in the nucleolus, thus activating p53. Besides MDM2, ARF has numerous other interacting partners that induce either cellular senescence or apoptosis in a p53-independent manner. This further complicates the dynamics of the ARF network. Expression of ARF is frequently disrupted in human cancers, mainly due to epigenetic and transcriptional regulation. Vigorous studies on various transcription factors that either positively or negatively regulate ARF transcription have been carried out. However, recent focus on posttranslational modifications, particularly ubiquitination, indicates wider dynamic controls of ARF than previously known. In this review, we discuss the role and dynamic regulation of ARF in senescence and cancer. [BMB Reports 2016; 49(11): 598-606].

Identification of AUXIN RESPONSE FACTOR gene family from Prunus sibirica and its expression analysis during mesocarp and kernel development.

PubMed

Niu, Jun; Bi, Quanxin; Deng, Shuya; Chen, Huiping; Yu, Haiyan; Wang, Libing; Lin, Shanzhi

2018-01-24

Auxin response factors (ARFs) in auxin signaling pathway are an important component that can regulate the transcription of auxin-responsive genes involved in almost all aspects of plant growth and development. To our knowledge, the comprehensive and systematic characterization of ARF genes has never been reported in Prunus sibirica, a novel woody biodiesel feedstock in China. In this study, we identified 14 PsARF genes with a perfect open reading frame (ORF) in P. sibirica by using its previous transcriptomic data. Conserved motif analysis showed that all identified PsARF proteins had typical DNA-binding and ARF domain, but 5 members (PsARF3, 8 10, 16 and 17) lacked the dimerization domain. Phylogenetic analysis of the ARF proteins generated from various plant species indicated that ARFs could be categorized into 4 major groups (Class I, II, III and IV), in which all identified ARFs from P. sibirica showed a closest relationship with those from P. mume. Comparison of the expression profiles of 14 PsARF genes in different developmental stages of Siberian apricot mesocarp (SAM) and kernel (SAK) reflected distinct temporal or spatial expression patterns for PsARF genes. Additionally, based on the expressed data from fruit and seed development of multiple plant species, we identified 1514 ARF-correlated genes using weighted gene co-expression network analysis (WGCNA). And the major portion of ARF-correlated gene was characterized to be involved in protein, nucleic acid and carbohydrate metabolic, transport and regulatory processes. In summary, we systematically and comprehensively analyzed the structure, expression pattern and co-expression network of ARF gene family in P. sibirica. All our findings provide theoretical foundation for the PsARF gene family and will pave the way for elucidating the precise role of PsARF genes in SAM and SAK development.

ADP-ribosylation factor arf6p may function as a molecular switch of new end take off in fission yeast

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

Fujita, Atsushi

2008-02-01

Small GTPases act as molecular switches in a wide variety of cellular processes. In fission yeast Schizosaccharomyces pombe, the directions of cell growth change from a monopolar manner to a bipolar manner, which is known as 'New End Take Off' (NETO). Here I report the identification of a gene, arf6{sup +}, encoding an ADP-ribosylation factor small GTPase, that may be essential for NETO. arf6{delta} cells completely fail to undergo NETO. arf6p localizes at both cell ends and presumptive septa in a cell-cycle dependent manner. And its polarized localization is not dependent on microtubules, actin cytoskeletons and some NETO factors (bud6p,more » for3p, tea1p, tea3p, and tea4p). Notably, overexpression of a fast GDP/GTP-cycling mutant of arf6p can advance the timing of NETO. These findings suggest that arf6p functions as a molecular switch for the activation of NETO in fission yeast.« less

The Arf GEF GBF1 and Arf4 synergize with the sensory receptor cargo, rhodopsin, to regulate ciliary membrane trafficking.

PubMed

Wang, Jing; Fresquez, Theresa; Kandachar, Vasundhara; Deretic, Dusanka

2017-12-01

The small GTPase Arf4 and the Arf GTPase-activating protein (GAP) ASAP1 cooperatively sequester sensory receptor cargo into transport carriers targeted to primary cilia, but the input that drives Arf4 activation in this process remains unknown. Here, we show, by using frog retinas and recombinant human proteins, that during the carrier biogenesis from the photoreceptor Golgi/ trans -Golgi network (TGN) a functional complex is formed between Arf4, the Arf guanine nucleotide exchange factor (GEF) GBF1 and the light-sensing receptor, rhodopsin. Rhodopsin and Arf4 bind the regulatory N-terminal dimerization and cyclophillin-binding (DCB)-homology upstream of Sec7 (HUS) domain of GBF1. The complex is sensitive to Golgicide A (GCA), a selective inhibitor of GBF1 that accordingly blocks rhodopsin delivery to the cilia, without disrupting the photoreceptor Golgi. The emergence of newly synthesized rhodopsin in the endomembrane system is essential for GBF1-Arf4 complex formation in vivo Notably, GBF1 interacts with the Arf GAP ASAP1 in a GCA-resistant manner. Our findings indicate that converging signals on GBF1 from the influx of cargo into the Golgi/TGN and the feedback from Arf4, combined with input from ASAP1, control Arf4 activation during sensory membrane trafficking to primary cilia. © 2017. Published by The Company of Biologists Ltd.

Human Krüppel-related 3 (HKR3) Is a Novel Transcription Activator of Alternate Reading Frame (ARF) Gene*

PubMed Central

Yoon, Jae-Hyeon; Choi, Won-Il; Jeon, Bu-Nam; Koh, Dong-In; Kim, Min-Kyeong; Kim, Myung-Hwa; Kim, Jungho; Hur, Sujin Susanne; Kim, Kyung-Sup; Hur, Man-Wook

2014-01-01

HKR3 (Human Krüppel-related 3) is a novel POK (POZ-domain Krüppel-like zinc-finger) family transcription factor. Recently, some of the POK (POZ-domain Krüppel-like zinc finger) family proteins have been shown to play roles in cell cycle arrest, apoptosis, cell proliferation, and oncogenesis. We investigated whether HKR3, an inhibitor of cell proliferation and an uncharacterized POK family protein, could regulate the cell cycle by controlling expression of genes within the p53 pathway (ARF-MDM2-TP53-p21WAF/CDKN1A). HKR3 potently activated the transcription of the tumor suppressor gene ARF by acting on the proximal promoter region (bp, −149∼+53), which contains Sp1 and FBI-1 binding elements (FREs). HKR3 interacted with the co-activator p300 to activate ARF transcription, which increased the acetylation of histones H3 and H4 within the proximal promoter. Oligonucleotide pull-down assays and ChIP assays revealed that HKR3 interferes with the binding of the proto-oncogenic transcription repressor FBI-1 to proximal FREs, thus derepressing ARF transcription. PMID:24382891

ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion

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

Vieira da Silva, Claudio; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Sao Paulo, Rua Botucatu, 862, 6o andar, 04023-062 Sao Paulo, SP; Alves da Silva, Erika

2009-01-16

Toxoplasma gondii infects a variety of different cell types in a range of different hosts. Host cell invasion by T. gondii occurs by active penetration of the host cell, a process previously described as independent of host actin polymerization. Also, the parasitophorous vacuole has been shown to resist fusion with endocytic and exocytic pathways of the host cell. ADP-ribosylation factor-6 (ARF6) belongs to the ARF family of small GTP-binding proteins. ARF6 regulates membrane trafficking and actin cytoskeleton rearrangements at the plasma membrane. Here, we have observed that ARF6 is recruited to the parasitophorous vacuole of tachyzoites of T. gondii RHmore » strain and it also plays an important role in the parasite cell invasion with activation of PI3-kinase and recruitment of PIP{sub 2} and PIP{sub 3} to the parasitophorous vacuole of invading parasites. Moreover, it was verified that maintenance of host cell actin cytoskeleton integrity is important to parasite invasion.« less

The auxin response factor gene family in banana: genome-wide identification and expression analyses during development, ripening, and abiotic stress

PubMed Central

Hu, Wei; Zuo, Jiao; Hou, Xiaowan; Yan, Yan; Wei, Yunxie; Liu, Juhua; Li, Meiying; Xu, Biyu; Jin, Zhiqiang

2015-01-01

Auxin signaling regulates various auxin-responsive genes via two types of transcriptional regulators, Auxin Response Factors (ARF) and Aux/IAA. ARF transcription factors act as critical components of auxin signaling that play important roles in modulating various biological processes. However, limited information about this gene family in fruit crops is currently available. Herein, 47 ARF genes were identified in banana based on its genome sequence. Phylogenetic analysis of the ARFs from banana, rice, and Arabidopsis suggested that the ARFs could be divided into four subgroups, among which most ARFs from the banana showed a closer relationship with those from rice than those from Arabidopsis. Conserved motif analysis showed that all identified MaARFs had typical DNA-binding and ARF domains, but 12 members lacked the dimerization domain. Gene structure analysis showed that the number of exons in MaARF genes ranged from 5 to 21, suggesting large variation amongst banana ARF genes. The comprehensive expression profiles of MaARF genes yielded useful information about their involvement in diverse tissues, different stages of fruit development and ripening, and responses to abiotic stresses in different varieties. Interaction networks and co-expression assays indicated the strong transcriptional response of banana ARFs and ARF-mediated networks in early fruit development for different varieties. Our systematic analysis of MaARFs revealed robust tissue-specific, development-dependent, and abiotic stress-responsive candidate MaARF genes for further functional assays in planta. These findings could lead to potential applications in the genetic improvement of banana cultivars, and yield new insights into the complexity of the control of MaARF gene expression at the transcriptional level. Finally, they support the hypothesis that ARFs are a crucial component of the auxin signaling pathway, which regulates a wide range of physiological processes. PMID:26442055

Arf6 guanine-nucleotide exchange factor, cytohesin-2, interacts with actinin-1 to regulate neurite extension.

PubMed

Torii, Tomohiro; Miyamoto, Yuki; Nakamura, Kazuaki; Maeda, Masahiro; Yamauchi, Junji; Tanoue, Akito

2012-09-01

Proper regulation of morphological changes in neuronal cells is essential for their differentiation. Complex signaling mechanisms mediate a variety of morphological changes such as formation of neurites. It is well established that a number of small GTPases control neurite behavior before the connection with the target tissue. However, their regulatory mechanisms remain to be fully understood. Here, we show that the Arf6 guanine-nucleotide exchange factor (GEF), cytohesin-2 (CYTH2), interacts with the cytoskeletal protein actinin-1 (ACTN1) and regulates neurite extension in N1E-115 cells used as the model. Knockdown of ACTN1, as well as that of CYTH2, in cells inhibits cellular Arf6 activity and neurite extension. The C-terminal polybasic region of CYTH2 participates in interacting directly with the EFh2 domain of ACTN1. Expression of CYTH2 mutant deficient of the EFh2 domain in cells also inhibits Arf6 activation and neurite extension. Furthermore, FRET analysis detects that the respective interactive region peptides, tagged with cell-permeable short peptides, greatly decrease Arf6 activation at growth cones in a time-dependent manner. Collectively, the signaling through CYTH2 and ACTN1 properly regulates neurite extension in N1E-115 cells, demonstrating the unexpected interaction of CYTH2 and ACTN1 in the regulation of cellular Arf6 activity involved in neurite extension. Copyright © 2012 Elsevier Inc. All rights reserved.

A Structure-Based Mechanism for Arf1-Dependent Recruitment of Coatomer to Membranes

PubMed Central

Yu, Xinchao; Breitman, Marianna; Goldberg, Jonathan

2012-01-01

Summary Budding of COPI-coated vesicles from Golgi membranes requires an Arf-family G protein and the coatomer complex recruited from cytosol. Arf is also required with coatomer-related clathrin adaptor complexes to bud vesicles from the trans-Golgi network and endosomal compartments. To understand the structural basis for Arf-dependent recruitment of a vesicular coat to the membrane, we determined the structure of Arf1 bound to the γζ-COP subcomplex of coatomer. Structure-guided biochemical analysis reveals that a second Arf1-GTP molecule binds to βδ-COP at a site common to the γ- and β-COP subunits. The Arf1-binding sites on coatomer are spatially related to PtdIns4,5P2-binding sites on the endocytic AP2 complex, providing evidence that the orientation of membrane binding is general for this class of vesicular coat proteins. A bivalent GTP-dependent binding mode has implications for the dynamics of coatomer interaction with the Golgi and for the selection of cargo molecules. PMID:22304919

A BAR domain in the N terminus of the Arf GAP ASAP1 affects membrane structure and trafficking of epidermal growth factor receptor.

PubMed

Nie, Zhongzhen; Hirsch, Dianne S; Luo, Ruibai; Jian, Xiaoying; Stauffer, Stacey; Cremesti, Aida; Andrade, Josefa; Lebowitz, Jacob; Marino, Michael; Ahvazi, Bijan; Hinshaw, Jenny E; Randazzo, Paul A

2006-01-24

Arf GAPs are multidomain proteins that function in membrane traffic by inactivating the GTP binding protein Arf1. Numerous Arf GAPs contain a BAR domain, a protein structural element that contributes to membrane traffic by either inducing or sensing membrane curvature. We have examined the role of a putative BAR domain in the function of the Arf GAP ASAP1. ASAP1's N terminus, containing the putative BAR domain together with a PH domain, dimerized to form an extended structure that bound to large unilamellar vesicles containing acidic phospholipids, properties that define a BAR domain. A recombinant protein containing the BAR domain of ASAP1, together with the PH and Arf GAP domains, efficiently bent the surface of large unilamellar vesicles, resulting in the formation of tubular structures. This activity was regulated by Arf1*GTP binding to the Arf GAP domain. In vivo, the tubular structures induced by ASAP1 mutants contained epidermal growth factor receptor (EGFR) and Rab11, and ASAP1 colocalized in tubular structures with EGFR during recycling of receptor. Expression of ASAP1 accelerated EGFR trafficking and slowed cell spreading. An ASAP1 mutant lacking the BAR domain had no effect. The N-terminal BAR domain of ASAP1 mediates membrane bending and is necessary for ASAP1 function. The Arf dependence of the bending activity is consistent with ASAP1 functioning as an Arf effector.

Ectopic expression of UGT84A2 delayed flowering by indole-3-butyric acid-mediated transcriptional repression of ARF6 and ARF8 genes in Arabidopsis.

PubMed

Zhang, Gui-Zhi; Jin, Shang-Hui; Li, Pan; Jiang, Xiao-Yi; Li, Yan-Jie; Hou, Bing-Kai

2017-12-01

Ectopic expression of auxin glycosyltransferase UGT84A2 in Arabidopsis can delay flowering through increased indole-3-butyric acid and suppressed transcription of ARF6, ARF8 and flowering-related genes FT, SOC1, AP1 and LFY. Auxins are critical regulators for plant growth and developmental processes. Auxin homeostasis is thus an important issue for plant biology. Here, we identified an indole-3-butyric acid (IBA)-specific glycosyltransferase, UGT84A2, and characterized its role in Arabidopsis flowering development. UGT84A2 could catalyze the glycosylation of IBA, but not indole-3-acetic acid (IAA). UGT84A2 transcription expression was clearly induced by IBA. When ectopically expressing in Arabidopsis, UGT84A2 caused obvious delay in flowering. Correspondingly, the increase of IBA level, the down-regulation of AUXIN RESPONSE FACTOR 6 (ARF6) and ARF8, and the down-regulation of flowering-related genes such as FLOWERING LOCUS T (FT), SUPPRESSOR OF OVEREXPRESSION OF CO1(SOC1), APETALA1 (AP1), and LEAFY(LFY) were observed in transgenic plants. When exogenously applying IBA to wild-type plants, the late flowering phenotype, the down-regulation of ARF6, ARF8 and flowering-related genes recurred. We examined the arf6arf8 double mutants and found that the expression of flowering-related genes was also substantially decreased in these mutants. Together, our results suggest that glycosyltransferase UGT84A2 may be involved in flowering regulation through indole-3-butyric acid-mediated transcriptional repression of ARF6, ARF8 and downstream flowering pathway genes.

The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4.

PubMed

Isabet, Tatiana; Montagnac, Guillaume; Regazzoni, Karine; Raynal, Bertrand; El Khadali, Fatima; England, Patrick; Franco, Michel; Chavrier, Philippe; Houdusse, Anne; Ménétrey, Julie

2009-09-16

The JNK-interacting proteins, JIP3 and JIP4, are specific effectors of the small GTP-binding protein ARF6. The interaction of ARF6-GTP with the second leucine zipper (LZII) domains of JIP3/JIP4 regulates the binding of JIPs to kinesin-1 and dynactin. Here, we report the crystal structure of ARF6-GTP bound to the JIP4-LZII at 1.9 A resolution. The complex is a heterotetramer with dyad symmetry arranged in an ARF6-(JIP4)(2)-ARF6 configuration. Comparison of the ARF6-JIP4 interface with the equivalent region of ARF1 shows the structural basis of JIP4's specificity for ARF6. Using site-directed mutagenesis and surface plasmon resonance, we further show that non-conserved residues at the switch region borders are the key structural determinants of JIP4 specificity. A structure-derived model of the association of the ARF6-JIP3/JIP4 complex with membranes shows that the JIP4-LZII coiled-coil should lie along the membrane to prevent steric hindrances, resulting in only one ARF6 molecule bound. Such a heterotrimeric complex gives insights to better understand the ARF6-mediated motor switch regulatory function.

The yeast Arf-GAP Glo3p is required for the endocytic recycling of cell surface proteins.

PubMed

Kawada, Daiki; Kobayashi, Hiromu; Tomita, Tsuyoshi; Nakata, Eisuke; Nagano, Makoto; Siekhaus, Daria Elisabeth; Toshima, Junko Y; Toshima, Jiro

2015-01-01

Small GTP-binding proteins of the Ras superfamily play diverse roles in intracellular trafficking. Among them, the Rab, Arf, and Rho families function in successive steps of vesicle transport, in forming vesicles from donor membranes, directing vesicle trafficking toward target membranes and docking vesicles onto target membranes. These proteins act as molecular switches that are controlled by a cycle of GTP binding and hydrolysis regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). In this study we explored the role of GAPs in the regulation of the endocytic pathway using fluorescently labeled yeast mating pheromone α-factor. Among 25 non-essential GAP mutants, we found that deletion of the GLO3 gene, encoding Arf-GAP protein, caused defective internalization of fluorescently labeled α-factor. Quantitative analysis revealed that glo3Δ cells show defective α-factor binding to the cell surface. Interestingly, Ste2p, the α-factor receptor, was mis-localized from the plasma membrane to the vacuole in glo3Δ cells. Domain deletion mutants of Glo3p revealed that a GAP-independent function, as well as the GAP activity, of Glo3p is important for both α-factor binding and Ste2p localization at the cell surface. Additionally, we found that deletion of the GLO3 gene affects the size and number of Arf1p-residing Golgi compartments and causes a defect in transport from the TGN to the plasma membrane. Furthermore, we demonstrated that glo3Δ cells were defective in the late endosome-to-TGN transport pathway, but not in the early endosome-to-TGN transport pathway. These findings suggest novel roles for Arf-GAP Glo3p in endocytic recycling of cell surface proteins. Copyright © 2014 Elsevier B.V. All rights reserved.

Valproic acid-inducible Arl4D and cytohesin-2/ARNO, acting through the downstream Arf6, regulate neurite outgrowth in N1E-115 cells.

PubMed

Yamauchi, Junji; Miyamoto, Yuki; Torii, Tomohiro; Mizutani, Reiko; Nakamura, Kazuaki; Sanbe, Atsushi; Koide, Hiroshi; Kusakawa, Shinji; Tanoue, Akito

2009-07-15

The mood-stabilizing agent valproic acid (VPA) potently promotes neuronal differentiation. As yet, however, little is known about the underlying molecular mechanism. Here, we show that VPA upregulates cytohesin-2 and mediates neurite outgrowth in N1E-115 neuroblastoma cells. Cytohesin-2 is the guanine-nucleotide exchange factor (GEF) for small GTPases of the Arf family; it regulates many aspects of cellular functions including morphological changes. Treatment with the specific cytohesin family inhibitor SecinH3 or knockdown of cytohesin-2 with its siRNA results in blunted induction of neurite outgrowth in N1E-115 cells. The outgrowth is specifically inhibited by siRNA knockdown of Arf6, but not by that of Arf1. Furthermore, VPA upregulates Arl4D, an Arf-like small GTPase that has recently been identified as the regulator that binds to cytohesin-2. Arl4D knockdown displays an inhibitory effect on neurite outgrowth resulting from VPA, while expression of constitutively active Arl4D induces outgrowth. We also demonstrate that the addition of cell-permeable peptide, coupling the cytohesin-2-binding region of Arl4D into cells, reduces the effect of VPA. Thus, Arl4D is a previously unknown regulator of neurite formation through cytohesin-2 and Arf6, providing another example that the functional interaction of two different small GTPases controls an important cellular function.

Expression of a dominant allele of human ARF1 inhibits membrane traffic in vivo

PubMed Central

1994-01-01

ADP-ribosylation factor (ARF) proteins and inhibitory peptides derived from ARFs have demonstrated activities in a number of in vitro assays that measure ER-to-Golgi and intra-Golgi transport and endosome fusion. To better understand the roles of ARF proteins in vivo, stable cell lines were obtained from normal rat kidney (NRK) cells transfected with either wild-type or a dominant activating allele ([Q71L]) of the human ARF1 gene under the control of the interferon-inducible mouse Mx1 promoter. Upon addition of interferon, expression of ARF1 proteins increased with a half-time of 7-8 h, as determined by immunoblot analysis. Induction of mutant ARF1, but not wild-type ARF1, led to an inhibition of protein secretion with kinetics similar to that observed for induction of protein expression. Examination of the Golgi apparatus and the ER by indirect immunofluorescence or transmission electron microscopy revealed that expression of low levels of mutant ARF1 protein correlated with a dramatic increase in vesiculation of the Golgi apparatus and expansion of the ER lumen, while expression of substantially higher levels of wild-type ARF1 had no discernible effect. Endocytosis was also inhibited by expression of mutant ARF1, but not by the wild-type protein. Finally, the expression of [Q71L]ARF1, but not wild-type ARF1, antagonized the actions of brefeldin A, as determined by the delayed loss of ARF and beta-COP from Golgi membranes and disruption of the Golgi apparatus. General models for the actions of ARF1 in membrane traffic events are discussed. PMID:8294513

ARF tumor suppression in the nucleolus.

PubMed

Maggi, Leonard B; Winkeler, Crystal L; Miceli, Alexander P; Apicelli, Anthony J; Brady, Suzanne N; Kuchenreuther, Michael J; Weber, Jason D

2014-06-01

Since its discovery close to twenty years ago, the ARF tumor suppressor has played a pivotal role in the field of cancer biology. Elucidating ARF's basal physiological function in the cell has been the focal interest of numerous laboratories throughout the world for many years. Our current understanding of ARF is constantly evolving to include novel frameworks for conceptualizing the regulation of this critical tumor suppressor. As a result of this complexity, there is great need to broaden our understanding of the intricacies governing the biology of the ARF tumor suppressor. The ARF tumor suppressor is a key sensor of signals that instruct a cell to grow and proliferate and is appropriately localized in nucleoli to limit these processes. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease. Copyright © 2014 Elsevier B.V. All rights reserved.

ELMOD1 Stimulates ARF6-GTP Hydrolysis to Stabilize Apical Structures in Developing Vestibular Hair Cells.

PubMed

Krey, Jocelyn F; Dumont, Rachel A; Wilmarth, Philip A; David, Larry L; Johnson, Kenneth R; Barr-Gillespie, Peter G

2018-01-24

Sensory hair cells require control of physical properties of their apical plasma membranes for normal development and function. Members of the ADP-ribosylation factor (ARF) small GTPase family regulate membrane trafficking and cytoskeletal assembly in many cells. We identified ELMO domain-containing protein 1 (ELMOD1), a guanine nucleoside triphosphatase activating protein (GAP) for ARF6, as the most highly enriched ARF regulator in hair cells. To characterize ELMOD1 control of trafficking, we analyzed mice of both sexes from a strain lacking functional ELMOD1 [roundabout ( rda )]. In rda/rda mice, cuticular plates of utricle hair cells initially formed normally, then degenerated after postnatal day 5; large numbers of vesicles invaded the compromised cuticular plate. Hair bundles initially developed normally, but the cell's apical membrane lifted away from the cuticular plate, and stereocilia elongated and fused. Membrane trafficking in type I hair cells, measured by FM1-43 dye labeling, was altered in rda/rda mice. Consistent with the proposed GAP role for ELMOD1, the ARF6 GTP/GDP ratio was significantly elevated in rda/rda utricles compared with controls, and the level of ARF6-GTP was correlated with the severity of the rda/rda phenotype. These results suggest that conversion of ARF6 to its GDP-bound form is necessary for final stabilization of the hair bundle. SIGNIFICANCE STATEMENT Assembly of the mechanically sensitive hair bundle of sensory hair cells requires growth and reorganization of apical actin and membrane structures. Hair bundles and apical membranes in mice with mutations in the Elmod1 gene degenerate after formation, suggesting that the ELMOD1 protein stabilizes these structures. We show that ELMOD1 is a GTPase-activating protein in hair cells for the small GTP-binding protein ARF6, known to participate in actin assembly and membrane trafficking. We propose that conversion of ARF6 into the GDP-bound form in the apical domain of hair cells is

Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling.

PubMed

Pawar, Archana; Meier, Jeremy A; Dasgupta, Anwesha; Diwanji, Neha; Deshpande, Neha; Saxena, Kritika; Buwa, Natasha; Inchanalkar, Siddhi; Schwartz, Martin Alexander; Balasubramanian, Nagaraj

2016-09-01

Integrin dependent regulation of growth factor signalling confers anchorage dependence that is deregulated in cancers. Downstream of integrins and oncogenic Ras the small GTPase Ral is a vital mediator of adhesion dependent trafficking and signalling. This study identifies a novel regulatory crosstalk between Ral and Arf6 that controls Ral function in cells. In re-adherent mouse fibroblasts (MEFs) integrin dependent activation of RalA drives Arf6 activation. Independent of adhesion constitutively active RalA and RalB could both however activate Arf6. This is further conserved in oncogenic H-Ras containing bladder cancer T24 cells, which express anchorage independent active Ral that supports Arf6 activation. Arf6 mediates active Ral-exocyst dependent delivery of raft microdomains to the plasma membrane that supports anchorage independent growth signalling. Accordingly in T24 cells the RalB-Arf6 crosstalk is seen to preferentially regulate anchorage independent Erk signalling. Active Ral we further find uses a Ral-RalBP1-ARNO-Arf6 pathway to mediate Arf6 activation. This study hence identifies Arf6, through this regulatory crosstalk, to be a key downstream mediator of Ral isoform function along adhesion dependent pathways in normal and cancer cells. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Discrete Determinants in ArfGAP2/3 Conferring Golgi Localization and Regulation by the COPI Coat

PubMed Central

Kliouchnikov, Lena; Bigay, Joëlle; Mesmin, Bruno; Parnis, Anna; Rawet, Moran; Goldfeder, Noga; Antonny, Bruno

2009-01-01

From yeast to mammals, two types of GTPase-activating proteins, ArfGAP1 and ArfGAP2/3, control guanosine triphosphate (GTP) hydrolysis on the small G protein ADP-ribosylation factor (Arf) 1 at the Golgi apparatus. Although functionally interchangeable, they display little similarity outside the catalytic GTPase-activating protein (GAP) domain, suggesting differential regulation. ArfGAP1 is controlled by membrane curvature through its amphipathic lipid packing sensor motifs, whereas Golgi targeting of ArfGAP2 depends on coatomer, the building block of the COPI coat. Using a reporter fusion approach and in vitro assays, we identified several functional elements in ArfGAP2/3. We show that the Golgi localization of ArfGAP3 depends on both a central basic stretch and a carboxy-amphipathic motif. The basic stretch interacts directly with coatomer, which we found essential for the catalytic activity of ArfGAP3 on Arf1-GTP, whereas the carboxy-amphipathic motif interacts directly with lipid membranes but has minor role in the regulation of ArfGAP3 activity. Our findings indicate that the two types of ArfGAP proteins that reside at the Golgi use a different combination of protein–protein and protein–lipid interactions to promote GTP hydrolysis in Arf1-GTP. PMID:19109418

Molecular analysis of ARF1 expression profiles during development of physic nut (Jatropha curcas L.).

PubMed

Qin, Xiaobo; Lin, Fanrong; Lii, Yifan; Gou, Chunbao; Chen, Fang

2011-03-01

A cDNA clone designated arf1 was isolated from a physic nut (Jatropha curcas L.) endosperm cDNA library which encodes a small GTP-binding protein and has significant homology to ADP-ribosylation factors (ARF) in plants, animals and microbes. The cDNA contains an open reading frame that encodes a polypeptide of 181 amino acids with a calculated molecular mass of 20.7 kDa. The deduced amino acid sequence showed high homology to known ARFs from other organisms. The products of the arf1 obtained by overexpression in E. coli revealed the specific binding activity toward GTP. The expression of arf1 was observed in flowers, roots, stems and leaves as analyzed by RT-PCR, and its transcriptional level was highest in flowers. In particular, the accumulation of arf1 transcripts was different under various environmental stresses in seedlings. The results suggest that arf1 plays distinct physiological roles in Jatropha curcas cells.

Retrograde transport from the yeast Golgi is mediated by two ARF GAP proteins with overlapping function.

PubMed Central

Poon, P P; Cassel, D; Spang, A; Rotman, M; Pick, E; Singer, R A; Johnston, G C

1999-01-01

ARF proteins, which mediate vesicular transport, have little or no intrinsic GTPase activity. They rely on the actions of GTPase-activating proteins (GAPs) for their function. The in vitro GTPase activity of the Saccharomyces cerevisiae ARF proteins Arf1 and Arf2 is stimulated by the yeast Gcs1 protein, and in vivo genetic interactions between arf and gcs1 mutations implicate Gcs1 in vesicular transport. However, the Gcs1 protein is dispensable, indicating that additional ARF GAP proteins exist. We show that the structurally related protein Glo3, which is also dispensable, also exhibits ARF GAP activity. Genetic and in vitro approaches reveal that Glo3 and Gcs1 have an overlapping essential function at the endoplasmic reticulum (ER)-Golgi stage of vesicular transport. Mutant cells deficient for both ARF GAPs cannot proliferate, undergo a dramatic accumulation of ER and are defective for protein transport between ER and Golgi. The glo3Delta and gcs1Delta single mutations each interact with a sec21 mutation that affects a component of COPI, which mediates vesicular transport within the ER-Golgi shuttle, while increased dosage of the BET1, BOS1 and SEC22 genes encoding members of a v-SNARE family that functions within the ER-Golgi alleviates the effects of a glo3Delta mutation. An in vitro assay indicates that efficient retrieval from the Golgi to the ER requires these two proteins. These findings suggest that Glo3 and Gcs1 ARF GAPs mediate retrograde vesicular transport from the Golgi to the ER. PMID:9927415

Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning.

PubMed

Wesolowski, Jordan; Weber, Mary M; Nawrotek, Agata; Dooley, Cheryl A; Calderon, Mike; St Croix, Claudette M; Hackstadt, Ted; Cherfils, Jacqueline; Paumet, Fabienne

2017-05-02

The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion. IMPORTANCE Chlamydia trachomatis is an important cause of morbidity and a significant economic burden in the world. However, how Chlamydia develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered Chlamydia mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified

The small GTPase Arf6 regulates sea urchin morphogenesis

PubMed Central

Stepicheva, Nadezda A.; Dumas, Megan; Kobi, Priscilla; Donaldson, Julie G.; Song, Jia L.

2017-01-01

The small GTPase Arf6 is a conserved protein that is expressed in all metazoans. Arf6 remodels cytoskeletal actin and mediates membrane protein trafficking between the plasma membrane in its active form and endosomal compartments in its inactive form. While a rich knowledge exists for the cellular functions of Arf6, relatively little is known about its physiological role in development. This study examines the function of Arf6 in mediating cellular morphogenesis in early development. We dissect the function of Arf6 with a loss-of-function morpholino and constitutively active Arf6-Q67L construct. We focus on the two cell types that undergo active directed migration: the primary mesenchyme cells (PMCs) that give rise to the sea urchin skeleton and endodermal cells that form the gut. Our results indicate that Arf6 plays an important role in skeleton formation and PMC migration, in part due to its ability to remodel actin. We also found that embryos injected with Arf6 morpholino have gastrulation defects and embryos injected with constitutively active Arf6 have endodermal cells detached from the gut epithelium with decreased junctional cadherin staining, indicating that Arf6 may mediate the recycling of cadherin. Thus, Arf6 impacts cells that undergo coordinated movement to form embryonic structures in the developing embryo. PMID:28188999

The involvement of InMIR167 in the regulation of expression of its target gene InARF8, and their participation in the vegetative and generative development of Ipomoea nil plants.

PubMed

Glazińska, Paulina; Wojciechowski, Waldemar; Wilmowicz, Emilia; Zienkiewicz, Agnieszka; Frankowski, Kamil; Kopcewicz, Jan

2014-02-15

The plant hormone auxin plays a critical role in regulating plant growth and development. Recent advances have been made that having improved our understanding of auxin response pathways, primarily by characterizing the genes encoding auxin response factors (ARFs) in Arabidopsis. In addition, the expression of some ARFs is regulated by microRNAs (miRNAs). In Arabidopsis thaliana, ARF6 and ARF8 are targeted by miR167, whereas ARF10, ARF16 and ARF17 are targeted by miR160. Nevertheless, little is known about any possible interactions between miRNAs and the auxin signaling pathway during plant development. In this study, we isolated the miR167 target gene InARF8 cDNA from the cotyledons of the short day plant (SDP) Ipomoea nil (named also Pharbitis nil). Additionally, the In-miR167 precursor was identified from the I. nil EST database and analyses of InARF8 mRNA, In-pre-miR167 and mature miR167 accumulation in the plant's vegetative and generative organs were performed. The identified cDNA of InARF8 contains a miR167 complementary sequence and shows significant similarity to ARF8 cDNAs of other plant species. The predicted amino acid sequence of InARF8 includes all of the characteristic domains for ARF family transcription factors (B3 DNA-binding domain, AUX/IAA-CTD and a glutamine-rich region). Quantitative RT-PCR reactions and in situ hybridization indicated that InARF8 was expressed primarily in the shoot apices, leaf primordia and hypocotyls of I. nil seedlings, as well as in flower pistils and petals. The InARF8 transcript level increased consistently during the entire period of pistil development, whereas in the stamens, the greatest transcriptional activity occurred only during the intensive elongation phase. Additionally, an expression analysis of both the precursor In-pre-miR167 molecules identified and mature miRNA was performed. We observed that, in most of the organs examined, the InARF8 expression pattern was opposite to that of MIR167, indicating that

Vesicular transport protein Arf6 modulates cytoskeleton dynamics for polar body extrusion in mouse oocyte meiosis.

PubMed

Duan, Xing; Zhang, Hao-Lin; Pan, Meng-Hao; Zhang, Yu; Sun, Shao-Chen

2018-02-01

Arf6 (ADP-ribosylation factor 6) is known to play important roles in membrane dynamics through the regulation of actin filament reorganization for multiple cellular processes such as cytokinesis, phagocytosis, cell migration and tumor cell invasion. However, the functions of Arf6 in mammalian oocyte meiosis have not been clarified. In present study we showed that Arf6 expressed in mouse oocytes and was mainly distributed around the spindle during meiosis. Depletion of Arf6 by morpholino microinjection caused oocytes failing to extrude first polar body. Further analysis indicated that Arf6 knock down caused the aberrant actin distribution, which further induced the failure of meiotic spindle movement. And the loss of oocyte polarity also confirmed this. The regulation of Arf6 on actin filaments in mouse oocytes might be due to its effects on the phosphorylation level of cofilin and the expression of Arp2/3 complex. Moreover, we found that the decrease of Arf6 caused the disruption of spindle formation, indicating the multiple roles of Arf6 on cytoskeleton dynamics in meiosis. In summary, our results indicated that Arf6 was involved in mouse oocyte meiosis through its functional roles in actin-mediated spindle movement and spindle organization. Copyright © 2017 Elsevier B.V. All rights reserved.

Kinetics of Interaction between ADP-ribosylation Factor-1 (Arf1) and the Sec7 Domain of Arno Guanine Nucleotide Exchange Factor, Modulation by Allosteric Factors, and the Uncompetitive Inhibitor Brefeldin A

PubMed Central

Rouhana, Jad; Padilla, André; Estaran, Sébastien; Bakari, Sana; Delbecq, Stephan; Boublik, Yvan; Chopineau, Joel; Pugnière, Martine; Chavanieu, Alain

2013-01-01

The GDP/GTP nucleotide exchange of Arf1 is catalyzed by nucleotide exchange factors (GEF), such as Arno, which act through their catalytic Sec7 domain. This exchange is a complex mechanism that undergoes conformational changes and intermediate complex species involving several allosteric partners such as nucleotides, Mg2+, and Sec7 domains. Using a surface plasmon resonance approach, we characterized the kinetic binding parameters for various intermediate complexes. We first confirmed that both GDP and GTP counteract equivalently to the free-nucleotide binary Arf1-Arno complex stability and revealed that Mg2+ potentiates by a factor of 2 the allosteric effect of GDP. Then we explored the uncompetitive inhibitory mechanism of brefeldin A (BFA) that conducts to an abortive pentameric Arf1-Mg2+-GDP-BFA-Sec7 complex. With BFA, the association rate of the abortive complex is drastically reduced by a factor of 42, and by contrast, the 15-fold decrease of the dissociation rate concurs to stabilize the pentameric complex. These specific kinetic signatures have allowed distinguishing the level and nature as well as the fate in real time of formed complexes according to experimental conditions. Thus, we showed that in the presence of GDP, the BFA-resistant Sec7 domain of Arno can also associate to form a pentameric complex, which suggests that the uncompetitive inhibition by BFA and the nucleotide allosteric effect combine to stabilize such abortive complex. PMID:23255605

Pathogenesis of persistent hyperplastic primary vitreous in mice lacking the arf tumor suppressor gene.

PubMed

Martin, Amy C; Thornton, J Derek; Liu, Jiewiu; Wang, XiaoFei; Zuo, Jian; Jablonski, Monica M; Chaum, Edward; Zindy, Frederique; Skapek, Stephen X

2004-10-01

Persistent hyperplastic primary vitreous (PHPV) is an idiopathic developmental eye disease associated with failed involution of the hyaloid vasculature. The present work addressed the pathogenesis of PHPV in a mouse model that replicates many aspects of the human disease. Ophthalmoscopic and histologic analyses documented pathologic processes in eyes of mice lacking the Arf gene compared with Ink4a-deficient and wild-type control animals. Immunohistochemical staining, in situ hybridization, and RT-PCR demonstrated the expression of relevant gene products. Arf gene expression was determined by in situ hybridization using wholemounts of wild-type mouse eyes and by immunofluorescence staining for green fluorescent protein (GFP) in Arf(+/GFP) heterozygous knock-in mouse eyes. Abnormalities in Arf(-/-) mice mimicked those found in patients with severe PHPV. The mice had microphthalmia; fibrovascular, retrolental tissue containing retinal pigment epithelial cells and remnants of the hyaloid vascular system; posterior lens capsule destruction with lens degeneration and opacity; and severe retinal dysplasia and detachment. Eyes of mice lacking the overlapping Ink4a gene were normal. Arf was selectively expressed in perivascular cells within the vitreous of the postnatal eye. Cells composing the retrolental mass in Arf(-/-) mice expressed the Arf promoter. The remnant hyaloid vessels expressed Flk-1. Its ligand, vascular endothelial growth factor (Vegf), was expressed in the retrolental tissue and the adjacent dysplastic neuroretina. Arf(-/-) mice have features that accurately mimic severe PHPV. In the HVS, Arf expression in perivascular cells may block their accumulation or repress Vegf expression to promote HVS involution and prevent PHPV.

Expression of ADP-ribosylation factor (ARF)-like protein 6 during mouse embryonic development.

PubMed

Takada, Tatsuyuki; Iida, Keiko; Sasaki, Hiroshi; Taira, Masanori; Kimura, Hiroshi

2005-01-01

ADP-ribosylation factor (ARF)-like protein 6 (ARL6) is a member of the ARF-like protein (ARL) subfamily of small GTPases (Moss, 1995; Chavrier, 1999). ARLs are highly conserved through evolution and most of them possess the consensus sequence required for GTP binding and hydrolysis (Pasquallato, 2002). Among ARLs, ARL6 which was initially isolated from a J2E erythroleukemic cell line is divergent in its consensus sequences and its expression has been shown to be limited to the brain and kidney in adult mouse (Ingley, 1999). Recently, it was reported that mutations of the ARL6 gene cause type 3 Bardet-Biedl syndrome in humans and that ARL6 is involved in ciliary transport in C. elegans (Chiang, 2004; Fan, 2004). Here, we investigated the expression pattern of ARL6 during early mouse development by whole-mount in situ hybridization and found that interestingly, ARL6 mRNA was localized around the node at 7.0-7.5 days post coitum (dpc) embryos, while weak expression was also found in the ectoderm. At the later stage (8.5 dpc) ARL6 was expressed in the neural plate and probably in the somites. Based on these results, a possible role of ARL6 in early development is discussed in relation to the findings in human and C. elegans (Chiang, 2004; Fan, 2004).

ArfB links protein lipidation and endocytosis to polarized growth of Aspergillus nidulans

PubMed Central

Lee, Soo Chan

2008-01-01

Aspergillus nidulans undergoes polarized hyphal growth during the majority of its life cycle. Regulatory mechanisms for hyphal polarity have been intensively investigated in a variety of filamentous fungi. Two important cellular processes, which have received recent attention, include protein myristoylation and endocytosis. It is clear that protein myristoylation is essential for polarity establishment because germinating A. nidulans conidia lost polarity in the presence of cerulenin, a lipid metabolism inhibitor and in an N-myristoyl transferase mutant background. Only 41 predicted proteins encoded by A. nidulans posses an N-myristoylation motif, one of which is ADP ribosylation factor B (ArfB). Disruption of ArfB leads to failure of polarity establishment and maintenance during early morphogenesis and in a delay in endocytosis. Therefore, ArfB connects N-myristoylation and endocytosis to polarized growth. Exocytotic vesicle trafficking through the Spitzenkörper may also require Arf proteins in their role in vesicle formation. Taken together, ArfB is one of the important key components for the fungal hyphal growth. PMID:19704790

Arf6 controls platelet spreading and clot retraction via integrin αIIbβ3 trafficking

PubMed Central

Huang, Yunjie; Joshi, Smita; Xiang, Binggang; Kanaho, Yasunori; Li, Zhenyu; Bouchard, Beth A.; Moncman, Carole L.

2016-01-01

Platelet and megakaryocyte endocytosis is important for loading certain granule cargo (ie, fibrinogen [Fg] and vascular endothelial growth factor); however, the mechanisms of platelet endocytosis and its functional acute effects are understudied. Adenosine 5'-diphosphate–ribosylation factor 6 (Arf6) is a small guanosine triphosphate–binding protein that regulates endocytic trafficking, especially of integrins. To study platelet endocytosis, we generated platelet-specific Arf6 knockout (KO) mice. Arf6 KO platelets had less associated Fg suggesting that Arf6 affects αIIbβ3-mediated Fg uptake and/or storage. Other cargo was unaffected. To measure Fg uptake, mice were injected with biotinylated- or fluorescein isothiocyanate (FITC)–labeled Fg. Platelets from the injected Arf6 KO mice showed lower accumulation of tagged Fg, suggesting an uptake defect. Ex vivo, Arf6 KO platelets were also defective in FITC-Fg uptake and storage. Immunofluorescence analysis showed initial trafficking of FITC-Fg to a Rab4-positive compartment followed by colocalization with Rab11-positive structures, suggesting that platelets contain and use both early and recycling endosomes. Resting and activated αIIbβ3 levels, as measured by flow cytometry, were unchanged; yet, Arf6 KO platelets exhibited enhanced spreading on Fg and faster clot retraction. This was not the result of alterations in αIIbβ3 signaling, because myosin light-chain phosphorylation and Rac1/RhoA activation were unaffected. Consistent with the enhanced clot retraction and spreading, Arf6 KO mice showed no deficits in tail bleeding or FeCl3-induced carotid injury assays. Our studies present the first mouse model for defining the functions of platelet endocytosis and suggest that altered integrin trafficking may affect the efficacy of platelet function. PMID:26738539

Arf6 controls platelet spreading and clot retraction via integrin αIIbβ3 trafficking.

PubMed

Huang, Yunjie; Joshi, Smita; Xiang, Binggang; Kanaho, Yasunori; Li, Zhenyu; Bouchard, Beth A; Moncman, Carole L; Whiteheart, Sidney W

2016-03-17

Platelet and megakaryocyte endocytosis is important for loading certain granule cargo (ie, fibrinogen [Fg] and vascular endothelial growth factor); however, the mechanisms of platelet endocytosis and its functional acute effects are understudied. Adenosine 5'-diphosphate-ribosylation factor 6 (Arf6) is a small guanosine triphosphate-binding protein that regulates endocytic trafficking, especially of integrins. To study platelet endocytosis, we generated platelet-specific Arf6 knockout (KO) mice. Arf6 KO platelets had less associated Fg suggesting that Arf6 affects αIIbβ3-mediated Fg uptake and/or storage. Other cargo was unaffected. To measure Fg uptake, mice were injected with biotinylated- or fluorescein isothiocyanate (FITC)-labeled Fg. Platelets from the injected Arf6 KO mice showed lower accumulation of tagged Fg, suggesting an uptake defect. Ex vivo, Arf6 KO platelets were also defective in FITC-Fg uptake and storage. Immunofluorescence analysis showed initial trafficking of FITC-Fg to a Rab4-positive compartment followed by colocalization with Rab11-positive structures, suggesting that platelets contain and use both early and recycling endosomes. Resting and activated αIIbβ3 levels, as measured by flow cytometry, were unchanged; yet, Arf6 KO platelets exhibited enhanced spreading on Fg and faster clot retraction. This was not the result of alterations in αIIbβ3 signaling, because myosin light-chain phosphorylation and Rac1/RhoA activation were unaffected. Consistent with the enhanced clot retraction and spreading, Arf6 KO mice showed no deficits in tail bleeding or FeCl3-induced carotid injury assays. Our studies present the first mouse model for defining the functions of platelet endocytosis and suggest that altered integrin trafficking may affect the efficacy of platelet function. © 2016 by The American Society of Hematology.

Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion

PubMed Central

Rennoll-Bankert, Kristen E.; Rahman, M. Sayeedur; Gillespie, Joseph J.; Guillotte, Mark L.; Kaur, Simran J.; Lehman, Stephanie S.; Beier-Sexton, Magda; Azad, Abdu F.

2015-01-01

Bacterial Sec7-domain-containing proteins (RalF) are known only from species of Legionella and Rickettsia, which have facultative and obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS) effector, is a guanine nucleotide exchange factor (GEF) of ADP-ribosylation factors (Arfs), activating and recruiting host Arf1 to the Legionella-containing vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus Group) RalF is a functional Arf-GEF that localizes to the host plasma membrane and interacts with the actin cytoskeleton via a unique C-terminal domain. As RalF is differentially encoded across Rickettsia species (e.g., pseudogenized in all Spotted Fever Group species), it may function in lineage-specific biology and pathogenicity. Herein, we demonstrate RalF of R. typhi (Typhus Group) interacts with the Rickettsia T4SS coupling protein (RvhD4) via its proximal C-terminal sequence. RalF is expressed early during infection, with its inactivation via antibody blocking significantly reducing R. typhi host cell invasion. For R. typhi and R. felis (Transitional Group), RalF ectopic expression revealed subcellular localization with the host plasma membrane and actin cytoskeleton. Remarkably, R. bellii (Ancestral Group) RalF showed perinuclear localization reminiscent of ectopically expressed Legionella RalF, for which it shares several structural features. For R. typhi, RalF co-localization with Arf6 and PI(4,5)P2 at entry foci on the host plasma membrane was determined to be critical for invasion. Thus, we propose recruitment of PI(4,5)P2 at entry foci, mediated by RalF activation of Arf6, initiates actin remodeling and ultimately facilitates bacterial invasion. Collectively, our characterization of RalF as an invasin suggests that, despite carrying a similar Arf-GEF unknown from other bacteria, different intracellular lifestyles across Rickettsia and Legionella species have driven divergent roles for Ral

Arf Suppresses Hepatic Vascular Neoplasia in a Carcinogen-Exposed Murine Model

PubMed Central

Busch, Stephanie E; Gurley, Kay E; Moser, Russell D; Kemp, Christopher J

2013-01-01

Hepatic haemangiosarcoma is a deadly malignancy whose aetiology remains poorly understood. Inactivation of the CDKN2A locus, which houses the ARF and p16INK4a tumour suppressor genes, is a common event in haemangiosarcoma patients, but the precise role of ARF in vascular tumourigenesis is unknown. To determine the extent to which ARF suppresses vascular neoplasia, we examined the incidence of hepatic vascular lesions in Arf-deficient mice exposed to the carcinogen urethane (i.p. 1 mg/g). Loss of Arf resulted in elevated morbidity and increased the incidence of both haemangiomas and incipient haemangiosarcomas. Suppression of vascular lesion development by ARF was heavily dependent on both Arf gene-dosage and the genetic strain of the mouse. Trp53-deficient mice also developed hepatic vascular lesions after exposure to urethane, suggesting that ARF signals through a p53-dependent pathway to inhibit the development of hepatic haemangiosarcoma. Our findings provide strong evidence that inactivation of Arf is a causative event in vascular neoplasia and suggest that the ARF pathway may be a novel molecular target for therapeutic intervention in haemangiosarcoma patients. PMID:22430984

GLTSCR2 promotes the nucleoplasmic translocation and subsequent degradation of nucleolar ARF.

PubMed

Lee, Sun; Cho, Young-Eun; Kim, Sang-Hoon; Kim, Yong-Jun; Park, Jae-Hoon

2017-03-07

The alternative reading frame protein (p14ARF/ARF) is a key determinant of cell fate, acting as a potent tumor suppressor through a p53/MDM2-dependent pathway or promoting apoptosis in a p53-independent manner. The ARF protein is mainly expressed in the nucleolus and sequestered by nucleophosmin (NPM), whereas ARF-binding proteins, including p53 and MDM2, predominantly reside in the nucleoplasm. This raises the question of how nucleolar ARF binds nucleoplasmic signaling proteins to suppress tumor growth or inhibit cell cycle progression. GLTSCR2 (also known as PICT-1) is a nucleolar protein involved in both tumor suppression and oncogenesis in concert with p53, NPM, and/or MYC. Here, we show that GLTSCR2 increases nucleoplasmic ARF translocation and its degradation. Specifically, GLTSCR2 bound to ARF, and GLTSCR2-ARF complexes were released to the nucleoplasm, where GLTSCR2 increased the binding affinity of ARF for ULF/TRIP12 (a nucleoplasmic E3-ubiquitin ligase of ARF) and enhanced ARF degradation through the polyubiquitination pathway. Our results demonstrate that nucleolar/nucleoplasmic GLTSCR2 is a strong candidate for promoting the subcellular localization and protein stability of ARF.

Machineries regulating the activity of the small GTPase Arf6 in cancer cells are potential targets for developing innovative anti-cancer drugs.

PubMed

Yamauchi, Yohei; Miura, Yuki; Kanaho, Yasunori

2017-01-01

The Small GTPase ADP-ribosylation factor 6 (Arf6) functions as the molecular switch in cellular signaling pathways by cycling between GDP-bound inactive and GTP-bound active form, which is precisely regulated by two regulators, guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Numerous studies have shown that these machineries play critical roles in tumor angiogenesis/growth and cancer cell invasion/metastasis through regulating the cycling of Arf6. Here, we summarize accumulating knowledge for involvement of Arf6 GEFs/GAPs and small molecule inhibitors of Arf6 signaling/cycling in cancer progression, and discuss possible strategies for developing innovative anti-cancer drugs targeting Arf6 signaling/cycling. Copyright © 2016 Elsevier Ltd. All rights reserved.

HIV-1 requires Arf6-mediated membrane dynamics to efficiently enter and infect T lymphocytes

PubMed Central

García-Expósito, Laura; Barroso-González, Jonathan; Puigdomènech, Isabel; Machado, José-David; Blanco, Julià; Valenzuela-Fernández, Agustín

2011-01-01

As the initial barrier to viral entry, the plasma membrane along with the membrane trafficking machinery and cytoskeleton are of fundamental importance in the viral cycle. However, little is known about the contribution of plasma membrane dynamics during early human immunodeficiency virus type 1 (HIV-1) infection. Considering that ADP ribosylation factor 6 (Arf6) regulates cellular invasion via several microorganisms by coordinating membrane trafficking, our aim was to study the function of Arf6-mediated membrane dynamics on HIV-1 entry and infection of T lymphocytes. We observed that an alteration of the Arf6–guanosine 5′-diphosphate/guanosine 5′-triphosphate (GTP/GDP) cycle, by GDP-bound or GTP-bound inactive mutants or by specific Arf6 silencing, inhibited HIV-1 envelope–induced membrane fusion, entry, and infection of T lymphocytes and permissive cells, regardless of viral tropism. Furthermore, cell-to-cell HIV-1 transmission of primary human CD4+ T lymphocytes was inhibited by Arf6 knockdown. Total internal reflection fluorescence microscopy showed that Arf6 mutants provoked the accumulation of phosphatidylinositol-(4,5)-biphosphate–associated structures on the plasma membrane of permissive cells, without affecting CD4-viral attachment but impeding CD4-dependent HIV-1 entry. Arf6 silencing or its mutants did not affect fusion, entry, and infection of vesicular stomatitis virus G–pseudotyped viruses or ligand-induced CXCR4 or CCR5 endocytosis, both clathrin-dependent processes. Therefore we propose that efficient early HIV-1 infection of CD4+ T lymphocytes requires Arf6-coordinated plasma membrane dynamics that promote viral fusion and entry. PMID:21346189

Over-expression of mango (Mangifera indica L.) MiARF2 inhibits root and hypocotyl growth of Arabidopsis.

PubMed

Wu, Bei; Li, Yun-He; Wu, Jian-Yong; Chen, Qi-Zhu; Huang, Xia; Chen, Yun-Feng; Huang, Xue-Lin

2011-06-01

An auxin response factor 2 gene, MiARF2, was cloned in our previous study [1] from the cotyledon section of mango (Mangifera indica L. cv. Zihua) during adventitious root formation, which shares an 84% amino acid sequence similarity to Arabidopsis ARF2. This study was to examine the effects of over-expression of the full-length MiARF2 open reading frame on the root and hypocotyl growth in Arabidopsis. Phenotype analysis showed that the T(3) transgenic lines had about 20-30% reduction in the length of hypocotyls and roots of the seedlings in comparison with the wild-type. The transcription levels of ANT and ARGOS genes which play a role in controlling organ size and cell proliferation in the transgenic seedlings also decreased. Therefore, the inhibited root and hypocotyl growth in the transgenic seedlings may be associated with the down-regulated transcription of ANT and ARGOS by the over-expression of MiARF2. This study also suggests that although MiARF2 only has a single DNA-binding domain (DBD), it can function as other ARF-like proteins containing complete DBD, middle region (MR) and carboxy-terminal dimerization domain (CTD).

Persistent hyperplastic primary vitreous due to somatic mosaic deletion of the arf tumor suppressor.

PubMed

Thornton, J Derek; Swanson, Doug J; Mary, Michelle N; Pei, Deqing; Martin, Amy C; Pounds, Stanley; Goldowitz, Dan; Skapek, Stephen X

2007-02-01

Mice lacking the Arf tumor-suppressor gene develop eye disease reminiscent of persistent hyperplastic primary vitreous (PHPV). The current work explores mechanisms by which Arf promotes eye development, and its absence causes a PHPV-like disease. Chimeric mice were made by fusing wild-type and Arf(-/-) morulae. In these experiments, wild-type cells are identified by transgenic expression of GFP from a constitutive promoter. PCR-based genotyping and quantitative analyses after immunofluorescence staining of tissue and cultured cells documented the relative contribution of wild-type and Arf(-/-) cells to different tissues in the eye and different types of cells in the vitreous. The contributions of the Arf(-/-) lineage to the tail DNA, cornea, retina, and retina pigment epithelium (RPE) correlated with each other in wild-type<-->Arf(-/-) chimeric mice. Newborn chimeras had primary vitreous hyperplasia, evident as a retrolental mass. The mass was usually present when the proportion of Arf(-/-) cells was relatively high and absent when the Arf(-/-) proportion was low. The Pdgfrbeta- and Sma-expressing cells within the mass arose predominantly from the Arf(-/-) population. Ectopic Arf expression induced smooth muscle proteins in cultured pericyte-like cells, and Arf and Sma expression overlapped in hyaloid vessels. In the mouse model, loss of Arf in only a subset of cells causes a PHPV-like disease. The data indicate that both cell autonomous and non-cell autonomous effects of Arf may contribute to its role in vitreous development.

Arf6 regulates EGF-induced internalization of E-cadherin in breast cancer cells.

PubMed

Xu, Rui; Zhang, Yujie; Gu, Luo; Zheng, Jianchao; Cui, Jie; Dong, Jing; Du, Jun

2015-01-01

E-cadherin internalization facilitates dissolution of adherens junctions and promotes tumor cell epithelial-mesenchymal transition (EMT) and migration. Our previous results have shown that Arf6 exerts pro-migratory action in breast cancer cells after EGF stimulation. Despite the fact that EGF signaling stimulates EMT of breast cancer cells, the effect of Arf6 on internalization of E-cadherin of breast cancer cells under EGF treatment remains to be determined. Here, we showed that EGF dose-dependently stimulated E-cadherin internalization by MCF-7 cells with the maximal effect at 50 ng/ml. Meanwhile, EGF treatment markedly increased Arf6 activation. Arf6 was involved in complexes of E-cadherin, and more E-cadherin was pulled down with Arf6 when the activity of the latter was increased. Immunoblotting and immunofluorescence assays showed that transfection breast cancer cells with Arf6-T27N or Arf6 siRNA suppressed EGF-induced E-cadherin internalization. Taken together, our study demonstrated that Arf6 activation plays a potential role in EGF-induced E-cadherin internalization, providing new mechanism underlying the effect of Arf6 on promoting breast cancer cell metastasis.

IGFBP2 is a candidate biomarker for Ink4a-Arf status and a therapeutic target for high-grade gliomas.

PubMed

Moore, Lynette M; Holmes, Kristen M; Smith, Sarah M; Wu, Ying; Tchougounova, Elena; Uhrbom, Lene; Sawaya, Raymond; Bruner, Janet M; Fuller, Gregory N; Zhang, Wei

2009-09-29

The levels of insulin-like growth factor-binding protein 2 (IGFBP2) are elevated during progression of many human cancers. By using a glial-specific transgenic mouse system (RCAS/Ntv-a), we reported previously that IGFBP2 is an oncogenic factor for glioma progression in combination with platelet-derived growth factor-beta (PDGFB). Because the INK4a-ARF locus is often deleted in high-grade gliomas (anaplastic oligodendroglioma and glioblastoma), we investigated the effect of the Ink4a-Arf-null background on IGFBP2-mediated progression of PDGFB-initiated oligodendroglioma. We demonstrate here that homozygous deletion of Ink4a-Arf bypasses the requirement of exogenously introduced IGFBP2 for glioma progression. Instead, absence of Ink4a-Arf resulted in elevated endogenous tumor cell IGFBP2. An inverse relationship between p16(INK4a) and IGFBP2 expression was also observed in human glioma tissue samples and in 90 different cancer cell lines by using Western blotting and reverse-phase protein lysate arrays. When endogenous IGFBP2 expression was attenuated by an RCAS vector expressing antisense IGFBP2 in our mouse model, a decreased incidence of anaplastic oligodendroglioma as well as prolonged survival was observed. Thus, p16(INK4a) is a negative regulator of the IGFBP2 oncogene. Loss of Ink4a-Arf results in increased IGFBP2, which contributes to glioma progression, thereby implicating IGFBP2 as a marker and potential therapeutic target for Ink4a-Arf-deleted gliomas.

IGFBP2 is a candidate biomarker for Ink4a-Arf status and a therapeutic target for high-grade gliomas

PubMed Central

Moore, Lynette M.; Holmes, Kristen M.; Smith, Sarah M.; Wu, Ying; Tchougounova, Elena; Uhrbom, Lene; Sawaya, Raymond; Bruner, Janet M.; Fuller, Gregory N.; Zhang, Wei

2009-01-01

The levels of insulin-like growth factor-binding protein 2 (IGFBP2) are elevated during progression of many human cancers. By using a glial-specific transgenic mouse system (RCAS/Ntv-a), we reported previously that IGFBP2 is an oncogenic factor for glioma progression in combination with platelet-derived growth factor-β (PDGFB). Because the INK4a-ARF locus is often deleted in high-grade gliomas (anaplastic oligodendroglioma and glioblastoma), we investigated the effect of the Ink4a-Arf-null background on IGFBP2-mediated progression of PDGFB-initiated oligodendroglioma. We demonstrate here that homozygous deletion of Ink4a-Arf bypasses the requirement of exogenously introduced IGFBP2 for glioma progression. Instead, absence of Ink4a-Arf resulted in elevated endogenous tumor cell IGFBP2. An inverse relationship between p16INK4a and IGFBP2 expression was also observed in human glioma tissue samples and in 90 different cancer cell lines by using Western blotting and reverse-phase protein lysate arrays. When endogenous IGFBP2 expression was attenuated by an RCAS vector expressing antisense IGFBP2 in our mouse model, a decreased incidence of anaplastic oligodendroglioma as well as prolonged survival was observed. Thus, p16INK4a is a negative regulator of the IGFBP2 oncogene. Loss of Ink4a-Arf results in increased IGFBP2, which contributes to glioma progression, thereby implicating IGFBP2 as a marker and potential therapeutic target for Ink4a-Arf-deleted gliomas. PMID:19805356

ARF6 directs axon transport and traffic of integrins and regulates axon growth in adult DRG neurons.

PubMed

Eva, Richard; Crisp, Sarah; Marland, Jamie R K; Norman, Jim C; Kanamarlapudi, Venkateswarlu; ffrench-Constant, Charles; Fawcett, James W

2012-07-25

Integrins are involved in axon growth and regeneration. Manipulation of integrins is a route to promoting axon regeneration and understanding regeneration failure in the CNS. Expression of α9 integrin promotes axon regeneration, so we have investigated α9β1 trafficking and transport in axons and at the growth cone. We have previously found that α9 and β1 integrins traffic via Rab11-positive recycling endosomes in peripheral axons and growth cones. However, transport via Rab11 is slow, while rapid transport occurs in vesicles lacking Rab11. We have further studied α9 and β1 integrin transport and traffic in adult rat dorsal root ganglion axons and PC12 cells. Integrins are in ARF6 vesicles during rapid axonal transport and during trafficking in the growth cone. We report that rapid axonal transport of these integrins and their trafficking at the cell surface is regulated by ARF6. ARF6 inactivation by expression of ACAP1 leads to increased recycling of β1 integrins to the neuronal surface and to increased anterograde axonal transport. ARF6 activation by expression of the neuronal guanine nucleotide exchange factors, ARNO or EFA6, increases retrograde integrin transport in axons and increases integrin internalization. ARF6 inactivation increases integrin-mediated outgrowth, while activation decreases it. The coordinated changes in integrin transport and recycling resulting from ARF6 activation or inactivation are the probable mechanism behind this regulation of axon growth. Our data suggest a novel mechanism of integrin traffic and transport in peripheral axons, regulated by the activation state of ARF6, and suggest that ARF6 might be targeted to enhance integrin-dependent axon regeneration after injury.

Genetic Alterations of RDINK4/ARF Enhancer in Human Cancer Cells

PubMed Central

Li, Junan; Knobloch, Thomas J.; Poi, Ming J.; Zhang, Zhaoxia; Davis, Andrew T.; Muscarella, Peter; Weghorst, Christopher M.

2017-01-01

Recent identification of an enhancer element, RDINK4/ARF (RD), in the prominent INK4/ARF locus provides a novel mechanism to simultaneously regulate the transcription of p15INK4B (p15), p14ARF, and p16INK4A (p16) tumor suppressor genes. While genetic inactivation of p15, p14ARF, and p16 in human tumors has been extensively studied, little is known about genetic alterations of RD and its impact on p15, p14ARF, and p16 in human cancer. The purpose of this study was to investigate the potential existence of genetic alterations of RD in human cancer cells. DNAs extracted from 17 different cancer cell lines and 31 primary pheochromocytoma tumors were analyzed for deletion and mutation of RD using qPCR and direct DNA sequencing. We found that RD was deleted in human cancer cell lines and pheochromocytoma tumors at frequencies of 41.2% (7/17) and 13.0% (4/31), respectively. While some of these RD deletion events occurred along with deletions of the entire INK4/ARF locus, other RD deletion events were independent of genetic alterations in p15, p14ARF, and p16. Furthermore, the status of RD was poorly associated with the expression of p15, p14ARF, and p16 in tested cancer cell lines and tumors. This study demonstrates for the first time that deletion of the RD enhancer is a prevalent event in human cancer cells. Its implication in carcinogenesis remains to be further explored. PMID:23065809

Pathogenesis of Persistent Hyperplastic Primary Vitreous in Mice Lacking the Arf Tumor Suppressor Gene

PubMed Central

Martin, Amy C.; Thornton, J. Derek; Liu, Jiewiu; Wang, XiaoFei; Zuo, Jian; Jablonski, Monica M.; Chaum, Edward; Zindy, Frederique; Skapek, Stephen X.

2006-01-01

Purpose Persistent hyperplastic primary vitreous (PHPV) is an idiopathic developmental eye disease associated with failed involution of the hyaloid vasculature. The present work addressed the pathogenesis of PHPV in a mouse model that replicates many aspects of the human disease. Methods Ophthalmoscopic and histologic analyses documented pathologic processes in eyes of mice lacking the Arf gene compared with Ink4a-deficient and wild-type control animals. Immunohistochemical staining, in situ hybridization, and RT-PCR demonstrated the expression of relevant gene products. Arf gene expression was determined by in situ hybridization using wholemounts of wild-type mouse eyes and by immunofluorescence staining for green fluores-cent protein (GFP) in Arf+/GFP heterozygous knock-in mouse eyes. Results Abnormalities in Arf−/− mice mimicked those found in patients with severe PHPV. The mice had microphthalmia; fibrovascular, retrolental tissue containing retinal pigment epithelial cells and remnants of the hyaloid vascular system; posterior lens capsule destruction with lens degeneration and opacity; and severe retinal dysplasia and detachment. Eyes of mice lacking the overlapping Ink4a gene were normal. Arf was selectively expressed in perivascular cells within the vitreous of the postnatal eye. Cells composing the retrolental mass in Arf−/− mice expressed the Arf promoter. The remnant hyaloid vessels expressed Flk-1. Its ligand, vascular endothelial growth factor (Vegf), was expressed in the retrolental tissue and the adjacent dysplastic neuroretina. Conclusions Arf−/− mice have features that accurately mimic severe PHPV. In the HVS, Arf expression in perivascular cells may block their accumulation or repress Vegf expression to promote HVS involution and prevent PHPV. PMID:15452040

ARF6-dependent regulation of P2Y receptor traffic and function in human platelets.

PubMed

Kanamarlapudi, Venkateswarlu; Owens, Sian E; Saha, Keya; Pope, Robert J; Mundell, Stuart J

2012-01-01

Adenosine diphosphate (ADP) is a critical regulator of platelet activation, mediating its actions through two G protein-coupled receptors, the P2Y(1) and P2Y(12) purinoceptors. Recently, we demonstrated that P2Y(1) and P2Y(12) purinoceptor activities are rapidly and reversibly modulated in human platelets, revealing that the underlying mechanism requires receptor internalization and subsequent trafficking as an essential part of this process. In this study we investigated the role of the small GTP-binding protein ADP ribosylation factor 6 (ARF6) in the internalization and function of P2Y(1) and P2Y(12) purinoceptors in human platelets. ARF6 has been implicated in the internalization of a number of GPCRs, although its precise molecular mechanism in this process remains unclear. In this study we show that activation of either P2Y(1) or P2Y(12) purinoceptors can stimulate ARF6 activity. Further blockade of ARF6 function either in cell lines or human platelets blocks P2Y purinoceptor internalization. This blockade of receptor internalization attenuates receptor resensitization. Furthermore, we demonstrate that Nm23-H1, a nucleoside diphosphate (NDP) kinase regulated by ARF6 which facilitates dynamin-dependent fission of coated vesicles during endocytosis, is also required for P2Y purinoceptor internalization. These data describe a novel function of ARF6 in the internalization of P2Y purinoceptors and demonstrate the integral importance of this small GTPase upon platelet ADP receptor function.

Improved therapeutic effectiveness by combining recombinant p14(ARF) with antisense complementary DNA of EGFR in laryngeal squamous cell carcinoma.

PubMed

Liu, Feng; Du, JinTao; Xian, Junming; Liu, Yafeng; Liu, Shixi; Lin, Yan

2015-01-01

The tumor suppressor p14(ARF) and proto-oncogene epidermal growth factor receptor (EGFR) play important roles in the development of laryngeal squamous cell carcinoma (LSCC). This study was aimed to determine whether combining recombinant p14(ARF) with antisense complementary DNA of EGFR could improve the therapeutic effectiveness in LSCC. After human larynx cancer cells (Hep-2) were infected with recombinant adenoviruses (Ad-p14(ARF) and Ad-antisense EGFR) together or alone in vitro, the proliferation and cell cycle distribution of Hep-2 cells were detected by MTT assay and flow cytometer analysis, respectively. Furthermore, the antitumor effects of recombinant adenoviruses together or alone on Hep-2 xenografts were examined in vivo. The levels of p14(ARF) and EGFR expressed in Hep-2 cells and xenografts were determined by western blot assay. Ad-p14(ARF) combining with Ad-antisense EGFR markedly inhibited the Hep-2 proliferation compared with alone (P=0.001, P=0.002 respectively). Combination of Ad-p14(ARF) and Ad-antisense EGFR led to the proportion of Hep-2 cells in G0/G1 phases increased by up to 86.9%. The down-expression of EGFR protein and overexpression of p14(ARF) protein were observed in vitro and in vivo, and this effect was preserved when Ad-p14(ARF) was combined with Ad-antisense EGFR. Besides, Ad-p14(ARF) plus Ad-antisense EGFR significantly (P<0.05) increased the antitumor activity against Hep-2 tumor xenografts comparing with Ad-p14(ARF) or Ad-antisense EGFR alone. Combination Ad-p14(ARF) with Ad-antisense EGFR significantly increased the antitumor responses in LSCC. An effectively potential gene therapy to prevent proliferation of LSCC was provided. Copyright © 2015 Elsevier Inc. All rights reserved.

Role of ARF6 in internalization of metal-binding proteins, metallothionein and transferrin, and cadmium-metallothionein toxicity in kidney proximal tubule cells

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

Wolff, Natascha A.; Lee, Wing-Kee; Abouhamed, Marouan

2008-07-01

Filtered metal-protein complexes, such as cadmium-metallothionein-1 (CdMT-1) or transferrin (Tf) are apically endocytosed partly via megalin/cubilin by kidney proximal tubule (PT) cells where CdMT-1 internalization causes apoptosis. Small GTPase ARF (ADP-ribosylation factor) proteins regulate endocytosis and vesicular trafficking. We investigated roles of ARF6, which has been shown to be involved in internalization of ligands and endocytic trafficking in PT cells, following MT-1/CdMT-1 and Tf uptake by PT cells. WKPT-0293 Cl.2 cells derived from rat PT S1 segment were transfected with hemagglutinin-tagged wild-type (ARF6-WT) or dominant negative (ARF6-T27N) forms of ARF6. Using immunofluorescence, endogenous ARF6 was associated with the plasma membranemore » (PM) as well as juxtanuclear and co-localized with Rab5a and Rab11 involved in early and recycling endosomal trafficking. Immunofluorescence staining of megalin showed reduced surface labelling in ARF6 dominant negative (ARF6-DN) cells. Intracellular Alexa Fluor 546-conjugated MT-1 uptake was reduced in ARF6-DN cells and CdMT-1 (14.8 {mu}M for 24 h) toxicity was significantly attenuated from 27.3 {+-} 3.9% in ARF6-WT to 11.1 {+-} 4.0% in ARF6-DN cells (n = 6, P < 0.02). Moreover, reduced Alexa Fluor 546-conjugated Tf uptake was observed in ARF-DN cells (75.0 {+-} 4.6% versus 3.9 {+-} 3.9% of ARF6-WT cells, n = 3, P < 0.01) and/or remained near the PM (89.3 {+-} 5. 6% versus 45.2 {+-} 14.3% of ARF6-WT cells, n = 3, P < 0.05). In conclusion, the data support roles for ARF6 in receptor-mediated endocytosis and trafficking of MT-1/Tf to endosomes/lysosomes and CdMT-1 toxicity of PT cells.« less

Sec71 functions as a GEF for the small GTPase Arf1 to govern dendrite pruning of Drosophila sensory neurons.

PubMed

Wang, Yan; Zhang, Heng; Shi, Meng; Liou, Yih-Cherng; Lu, Lei; Yu, Fengwei

2017-05-15

Pruning, whereby neurons eliminate their excess neurites, is central for the maturation of the nervous system. In Drosophila , sensory neurons, ddaCs, selectively prune their larval dendrites without affecting their axons during metamorphosis. However, it is unknown whether the secretory pathway plays a role in dendrite pruning. Here, we show that the small GTPase Arf1, an important regulator of the secretory pathway, is specifically required for dendrite pruning of ddaC/D/E sensory neurons but dispensable for apoptosis of ddaF neurons. Analyses of the GTP- and GDP-locked forms of Arf1 indicate that the cycling of Arf1 between GDP-bound and GTP-bound forms is essential for dendrite pruning. We further identified Sec71 as a guanine nucleotide exchange factor for Arf1 that preferentially interacts with its GDP-bound form. Like Arf1, Sec71 is also important for dendrite pruning, but not for apoptosis, of sensory neurons. Arf1 and Sec71 are interdependent for their localizations on Golgi. Finally, we show that the Sec71/Arf1-mediated trafficking process is a prerequisite for Rab5-dependent endocytosis to facilitate endocytosis and degradation of the cell-adhesion molecule Neuroglian (Nrg). © 2017. Published by The Company of Biologists Ltd.

The Arf GAP CNT-2 regulates the apoptotic fate in C. elegans asymmetric neuroblast divisions.

PubMed

Singhvi, Aakanksha; Teuliere, Jerome; Talavera, Karla; Cordes, Shaun; Ou, Guangshuo; Vale, Ronald D; Prasad, Brinda C; Clark, Scott G; Garriga, Gian

2011-06-07

During development, all cells make the decision to live or die. Although the molecular mechanisms that execute the apoptotic program are well defined, less is known about how cells decide whether to live or die. In C. elegans, this decision is linked to how cells divide asymmetrically [1, 2]. Several classes of molecules are known to regulate asymmetric cell divisions in metazoans, yet these molecules do not appear to control C. elegans divisions that produce apoptotic cells [3]. We identified CNT-2, an Arf GTPase-activating protein (GAP) of the AGAP family, as a novel regulator of this type of neuroblast division. Loss of CNT-2 alters daughter cell size and causes the apoptotic cell to adopt the fate of its sister cell, resulting in extra neurons. CNT-2's Arf GAP activity is essential for its function in these divisions. The N terminus of CNT-2, which contains a GTPase-like domain that defines the AGAP class of Arf GAPs, negatively regulates CNT-2's function. We provide evidence that CNT-2 regulates receptor-mediated endocytosis and consider the implications of its role in asymmetric cell divisions. Copyright © 2011 Elsevier Ltd. All rights reserved.

The human ARF tumor suppressor senses blastema activity and suppresses epimorphic tissue regeneration

PubMed Central

Hesse, Robert G; Kouklis, Gayle K; Ahituv, Nadav; Pomerantz, Jason H

2015-01-01

The control of proliferation and differentiation by tumor suppressor genes suggests that evolution of divergent tumor suppressor repertoires could influence species’ regenerative capacity. To directly test that premise, we humanized the zebrafish p53 pathway by introducing regulatory and coding sequences of the human tumor suppressor ARF into the zebrafish genome. ARF was dormant during development, in uninjured adult fins, and during wound healing, but was highly expressed in the blastema during epimorphic fin regeneration after amputation. Regenerative, but not developmental signals resulted in binding of zebrafish E2f to the human ARF promoter and activated conserved ARF-dependent Tp53 functions. The context-dependent activation of ARF did not affect growth and development but inhibited regeneration, an unexpected distinct tumor suppressor response to regenerative versus developmental environments. The antagonistic pleiotropic characteristics of ARF as both tumor and regeneration suppressor imply that inducing epimorphic regeneration clinically would require modulation of ARF –p53 axis activation. DOI: http://dx.doi.org/10.7554/eLife.07702.001 PMID:26575287

ArF halftone PSM cleaning process optimization for next-generation lithography

NASA Astrophysics Data System (ADS)

Son, Yong-Seok; Jeong, Seong-Ho; Kim, Jeong-Bae; Kim, Hong-Seok

2000-07-01

ArF lithography which is expected for the next generation optical lithography is adapted for 0.13 micrometers design-rule and beyond. ArF half-tone phase shift mask (HT PSM) will be applied as 1st generation of ArF lithography. Also ArF PSM cleaning demands by means of tighter controls related to phase angle, transmittance and contamination on the masks. Phase angle on ArF HT PSM should be controlled within at least +/- 3 degree and transmittance controlled within at least +/- 3 percent after cleaning process and pelliclization. In the cleaning process of HT PSM, requires not only the remove the particle on mask, but also control to half-tone material for metamorphosis. Contamination defects on the Qz of half tone type PSM is not easy to remove on the photomask surface. New technology and methods of cleaning will be developed in near future, but we try to get out for limit contamination on the mask, without variation of phase angle and transmittance after cleaning process.

ADP-Ribosylation Factor 6 and a Functional PIX/p95-APP1 Complex Are Required for Rac1B-mediated Neurite Outgrowth

PubMed Central

Albertinazzi, Chiara; Za, Lorena; Paris, Simona; de Curtis, Ivan

2003-01-01

The mechanisms coordinating adhesion, actin organization, and membrane traffic during growth cone migration are poorly understood. Neuritogenesis and branching from retinal neurons are regulated by the Rac1B/Rac3 GTPase. We have identified a functional connection between ADP-ribosylation factor (Arf) 6 and p95-APP1 during the regulation of Rac1B-mediated neuritogenesis. P95-APP1 is an ADP-ribosylation factor GTPase-activating protein (ArfGAP) of the GIT family expressed in the developing nervous system. We show that Arf6 has a predominant role in neurite extension compared with Arf1 and Arf5. Cotransfection experiments indicate a specific and cooperative potentiation of neurite extension by Arf6 and the carboxy-terminal portion of p95-APP1. Localization studies in neurons expressing different p95-derived constructs show a codistribution of p95-APP1 with Arf6, but not Arf1. Moreover, p95-APP1–derived proteins with a mutated or deleted ArfGAP domain prevent Rac1B-induced neuritogenesis, leading to PIX-mediated accumulation at large Rab11-positive endocytic vesicles. Our data support a role of p95-APP1 as a specific regulator of Arf6 in the control of membrane trafficking during neuritogenesis. PMID:12686588

Poliovirus Proteins Induce Membrane Association of GTPase ADP-Ribosylation Factor

PubMed Central

Belov, George A.; Fogg, Mark H.; Ehrenfeld, Ellie

2005-01-01

Poliovirus infection results in the disintegration of intracellular membrane structures and formation of specific vesicles that serve as sites for replication of viral RNA. The mechanism of membrane rearrangement has not been clearly defined. Replication of poliovirus is sensitive to brefeldin A (BFA), a fungal metabolite known to prevent normal function of the ADP-ribosylation factor (ARF) family of small GTPases. During normal membrane trafficking in uninfected cells, ARFs are involved in vesicle formation from different intracellular sites through interaction with numerous regulatory and coat proteins as well as in regulation of phospholipase D activity and cytoskeleton modifications. We demonstrate here that ARFs 3 and 5, but not ARF6, are translocated to membranes in HeLa cell extracts that are engaged in translation of poliovirus RNA. The accumulation of ARFs on membranes correlates with active replication of poliovirus RNA in vitro, whereas ARF translocation to membranes does not occur in the presence of BFA. ARF translocation can be induced independently by synthesis of poliovirus 3A or 3CD proteins, and we describe mutations that abolished this activity. In infected HeLa cells, an ARF1-enhanced green fluorescent protein fusion redistributes from Golgi stacks to the perinuclear region, where poliovirus RNA replication occurs. Taken together, the data suggest an involvement of ARF in poliovirus RNA replication. PMID:15890959

Molecular cloning, characterization, and expression of human ADP-ribosylation factors: Two guanine nucleotide-dependent activators of cholera toxin

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

Bobak, D.A.; Nightingale, M.S.; Murtagh, J.J.

1989-08-01

ADP-ribosylation factors (ARFs) are small guanine nucleotide-binding proteins that enhance the enzymatic activities of cholera toxin. Two ARF cDNAs, ARF1 and ARF3, were cloned from a human cerebellum library. Based on deduced amino acid sequences and patterns of hybridization of cDNA and oligonucleotide probes with mammalian brain poly(A){sup +} RNA, human ARF1 is the homologue of bovine ARF1. Human ARF3, which differs from bovine ARF1 and bovine ARF2, appears to represent a newly identified third type of ARF. Hybridization patterns of human ARF cDNA and clone-specific oligonucleotides with poly(A){sup +} RNA are consistent with the presence of at least two,more » and perhaps four, separate ARF messages in human brain. In vitro translation of ARF1, ARF2, and ARF3 produced proteins that behaved, by SDS/PAGE, similar to a purified soluble brain ARF. Deduced amino acid sequences of human ARF1 and ARF3 contain regions, similar to those in other G proteins, that are believed to be involved in GTP binding and hydrolysis. ARFS also exhibit a modest degree of homology with a bovine phospholipase C. The observations reported here support the conclusion that the ARFs are members of a multigene family of small guanine nucleotide-binding proteins. Definition of the regulation of ARF mRNAs and of function(s) of recombinant ARF proteins will aid in the elucidation of the physiologic role(s) of ARFs.« less

Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs

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

Kurayoshi, Kenta; Ozono, Eiko; Iwanaga, Ritsuko

Highlights: • ARF promoter showed higher responsiveness to deregulated E2F activity than the E2F1 promoter. • ARF promoter showed higher cancer cell-specificity than E2F1 promoter to drive gene expression. • HSV-TK driven by ARF promoter showed higher cancer cell-specific cytotoxicity than that driven by E2F1 promoter. - Abstract: In current cancer treatment protocols, such as radiation and chemotherapy, side effects on normal cells are major obstacles to radical therapy. To avoid these side effects, a cancer cell-specific approach is needed. One way to specifically target cancer cells is to utilize a cancer specific promoter to express a cytotoxic gene (suicidemore » gene therapy) or a viral gene required for viral replication (oncolytic virotherapy). For this purpose, the selected promoter should have minimal activity in normal cells to avoid side effects, and high activity in a wide variety of cancers to obtain optimal therapeutic efficacy. In contrast to the AFP, CEA and PSA promoters, which have high activity only in a limited spectrum of tumors, the E2F1 promoter exhibits high activity in wide variety of cancers. This is based on the mechanism of carcinogenesis. Defects in the RB pathway and activation of the transcription factor E2F, the main target of the RB pathway, are observed in almost all cancers. Consequently, the E2F1 promoter, which is mainly regulated by E2F, has high activity in wide variety of cancers. However, E2F is also activated by growth stimulation in normal growing cells, suggesting that the E2F1 promoter may also be highly active in normal growing cells. In contrast, we found that the tumor suppressor ARF promoter is activated by deregulated E2F activity, induced by forced inactivation of pRB, but does not respond to physiological E2F activity induced by growth stimulation. We also found that the deregulated E2F activity, which activates the ARF promoter, is detected only in cancer cell lines. These observations suggest that ARF

Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning

PubMed Central

Wesolowski, Jordan; Weber, Mary M.; Nawrotek, Agata; Dooley, Cheryl A.; Calderon, Mike; St. Croix, Claudette M.; Hackstadt, Ted; Cherfils, Jacqueline

2017-01-01

ABSTRACT The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion. PMID:28465429

Suppression of breast cancer metastasis through the inactivation of ADP-ribosylation factor 1.

PubMed

Xie, Xiayang; Tang, Shou-Ching; Cai, Yafei; Pi, Wenhu; Deng, Libin; Wu, Guangyu; Chavanieu, Alain; Teng, Yong

2016-09-06

Metastasis is the major cause of cancer-related death in breast cancer patients, which is controlled by specific sets of genes. Targeting these genes may provide a means to delay cancer progression and allow local treatment to be more effective. We report for the first time that ADP-ribosylation factor 1 (ARF1) is the most amplified gene in ARF gene family in breast cancer, and high-level amplification of ARF1 is associated with increased mRNA expression and poor outcomes of patients with breast cancer. Knockdown of ARF1 leads to significant suppression of migration and invasion in breast cancer cells. Using the orthotopic xenograft model in NSG mice, we demonstrate that loss of ARF1 expression in breast cancer cells inhibits pulmonary metastasis. The zebrafish-metastasis model confirms that the ARF1 gene depletion suppresses breast cancer cells to metastatic disseminate throughout fish body, indicating that ARF1 is a very compelling target to limit metastasis. ARF1 function largely dependents on its activation and LM11, a cell-active inhibitor that specifically inhibits ARF1 activation through targeting the ARF1-GDP/ARNO complex at the Golgi, significantly impairs metastatic capability of breast cancer cell in zebrafish. These findings underline the importance of ARF1 in promoting metastasis and suggest that LM11 that inhibits ARF1 activation may represent a potential therapeutic approach to prevent or treat breast cancer metastasis.

Neurotrophin responsiveness of sympathetic neurons is regulated by rapid mobilization of the p75 receptor to the cell surface through TrkA activation of Arf6.

PubMed

Edward Hickman, F; Stanley, Emily M; Carter, Bruce D

2018-05-22

The p75 neurotrophin receptor (p75NTR) plays an integral role in patterning the sympathetic nervous system during development. Initially, p75NTR is expressed at low levels as sympathetic axons project toward their targets, which enables neurotrophin-3 (NT3) to activate TrkA receptors and promote growth. Upon reaching nerve growth factor (NGF) producing tissues, p75NTR is up regulated resulting in formation of TrkA-p75 complexes, which are high affinity binding sites selective for NGF, thereby blunting NT3 signaling. The level of p75NTR expressed on the neuron surface is instrumental in regulating trophic factor response; however, the mechanisms by which p75NTR expression is regulated are poorly understood. Here, we demonstrate a rapid, translation independent increase in surface expression of p75NTR in response to NGF in rat sympathetic neurons. p75NTR was mobilized to the neuron surface from GGA3-postitive vesicles through activation of the GTPase Arf6, which was stimulated by NGF, but not NT3 binding to TrkA. Arf6 activation required PI3 kinase activity and was prevented by an inhibitor of the cytohesin family of Arf6 GEFs. Overexpression of a constitutively active Arf6 mutant (Q67L) was sufficient to significantly increase surface expression of p75NTR even in the absence of NGF. Functionally, expression of active Arf6 markedly attenuated the ability of NT3 to promote neuronal survival and neurite outgrowth while the NGF response was unaltered. These data suggest that NGF activation of Arf6 through TrkA is critical for the increase in p75NTR surface expression that enables the switch in neurotrophin responsiveness during development in the sympathetic nervous system. SIGNIFICANCE STATEMENT p75NTR is instrumental in the regulation of neuronal survival and apoptosis during development and is also implicated as a contributor to aberrant neurodegeneration in numerous conditions. Therefore, a better understanding of the mechanisms that mediate p75NTR surface

Increased Arf/p53 activity in stem cells, aging and cancer.

PubMed

Carrasco-Garcia, Estefania; Moreno, Manuel; Moreno-Cugnon, Leire; Matheu, Ander

2017-04-01

Arf/p53 pathway protects the cells against DNA damage induced by acute stress. This characteristic is the responsible for its tumor suppressor activity. Moreover, it regulates the chronic type of stress associated with aging. This is the basis of its anti-aging activity. Indeed, increased gene dosage of Arf/p53 displays elongated longevity and delayed aging. At a cellular level, it has been recently shown that increased dosage of Arf/p53 delays age-associated stem cell exhaustion and the subsequent decline in tissue homeostasis and regeneration. However, p53 can also promote aging if constitutively activated. In this context, p53 reduces tissue regeneration, which correlates with premature exhaustion of stem cells. We discuss here the current evidence linking the Arf/p53 pathway to the processes of aging and cancer through stem cell regulation. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Isolation of cucumber CsARF cDNAs and expression of the corresponding mRNAs during gravity-regulated morphogenesis of cucumber seedlings

NASA Astrophysics Data System (ADS)

Saito, Y.; Yamasaki, S.; Fujii, N.; Hagen, G.; Guilfoyle, T.; Takahashi, H.

Cucumber seedlings grown in a horizontal position develop a protuberance called peg on the lower side of the transition zone between the hypocotyl and the root. We have suggested that peg formation on the upper side of the gravistimulated transition zone is suppressed because cucumber seedlings grown in a vertical position or microgravity symmetrically develop two pegs on the transition zone. Plant hormone, auxin, is considered to play a crucial role in the gravity-regulated formation of peg. We have shown that the mRNAs of auxin-inducible genes (CsIAAs) isolated from cucumber accumulate more abundantly in the lower side of the transition zone than in the upper side when peg formation initiates. To reveal the mechanism of transcriptional regulation by auxin for peg formation, we isolated five cDNAs of Auxin Response Factors (ARFs) from cucumber and compared their mRNA accumulation with those of CsIAA1 and CsIAA2. The tissue specificity of mRNA accumulation of CsARF2 was similar to those of CsIAA1 and CsIAA2. The structural character of CsARF2 predicts it is transcriptional activator. These results suggest that CsARF2 may be involved in activation of the transcription of auxin-inducible genes including CsIAA1 for peg formation. Because mRNA accumulation of five CsARFs, including CsARF2, were affected by neither gravity nor auxin, transcriptional activity of CsARF2 may be regulated at post-transcriptional level to induce asymmetric mRNA accumulation of auxin-inducible genes in the transition zone.

The Arf-GDP-regulated recruitment of GBF1 to Golgi membranes requires domains HDS1 and HDS2 and a Golgi-localized protein receptor.

PubMed

Quilty, Douglas; Chan, Calvin J; Yurkiw, Katherine; Bain, Alexandra; Babolmorad, Ghazal; Melançon, Paul

2018-04-19

We previously proposed a novel mechanism by which the enzyme Golgi-specific Brefeldin A resistance factor 1 (GBF1) is recruited to the membranes of the cis -Golgi, based on in vivo experiments. Here, we extended our in vivo analysis on the production of regulatory Arf-GDP and observed that ArfGAP2 and ArfGAP3 do not play a role in GBF1 recruitment. We confirm that Arf-GDP localization is critical, as a TGN-localized Arf-GDP mutant protein fails to promote GBF1 recruitment. We also reported the establishment of an in vitro GBF1 recruitment assay that supports the regulation of GBF1 recruitment by Arf-GDP. This in vitro assay yielded further evidence for the requirement of a Golgi-localized protein because heat denaturation or protease treatment of Golgi membranes abrogated GBF1 recruitment. Finally, combined in vivo and in vitro measurements indicated that the recruitment to Golgi membranes via a putative receptor requires only the HDS1 and HDS2 domains in the C-terminal half of GBF1. © 2018. Published by The Company of Biologists Ltd.

Somatotropinomas, but not nonfunctioning pituitary adenomas, maintain a functional apoptotic RET/Pit1/ARF/p53 pathway that is blocked by excess GDNF.

PubMed

Diaz-Rodriguez, Esther; Garcia-Rendueles, Angela R; Ibáñez-Costa, Alejandro; Gutierrez-Pascual, Ester; Garcia-Lavandeira, Montserrat; Leal, Alfonso; Japon, Miguel A; Soto, Alfonso; Venegas, Eva; Tinahones, Francisco J; Garcia-Arnes, Juan A; Benito, Pedro; Angeles Galvez, Maria; Jimenez-Reina, Luis; Bernabeu, Ignacio; Dieguez, Carlos; Luque, Raul M; Castaño, Justo P; Alvarez, Clara V

2014-11-01

Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in

Crystallization and preliminary X-ray diffraction studies of hyperthermophilic archaeal Rieske-type ferredoxin (ARF) from Sulfolobus solfataricus P1.

PubMed

Kounosu, Asako; Hasegawa, Kazuya; Iwasaki, Toshio; Kumasaka, Takashi

2010-07-01

The hyperthermophilic archaeal Rieske-type [2Fe-2S] ferredoxin (ARF) from Sulfolobus solfataricus P1 contains a low-potential Rieske-type [2Fe-2S] cluster that has served as a tractable model for ligand-substitution studies on this protein family. Recombinant ARF harbouring a pET30a vector-derived N-terminal extension region plus a hexahistidine tag has been heterologously overproduced in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method using 0.05 M sodium acetate, 0.05 M HEPES, 2 M ammonium sulfate pH 5.5. The crystals diffracted to 1.85 A resolution and belonged to the tetragonal space group P4(3)2(1)2, with unit-cell parameters a = 60.72, c = 83.31 A. The asymmetric unit contains one protein molecule.

Auxin Response Factor Genes Repertoire in Mulberry: Identification, and Structural, Functional and Evolutionary Analyses

PubMed Central

Baranwal, Vinay Kumar; Negi, Nisha; Khurana, Paramjit

2017-01-01

Auxin Response Factors (ARFs) are at the core of the regulation mechanism for auxin-mediated responses, along with AUX/IAA proteins.They are critical in the auxin-mediated control of various biological responses including development and stress. A wild mulberry species genome has been sequenced and offers an opportunity to investigate this important gene family. A total of 17 ARFs have been identified from mulberry (Morus notabilis) which show a wide range of expression patterns. Of these 17 ARFs, 15 have strong acidic isoelectric point (pI) values and a molecular mass ranging from 52 kDa to 101 kDa. The putative promoters of these ARFs harbour cis motifs related to light-dependent responses, various stress responses and hormone regulations suggestive of their multifactorial regulation. The gene ontology terms for ARFs indicate their role in flower development, stress, root morphology and other such development and stress mitigation related activities. Conserved motif analysis showed the presence of all typical domains in all but four members that lack the PB1 domain and thus represent truncated ARFs. Expression analysis of these ARFs suggests their preferential expression in tissues ranging from leaf, root, winter bud, bark and male flowers. These ARFs showed differential expression in the leaf tissue of M. notabilis, Morus laevigata and Morus serrata. Insights gained from this analysis have implications in mulberry improvement programs. PMID:28841197

Putative terminator and/or effector functions of Arf GAPs in the trafficking of clathrin-coated vesicles.

PubMed

Kon, Shunsuke; Funaki, Tomo; Satake, Masanobu

2011-05-01

The role of ArfGAP1 as a terminator or effector in COPi-vesicle formation has been the subject of ongoing discussions. Here, the discussion on the putative terminator/effector functions has been enlarged to include Arf GAP members involved in the formation of clathrin-coated vesicles. ACAP1, whose role has been studied extensively, enhances the recycling of endocytosed proteins to the plasma membrane. Importantly, this positive role appears to be an overall reflection of both the terminator and effector activities attributed to ACAP1. Other Arf GAP subtypes have also been suggested to possess both terminator and effector activities. Interestingly, while most Arf GAP proteins regulate membrane trafficking by acting as facilitators, a few Arf GAP subtypes act as inhibitors.

Key roles of Arf small G proteins and biosynthetic trafficking for animal development.

PubMed

Rodrigues, Francisco F; Harris, Tony J C

2017-04-14

Although biosynthetic trafficking can function constitutively, it also functions specifically for certain developmental processes. These processes require either a large increase to biosynthesis or the biosynthesis and targeted trafficking of specific players. We review the conserved molecular mechanisms that direct biosynthetic trafficking, and discuss how their genetic disruption affects animal development. Specifically, we consider Arf small G proteins, such as Arf1 and Sar1, and their coat effectors, COPI and COPII, and how these proteins promote biosynthetic trafficking for cleavage of the Drosophila embryo, the growth of neuronal dendrites and synapses, extracellular matrix secretion for bone development, lumen development in epithelial tubes, notochord and neural tube development, and ciliogenesis. Specific need for the biosynthetic trafficking system is also evident from conserved CrebA/Creb3-like transcription factors increasing the expression of secretory machinery during several of these developmental processes. Moreover, dysfunctional trafficking leads to a range of developmental syndromes.

Crystallization and preliminary X-ray diffraction studies of hyperthermophilic archaeal Rieske-type ferredoxin (ARF) from Sulfolobus solfataricus P1

PubMed Central

Kounosu, Asako; Hasegawa, Kazuya; Iwasaki, Toshio; Kumasaka, Takashi

2010-01-01

The hyperthermophilic archaeal Rieske-type [2Fe–2S] ferredoxin (ARF) from Sulfolobus solfataricus P1 contains a low-potential Rieske-type [2Fe–2S] cluster that has served as a tractable model for ligand-substitution studies on this protein family. Recombinant ARF harbouring a pET30a vector-derived N-­terminal extension region plus a hexahistidine tag has been heterologously overproduced in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method using 0.05 M sodium acetate, 0.05 M HEPES, 2 M ammonium sulfate pH 5.5. The crystals diffracted to 1.85 Å resolution and belonged to the tetragonal space group P43212, with unit-cell parameters a = 60.72, c = 83.31 Å. The asymmetric unit contains one protein molecule. PMID:20606288

Poliovirus replication requires the N-terminus but not the catalytic Sec7 domain of ArfGEF GBF1.

PubMed

Belov, George A; Kovtunovych, Gennadiy; Jackson, Catherine L; Ehrenfeld, Ellie

2010-10-01

Viruses are intracellular parasites whose reproduction relies on factors provided by the host. The cellular protein GBF1 is critical for poliovirus replication. Here we show that the contribution of GBF1 to virus replication is different from its known activities in uninfected cells. Normally GBF1 activates the ADP-ribosylation factor (Arf) GTPases necessary for formation of COPI transport vesicles. GBF1 function is modulated by p115 and Rab1b. However, in polio-infected cells, p115 is degraded and neither p115 nor Rab1b knock-down affects virus replication. Poliovirus infection is very sensitive to brefeldin A (BFA), an inhibitor of Arf activation by GBF1. BFA targets the catalytic Sec7 domain of GBF1. Nevertheless the BFA block of polio replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. Replication of BFA-resistant poliovirus in the presence of BFA is uncoupled from Arf activation but is dependent on GBF1. Thus the function(s) of this protein essential for viral replication can be separated from those required for cellular metabolism. © Published 2010. This article is a US Government work and is in the public domain in the USA.

Investigation of the role of GBF1 in the replication of positive-sense single-stranded RNA viruses.

PubMed

Ferlin, Juliette; Farhat, Rayan; Belouzard, Sandrine; Cocquerel, Laurence; Bertin, Antoine; Hober, Didier; Dubuisson, Jean; Rouillé, Yves

2018-06-20

GBF1 has emerged as a host factor required for the replication of positive-sense single-stranded RNA viruses of different families, but its mechanism of action is still unknown. GBF1 is a guanine nucleotide exchange factor for Arf family members. Recently, we identified Arf4 and Arf5 (class II Arfs) as host factors required for the replication of hepatitis C virus (HCV), a GBF1-dependent virus. To assess whether a GBF1/class II Arf pathway is conserved among positive-sense single-stranded RNA viruses, we investigated yellow fever virus (YFV), Sindbis virus (SINV), coxsackievirus B4 (CVB4) and human coronavirus 229E (HCoV-229E). We found that GBF1 is involved in the replication of these viruses. However, using siRNA or CRISPR-Cas9 technologies, it was seen that the depletion of Arf1, Arf3, Arf4 or Arf5 had no impact on viral replication. In contrast, the depletion of Arf pairs suggested that class II Arfs could be involved in HCoV-229E, YFV and SINV infection, as for HCV, but not in CVB4 infection. In addition, another Arf pair, Arf1 and Arf4, appears to be essential for YFV and SINV infection, but not for infection by other viruses. Finally, CVB4 infection was not inhibited by any combination of Arf depletion. We conclude that the mechanism of action of GBF1 in viral replication appears not to be conserved, and that a subset of positive-sense single-stranded RNA viruses from different families might require class II Arfs for their replication.

HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.

PubMed

Shen, Qing-Tao; Ren, Xuefeng; Zhang, Rui; Lee, Il-Hyung; Hurley, James H

2015-10-23

The lentiviruses HIV and simian immunodeficiency virus (SIV) subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the adaptor protein 1 (AP-1) and AP-2 clathrin adaptors. We found that HIV-1 Nef and the guanosine triphosphatase Arf1 induced trimerization and activation of AP-1. Here we report the cryo-electron microscopy structures of the Nef- and Arf1-bound AP-1 trimer in the active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure and thus predicted a hexagonal assembly with inner and outer faces that bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat. Copyright © 2015, American Association for the Advancement of Science.

Selective amplification of an mRNA and related pseudogene for a human ADP-ribosylation factor, a guanine nucleotide-dependent protein activator of cholera toxin

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

Monaco, L.; Murtagh, J.J.; Newman, K.B.

1990-03-01

ADP-ribosylation factors (ARFs) are {approx}20-kDa proteins that act as GTP-dependent allosteric activators of cholera toxin. With deoxyinosine-containing degenerate oligonucleotide primers corresponding to conserved GTP-binding domains in ARFs, the polymerase chain reaction (PCR) was used to amplify simultaneously from human DNA portions of three ARF genes that include codons for 102 amino acids, with intervening sequences. Amplification products that differed in size because of differences in intron sizes were separated by agarose gel electrophoresis. One amplified DNA contained no introns and had a sequence different from those of known AFRs. Based on this sequence, selective oligonucleotide probes were prepared and usedmore » to isolate clone {Psi}ARF 4, a putative ARF pseudogene, from a human genomic library in {lambda} phage EMBL3. Reverse transcription-PCR was then used to clone from human poly(A){sup +} RNA the cDNA corresponding to the expressed homolog of {Psi}ARF 4, referred to as human ARF 4. It appears that {Psi}ARF 4 arose during human evolution by integration of processed ARF 4 mRNA into the genome. Human ARF 4 differs from previously identified mammalian ARFs 1, 2, and 3. Hybridization of ARF 4-specific oligonucleotide probes with human, bovine, and rat RNA revealed a single 1.8-kilobase mRNA, which was clearly distinguished from the 1.9-kilobase mRNA for ARF 1 in these tissues. The PCR provides a powerful tool for investigating diversity in this and other multigene families, especially with primers targeted at domains believed to have functional significance.« less

An AGEF-1/Arf GTPase/AP-1 Ensemble Antagonizes LET-23 EGFR Basolateral Localization and Signaling during C. elegans Vulva Induction

PubMed Central

Skorobogata, Olga; Escobar-Restrepo, Juan M.; Rocheleau, Christian E.

2014-01-01

LET-23 Epidermal Growth Factor Receptor (EGFR) signaling specifies the vulval cell fates during C. elegans larval development. LET-23 EGFR localization on the basolateral membrane of the vulval precursor cells (VPCs) is required to engage the LIN-3 EGF-like inductive signal. The LIN-2 Cask/LIN-7 Veli/LIN-10 Mint (LIN-2/7/10) complex binds LET-23 EGFR, is required for its basolateral membrane localization, and therefore, vulva induction. Besides the LIN-2/7/10 complex, the trafficking pathways that regulate LET-23 EGFR localization have not been defined. Here we identify vh4, a hypomorphic allele of agef-1, as a strong suppressor of the lin-2 mutant Vulvaless (Vul) phenotype. AGEF-1 is homologous to the mammalian BIG1 and BIG2 Arf GTPase guanine nucleotide exchange factors (GEFs), which regulate secretory traffic between the Trans-Golgi network, endosomes and the plasma membrane via activation of Arf GTPases and recruitment of the AP-1 clathrin adaptor complex. Consistent with a role in trafficking we show that AGEF-1 is required for protein secretion and that AGEF-1 and the AP-1 complex regulate endosome size in coelomocytes. The AP-1 complex has previously been implicated in negative regulation of LET-23 EGFR, however the mechanism was not known. Our genetic data indicate that AGEF-1 is a strong negative regulator of LET-23 EGFR signaling that functions in the VPCs at the level of the receptor. In line with AGEF-1 being an Arf GEF, we identify the ARF-1.2 and ARF-3 GTPases as also negatively regulating signaling. We find that the agef-1(vh4) mutation results in increased LET-23 EGFR on the basolateral membrane in both wild-type and lin-2 mutant animals. Furthermore, unc-101(RNAi), a component of the AP-1 complex, increased LET-23 EGFR on the basolateral membrane in lin-2 and agef-1(vh4); lin-2 mutant animals. Thus, an AGEF-1/Arf GTPase/AP-1 ensemble functions opposite the LIN-2/7/10 complex to antagonize LET-23 EGFR basolateral membrane localization and signaling

An AGEF-1/Arf GTPase/AP-1 ensemble antagonizes LET-23 EGFR basolateral localization and signaling during C. elegans vulva induction.

PubMed

Skorobogata, Olga; Escobar-Restrepo, Juan M; Rocheleau, Christian E

2014-10-01

LET-23 Epidermal Growth Factor Receptor (EGFR) signaling specifies the vulval cell fates during C. elegans larval development. LET-23 EGFR localization on the basolateral membrane of the vulval precursor cells (VPCs) is required to engage the LIN-3 EGF-like inductive signal. The LIN-2 Cask/LIN-7 Veli/LIN-10 Mint (LIN-2/7/10) complex binds LET-23 EGFR, is required for its basolateral membrane localization, and therefore, vulva induction. Besides the LIN-2/7/10 complex, the trafficking pathways that regulate LET-23 EGFR localization have not been defined. Here we identify vh4, a hypomorphic allele of agef-1, as a strong suppressor of the lin-2 mutant Vulvaless (Vul) phenotype. AGEF-1 is homologous to the mammalian BIG1 and BIG2 Arf GTPase guanine nucleotide exchange factors (GEFs), which regulate secretory traffic between the Trans-Golgi network, endosomes and the plasma membrane via activation of Arf GTPases and recruitment of the AP-1 clathrin adaptor complex. Consistent with a role in trafficking we show that AGEF-1 is required for protein secretion and that AGEF-1 and the AP-1 complex regulate endosome size in coelomocytes. The AP-1 complex has previously been implicated in negative regulation of LET-23 EGFR, however the mechanism was not known. Our genetic data indicate that AGEF-1 is a strong negative regulator of LET-23 EGFR signaling that functions in the VPCs at the level of the receptor. In line with AGEF-1 being an Arf GEF, we identify the ARF-1.2 and ARF-3 GTPases as also negatively regulating signaling. We find that the agef-1(vh4) mutation results in increased LET-23 EGFR on the basolateral membrane in both wild-type and lin-2 mutant animals. Furthermore, unc-101(RNAi), a component of the AP-1 complex, increased LET-23 EGFR on the basolateral membrane in lin-2 and agef-1(vh4); lin-2 mutant animals. Thus, an AGEF-1/Arf GTPase/AP-1 ensemble functions opposite the LIN-2/7/10 complex to antagonize LET-23 EGFR basolateral membrane localization and signaling.

Tobacco TTG2 and ARF8 function concomitantly to control flower colouring by regulating anthocyanin synthesis genes.

PubMed

Li, P; Chen, X; Sun, F; Dong, H

2017-07-01

Recently we elucidated that tobacco TTG2 cooperates with ARF8 to regulate the vegetative growth and seed production. Here we show that TTG2 and ARF8 control flower colouring by regulating expression of ANS and DFR genes, which function in anthocyanin biosynthesis. Genetic modifications that substantially altered expression levels of the TTG2 gene and production quantities of TTG2 protein were correlated with flower development and colouring. Degrees of flower colour were increased by TTG2 overexpression but decreased through TTG2 silencing, in coincidence with high and low concentrations of anthocyanins in flowers. Of five genes involved in the anthocyanin biosynthesis pathway, only ANS and DFR were TTG2-regulated and displayed enhancement and diminution of expression with TTG2 overexpression and silencing, respectively. The floral expression of ANS and DFR also needed a functional ARF8 gene, as ANS and DFR expression were attenuated by ARF8 silencing, which concomitantly diminished the role of TTG2 in anthocyanin production. While ARF8 required TTG2 to be expressed by itself and to regulate ANS and DFR expression, the concurrent presence of normally functional TTG2 and ARF8 was critical for floral production of anthocyanins and also for flower colouration. Our data suggest that TTG2 functions concomitantly with ARF8 to control degrees of flower colour by regulating expression of ANS and DFR, which are involved in the anthocyanin biosynthesis pathway. ARF8 depends on TTG2 to regulate floral expression of ANS and DFR with positive effects on anthocyanin production and flower colour. © 2017 German Botanical Society and The Royal Botanical Society of the Netherlands.

ArF excimer laser debrides burns without destruction of viable tissue: A pilot study.

PubMed

Prasad, Atulya; Sawicka, Katarzyna M; Pablo, Kelly B; Macri, Lauren K; Felsenstein, Jerome; Wynne, James J; Clark, Richard A F

2018-05-01

Recent evidence indicates that early removal of eschar by tangential debridement can promote healing. Laser debridement can be used for debridement of areas that prove challenging for debridement using tangential excision. In particular, irradiation with an ArF excimer laser ablates desiccated eschar and is self-terminating, preserving hydrated or viable tissue. Thermal burns were created on the flanks of two outbred, female Yorkshire pigs using aluminum bars heated to 70°C and applied for different lengths of time. Three days after injury, burns were debrided using an ArF excimer laser (193nm). Tissue was harvested immediately after debridement and 7days after debridement (10days after burn). Data from a pilot study demonstrates that ArF excimer laser irradiation removes burn eschar and promotes healing at 10days after burn. ArF excimer laser debridement is self-terminating and preserves underlying and adjacent perfused tissue. Potentially, this modality would be ideal for the complex curvilinear structures of the body. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Poliovirus Replication Requires the N-terminus but not the Catalytic Sec7 Domain of ArfGEF GBF1

PubMed Central

Belov, George A.; Kovtunovych, Gennadiy; Jackson, Catherine L.; Ehrenfeld, Ellie

2010-01-01

Viruses are intracellular parasites whose reproduction relies on factors provided by the host. The cellular protein GBF1 is critical for poliovirus replication. Here we show that the contribution of GBF1 to virus replication is different from its known activities in uninfected cells. Normally GBF1 activates the Arf GTPases necessary for formation of COPI transport vesicles. GBF1 function is modulated by p115 and Rab1b. However, in polio-infected cells, p115 is degraded and neither p115 nor Rab1b knock-down affects virus replication. Poliovirus infection is very sensitive to BFA, an inhibitor of Arf activation by GBF1. BFA targets the catalytic Sec7 domain of GBF1. Nevertheless the BFA block of polio replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. Replication of BFA-resistant poliovirus in the presence of BFA is uncoupled from Arf activation but is dependent on GBF1. Thus the function(s) of this protein essential for viral replication can be separated from those required for cellular metabolism. PMID:20497182

High miR156 Expression Is Required for Auxin-Induced Adventitious Root Formation via MxSPL26 Independent of PINs and ARFs in Malus xiaojinensis

PubMed Central

Xu, Xiaozhao; Li, Xu; Hu, Xingwang; Wu, Ting; Wang, Yi; Xu, Xuefeng; Zhang, Xinzhong; Han, Zhenhai

2017-01-01

Adventitious root formation is essential for the vegetative propagation of perennial woody plants. During the juvenile-to-adult phase change mediated by the microRNA156 (miR156), the adventitious rooting ability decreases dramatically in many species, including apple rootstocks. However, the mechanism underlying how miR156 affects adventitious root formation is unclear. In the present study, we showed that in the presence of the synthetic auxin indole-3-butyric acid (IBA), semi-lignified leafy cuttings from juvenile phase (Mx-J) and rejuvenated (Mx-R) Malus xiaojinensis trees exhibited significantly higher expression of miR156, PIN-FORMED1 (PIN1), PIN10, and rootless concerning crown and seminal roots-like (RTCS-like) genes, thus resulting in higher adventitious rooting ability than those from adult phase (Mx-A) trees. However, the expression of SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE26 (SPL26) and some auxin response factor (ARF) gene family members were substantially higher in Mx-A than in Mx-R cuttings. The expression of NbRTCS-like but not NbPINs and NbARFs varied with miR156 expression in tobacco (Nicotiana benthamiana) plants transformed with 35S:MdMIR156a6 or 35S:MIM156 constructs. Overexpressing the miR156-resistant MxrSPL genes in tobacco confirmed the involvement of MxSPL20, MxSPL21&22, and MxSPL26 in adventitious root formation. Together, high expression of miR156 was necessary for auxin-induced adventitious root formation via MxSPL26, but independent of MxPINs and MxARFs expression in M. xiaojinensis leafy cuttings. PMID:28674551

The Arf6 GTPase-activating proteins ARAP2 and ACAP1 define distinct endosomal compartments that regulate integrin α5β1 traffic.

PubMed

Chen, Pei-Wen; Luo, Ruibai; Jian, Xiaoying; Randazzo, Paul A

2014-10-31

Arf6 and the Arf6 GTPase-activating protein (GAP) ACAP1 are established regulators of integrin traffic important to cell adhesion and migration. However, the function of Arf6 with ACAP1 cannot explain the range of Arf6 effects on integrin-based structures. We propose that Arf6 has different functions determined, in part, by the associated Arf GAP. We tested this idea by comparing the Arf6 GAPs ARAP2 and ACAP1. We found that ARAP2 and ACAP1 had opposing effects on apparent integrin β1 internalization. ARAP2 knockdown slowed, whereas ACAP1 knockdown accelerated, integrin β1 internalization. Integrin β1 association with adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif (APPL)-positive endosomes and EEA1-positive endosomes was affected by ARAP2 knockdown and depended on ARAP2 GAP activity. ARAP2 formed a complex with APPL1 and colocalized with Arf6 and APPL in a compartment distinct from the Arf6/ACAP1 tubular recycling endosome. In addition, although ACAP1 and ARAP2 each colocalized with Arf6, they did not colocalize with each other and had opposing effects on focal adhesions (FAs). ARAP2 overexpression promoted large FAs, but ACAP1 overexpression reduced FAs. Taken together, the data support a model in which Arf6 has at least two sites of opposing action defined by distinct Arf6 GAPs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

p14(ARF) nuclear overexpression in aggressive B-cell lymphomas is a sensor of malfunction of the common tumor suppressor pathways.

PubMed

Sánchez-Aguilera, Abel; Sánchez-Beato, Margarita; García, Juan F; Prieto, Ignacio; Pollan, Marina; Piris, Miguel A

2002-02-15

p14(ARF), the alternative product from the human INK4a/ARF locus, antagonizes Hdm2 and mediates p53 activation in response to oncogenic stimuli. An immunohistochemical study of p14(ARF) expression in 74 samples of aggressive B-cell lymphomas was performed, demonstrating an array of different abnormalities. A distinct nucleolar expression pattern was detected in nontumoral tissue and a subset of lymphomas (50/74). In contrast, a group of cases (8/74) showed absence of p14(ARF) expression, dependent either on promoter hypermethylation or gene loss. Additionally, 16 out of 74 cases displayed an abnormal nuclear p14(ARF) overexpression not confined to the nucleoli, as confirmed by confocal microscopy, and that was associated with high levels of p53 and Hdm2. A genetic study of these cases failed to show any alteration in the p14(ARF) gene, but revealed the presence of p53 mutations in over 50% of these cases. An increased growth fraction and a more aggressive clinical course, with a shortened survival time, also characterized the group of tumors with p14(ARF) nuclear overexpression. Moreover, this p14(ARF) expression pattern was more frequent in tumors displaying accumulated alterations in the p53, p16(INK4a), and p27(KIP1) tumor supressors. These observations, together with the consideration of the central role of p14(ARF) in cell cycle control, suggest that p14(ARF) abnormal nuclear overexpression is a sensor of malfunction of the major cell cycle regulatory pathways, and consequently a marker of a high tumor aggressivity.

Comparison of Australian Recommended Food Score (ARFS) and Plasma Carotenoid Concentrations: A Validation Study in Adults

PubMed Central

Ashton, Lee; Williams, Rebecca; Rollo, Megan; Pezdirc, Kristine; Collins, Clare

2017-01-01

Diet quality indices can predict nutritional adequacy of usual intake, but validity should be determined. The aim was to assess the validity of total and sub-scale score within the Australian Recommended Food Score (ARFS), in relation to fasting plasma carotenoid concentrations. Diet quality and fasting plasma carotenoid concentrations were assessed in 99 overweight and obese adults (49.5% female, aged 44.6 ± 9.9 years) at baseline and after three months (198 paired observations). Associations were assessed using Spearman’s correlation coefficients and regression analysis, and agreement using weighted kappa (Kw). Small, significantly positive correlations were found between total ARFS and plasma concentrations of total carotenoids (r = 0.17, p < 0.05), β-cryptoxanthin (r = 0.18, p < 0.05), β-carotene (r = 0.20, p < 0.01), and α-carotene (r = 0.19, p < 0.01). Significant agreement between ARFS categories and plasma carotenoid concentrations was found for total carotenoids (Kw 0.12, p = 0.02), β-carotene (Kw 0.14, p < 0.01), and α-carotene (Kw 0.13, p < 0.01). In fully-adjusted regression models the only signification association with ARFS total score was for α-carotene (β = 0.19, p < 0.01), while ARFS meat and fruit sub-scales demonstrated significant relationships with α-carotene, β-carotene, and total carotenoids (p < 0.05). The weak associations highlight the issues with self-reporting dietary intakes in overweight and obese populations. Further research is required to evaluate the use of the ARFS in more diverse populations. PMID:28817083

Gibberellin application at pre-bloom in grapevines down-regulates the expressions of VvIAA9 and VvARF7, negative regulators of fruit set initiation, during parthenocarpic fruit development.

PubMed

Jung, Chan Jin; Hur, Youn Young; Yu, Hee-Ju; Noh, Jung-Ho; Park, Kyo-Sun; Lee, Hee Jae

2014-01-01

Fruit set is initiated only after fertilization and is tightly regulated primarily by gibberellins (GAs) and auxins. The application of either of these hormones induces parthenocarpy, fruit set without fertilization, but the molecular mechanism underlying this induction is poorly understood. In the present study, we have shown that the parthenocarpic fruits induced by GA application at pre-bloom result from the interaction of GA with auxin signaling. The transcriptional levels of the putative negative regulators of fruit set initiation, including Vitis auxin/indole-3-acetic acid transcription factor 9 (VvIAA9), Vitis auxin response factor 7 (VvARF7), and VvARF8 were monitored during inflorescence development in seeded diploid 'Tamnara' grapevines with or without GA application. Without GA application, VvIAA9, VvARF7, and VvARF8 were expressed at a relatively high level before full bloom, but decreased thereafter following pollination. After GA application at 14 days before full bloom (DBF); however, the expression levels of VvIAA9 and VvARF7 declined at 5 DBF prior to pollination. The effects of GA application on auxin levels or auxin signaling were also analyzed by monitoring the expression patterns of auxin biosynthesis genes and auxin-responsive genes with or without GA application. Transcription levels of the auxin biosynthesis genes Vitis anthranilate synthase β subunit (VvASB1-like), Vitis YUCCA2 (VvYUC2), and VvYUC6 were not significantly changed by GA application. However, the expressions of Vitis Gretchen Hagen3.2 (VvGH3.2) and VvGH3.3, auxin-responsive genes, were up-regulated from 2 DBF to full bloom with GA application. Furthermore, the Vitis GA signaling gene, VvDELLA was up-regulated by GA application during 12 DBF to 7 DBF, prior to down-regulation of VvIAA9 and VvARF7. These results suggest that VvIAA9 and VvARF7 are negative regulators of fruit set initiation in grapevines, and GA signaling is integrated with auxin signaling via VvDELLA during

The Opposing Roles of Nucleophosmin and the ARF Tumor Suppressor in Breast Cancer

DTIC Science & Technology

2005-04-01

3. Bertwistle, D ., M. Sugimoto, and C . J. Sherr. 2004. Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin...Kindbeiter, J. C . Sanchez, A. Greco, D . Hochstrasser, and J. J. Diaz. 2002. Functional proteomic analysis of human nucleolus. Mol Biol Cell 13:4100-9...21. Sherr, C . J., and J. D . Weber. 2000. The ARF/p53 pathway. Curr Opin Genet Dev 10:94-9. 22. Spector, D . L., R. L. Ochs, and H. Busch. 1984

PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence

PubMed Central

Ivanschitz, Lisa; Takahashi, Yuki; Jollivet, Florence; Ayrault, Olivier; Le Bras, Morgane; de Thé, Hugues

2015-01-01

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) recruit multiple partners, including p53 and many of its regulators. NBs are believed to facilitate several posttranslational modifications and are key regulators of senescence. PML, the organizer of NBs, is expressed as a number of splice variants that all efficiently recruit p53 partners. However, overexpression of only one of them, PML IV, triggers p53-driven senescence. Here, we show that PML IV specifically binds ARF, a key p53 regulator. Similar to ARF, PML IV enhances global SUMO-1 conjugation, particularly that of p53, resulting in p53 stabilization and activation. ARF interacts with and stabilizes the NB-associated UBC9 SUMO-conjugating enzyme, possibly explaining PML IV-enhanced SUMOylation. These results unexpectedly link two key tumor suppressors, highlighting their convergence for global control of SUMO conjugation, p53 activation, and senescence induction. PMID:26578773

PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence.

PubMed

Ivanschitz, Lisa; Takahashi, Yuki; Jollivet, Florence; Ayrault, Olivier; Le Bras, Morgane; de Thé, Hugues

2015-11-17

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) recruit multiple partners, including p53 and many of its regulators. NBs are believed to facilitate several posttranslational modifications and are key regulators of senescence. PML, the organizer of NBs, is expressed as a number of splice variants that all efficiently recruit p53 partners. However, overexpression of only one of them, PML IV, triggers p53-driven senescence. Here, we show that PML IV specifically binds ARF, a key p53 regulator. Similar to ARF, PML IV enhances global SUMO-1 conjugation, particularly that of p53, resulting in p53 stabilization and activation. ARF interacts with and stabilizes the NB-associated UBC9 SUMO-conjugating enzyme, possibly explaining PML IV-enhanced SUMOylation. These results unexpectedly link two key tumor suppressors, highlighting their convergence for global control of SUMO conjugation, p53 activation, and senescence induction.

MUC1-ARF-A Novel MUC1 Protein That Resides in the Nucleus and Is Expressed by Alternate Reading Frame Translation of MUC1 mRNA.

PubMed

Chalick, Michael; Jacobi, Oded; Pichinuk, Edward; Garbar, Christian; Bensussan, Armand; Meeker, Alan; Ziv, Ravit; Zehavi, Tania; Smorodinsky, Nechama I; Hilkens, John; Hanisch, Franz-Georg; Rubinstein, Daniel B; Wreschner, Daniel H

2016-01-01

Translation of mRNA in alternate reading frames (ARF) is a naturally occurring process heretofore underappreciated as a generator of protein diversity. The MUC1 gene encodes MUC1-TM, a signal-transducing trans-membrane protein highly expressed in human malignancies. Here we show that an AUG codon downstream to the MUC1-TM initiation codon initiates an alternate reading frame thereby generating a novel protein, MUC1-ARF. MUC1-ARF, like its MUC1-TM 'parent' protein, contains a tandem repeat (VNTR) domain. However, the amino acid sequence of the MUC1-ARF tandem repeat as well as N- and C- sequences flanking it differ entirely from those of MUC1-TM. In vitro protein synthesis assays and extensive immunohistochemical as well as western blot analyses with MUC1-ARF specific monoclonal antibodies confirmed MUC1-ARF expression. Rather than being expressed at the cell membrane like MUC1-TM, immunostaining showed that MUC1-ARF protein localizes mainly in the nucleus: Immunohistochemical analyses of MUC1-expressing tissues demonstrated MUC1-ARF expression in the nuclei of secretory luminal epithelial cells. MUC1-ARF expression varies in different malignancies. While the malignant epithelial cells of pancreatic cancer show limited expression, in breast cancer tissue MUC1-ARF demonstrates strong nuclear expression. Proinflammatory cytokines upregulate expression of MUC1-ARF protein and co-immunoprecipitation analyses demonstrate association of MUC1-ARF with SH3 domain-containing proteins. Mass spectrometry performed on proteins coprecipitating with MUC1-ARF demonstrated Glucose-6-phosphate 1-dehydrogenase (G6PD) and Dynamin 2 (DNM2). These studies not only reveal that the MUC1 gene generates a previously unidentified MUC1-ARF protein, they also show that just like its 'parent' MUC1-TM protein, MUC1-ARF is apparently linked to signaling and malignancy, yet a definitive link to these processes and the roles it plays awaits a precise identification of its molecular functions

The Arf-inducing Transcription Factor Dmp1 Encodes a Transcriptional Activator of Amphiregulin, Thrombospondin-1, JunB and Egr1

PubMed Central

Mallakin, Ali; Sugiyama, Takayuki; Kai, Fumitake; Taneja, Pankaj; Kendig, Robert D.; Frazier, Donna P.; Maglic, Dejan; Matise, Lauren A.; Willingham, Mark C.; Inoue, Kazushi

2009-01-01

Dmp1 (Dmtf1) encodes a Myb-like transcription factor implicated in tumor suppression through direct activation of the Arf-p53 pathway. The human DMP1 gene is frequently deleted in non-small cell lung cancers, especially those that retain wild-type INK4a/ARF and/or p53. To identify novel genes that are regulated by Dmp1, transcriptional profiles of lung tissue from Dmp1-null and wild-type mice were generated using the GeneChip Microarray. Comparative analysis of gene expression changes between the two groups resulted in identification of numerous genes that may be regulated by Dmp1. Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated. These target genes were chosen for further analyses since they are involved in cell proliferation, transcription, angiogenesis/metastasis, apoptosis, or DNA methylation, and thus could account for the tumor suppressor phenotype of Dmp1. Dmp1 directly bound to the genomic loci of Areg, Tsp-1, JunB and Egr1. Significant upregulation or downregulation of the novel Dmp1 target genes was observed upon transient expression of Dmp1 in alveolar epithelial cells, an effect which was nullified by the inhibition of de novo mRNA synthesis. Interestingly, these genes and their protein products were significantly downregulated or upregulated in the lungs from Dmp1-heterozygous mice as well. Identification of novel Dmp1 target genes not only provides insights into the effects of Dmp1 on global gene expression, but also sheds light on the mechanism of haploid insufficiency of Dmp1 in tumor suppression. PMID:19816943

Investigation on gas medium parameters for an ArF excimer laser through orthogonal experimental design

NASA Astrophysics Data System (ADS)

Song, Xingliang; Sha, Pengfei; Fan, Yuanyuan; Jiang, R.; Zhao, Jiangshan; Zhou, Yi; Yang, Junhong; Xiong, Guangliang; Wang, Yu

2018-02-01

Due to complex kinetics of formation and loss mechanisms, such as ion-ion recombination reaction, neutral species harpoon reaction, excited state quenching and photon absorption, as well as their interactions, the performance behavior of different laser gas medium parameters for excimer laser varies greatly. Therefore, the effects of gas composition and total gas pressure on excimer laser performance attract continual research studies. In this work, orthogonal experimental design (OED) is used to investigate quantitative and qualitative correlations between output laser energy characteristics and gas medium parameters for an ArF excimer laser with plano-plano optical resonator operation. Optimized output laser energy with good pulse to pulse stability can be obtained effectively by proper selection of the gas medium parameters, which makes the most of the ArF excimer laser device. Simple and efficient method for gas medium optimization is proposed and demonstrated experimentally, which provides a global and systematic solution. By detailed statistical analysis, the significance sequence of relevant parameter factors and the optimized composition for gas medium parameters are obtained. Compared with conventional route of varying single gas parameter factor sequentially, this paper presents a more comprehensive way of considering multivariables simultaneously, which seems promising in striking an appropriate balance among various complicated parameters for power scaling study of an excimer laser.

SCARFACE encodes an ARF-GAP that is required for normal auxin efflux and vein patterning in Arabidopsis.

PubMed

Sieburth, Leslie E; Muday, Gloria K; King, Edward J; Benton, Geoff; Kim, Sun; Metcalf, Kasee E; Meyers, Lindsay; Seamen, Emylie; Van Norman, Jaimie M

2006-06-01

To identify molecular mechanisms controlling vein patterns, we analyzed scarface (sfc) mutants. sfc cotyledon and leaf veins are largely fragmented, unlike the interconnected networks in wild-type plants. SFC encodes an ADP ribosylation factor GTPase activating protein (ARF-GAP), a class with well-established roles in vesicle trafficking regulation. Quadruple mutants of SCF and three homologs (ARF-GAP DOMAIN1, 2, and 4) showed a modestly enhanced vascular phenotype. Genetic interactions between sfc and pinoid and between sfc and gnom suggest a possible function for SFC in trafficking of auxin efflux regulators. Genetic analyses also revealed interaction with cotyledon vascular pattern2, suggesting that lipid-based signals may underlie some SFC ARF-GAP functions. To assess possible roles for SFC in auxin transport, we analyzed sfc roots, which showed exaggerated responses to exogenous auxin and higher auxin transport capacity. To determine whether PIN1 intracellular trafficking was affected, we analyzed PIN1:green fluorescent protein (GFP) dynamics using confocal microscopy in sfc roots. We found normal PIN1:GFP localization at the apical membrane of root cells, but treatment with brefeldin A resulted in PIN1 accumulating in smaller and more numerous compartments than in the wild type. These data suggest that SFC is required for normal intracellular transport of PIN1 from the plasma membrane to the endosome.

Association of genetic polymorphisms in GADD45A, MDM2, and p14{sup ARF} with the risk of chronic benzene poisoning in a Chinese occupational population

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

Sun Pin; Zhang Zhongbin; Wan Junxiang

2009-10-01

Benzene reactive metabolites can lead to DNA damage and trigger the p53-dependent defense responses to maintain genomic stability. We hypothesized that the p53-dependent genes may play a role in the development of chronic benzene poisoning (CBP). In a case-control study of 303 patients with benzene poisoning and 295 workers occupationally exposed to benzene in south China, we investigated associations between the risk of CBP and polymorphisms in three p53-dependent genes. Potential interactions of these polymorphisms with lifestyle factors were also explored. We found p14{sup ARF} rs3731245 polymorphism was associated with risk of CBP (P = 0.014). Compared with those carryingmore » the GG genotype, individuals carrying p14{sup ARF} rs3731245 GA+AA genotypes had a reduced risk of CBP ([adjusted odds ratio (OR{sub adj}) = 0.57, 95%CI = 0.36-0.89]. Further analysis showed p14{sup ARF} TGA/TAG diplotype was associated with an increased risk of CBP (P = 0.0006), whereas p14{sup ARF} TGG/TAA diplotype was associated with a decreased risk of CBP (P = 0.0000001). In addition, we found individuals carrying both MDM2 Del1518 WW genotype and p14{sup ARF} rs3731245 GA+AA genotypes had a lower risk of CBP (OR{sub adj} = 0.25; 95%CI = 0.10-0.62; P = 0.003). Although these results require confirmation and extension, our findings suggest that genetic polymorphisms in p14{sup ARF} may have an impact on the risk of CBP in the study population.« less

Characteristics and Efficacy of a Sterile Hyphomycete (ARF18), a New Biocontrol Agent for Heterodera glycines and Other Nematodes

PubMed Central

Kim, D. G.; Riggs, R. D.

1991-01-01

A filamentous, nonsporulating fungus, designated Arkansas Fungus 18 (ARF18), was isolated from 9 of 95 populations of Heterodera glycines, the soybean cyst nematode, in Arkansas. In petri dishes, ARF18 parasitized 89% of H. glycines eggs in cysts. The fungus also infected eggs of Meloidogyne incognita and eggs in cysts of Cactodera betulae, H. graminophila, H. lespedezae, H. leuceilyma, H. schachtii, and H. trifolii. In pot tests, reproduction of SCN was 70% less in untreated field soil that was naturally infested by ARF18 than in autoclaved field soil. Although ARF18 grew well at 25 C on cornmeal agar over a wide pH range, it did not sporulate on 28 media and thus could not be identified to genus or species. PMID:19283127

Characteristics and Efficacy of a Sterile Hyphomycete (ARF18), a New Biocontrol Agent for Heterodera glycines and Other Nematodes.

PubMed

Kim, D G; Riggs, R D

1991-07-01

A filamentous, nonsporulating fungus, designated Arkansas Fungus 18 (ARF18), was isolated from 9 of 95 populations of Heterodera glycines, the soybean cyst nematode, in Arkansas. In petri dishes, ARF18 parasitized 89% of H. glycines eggs in cysts. The fungus also infected eggs of Meloidogyne incognita and eggs in cysts of Cactodera betulae, H. graminophila, H. lespedezae, H. leuceilyma, H. schachtii, and H. trifolii. In pot tests, reproduction of SCN was 70% less in untreated field soil that was naturally infested by ARF18 than in autoclaved field soil. Although ARF18 grew well at 25 C on cornmeal agar over a wide pH range, it did not sporulate on 28 media and thus could not be identified to genus or species.

The Opposing Roles of Nucleophosmin and the ARF Tumor Suppressor in Breast Cancer

DTIC Science & Technology

2007-04-01

P ., R. K. Busch, B. C. Valdez, and H. Busch. 1996 . C23 interacts with B23, a putative nucleolar...beneficial anti-cancer activity of peptides in vivo. Injection of a peptide from the von Hippel -Lindau (VHL) tumor suppressor inhibited the growth and... 240 WT Arf -/- 1 2 3 4 5 0 C y to s o lic 3 H -M e th y l M e th io n in e c p m ( x 1 0 3 ) A 28S 18S WT chase (min): Arf -/- 120 240 120 240 N

Gibberellin Application at Pre-Bloom in Grapevines Down-Regulates the Expressions of VvIAA9 and VvARF7, Negative Regulators of Fruit Set Initiation, during Parthenocarpic Fruit Development

PubMed Central

Jung, Chan Jin; Hur, Youn Young; Yu, Hee-Ju; Noh, Jung-Ho; Park, Kyo-Sun; Lee, Hee Jae

2014-01-01

Fruit set is initiated only after fertilization and is tightly regulated primarily by gibberellins (GAs) and auxins. The application of either of these hormones induces parthenocarpy, fruit set without fertilization, but the molecular mechanism underlying this induction is poorly understood. In the present study, we have shown that the parthenocarpic fruits induced by GA application at pre-bloom result from the interaction of GA with auxin signaling. The transcriptional levels of the putative negative regulators of fruit set initiation, including Vitis auxin/indole-3-acetic acid transcription factor 9 (VvIAA9), Vitis auxin response factor 7 (VvARF7), and VvARF8 were monitored during inflorescence development in seeded diploid ‘Tamnara’ grapevines with or without GA application. Without GA application, VvIAA9, VvARF7, and VvARF8 were expressed at a relatively high level before full bloom, but decreased thereafter following pollination. After GA application at 14 days before full bloom (DBF); however, the expression levels of VvIAA9 and VvARF7 declined at 5 DBF prior to pollination. The effects of GA application on auxin levels or auxin signaling were also analyzed by monitoring the expression patterns of auxin biosynthesis genes and auxin-responsive genes with or without GA application. Transcription levels of the auxin biosynthesis genes Vitis anthranilate synthase β subunit (VvASB1-like), Vitis YUCCA2 (VvYUC2), and VvYUC6 were not significantly changed by GA application. However, the expressions of Vitis Gretchen Hagen3.2 (VvGH3.2) and VvGH3.3, auxin-responsive genes, were up-regulated from 2 DBF to full bloom with GA application. Furthermore, the Vitis GA signaling gene, VvDELLA was up-regulated by GA application during 12 DBF to 7 DBF, prior to down-regulation of VvIAA9 and VvARF7. These results suggest that VvIAA9 and VvARF7 are negative regulators of fruit set initiation in grapevines, and GA signaling is integrated with auxin signaling via VvDELLA during

[Arf6, RalA and BIRC5 protein expression in non small cell lung cancer].

PubMed

Knizhnik, A V; Kovaleva, O B; Laktionov, K K; Mochal'nikova, V V; Komel'kov, A V; Chevkina, E M; Zborovskaia, I B

2011-01-01

Evaluation of tumor markers expression pattern which determines individual progression parameters is one of the major topics in molecular oncopathology research. This work presents research on expression analysis of several Ras-Ral associated signal transduction pathway proteins (Arf6, RalA and BIRC5) in accordance with clinical criteria in non small cell lung cancer patients. Using Western-blot analysis and RT-PCR Arf6, RalA and BIRC5 expression has been analyzed in parallel in 53 non small cell lung cancer samples of different origin. Arf6 protein expression was elevated in 55% non small cell lung cancer tumor samples in comparison with normal tissue. In the group of squamous cell lung cancer Arf6 expression elevation was observed more often. RalA protein expression was decreased in comparison to normal tissue samples in 64% of non small cell lung cancer regardless to morphological structure. Correlation between RalA protein expression decrease and absence of regional metastases was revealed for squamous cell lung cancer. BIRC5 protein expression in tumor samples versus corresponding normal tissue was 1.3 times more often elevated in the squamous cell lung cancer group (in 76% tumor samples). At the same time elevation of BIRC5 expression was fixed only in 63% of adenocarcinoma tumor samples. A statistically significant decrease (p = 0.0158) of RalA protein expression and increase (p = 0.0498) of Arf6 protein expression in comparison with normal tissue was found for T1-2N0M0 and T1-2N1-2M0 groups of squamous cell lung cancer correspondingly.

PRL-3 promotes breast cancer progression by downregulating p14ARF-mediated p53 expression.

PubMed

Xie, Hua; Wang, Hao

2018-03-01

Prior studies have demonstrated that phosphatase of regenerating liver-3 (PRL-3) serves avital function in cell proliferation and metastasis in breast cancer. However, the molecular mechanisms underlying the function of PRL-3 in breast cancer remain unknown. PRL-3 expression was analyzed in 24 pairs of breast cancer and normal tissues using the reverse transcription-quantitative polymerase chain reaction assay. The results of the present study identified that the expression of PLR-3 in breast cancer tissues was increased 4.2-fold, compared with normal tissues. Notably, overexpression of PRL-3 significantly promoted the proliferation of cancer cells and inhibited endogenous p53 expression by downregulating the expression level of p14 alternate reading frame (p14 ARF ). In addition, decreased expression levels of PRL-3 resulted in decreased breast cancer cell proliferation and increased expression level of p14 ARF . These results suggested that PRL-3 enhances cell proliferation by downregulating p14 ARF expression, which results in decreased levels ofp53. The results of the present study demonstrated that PRL-3 promotes tumor proliferation by affecting the p14 ARF -p53 axis, and that it may serve as a prognostic marker for patients with breast cancer.

Endocytosis of hERG Is Clathrin-Independent and Involves Arf6

PubMed Central

Abuarab, Nada; Smith, Andrew J.; Hardy, Matthew E. L.; Elliott, David J. S.; Sivaprasadarao, Asipu

2013-01-01

The hERG potassium channel is critical for repolarisation of the cardiac action potential. Reduced expression of hERG at the plasma membrane, whether caused by hereditary mutations or drugs, results in long QT syndrome and increases the risk of ventricular arrhythmias. Thus, it is of fundamental importance to understand how the density of this channel at the plasma membrane is regulated. We used antibodies to an extracellular native or engineered epitope, in conjunction with immunofluorescence and ELISA, to investigate the mechanism of hERG endocytosis in recombinant cells and validated the findings in rat neonatal cardiac myocytes. The data reveal that this channel undergoes rapid internalisation, which is inhibited by neither dynasore, an inhibitor of dynamin, nor a dominant negative construct of Rab5a, into endosomes that are largely devoid of the transferrin receptor. These results support a clathrin-independent mechanism of endocytosis and exclude involvement of dynamin-dependent caveolin and RhoA mechanisms. In agreement, internalised hERG displayed marked overlap with glycosylphosphatidylinositol-anchored GFP, a clathrin-independent cargo. Endocytosis was significantly affected by cholesterol extraction with methyl-β-cyclodextrin and inhibition of Arf6 function with dominant negative Arf6-T27N-eGFP. Taken together, we conclude that hERG undergoes clathrin-independent endocytosis via a mechanism involving Arf6. PMID:24392021

p14ARF Post-Transcriptional Regulation of Nuclear Cyclin D1 in MCF-7 Breast Cancer Cells: Discrimination between a Good and Bad Prognosis?

PubMed Central

McGowan, Eileen M.; Tran, Nham; Alling, Nikki; Yagoub, Daniel; Sedger, Lisa M.; Martiniello-Wilks, Rosetta

2012-01-01

As part of a cell’s inherent protection against carcinogenesis, p14ARF is upregulated in response to hyperproliferative signalling to induce cell cycle arrest. This property makes p14ARF a leading candidate for cancer therapy. This study explores the consequences of reactivating p14ARF in breast cancer and the potential of targeting p14ARF in breast cancer treatment. Our results show that activation of the p14ARF-p53-p21-Rb pathway in the estrogen sensitive MCF-7 breast cancer cells induces many hallmarks of senescence including a large flat cell morphology, multinucleation, senescence-associated-β-gal staining, and rapid G1 and G2/M phase cell cycle arrest. P14ARF also induces the expression of the proto-oncogene cyclin D1, which is most often associated with a transition from G1-S phase and is highly expressed in breast cancers with poor clinical prognosis. In this study, siRNA knockdown of cyclin D1, p21 and p53 show p21 plays a pivotal role in the maintenance of high cyclin D1 expression, cell cycle and growth arrest post-p14ARF induction. High p53 and p14ARF expression and low p21/cyclin D1 did not cause cell-cycle arrest. Knockdown of cyclin D1 stops proliferation but does not reverse senescence-associated cell growth. Furthermore, cyclin D1 accumulation in the nucleus post-p14ARF activation correlated with a rapid loss of nucleolar Ki-67 protein and inhibition of DNA synthesis. Latent effects of the p14ARF-induced cellular processes resulting from high nuclear cyclin D1 accumulation included a redistribution of Ki-67 into the nucleoli, aberrant nuclear growth (multinucleation), and cell proliferation. Lastly, downregulation of cyclin D1 through inhibition of ER abrogated latent recurrence. The mediation of these latent effects by continuous expression of p14ARF further suggests a novel mechanism whereby dysregulation of cyclin D1 could have a double-edged effect. Our results suggest that p14ARF induced-senescence is related to late-onset breast cancer in

Alterations in RDINK4/ARF-mediated en bloc regulation of the INK4-ARF locus in human squamous cell carcinoma of the head and neck

PubMed Central

Poi, Ming J.; Knobloch, Thomas J.; Sears, Marta T.; Warner, Blake M.; Uhrig, Lana K.; Weghorst, Christopher M.; Li, Junan

2014-01-01

The presence of RDINK4/ARF (RD) enhancer in the INK4-ARF locus provides a novel mechanism to simultaneously increase the transcription of p15INK4b (p15), p14ARF (p14), and p16INK4a (p16). While such up-regulation can be repressed through interactions between RD and oncoproteins CDC6 and BMI1, little is known about the involvement of RD in cancer. In this study we investigated RD deletions in 30 squamous cell carcinoma of the head and neck (SCCHN) and the patient-matched High At-Risk Mucosa specimens (HARM, “phenotypically normal” tissues neighboring SCCHN foci but beyond the surgical resection margin). RD was deleted (homozygously/heterozygously) in SCCHN and HARM at the incidence of 36.7% (11/30) and 13.3% (4/30), respectively. In comparison, no RD deletion was detected in 26 oral buccal brush biopsy specimens from healthy donors. Both p16 and p14 were lowly expressed in SCCHN and HARM, and their mRNA expression levels were positively associated with each other (p<0.01). Moreover, BMI1 was highly expressed in both SCCHN and HARM, and BMI1 over-expression was associated with p16 down-regulation in SCCHN (p<0.05). These results indicate that RD deletion and BMI1 overexpression frequently occur in the early stage of oral carcinogenesis and BMI1 overexpression may down-regulate the transcription of p16 and p14 through interfering with RD. PMID:24302590

Structure of Plasmodium falciparum ADP-ribosylation factor 1

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

Cook, William J.; Smith, Craig D.; Senkovich, Olga

Vesicular trafficking may play a crucial role in the pathogenesis and survival of the malaria parasite. ADP-ribosylation factors (ARFs) are among the major components of vesicular trafficking pathways in eukaryotes. The crystal structure of ARF1 GTPase from Plasmodium falciparum has been determined in the GDP-bound conformation at 2.5 {angstrom} resolution and is compared with the structures of mammalian ARF1s.

The Opposing Roles of Nucleophosmin and the ARF Tumor Suppressor in Breast Cancer

DTIC Science & Technology

2006-04-01

born to be weak. Trends Cell Biol. 15:121–124. 26. Li, Y. P ., R. K. Busch, B. C. Valdez, and H. Busch. 1996 . C23 interacts with B23, a putative...peptides in vivo. Injection of a peptide from the von Hippel -Lindau (VHL) tumor suppressor inhibited the growth and invasiveness of renal tumor...NPM IB: NPM IB: p19ARF 1° 2° 3° 4° 5° s up er na ta nt 2 5 % i n p u t 28S 18S WT Arf -/- 120 240 120 240chase (min) N C N CN C N C

The calcium-sensing receptor changes cell shape via a beta-arrestin-1 ARNO ARF6 ELMO protein network.

PubMed

Bouschet, Tristan; Martin, Stéphane; Kanamarlapudi, Venkateswarlu; Mundell, Stuart; Henley, Jeremy M

2007-08-01

G-protein-coupled receptors (GPCRs) transduce the binding of extracellular stimuli into intracellular signalling cascades that can lead to morphological changes. Here, we demonstrate that stimulation of the calcium-sensing receptor (CaSR), a GPCR that promotes chemotaxis by detecting increases in extracellular calcium, triggers plasma membrane (PM) ruffling via a pathway that involves beta-arrestin 1, Arf nucleotide binding site opener (ARNO), ADP-ribosylating factor 6 (ARF6) and engulfment and cell motility protein (ELMO). Expression of dominant negative beta-arrestin 1 or its knockdown with siRNA impaired the CaSR-induced PM ruffling response. Expression of a catalytically inactive ARNO also reduced CaSR-induced PM ruffling. Furthermore, beta-arrestin 1 co-immunoprecipitated with the CaSR and ARNO under resting conditions. Agonist treatment did not markedly alter beta-arrestin 1 binding to the CaSR or to ARNO but it did elicit the translocation and colocalisation of the CaSR, beta-arrestin 1 and ARNO to membrane protrusions. Furthermore, ARF6 and ELMO, two proteins known to couple ARNO to the cytoskeleton, were required for CaSR-dependent morphological changes and translocated to the PM ruffles. These data suggest that cells ruffle upon CaSR stimulation via a mechanism that involves translocation of beta-arrestin 1 pre-assembled with the CaSR or ARNO, and that ELMO plays an essential role in this CaSR-signalling-induced cytoskeletal reorganisation.

Development of South Dakota accident reduction factors

DOT National Transportation Integrated Search

1998-08-01

This report offers the methodology and findings of the first project to develop Accident Reduction Factors (ARFs) and Severity Reduction Ratios (SRRs) for the state of South Dakota. The ARFs and SRRs of this project focused on Hazard Elimination and ...

9Å structure of the COPI coat reveals that the Arf1 GTPase occupies two contrasting molecular environments

PubMed Central

Dodonova, Svetlana O; Aderhold, Patrick; Kopp, Juergen; Ganeva, Iva; Röhling, Simone; Hagen, Wim J H; Sinning, Irmgard; Wieland, Felix; Briggs, John A G

2017-01-01

COPI coated vesicles mediate trafficking within the Golgi apparatus and between the Golgi and the endoplasmic reticulum. Assembly of a COPI coated vesicle is initiated by the small GTPase Arf1 that recruits the coatomer complex to the membrane, triggering polymerization and budding. The vesicle uncoats before fusion with a target membrane. Coat components are structurally conserved between COPI and clathrin/adaptor proteins. Using cryo-electron tomography and subtomogram averaging, we determined the structure of the COPI coat assembled on membranes in vitro at 9 Å resolution. We also obtained a 2.57 Å resolution crystal structure of βδ-COP. By combining these structures we built a molecular model of the coat. We additionally determined the coat structure in the presence of ArfGAP proteins that regulate coat dissociation. We found that Arf1 occupies contrasting molecular environments within the coat, leading us to hypothesize that some Arf1 molecules may regulate vesicle assembly while others regulate coat disassembly. DOI: http://dx.doi.org/10.7554/eLife.26691.001 PMID:28621666

C/EBPbeta represses p53 to promote cell survival downstream of DNA damage independent of oncogenic Ras and p19(Arf).

PubMed

Ewing, S J; Zhu, S; Zhu, F; House, J S; Smart, R C

2008-11-01

CCAAT/enhancer-binding protein-beta (C/EBPbeta) is a mediator of cell survival and tumorigenesis. When C/EBPbeta(-/-) mice are treated with carcinogens that produce oncogenic Ras mutations in keratinocytes, they respond with abnormally elevated keratinocyte apoptosis and a block in skin tumorigenesis. Although this aberrant carcinogen-induced apoptosis results from abnormal upregulation of p53, it is not known whether upregulated p53 results from oncogenic Ras and its ability to induce p19(Arf) and/or activate DNA-damage response pathways or from direct carcinogen-induced DNA damage. We report that p19(Arf) is dramatically elevated in C/EBPbeta(-/-) epidermis and that C/EBPbeta represses a p19(Arf) promoter reporter. To determine whether p19(Arf) is responsible for the proapoptotic phenotype in C/EBPbeta(-/-) mice, C/EBPbeta(-/-);p19(Arf-/-) mice were generated. C/EBPbeta(-/-);p19(Arf-/-) mice responded to carcinogen treatment with increased p53 and apoptosis, indicating p19(Arf) is not essential. To ascertain whether oncogenic Ras activation induces aberrant p53 and apoptosis in C/EBPbeta(-/-) epidermis, we generated K14-ER:Ras;C/EBPbeta(-/-) mice. Oncogenic Ras activation induced by 4-hydroxytamoxifen did not produce increased p53 or apoptosis. Finally, when C/EBPbeta(-/-) mice were treated with differing types of DNA-damaging agents, including alkylating chemotherapeutic agents, they displayed aberrant levels of p53 and apoptosis. These results indicate that C/EBPbeta represses p53 to promote cell survival downstream of DNA damage and suggest that inhibition of C/EBPbeta may be a target for cancer cotherapy to increase the efficacy of alkylating chemotherapeutic agents.

Role of the ARF Tumor Suppressor in Prostate Cancer

DTIC Science & Technology

2005-10-01

found that ARF expression is absence from highly proliferative prostate adenocarcinomas and this correlates with the increased expression of the p53...prostate is unknown. The preliminary data for my orginal proposal indicated that prostate adenocarcinomas typically maintain wild type p53 (97%), but...independent mechanisms to regulate prostate cell proliferation. Table 1. Protein Expression in Prostate Adenocarcinomas Human prostate tissue samples

Novel Missense Mutation A789V in IQSEC2 Underlies X-Linked Intellectual Disability in the MRX78 Family

PubMed Central

Kalscheuer, Vera M.; James, Victoria M.; Himelright, Miranda L.; Long, Philip; Oegema, Renske; Jensen, Corinna; Bienek, Melanie; Hu, Hao; Haas, Stefan A.; Topf, Maya; Hoogeboom, A. Jeannette M.; Harvey, Kirsten; Walikonis, Randall; Harvey, Robert J.

2016-01-01

Disease gene discovery in neurodevelopmental disorders, including X-linked intellectual disability (XLID) has recently been accelerated by next-generation DNA sequencing approaches. To date, more than 100 human X chromosome genes involved in neuronal signaling pathways and networks implicated in cognitive function have been identified. Despite these advances, the mutations underlying disease in a large number of XLID families remained unresolved. We report the resolution of MRX78, a large family with six affected males and seven affected females, showing X-linked inheritance. Although a previous linkage study had mapped the locus to the short arm of chromosome X (Xp11.4-p11.23), this region contained too many candidate genes to be analyzed using conventional approaches. However, our X-chromosome exome resequencing, bioinformatics analysis and inheritance testing revealed a missense mutation (c.C2366T, p.A789V) in IQSEC2, encoding a neuronal GDP-GTP exchange factor for Arf family GTPases (ArfGEF) previously implicated in XLID. Molecular modeling of IQSEC2 revealed that the A789V substitution results in the insertion of a larger side-chain into a hydrophobic pocket in the catalytic Sec7 domain of IQSEC2. The A789V change is predicted to result in numerous clashes with adjacent amino acids and disruption of local folding of the Sec7 domain. Consistent with this finding, functional assays revealed that recombinant IQSEC2A789V was not able to catalyze GDP-GTP exchange on Arf6 as efficiently as wild-type IQSEC2. Taken together, these results strongly suggest that the A789V mutation in IQSEC2 is the underlying cause of XLID in the MRX78 family. PMID:26793055

Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses

PubMed Central

Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

2017-01-01

Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs, including DnARF1, DnARF4, and DnARF6, were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1, DnARF4, and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale. To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment. PMID:28471373

Identification and Expression Profiling of the Auxin Response Factors in Dendrobium officinale under Abiotic Stresses.

PubMed

Chen, Zhehao; Yuan, Ye; Fu, Di; Shen, Chenjia; Yang, Yanjun

2017-05-04

Auxin response factor (ARF) proteins play roles in plant responses to diverse environmental stresses by binding specifically to the auxin response element in the promoters of target genes. Using our latest public Dendrobium transcriptomes, a comprehensive characterization and analysis of 14 DnARF genes were performed. Three selected DnARFs , including DnARF1 , DnARF4 , and DnARF6 , were confirmed to be nuclear proteins according to their transient expression in epidermal cells of Nicotiana benthamiana leaves. Furthermore, the transcription activation abilities of DnARF1 , DnARF4 , and DnARF6 were tested in a yeast system. Our data showed that DnARF6 is a transcriptional activator in Dendrobium officinale . To uncover the basic information of DnARF gene responses to abiotic stresses, we analyzed their expression patterns under various hormones and abiotic treatments. Based on our data, several hormones and significant stress responsive DnARF genes have been identified. Since auxin and ARF genes have been identified in many plant species, our data is imperative to reveal the function of ARF mediated auxin signaling in the adaptation to the challenging Dendrobium environment.

Pokemon enhances proliferation, cell cycle progression and anti-apoptosis activity of colorectal cancer independently of p14ARF-MDM2-p53 pathway.

PubMed

Zhao, Yi; Yao, Yun-hong; Li, Li; An, Wei-fang; Chen, Hong-zen; Sun, Li-ping; Kang, Hai-xian; Wang, Sen; Hu, Xin-rong

2014-12-01

Pokemon has been showed to directly suppress p14(ARF) expression and also to overexpress in multiple cancers. However, p14(ARF)-MDM2-p53 pathway is usually aberrant in colorectal cancer (CRC). The aim is to confirm whether Pokemon plays a role in CRC and explore whether Pokemon works through p14(ARF)-MDM2-p53 pathway in CRC. Immunohistochemistry for Pokemon, p14(ARF) and Mtp53 protein was applied to 45 colorectal epitheliums (CREs), 42 colorectal adenomas (CRAs) and 66 CRCs. Pokemon was knocked down with RNAi technique in CRC cell line Lovo to detect mRNA expression of p14(ARF) with qRT-PCR, cell proliferation with CCK8 assay, and cell cycle and apoptosis with flowcytometry analysis. The protein expression rates were significantly higher in CRC (75.8%) than in CRE (22.2 %) or CRA (38.1%) for Pokemon and higher in CRC (53.0%) than in CRE (0) or CRA (4.8%) for Mtp53, but not significantly different in CRC (86.4 %) versus CRE (93.3%) or CRA (90.5 %) for p14(ARF). Higher expression rate of Pokemon was associated with lymph node metastasis and higher Duke's stage. After knockdown of Pokemon in Lovo cells, the mRNA level of p14(ARF) was not significantly changed, the cell proliferation ability was decreased by 20.6%, cell cycle was arrested by 55.7% in G0/G1 phase, and apoptosis rate was increased by 19.0%. Pokemon enhanced the oncogenesis of CRC by promoting proliferation, cell cycle progression and anti-apoptosis activity of CRC cells independently of p14(ARF)-MDM2-p53 pathway. This finding provided a novel idea for understanding and further studying the molecular mechanism of Pokemon on carcinogenesis of CRC.

Genome-wide identification and transcriptional profiling analysis of auxin response-related gene families in cucumber

PubMed Central

2014-01-01

Background Auxin signaling has a vital function in the regulation of plant growth and development, both which are known to be mediated by auxin-responsive genes. So far, significant progress has been made toward the identification and characterization of auxin-response genes in several model plants, while no systematic analysis for these families was reported in cucumber (Cucumis sativus L.), a reference species for Cucurbitaceae crops. The comprehensive analyses will help design experiments for functional validation of their precise roles in plant development and stress responses. Results A genome-wide search for auxin-response gene homologues identified 16 auxin-response factors (ARFs), 27 auxin/indole acetic acids (Aux/IAAs), 10 Gretchen Hagen 3 (GH3s), 61 small auxin-up mRNAs (SAURs), and 39 lateral organ boundaries (LBDs) in cucumber. Sequence analysis together with the organization of putative motifs indicated the potential diverse functions of these five auxin-related family members. The distribution and density of auxin response-related genes on chromosomes were not uniform. Evolutionary analysis showed that the chromosomal segment duplications mainly contributed to the expansion of the CsARF, CsIAA, CsGH3, and CsLBD gene families. Quantitative real-time RT-PCR analysis demonstrated that many ARFs, AUX/IAAs, GH3s, SAURs, and LBD genes were expressed in diverse patterns within different organs/tissues and during different development stages. They were also implicated in IAA, methyl jasmonic acid, or salicylic acid response, which is consistent with the finding that a great number of diverse cis-elements are present in their promoter regions involving a variety of signaling transduction pathways. Conclusion Genome-wide comparative analysis of auxin response-related family genes and their expression analysis provide new evidence for the potential role of auxin in development and hormone response of plants. Our data imply that the auxin response genes may be

Design and Lithographic Characteristics of Alicyclic Fluoropolymer for ArF Chemically Amplified Resists

NASA Astrophysics Data System (ADS)

Maeda, Katsumi; Nakano, Kaichiro; Shirai, Masamitsu

2006-12-01

We designed a novel alicyclic fluoropolymer, poly[3-hydroxy-4-(hexafluoro-2-hydroxyisopropyl)tricyclodecene], as an ArF (193 nm) chemically amplified resist. This fluoropolymer has a hexafluoroisopropanol group as an alkaline soluble unit and a hydroxyl group for improving adhesion. This polymer also exhibited a high transparency of 93%/150 nm at 193 nm, high thermal stability (355 °C), and a good adhesion to a Si substrate compared with a poly(norbornene) with a hexafluoroisopropanol group. The etching rate of our developed fluoropolymer for CF4 gas was 1.29 times that of the KrF resist. Moreover, a chemically amplified positive resist comprising an ethoxymethyl-protected polymer and a photoacid generator achieved a 110 nm line-and-space pattern with an ArF exposure.

Three-dimensional aspects of the shrinking phenomenon of ArF resist

NASA Astrophysics Data System (ADS)

Laufer, Ido; Eytan, Giora E.; Dror, Ophir

2002-07-01

Previous studies of the interaction of electron beams with different types of ArF resists have shown the undesired phenomenon of the resist shrinkage. The lateral component of this shrinkage has been detected and quantified easily by SEM CD measurements. However, the vertical extent of this phenomenon has to date remained unknown. In this work we present measurements of the changes in height and sidewall angles of an ArF line by using a new e-beam tilting ability of the Vera SEM 3D. The 3D measurement results show that the height of the line shrinks in similar proportions to the top and bottom CDs, with a difference in the magnitude. Due to higher penetration depth of the e-beam on the top of the line than on the sidewall, the vertical shrinkage reaches steady state more rapidly than the lateral shrinkage. We also found a slight reduction in sidewall angle, which is less than one degree even under high e-beam exposure.

Quartz 9-inch size mask blanks for ArF PSM (Phase Shift Mask)

NASA Astrophysics Data System (ADS)

Harashima, Noriyuki; Isozaki, Tatsuya; Kawanishi, Arata; Kanai, Shuichiro; Kageyama, Kagehiro; Iso, Hiroyuki; Chishima, Tatsuya

2017-07-01

Semiconductor technology nodes are steadily miniaturizing. On the other hand, various efforts have been made to reduce costs, mass production lines have shifted from 200 mmφ of Si wafer to 300 mmφ, and technology development of Si wafer 450 mmφ is also in progress. As a photomask, 6-inch size binary Cr mask has been used for many years, but in recent years, the use of 9-inch binary Cr masks for Proximity Lithography Process in automotive applications, MEMS, packages, etc. has increased, and cost reduction has been taken. Since the miniaturization will progress in the above applications in the future, products corresponding to miniaturization are also desired in 9-inch photomasks. The high grade Cr - binary mask blanks used in proximity exposure process, there is a prospect of being able to use it by ULVAC COATING CORPORATION's tireless research. As further demands for miniaturization, KrF and ArF Lithography Process, which are used for steppers and scanners , there are also a demand for 9-inch size Mask Blanks. In ULVAC COATING CORPORATION, we developed a 9 - inch size KrF PSM mask Blanks prototype in 2016 and proposed a new high grade 9 - inch photomask. This time, we have further investigated and developed 9-inch size ArF PSM Mask Blanks corresponding to ArF Lithography Process, so we report it.

Happiness among Adolescent Students in Thailand: Family and Non-Family Factors

ERIC Educational Resources Information Center

Gray, Rossarin Soottipong; Chamratrithirong, Aphichat; Pattaravanich, Umaporn; Prasartkul, Pramote

2013-01-01

This paper explores family and non-family factors contributing to happiness among students aged 15-18 in Thailand. Data come from the Social and Cultural Situation and Mental Health Survey (n = 905). Based on regression analysis, family factors are more important than non- family factors in explaining the variations in adolescents' happiness.…

Structure of the catalytic domain of Plasmodium falciparum ARF GTPase-activating protein (ARFGAP)

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

Cook, William J.; Senkovich, Olga; Chattopadhyay, Debasish

2012-03-26

The crystal structure of the catalytic domain of the ADP ribosylation factor GTPase-activating protein (ARFGAP) from Plasmodium falciparum has been determined and refined to 2.4 {angstrom} resolution. Multiwavelength anomalous diffraction (MAD) data were collected utilizing the Zn{sup 2+} ion bound at the zinc-finger domain and were used to solve the structure. The overall structure of the domain is similar to those of mammalian ARFGAPs. However, several amino-acid residues in the area where GAP interacts with ARF1 differ in P. falciparum ARFGAP. Moreover, a number of residues that form the dimer interface in the crystal structure are unique in P. falciparummore » ARFGAP.« less

The Area Resource File: ARF. A Manpower Planning and Research Tool.

ERIC Educational Resources Information Center

Applied Management Sciences, Inc., Silver Spring, MD.

This publication describes the Area Resource File (ARF), a computer-based, county-specific health information system with broad analytical capabilities which utilizes manpower and manpower-related data that are available on a compatible basis for all counties in the United States, and which was developed to summarize statistics from many disparate…

The processed isoform of the translation termination factor eRF3 localizes to the nucleus to interact with the ARF tumor suppressor

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

Hashimoto, Yoshifumi; Kumagai, Naomichi; Hosoda, Nao

2014-03-14

Highlights: • So far, eRF3 has been thought to function exclusively in the cytoplasm. • eRF3 is a nucleo-cutoplasmic shuttling protein. • eRF3 has a leptomycin-sensitive nuclear export signal (NES). • Removal of NES by proteolytic cleavage allows eRF3 to translocate to the nucleus. • The processed eRF3 (p-eRF3) interacts with a nuclear tumor suppressor ARF. - Abstract: The eukaryotic releasing factor eRF3 is a multifunctional protein that plays pivotal roles in translation termination as well as the initiation of mRNA decay. eRF3 also functions in the regulation of apoptosis; eRF3 is cleaved at Ala73 by an as yet unidentifiedmore » protease into processed isoform of eRF3 (p-eRF3), which interacts with the inhibitors of apoptosis proteins (IAPs). The binding of p-eRF3 with IAPs leads to the release of active caspases from IAPs, which promotes apoptosis. Although full-length eRF3 is localized exclusively in the cytoplasm, p-eRF3 localizes in the nucleus as well as the cytoplasm. We here focused on the role of p-eRF3 in the nucleus. We identified leptomycin-sensitive nuclear export signal (NES) at amino acid residues 61–71 immediately upstream of the cleavage site Ala73. Thus, the proteolytic cleavage of eRF3 into p-eRF3 leads to release an amino-terminal fragment containing NES to allow the relocalization of eRF3 into the nucleus. Consistent with this, p-eRF3 more strongly interacted with the nuclear ARF tumor suppressor than full-length eRF3. These results suggest that while p-eRF3 interacts with IAPs to promote apoptosis in the cytoplasm, p-eRF3 also has some roles in regulating cell death in the nucleus.« less

Effect of myristoylated N-terminus of Arf1 on the bending rigidity of phospholipid membranes

NASA Astrophysics Data System (ADS)

Burrola Gabilondo, Beatriz; Zhou, Hernan; Randazzo, Paul A.; Losert, Wolfgang

2010-03-01

The protein Arf1 is part of the COPI vesicle transport process from the Golgi to the ER. It binds to membranes via a myristoylated N-terminus and it has been shown to tubulate Large Unilamellar Vesicles. The effect of the N-terminus of Arf1 on physical properties of membranes has not been studied, with the exception of curvature. We previously found that the myristoylated N-terminus increases the packing of the lipid molecules, but has no effect on the lateral mobility. We tested the hypothesis that myristoylated peptides affect the bending rigidity of phospholipid Giant Unilamellar Vesicles (GUV). We use optical tweezers to pull tethers from GUV and measure the force of pulling the tether, as well as the retraction speed of the tether once it is released. We also used flicker spectroscopy to estimate the values of the mechanical properties of GUV. We will present results of the force and tether retraction measurements, as well as mechanical properties estimates from flicker, for GUV in the presence of varying concentrations of myristoylated and non-myristoylated N-terminus of Arf1, and compare these with measurements for GUV in the absence of peptide.

Gap Fill Materials Using Cyclodextrin Derivatives in ArF Lithography

NASA Astrophysics Data System (ADS)

Takei, Satoshi; Shinjo, Tetsuya; Sakaida, Yasushi; Hashimoto, Keisuke

2007-11-01

High planarizing gap fill materials based on β-cyclodextrin in ArF photoresist under-layer materials have been developed for fast etching in CF4 gas. Gap fill materials used in the via-first dual damascene process need to have high etch rates to prevent crowning or fencing on top of the trench after etching and a small thickness bias between the dense and blanket areas to minimize issues observed during trench lithography by narrowing the process latitude. Cyclodextrin is a circular oligomer with a nanoscale porous structure that has a high number of oxygen atoms, as calculated using the Ohnishi parameter, providing high etch rates. Additionally, since gap fill materials using cyclodextrin derivatives have low viscosities and molecular weights, they are expected to exhibit excellent flow properties and minimal thermal shrinkage during baking. In this paper, we describe the composition and basic film properties of gap fill materials; planarization in the via-first dual damascene process and etch rates in CF4 gas compared with dextrin with α-glycoside bonds in polysaccharide, poly(2-hydroxypropyl methacrylate) and poly(4-hydroxystyrene). The β-cyclodextrin used in this study was obtained by esterifying the hydroxyl groups of dextrin resulting in improved wettability on via substrates and solubility in photoresist solvents such as propylene glycol monomethyl ether, propylene glycol monomethyl ether acetate and ethyl lactate. Gap fill materials using cyclodextrin derivatives showed good planarization and via filling performance without observing voids in via holes. In addition to superior via filling performance, the etch rate of gap fill materials using β-cyclodextrin derivatives was 2.8-2.9 times higher than that of an ArF photoresist, evaluated under CF4 gas conditions by reactive ion etching. These results were attributed to the combination of both nanoscale porous structures and a high density of oxygen atoms in our gap fill materials using cyclodextrin

Analysis of risk factors of type a aortic dissection (TAAD) operation of frozen elephant trunk and total arch replacement.

PubMed

Shang, W; Ma, M; Ge, Y-P; Liu, N; Zhu, J-M; Sun, L-Z

2016-11-01

To investigate the incidence and risk factors of acute renal failure (ARF) after operation of frozen elephant trunk and total arch replacement for acute thoracic aortic aneurysm and dissection (TAAD) with mild hypothermic circulatory arrest (MHCA), and to analyze the long-term survival rate of the patients with ARF. From February 2009 to March 2015, patients with acute TAAD accepted operation of frozen elephant trunk and total arch replacement were enrolled. Those patients who were treated with renal replacement treatment (RRT) before the operation were excluded. The age, gender, cardiovascular disease history, preoperative serum creatinine and extracorporeal circulation duration in operation were recorded. On the basis of requiring RRT after TAAD operation, the patients were divided into ARF group and non-ARF group. The risk factors of ARF after TAAD operation were assessed by univariate and multivariate analysis. After completion of clinical follow-up, Kaplan-Meier curve was drawn to analyze five-year survival. A total of 524 patients were included in the study. 51 cases of them got postoperative ARF. The incidence was 9.7%. The mortality rate of ARF group in the hospital was significantly higher than non-ARF group (25.5% vs. 3.6%; p<0.001). Univariate analysis showed that there was statistically significant difference in the age, gender, hypertension history, preoperative serum creatinine ≥200 µmol/L, extracorporeal circulation duration ≥260 min and combined with coronary artery bypass surgery simultaneously (p<0.05). Multiple logistic regression analysis showed that there were three independent risk factors of ARF after the operation, including hypertension (p=0.031, OR=2.377), preoperative serum creatinine ≥200 µmol/L (p=0.005, OR=4.451) and extracorporeal circulation duration ≥260 min (p=0.002, OR=3.295). The total five-year survival rate of ARF group after the operation was 56%. There was no statistically significant difference in the five

The Human ARF Cell Cycle Regulatory Gene Promoter Is a CpG Island Which Can Be Silenced by DNA Methylation and Down-Regulated by Wild-Type p53

PubMed Central

Robertson, Keith D.; Jones, Peter A.

1998-01-01

The INK4a/ARF locus encodes two proteins involved in tumor suppression in a manner virtually unique in mammalian cells. Distinct first exons, driven from separate promoters, splice onto a common exon 2 and 3 but utilize different reading frames to produce two completely distinct proteins, both of which play roles in cell cycle control. INK4a, a critical element of the retinoblastoma gene pathway, binds to and inhibits the activities of CDK4 and CDK6, while ARF, a critical element of the p53 pathway, increases the level of functional p53 via interaction with MDM2. Here we clone and characterize the promoter of the human ARF gene and show that it is a CpG island characteristic of a housekeeping gene which contains numerous Sp1 sites. Both ARF and INK4a are coordinately expressed in cells except when their promoter regions become de novo methylated. In one of these situations, ARF transcription could be reactivated by treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine, and the reactivation kinetics of ARF and INK4a were found to differ slightly in a cell line in which both genes were silenced by methylation. The ARF promoter was also found to be highly responsive to E2F1 expression, in keeping with previous results at the RNA level. Lastly, transcription from the ARF promoter was down-regulated by wild-type p53 expression, and the magnitude of the effect correlated with the status of the endogenous p53 gene. This finding points to the existence of an autoregulatory feedback loop between p53, MDM2, and ARF, aimed at keeping p53 levels in check. PMID:9774662

Cloning of an ADP-ribosylation factor gene from banana (Musa acuminata) and its expression patterns in postharvest ripening fruit.

PubMed

Wang, Yuan; Wu, Jing; Xu, Bi-Yu; Liu, Ju-Hua; Zhang, Jian-Bin; Jia, Cai-Hong; Jin, Zhi-Qiang

2010-08-15

A full-length cDNA encoding an ADP-ribosylation factor (ARF) from banana (Musa acuminata) fruit was cloned and named MaArf. It contains an open reading frame encoding a 181-amino-acid polypeptide. Sequence analysis showed that MaArf shared high similarity with ARF of other plant species. The genomic sequence of MaArf was also obtained using polymerase chain reaction (PCR). Sequence analysis showed that MaArf was a split gene containing five exons and four introns in genomic DNA. Reverse-transcriptase PCR was used to analyze the spatial expression of MaArf. The results showed that MaArf was expressed in all the organs examined: root, rhizome, leaf, flower and fruit. Real-time quantitative PCR was used to explore expression patterns of MaArf in postharvest banana. There was differential expression of MaArf associated with ethylene biosynthesis. In naturally ripened banana, expression of MaArf was in accordance with ethylene biosynthesis. However, in 1-methylcyclopropene-treated banana, the expression of MaArf was inhibited and changed little. When treated with ethylene, MaArf expression in banana fruit significantly increased in accordance with ethylene biosynthesis; the peak of MaArf was 3 d after harvest, 11 d earlier than for naturally ripened banana fruits. These results suggest that MaArf is induced by ethylene in regulating postharvest banana ripening. Finally, subcellular localization assays showed the MaArf protein in the cytoplasm. Copyright 2010 Elsevier GmbH. All rights reserved.

The THO Complex Non-Cell-Autonomously Represses Female Germline Specification through the TAS3-ARF3 Module.

PubMed

Su, Zhenxia; Zhao, Lihua; Zhao, Yuanyuan; Li, Shaofang; Won, SoYoun; Cai, Hanyang; Wang, Lulu; Li, Zhenfang; Chen, Piaojuan; Qin, Yuan; Chen, Xuemei

2017-06-05

In most sexually reproducing plants, a single somatic, sub-epidermal cell in an ovule is selected to differentiate into a megaspore mother cell, which is committed to giving rise to the female germline. However, it remains unclear how intercellular signaling among somatic cells results in only one cell in the sub-epidermal layer differentiating into the megaspore mother cell. Here we uncovered a role of the THO complex in restricting the megaspore mother cell fate to a single cell. Mutations in TEX1, HPR1, and THO6, components of the THO/TREX complex, led to the formation of multiple megaspore mother cells, which were able to initiate gametogenesis. We demonstrated that TEX1 repressed the megaspore mother cell fate by promoting the biogenesis of TAS3-derived trans-acting small interfering RNA (ta-siRNA), which represses ARF3 expression. The TEX1 protein was present in epidermal cells, but not in the germline, and, through TAS3-derived ta-siRNA, restricted ARF3 expression to the medio domain of ovule primordia. Expansion of ARF3 expression into lateral epidermal cells in a TAS3 ta-siRNA-insensitive mutant led to the formation of supernumerary megaspore mother cells, suggesting that TEX1- and TAS3-mediated restriction of ARF3 expression limits excessive megaspore mother cell formation non-cell-autonomously. Our findings reveal the role of a small-RNA pathway in the regulation of female germline specification in Arabidopsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

ADP-Ribosylation Factor 6 Regulates a Novel Plasma Membrane Recycling Pathway

PubMed Central

Radhakrishna, Harish; Donaldson, Julie G.

1997-01-01

ADP-ribosylation factor (ARF) 6 localizes to the plasma membrane (PM) in its GTP state and to a tubulovesicular compartment in its GDP state in HeLa cells that express wild-type or mutant forms of this GTPase. Aluminum fluoride (AlF) treatment of ARF6-transfected cells redistributes ARF6 to the PM and stimulates the formation of actin-rich surface protrusions. Here we show that cytochalasin D (CD) treatment inhibited formation of the AlF-induced protrusions and shifted the distribution of ARF6 to a tubular membrane compartment emanating from the juxtanuclear region of cells, which resembled the compartment where the GTP-binding defective mutant of ARF6 localized. This membrane compartment was distinct from transferrin-positive endosomes, could be detected in the absence of ARF6 overexpression or CD treatment, and was accessible to loading by PM proteins lacking clathrin/AP-2 cytoplasmic targeting sequences, such as the IL-2 receptor α subunit Tac. ARF6 and surface Tac moved into this compartment and back out to the PM in the absence of pharmacologic treatment. Whereas AlF treatment blocked internalization, CD treatment blocked the recycling of wild-type ARF6 and Tac back to the PM; these blocks were mimicked by expression of ARF6 mutants Q67L and T27N, which were predicted to be in either the GTP- or GDP-bound state, respectively. Thus, the ARF6 GTP cycle regulates this membrane traffic pathway. The delivery of ARF6 and membrane to defined sites along the PM may provide components necessary for remodeling the cell surface and the underlying actin cytoskeleton. PMID:9314528

ASC-J9(®) suppresses castration resistant prostate cancer progression via degrading the enzalutamide-induced androgen receptor mutant AR-F876L.

PubMed

Wang, Ronghao; Lin, Wanying; Lin, Changyi; Li, Lei; Sun, Yin; Chang, Chawnshang

2016-08-28

Androgen deprivation therapy (ADT) with the newly developed powerful anti-androgen enzalutamide (Enz, also known as MDV3100) has promising therapeutic effects to suppress castration resistant prostate cancer (CRPC) and extending patients' lives an extra 4.8 months. However, most Enz therapy eventually fails with the development of Enz resistance. The detailed mechanisms how CRPC develops Enz resistance remain unclear and may involve multiple mechanisms. Among them, the induction of the androgen receptor (AR) mutant AR-F876L in some CRPC patients may represent one driving force that confers Enz resistance. Here, we demonstrate that the AR degradation enhancer, ASC-J9(®), not only degrades wild-type AR, but also has the ability to target AR-F876L. The consequence of suppressing AR-F876L may then abrogate AR-F876L mediated CRPC cell proliferation and metastasis. Thus, developing ASC-J9(®) as a new therapeutic approach may represent a novel therapy to better suppress CRPC that has already developed Enz resistance. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The p16INK4alpha/p19ARF gene mutations are infrequent and are mutually exclusive to p53 mutations in Indian oral squamous cell carcinomas.

PubMed

Kannan, K; Munirajan, A K; Krishnamurthy, J; Bhuvarahamurthy, V; Mohanprasad, B K; Panishankar, K H; Tsuchida, N; Shanmugam, G

2000-03-01

Eighty-seven untreated primary oral squamous cell carcinomas (SCCs) associated with betel quid and tobacco chewing from Indian patients were analysed for the presence of mutations in the commonly shared exon 2 of p16INK4alpha/p19ARF genes. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing analysis were used to detect mutations. SSCP analysis indicated that only 9% (8/87) of the tumours had mutation in p16INK4alpha/p19ARF genes. Seventy-two tumours studied here were previously analysed for p53 mutations and 21% (15/72) of them were found to have mutations in p53 gene. Only one tumour was found to have mutation at both p53 and p16INK4alpha/p19ARF genes. Thus, the mutation rates observed were 21% for p53, 9% for p16INK4alpha/p19ARF, and 1% for both. Sequencing analysis revealed two types of mutations; i) G to C (GCAG to CCAG) transversion type mutation at intron 1-exon 2 splice junction and ii) another C to T transition type mutation resulting in CGA to TGA changing arginine to a termination codon at p16INK4alpha gene codon 80 and the same mutation will alter codon 94 of p19ARF gene from CCG to CTG (proline to leucine). These results suggest that p16INK4alpha/p19ARF mutations are less frequent than p53 mutations in Indian oral SCCs. The p53 and p16INK4alpha/p19ARF mutational events are independent and are mutually exclusive suggesting that mutational inactivation of either p53 or p16INK4alpha/p19ARF may alleviate the need for the inactivation of the other gene.

Class II ADP-ribosylation factors are required for efficient secretion of dengue viruses.

PubMed

Kudelko, Mateusz; Brault, Jean-Baptiste; Kwok, Kevin; Li, Ming Yuan; Pardigon, Nathalie; Peiris, J S Malik; Bruzzone, Roberto; Desprès, Philippe; Nal, Béatrice; Wang, Pei Gang

2012-01-02

Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins.

Defect printability of ArF alternative phase-shift mask: a critical comparison of simulation and experiment

NASA Astrophysics Data System (ADS)

Ozawa, Ken; Komizo, Tooru; Ohnuma, Hidetoshi

2002-07-01

An alternative phase shift mask (alt-PSM) is a promising device for extending optical lithography to finer design rules. There have been few reports, however, on the mask's ability to identify phase defects. We report here an alt-PSM of a single-trench type with undercut for ArF exposure, with programmed phase defects used to evaluate defect printability by measuring aerial images with a Zeiss MSM193 measuring system. The experimental results are simulated using the TEMPEST program. First, a critical comparison of the simulation and the experiment is conducted. The actual measured topographies of quartz defects are used in the simulation. Moreover, a general simulation study on defect printability using an alt-PSM for ArF exposure is conducted. The defect dimensions, which produce critical CD errors, are determined by simulation that takes into account the full 3-dimensional structure of phase defects as well as a simplified structure. The critical dimensions of an isolated bump defect identified by the alt-PSM of a single-trench type with undercut for ArF exposure are 300 nm in bottom dimension and 74 degrees in height (phase) for the real shape, where the depth of wet-etching is 100 nm and the CD error limit is +/- 5 percent.

Interaction of a Blumeria graminis f. sp. hordei effector candidate with a barley ARF-GAP suggests that host vesicle trafficking is a fungal pathogenicity target.

PubMed

Schmidt, Sarah M; Kuhn, Hannah; Micali, Cristina; Liller, Corinna; Kwaaitaal, Mark; Panstruga, Ralph

2014-08-01

Filamentous phytopathogens, such as fungi and oomycetes, secrete effector proteins to establish successful interactions with their plant hosts. In contrast with oomycetes, little is known about effector functions in true fungi. We used a bioinformatics pipeline to identify Blumeria effector candidates (BECs) from the obligate biotrophic barley powdery mildew pathogen, Blumeria graminis f. sp. hordei (Bgh). BEC1-BEC5 are expressed at different time points during barley infection. BEC1, BEC2 and BEC4 have orthologues in the Arabidopsis thaliana-infecting powdery mildew fungus Golovinomyces orontii. Arabidopsis lines stably expressing the G. orontii BEC2 orthologue, GoEC2, are more susceptible to infection with the non-adapted fungus Erysiphe pisi, suggesting that GoEC2 contributes to powdery mildew virulence. For BEC3 and BEC4, we identified thiopurine methyltransferase, a ubiquitin-conjugating enzyme, and an ADP ribosylation factor-GTPase-activating protein (ARF-GAP) as potential host targets. Arabidopsis knockout lines of the respective HvARF-GAP orthologue (AtAGD5) allowed higher entry levels of E. pisi, but exhibited elevated resistance to the oomycete Hyaloperonospora arabidopsidis. We hypothesize that ARF-GAP proteins are conserved targets of powdery and downy mildew effectors, and we speculate that BEC4 might interfere with defence-associated host vesicle trafficking. © 2013 BSPP AND JOHN WILEY & SONS LTD.

HBEGF promotes gliomagenesis in the context of Ink4a/Arf and Pten loss

PubMed Central

Shin, Clifford H.; Robinson, James P.; Sonnen, Joshua A.; Welker, Adam E.; Yu, Diana X.; VanBrocklin, Matthew W.; Holmen, Sheri L.

2017-01-01

Heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) is a ligand for the epidermal growth factor receptor (EGFR), one of the most commonly amplified receptor tyrosine kinases (RTK) in glioblastoma. While HBEGF has been found to be expressed in a subset of malignant gliomas, its sufficiency for glioma initiation has not been evaluated. In this study, we demonstrate that HBEGF can initiate glioblastoma (GBM) in mice in the context of Ink4a/Arf and Pten loss, and that these tumors are similar to the classical GBM subtype observed in patients. Isogenic astrocytes from these mice showed activation not only of Egfr but also the RTK Axl in response to HBEGF stimulation. Deletion of either Egfr or Axl decreased the tumorigenic properties of HBEGF transformed cells; however only EGFR was able to rescue the phenotype in cells lacking both RTKs indicating that Egfr is required for activation of Axl in this context. Silencing of HBEGF in vivo resulted in tumor regression and significantly increased survival suggesting that HBEGF may be a clinically relevant target. PMID:28368403

Family Factors Related to Adolescent Autonomy.

ERIC Educational Resources Information Center

Pardeck, Jean A.; Pardeck, John T.

1990-01-01

Analyzes role that the family plays in the development of adolescent autonomy. Three family factors are analyzed in relation to the development of adolescent autonomy: parenting styles, family interaction, and transitions related to the family life cycle. (Author/NB)

Class II ADP-ribosylation Factors Are Required for Efficient Secretion of Dengue Viruses*

PubMed Central

Kudelko, Mateusz; Brault, Jean-Baptiste; Kwok, Kevin; Li, Ming Yuan; Pardigon, Nathalie; Peiris, J. S. Malik; Bruzzone, Roberto; Desprès, Philippe; Nal, Béatrice; Wang, Pei Gang

2012-01-01

Identification and characterization of virus-host interactions are very important steps toward a better understanding of the molecular mechanisms responsible for disease progression and pathogenesis. To date, very few cellular factors involved in the life cycle of flaviviruses, which are important human pathogens, have been described. In this study, we demonstrate a crucial role for class II Arf proteins (Arf4 and Arf5) in the dengue flavivirus life cycle. We show that simultaneous depletion of Arf4 and Arf5 blocks recombinant subviral particle secretion for all four dengue serotypes. Immunostaining analysis suggests that class II Arf proteins are required at an early pre-Golgi step for dengue virus secretion. Using a horseradish peroxidase protein fused to a signal peptide, we show that class II Arfs act specifically on dengue virus secretion without altering the secretion of proteins through the constitutive secretory pathway. Co-immunoprecipitation data demonstrate that the dengue prM glycoprotein interacts with class II Arf proteins but not through its C-terminal VXPX motif. Finally, experiments performed with replication-competent dengue and yellow fever viruses demonstrate that the depletion of class II Arfs inhibits virus secretion, thus confirming their implication in the virus life cycle, although data obtained with West Nile virus pointed out the differences in virus-host interactions among flaviviruses. Our findings shed new light on a molecular mechanism used by dengue viruses during the late stages of the life cycle and demonstrate a novel function for class II Arf proteins. PMID:22105072

MDM2 is an important prognostic and predictive factor for platin-pemetrexed therapy in malignant pleural mesotheliomas and deregulation of P14/ARF (encoded by CDKN2A) seems to contribute to an MDM2-driven inactivation of P53.

PubMed

Walter, R F H; Mairinger, F D; Ting, S; Vollbrecht, C; Mairinger, T; Theegarten, D; Christoph, D C; Schmid, K W; Wohlschlaeger, J

2015-03-03

Malignant pleural mesothelioma (MPM) is a highly aggressive tumour that is first-line treated with a combination of cisplatin and pemetrexed. Until now, predictive and prognostic biomarkers are lacking, making it a non-tailored therapy regimen with unknown outcome. P53 is frequently inactivated in MPM, but mutations are extremely rare. MDM2 and P14/ARF are upstream regulators of P53 that may contribute to P53 inactivation. A total of 72 MPM patients were investigated. MDM2 immunoexpression was assessed in 65 patients. MDM2 and P14/ARF mRNA expression was analysed in 48 patients of the overall collective. The expression results were correlated to overall survival (OS) and progression-free survival (PFS). OS and PFS correlated highly significantly with MDM2 mRNA and protein expression, showing a dismal prognosis for patients with elevated MDM2 expression (for OS: Score (logrank) test: P⩽0.002, and for PFS: Score (logrank) test; P<0.007). MDM2 was identified as robust prognostic and predictive biomarker for MPM on the mRNA and protein level. P14/ARF mRNA expression reached no statistical significance, but Kaplan-Meier curves distinguished patients with low P14/ARF expression and hence shorter survival from patients with higher expression and prolonged survival. MDM2 is a prognostic and predictive marker for a platin-pemetrexed therapy of patients with MPMs. Downregulation of P14/ARF expression seems to contribute to MDM2-overexpression-mediated P53 inactivation in MPM patients.

Temperature monitoring by infrared radiation measurements during ArF excimer laser ablation with cornea

NASA Astrophysics Data System (ADS)

Ishihara, Miya; Arai, Tsunenori; Sato, Shunichi; Nakano, Hironori; Obara, Minoru; Kikuchi, Makoto

1999-06-01

We measured infrared thermal radiation from porcine cornea during various fluences ArF excimer laser ablations with 1 microsecond(s) rise time. To obtain absolute temperature by means of Stefan-Boltzman law of radiation, we carried out a collection efficiency and detective sensitivity by a pre-experiment using panel heater. We measured the time course of the thermal radiation intensity with various laser fluences. We studied the relation between the peak cornea temperature during the ablation and irradiation fluences. We found the ablation situations, i.e., sub-ablation threshold, normal thermal ablation, and over-heated ablation, may be judged by both of the measured temperature transient waveforms and peak temperature. The boundary fluences corresponding to normal thermal ablation were 90 and 160 mJ/cm2. Our fast remote temperature monitoring during cornea ablation might be useful to control ablation quality/quantity of the cornea ArF laser ablation, that is PRK.

C/EBPβ represses p53 to promote cell survival downstream of DNA damage independent of oncogenic Ras and p19Arf

PubMed Central

Ewing, SJ; Zhu, S; Zhu, F; House, JS; Smart, RC

2013-01-01

CCAAT/enhancer-binding protein-β (C/EBPβ) is a mediator of cell survival and tumorigenesis. When C/EBPβ−/− mice are treated with carcinogens that produce oncogenic Ras mutations in keratinocytes, they respond with abnormally elevated keratinocyte apoptosis and a block in skin tumorigenesis. Although this aberrant carcinogen-induced apoptosis results from abnormal upregulation of p53, it is not known whether upregulated p53 results from oncogenic Ras and its ability to induce p19Arf and/or activate DNA-damage response pathways or from direct carcinogen-induced DNA damage. We report that p19Arf is dramatically elevated in C/EBPβ−/− epidermis and that C/EBPβ represses a p19Arf promoter reporter. To determine whether p19Arf is responsible for the proapoptotic phenotype in C/EBPβ−/− mice, C/EBPβ−/−;p19Arf−/− mice were generated. C/EBPβ−/−;p19Arf−/− mice responded to carcinogen treatment with increased p53 and apoptosis, indicating p19Arf is not essential. To ascertain whether oncogenic Ras activation induces aberrant p53 and apoptosis in C/EBPβ−/− epidermis, we generated K14-ER:Ras; C/EBPβ−/− mice. Oncogenic Ras activation induced by 4-hydroxytamoxifen did not produce increased p53 or apoptosis. Finally, when C/EBPβ−/− mice were treated with differing types of DNA-damaging agents, including alkylating chemotherapeutic agents, they displayed aberrant levels of p53 and apoptosis. These results indicate that C/EBPβ represses p53 to promote cell survival downstream of DNA damage and suggest that inhibition of C/EBPβ may be a target for cancer cotherapy to increase the efficacy of alkylating chemotherapeutic agents. PMID:18636078

Brefeldin A Inhibits Cell-Free, De Novo Synthesis of Poliovirus

PubMed Central

Cuconati, Andrea; Molla, Akhteruzzaman; Wimmer, Eckard

1998-01-01

Brefeldin A (BFA), an inhibitor of intracellular vesicle-dependent secretory transport, is a potent inhibitor of poliovirus RNA replication in infected cells. We have determined that the unknown mechanism of BFA inhibition of replication is reproduced in the cell-free poliovirus translation, replication, and encapsidation system. Furthermore, we provide evidence suggesting that the cellular mechanism targeted by BFA, the GTP-dependent synthesis of secretory transport vesicles, may be involved in viral RNA replication in the system via a soluble cellular GTP-binding and -hydrolyzing activity. This activity is related to the ARF (ADP-ribosylation factor) family of GTP-binding proteins. ARFs are required for the formation of several classes of secretory vesicles, and some family members are indirectly inactivated by BFA. Peptides that function as competitive inhibitors of ARF activity in cell-free transport systems also inhibit poliovirus RNA replication, and this inhibitory effect can be countered by the addition of exogenous ARF. We suggest that BFA inhibition of replication is diagnostic of a requirement for ARF activity in the cell-free system. PMID:9658088

The Structure of RalF, an ADP-Ribosylation Factor Guanine Nucleotide Exchange Factor from Legionella pneumophila, Reveals the Presence of a Cap over the Active Site

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

Amor,J.; Swails, J.; Zhu, X.

2005-01-01

The Legionella pneumophila protein RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine nucleotide exchange factors, has suggested that recruitment of Arf is an early step in pathogenesis. We have determined the crystal structure of RalF and of the isolated Sec7 domain and found that RalF is made up of two domains. The Sec7 domain is homologous to mammalian Sec7 domains. The C-terminal domain forms amore » cap over the active site in the Sec7 domain and contains a conserved folding motif, previously observed in adaptor subunits of vesicle coat complexes. The importance of the capping domain and of the glutamate in the 'glutamic finger,' conserved in all Sec7 domains, to RalF functions was examined using three different assays. These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities.« less

EFFECTS OF LASER RADIATION ON MATTER. LASER PLASMA Annealing of induced absorption in quartz glasses by ArF laser radiation

NASA Astrophysics Data System (ADS)

Sergeev, P. B.; Sergeev, A. P.

2010-11-01

Annealing of individual bands of electron-beam-induced absorption (IA) in the region of 150 — 400 nm in KS-4V, KU-1, and Corning 7980 (ArF Grade) quartz glasses by ArF laser radiation is studied. It is shown that the phototransformation of the IA spectra occurs mainly due to a significant decrease in the amplitudes of bands at λ = 183.5, 213, and 260 nm. The role played by interstitial oxygen, hydrogen, and chlorine in the formation and relaxation of glass defects is considered.

Rayleigh rejection filters for 193-nm ArF laser Raman spectroscopy

NASA Technical Reports Server (NTRS)

Mckenzie, Robert L.

1993-01-01

Selected organic absorbers and their solvents are evaluated as spectral filters for the rejection of 193-nm Rayleigh light associated with the use of an ArF excimer laser for Raman spectroscopy. A simply constructed filter cell filled with 0.5 percent acetone in water and an optical path of 7 mm is shown effectively to eliminate stray Rayleigh light underlying the Raman spectrum from air while transmitting 60 percent of the Raman light scattered by O2.

Somatic INK4a-ARF locus mutations: a significant mechanism of gene inactivation in squamous cell carcinomas of the head and neck.

PubMed

Poi, M J; Yen, T; Li, J; Song, H; Lang, J C; Schuller, D E; Pearl, D K; Casto, B C; Tsai, M D; Weghorst, C M

2001-01-01

The INK4a-ARF locus is located on human chromosome 9p21 and is known to encode two functionally distinct tumor-suppressor genes. The p16(INK4a) (p16) tumor-suppressor gene product is a negative regulator of cyclin-dependent kinases 4 and 6, which in turn positively regulate progression of mammalian cells through the cell cycle. The p14(ARF) tumor-suppressor gene product specifically interacts with human double minute 2, leading to the subsequent stabilization of p53 and G(1) arrest. Previous investigations analyzing the p16 gene in squamous cell carcinomas of the head and neck (SCCHNs) have suggested the predominate inactivating events to be homozygous gene deletions and hypermethylation of the p16 promoter. Somatic mutational inactivation of p16 has been reported to be low (0-10%, with a combined incidence of 25 of 279, or 9%) and to play only a minor role in the development of SCCHN. The present study examined whether this particular mechanism of INK4a/ARF inactivation, specifically somatic mutation, has been underestimated in SCCHN by determining the mutational status of the p16 and p14(ARF) genes in 100 primary SCCHNs with the use of polymerase chain reaction technology and a highly sensitive, nonradioactive modification of single-stranded conformational polymorphism (SSCP) analysis termed "cold" SSCP. Exons 1alpha, 1beta, and 2 of INK4a/ARF were amplified using intron-based primers or a combination of intron- and exon-based primers. A total of 27 SCCHNs (27%) exhibited sequence alterations in this locus, 22 (22%) of which were somatic sequence alterations and five (5%) of which were a single polymorphism in codon 148. Of the 22 somatic alterations, 20 (91%) directly or indirectly involved exon 2, and two (9%) were located within exon 1alpha. No mutations were found in exon 1beta. All 22 somatic mutations would be expected to yield altered p16 proteins, but only 15 of them should affect p14(ARF) proteins. Specific somatic alterations included microdeletions or

Exclusion of Integrins from CNS Axons Is Regulated by Arf6 Activation and the AIS

PubMed Central

Franssen, Elske H. P.; Zhao, Rong-Rong; Koseki, Hiroaki; Kanamarlapudi, Venkateswarlu; Hoogenraad, Casper C.

2015-01-01

Integrins are adhesion and survival molecules involved in axon growth during CNS development, as well as axon regeneration after injury in the peripheral nervous system (PNS). Adult CNS axons do not regenerate after injury, partly due to a low intrinsic growth capacity. We have previously studied the role of integrins in axon growth in PNS axons; in the present study, we investigate whether integrin mechanisms involved in PNS regeneration may be altered or lacking from mature CNS axons by studying maturing CNS neurons in vitro. In rat cortical neurons, we find that integrins are present in axons during initial growth but later become restricted to the somato-dendritic domain. We investigated how this occurs and whether it can be altered to enhance axonal growth potential. We find a developmental change in integrin trafficking; transport becomes predominantly retrograde throughout axons, but not dendrites, as neurons mature. The directionality of transport is controlled through the activation state of ARF6, with developmental upregulation of the ARF6 GEF ARNO enhancing retrograde transport. Lowering ARF6 activity in mature neurons restores anterograde integrin flow, allows transport into axons, and increases axon growth. In addition, we found that the axon initial segment is partly responsible for exclusion of integrins and removal of this structure allows integrins into axons. Changing posttranslational modifications of tubulin with taxol also allows integrins into the proximal axon. The experiments suggest that the developmental loss of regenerative ability in CNS axons is due to exclusion of growth-related molecules due to changes in trafficking. PMID:26019348

Mdm2 overexpression and p14(ARF) inactivation are two mutually exclusive events in primary human lung tumors.

PubMed

Eymin, Béatrice; Gazzeri, Sylvie; Brambilla, Christian; Brambilla, Elisabeth

2002-04-18

Pathways involving p53 and pRb tumor suppressor genes are frequently deregulated during lung carcinogenesis. Through its location at the interface of these pathways, Mdm2 can modulate the function of both p53 and pRb genes. We have examined here the pattern of expression of Mdm2 in a series of 192 human lung carcinomas of all histological types using both immunohistochemical and Western blot analyses and four distinct antibodies mapping different epitopes onto the Mdm2 protein. Using Immunohistochemistry (IHC), Mdm2 was overexpressed as compared to normal lung in 31% (60 out of 192) of all tumors analysed, whatever their histological types. Western blotting was performed on 28 out of the 192 tumoral samples. Overexpression of p85/90, p74/76 and p57 Mdm2 isoforms was detected in 18% (5 out of 28), 25% (7 out of 28) and 39% (11 out of 28) of the cases respectively. Overall, overexpression of at least one isoform was observed in 14 out of 28 (50%) lung tumors and concomittant overexpression of at least two isoforms in 7 out of 28 (25%) cases. A good concordance (82%) was observed between immunohistochemical and Western blot data. Interestingly, a highly significant inverse relationship was detected between p14(ARF) loss and Mdm2 overexpression either in NSCLC (P=0.0089) or in NE lung tumors (P<0.0001). Furthermore, a Mdm2/p14(ARF) >1 ratio was correlated with a high grade phenotype among NE tumors overexpressing Mdm2 (P=0.0021). Taken together, these data strongly suggest that p14(ARF)and Mdm2 act on common pathway(s) to regulate p53 and/or pRb-dependent or independent functions and that the Mdm2 : p14(ARF) ratio might act as a rheostat in modulating the activity of both proteins.

A systematic review of risk and protective factors associated with family related violence in refugee families.

PubMed

Timshel, Isabelle; Montgomery, Edith; Dalgaard, Nina Thorup

2017-08-01

The current systematic review summarizes the evidence from studies examining the risk and protective factors associated with family related violence in refugee families. Data included 15 peer-reviewed qualitative and quantitative studies. In order to gain an overview of the identified risk and protective factors an ecological model was used to structure the findings. At the individual level, parental trauma experiences/mental illness, substance abuse and history of child abuse were found to be risk factors. Family level risk factors included parent-child interaction, family structure and family acculturation stress. At the societal level low socioeconomic status was identified as a risk factor. Cultural level risk factors included patriarchal beliefs. Positive parental coping strategies were a protective factor. An ecological analysis of the results suggests that family related violence in refugee families is a result of accumulating, multiple risk factors on the individual, familial, societal and cultural level. The findings suggest that individual trauma and exile related stress do not only affect the individual but have consequences at a family level. Thus, interventions targeting family related violence should not only include the individual, but the family. Copyright © 2017 Elsevier Ltd. All rights reserved.

The areal reduction factor: A new analytical expression for the Lazio Region in central Italy

NASA Astrophysics Data System (ADS)

Mineo, C.; Ridolfi, E.; Napolitano, F.; Russo, F.

2018-05-01

For the study and modeling of hydrological phenomena, both in urban and rural areas, a proper estimation of the areal reduction factor (ARF) is crucial. In this paper, we estimated the ARF from observed rainfall data as the ratio between the average rainfall occurring in a specific area and the point rainfall. Then, we compared the obtained ARF values with some of the most widespread empirical approaches in literature which are used when rainfall observations are not available. Results highlight that the literature formulations can lead to a substantial over- or underestimation of the ARF estimated from observed data. These findings can have severe consequences, especially in the design of hydraulic structures where empirical formulations are extensively applied. The aim of this paper is to present a new analytical relationship with an explicit dependence on the rainfall duration and area that can better represent the ARF-area trend over the area case of study. The analytical curve presented here can find an important application to estimate the ARF values for design purposes. The test study area is the Lazio Region (central Italy).

Spatial and temporal expression patterns of auxin response transcription factors in the syncytium induced by the beet cyst nematode Heterodera schachtii in Arabidopsis.

PubMed

Hewezi, Tarek; Piya, Sarbottam; Richard, Geoffrey; Rice, J Hollis

2014-09-01

Plant-parasitic cyst nematodes induce the formation of a multinucleated feeding site in the infected root, termed the syncytium. Recent studies point to key roles of the phytohormone auxin in the regulation of gene expression and establishment of the syncytium. Nevertheless, information about the spatiotemporal expression patterns of the transcription factors that mediate auxin transcriptional responses during syncytium formation is limited. Here, we provide a gene expression map of 22 auxin response factors (ARFs) during the initiation, formation and maintenance stages of the syncytium induced by the cyst nematode Heterodera schachtii in Arabidopsis. We observed distinct and overlapping expression patterns of ARFs throughout syncytium development phases. We identified a set of ARFs whose expression is predominantly located inside the developing syncytium, whereas others are expressed in the neighbouring cells, presumably to initiate specific transcriptional programmes required for their incorporation within the developing syncytium. Our analyses also point to a role of certain ARFs in determining the maximum size of the syncytium. In addition, several ARFs were found to be highly expressed in fully developed syncytia, suggesting a role in maintaining the functional phenotype of mature syncytia. The dynamic distribution and overlapping expression patterns of various ARFs seem to be essential characteristics of ARF activity during syncytium development. © 2014 BSPP AND JOHN WILEY & SONS LTD.

HBEGF promotes gliomagenesis in the context of Ink4a/Arf and Pten loss.

PubMed

Shin, C H; Robinson, J P; Sonnen, J A; Welker, A E; Yu, D X; VanBrocklin, M W; Holmen, S L

2017-08-10

Heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) is a ligand for the EGF receptor (EGFR), one of the most commonly amplified receptor tyrosine kinases (RTKs) in glioblastoma (GBM). While HBEGF has been found to be expressed in a subset of malignant gliomas, its sufficiency for glioma initiation has not been evaluated. In this study, we demonstrate that HBEGF can initiate GBM in mice in the context of Ink4a/Arf and Pten loss, and that these tumors are similar to the classical GBM subtype observed in patients. Isogenic astrocytes from these mice showed activation not only of Egfr but also the RTK Axl in response to HBEGF stimulation. Deletion of either Egfr or Axl decreased the tumorigenic properties of HBEGF-transformed cells; however, only EGFR was able to rescue the phenotype in cells lacking both RTKs indicating that Egfr is required for activation of Axl in this context. Silencing of HBEGF in vivo resulted in tumor regression and significantly increased survival, suggesting that HBEGF may be a clinically relevant target.

AUXIN RESPONSE FACTOR17 Is Essential for Pollen Wall Pattern Formation in Arabidopsis1[C][W][OA

PubMed Central

Yang, Jun; Tian, Lei; Sun, Ming-Xi; Huang, Xue-Yong; Zhu, Jun; Guan, Yue-Feng; Jia, Qi-Shi; Yang, Zhong-Nan

2013-01-01

In angiosperms, pollen wall pattern formation is determined by primexine deposition on the microspores. Here, we show that AUXIN RESPONSE FACTOR17 (ARF17) is essential for primexine formation and pollen development in Arabidopsis (Arabidopsis thaliana). The arf17 mutant exhibited a male-sterile phenotype with normal vegetative growth. ARF17 was expressed in microsporocytes and microgametophytes from meiosis to the bicellular microspore stage. Transmission electron microscopy analysis showed that primexine was absent in the arf17 mutant, which leads to pollen wall-patterning defects and pollen degradation. Callose deposition was also significantly reduced in the arf17 mutant, and the expression of CALLOSE SYNTHASE5 (CalS5), the major gene for callose biosynthesis, was approximately 10% that of the wild type. Chromatin immunoprecipitation and electrophoretic mobility shift assays showed that ARF17 can directly bind to the CalS5 promoter. As indicated by the expression of DR5-driven green fluorescent protein, which is an synthetic auxin response reporter, auxin signaling appeared to be specifically impaired in arf17 anthers. Taken together, our results suggest that ARF17 is essential for pollen wall patterning in Arabidopsis by modulating primexine formation at least partially through direct regulation of CalS5 gene expression. PMID:23580594

Bmi1 represses Ink4a/Arf and Hox genes to regulate stem cells in the rodent incisor

PubMed Central

Biehs, Brian; Hu, Jimmy Kuang-Hsien; Strauli, Nicolas B.; Sangiorgi, Eugenio; Jung, Heekyung; Heber, Ralf-Peter; Ho, Sunita; Goodwin, Alice F.; Dasen, Jeremy S.; Capecchi, Mario R.; Klein, Ophir D.

2013-01-01

The polycomb group gene Bmi1 is required for maintenance of adult stem cells in many organs1, 2. Inactivation of Bmi1 leads to impaired stem cell self-renewal due to deregulated gene expression. One critical target of BMI1 is Ink4a/Arf, which encodes the cell cycle inhibitors p16ink4a and p19Arf3. However, deletion of Ink4a/Arf only partially rescues Bmi1 null phenotypes4, indicating that other important targets of BMI1 exist. Here, using the continuously-growing mouse incisor as a model system, we report that Bmi1 is expressed by incisor stem cells and that deletion of Bmi1 resulted in fewer stem cells, perturbed gene expression, and defective enamel production. Transcriptional profiling revealed that Hox expression is normally repressed by BMI1 in the adult, and functional assays demonstrated that BMI1-mediated repression of Hox genes preserves the undifferentiated state of stem cells. As Hox gene upregulation has also been reported in other systems when Bmi1 is inactivated1, 2, 5–7, our findings point to a general mechanism whereby BMI1-mediated repression of Hox genes is required for the maintenance of adult stem cells and for prevention of inappropriate differentiation. PMID:23728424

Ablation and cone formation mechanism on CR-39 by ArF laser irradiation

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

Shakeri Jooybari, B., E-mail: baninshakery@gmail.com, E-mail: hafarideh@aut.ac.ir; Nuclear Science and Technology Research Institute NSRT, Tehran; Afarideh, H., E-mail: baninshakery@gmail.com, E-mail: hafarideh@aut.ac.ir

In this work, chemical properties, surface modification, and micro structures formation on ablated polyallyl di-glycol carbonate (CR-39) polymer by ArF laser irradiation (λ = 193 nm) at various fluences and pulse number were investigated. CR-39 samples have been irradiated with an ArF laser (193 nm) at a repetition rate of 1 Hz. Threshold fluence of ablation and effective absorption coefficient of CR-39 were determined. Conical microstructures (Taylor cone) formed on laser-ablated CR-39 exhibit: smooth, Taylor cone shape walls and sharp tips together with interference and well defined fringe-structure with a period of 230 nm, around cone base. Mechanism of cone formation and cone evolution of CR-39more » ablated surface were investigated by change of fluences (at a given pulse number) and pulse number (at a given fluence). Cone height, cone base, and region of interface were increased in micrometer steps by increasing the total fluence. Depression on the base of the cone and the circular fringe were simulated. FTIR spectra were measured and energy dispersive x-ray analysis of irradiated and un-irradiated samples was performed.« less

A design of energy detector for ArF excimer lasers

NASA Astrophysics Data System (ADS)

Feng, Zebin; Han, Xiaoquan; Zhou, Yi; Bai, Lujun

2017-08-01

ArF excimer lasers with short wavelength and high photon energy are widely applied in the field of integrated circuit lithography, material processing, laser medicine, and so on. Excimer laser single pulse energy is a very important parameter in the application. In order to detect the single pulse energy on-line, one energy detector based on photodiode was designed. The signal processing circuit connected to the photodiode was designed so that the signal obtained by the photodiode was amplified and the pulse width was broadened. The amplified signal was acquired by a data acquisition card and stored in the computer for subsequent data processing. The peak of the pulse signal is used to characterize the single pulse energy of ArF excimer laser. In every condition of deferent pulse energy value levels, a series of data about laser pulses energy were acquired synchronously using the Ophir energy meter and the energy detector. A data set about the relationship between laser pulse energy and the peak of the pulse signal was acquired. Then, by using the data acquired, a model characterizing the functional relationship between the energy value and the peak value of the pulse was trained based on an algorithm of machine learning, Support Vector Regression (SVR). By using the model, the energy value can be obtained directly from the energy detector designed in this project. The result shows that the relative error between the energy obtained by the energy detector and by the Ophir energy meter is less than 2%.

PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a.

PubMed

Yamaoka, Mami; Ando, Tomomi; Terabayashi, Takeshi; Okamoto, Mitsuhiro; Takei, Masahiro; Nishioka, Tomoki; Kaibuchi, Kozo; Matsunaga, Kohichi; Ishizaki, Ray; Izumi, Tetsuro; Niki, Ichiro; Ishizaki, Toshimasa; Kimura, Toshihide

2016-02-01

In secretory cells, endocytosis is coupled to exocytosis to enable proper secretion. Although endocytosis is crucial to maintain cellular homeostasis before and after secretion, knowledge about secretagogue-induced endocytosis in secretory cells is still limited. Here, we searched for proteins that interacted with the Rab27a GTPase-activating protein (GAP) EPI64 (also known as TBC1D10A) and identified the Arf6 guanine-nucleotide-exchange factor (GEF) ARNO (also known as CYTH2) in pancreatic β-cells. We found that the insulin secretagogue glucose promotes phosphatidylinositol (3,4,5)-trisphosphate (PIP3) generation through phosphoinositide 3-kinase (PI3K), thereby recruiting ARNO to the intracellular side of the plasma membrane. Peripheral ARNO promotes clathrin assembly through its GEF activity for Arf6 and regulates the early stage of endocytosis. We also found that peripheral ARNO recruits EPI64 to the same area and that the interaction requires glucose-induced endocytosis in pancreatic β-cells. Given that GTP- and GDP-bound Rab27a regulate exocytosis and the late stage of endocytosis, our results indicate that the glucose-induced activation of PI3K plays a pivotal role in exocytosis-endocytosis coupling, and that ARNO and EPI64 regulate endocytosis at distinct stages. © 2016. Published by The Company of Biologists Ltd.

Family climates: family factors specific to disturbed eating and bulimia nervosa.

PubMed

Laliberté, M; Boland, F J; Leichner, P

1999-09-01

More than a decade of research has characterized the families of individuals with bulimia and bulimia anorexia (Anorexia Nervosa, Binge/Purging Type) as less expressive, less cohesive, and experiencing more conflicts than normal control families. This two-part study investigated variables believed more directly related to disturbed eating and bulimia as contributing to a "family climate for eating disorders." In Study 1. a nonclinical sample of 324 women who had just left home for college and a sample of 121 mothers evaluated their families. Principal-components analyses revealed the same factor structure for both students and mothers, with Family Body Satisfaction, Family Social Appearance Orientation, and Family Achievement Emphasis loading together, representing the hypothesized family climate for eating disorders: the remaining variables loaded with the more traditional family process variables (conflict, cohesion, expressiveness), representing a more general family dysfunction. As predicted, the family climate for eating disorders factor score was a more powerful predictor of disturbed eating. Study 2 extended these findings into a clin ical population, examining whether the family climate for eating disorders variables would distinguish individuals with bulimia from both depressed and healthy controls. Groups of eating-disordered patients (n = 40) and depressed (n = 17) and healthy (n = 27) controls completed family measures. The eating-disordered group scored significantly higher on family climate variables than control groups. Family process variables distinguished clinical groups (depressed and eating disordered) from healthy controls, but not from one another. Controlling for depression removed group differences on family process variables, but family climate variables continued to distinguish the eating-disordered group from both control groups. Indications for further research are discussed.

Collateral damage-free debridement using 193nm ArF laser

NASA Astrophysics Data System (ADS)

Wynne, James J.; Felsenstein, Jerome M.; Trzcinski, Robert; Zupanski-Nielsen, Donna; Connors, Daniel P.

2011-03-01

Burn eschar and other necrotic areas of the skin and soft tissue are anhydrous compared to the underlying viable tissue. A 193 nm ArF excimer laser, emitting electromagnetic radiation at 6.4 eV at fluence exceeding the ablation threshold, will debride such necrotic areas. Because such radiation is strongly absorbed by aqueous chloride ions through the nonthermal process of electron photodetachment, debridement will cease when hydrated (with chloride ions) viable tissue is exposed, avoiding collateral damage to this tissue. Such tissue will be sterile and ready for further treatment, such as a wound dressing and/or a skin graft.

Incidence, risk factors, and prognosis of gastrointestinal hemorrhage complicating acute renal failure.

PubMed

Fiaccadori, E; Maggiore, U; Clima, B; Melfa, L; Rotelli, C; Borghetti, A

2001-04-01

Few prospective data are currently available on acute gastrointestinal hemorrhage (AGIH) as a complication of acute renal failure (ARF). The aim of the present study was to define incidence, sources, risk factors, and outcome of AGIH in patients with ARF. We performed a prospective study on an inception cohort of 514 patients admitted for ARF to a nephrology intermediate care unit. Data on clinical risk factors for bleeding, frequency of occurrence of AGIH, length of hospital stay, and in-hospital mortality were collected. Independent predictors of AGIH were identified. The relative odds of death and the relative increase in length of hospital stay associated with AGIH were calculated after adjusting for baseline comorbidities. Sixty-nine patients out of 514 [13.4% (95% CI, 10.6 to 16.7)] had AGIH as a complication of ARF; 59 were upper AGIH. Forty patients had clinically important bleeding. Erosions and/or ulcers accounted for 71% of cases of upper AGIH. Independent baseline predictors of AGIH were represented by severity of illness [odds ratio 1.45 (95% CI, 1.05 to 2.01) for every 10 point increase in APACHE II score], low platelet count [<50,000 mm3; 3.71 (1.70 to 8.11)], noncirrhotic chronic hepatic disease [2.22 (1.09 to 4.55)], liver cirrhosis [3.38 (1.50 to 7.60)], de novo ARF [2.77 (1.30 to 5.90)], and severe ARF [2.07 (1.10 to 3.88)]. In-hospital mortality was 63.8% in patients with AGIH and 34.2% in the other patients; after adjusting for baseline confounders, AGIH remained significantly associated with an increase in both mortality [2.57 (1.30 to 5.09), P = 0.006] and length of hospital stay [37% (1 to 87%), P = 0.047]. AGIH and clinically important bleeding are frequent complications of ARF. In this clinical condition, AGIH is more often due to upper gastrointestinal bleeding and is associated with a significantly increased risk of death and length of hospital stay. Both renal and extrarenal risk factors are related to the occurrence of AGIH.

Arabidopsis ARF-GTP exchange factor, GNOM, mediates transport required for innate immunity and focal accumulation of syntaxin PEN1

PubMed Central

Nielsen, Mads Eggert; Feechan, Angela; Böhlenius, Henrik; Ueda, Takashi; Thordal-Christensen, Hans

2012-01-01

Penetration resistance to powdery mildew fungi, conferred by localized cell wall appositions (papillae), is one of the best-studied processes in plant innate immunity. The syntaxin PENETRATION (PEN)1 is required for timely appearance of papillae, which contain callose and extracellular membrane material, as well as PEN1 itself. Appearance of membrane material in papillae suggests secretion of exosomes. These are potentially derived from multivesicular bodies (MVBs), supported by our observation that ARA6-labeled organelles assemble at the fungal attack site. However, the trafficking components that mediate delivery of extracellular membrane material are unknown. Here, we show that the delivery is independent of PEN1 function. Instead, we find that application of brefeldin (BF)A blocks the papillary accumulation of GFP-PEN1–labeled extracellular membrane and callose, while impeding penetration resistance. We subsequently provide evidence indicating that the responsible BFA-sensitive ADP ribosylation factor–GTP exchange factor (ARF-GEF) is GNOM. Firstly, analysis of the transheterozygote gnomB4049/emb30-1 (gnomB/E) mutant revealed a delay in papilla formation and reduced penetration resistance. Furthermore, a BFA-resistant version of GNOM restored the BFA-sensitive papillary accumulation of GFP-PEN1 and callose. Our data, therefore, provide a link between GNOM and disease resistance. We suggest that papilla formation requires rapid reorganization of material from the plasma membrane mediated by GNOM. The papilla material is subsequently presumed to be sorted into MVBs and directed to the site of fungal attack, rendering the epidermal plant cell inaccessible for the invading powdery mildew fungus. PMID:22733775

Loss of p19Arf in a Rag1−/− B-cell precursor population initiates acute B-lymphoblastic leukemia

PubMed Central

Hauer, Julia; Mullighan, Charles; Morillon, Estelle; Wang, Gary; Bruneau, Julie; Brousse, Nicole; Lelorc'h, Marc; Romana, Serge; Boudil, Amine; Tiedau, Daniela; Kracker, Sven; Bushmann, Frederic D.; Borkhardt, Arndt; Fischer, Alain; Hacein-Bey-Abina, Salima

2011-01-01

In human B-acute lymphoblastic leukemia (B-ALL), RAG1-induced genomic alterations are important for disease progression. However, given that biallelic loss of the RAG1 locus is observed in a subset of cases, RAG1's role in the development of B-ALL remains unclear. We chose a p19Arf−/−Rag1−/− mouse model to confirm the previously published results concerning the contribution of CDKN2A (p19ARF /INK4a) and RAG1 copy number alterations in precursor B cells to the initiation and/or progression to B-acute lymphoblastic leukemia (B-ALL). In this murine model, we identified a new, Rag1-independent leukemia-initiating mechanism originating from a Sca1+CD19+ precursor cell population and showed that Notch1 expression accelerates the cells' self-renewal capacity in vitro. In human RAG1-deficient BM, a similar CD34+CD19+ population expressed p19ARF. These findings suggest that combined loss of p19Arf and Rag1 results in B-cell precursor leukemia in mice and may contribute to the progression of precursor B-ALL in humans. PMID:21622646

Is familial risk for depression confounded by individual and familial socioeconomic factors and neighborhood environmental factors? A 7-year follow-up study in Sweden.

PubMed

Hamano, Tsuyoshi; Li, Xinjun; Lönn, Sara Larsson; Nabika, Toru; Sundquist, Jan; Sundquist, Kristina

2018-05-16

Family history of depression is an important risk factor for depression. The aim of this study was to examine whether the effect of family history of depression is confounded by individual and familial socioeconomic factors (i.e., country of origin, educational attainment, family income and mobility) and neighborhood environmental factors (i.e., neighborhood deprivation and neighborhood social capital). The study population comprised 188,907 individuals aged 20-44 years from a nationwide sample of primary care centers in Sweden. Among these individuals, 22,014 with a first event of depression (6,486 men and 15,528 women) were identified during the 7-year follow-up period. Family history of depression was defined as depression in at least one parent. Cross-classified multilevel logistic regression models were used to calculate odds ratios with 95% credible intervals. Increased familial odds were observed after adjustment for individual and familial socioeconomic factors and neighborhood environmental factors for both men and women. Our results suggest that family history of depression is an independent risk factor for depression. Offspring of parents with depression are important targets for disease prevention, regardless of individual and familial socioeconomic factors and neighborhood environmental factors. Copyright © 2018. Published by Elsevier B.V.

Effects of Some Pesticides on the Growth of ARF18 and Its Pathogenicity to Heterodera glycines

PubMed Central

Kim, D. G.; Riggs, R. D.

1998-01-01

The effects of 22 pesticides on the mycelial growth and pathogenicity of the biocontrol fungus ARFI8 to Heterodera glycines were tested in vitro. The chemicals were added to agar at 10, 100, and 1,000 ppm a.i.; a block of agar containing the fungus was added to each test concentration; and fungal growth was measured. Subsequently, a block of the fungus on the pesticide-containing agar was used to determine the ability of the fungus to parasitize eggs of H. glycines. Aldicarb, bentazone, and chlorothalonil had little or no effect on fungal growth, whereas benomyl and thiophanate methyl completely inhibited growth of the fungus at 10 ppm. The relative insensitivity of ARF18 to certain pesticides would permit selected use of those pesticides with ARF18 in an integrated control program if the effects on the fungus in the field are similar to results from petri dish studies. PMID:19274211

Precipitation areal-reduction factor estimation using an annual-maxima centered approach

USGS Publications Warehouse

Asquith, W.H.; Famiglietti, J.S.

2000-01-01

The adjustment of precipitation depth of a point storm to an effective (mean) depth over a watershed is important for characterizing rainfall-runoff relations and for cost-effective designs of hydraulic structures when design storms are considered. A design storm is the precipitation point depth having a specified duration and frequency (recurrence interval). Effective depths are often computed by multiplying point depths by areal-reduction factors (ARF). ARF range from 0 to 1, vary according to storm characteristics, such as recurrence interval; and are a function of watershed characteristics, such as watershed size, shape, and geographic location. This paper presents a new approach for estimating ARF and includes applications for the 1-day design storm in Austin, Dallas, and Houston, Texas. The approach, termed 'annual-maxima centered,' specifically considers the distribution of concurrent precipitation surrounding an annual-precipitation maxima, which is a feature not seen in other approaches. The approach does not require the prior spatial averaging of precipitation, explicit determination of spatial correlation coefficients, nor explicit definition of a representative area of a particular storm in the analysis. The annual-maxima centered approach was designed to exploit the wide availability of dense precipitation gauge data in many regions of the world. The approach produces ARF that decrease more rapidly than those from TP-29. Furthermore, the ARF from the approach decay rapidly with increasing recurrence interval of the annual-precipitation maxima. (C) 2000 Elsevier Science B.V.The adjustment of precipitation depth of a point storm to an effective (mean) depth over a watershed is important for characterizing rainfall-runoff relations and for cost-effective designs of hydraulic structures when design storms are considered. A design storm is the precipitation point depth having a specified duration and frequency (recurrence interval). Effective depths are

Family Factors Affecting Retention: A Review of the Literature

DTIC Science & Technology

1989-03-01

leadership has begun to recognize that career and reenlistment decisions are often family decisions, research incorporating family factors have...tentative links among these factors and between these factors and retention. There is much to be learned in order to provide Army leadership with the...questions are tied to key policy questions that Army leadership has asked of the AFRP. Rsac QLuestions: 1. What family factors inmact on retention? 2

Organ size control is dominant over Rb family inactivation to restrict proliferation in vivo.

PubMed

Ehmer, Ursula; Zmoos, Anne-Flore; Auerbach, Raymond K; Vaka, Dedeepya; Butte, Atul J; Kay, Mark A; Sage, Julien

2014-07-24

In mammals, a cell's decision to divide is thought to be under the control of the Rb/E2F pathway. We previously found that inactivation of the Rb family of cell cycle inhibitors (Rb, p107, and p130) in quiescent liver progenitors leads to uncontrolled division and cancer initiation. Here, we show that, in contrast, deletion of the entire Rb gene family in mature hepatocytes is not sufficient for their long-term proliferation. The cell cycle block in Rb family mutant hepatocytes is independent of the Arf/p53/p21 checkpoint but can be abrogated upon decreasing liver size. At the molecular level, we identify YAP, a transcriptional regulator involved in organ size control, as a factor required for the sustained expression of cell cycle genes in hepatocytes. These experiments identify a higher level of regulation of the cell cycle in vivo in which signals regulating organ size are dominant regulators of the core cell cycle machinery. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Generating Two-Dimensional Repertoire of siRNA Linc-ROR and siRNA mRNA ARF6 from the lincRNA-RoR/miR-145/ARF6 expression Pathway that involved in the progression of Triple Negative Breast Cancer

NASA Astrophysics Data System (ADS)

Aditya Parikesit, Arli; Nurdiansyah, Rizki

2018-01-01

The research for finding the cure for breast cancer is currently entering the interesting phase of the transcriptomics based method. With the application of Next Generation Sequencing (NGS), molecular information on breast cancer could be gathered. Thus, both in silico and wet lab research has determined that the role of lincRNA-RoR/miR-145/ARF6 expression Pathway could not be ignored as one of the cardinal starting points for Triple-Negative Breast Cancer (TNBC). As the most hazardous type of breast cancer, TNBC should be treated with the most advanced approach that available in the scientific community. Bioinformatics approach has found the possible siRNA-based drug candidates for TNBC. It was found that siRNA that interfere with lincRNA-ROR and mRNA ARF6 could be a feasible opportunity as the drug candidate for TNBC. However, this claim should be validated with more thorough thermodynamics and kinetics computational approach as the comprehensive way to comprehend their molecular repertoire. In this respect, the claim was validated using various tools such as the RNAfold server to determine the 2D structure, Barriers server to comprehend the RNA folding kinetics, RNAeval server to validate the siRNA-target interaction. It was found that the thermodynamics and kinetics repertoire of the siRNA are indeed rational and feasible. In this end, our computation approach has proven that our designed siRNA could interact with lincRNA-RoR/miR-145/ARF6 expression Pathway.

ADP-ribosylation factor6 regulates both [3H]-noradrenaline and [14C]-glutamate exocytosis through phosphatidylinositol 4,5-bisphosphate.

PubMed

Zheng, Qian; Bobich, Joseph A

2004-10-01

GTP phosphohydrolase (cell regulating) (EC 3.6.1.47, ADP-ribosylation factor6, ARF6) has been shown to play an important role in different steps of membrane trafficking. It also regulates chromaffin granule exocytosis through phosphatidylcholine phosphatidohydrolase (EC 3.1.4.14, PLD) activation. In this study, the role of ARF6 in neurotransmitter release from both dense-core granules (DCGs) and synaptic vesicles (SVs) in rat brain cortex nerve endings was investigated. We observed that synaptosomal ARF6 is largely particulate but moves to a less easily pelleted compartment upon nerve ending stimulation. We also found that direct inhibition of ARF6 by a specific antibody or interference with ARF6 downstream effects by a myristoylated N-terminal ARF6 peptide both significantly decreased both [3H]-noradrenaline and [14C]-glutamate exocytosis. Addition of phosphatidic acid (PA) and phosphatidylinositol 4,5-bisphosphate (PIP2) partially or completely restored exocytosis. These findings suggest that ARF6 plays important regulatory roles for both DCG and SV exocytosis by activating PLD and ATP:1-phosphatidyl-1D-myo-inositol 4-phosphate 5-phosphotransferase (EC 2.7.1.68, PI4P-5K) to enhance PIP2 synthesis and nerve ending membrane trafficking.

Family factors in end-of-life decision-making: family conflict and proxy relationship.

PubMed

Parks, Susan Mockus; Winter, Laraine; Santana, Abbie J; Parker, Barbara; Diamond, James J; Rose, Molly; Myers, Ronald E

2011-02-01

Few studies have examined proxy decision-making regarding end-of-life treatment decisions. Proxy accuracy is defined as whether proxy treatment choices are consistent with the expressed wishes of their index elder. The purpose of this study was to examine proxy accuracy in relation to two family factors that may influence proxy accuracy: perceived family conflict and type of elder-proxy relationship. Telephone interviews with 202 community-dwelling elders and their proxy decision makers were conducted including the Life-Support Preferences Questionnaire (LSPQ), and a measure of family conflict, and sociodemographic characteristics, including type of relationship. Elder-proxy accuracy was associated with the type of elder-proxy relationship. Adult children demonstrated the lowest elder-proxy accuracy and spousal proxies the highest elder-proxy accuracy. Elder-proxy accuracy was associated with family conflict. Proxies reporting higher family conflict had lower elder-proxy accuracy. No interaction between family conflict and relationship type was revealed. Spousal proxies were more accurate in their substituted judgment than adult children, and proxies who perceive higher degree of family conflict tended to be less accurate than those with lower family conflict. Health care providers should be aware of these family factors when discussing advance care planning.

Identification of Atg2 and ArfGAP1 as Candidate Genetic Modifiers of the Eye Pigmentation Phenotype of Adaptor Protein-3 (AP-3) Mutants in Drosophila melanogaster.

PubMed

Rodriguez-Fernandez, Imilce A; Dell'Angelica, Esteban C

2015-01-01

The Adaptor Protein (AP)-3 complex is an evolutionary conserved, molecular sorting device that mediates the intracellular trafficking of proteins to lysosomes and related organelles. Genetic defects in AP-3 subunits lead to impaired biogenesis of lysosome-related organelles (LROs) such as mammalian melanosomes and insect eye pigment granules. In this work, we have performed a forward screening for genetic modifiers of AP-3 function in the fruit fly, Drosophila melanogaster. Specifically, we have tested collections of large multi-gene deletions--which together covered most of the autosomal chromosomes-to identify chromosomal regions that, when deleted in single copy, enhanced or ameliorated the eye pigmentation phenotype of two independent AP-3 subunit mutants. Fine-mapping led us to define two non-overlapping, relatively small critical regions within fly chromosome 3. The first critical region included the Atg2 gene, which encodes a conserved protein involved in autophagy. Loss of one functional copy of Atg2 ameliorated the pigmentation defects of mutants in AP-3 subunits as well as in two other genes previously implicated in LRO biogenesis, namely Blos1 and lightoid, and even increased the eye pigment content of wild-type flies. The second critical region included the ArfGAP1 gene, which encodes a conserved GTPase-activating protein with specificity towards GTPases of the Arf family. Loss of a single functional copy of the ArfGAP1 gene ameliorated the pigmentation phenotype of AP-3 mutants but did not to modify the eye pigmentation of wild-type flies or mutants in Blos1 or lightoid. Strikingly, loss of the second functional copy of the gene did not modify the phenotype of AP-3 mutants any further but elicited early lethality in males and abnormal eye morphology when combined with mutations in Blos1 and lightoid, respectively. These results provide genetic evidence for new functional links connecting the machinery for biogenesis of LROs with molecules implicated in

eMelanoBase: an online locus-specific variant database for familial melanoma.

PubMed

Fung, David C Y; Holland, Elizabeth A; Becker, Therese M; Hayward, Nicholas K; Bressac-de Paillerets, Brigitte; Mann, Graham J

2003-01-01

A proportion of melanoma-prone individuals in both familial and non-familial contexts has been shown to carry inactivating mutations in either CDKN2A or, rarely, CDK4. CDKN2A is a complex locus that encodes two unrelated proteins from alternately spliced transcripts that are read in different frames. The alpha transcript (exons 1alpha, 2, and 3) produces the p16INK4A cyclin-dependent kinase inhibitor, while the beta transcript (exons 1beta and 2) is translated as p14ARF, a stabilizing factor of p53 levels through binding to MDM2. Mutations in exon 2 can impair both polypeptides and insertions and deletions in exons 1alpha, 1beta, and 2, which can theoretically generate p16INK4A-p14ARF fusion proteins. No online database currently takes into account all the consequences of these genotypes, a situation compounded by some problematic previous annotations of CDKN2A-related sequences and descriptions of their mutations. As an initiative of the international Melanoma Genetics Consortium, we have therefore established a database of germline variants observed in all loci implicated in familial melanoma susceptibility. Such a comprehensive, publicly accessible database is an essential foundation for research on melanoma susceptibility and its clinical application. Our database serves two types of data as defined by HUGO. The core dataset includes the nucleotide variants on the genomic and transcript levels, amino acid variants, and citation. The ancillary dataset includes keyword description of events at the transcription and translation levels and epidemiological data. The application that handles users' queries was designed in the model-view-controller architecture and was implemented in Java. The object-relational database schema was deduced using functional dependency analysis. We hereby present our first functional prototype of eMelanoBase. The service is accessible via the URL www.wmi.usyd.edu.au:8080/melanoma.html. Copyright 2002 Wiley-Liss, Inc.

[Family environment risk factors of depression in adolescence].

PubMed

Greszta, Elzbieta

2006-01-01

General psychosocial theories of developmental psychopathology assert that family environment plays a significant role in forming both adaptive and maladaptive functioning of children. Also virtually all theories of depression assert that faulty parent-child relationships play a major role in the aetiology of this disorder. According these theoretical formulations familial risk factors have been the focus of most research on depression in adolescence. Several studies have shown that insecure attachment and parenting characterized by coldness, rejection, harsh discipline and unsupportive behaviour is positively related to adolescent depressive symptoms. Some research indicates that authoritative parenting, conceptualized as a composite of warmth, accept-involvement, firm control, and democratic discipline, is associated with the least depressive symptoms among adolescents. Pathogenetic factors within the family environment, such as parental depression, changes of family structure, violence or neglect, can also contribute to depression in adolescence. A causal relationship between anomalous parenting and depression is probably the interplay among genetic, cognitive, emotional, interpersonal and family environmental factors.

The WRKY transcription factor family in Brachypodium distachyon.

PubMed

Tripathi, Prateek; Rabara, Roel C; Langum, Tanner J; Boken, Ashley K; Rushton, Deena L; Boomsma, Darius D; Rinerson, Charles I; Rabara, Jennifer; Reese, R Neil; Chen, Xianfeng; Rohila, Jai S; Rushton, Paul J

2012-06-22

A complete assembled genome sequence of wheat is not yet available. Therefore, model plant systems for wheat are very valuable. Brachypodium distachyon (Brachypodium) is such a system. The WRKY family of transcription factors is one of the most important families of plant transcriptional regulators with members regulating important agronomic traits. Studies of WRKY transcription factors in Brachypodium and wheat therefore promise to lead to new strategies for wheat improvement. We have identified and manually curated the WRKY transcription factor family from Brachypodium using a pipeline designed to identify all potential WRKY genes. 86 WRKY transcription factors were found, a total higher than all other current databases. We therefore propose that our numbering system (BdWRKY1-BdWRKY86) becomes the standard nomenclature. In the JGI v1.0 assembly of Brachypodium with the MIPS/JGI v1.0 annotation, nine of the transcription factors have no gene model and eleven gene models are probably incorrectly predicted. In total, twenty WRKY transcription factors (23.3%) do not appear to have accurate gene models. To facilitate use of our data, we have produced The Database of Brachypodium distachyon WRKY Transcription Factors. Each WRKY transcription factor has a gene page that includes predicted protein domains from MEME analyses. These conserved protein domains reflect possible input and output domains in signaling. The database also contains a BLAST search function where a large dataset of WRKY transcription factors, published genes, and an extensive set of wheat ESTs can be searched. We also produced a phylogram containing the WRKY transcription factor families from Brachypodium, rice, Arabidopsis, soybean, and Physcomitrella patens, together with published WRKY transcription factors from wheat. This phylogenetic tree provides evidence for orthologues, co-orthologues, and paralogues of Brachypodium WRKY transcription factors. The description of the WRKY transcription factor

Workplace Factors Associated with Family Dinner Behaviors

ERIC Educational Resources Information Center

Allen, Tammy D.; Shockley, Kristen M.; Poteat, Laura F.

2008-01-01

This study investigated relationships between workplace factors and family dinners. We examined two aspects of the family dinner, the frequency that the entire family typically has dinner together each week and the frequency that children eat fast food for dinner. Participants were 220 parents who worked at least 20 h a week and had at least one…

Controllable Change of Photoluminescence Spectra of Silicone Rubber Modified by 193 nm ArF Excimer Laser

NASA Astrophysics Data System (ADS)

Okoshi, Masayuki; Iyono, Minako; Inoue, Narumi

2009-12-01

Photoluminescence spectra of silicone rubber ([SiO(CH3)2]n) photochemically modified by a 193 nm ArF excimer laser was found to be controllable. Compared with the modification in air, the photoluminescence spectra could be blueshifted by the modification in vacuum or the additional irradiation of ArF excimer laser in vacuum after the modification in air. To redshift, on the other hand, the additional irradiation of a 157 nm F2 laser in air after the modification in air, the modification in oxygen gas, or the postannealing after the modification in oxygen gas was effective. The blue and redshifts of the photoluminescence were essentially due to the acceleration of reduction and oxidation reactions of silicone rubber, respectively, because the photoluminescence derives its origin from oxygen deficiency centers and peroxy centers of the silica structure in the modified silicone rubber. On the basis of the spectra changes, colorful light-guiding sheets made of silicone rubber under illumination of a 375 nm light-emitting diode were successfully fabricated for cellular phone use.

[Comparison of the factors influencing children's self-esteem between two parent families and single parent families].

PubMed

Sok, Sohyune R; Shin, Sung Hee

2010-06-01

This study was done to compare factors influencing children's self-esteem between two parent families and single parent families. The participants were 692 children aged 11 to 13 yr (388 in two parent families and 304 in single parent families) recruited from 20 community agencies and 5 elementary schools in Gyeonggi Province and Seoul City, South Korea. Data were collected from May to July, 2007 using a survey questionnaire containing items on self-esteem, internal control, problematic behavior, school record, family hardiness, parent-child communication and social support. The data were analyzed using SPSS 15.0 program and factors affecting children's self-esteem were analyzed by stepwise multiple regression. Scores for the study variables were significantly different between the two groups. The factors influencing children's self-esteem were also different according to family type. For two parent families, internal control, problematic behavior, school record, and parent-child communication significantly predicted the level of self-esteem (adjusted R(2)=.505, p<.001). For single parent families, social support, family hardiness, internal control, problematic behavior, school record, and parent-child communication significantly predicted the level of self-esteem (adjusted R(2)=.444, p<.001). Nurse working with children should consider family type-specific factors influencing their self-esteem.

Blue light alters miR167 expression and microRNA-targeted auxin response factor genes in Arabidopsis thaliana plants.

PubMed

Pashkovskiy, Pavel P; Kartashov, Alexander V; Zlobin, Ilya E; Pogosyan, Sergei I; Kuznetsov, Vladimir V

2016-07-01

The effect of blue LED (450 nm) on the photomorphogenesis of Arabidopsis thaliana Col-0 plants and the transcript levels of several genes, including miRNAs, photoreceptors and auxin response factors (ARF) was investigated. It was observed that blue light accelerated the generative development, reduced the rosette leaf number, significantly reduced the leaf area, dry biomass and led to the disruption of conductive tissue formation. The blue LED differentially influenced the transcript levels of several phytochromes (PHY a, b, c, d, and e), cryptochromes (CRY 1 and 2) and phototropins (PHOT 1 and 2). At the same time, the blue LED significantly increased miR167 expression compared to a fluorescent lamp or white LEDs. This increase likely resulted in the enhanced transcription of the auxin response factor genes ARF4 and ARF8, which are regulated by this miRNA. These findings support the hypothesis that the effects of blue light on A. thaliana are mediated by auxin signalling pathway involving miRNA-dependent regulation of ARF gene expression. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Personality Factors in the Long Life Family Study

PubMed Central

2013-01-01

Objectives. To evaluate personality profiles of Long Life Family Study participants relative to population norms and offspring of centenarians from the New England Centenarian Study. Method. Personality domains of agreeableness, conscientiousness, extraversion, neuroticism, and openness were assessed with the NEO Five-Factor Inventory in 4,937 participants from the Long Life Family Study (mean age 70 years). A linear mixed model of age and gender was implemented adjusting for other covariates. Results. A significant age trend was found in all five personality domains. On average, the offspring generation of long-lived families scored low in neuroticism, high in extraversion, and within average values for the other three domains. Older participants tended to score higher in neuroticism and lower in the other domains compared with younger participants, but the estimated scores generally remained within average population values. No significant differences were found between long-lived family members and their spouses. Discussion. Personality factors and more specifically low neuroticism and high extraversion may be important for achieving extreme old age. In addition, personality scores of family members were not significantly different from those of their spouses, suggesting that environmental factors may play a significant role in addition to genetic factors. PMID:23275497

The WRKY transcription factor family in Brachypodium distachyon

PubMed Central

2012-01-01

Background A complete assembled genome sequence of wheat is not yet available. Therefore, model plant systems for wheat are very valuable. Brachypodium distachyon (Brachypodium) is such a system. The WRKY family of transcription factors is one of the most important families of plant transcriptional regulators with members regulating important agronomic traits. Studies of WRKY transcription factors in Brachypodium and wheat therefore promise to lead to new strategies for wheat improvement. Results We have identified and manually curated the WRKY transcription factor family from Brachypodium using a pipeline designed to identify all potential WRKY genes. 86 WRKY transcription factors were found, a total higher than all other current databases. We therefore propose that our numbering system (BdWRKY1-BdWRKY86) becomes the standard nomenclature. In the JGI v1.0 assembly of Brachypodium with the MIPS/JGI v1.0 annotation, nine of the transcription factors have no gene model and eleven gene models are probably incorrectly predicted. In total, twenty WRKY transcription factors (23.3%) do not appear to have accurate gene models. To facilitate use of our data, we have produced The Database of Brachypodium distachyon WRKY Transcription Factors. Each WRKY transcription factor has a gene page that includes predicted protein domains from MEME analyses. These conserved protein domains reflect possible input and output domains in signaling. The database also contains a BLAST search function where a large dataset of WRKY transcription factors, published genes, and an extensive set of wheat ESTs can be searched. We also produced a phylogram containing the WRKY transcription factor families from Brachypodium, rice, Arabidopsis, soybean, and Physcomitrella patens, together with published WRKY transcription factors from wheat. This phylogenetic tree provides evidence for orthologues, co-orthologues, and paralogues of Brachypodium WRKY transcription factors. Conclusions The description

Genetic factors in familial aggregation of blood pressure of Portuguese nuclear families.

PubMed

Fermino, Rogério César; Seabra, André; Garganta, Rui; Maia, José António Ribeiro

2009-03-01

Despite of the increase in the prevalence of hypertension in Portugal, the importance of genetic factors in blood pressure (BP) has not been studied extensively in our country. To verify the indirect presence of vertical transmission of genetic factors between parents and children in BP values, and to estimate the magnitude of genetic factors contributing for variation in BP values in the population. Sample size comprises 367 individuals (164 parents and 203 children) pertaining the 107 nuclear families participating in 'Familias Activas' project, proceeding from different regions of North Portugal. The BP was measured with Omron model M6 (HEM-7001-E) digital device. SPSS 15.0 was used for data analysis; PEDSTATS was used to verify the structure of each family data. Familial correlations and heritability estimates were computed in FCOR and ASSOC modules of S.A.G.E. version 5.3. For systolic BP (SBP), correlation values were low to moderate (0.21< or = r < or =0.35); for diastolic BP (DBP) values were found to be moderate (0.24< or = r < or =0. 50). Genetic factors explain 43 and 49% of the total variation in SBP and DBP, respectively. A moderate amount of the SBP and the DBP is accounted for by genetic factors.

Familial psychological factors are associated with encopresis.

PubMed

Akdemir, Devrim; Çengel Kültür, S Ebru; Saltık Temizel, İnci Nur; Zeki, Ayşe; Şenses Dinç, Gülser

2015-01-01

The aim of this study was to assess maternal psychiatric symptoms, family functioning and parenting styles in children with encopresis. Forty-one children with encopresis were compared to 29 children without any psychiatric disorder. Higher maternal psychiatric symptoms were found in children with encopresis. The general family functioning and strictness/supervision in parenting were significant predictors of encopresis. Family functioning may be screened in children with encopresis, especially when standard interventions have had limited success. Identification and treatment of familial factors may enhance the treatment efficacy in encopresis. © 2014 Japan Pediatric Society.

Factors Determining the Incidence of Suicide within Families

ERIC Educational Resources Information Center

Farber, Maurice L.

1977-01-01

This paper addresses itself to the reasons why suicide tends to repeat in some families. Factors include entire family exposure to stresses, grief, and guilt induced by suicide, the provision of a model by the original suicide, suicidogenic interpersonal styles in families, suicidogenic child-rearing practice, and innate predispositions to…

Hepatitis A complicated with acute renal failure and high hepatocyte growth factor: A case report.

PubMed

Oe, Shinji; Shibata, Michihiko; Miyagawa, Koichiro; Honma, Yuichi; Hiura, Masaaki; Abe, Shintaro; Harada, Masaru

2015-08-28

A 58-year-old man was admitted to our hospital. Laboratory data showed severe liver injury and that the patient was positive for immunoglobulin M anti-hepatitis A virus (HAV) antibodies. He was also complicated with severe renal dysfunction and had an extremely high level of serum hepatocyte growth factor (HGF). Therefore, he was diagnosed with severe acute liver failure with acute renal failure (ARF) caused by HAV infection. Prognosis was expected to be poor because of complications by ARF and high serum HGF. However, liver and renal functions both improved rapidly without intensive treatment, and he was subsequently discharged from our hospital on the 21(st) hospital day. Although complication with ARF and high levels of serum HGF are both important factors predicting poor prognosis in acute liver failure patients, the present case achieved a favorable outcome. Endogenous HGF might play an important role as a regenerative effector in injured livers and kidneys.

Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

PubMed Central

2010-01-01

Background Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated

Family protective factors among urban African American youth.

PubMed

McCabe, K M; Clark, R; Barnett, D

1999-06-01

Examined the relations among family protective factors, stressful events, and behavioral adjustment of 64 African American 6th graders. The youths reported on family stressors, father-figure involvement, and kin support. Their primary caregivers reported on parenting, father-figure involvement, and family stressors. Teachers reported on child social skill deficits, acting out, and shy or anxious behavior. Based on regression analyses, stress exposure associated positively with child social skill deficits, acting out, and shy or anxious behavior. Parental warmth was associated negatively with shy or anxious behavior. Parental use of corporal punishment was associated positively with child acting out. For youth exposed to high numbers of family stressors, parental demandingness was associated negatively with child acting out and kin support was associated negatively with acting out and shy or anxious behavior, suggesting that these family factors partially shield children from the negative effects of stress.

Neon reduction program on Cymer ArF light sources

NASA Astrophysics Data System (ADS)

Kanawade, Dinesh; Roman, Yzzer; Cacouris, Ted; Thornes, Josh; O'Brien, Kevin

2016-03-01

In response to significant neon supply constraints, Cymer has responded with a multi-part plan to support its customers. Cymer's primary objective is to ensure that reliable system performance is maintained while minimizing gas consumption. Gas algorithms were optimized to ensure stable performance across all operating conditions. The Cymer neon support plan contains four elements: 1. Gas reduction program to reduce neon by >50% while maintaining existing performance levels and availability; 2. short-term containment solutions for immediate relief. 3. qualification of additional gas suppliers; and 4. long-term recycling/reclaim opportunity. The Cymer neon reduction program has shown excellent results as demonstrated through the comparison on standard gas use versus the new >50% reduced neon performance for ArF immersion light sources. Testing included stressful conditions such as repetition rate, duty cycle and energy target changes. No performance degradation has been observed over typical gas lives.

Precipitation areal-reduction factor estimation using an annual-maxima centered approach

NASA Astrophysics Data System (ADS)

Asquith, W. H.; Famiglietti, J. S.

2000-04-01

The adjustment of precipitation depth of a point storm to an effective (mean) depth over a watershed is important for characterizing rainfall-runoff relations and for cost-effective designs of hydraulic structures when design storms are considered. A design storm is the precipitation point depth having a specified duration and frequency (recurrence interval). Effective depths are often computed by multiplying point depths by areal-reduction factors (ARF). ARF range from 0 to 1, vary according to storm characteristics, such as recurrence interval; and are a function of watershed characteristics, such as watershed size, shape, and geographic location. This paper presents a new approach for estimating ARF and includes applications for the 1-day design storm in Austin, Dallas, and Houston, Texas. The approach, termed "annual-maxima centered," specifically considers the distribution of concurrent precipitation surrounding an annual-precipitation maxima, which is a feature not seen in other approaches. The approach does not require the prior spatial averaging of precipitation, explicit determination of spatial correlation coefficients, nor explicit definition of a representative area of a particular storm in the analysis. The annual-maxima centered approach was designed to exploit the wide availability of dense precipitation gauge data in many regions of the world. The approach produces ARF that decrease more rapidly than those from TP-29. Furthermore, the ARF from the approach decay rapidly with increasing recurrence interval of the annual-precipitation maxima.

The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin

PubMed Central

Arnold, Miranda; Cross, Rebecca; Singleton, Kaela S.; Zlatic, Stephanie; Chapleau, Christopher; Mullin, Ariana P.; Rolle, Isaiah; Moore, Carlene C.; Theibert, Anne; Pozzo-Miller, Lucas; Faundez, Victor; Larimore, Jennifer

2016-01-01

AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle-associated protein complexes adaptor protein 3 (AP-3) and Biogenesis of Lysosome Related Organelles Complex-1 (BLOC-1). Overexpression of AGAP1 in non-neuronal cells results in an accumulation of endosomal cargoes, which suggests a role in endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene for two neurodevelopmental disorders, autism spectrum disorder (ASD) and schizophrenia (SZ); yet its localization and function in neurons have not been described. Here, we describe that AGAP1 localizes to axons, dendrites, dendritic spines and synapses, colocalizing preferentially with markers of early and recycling endosomes. Functional studies reveal overexpression and down-regulation of AGAP1 affects both neuronal endosomal trafficking and dendritic spine morphology, supporting a role for AGAP1 in the recycling endosomal trafficking involved in their morphogenesis. Finally, we determined the sensitivity of AGAP1 expression to mutations in the DTNBP1 gene, which is associated with neurodevelopmental disorder, and found that AGAP1 mRNA and protein levels are selectively reduced in the null allele of the mouse ortholog of DTNBP1. We postulate that endosomal trafficking contributes to the pathogenesis of neurodevelopmental disorders affecting dendritic spine morphology, and thus excitatory synapse structure and function. PMID:27713690

The impact of family factors on IQ in pediatric medically refractory epilepsy.

PubMed

Puka, Klajdi; Smith, Mary Lou; Widjaja, Elysa

2017-02-01

To evaluate whether family factors were associated with intellectual functioning among children with medically refractory epilepsy, and whether family factors moderate the relationship between patient/epilepsy-related variables and intellectual functioning. Children aged 4 to 18 years with medically refractory epilepsy who were evaluated for surgical candidacy were recruited. The authors assessed the association of intellectual quotient (IQ) with patient, epilepsy, and family factors. Family factors included parental education, household income, and validated parent-report measures of family functioning, family mastery and social support, and family demands. Univariable analyses showed that higher IQ scores were associated with an older age of epilepsy onset (β = .260, p = .009), fewer antiepileptic drugs (β = .248, p = .013), a shorter duration (β = .384, p < .001) and percentage of life with epilepsy (β = .419, p < .001), unilobar epileptogenic foci relative to multilobar foci (β = .274, p = .006), and lower family demands (β = .211, p = .035). In multivariable analysis, unilobar epileptogenic foci (p = .010) and a shorter percentage of life with epilepsy (p = .001) remained significant predictors of IQ. Exploratory moderation analyses found the relationship between the extent of epileptogenic foci and IQ to be moderated by family demands (p = .004); specifically, patients with unilobar epileptogenic onset had similar IQ scores irrespective of family demands, whereas patients with multilobar foci had lower IQ scores with increasing family demands. Family factors did not have a large impact on IQ among children with medically refractory epilepsy, although the moderating effect of family demands deserves further study. Epilepsy-related factors in this patient group may weaken the link between child IQ and family factors. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

GENOME-ENABLED DISCOVERY OF CARBON SEQUESTRATION GENES IN POPLAR

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

DAVIS J M

2007-10-11

Plants utilize carbon by partitioning the reduced carbon obtained through photosynthesis into different compartments and into different chemistries within a cell and subsequently allocating such carbon to sink tissues throughout the plant. Since the phytohormones auxin and cytokinin are known to influence sink strength in tissues such as roots (Skoog & Miller 1957, Nordstrom et al. 2004), we hypothesized that altering the expression of genes that regulate auxin-mediated (e.g., AUX/IAA or ARF transcription factors) or cytokinin-mediated (e.g., RR transcription factors) control of root growth and development would impact carbon allocation and partitioning belowground (Fig. 1 - Renewal Proposal). Specifically, themore » ARF, AUX/IAA and RR transcription factor gene families mediate the effects of the growth regulators auxin and cytokinin on cell expansion, cell division and differentiation into root primordia. Invertases (IVR), whose transcript abundance is enhanced by both auxin and cytokinin, are critical components of carbon movement and therefore of carbon allocation. Thus, we initiated comparative genomic studies to identify the AUX/IAA, ARF, RR and IVR gene families in the Populus genome that could impact carbon allocation and partitioning. Bioinformatics searches using Arabidopsis gene sequences as queries identified regions with high degrees of sequence similarities in the Populus genome. These Populus sequences formed the basis of our transgenic experiments. Transgenic modification of gene expression involving members of these gene families was hypothesized to have profound effects on carbon allocation and partitioning.« less

Family environment and its relation to adolescent personality factors.

PubMed

Forman, S G; Forman, B D

1981-04-01

Investigated the relationship between family social climate characteristics and adolescent personality functioning. The High School Personality Questionnaire (HSPQ) was administered to 80 high school students. These students and their parents also completed the Family Environment Scale (FES). Results of a stepwise multiple regression analysis indicated that one or more HSPQ scales had significant associations with each FES scale. Significant variance in child behavior was attributed to family social system functioning; however, no single family variable accounted for a major portion of the variance to the exclusion of other factors. It was concluded that child behavior varies with total system functioning, more than with separate system factors.

Molecular dynamics simulations of membrane deformation induced by amphiphilic helices of Epsin, Sar1p, and Arf1

NASA Astrophysics Data System (ADS)

Li, Zhen-Lu

2018-03-01

The N-terminal amphiphilic helices of proteins Epsin, Sar1p, and Arf1 play a critical role in initiating membrane deformation. The interactions of these amphiphilic helices with the lipid membranes are investigated in this study by combining the all-atom and coarse-grained simulations. In the all-atom simulations, the amphiphilic helices of Epsin and Sar1p are found to have a shallower insertion depth into the membrane than the amphiphilic helix of Arf1, but remarkably, the amphiphilic helices of Epsin and Sar1p induce higher asymmetry in the lipid packing between the two monolayers of the membrane. The insertion depth of amphiphilic helix into the membrane is determined not only by the overall hydrophobicity but also by the specific distributions of polar and non-polar residues along the helix. To directly compare their ability to deform the membrane, the coarse-grained simulations are performed to investigate the membrane deformation under the insertion of multiple helices. Project supported by the National Natural Science Foundation of China (Grant Nos. 91427302 and 11474155).

Manipulation of Auxin Response Factor 19 affects seed size in the woody perennial Jatropha curcas

PubMed Central

Sun, Yanwei; Wang, Chunming; Wang, Ning; Jiang, Xiyuan; Mao, Huizhu; Zhu, Changxiang; Wen, Fujiang; Wang, Xianghua; Lu, Zhijun; Yue, Genhua; Xu, Zengfu; Ye, Jian

2017-01-01

Seed size is a major determinant of seed yield but few is known about the genetics controlling of seed size in plants. Phytohormones cytokinin and brassinosteroid were known to be involved in the regulation of herbaceous plant seed development. Here we identified a homolog of Auxin Response Factor 19 (JcARF19) from a woody plant Jatropha curcas and genetically demonstrated its functions in controlling seed size and seed yield. Through Virus Induced Gene Silencing (VIGS), we found that JcARF19 was a positive upstream modulator in auxin signaling and may control plant organ size in J. curcas. Importantly, transgenic overexpression of JcARF19 significantly increased seed size and seed yield in plants Arabidopsis thaliana and J. curcas, indicating the importance of auxin pathway in seed yield controlling in dicot plants. Transcripts analysis indicated that ectopic expression of JcARF19 in J. curcas upregulated auxin responsive genes encoding essential regulators in cell differentiation and cytoskeletal dynamics of seed development. Our data suggested the potential of improving seed traits by precisely engineering auxin signaling in woody perennial plants. PMID:28102350

Areal-reduction factors for the precipitation of the 1-day design storm in Texas

USGS Publications Warehouse

Asquith, William H.

1999-01-01

The reduction of the precipitation depth from a design storm for a point to an effective (mean) depth over a watershed often is important for cost-effective design of hydraulic structures by reducing the volume of precipitation. A design storm for a point is the depth of precipitation that has a specified duration and frequency (recurrence interval). The effective depth can be calculated by multiplying the design-storm depth by an areal-reduction factor (ARF). ARF ranges from 0 to 1, varies with the recurrence interval of the design storm, and is a function of watershed characteristics such as watershed size and shape, geographic location, and time of year that the design storm occurs. This report documents an investigation of ARF by the U.S. Geological Survey, in cooperation with the Texas Department of Transportation, for the 1-day design storm for Austin, Dallas, and Houston, Texas. The ?annual maxima-centered? approach used in this report specifically considers the distribution of concurrent precipitation surrounding an annual precipitation maxima. Unlike previously established approaches, the annual maxima-centered approach does not require the spatial averaging of precipitation nor explicit definition of a representative area of a particular storm in the analysis. Graphs of the relation between ARF and circular watershed area (to about 7,000 square miles) are provided, and a technique to calculate ARF for noncircular watersheds is discussed.

Structural basis for the auxin-induced transcriptional regulation by Aux/IAA17.

PubMed

Han, Mookyoung; Park, Yangshin; Kim, Iktae; Kim, Eun-Hee; Yu, Tae-Kyung; Rhee, Sangkee; Suh, Jeong-Yong

2014-12-30

Auxin is the central hormone that regulates plant growth and organ development. Transcriptional regulation by auxin is mediated by the auxin response factor (ARF) and the repressor, AUX/IAA. Aux/IAA associates with ARF via domain III-IV for transcriptional repression that is reversed by auxin-induced Aux/IAA degradation. It has been known that Aux/IAA and ARF form homo- and hetero-oligomers for the transcriptional regulation, but what determines their association states is poorly understood. Here we report, to our knowledge, the first solution structure of domain III-IV of Aux/IAA17 (IAA17), and characterize molecular interactions underlying the homotypic and heterotypic oligomerization. The structure exhibits a compact β-grasp fold with a highly dynamic insert helix that is unique in Aux/IAA family proteins. IAA17 associates to form a heterogeneous ensemble of front-to-back oligomers in a concentration-dependent manner. IAA17 and ARF5 associate to form homo- or hetero-oligomers using a common scaffold and binding interfaces, but their affinities vary significantly. The equilibrium dissociation constants (KD) for homo-oligomerization are 6.6 μM and 0.87 μM for IAA17 and ARF5, respectively, whereas hetero-oligomerization reveals a ∼ 10- to ∼ 100-fold greater affinity (KD = 73 nM). Thus, individual homo-oligomers of IAA17 and ARF5 spontaneously exchange their subunits to form alternating hetero-oligomers for transcriptional repression. Oligomerization is mainly driven by electrostatic interactions, so that charge complementarity at the interface determines the binding affinity. Variable binding affinity by surface charge modulation may effectively regulate the complex interaction network between Aux/IAA and ARF family proteins required for the transcriptional control of auxin-response genes.

Effectiveness of the GoCheck Kids Vision Screener in Detecting Amblyopia Risk Factors.

PubMed

Peterseim, M Millicent W; Rhodes, Ryan S; Patel, Rupa N; Wilson, M Edward; Edmondson, Luke E; Logan, Sarah A; Cheeseman, Edward W; Shortridge, Emily; Trivedi, Rupal H

2018-03-01

The GoCheck Kids smartphone photoscreening app (Gobiquity Mobile Health, Scottsdale, Arizona, USA), introduced in 2014, is marketed to pediatricians with little published validation. We wished to evaluate the GoCheck Kids Screener for accuracy in detecting amblyopia risk factors (ARF) using 2013 American Association for Pediatric Ophthalmology and Strabismus guidelines. Validity assessment. Children 6 months to 6 years of age presenting from October 2016 to August 2017 were included. Children were screened with the GoCheck preloaded Nokia Lumia 1020, software version 4.6 with image processing version R4d, prior to undergoing a comprehensive eye examination by a pediatric ophthalmologist masked to the screener results. Determination of the presence of age-specific ARF was made based upon the examination and compared with the GoCheck recommendation. A total of 206 children were included (average age 43 months). When compared to examination, GoCheck had a sensitivity of 76.0% and specificity of 67.2% in detecting ARF. Positive predictive value was 57.0% and negative predictive value 83.0%. The screener results of 13 children were changed from "no risk factors" to "risk factors identified" based on the GoCheck remote review process. Four images remained "not gradable" and screening was unsuccessful in 3 children. In our high-risk population, this version of the Gocheck Kids smartphone app was useful in identifying ARF in children who are often not able to cooperate with visual acuity testing. This study informs pediatricians about the efficacy of this new screener as they make decisions about how to best detect vision problems in young children. Copyright © 2018 Elsevier Inc. All rights reserved.

Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP.

PubMed

Waheed, Sana; Dorjbal, Batsukh; Hamilton, Chad A; Maxwell, G Larry; Rodriguez, Gustavo C; Syed, Viqar

2017-12-26

Previously, we have demonstrated that progesterone and calcitriol synergistically inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and causing cell cycle arrest. Metastasis is the main reason of mortality in cancer patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and metastasis. We examined the effects of progesterone, calcitriol and progesterone-calcitriol combination on metastasis promoting proteins in endometrial cancer. Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial tumors and in cancer cell lines compared to normal tissues and immortalized EM-E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins significantly inhibited the invasiveness of the cancer cells. The expression levels of all three proteins was reduced with progesterone and progesterone-calcitriol combination treatment, whereas calcitriol alone showed no effect on their expression but moderately decreased MT1-MMP activity. Fluorescence microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol-treated endometrial cancer cells. However, progesterone and calcitriol-progesterone combination treatment revealed MT1-MMP in the cytoplasm. Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9, and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both progesterone and progesterone-calcitriol combination treated cells as well as in MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer dissemination and may have therapeutic benefits for endometrial cancer patients.

Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP

PubMed Central

Waheed, Sana; Dorjbal, Batsukh; Hamilton, Chad A.; Maxwell, G. Larry; Rodriguez, Gustavo C.; Syed, Viqar

2017-01-01

Previously, we have demonstrated that progesterone and calcitriol synergistically inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and causing cell cycle arrest. Metastasis is the main reason of mortality in cancer patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and metastasis. We examined the effects of progesterone, calcitriol and progesterone-calcitriol combination on metastasis promoting proteins in endometrial cancer. Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial tumors and in cancer cell lines compared to normal tissues and immortalized EM-E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins significantly inhibited the invasiveness of the cancer cells. The expression levels of all three proteins was reduced with progesterone and progesterone-calcitriol combination treatment, whereas calcitriol alone showed no effect on their expression but moderately decreased MT1-MMP activity. Fluorescence microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol-treated endometrial cancer cells. However, progesterone and calcitriol-progesterone combination treatment revealed MT1-MMP in the cytoplasm. Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9, and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both progesterone and progesterone-calcitriol combination treated cells as well as in MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer dissemination and may have therapeutic benefits for endometrial cancer patients. PMID:29371931

[Comparison of the factors influencing young adolescents' aggression according to family structure].

PubMed

Yun, Eun Kyoung; Shin, Sung Hee

2013-06-01

This cross-sectional study was done to compare factors influencing young adolescents' aggression according to family structure. Participants were 680 young adolescents aged 11 to 15 years (113 in single father families, 136 in single mother families, 49 in grandparent families, and 382 in both-parent families). All measures were self-administered. Data were analyzed using SPSS 18.0 program and factors affecting young adolescents' aggression were analyzed by stepwise multiple regression. Levels of young adolescents' aggression and all variables were significantly different among the four family structure groups. Factors influencing young adolescents' aggression were also different according to these 4 groups. For single father families, depression-anxiety and family hardiness significantly predicted the level of young adolescents' aggression (adjusted R square=.37, p<.001). For single mother families, depression-anxiety, gender, and friends' support significantly predicted the level of young adolescents' aggression (adjusted R square=.58, p<.001). For grandparent families, depression-anxiety and family support significantly predicted the level of young adolescents' aggression (adjusted R square=.58, p<.001). For both-parent families, depression-anxiety, family hardiness, and friends' support significantly predicted the level of young adolescents' aggression (adjusted R square=.48, p<.001). Nurses working with young adolescents should consider family structure-specific factors influencing aggression in this population.

Teachers' Knowledge of Children's Exposure to Family Risk Factors: Accuracy and Usefulness

ERIC Educational Resources Information Center

Dwyer, Sarah B.; Nicholson, Jan M.; Battistutta, Diana; Oldenburg, Brian

2005-01-01

Teachers' knowledge of children's exposure to family risk factors was examined using the Family Risk Factor Checklist-Teacher. Data collected for 756 children indicated that teachers had accurate knowledge of children's exposure to factors such as adverse life events and family socioeconomic status, which predicted children's mental health…

Factors associated with family-centered involvement in family practice--a cross-sectional multivariate analysis.

PubMed

Deutsch, Tobias; Frese, Thomas; Sandholzer, Hagen

2014-01-01

The importance of a family-centered approach in family practice has been emphasized. Knowledge about factors associated with higher family-centered involvement seems beneficial to stimulate its realization. German office-based family physicians completed a questionnaire addressing several aspects of family-centered care. Logistic regression was used to identify associations with the involvement overall and in different domains: routine inquiry and documentation of family-related information, family orientation regarding diagnosis and treatment, family-oriented dialogues, family conferences, and case-related collaboration with marriage and family therapists. We found significant associations between physicians' family-centered involvement and expected patient receptiveness, perceived impact of the family's influence on health, self-perceived psychosocial family-care competences (overall and concerning concepts for family orientation, psychosocial intervention in family conferences, and the communication of the idea of family counseling), advanced training in psychosocial primary care (PPC), personal acquaintance with family therapists (regarding case-related collaboration), and rural office environment. Increased emphasis on the family's influence on health in medical education and training, the provision of concepts for a family-centered perspective, and versatile skills for psychosocial intervention and inquiry of patient preferences, as well as the strengthening of networking between family physicians and family therapists, might promote the family-centered approach in family practice.

A familial factor in the development of colour agnosia.

PubMed

Nijboer, Tanja C W; van Zandvoort, Martine J E; de Haan, Edward H F

2007-04-09

An important aspect of research into the link between genes and behaviour concerns the identification of familial determination. There is evidence for familial factors in selective deficits, such as developmental dyslexia and developmental prosopagnosia. Colour agnosia concerns a selective neuropsychological condition in which colour perception is intact, while the identification and naming of colour is disrupted. We recently demonstrated that this deficit can occur as a developmental deficit. Here, we show that there is a familial factor in the development of colour agnosia by reporting the colour processing abilities of the mother and the daughters of a man with developmental colour agnosia.

The Returned Prisoner of War: Factors in Family Reintegration

ERIC Educational Resources Information Center

McCubin, Hamilton I.; And Others

1975-01-01

Longitudinal study on 48 families of returned prisoners of war to identify factors to explain degree of reintegration of returnee into his family system. Four sets of data were considered: (1) background characteristics of husband and wife; (2) indices of family preparedness; (3) returnees' prison experiences and their psychiatric status; (4)…

The impact of social and family-related factors on women's stress experience in household and family work.

PubMed

Sperlich, Stefanie; Geyer, Siegfried

2015-03-01

This study explores the contribution of social and family-related factors to women's experience of an effort-reward imbalance (ERI) in household and family work. Using a population-based sample of German mothers (n = 3,129), we performed stepwise logistic regression analysis in order to determine the relative impact of social and family-related factors on ERI. All factors investigated showed a significant association with at least one ERI component. Considering all predictors simultaneously in the multivariate analysis resulted in a decrease in significance of socioeconomic status in explaining the effort-reward ratio while the impact on low reward partly remained significant. In addition, age of youngest child, number of children, lower levels of perceived social support, domestic work inequity and negative work-to-family spillover, irrespective of being half- or full-time employed, revealed to be important in predicting ERI. The experience of ERI in domestic work is influenced by the social and family environment. Particularly among socially disadvantaged mothers, lack of social recognition for household and family work proved to be a relevant source of psychosocial stress.

Family Factors Predicting Categories of Suicide Risk

ERIC Educational Resources Information Center

Randell, Brooke P.; Wang, Wen-Ling; Herting, Jerald R.; Eggert, Leona L.

2006-01-01

We compared family risk and protective factors among potential high school dropouts with and without suicide-risk behaviors (SRB) and examined the extent to which these factors predict categories of SRB. Subjects were randomly selected from among potential dropouts in 14 high schools. Based upon suicide-risk status, 1,083 potential high school…

The transcription factor EGR1 localizes to the nucleolus and is linked to suppression of ribosomal precursor synthesis.

PubMed

Ponti, Donatella; Bellenchi, Gian Carlo; Puca, Rosa; Bastianelli, Daniela; Maroder, Marella; Ragona, Giuseppe; Roussel, Pascal; Thiry, Marc; Mercola, Dan; Calogero, Antonella

2014-01-01

EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.

Arf6 controls beta-amyloid production by regulating macropinocytosis of the Amyloid Precursor Protein to lysosomes.

PubMed

Tang, Weihao; Tam, Joshua H K; Seah, Claudia; Chiu, Justin; Tyrer, Andrea; Cregan, Sean P; Meakin, Susan O; Pasternak, Stephen H

2015-07-14

Alzheimer's disease (AD) is characterized by the deposition of Beta-Amyloid (Aβ) peptides in the brain. Aβ peptides are generated by cleavage of the Amyloid Precursor Protein (APP) by the β - and γ - secretase enzymes. Although this process is tightly linked to the internalization of cell surface APP, the compartments responsible are not well defined. We have found that APP can be rapidly internalized from the cell surface to lysosomes, bypassing early and late endosomes. Here we show by confocal microscopy and electron microscopy that this pathway is mediated by macropinocytosis. APP internalization is enhanced by antibody binding/crosslinking of APP suggesting that APP may function as a receptor. Furthermore, a dominant negative mutant of Arf6 blocks direct transport of APP to lysosomes, but does not affect classical endocytosis to endosomes. Arf6 expression increases through the hippocampus with the development of Alzheimer's disease, being expressed mostly in the CA1 and CA2 regions in normal individuals but spreading through the CA3 and CA4 regions in individuals with pathologically diagnosed AD. Disruption of lysosomal transport of APP reduces both Aβ40 and Aβ42 production by more than 30 %. Our findings suggest that the lysosome is an important site for Aβ production and that altering APP trafficking represents a viable strategy to reduce Aβ production.

The Development and Validation of the Inventory of Family Protective Factors: A Brief Assessment for Family Counseling

ERIC Educational Resources Information Center

Gardner, Deborah L.; Huber, Charles H.; Steiner, Robert; Vazquez, Luis A.; Savage, Todd A.

2008-01-01

This article describes the three-stage protocol employed in development and validation of the Inventory of Family Protective Factors (IFPF), a brief-form formal instrument intended to assess the primary protective factors that contribute to family resilience. Following construction of the instrument, data collections and analyses of a total sample…

Family History Is a Risk Factor for COPD

PubMed Central

Hokanson, John E.; Lynch, David A.; Washko, George R.; Make, Barry J.; Crapo, James D.; Silverman, Edwin K.

2011-01-01

Background: Studies have shown that family history is a risk factor for COPD, but have not accounted for family history of smoking. Therefore, we sought to identify the effects of family history of smoking and family history of COPD on COPD susceptibility. Methods: We compared 821 patients with COPD to 776 control smokers from the Genetic Epidemiology of COPD (COPDGene) Study. Questionnaires captured parental histories of smoking and COPD, as well as childhood environmental tobacco smoke (ETS) exposure. Socioeconomic status was defined by educational achievement. Results: Parental history of smoking (85.5% case patients, 82.9% control subjects) was more common than parental history of COPD (43.0% case patients, 30.8% control subjects). In a logistic regression model, parental history of COPD (OR, 1.73; P < .0001) and educational level (OR, 0.48 for some college vs no college; P < .0001) were significant predictors of COPD, but parental history of smoking and childhood ETS exposure were not significant. The population-attributable risk from COPD family history was 18.6%. Patients with COPD with a parental history had more severe disease, with lower lung function, worse quality of life, and more frequent exacerbations. There were nonsignificant trends for more severe emphysema and airway disease on quantitative chest CT scans. Conclusions: Family history of COPD is a strong risk factor for COPD, independent of family history of smoking, personal lifetime smoking, or childhood ETS exposure. Although further studies are required to identify genetic variants that influence COPD susceptibility, clinicians should question all smokers, especially those with known or suspected COPD, regarding COPD family history. PMID:21310839

Ethnic Differences in Family Factors Related to Early Drug Initiation*

PubMed Central

CATALANO, RICHARD F.; MORRISON, DIANE M.; WELLS, ELIZABETH A.; GILLMORE, MARY R.; IRITANI, BONITA; HAWKINS, J. DAVID

2007-01-01

The literature on family predictors of substance use for the general population is reviewed and compared to findings for three specific ethnic groups: black, white and Asian-Americans. Rates of substance use initiation are examined in a sample of 919 urban 5th-grade students. Ethnic differences on measures of family predictors are examined and significant ethnic differences are found on several of these factors. Finally, separate regressions for black, white and Asian American youths of family factors on the variety of substances initiated examine ethnic similarities and differences in predictors. The results demonstrate significant differences by ethnicity in family management practices, involvement in family activity, sibling deviance, parental disapproval of children's drinking and family structure. The regression equations identified unique as well as common predictors of the variety of substances initiated by the end of 5th grade. Implications of the results are discussed. PMID:1285743

Prevention of childhood obesity: sociocultural and familial factors.

PubMed

Bruss, Mozhdeh B; Morris, Joseph; Dannison, Linda

2003-08-01

This study examined sociocultural and familial factors related to the prevention of childhood obesity. Primary caregivers of 6- to 10-year-old children representing several ethnic populations in Saipan participated in 4 focus groups (N=32). Trained moderators used semi-structured interviews and qualitative methods were used in data analysis. A central theme with several related factors emerged. The theme was a conflict expressed by the primary caregiver between sociocultural values, family expectations, traditional dietary beliefs and attitudes, and knowledge about food and disease. These findings have important implications for designing culturally sensitive interventions for prevention of childhood obesity.

Reliable high-power injection locked 6kHz 60W laser for ArF immersion lithography

NASA Astrophysics Data System (ADS)

Watanabe, Hidenori; Komae, Shigeo; Tanaka, Satoshi; Nohdomi, Ryoichi; Yamazaki, Taku; Nakarai, Hiroaki; Fujimoto, Junichi; Matsunaga, Takashi; Saito, Takashi; Kakizaki, Kouji; Mizoguchi, Hakaru

2007-03-01

Reliable high power 193nm ArF light source is desired for the successive growth of ArF-immersion technology for 45nm node generation. In 2006, Gigaphoton released GT60A, high power injection locked 6kHz/60W/0.5pm (E95) laser system, to meet the demands of semiconductor markets. In this paper, we report key technologies for reliable mass production GT laser systems and GT60A high durability performance test results up to 20 billion pulses.

Environmental risk factors and their impact on the age of onset of schizophrenia: Comparing familial to non-familial schizophrenia.

PubMed

Scherr, Martin; Hamann, Melanie; Schwerthöffer, Dirk; Froböse, Teresa; Vukovich, Ruth; Pitschel-Walz, Gabriele; Bäuml, Josef

2012-04-01

Several risk factors for schizophrenia have yet been identified. The aim of our study was to investigate how certain childhood and adolescent risk factors predict the age of onset of psychosis in patients with and without a familial component (i.e. a relative with schizophrenia or schizoaffective disorder). Aside from the age of onset of psychosis, we examined the risk factors for schizophrenia including obstetric complications, birth during winter or spring, behavioral deviances or delayed motor and speech development, exposure to adverse life events and exposure to substance use within a group of 100 patients (45 female, 55 male) with a mean age (± standard deviation) of 35.15 ± 13.21. Birth complications and cannabis abuse are predictors for an earlier onset of schizophrenia in patients with non-familial schizophrenia. No environmental risk factors for an earlier age of onset in familial schizophrenia have been identified. Certain environmental risk factors for schizophrenia seem to have an impact on the age of onset of psychosis in non-familial schizophrenia, they do not seem to have an impact on familial schizophrenia.

Emotional well-being in children with epilepsy: Family factors as mediators and moderators.

PubMed

Goodwin, Shane W; Wilk, Piotr; Karen Campbell, M; Speechley, Kathy N

2017-11-01

Our objective was to examine the relationships of factors associated with children's emotional well-being 2 years after diagnosis, and to examine if these relationships are mediated or moderated by family factors. Data came from a multicenter prospective cohort study of children with newly diagnosed epilepsy from across Canada (Health-Related Quality of Life in Children with Epilepsy Study; HERQULES, n = 373). Emotional well-being was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). The relationships between clinical factors, family factors, and emotional well-being were assessed using multiple regression analyses. Family functioning, family stress, and repertoire of resources that the families had to adapt to stressful events were significantly associated with poor emotional well-being 2 years after diagnosis (p < 0.05) in the multivariable analysis. The effect of parental depressive symptoms was partially mediated by family functioning and family stress (p < 0.01 and p = 0.02, respectively). Family resources acted as a moderator in the relationship between severity of epilepsy and emotional well-being (p < 0.05). Based on our findings, efforts to strengthen the family environment may warrant attention. We suggest that clinicians take a family centered care approach by including families in treatment planning. Family centered care has been shown to improve family well-being and coping and in turn may reduce the impact of clinical factors on emotional well-being to improve long-term health-related quality of life. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Family Factors and Primary Students' Reading Attainment: A Chinese Community Perspective

ERIC Educational Resources Information Center

Ko, Hwa Wei; Chan, Yi Ling

2009-01-01

This study examined the relationship between students' reading attainment scores and key family environmental factors in Chinese and non-Chinese communities. Six family environmental factors were considered: parents' evaluation of their offspring's early literacy skills, early home literacy activities (EHLA), reading activities involving parents…

Factor analysis shows association between family activity environment and children's health behaviour.

PubMed

Hendrie, Gilly A; Coveney, John; Cox, David N

2011-12-01

To characterise the family activity environment in a questionnaire format, assess the questionnaire's reliability and describe its predictive ability by examining the relationships between the family activity environment and children's health behaviours - physical activity, screen time and fruit and vegetable intake. This paper describes the creation of a tool, based on previously validated scales, adapted from the food domain. Data are from 106 children and their parents (Adelaide, South Australia). Factor analysis was used to characterise factors within the family activity environment. Pearson-Product Moment correlations between the family environment and child outcomes, controlling for demographic variation, were examined. Three factors described the family activity environment - parental activity involvement, opportunity for role modelling and parental support for physical activity - and explained 37.6% of the variance. Controlling for demographic factors, the scale was significantly correlated with children's health behaviour - physical activity (r=0.27), screen time (r=-0.24) and fruit and vegetable intake (r=0.34). The family activity environment questionnaire shows high internal consistency and moderate predictive ability. This study has built on previous research by taking a more comprehensive approach to measuring the family activity environment. This research suggests the family activity environment should be considered in family-based health promotion interventions. © 2011 The Authors. ANZJPH © 2011 Public Health Association of Australia.

Family factors contributing to emotional and behavioral problems in Korean adolescents with epilepsy.

PubMed

Han, Su-Hyun; Lee, Sang-Ahm; Eom, Soyong; Kim, Heung-Dong

2016-03-01

We aimed to determine whether different aspects of family functioning are associated with emotional and behavioral problems in adolescents with epilepsy and, if not, to document any indirect associations mediated by other family factors. This was a cross-sectional, multicenter study. A total of 297 adolescents with epilepsy and their parents participated. Adolescent psychopathology was measured using the Youth Self-Report. Family factors were classified into proximal (parent-child interaction), distal (parent characteristics), and contextual factors (family characteristics) in accordance to their level of proximity to the adolescent's everyday life. Regression analyses were used to analyze the unique and combined predictive power of family factors in relation to psychopathology. In total, 44 (14.8%) and 51 (17.2%) adolescents with epilepsy scored above the borderline cutoff (T-score ≥ 60) of internalizing and externalizing problems, respectively. Proximal and distal factors were independently associated with both internalizing and externalizing problems. High levels of parental depressive mood and parental overcontrol were the strongest factors contributing to internalizing and externalizing problems, respectively. Contextual factors were indirectly associated with both internalizing and externalizing problems through more proximal factors. Both proximal and distal family factors affect psychopathology in Korean adolescents with epilepsy. Parental feelings of depression and parental overcontrol are the strongest factors contributing to internalizing and externalizing problems, respectively. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrative Families and Systems Treatment: A Middle Path toward Integrating Common and Specific Factors in Evidence-Based Family Therapy

ERIC Educational Resources Information Center

Fraser, J. Scott; Solovey, Andrew D.; Grove, David; Lee, Mo Yee; Greene, Gilbert J.

2012-01-01

A moderate common factors approach is proposed as a synthesis or middle path to integrate common and specific factors in evidence-based approaches to high-risk youth and families. The debate in family therapy between common and specific factors camps is reviewed and followed by suggestions from the literature for synthesis and creative flexibility…

The ArF laser for the next-generation multiple-patterning immersion lithography supporting green operations

NASA Astrophysics Data System (ADS)

Ishida, Keisuke; Ohta, Takeshi; Miyamoto, Hirotaka; Kumazaki, Takahito; Tsushima, Hiroaki; Kurosu, Akihiko; Matsunaga, Takashi; Mizoguchi, Hakaru

2016-03-01

Multiple patterning ArF immersion lithography has been expected as the promising technology to satisfy tighter leading edge device requirements. One of the most important features of the next generation lasers will be the ability to support green operations while further improving cost of ownership and performance. Especially, the dependence on rare gases, such as Neon and Helium, is becoming a critical issue for high volume manufacturing process. The new ArF excimer laser, GT64A has been developed to cope with the reduction of operational costs, the prevention against rare resource shortage and the improvement of device yield in multiple-patterning lithography. GT64A has advantages in efficiency and stability based on the field-proven injection-lock twin-chamber platform (GigaTwin platform). By the combination of GigaTwin platform and the advanced gas control algorithm, the consumption of rare gases such as Neon is reduced to a half. And newly designed Line Narrowing Module can realize completely Helium free operation. For the device yield improvement, spectral bandwidth stability is important to increase image contrast and contribute to the further reduction of CD variation. The new spectral bandwidth control algorithm and high response actuator has been developed to compensate the offset due to thermal change during the interval such as the period of wafer exchange operation. And REDeeM Cloud™, new monitoring system for managing light source performance and operations, is on-board and provides detailed light source information such as wavelength, energy, E95, etc.

Factors associated with family violence by persons with psychiatric disorders.

PubMed

Labrum, Travis; Solomon, Phyllis L

2016-10-30

Family violence by persons with psychiatric disorders (PD) is a highly under-researched area. The primary objective of the present analysis was to identify perpetrator, victim, and interaction/relationship factors associated with this phenomenon. The secondary objective was to examine the extent to which the relationship between caregiving and family violence was mediated by limit-setting practices used towards relatives with PD. 573 adults across the U.S. with an adult relative with PD completed an online survey. Multivariate logistic regression was performed examining the association of factors with the occurrence of family violence. Mediation was assessed with Sobel testing. Family violence was significantly associated with the following factors: perpetrator-income, illegal drug use, psychiatric hospitalization, treatment attendance, and use of medications; victim-age, employment status, income, and mental health status; interaction/relationship-parental relationship, co-residence, use of limit-setting practices, representative payeeship, and unofficial money management. Mediation was statistically significant. Increasing access to mental health and/or substance abuse treatment may decrease the risk of family violence. Interventions may benefit from attempting to decrease/modify the use of limit-setting practices. Where family representative payeeship or unofficial money management exists, it is advisable for practitioners to assess and address financial coercion and promote greater collaboration in financial decision-making. Published by Elsevier Ireland Ltd.

Effects of Site-Directed Mutagenesis of Escherichia coli Heat-Labile Enterotoxin on ADP-Ribosyltransferase Activity and Interaction with ADP-Ribosylation Factors

PubMed Central

A. Stevens, Linda; Moss, Joel; Vaughan, Martha; Pizza, Mariagrazia; Rappuoli, Rino

1999-01-01

Escherichia coli heat-labile enterotoxin (LT), an oligomeric protein with one A subunit (LTA) and five B subunits, exerts its effects via the ADP-ribosylation of Gsα, a guanine nucleotide-binding (G) protein that activates adenylyl cyclase. LTA also ADP-ribosylates simple guanidino compounds (e.g., arginine) and catalyzes its own auto-ADP-ribosylation. All LTA-catalyzed reactions are enhanced by ADP-ribosylation factors (ARFs), 20-kDa guanine nucleotide-binding proteins. Replacement of arginine-7 (R7K), valine-53 (V53D), serine-63 (S63K), valine 97 (V97K), or tyrosine-104 (Y104K) in LTA resulted in fully assembled but nontoxic proteins. S63K, V53D, and R7K are catalytic-site mutations, whereas V97K and Y104K are amino acid replacements adjacent to and outside of the catalytic site, respectively. The effects of mutagenesis were quantified by measuring ADP-ribosyltransferase activity (i.e., auto-ADP-ribosylation and ADP-ribosylagmatine synthesis) and interaction with ARF (i.e., inhibition of ARF-stimulated cholera toxin ADP-ribosyltransferase activity and effects of ARF on mutant auto-ADP-ribosylation). All mutants were inactive in the ADP-ribosyltransferase assay; however, auto-ADP-ribosylation in the presence of recombinant human ARF6 was detected, albeit much less than that of native LT (Y104K > V53D > V97K > R7K, S63K). Based on the lack of inhibition by free ADP-ribose, the observed auto-ADP-ribosylation activity was enzymatic and not due to the nonenzymatic addition of free ADP-ribose. V53D, S63K, and R7K were more effective than Y104K or V97K in blocking ARF stimulation of cholera toxin ADP-ribosyltransferase. Based on these data, it appears that ARF-binding and catalytic sites are not identical and that a region outside the NAD cleft may participate in the LTA-ARF interaction. PMID:9864224

ArF step-and-scan system with 0.75 NA for the 0.10μm node

NASA Astrophysics Data System (ADS)

Vleeming, Bert; Heskamp, Barbra; Bakker, Hans; Verstappen, Leon; Finders, Jo; Stoeten, Jan; Boerret, Rainer; Roempp, Oliver

2001-09-01

It is widely expected that 193 nm lithography will be the technology of choice for volume production of the 0.10 micrometer device generation. For this purpose the PAS5500/1100TM Step & Scan system, the second generation ArF tool, was developed. It is based on the PAS5500/900TM, the body of which has been adapted to fit the new 0.75 NA StarlithTM projection optics. This high NA enables mass manufacturing of devices following the 0.10 micrometer design rule. The system features a 10 W 2 kHz ArF laser and the AERIALTM II illuminator that can be equipped with a QUASARTM (multipole) option. In order to minimize wafer processing influences on overlay performance ATHENATM off- axis alignment with phase modulator is implemented. The usage of Reticle Blue Alignment will further improve overlay as well as increase the system stability. In this paper the PAS5500/1100TM system layout is discussed and the first imaging and overlay results are presented. Imaging performance is illustrated by SEM pictures of 0.10 micrometer dense lines, 0.15, 0.13 and 0.12 micrometer dense contact holes, 0.10 micrometer DRAM isolation patterns, image plane deviation and system distortion fingerprints. Alignment reproducibility and single machine overlay results demonstrate the overlay capability.

Inactivation of INK4a and ARF induces myocardial proliferation and improves cardiac repair following ischemia‑reperfusion.

PubMed

An, Songtao; Chen, Yan; Gao, Chuanyu; Qin, Bingyu; Du, Xianhui; Meng, Fanmin; Qi, Yanyan

2015-10-01

The growth of the heart during mammalian embryonic development is primarily dependent on an increase in the number of cardiomyocytes (CM). However, shortly following birth, CMs cease proliferating and further growth of the myocardium is achieved via hypertrophic expansion of the existing CM population. The cyclin-dependent kinase inhibitor 2A (Cdkn2a) locus encodes overlapping genes for two tumor suppressor proteins, p16INK4a and p19 alternative reading frame (ARF). To determine whether decreased Cdkn2a gene expression results in improved cardiac regeneration in vitro and in vivo following cardiac injury, the proliferation of CMs isolated from Cdkn2a knockout (KO) and wild‑type (WT) mice in vitro and in vivo were evaluated following generation of ischemia reperfusion (IR) injury. The KO mice demonstrated enhanced CM proliferation not only in vitro, but also in vivo. Furthermore, heart function was improved and scar size was decreased in the KO mice compared with that of the WT mice. The results also indicated that microRNA (miR)‑1 and miR‑195 expression levels associated with cell proliferation were reduced following IR injury in KO mice compared with those of WT mice. These results suggested that the inactivation of INK4a and ARF stimulated CM proliferation and promoted cardiac repair.

Sociocultural and Familial Factors Associated with Weight Bias Internalization

PubMed Central

Pearl, Rebecca L.; Wadden, Thomas A.; Shaw Tronieri, Jena; Chao, Ariana M.; Alamuddin, Naji; Bakizada, Zayna M.; Pinkasavage, Emilie; Berkowitz, Robert I.

2018-01-01

Background/Aims Sociocultural and familial factors associated with weight bias internalization (WBI) are currently unknown. The present study explored the relationship between interpersonal sources of weight stigma, family weight history, and WBI. Methods Participants with obesity (N = 178, 87.6% female, 71.3% black) completed questionnaires that assessed the frequency with which they experienced weight stigma from various interpersonal sources. Participants also reported the weight status of their family members and completed measures of WBI, depression, and demographics. Participant height and weight were measured to calculate body mass index (BMI). Results Linear regression results (controlling for demographics, BMI, and depression) showed that stigmatizing experiences from family and work predicted greater WBI. Experiencing weight stigma at work was associated with WBI above and beyond the effects of other sources of stigma. Participants who reported higher BMIs for their mothers had lower levels of WBI. Conclusion Experiencing weight stigma from family and at work may heighten WBI, while having a mother with a higher BMI may be a protective factor against WBI. Prospective research is needed to understand WBI's developmental course and identify mechanisms that increase or mitigate its risk. PMID:29656285

Assessment of family functioning in Caucasian and Hispanic Americans: reliability, validity, and factor structure of the Family Assessment Device.

PubMed

Aarons, Gregory A; McDonald, Elizabeth J; Connelly, Cynthia D; Newton, Rae R

2007-12-01

The purpose of this study was to examine the factor structure, reliability, and validity of the Family Assessment Device (FAD) among a national sample of Caucasian and Hispanic American families receiving public sector mental health services. A confirmatory factor analysis conducted to test model fit yielded equivocal findings. With few exceptions, indices of model fit, reliability, and validity were poorer for Hispanic Americans compared with Caucasian Americans. Contrary to our expectation, an exploratory factor analysis did not result in a better fitting model of family functioning. Without stronger evidence supporting a reformulation of the FAD, we recommend against such a course of action. Findings highlight the need for additional research on the role of culture in measurement of family functioning.

Comprehensive mutation analysis of PIK3CA, p14ARF, p16INK4a and p21Waf1/Cip1 genes is suggestive of a non- neoplastic nature of phenytoin induced gingival overgrowth.

PubMed

Swamikannu, Bhuminathan; Kumar, Kishore S; Jayesh, Raghavendra S; Rajendran, Senthilnathan; Muthupalani, Rajendran Shanmugam; Ramanathan, Arvind

2013-01-01

Dilantin sodium (phenytoin) is an antiepileptic drug, which is routinely used to control generalized tonic clonic seizure and partial seizure episodes. A few case reports of oral squamous cell carcinomas arising from regions of phenytoin induced gingival overgrowth (GO), and overexpression of mitogenic factors and p53 have presented this condition as a pathology with potential to transform into malignancy. We recently investigated the genetic status of p53 and H-ras, which are known to be frequently mutated in Indian oral carcinomas in GO tissues and found them to only contain wild type sequences, which suggested a non-neoplastic nature of phenytoin induced GO. However, besides p53 and H-ras, other oncogenes and tumor suppressors such as PIK3CA, p14ARF, p16INK4a and p21Waf1/Cip1, are frequently altered in oral squamous cell carcinoma, and hence are required to be analyzed in phenytoin induced GO tissues to be affirmative of its non-neoplastic nature. 100ng of chromosomal DNA isolated from twenty gingival overgrowth tissues were amplified with primers for exons 9 and 20 of PIK3CA, exons 1α, 1β and 2 of p16INK4a and p14ARF, and exon 2 of p21Waf1/Cip1, in independent reactions. PCR amplicons were subsequently gel purified and eluted products were sequenced. Sequencing analysis of the twenty samples of phenytoin induced gingival growth showed no mutations in the analyzed exons of PIK3CA, p14ARF, p16INK4a and p21Waf1/Cip1. The present data indicate that the mutational alterations of genes, PIK3CA, p14ARF, p16INK4a and p21Waf1/Cip1 that are frequently mutated in oral squamous cell carcinomas are rare in phenytoin induced gingival growth. Thus the findings provide further evidence that phenytoin induced gingival overgrowth as a non-neoplastic lesion, which may be considered as clinically significant given the fact that the epileptic patients are routinely administered with phenytoin for the rest of their lives to control seizure episodes.

Protective Family Factors in the Context of Neighborhood: Promoting Positive School Outcomes

ERIC Educational Resources Information Center

Woolley, Michael E.; Grogan-Kaylor, Andrew

2006-01-01

Three developmental contexts--school, neighborhood, and family--influence school outcomes. The focus of the current investigation was on the promotive role of 4 family factors--family satisfaction, family support, family integration, and home academic culture--on 3 school outcomes. These outcomes included student self-reported sense of school…

Family obligation values as a protective and vulnerability factor among low-income adolescent girls.

PubMed

Milan, Stephanie; Wortel, Sanne

2015-06-01

Adolescents' beliefs about family obligation often reflect cultural variations in their family context, and thus are important for understanding development among diverse youth. In this study, we test hypotheses about the role of family obligation values in risk behavior and mental health in a sample of 194 low-income adolescent girls (mean age = 15.2; 58% Latina, 28% African-American/Black). We hypothesized that family obligation values can be both a protective and vulnerability factor, depending on the type of outcome and the presence of other risk factors. Across the sample, higher family obligation values tended to occur with indicators of positive family functioning (e.g., more frequent communication, less maternal hostility) based on mother and adolescent reports. As hypothesized, family obligation values moderated the relationship between established risk factors and adjustment in distinct ways, such that high family obligation values decreased risk in some domains (i.e., a protective factor) but increased risk in other domains (i.e., a vulnerability factor). Specifically, high family obligation values diminished the relationship between peer norms for risky behavior (sex and substance use) and individual engagement in those behaviors. At the same time, high family obligation values magnified the relationship between exposure to negative life events and poor mental health (PTSD and depressive symptoms). The results suggest that family obligation is an important but complex aspect of development among diverse adolescent girls.

Marriage and Family Therapy Students' Experience with Common Factors Training.

PubMed

Fife, Stephen T; D'Aniello, Carissa; Scott, Sarah; Sullivan, Erin

2018-04-27

With the increased empirical and theoretical support for common factors in the psychotherapy literature, marriage and family therapy (MFT) scholars have begun discussing the inclusion of common factors in MFT training. However, there is very little empirical research on common factors training or how to include common factors in MFT curricula. The purpose of this phenomenological study was to investigate MFT students' experience with common factors training. Seventeen master's degree students who received training in common factors participated in the study. Data was comprised of participants' journal reflections and focus group interviews on their experience learning about common factors and how this influenced their work with clients. Participants' responses to the training were overwhelmingly positive and highlighted the ways in which studying common factors enhanced their confidence, understanding of MFT models, conceptual abilities, and clinical practice. Additional results and discussion about incorporating common factors in MFT training are presented. © 2018 American Association for Marriage and Family Therapy.

Socioeconomic development, family income, and psychosocial risk factors: a study of families with children in public elementary school.

PubMed

Assis, Simone Gonçalves de; Pires, Thiago; Pesce, Renata Pires; Avanci, Joviana Quintes; Oliveira, Raquel V C

2011-01-01

This article aims to evaluate the effects of Brazil's recent economic growth on the monetary income, consumption patterns, and risk exposures of families with children enrolled in the public elementary school system in São Gonçalo, Rio de Janeiro State, Brazil. The article analyzes the following information on families of 447 children that participated in two waves in a longitudinal study: social stratum, per capita family income, evolution in income over a three-year period, and psychosocial factors. The findings showed a 74.8% increase in the families' income, accompanied by an increase in the consumption of material assets and access to health services. This increase should not be interpreted as a guarantee of improved living and health conditions, since it was spent on basic products and needs that do not substantially affect the families' form of social inclusion. Psychosocial risk factors were frequent among the families, but decreased during the study period, which may either reflect the improved family situation or result from the later stage in child development.

MEKK1 is a Novel Regulator of the Dmp1-Arf-p53 Pathway and Prognostic Indicator in Breast Cancer

DTIC Science & Technology

2012-12-01

hDMP1, INK4a/ARF, p53 or Hdm2 amplification. Kaplan -Meier analyses have been conducted to study the impact for the impact of loss or gain of each locus on...Palma P, Pellegrini S, Fina P et al. Mdm2 gene alterations and mdm2 protein expression in breast carcinomas. J Pathol 1995; 175: 31–38. 21 Turbin DA

Modifiable factors associated with caregiver burden among family caregivers of terminally ill Korean cancer patients.

PubMed

Yoon, Seok-Joon; Kim, Jong-Sung; Jung, Jin-Gyu; Kim, Sung-Soo; Kim, Samyong

2014-05-01

Higher caregiver burden is associated with poor quality of life among family caregivers. However, in Korea, very few studies have examined factors associated with caregiver burden. The present study investigated factors associated with caregiver burden among family caregivers of terminally ill Korean cancer patients, particularly modifiable factors as a potential target of intervention strategies. A cross-sectional study using self-administered questionnaires was performed. Sixty-four family caregivers of terminally ill cancer patients who were admitted to the hospice-palliative care unit of a university hospital in South Korea were included. To identify caregiver burden, the Caregiver Reaction Assessment scale (CRA) was used in this study. Time spent in providing care per day, number of visits per week from other family members, family functioning, and a positive subscale, self-esteem, of the CRA were deemed as modifiable factors. Other sociodemographic, caregiving characteristics of the subjects were non-modifiable factors. Longer time spent providing care per day, fewer weekly visits from other family members, poor family functioning, and low self-esteem were considered as modifiable factors associated with caregiver burden. Low monthly income and the spouse being the family caregiver were non-modifiable factors. Our study has practical significance in that it identifies modifiable factors that can be used to devise intervention strategies. Developing and applying such intervention strategies for alleviating the factors associated with high caregiver burden could be important for improving the quality of life of both patients and their families.

Drug-related acute renal failure in hospitalised patients.

PubMed

Iavecchia, Lujan; Cereza García, Gloria; Sabaté Gallego, Mònica; Vidal Guitart, Xavier; Ramos Terrades, Natalia; de la Torre, Judith; Segarra Medrano, Alfons; Agustí Escasany, Antònia

2015-01-01

The information available on the incidence and the characteristics of patients with acute renal failure (ARF) related to drugs is scarce. To estimate the incidence of drug-related ARF in hospitalised patients and to compare their characteristics with those of patients with ARF due to other causes. We selected a prospective cohort of patients with ARF during hospital admission (July 2010-July 2011). Information on patients' demographics, medical antecedents, ARF risk factors, ARF severity according to the RIFLE classification and hospital drug administration was collected. We analysed the relationship of drugs with the ARF episodes using Spanish Pharmacovigilance System methods and algorithm. A total of 194 cases had an episode of hospital-acquired ARF. The median age of patients was 72 years [IQR 20]; 60% were men. The ARF incidence during hospitalization was 9.6 per 1,000 admissions. According to the RIFLE classification, a risk of kidney damage or kidney injury was present in 77.8% of cases. In 105 (54.1%) cases, ARF was drug-related; the drugs most frequently involved were diuretics, agents acting on the renin-angiotensin system, immunosuppressants, β-blocking agents, calcium channel blockers, contrast media and non-steroid anti-inflammatory drugs. Patients with drug-related ARF had more multi-morbidity, fewer ARF risk factors and lower mortality. Half of ARF episodes during hospitalisation were drug related. Patients with drug-related ARF had higher cardiovascular morbidity than those with ARF related to other causes, but they had a lower frequency of ARF risk factors and mortality. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Multiple Levels of Family Factors and Oppositional Defiant Disorder Symptoms Among Chinese Children.

PubMed

Lin, Xiuyun; Li, Longfeng; Heath, Melissa A; Chi, Peilian; Xu, Shousen; Fang, Xiaoyi

2018-03-01

Family factors are closely associated with child developmental outcomes. This study examined the relationship of oppositional defiant disorder (ODD) symptoms and factors at whole family, dyadic, and individual levels in Chinese children. Participants, who were recruited from 14 primary schools in north, east, and south-west China, included 80 father-child dyads and 169 mother-child dyads. Children in the participating dyads were previously diagnosed with ODD. Results revealed that family cohesion/adaptability was indirectly associated with ODD symptoms via parent-child relationship and child emotion regulation. Parent-child relationship affected ODD symptoms directly and indirectly through child emotion regulation. In addition, the effects of family cohesion/adaptability on parent emotion regulation and child emotion regulation were mediated by the parent-child relationship. The tested model provides a comprehensive framework of how family factors at multiple levels are related to child ODD symptoms and highlights the importance of understanding child emotional and behavioral problems within the family context, more specifically within the multiple levels of family relationships. © 2016 Family Process Institute.

A coherent transcriptional feed-forward motif model for mediating auxin-sensitive PIN3 expression during lateral root development

PubMed Central

Chen, Qian; Liu, Yang; Maere, Steven; Lee, Eunkyoung; Van Isterdael, Gert; Xie, Zidian; Xuan, Wei; Lucas, Jessica; Vassileva, Valya; Kitakura, Saeko; Marhavý, Peter; Wabnik, Krzysztof; Geldner, Niko; Benková, Eva; Le, Jie; Fukaki, Hidehiro; Grotewold, Erich; Li, Chuanyou; Friml, Jiří; Sack, Fred; Beeckman, Tom; Vanneste, Steffen

2015-01-01

Multiple plant developmental processes, such as lateral root development, depend on auxin distribution patterns that are in part generated by the PIN-formed family of auxin-efflux transporters. Here we propose that AUXIN RESPONSE FACTOR7 (ARF7) and the ARF7-regulated FOUR LIPS/MYB124 (FLP) transcription factors jointly form a coherent feed-forward motif that mediates the auxin-responsive PIN3 transcription in planta to steer the early steps of lateral root formation. This regulatory mechanism might endow the PIN3 circuitry with a temporal ‘memory' of auxin stimuli, potentially maintaining and enhancing the robustness of the auxin flux directionality during lateral root development. The cooperative action between canonical auxin signalling and other transcription factors might constitute a general mechanism by which transcriptional auxin-sensitivity can be regulated at a tissue-specific level. PMID:26578065

Homelessness in female-headed families: childhood and adult risk and protective factors.

PubMed Central

Bassuk, E L; Buckner, J C; Weinreb, L F; Browne, A; Bassuk, S S; Dawson, R; Perloff, J N

1997-01-01

OBJECTIVES: To identify risk and protective factors for family homelessness, a case-control study of homeless and low-income, never-homeless families, all female-headed, was conducted. METHODS: Homeless mothers (n = 220) were enrolled from family shelters in Worcester, Mass. Low-income housed mothers receiving welfare (n = 216) formed the comparison group. The women completed an interview covering socioeconomic, social support, victimization, mental health, substance use, and health domains. RESULTS: Childhood predictors of family homelessness included foster care placement and respondent's mother's use of drugs. Independent risk factors in adulthood included minority status, recent move to Worcester, recent eviction, interpersonal conflict, frequent alcohol or heroin use, and recent hospitalization for a mental health problem. Protective factors included being a primary tenant, receiving cash assistance or a housing subsidy, graduating from high school, and having a larger social network. CONCLUSIONS: Factors that compromise an individual's economic and social resources are associated with greater risk of losing one's home. PMID:9103104

Family Therapy and Group Counseling: Therapeutic Factors and the Chemically Dependent Adolescent.

ERIC Educational Resources Information Center

Weis, David M.; And Others

1988-01-01

Suggests a combination of family therapy and group counseling in the treatment of chemically dependent adolescents. Explores the development of the individual in the family and examines the literature on therapeutic factors present in group and family therapy. Includes example for practitioners interested in combining group and family therapy…

Separation of cognitive impairments in attention-deficit/hyperactivity disorder into 2 familial factors.

PubMed

Kuntsi, Jonna; Wood, Alexis C; Rijsdijk, Frühling; Johnson, Katherine A; Andreou, Penelope; Albrecht, Björn; Arias-Vasquez, Alejandro; Buitelaar, Jan K; McLoughlin, Gráinne; Rommelse, Nanda N J; Sergeant, Joseph A; Sonuga-Barke, Edmund J; Uebel, Henrik; van der Meere, Jaap J; Banaschewski, Tobias; Gill, Michael; Manor, Iris; Miranda, Ana; Mulas, Fernando; Oades, Robert D; Roeyers, Herbert; Rothenberger, Aribert; Steinhausen, Hans-Christoph; Faraone, Stephen V; Asherson, Philip

2010-11-01

Attention-deficit/hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots or separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. To determine, by using a multivariate familial factor analysis approach, whether 1 or more familial factors underlie the slow and variable reaction times, impaired response inhibition, and choice impulsivity associated with ADHD. An ADHD and control sibling-pair design. Belgium, Germany, Ireland, Israel, Spain, Switzerland, and the United Kingdom. A total of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with combined-subtype ADHD), and 345 control participants. Performance on a 4-choice reaction time task, a go/no-go inhibition task, and a choice-delay task. The final model consisted of 2 familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98% to 100% of the familial influences on mean reaction time and reaction time variability. The second, smaller factor, reflecting 13% of the familial variance of ADHD, captured 62% to 82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model because of poor fit. The findings suggest the existence of 2 familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the 2 cognitive impairments is consistent with recent theoretical models--a developmental model and an arousal-attention model--of 2 separable underlying processes in ADHD. Future research that tests the familial model within a developmental framework may inform

A spotlight on preschool: the influence of family factors on children's early literacy skills.

PubMed

Heath, Steve M; Bishop, Dorothy V M; Bloor, Kimberley E; Boyle, Gemma L; Fletcher, Janet; Hogben, John H; Wigley, Charles A; Yeong, Stephanie H M

2014-01-01

Phonological awareness, letter knowledge, oral language (including sentence recall) and rapid automatised naming are acknowledged within-child predictors of literacy development. Separate research has identified family factors including socio-economic status, parents' level of education and family history. However, both approaches have left unexplained significant amounts of variance in literacy outcomes. This longitudinal study sought to improve prospective classification accuracy for young children at risk of literacy failure by adding two new family measures (parents' phonological awareness and parents' perceived self-efficacy), and then combining the within-child and family factors. Pre-literacy skills were measured in 102 four year olds (46 girls and 56 boys) at the beginning of Preschool, and then at the beginning and end of Kindergarten, when rapid automatised naming was also measured. Family factors data were collected at the beginning of Preschool, and children's literacy outcomes were measured at the end of Year 1 (age 6-7 years). Children from high-risk backgrounds showed poorer literacy outcomes than low-risk students, though three family factors (school socio-economic status, parents' phonological awareness, and family history) typically accounted for less Year 1 variance than the within-child factors. Combining these family factors with the end of Kindergarten within-child factors provided the most accurate classification (i.e., sensitivity = .85; specificity = .90; overall correct = .88). Our approach would identify at-risk children for intervention before they began to fail. Moreover, it would be cost-effective because although few at-risk children would be missed, allocation of unnecessary educational resources would be minimised.

Consanguinity and family clustering of male factor infertility in Lebanon.

PubMed

Inhorn, Marcia C; Kobeissi, Loulou; Nassar, Zaher; Lakkis, Da'ad; Fakih, Michael H

2009-04-01

To investigate the influence of consanguineous marriage on male factor infertility in Lebanon, where rates of consanguineous marriage remain high (29.6% among Muslims, 16.5% among Christians). Clinic-based, case-control study, using reproductive history, risk factor interview, and laboratory-based semen analysis. Two IVF clinics in Beirut, Lebanon, during an 8-month period (January-August 2003). One hundred twenty infertile male patients and 100 fertile male controls, distinguished by semen analysis and reproductive history. None. Standard clinical semen analysis. The rates of consanguineous marriage were relatively high among the study sample. Patients (46%) were more likely than controls (37%) to report first-degree (parental) and second-degree (grandparental) consanguinity. The study demonstrated a clear pattern of family clustering of male factor infertility, with patients significantly more likely than controls to report infertility among close male relatives (odds ratio = 2.58). Men with azoospermia and severe oligospermia showed high rates of both consanguinity (50%) and family clustering (41%). Consanguineous marriage is a socially supported institution throughout the Muslim world, yet its relationship to infertility is poorly understood. This study demonstrated a significant association between consanguinity and family clustering of male factor infertility cases, suggesting a strong genetic component.

Family Factors and Student Outcomes. PRGS Dissertation

ERIC Educational Resources Information Center

Xia, Nailing

2010-01-01

There is considerable debate about the relative importance of family versus school factors in producing academic and nonacademic student outcomes, and whether and how their impacts vary across different student groups. In addition to critically reviewing and synthesizing earlier work, this study extends the literature by (a) using the ECLS-K, a…

Multi-Level Family Factors and Affective and Behavioral Symptoms of Oppositional Defiant Disorder in Chinese Children

PubMed Central

Tang, Yixin; Lin, Xiuyun; Chi, Peilian; Zhou, Qing; Hou, Xiangning

2017-01-01

Given the important role of family environment in children's psychological development, the objective of this study was to examine the linkages between family factors at the whole, dyadic, and individual levels and two dimensions (affective and behavioral) of Oppositional Defiant Disorder (ODD) symptoms in Chinese children. Participants comprised of 80 father-child dyads and 169 mother-child dyads from families with ODD children. The results indicated that multilevel family factors were differently associated with children's affective and behavioral ODD symptoms. All the family factors at the dyadic and individual levels were significantly associated with child affective ODD symptoms. However, only the most proximal factors (parent-child relationship and child emotion regulation, which were directly related to child) were significantly related to child behavioral ODD symptoms. The present study extends the current knowledge regarding the relationships between family factors and two dimensions of child ODD symptoms by testing the comprehensive multilevel family factors model. This study also recommends that future interventions for ODD children should consider the multi-level family factors to enhance intervention efficacy. PMID:28713321

Neighborhood, Family, and Peer Factors Associated with Early Adolescent Smoking and Alcohol Use.

PubMed

Cambron, Christopher; Kosterman, Rick; Catalano, Richard F; Guttmannova, Katarina; Hawkins, J David

2018-02-01

There is broad agreement that neighborhood contexts are important for adolescent development, but there is less consensus about their association with adolescent smoking and alcohol use. Few studies have examined associations between neighborhood socioeconomic contexts and smoking and alcohol use while also accounting for differences in family and peer risk factors for substance use. Data drawn from the Seattle Social Development Project (N = 808), a gender-balanced (female = 49%), multiethnic, theory-driven longitudinal study originating in Seattle, WA, were used to estimate trajectories of smoking and alcohol use from 5th to 9th grade. Time-varying measures of neighborhood socioeconomic, family, and peer factors were associated with smoking and alcohol use at each wave after accounting for average growth in smoking and alcohol use over time and demographic differences. Results indicated that living in more socioeconomically disadvantaged neighborhoods, lower family income, lower family general functioning, more permissive family smoking environments, and affiliation with deviant peers were independently associated with increased smoking. Lower family functioning, more permissive family alcohol use environments, and deviant peers were independently associated with increased alcohol use. The effect of neighborhood disadvantage on smoking was mediated by family income and deviant peers while the effect of neighborhood disadvantage on alcohol use was mediated by deviant peers alone. Family functioning and family substance use did not mediate associations between neighborhood disadvantage and smoking or alcohol use. The results highlight the importance of neighborhood, family, and peer factors in early adolescent smoking and alcohol use. Future studies should examine the unique association of neighborhood disadvantage with adolescent smoking net of family socioeconomics, functioning, and substance use, as well as peer affiliations. Better understanding of the

Risk Factors for Noninvasive Ventilation Failure in Critically Ill Subjects With Confirmed Influenza Infection.

PubMed

Rodríguez, Alejandro; Ferri, Cristina; Martin-Loeches, Ignacio; Díaz, Emili; Masclans, Joan R; Gordo, Federico; Sole-Violán, Jordi; Bodí, María; Avilés-Jurado, Francesc X; Trefler, Sandra; Magret, Monica; Moreno, Gerard; Reyes, Luis F; Marin-Corral, Judith; Yebenes, Juan C; Esteban, Andres; Anzueto, Antonio; Aliberti, Stefano; Restrepo, Marcos I

2017-10-01

Despite wide use of noninvasive ventilation (NIV) in several clinical settings, the beneficial effects of NIV in patients with hypoxemic acute respiratory failure (ARF) due to influenza infection remain controversial. The aim of this study was to identify the profile of patients with risk factors for NIV failure using chi-square automatic interaction detection (CHAID) analysis and to determine whether NIV failure is associated with ICU mortality. This work was a secondary analysis from prospective and observational multi-center analysis in critically ill subjects admitted to the ICU with ARF due to influenza infection requiring mechanical ventilation. Three groups of subjects were compared: (1) subjects who received NIV immediately after ICU admission for ARF and then failed (NIV failure group); (2) subjects who received NIV immediately after ICU admission for ARF and then succeeded (NIV success group); and (3) subjects who received invasive mechanical ventilation immediately after ICU admission for ARF (invasive mechanical ventilation group). Profiles of subjects with risk factors for NIV failure were obtained using CHAID analysis. Of 1,898 subjects, 806 underwent NIV, and 56.8% of them failed. Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, infiltrates in chest radiograph, and ICU mortality (38.4% vs 6.3%) were higher ( P < .001) in the NIV failure than in the NIV success group. SOFA score was the variable most associated with NIV failure, and 2 cutoffs were determined. Subjects with SOFA ≥ 5 had a higher risk of NIV failure (odds ratio = 3.3, 95% CI 2.4-4.5). ICU mortality was higher in subjects with NIV failure (38.4%) compared with invasive mechanical ventilation subjects (31.3%, P = .018), and NIV failure was associated with increased ICU mortality (odds ratio = 11.4, 95% CI 6.5-20.1). An automatic and non-subjective algorithm based on CHAID decision-tree analysis can help to define the

Factors associated with school-aged children's body mass index in Korean American families.

PubMed

Jang, Myoungock; Grey, Margaret; Sadler, Lois; Jeon, Sangchoon; Nam, Soohyun; Song, Hee-Jung; Whittemore, Robin

2017-08-01

To examine factors associated with children's body mass index and obesity-risk behaviours in Korean American families. Limited data are available about family factors related to overweight and obesity in Korean American children. A cross-sectional study. Convenient sampling was employed to recruit Korean American families in the Northeast of the United States between August 2014 and January 2015. Child, family and societal/demographic/community factors were measured with self-report questionnaires completed by mothers and children. Height and weight were measured to calculate body mass index. Data were analyzed using mixed effects models incorporating within-group correlation in siblings. The sample included 170 Korean American children and 137 mothers. In bivariate analyses, more child screen time, number of children in the household, greater parental underestimation of child's weight and children's participation in the school lunch program were significantly associated with higher child body mass index. In multivariate analyses that included variables showing significant bivariate relationship, no variable was associated with child body mass index. There were no child, family and societal/demographic/community factors related to child body mass index in Korean American families in the multivariate analysis, which is contrary to research in other racial/ethnic groups. In bivariate analyses, there is evidence that some factors were significantly related to child body mass index. Further research is needed to understand the unique behavioural, social and cultural features that contribute to childhood obesity in Korean American families. © 2017 John Wiley & Sons Ltd.

Leaving Home: The Role of Individual and Familial Factors.

ERIC Educational Resources Information Center

Sherrod, Lonnie R.

1996-01-01

Discusses the significance of research on the transition to adulthood, examining social-historical changes that may increase the role of individual and familial factors structuring this phase of the life course. Reviews leaving home in regard to its importance as a factor in late adolescence and the transition to adulthood. (HTH)

Quantitative Analysis of Guanine Nucleotide Exchange Factors (GEFs) as Enzymes

PubMed Central

Randazzo, Paul A; Jian, Xiaoying; Chen, Pei-Wen; Zhai, Peng; Soubias, Olivier; Northup, John K

2014-01-01

The proteins that possess guanine nucleotide exchange factor (GEF) activity, which include about ~800 G protein coupled receptors (GPCRs),1 15 Arf GEFs,2 81 Rho GEFs,3 8 Ras GEFs,4 and others for other families of GTPases,5 catalyze the exchange of GTP for GDP on all regulatory guanine nucleotide binding proteins. Despite their importance as catalysts, relatively few exchange factors (we are aware of only eight for ras superfamily members) have been rigorously characterized kinetically.5–13 In some cases, kinetic analysis has been simplistic leading to erroneous conclusions about mechanism (as discussed in a recent review14). In this paper, we compare two approaches for determining the kinetic properties of exchange factors: (i) examining individual equilibria, and; (ii) analyzing the exchange factors as enzymes. Each approach, when thoughtfully used,14,15 provides important mechanistic information about the exchange factors. The analysis as enzymes is described in further detail. With the focus on the production of the biologically relevant guanine nucleotide binding protein complexed with GTP (G•GTP), we believe it is conceptually simpler to connect the kinetic properties to cellular effects. Further, the experiments are often more tractable than those used to analyze the equilibrium system and, therefore, more widely accessible to scientists interested in the function of exchange factors. PMID:25332840

Family and social environmental factors associated with aggression among Chinese adolescents.

PubMed

Dou, Chunxia; Wei, Zhen; Jin, Ke; Wang, He; Wang, Xiulan; Peng, Ziwen

2015-09-01

Family and school environments are assumed to be associated with and influence aggressive behaviors. However, which specific risk factors within these environments that are associated with aggressive behavior are unclear. The goal of this study is to identify family and social environmental qualities that are related to aggression among Chinese adolescents. Survey data were obtained from 3,213 randomly selected urban high school students ages 10 through 18 in southern China. Lower parental attachment, higher family income, mother's higher education levels, father's parenting goals, rough or changeable parenting styles, unsuitable peer relationships, and inadequate social atmospheres at school serve as risk factors for aggression among Chinese adolescents. Our findings provide some implications for understanding aggression among adolescents and suggests possible interventions to help overcome potential environmental risk factors and thus to prevent aggressive behavior in school. (c) 2015 APA, all rights reserved).

Common familial risk factors for schizophrenia and diabetes mellitus.

PubMed

Foley, Debra L; Mackinnon, Andrew; Morgan, Vera A; Watts, Gerald F; Castle, David J; Waterreus, Anna; Galletly, Cherrie A

2016-05-01

The co-occurrence of type 2 diabetes and psychosis is an important form of medical comorbidity within individuals, but no large-scale study has evaluated comorbidity within families. The aim of this study was to determine whether there is evidence for familial comorbidity between type 2 diabetes and psychosis. Data were analysed from an observational study of a nationally representative sample of 1642 people with psychosis who were in contact with psychiatric services at the time of survey (The 2010 Australian National Survey of Psychosis). Participants were aged 18-64 years and met World Health Organization's International Classification of Diseases, 10th Revision diagnostic criteria for a psychotic disorder (857 with schizophrenia, 319 with bipolar disorder with psychotic features, 293 with schizoaffective disorder, 81 with depressive psychosis and 92 with delusional disorder or other non-organic psychoses). Logistic regression was used to estimate the association between a family history of diabetes and a family history of schizophrenia. A positive family history of diabetes was associated with a positive family history of schizophrenia in those with a psychotic disorder (odds ratio = 1.35, p = 0.01, adjusted for age and gender). The association was different in those with an affective versus non-affective psychosis (odds ratio = 0.613, p = 0.019, adjusted for age and gender) and was significant only in those with a non-affective psychosis, specifically schizophrenia (odds ratio = 1.58, p = 0.005, adjusted for age and sex). Adjustment for demographic factors in those with schizophrenia slightly strengthened the association (odds ratio = 1.74, p = 0.001, adjusted for age, gender, diagnosis, ethnicity, education, employment, income and marital status). Elevated risk for type 2 diabetes in people with schizophrenia is not simply a consequence of antipsychotic medication; type 2 diabetes and schizophrenia share familial risk factors. © The Royal Australian and New

Factors associated with young adults' knowledge regarding family history of Stroke 1

PubMed Central

Lima, Maria Jose Melo Ramos; Moreira, Thereza Maria Magalhães; Florêncio, Raquel Sampaio; Braga, Predro

2016-01-01

ABSTRACT Objective: to analyze the factors associated with young adults' knowledge regarding family history of stroke. Method: an analytical transversal study, with 579 young adults from state schools, with collection of sociodemographic, clinical and risk factor-related variables, analyzed using logistic regression (backward elimination). Results: a statistical association was detected between age, civil status, and classification of arterial blood pressure and abdominal circumference with knowledge of family history of stroke. In the final logistic regression model, a statistical association was observed between knowledge regarding family history of stroke and the civil status of having a partner (ORa=1.61[1.07-2.42]; p=0.023), abdominal circumference (ORa=0.98[0.96-0.99]; p=0.012) and normal arterial blood pressure (ORa=2.56[1.19-5.52]; p=0.016). Conclusion: an association was observed between socioeconomic factors and risk factors for stroke and knowledge of family history of stroke, suggesting the need for health education or even educational programs on this topic for the clientele in question. PMID:27878217

A qualitative study of factors in nurses' and physicians' decision-making related to family presence during resuscitation.

PubMed

Twibell, Renee; Siela, Debra; Riwitis, Cheryl; Neal, Alexis; Waters, Nicole

2018-01-01

To explore the similarities and differences in factors that influence nurses' and physicians' decision-making related to family presence during resuscitation. Despite the growing acceptance of family presence during resuscitation worldwide, healthcare professionals continue to debate the risks and benefits of family presence. As many hospitals lack a policy to guide family presence during resuscitation, decisions are negotiated by resuscitation teams, families and patients in crisis situations. Research has not clarified the factors that influence the decision-making processes of nurses and physicians related to inviting family presence. This is the first study to elicit written data from healthcare professionals to explicate factors in decision-making about family presence. Qualitative exploratory-descriptive. Convenience samples of registered nurses (n = 325) and acute care physicians (n = 193) from a Midwestern hospital in the United States of America handwrote responses to open-ended questions about family presence. Through thematic analysis, decision-making factors for physicians and nurses were identified and compared. Physicians and nurses evaluated three similar factors and four differing factors when deciding to invite family presence during resuscitation. Furthermore, nurses and physicians weighted the factors differently. Physicians weighted most heavily the family's potential to disrupt life-saving efforts and compromise patient care and then the family's knowledge about resuscitations. Nurses heavily weighted the potential for the family to be traumatised, the potential for the family to disrupt the resuscitation, and possible family benefit. Nurses and physicians considered both similar and different factors when deciding to invite family presence. Physicians focused on the patient primarily, while nurses focused on the patient, family and resuscitation team. Knowledge of factors that influence the decision-making of interprofessional colleagues

The Self-Report Family Inventory: An Exploratory Factor Analysis

ERIC Educational Resources Information Center

Goodrich, Kristopher M.; Selig, James P.; Trahan, Don P., Jr.

2012-01-01

Researchers explored the factor structure of the Self-Report Family Inventory with a sample of heterosexual parents who have a son or daughter who self-identifies as lesbian, gay, or bisexual. Results suggest that a two-factor solution is appropriate. Research and clinical implications are offered. (Contains 1 figure and 2 tables.)

Family Engagement in Education in Uttar Pradesh, India: Factors Associated with the Involvement of Families in Their Children's Education

ERIC Educational Resources Information Center

Sanchez, Amanda Joy

2011-01-01

The purpose of this study was to examine the extent to which families within the Shravasti district of Uttar Pradesh, India are engaged in their children's education, as well as to examine the child, family, school, and community factors that are potentially associated with families' involvement in their children's education. Additionally,…

Dual DNA binding property of ABA insensitive 3 like factors targeted to promoters responsive to ABA and auxin.

PubMed

Nag, Ronita; Maity, Manas Kanti; Dasgupta, Maitrayee

2005-11-01

The ABA responsive ABI3 and the auxin responsive ARF family of transcription factors bind the CATGCATG (Sph) and TGTCTC core motifs in ABA and auxin response elements (ABRE and AuxRE), respectively. Several evidences indicate ABI3s to act downstream to auxin too. Because DNA binding domain of ABI3s shows significant overlap with ARFs we enquired whether auxin responsiveness through ABI3s could be mediated by their binding to canonical AuxREs. Investigations were undertaken through in vitro gel mobility shift assays (GMSA) using the DNA binding domain B3 of PvAlf (Phaseolus vulgaris ABI3 like factor) and upstream regions of auxin responsive gene GH3 (-267 to -141) and ABA responsive gene Em (-316 to -146) harboring AuxRE and ABRE, respectively. We demonstrate that B3 domain of PvAlf could bind AuxRE only when B3 was associated with its flanking domain B2 (B2B3). Such strict requirement of B2 domain was not observed with ABRE, where B3 could bind with or without being associated with B2. This dual specificity in DNA binding of ABI3s was also demonstrated with nuclear extracts of cultured cells of Arachis hypogea. Supershift analysis of ABRE and AuxRE bound nuclear proteins with antibodies raised against B2B3 domains of PvAlf revealed that ABI3 associated complexes were detectable in association with both cis elements. Competition GMSA confirmed the same complexes to bind ABRE and AuxRE. This dual specificity of ABI3 like factors in DNA binding targeted to natural promoters responsive to ABA and auxin suggests them to have a potential role in conferring crosstalk between these two phytohormones.

Cultural Factors in Collegiate Eating Disorder Pathology: When Family Culture Clashes with Individual Culture

ERIC Educational Resources Information Center

Tomiyama, A. Janet; Mann, Traci

2008-01-01

Objective: The authors evaluated the validity of familial enmeshment (extreme proximity in family relationships) as a risk factor for eating disorders across cultural value orientations. They tested the hypothesis that although familial enmeshment may be a risk factor for eating disorder pathology for (1) participants of non-Asian descent or (2)…

Sex differences in factors contributing to family-to-work and work-to-family conflict in Japanese civil servants.

PubMed

Fujimura, Yuko; Sekine, Michikazu; Tatsuse, Takashi

2014-01-01

As the number of dual-earner couples in Japan has increased, work-life balance has become important. This study aimed to examine the factors that contribute to work-family conflict. The participants included 3,594 (2,332 men and 1,262 women) civil servants aged 20-59 working for local government on the west coast of Japan. Logistic regression analysis was used to evaluate whether work, family, or lifestyle characteristics were associated with work-family conflict. For men, family-to-work conflict was associated with being elderly, having low-grade employment, working long hours, raising children, and sleeping shorter hours. For women, being married and raising children were strong determinants of family-to-work conflict, and being middle-aged, working long hours, and sleeping shorter hours were also associated with this type of conflict. Regarding work-to-family conflict, working long hours was the strongest determinant of conflict in both sexes. In men, being elderly, living with family, eating dinner late, and sleeping shorter hours were also associated with work-to-family conflict. In women, having high-grade employment, being married, raising children, and eating dinner late were associated with work-to-family conflict. This study showed that working long hours was the primary determinant of work-to-family conflict in both sexes and that being married and raising children were strong factors of family-to-work conflict in women only. Sex differences may reflect divergence of the social and domestic roles of men and women in Japanese society. To improve the work-life balance, general and sex-specific health policies may be required.

Genetic liability, prenatal health, stress and family environment: risk factors in the Harvard Adolescent Family High Risk for schizophrenia study.

PubMed

Walder, Deborah J; Faraone, Stephen V; Glatt, Stephen J; Tsuang, Ming T; Seidman, Larry J

2014-08-01

The familial ("genetic") high-risk (FHR) paradigm enables assessment of individuals at risk for schizophrenia based on a positive family history of schizophrenia in first-degree, biological relatives. This strategy presumes genetic transmission of abnormal traits given high heritability of the illness. It is plausible, however, that adverse environmental factors are also transmitted in these families. Few studies have evaluated both biological and environmental factors within a FHR study of adolescents. We conceptualize four precursors to psychosis pathogenesis: two biological (genetic predisposition, prenatal health issues (PHIs)) and two environmental (family environment, stressful life events (SLEs)). Participants assessed between 1998 and 2007 (ages 13-25) included 40 (20F/20M) adolescents at FHR for schizophrenia (FHRs) and 55 (31F/24M) community controls. 'Genetic load' indexed number of affected family members relative to pedigree size. PHI was significantly greater among FHRs, and family cohesion and expressiveness were less (and family conflict was higher) among FHRs; however, groups did not significantly differ in SLE indices. Among FHRs, genetic liability was significantly associated with PHI and family expressiveness. Prenatal and family environmental disruptions are elevated in families with a first-degree relative with schizophrenia. Findings support our proposed 'polygenic neurodevelopmental diathesis-stress model' whereby psychosis susceptibility (and resilience) involves the independent and synergistic confluence of (temporally-sensitive) biological and environmental factors across development. Recognition of biological and social environmental influences across critical developmental periods points to key issues relevant for enhanced identification of psychosis susceptibility, facilitation of more precise models of illness risk, and development of novel prevention strategies. Copyright © 2014 Elsevier B.V. All rights reserved.

EHB1 and AGD12, two calcium-dependent proteins affect gravitropism antagonistically in Arabidopsis thaliana.

PubMed

Dümmer, Michaela; Michalski, Christian; Essen, Lars-Oliver; Rath, Magnus; Galland, Paul; Forreiter, Christoph

2016-11-01

The ADP-RIBOSYLATION FACTOR GTPase-ACTIVATING PROTEIN (AGD) 12, a member of the ARF-GAP protein family, affects gravitropism in Arabidopsis thaliana. A loss-of-function mutant lacking AGD12 displayed diminished gravitropism in roots and hypocotyls indicating that both organs are affected by this regulator. AGD12 is structurally related to ENHANCED BENDING (EHB) 1, previously described as a negative effector of gravitropism. In contrast to agd12 mutants, ehb1 loss-of function seedlings displayed enhanced gravitropic bending. While EHB1 and AGD12 both possess a C-terminal C2/CaLB-domain, EHB1 lacks the N-terminal ARF-GAP domain present in AGD12. Subcellular localization analysis using Brefeldin A indicated that both proteins are elements of the trans Golgi network. Physiological analyses provided evidence that gravitropic signaling might operate via an antagonistic interaction of ARF-GAP (AGD12) and EHB1 in their Ca 2+ -activated states. Copyright © 2016 Elsevier GmbH. All rights reserved.

Removal of sulfur compounds from diesel using ArF laser and oxygen.

PubMed

Gondal, M A; Siddiqui, M N; Al-Hooshani, K

2013-01-01

A laser-based technique for deep desulfurization of diesel and other hydrocarbon fuels by removal of dimethyldibenzothiophene (DMDBT), a persistent sulfur contaminant in fuel oils has been developed. We report a selective laser excitation of DMDBT in diesel and model compounds such as n-hexane in a reaction chamber under oxygen environment where oxidative reactions can take place. ArF laser emitting at 193 nm was employed for excitation of oxygen and DMDBT, while for process optimization, the laser energy was varied from 50 to 200 mJ/cm(2). The laser-irradiated DMDBT solution under continuous oxygen flow was analyzed by UV absorption spectrometer to determine the photochemical oxidative degradation of DMDBT. In just 5 min of laser irradiation time, almost 95% DMDBT was depleted in a diesel containing 200 ppm of DMDBT. This article provides a new method for the removal of sulfur compounds from diesel by laser based photochemical process.

193 nm ArF laser ablation and patterning of chitosan thin films

NASA Astrophysics Data System (ADS)

Aesa, A. A.; Walton, C. D.

2018-06-01

This paper reports laser ablation studies on spin-coated biopolymer chitosan films, β-l,4-1inked 2-amino-2-deoxy- d-glucopyranose. Chitosan has been irradiated using an ArF laser emitting at 193 nm. An ablation threshold of F T = 85±8 mJ cm-2 has been determined from etch rate measurements. Laser-ablated chitosan is characterised using white light interferometry, scanning electron microscopy, and thermo-gravimetric analysis. Laser ablation of chitosan is discussed in terms of thermal and photoacoustic mechanisms. Heat transfer is simulated to assist in the understanding of laser-irradiated chitosan using a finite-element method and the software package COMSOL Multi-Physics™. As a demonstrator, a micro-array of square structures in the form of a crossed grating has been fabricated by laser ablation using a mask projection scanning method. The initial investigations show no evidence of thermal damage occurring to the adjacent chitosan when operating at a moderately low laser fluence of 110 mJ cm-2.

ABFs, a family of ABA-responsive element binding factors.

PubMed

Choi, H; Hong, J; Ha, J; Kang, J; Kim, S Y

2000-01-21

Abscisic acid (ABA) plays an important role in environmental stress responses of higher plants during vegetative growth. One of the ABA-mediated responses is the induced expression of a large number of genes, which is mediated by cis-regulatory elements known as abscisic acid-responsive elements (ABREs). Although a number of ABRE binding transcription factors have been known, they are not specifically from vegetative tissues under induced conditions. Considering the tissue specificity of ABA signaling pathways, factors mediating ABA-dependent stress responses during vegetative growth phase may thus have been unidentified so far. Here, we report a family of ABRE binding factors isolated from young Arabidopsis plants under stress conditions. The factors, isolated by a yeast one-hybrid system using a prototypical ABRE and named as ABFs (ABRE binding factors) belong to a distinct subfamily of bZIP proteins. Binding site selection assay performed with one ABF showed that its preferred binding site is the strong ABRE, CACGTGGC. ABFs can transactivate an ABRE-containing reporter gene in yeast. Expression of ABFs is induced by ABA and various stress treatments, whereas their induction patterns are different from one another. Thus, a new family of ABRE binding factors indeed exists that have the potential to activate a large number of ABA/stress-responsive genes in Arabidopsis.

Some factors affecting acceptance of family planning in Manus.

PubMed

Avue, B; Freeman, P

1991-12-01

This paper examines selected factors affecting the acceptance and delivery of modern family planning from health centres in Manus. A survey was carried out of mothers attending Maternal and Child Health clinics and a written questionnaire was given to health workers. The survey of mothers demonstrated the importance of the husband's approval for contraceptive practice and showed that knowledge about traditional methods of family planning is widespread. The health workers' questionnaire demonstrated a high level of dissatisfaction with the current family planning program delivered by health clinics: 45% found the program ineffective; 68% wrote that health workers' attitudes discouraged mothers from attending for family planning. The perceived and actual benefits and costs of children and the role of men should be assessed locally before planning future family planning programs. Widespread retraining and motivating of health workers is essential if improved coverage is to be achieved through health services. The efficacy of alternative methods of delivery of family planning such as local community-based and social marketing programs should also be investigated.

Factors that Affect Suicide Attempts of Adolescents in Multicultural Families in Korea.

PubMed

Park, Subin; Lee, Yeeun

2016-11-28

We examined the factors that affect suicide attempts adolescents multicultural families in South Korea. The participants were 727 adolescents whose mothers and/or fathers were born outside of South Korea (376 males and 351 females). Among them, 41 (weighted prevalence 6.2%) had attempted suicide during the last 12 months. Female gender, residence in large cities (compared with in rural areas), living with relatives/alone/with friends/in a dormitory or living in a facility (compared with living with family), high and low socio-economic status (compared with a middle level), high and low academic performance (compared with a middle level), severe perceived stress (compared with non-severe stress), conflicts with a teacher (compared with conflicts with parent), and foreign-father/-parent families (compared with foreign-mother family) were associated with increased odds of suicide attempt. The results indicate that greater awareness of the possibility of suicidal behavior is prudent for adolescents in multicultural families with certain risk factors, such as being from a foreign-parents family, living separately from the family, and having conflicts with a teacher.

Factors affecting frequency of communication about family health history with family members and doctors in a medically underserved population.

PubMed

Kaphingst, Kimberly A; Goodman, Melody; Pandya, Chintan; Garg, Priyanka; Stafford, Jewel; Lachance, Christina

2012-08-01

Family history contributes to risk for many common chronic diseases. Little research has investigated patient factors affecting communication of this information. 1061 adult community health center patients were surveyed. We examined factors related to frequency of discussions about family health history (FHH) with family members and doctors. Patients who talked frequently with family members about FHH were more likely to report a family history of cancer (p =.012) and heart disease (p < .001), seek health information frequently in newspapers (p < .001) and in general (p < .001), and be female (p < .001). Patients who talked frequently with doctors about FHH were more likely to report a family history of heart disease (p = .011), meet physical activity recommendations (p = .022), seek health information frequently in newspapers (p < .001) and in general (p < .001), be female (p < .001), and not have experienced racial discrimination in healthcare (p < .001). Patients with a family history of some diseases, those not meeting physical activity recommendations, and those who do not frequently seek health information may not have ongoing FHH discussions. Interventions are needed to encourage providers to update patients' family histories systematically and assist patients in initiating FHH conversations in order to use this information for disease prevention and control. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Children's disaster reactions: the influence of family and social factors.

PubMed

Pfefferbaum, Betty; Jacobs, Anne K; Houston, J Brian; Griffin, Natalie

2015-07-01

This review examines family (demographics, parent reactions and interactions, and parenting style) and social (remote effects, disaster media coverage, exposure to secondary adversities, and social support) factors that influence children's disaster reactions. Lower family socioeconomic status, high parental stress, poor parental coping, contact with media coverage, and exposure to secondary adversities have been associated with adverse outcomes. Social support may provide protection to children in the post-disaster environment though more research is needed to clarify the effects of certain forms of social support. The interaction of the factors described in this review with culture needs further exploration.

[Family factors influence active commuting to school in Spanish children].

PubMed

Rodríguez-López, Carlos; Villa-González, Emilio; Pérez-López, Isaac J; Delgado-Fernández, Manuel; Ruiz, Jonatan R; Chillón, Palma

2013-01-01

Active commuting to school is associated to higher levels of physical activity among children. Family factors may influence on this behaviour. The objective was to analyze the association between parents' occupational activity and parents' mode of commuting to work with the mode of commuting of their children. A total of 721 families from 4 primary schools in the province of Granada participated in this study. Families reported a questionnaire about mode of commuting of their children, parents' occupational activity and mode of commuting to work, distance and travel time to school. Associations between family's occupational activity and mode of commuting to work with mode of commuting to school of their children were examined using binary logistic regression analysis adjusting for age and children's distance to school. Children whose parents did not work used to engage in higher levels of active commuting to school than those whose parents worked (p = 0,023; OR: 2,67; 95% CI: 1,14-6,23). Children whose parents used to commute actively to work used to engage in higher levels of active commuting to school than those whose parents both used passive modes of commuting to work (p = 0,014; OR: 6,30; 95% CI: 1,45-27,26). Family factors are related to mode of commuting to school in children: Unemployed families and employed families where parent are active commuters to work are more used to have children that commuted to school using active modes. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

Slow cortical potentials in migraine families are associated with psychosocial factors.

PubMed

Gerber, Wolf-Dieter; Stephani, Ulrich; Kirsch, Ellen; Kropp, Peter; Siniatchkin, Michael

2002-04-01

The aim of the study was the determination of the relationships between neurophysiological and psychosocial factors within the pathogenesis of migraine. The contingent negative variation (CNV), parent-child interactions and theirs relationship were investigated in 30 families with a migraine child and 20 healthy families. (1) None of the groups of children, independent of diagnosis, differed according to amplitude or habituation of the CNV. (2) Parents from migraine families exerted significantly more control over migraine children compared with interactions with healthy brothers/sisters. (3) The strong relation between CNV habituation/amplitude and abnormal pattern of parent-child interactions (especially overwhelming dominance and control) was found only for young migraineurs. This relation was not seen in healthy families or for healthy siblings of migraine children. This study provides significant evidence for a strong influence of family interactions on the development and maintenance of neurophysiological abnormalities in the migraineous headache. The role of psychosocial factors in the etiopathogenesis of migraine has to be investigated in further studies in more detail.

Factors determining family planning in Catalonia. Sources of inequity

PubMed Central

2012-01-01

Introduction In recent decades, the foreign population in Spain has increased significantly, particularly for Catalonia, an autonomous region of Spain (2.90% in 2000 and 15.95% in 2010) and in particular Girona province (6.18% in 2000 and 21.55% in 2010). Several studies have shown a lower use of family planning methods by immigrants. This same trend is observed in Spain. The objective of this paper is to determine the existence of differences and possible sources of inequity in the use of family planning methods among health service users in Catalonia (Spain) by sex, health status, place of birth and socioeconomic conditions. Methods Data were taken from an ad-hoc questionnaire which was compiled following a qualitative stage of individual interviews. Said questionnaire was administered to 1094 Catalan public health service users during 2007. A complete descriptive analysis was carried out for variables related to public health service users’ sociodemographic characteristics and variables indicating knowledge and use of family planning methods, and bivariate relationships were analysed by means of chi-square contrasts. Considering the use (or non-use) of family planning methods as a dependent variable and a set of demographic, socioeconomic and health status variables as explanatory factors, the relationship was modelled using mixed models. Results The analysed sample is comprised of 54.3% women and 45.7% men, with 74.3% natives (or from the EU) and 25.7% economic immigrants. 54.8% use some method of family planning, the condom (46.7%) and the pill (28.0%) being the two most frequently used methods. Statistical modelling indicates that those factors which most influence the use of family planning methods are level of education (30.59% and 39.29% more likelihood) and having children over 14 (35.35% more likelihood). With regard to the origin of the user, we observe that patients from North Africa,sub. Saharan Africa and Asia are less likely to use family planning

Factors determining family planning in Catalonia. Sources of inequity.

PubMed

Saurina, Carme; Vall-Llosera, Laura; Saez, Marc

2012-07-20

In recent decades, the foreign population in Spain has increased significantly, particularly for Catalonia, an autonomous region of Spain (2.90% in 2000 and 15.95% in 2010) and in particular Girona province (6.18% in 2000 and 21.55% in 2010). Several studies have shown a lower use of family planning methods by immigrants. This same trend is observed in Spain. The objective of this paper is to determine the existence of differences and possible sources of inequity in the use of family planning methods among health service users in Catalonia (Spain) by sex, health status, place of birth and socioeconomic conditions. Data were taken from an ad-hoc questionnaire which was compiled following a qualitative stage of individual interviews. Said questionnaire was administered to 1094 Catalan public health service users during 2007. A complete descriptive analysis was carried out for variables related to public health service users' sociodemographic characteristics and variables indicating knowledge and use of family planning methods, and bivariate relationships were analysed by means of chi-square contrasts. Considering the use (or non-use) of family planning methods as a dependent variable and a set of demographic, socioeconomic and health status variables as explanatory factors, the relationship was modelled using mixed models. The analysed sample is comprised of 54.3% women and 45.7% men, with 74.3% natives (or from the EU) and 25.7% economic immigrants. 54.8% use some method of family planning, the condom (46.7%) and the pill (28.0%) being the two most frequently used methods. Statistical modelling indicates that those factors which most influence the use of family planning methods are level of education (30.59% and 39.29% more likelihood) and having children over 14 (35.35% more likelihood). With regard to the origin of the user, we observe that patients from North Africa,sub. Saharan Africa and Asia are less likely to use family planning methods (36.68%, 38.59% and 70

Maternal and family factors and child eating pathology: risk and protective relationships

PubMed Central

2014-01-01

Background Previous studies have found associations between maternal and family factors and child eating disorder symptoms. However, it is not clear whether family factors predict eating disorder symptoms specifically, or relate to more general child psychopathology, of which eating disorder symptoms may be one component. This study aimed to identify maternal and family factors that may predict increases or decreases in child eating disorder symptoms over time, accounting for children’s body mass index z-scores and levels of general psychological distress. Methods Participants were 221 mother-child dyads from the Childhood Growth and Development Study, a prospective cohort study in Western Australia. Participants were assessed at baseline, 1-year follow-up and 2-year follow-up using interview and self-report measures. Children had a mean age of 10 years at baseline and 46% were male. Linear mixed models and generalised estimating equations were used to identify predictors of children’s eating disorder symptoms, with outcome variables including a global index of eating disorder psychopathology, levels of dietary restraint, levels of emotional eating, and the presence of loss of control (‘binge’) eating. Results Children of mothers with a current or past eating disorder reported significantly higher levels of global eating disorder symptoms and emotional eating than other children, and mothers with a current or past eating disorder reported significantly more concern about their children’s weight than other mothers. Maternal concern about child weight, rather than maternal eating disorder symptoms, was significant in predicting child eating disorder symptoms over time. Family exposure to stress and low maternal education were additional risk factors for eating disorder symptoms, whilst child-reported family satisfaction was a protective factor. Conclusions After adjusting for relevant confounding variables, maternal concern about child weight, children�

Family factors associated with auto-aggressiveness in adolescents in Croatia.

PubMed

Tripković, Mara; Francisković, Tanja; Grgić, Neda; Ercegović, Nela; Graovac, Mirjana; Zecević, Iva

2013-12-01

The aim of this research is to look into the roles of families' social situation and cohesion in adolescent auto-aggressiveness in Croatia. The research was conducted on a sample of Zagreb high school students which encompassed 701 pupils of both genders aged 14-19. The basic demographic data were obtained using the Structured Demographic and Family Data Questionnaire. Auto-aggressiveness was tested using a section of the Report on Youth Aged 11-18 and the Scale of Auto-destructiveness--SAD, whereas the family cohesion was tested with the Family Adaptability and Cohesion Evaluation Scales FACES III. The obtained results show differences according to the gender: girls are more prone to auto-aggressiveness than boys (t = -3.385, df = 565, p = 0.001) and girls more often show symptoms of destructiveness (t = -3.809, df = 637, p < 0.001) and anxiety (t = -6.562, df = 640, p < 0.001), while boys show pronounced aggressiveness (t = 2.655, df = 653, p = 0.008). Significant family factors associated with auto-aggressiveness are parents' marital status (chi2 = 18.039, df = 4, p = 0.001), their financial situation (F(2.548) = 4.604, p = 0.010), alcoholic father (chi2 = 9.270, df = 2, p = 0.010), mentally ill mother (t = 5.264, df = 541, p < 0.001), as well as mentally ill father (t = 4.744, df = 529, p < 0.001), and corporal punishment by mother (F(2.542) = 8.132, p < 0.001) or father (F(2.530) = 5.341, p = 0.005). Adolescents from split families show more auto-aggressiveness. Family cohesion appears to be considerably associated with auto-aggressiveness and the adolescents that see their families as less cohesive have more mental problems (chi2 = 29.98, df = 2, p < 0.001). There is a connection between auto-destructive behavior in adolescents and family factors. Knowledge of family's social situation and cohesion may help understand, prevent and treat auto-aggressiveness in adolescents.

Familial aggregation and linkage analysis with covariates for metabolic syndrome risk factors.

PubMed

Naseri, Parisa; Khodakarim, Soheila; Guity, Kamran; Daneshpour, Maryam S

2018-06-15

Mechanisms of metabolic syndrome (MetS) causation are complex, genetic and environmental factors are important factors for the pathogenesis of MetS In this study, we aimed to evaluate familial and genetic influences on metabolic syndrome risk factor and also assess association between FTO (rs1558902 and rs7202116) and CETP(rs1864163) genes' single nucleotide polymorphisms (SNP) with low HDL_C in the Tehran Lipid and Glucose Study (TLGS). The design was a cross-sectional study of 1776 members of 227 randomly-ascertained families. Selected families contained at least one affected metabolic syndrome and at least two members of the family had suffered a loss of HDL_C according to ATP III criteria. In this study, after confirming the familial aggregation with intra-trait correlation coefficients (ICC) of Metabolic syndrome (MetS) and the quantitative lipid traits, the genetic linkage analysis of HDL_C was performed using conditional logistic method with adjusted sex and age. The results of the aggregation analysis revealed a higher correlation between siblings than between parent-offspring pairs representing the role of genetic factors in MetS. In addition, the conditional logistic model with covariates showed that the linkage results between HDL_C and three marker, rs1558902, rs7202116 and rs1864163 were significant. In summary, a high risk of MetS was found in siblings confirming the genetic influences of metabolic syndrome risk factor. Moreover, the power to detect linkage increases in the one parameter conditional logistic model regarding the use of age and sex as covariates. Copyright © 2018. Published by Elsevier B.V.

Child and Family Factors Associated With Child Maltreatment in Vietnam.

PubMed

Tran, Nhu K; van Berkel, Sheila R; van IJzendoorn, Marinus H; Alink, Lenneke R A

2018-04-01

This study aims to explore possible risk factors for child maltreatment in Vietnam by investigating the association of child and family factors with different types of child maltreatment (i.e., sexual abuse, physical abuse, emotional abuse, witnessing parental conflict, and neglect) and the occurrence of multiple types of child maltreatment. Cross-sectional data of 1,851 secondary and high school students aged 12 to 17 years (47.3% boys) in four provinces of Northern Vietnam were obtained using self-report questionnaires. Results indicated that the likelihood of emotional abuse, witnessing parental conflict, and experiencing multiple types of child maltreatment during lifetime increased with age. Boys had a higher risk than girls on lifetime sexual abuse, and past year and lifetime physical abuse. Living in a single parent family was the risk factor related to most types of child maltreatment including lifetime sexual abuse, neglect, and multiple types of child maltreatment, and both past year and lifetime witnessing parental conflict. Interestingly, low socioeconomic status (SES) and parental unemployment were associated with a decreased risk on experiencing emotional abuse in the past year and during lifetime, respectively. "Tiger parenting," a parenting style observed frequently in East Asian parents, may be more common in families with high SES and might explain this finding. This study highlights the importance of prioritizing single parent families in parenting programs and implementing child maltreatment interventions early because of the risk on child maltreatment increased with age. More research on emotional abuse and "Tiger parenting" in Vietnam could clarify the association of emotional abuse with high SES and parental employment. Finally, the underlying mechanisms of the risk factors in Vietnam should be studied more to inform interventions.

Ras-like family small GTPases genes in Nilaparvata lugens: Identification, phylogenetic analysis, gene expression and function in nymphal development

PubMed Central

Wang, Weixia; Li, Kailong; Wan, Pinjun; Lai, Fengxiang; Fu, Qiang; Zhu, Tingheng

2017-01-01

Twenty-nine cDNAs encoding Ras-like family small GTPases (RSGs) were cloned and sequenced from Nilaparvata lugens. Twenty-eight proteins are described here: 3 from Rho, 2 from Ras, 9 from Arf and 14 from Rabs. These RSGs from N.lugens have five conserved G-loop motifs and displayed a higher degree of sequence conservation with orthologues from insects. RT-qPCR analysis revealed NlRSGs expressed at all life stages and the highest expression was observed in hemolymph, gut or wing for most of NlRSGs. RNAi demonstrated that eighteen NlRSGs play a crucial role in nymphal development. Nymphs with silenced NlRSGs failed to molt, eclosion or development arrest. The qRT-PCR analysis verified the correlation between mortality and the down-regulation of the target genes. The expression level of nuclear receptors, Kr-h1, Hr3, FTZ-F1 and E93 involved in 20E and JH signal pathway was impacted in nymphs with silenced twelve NlRSGs individually. The expression of two halloween genes, Cyp314a1 and Cyp315a1 involved in ecdysone synthesis, decreased in nymphs with silenced NlSar1 or NlArf1. Cyp307a1 increased in nymphs with silenced NlArf6. In N.lugens with silenced NlSRβ, NlSar1 and NlRab2 at 9th day individually, 0.0% eclosion rate and almost 100.0% mortality was demonstrated. Further analysis showed NlSRβ could be served as a candidate target for dsRNA-based pesticides for N.lugens control. PMID:28241066

Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals.

PubMed

Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen; Ma, Haoli

2017-10-08

The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three ( Physcomitrella patens ) to 63 ( Glycine max ). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution.

Evolution Analysis of the Aux/IAA Gene Family in Plants Shows Dual Origins and Variable Nuclear Localization Signals

PubMed Central

Wu, Wentao; Liu, Yaxue; Wang, Yuqian; Li, Huimin; Liu, Jiaxi; Tan, Jiaxin; He, Jiadai; Bai, Jingwen

2017-01-01

The plant hormone auxin plays pivotal roles in many aspects of plant growth and development. The auxin/indole-3-acetic acid (Aux/IAA) gene family encodes short-lived nuclear proteins acting on auxin perception and signaling, but the evolutionary history of this gene family remains to be elucidated. In this study, the Aux/IAA gene family in 17 plant species covering all major lineages of plants is identified and analyzed by using multiple bioinformatics methods. A total of 434 Aux/IAA genes was found among these plant species, and the gene copy number ranges from three (Physcomitrella patens) to 63 (Glycine max). The phylogenetic analysis shows that the canonical Aux/IAA proteins can be generally divided into five major clades, and the origin of Aux/IAA proteins could be traced back to the common ancestor of land plants and green algae. Many truncated Aux/IAA proteins were found, and some of these truncated Aux/IAA proteins may be generated from the C-terminal truncation of auxin response factor (ARF) proteins. Our results indicate that tandem and segmental duplications play dominant roles for the expansion of the Aux/IAA gene family mainly under purifying selection. The putative nuclear localization signals (NLSs) in Aux/IAA proteins are conservative, and two kinds of new primordial bipartite NLSs in P. patens and Selaginella moellendorffii were discovered. Our findings not only give insights into the origin and expansion of the Aux/IAA gene family, but also provide a basis for understanding their functions during the course of evolution. PMID:28991190

Adaptation and validation of the Inventory of Family Protective Factors for the Portuguese culture

PubMed Central

Augusto, Cláudia Cristina Vieira Carvalho de Oliveira Ferreira; Araújo, Beatriz Rodrigues; Rodrigues, Vítor Manuel Costa Pereira; de Figueiredo, Maria do Céu Aguiar Barbieri

2014-01-01

OBJECTIVES: to adapt and validate the Inventory of Family Protective Factors (IFPF) for the Portuguese culture. This instrument assesses protective factors that contribute to family resilience. Studies addressing resilience are embedded within the salutogenic paradigm, i.e. it addresses protective factors of individuals or groups without underestimating risk factors or vulnerability. METHOD: in order to assess the IFPF's linguistic and conceptual equivalence, the instrument was translated, retro-translated and the think-aloud protocol was used. We then verified the instrument's sensitiveness, reliability and validity of results to assess its psychometric characteristics. A factor analysis was performed of the principal components with varimax rotation of the scale's items and Cronbach's alpha coefficient was calculated for each dimension. A total of 85 families with disabled children, selected through simple random sampling, self-administered the instrument. RESULTS: the IFPF presents psychometric characteristics that are appropriate for the Portuguese population (Cronbach's alpha = .90). CONCLUSION: the IFPF was adapted and validated for the Portuguese culture and is an instrument to be used in studies intended to assess protective factors of family resilience. PMID:25591096

Adaptation and validation of the Inventory of Family Protective Factors for the Portuguese culture.

PubMed

Augusto, Cláudia Cristina Vieira Carvalho de Oliveira Ferreira; Araújo, Beatriz Rodrigues; Rodrigues, Vítor Manuel Costa Pereira; de Figueiredo, Maria do Céu Aguiar Barbieri

2014-01-01

to adapt and validate the Inventory of Family Protective Factors (IFPF) for the Portuguese culture. This instrument assesses protective factors that contribute to family resilience. Studies addressing resilience are embedded within the salutogenic paradigm, i.e. it addresses protective factors of individuals or groups without underestimating risk factors or vulnerability. in order to assess the IFPF's linguistic and conceptual equivalence, the instrument was translated, retro-translated and the think-aloud protocol was used. We then verified the instrument's sensitiveness, reliability and validity of results to assess its psychometric characteristics. A factor analysis was performed of the principal components with varimax rotation of the scale's items and Cronbach's alpha coefficient was calculated for each dimension. A total of 85 families with disabled children, selected through simple random sampling, self-administered the instrument. the IFPF presents psychometric characteristics that are appropriate for the Portuguese population (Cronbach's alpha = .90). the IFPF was adapted and validated for the Portuguese culture and is an instrument to be used in studies intended to assess protective factors of family resilience.

A Spotlight on Preschool: The Influence of Family Factors on Children’s Early Literacy Skills

PubMed Central

Heath, Steve M.; Bishop, Dorothy V. M.; Bloor, Kimberley E.; Boyle, Gemma L.; Fletcher, Janet; Hogben, John H.; Wigley, Charles A.; Yeong, Stephanie H. M.

2014-01-01

Rationale Phonological awareness, letter knowledge, oral language (including sentence recall) and rapid automatised naming are acknowledged within-child predictors of literacy development. Separate research has identified family factors including socio-economic status, parents’ level of education and family history. However, both approaches have left unexplained significant amounts of variance in literacy outcomes. This longitudinal study sought to improve prospective classification accuracy for young children at risk of literacy failure by adding two new family measures (parents’ phonological awareness and parents’ perceived self-efficacy), and then combining the within-child and family factors. Method Pre-literacy skills were measured in 102 four year olds (46 girls and 56 boys) at the beginning of Preschool, and then at the beginning and end of Kindergarten, when rapid automatised naming was also measured. Family factors data were collected at the beginning of Preschool, and children’s literacy outcomes were measured at the end of Year 1 (age 6–7 years). Results Children from high-risk backgrounds showed poorer literacy outcomes than low-risk students, though three family factors (school socio-economic status, parents’ phonological awareness, and family history) typically accounted for less Year 1 variance than the within-child factors. Combining these family factors with the end of Kindergarten within-child factors provided the most accurate classification (i.e., sensitivity = .85; specificity = .90; overall correct = .88). Implications Our approach would identify at-risk children for intervention before they began to fail. Moreover, it would be cost-effective because although few at-risk children would be missed, allocation of unnecessary educational resources would be minimised. PMID:24751691

Factors associated with intensiveness of use of child preventive health services in Taiwan: a comparative study between cross-cultural immigrant families and native-born families.

PubMed

Chien, Su-Chen; Yeh, Yen-Po; Wu, Jyun-Yi; Lin, Chun-Hsiu; Chang, Pei-Chi; Fang, Chiung-Hui; Yang, Hao-Jan

2013-01-01

To compare intensiveness of use of child preventive health services (CPHS) between cross-cultural immigrant families and native-born families in Taiwan and to explore factors associated with differences in intensiveness of CPHS use. Cross-cultural immigrant families were defined as families where the mother was an immigrant from another southeast Asian country. In native-born families, both parents were Taiwanese-born. Data were collected from 318 immigrant mothers and 340 native-born mothers of children aged 7 years or younger in a cross-sectional survey in central Taiwan. A social determinants framework of health inequities was constructed, and ordinal logistic regression models were used to examine the effect of four domains of intermediary determinants on the relationship between family type and underuse of CPHS: CPHS-related factors, medical-related factors, maternal acculturation factors, and sociodemographic/socioeconomic characteristics. Cross-cultural immigrant families were less likely to intensively use CPHS than native-born families. This difference appeared to be mediated by the greater likelihood of having an older child or a lower educated father in cross-cultural families. Findings of this study highlight the importance of promoting health behaviors and combating health inequities and social inequalities for cross-cultural immigrant families in Taiwan from a sociodemographic/socioeconomic and political context.

Family History of Sudden Cardiac Death of the Young: Prevalence and Associated Factors

PubMed Central

White, Michelle J.; Duquette, Debra; Bach, Janice; Rafferty, Ann P.; Fussman, Chris; Sharangpani, Ruta; Russell, Mark W.

2015-01-01

Sudden cardiac death of the young (SCDY) is a devastating event for families and communities. Family history is a significant risk factor for this potentially preventable cause of death, however a complete and detailed family history is not commonly obtained during routine health maintenance visits. To estimate the proportion of adults with a family history of SCDY, the Michigan Department of Health and Human Services (MDHHS) Genomics Program included two questions within the 2007 Michigan Behavioral Risk Factor Survey (MiBRFS). Prevalence estimates and 95% confidence intervals were calculated. Among adults in Michigan, 6.3% reported a family history of SCDY, with a greater prevalence among blacks, those with lower household income, and those with less education. Among those reporting a family history of SCDY, 42.3% had at least one first-degree relative and 26.2% had multiple affected family members. This is the first study to demonstrate the prevalence of family history of SCDY while also highlighting key sociodemographic characteristics associated with increased prevalence. These findings should guide evidence-based interventions to reach those at greatest risk. PMID:27417815

Psychological, behavioral and familial factors in obese Cuban children and adolescents.

PubMed

Pérez, Lourdes M; García, Keytel; Herrera, Raúl

2013-10-01

The global prevalence of obesity has reached alarming proportions. In Cuba, the rise in numbers of children who are overweight or obese, especially preschoolers and adolescents, is similar to that observed in developed countries. Beyond the physical risk factors, there is evidence that obesity has negative psychological, social, academic and economic effects. Describe the psychological, behavioral and familial factors present in a group of obese children and adolescents in Cuba. This is a qualitative cross-sectional study of 202 obese children and adolescents aged 3-18 years, with an average age of 9.9 years, seen at the Medical-Surgical Research Center (Havana) psychology service from January 2009 through December 2012. Techniques included interviews of patients and parents, projective drawings and the Rotter Incomplete Sentence Blank. Unhealthy eating habits were reported in 96% of obese children and adolescents, and sedentary lifestyles in 88.1%. Emotional state was affected in 80.2%, and in 72.3% there were family attitudes with potential to produce psychological disturbances in children. Psychological, behavioral, and familial factors known to foster development and perpetuation of obesity were observed in the majority of cases. This is a first diagnostic stage that will aid in design and implementation of a psychological intervention program for obese and overweight children and their families.

The Avid Adolescent Reader Revisited: Gender Differences and Their Association with Family Factors

ERIC Educational Resources Information Center

Chen, Su-Yen; Lu, Luo

2012-01-01

As a follow-up study to a cross-sectional national study that established the linkage between gender as well as family factors and the likelihood of being Taiwanese adolescent readers, this study attempted to utilize the same data set with longitudinal data to explore whether the association between family factors and being an avid adolescent…

The role of family and maternal factors in childhood obesity.

PubMed

Gibson, Lisa Y; Byrne, Susan M; Davis, Elizabeth A; Blair, Eve; Jacoby, Peter; Zubrick, Stephen R

2007-06-04

To investigate the relationship between a child's weight and a broad range of family and maternal factors. Cross-sectional data from a population-based prospective study, collected between January 2004 and December 2005, for 329 children aged 6-13 years (192 healthy weight, 97 overweight and 40 obese) and their mothers (n=265) recruited from a paediatric hospital endocrinology department and eight randomly selected primary schools in Perth, Western Australia. Height, weight and body mass index (BMI) of children and mothers; demographic information; maternal depression, anxiety, stress and self-esteem; general family functioning; parenting style; and negative life events. In a multilevel model, maternal BMI and family structure (single-parent v two-parent families) were the only significant predictors of child BMI z scores. Childhood obesity is not associated with adverse maternal or family characteristics such as maternal depression, negative life events, poor general family functioning or ineffective parenting style. However, having an overweight mother and a single-parent (single-mother) family increases the likelihood of a child being overweight or obese.

Family and Social Environmental Factors Associated with Aggression among Chinese Adolescents

ERIC Educational Resources Information Center

Dou, Chunxia; Wei, Zhen; Jin, Ke; Wang, He; Wang, Xiulan; Peng, Ziwen

2015-01-01

Family and school environments are assumed to be associated with and influence aggressive behaviors. However, which specific risk factors within these environments that are associated with aggressive behavior are unclear. The goal of this study is to identify family and social environmental qualities that are related to aggression among Chinese…

Individual Characteristics, Family Factors, and Classroom Experiences as Predictors of Low-Income Kindergarteners' Social Skills.

PubMed

Griffith, Shayl; Arnold, David; Voegler-Lee, Mary-Ellen; Kupersmidt, Janis

2016-01-01

There has been increasing awareness of the need for research and theory to take into account the intersection of individual characteristics and environmental contexts when examining predictors of child outcomes. The present longitudinal, multi-informant study examined the cumulative and interacting contributions of child characteristics (language skills, inattention/hyperactivity, and aggression) and preschool and family contextual factors in predicting kindergarten social skills in 389 low-income preschool children. Child characteristics and classroom factors, but not family factors, predicted teacher-rated kindergarten social skills, while child characteristics alone predicted change in teacher-rated social skills from preschool to kindergarten. Child characteristics and family factors, but not classroom factors, predicted parent-rated kindergarten social skills. Family factors alone predicted change in parent-rated social skills from preschool to kindergarten. Individual child characteristics did not interact with family or classroom factors in predicting parent- or teacher-rated social skills, and support was therefore found for an incremental, rather than an interactive, predictive model of social skills. The findings underscore the importance of assessing outcomes in more than one context, and of considering the impact of both individual and environmental contextual factors on children's developing social skills when designing targeted intervention programs to prepare children for kindergarten.

Individual Characteristics, Family Factors, and Classroom Experiences as Predictors of Low-Income Kindergarteners’ Social Skills

PubMed Central

Griffith, Shayl; Arnold, David; Voegler-Lee, Mary-Ellen; Kupersmidt, Janis

2017-01-01

There has been increasing awareness of the need for research and theory to take into account the intersection of individual characteristics and environmental contexts when examining predictors of child outcomes. The present longitudinal, multi-informant study examined the cumulative and interacting contributions of child characteristics (language skills, inattention/hyperactivity, and aggression) and preschool and family contextual factors in predicting kindergarten social skills in 389 low-income preschool children. Child characteristics and classroom factors, but not family factors, predicted teacher-rated kindergarten social skills, while child characteristics alone predicted change in teacher-rated social skills from preschool to kindergarten. Child characteristics and family factors, but not classroom factors, predicted parent-rated kindergarten social skills. Family factors alone predicted change in parent-rated social skills from preschool to kindergarten. Individual child characteristics did not interact with family or classroom factors in predicting parent- or teacher-rated social skills, and support was therefore found for an incremental, rather than an interactive, predictive model of social skills. The findings underscore the importance of assessing outcomes in more than one context, and of considering the impact of both individual and environmental contextual factors on children’s developing social skills when designing targeted intervention programs to prepare children for kindergarten. PMID:28804528

Family, friend, and media factors are associated with patterns of weight-control behavior among adolescent girls.

PubMed

Balantekin, Katherine N; Birch, Leann L; Savage, Jennifer S

2018-04-01

To examine the relationship of family, friend, and media factors on weight-control group membership at 15 years separately and in a combined model. Subjects included 166 15 year girls. Latent class analysis identified four patterns of weight-control behaviors: non-dieters, lifestyle, dieters, and extreme dieters. Family (family functioning, priority of the family meals, maternal/paternal weight-teasing, and mother's/father's dieting), friend (weight-teasing and dieting), and media variables (media sensitivity and weekly TV time) were included as predictors of weight-control group membership. Family functioning and priority of family meals predicted membership in the Extreme Dieters group, and maternal weight-teasing predicted membership in both dieters and extreme dieters. Friend's dieting and weight-teasing predicted membership in both dieters and extreme dieters. Media sensitivity was significantly associated with membership in lifestyle, dieters, and extreme dieters. In a combined influence model with family, friend, and media factors included, the following remained significantly associated with weight-control group membership: family functioning, friends' dieting, and media sensitivity. Family, friends, and the media are three sources of sociocultural influence, which play a role in adolescent girls' use of patterns of weight-control behaviors; family functioning was a protective factor, whereas friend's dieting and media sensitivity were risk factors. These findings emphasize the need for multidimensional interventions, addressing risk factors for dieting and use of unhealthy weight-control behaviors at the family, peer, and community (e.g., media) levels.

To what extent is the familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors?

PubMed

Jiang, Xia; Frisell, Thomas; Askling, Johan; Karlson, Elizabeth W; Klareskog, Lars; Alfredsson, Lars; Källberg, Henrik

2015-02-01

Family history of rheumatoid arthritis (RA) is one of the strongest risk factors for developing RA, and information on family history is, therefore, routinely collected in clinical practice. However, as more genetic and environmental risk factors shared by relatives are identified, the importance of family history may diminish. The aim of this study was to determine how much of the familial risk of RA can be explained by established genetic and nongenetic risk factors. History of RA among first-degree relatives of individuals in the Epidemiological Investigation of Rheumatoid Arthritis case-control study was assessed through linkage to the Swedish Multigeneration Register and the Swedish Patient Register. We used logistic regression models to investigate the decrease in familial risk after successive adjustment for combinations of nongenetic risk factors (smoking, alcohol intake, parity, silica exposure, body mass index, fatty fish consumption, and education), and genetic risk factors (shared epitope [SE] and 76 single-nucleotide polymorphisms [SNPs]). Established nongenetic risk factors did not explain familial risk of either seropositive or seronegative RA to any significant degree. Genetic risk factors accounted for a limited proportion of the familial risk of seropositive RA (unadjusted odds ratio [OR] 4.10, SE-adjusted OR 3.72, SNP-adjusted OR 3.46, and SE and SNP-adjusted OR 3.35). Established risk factors only provided an explanation for familial risk of RA in minor part, suggesting that many (familial) risk factors remain to be identified, in particular for seronegative RA. Family history of RA therefore remains an important clinical risk factor for RA, the value of which has not yet been superseded by other information. There is thus a need for further etiologic studies of both seropositive and seronegative RA. Copyright © 2015 by the American College of Rheumatology.

Family Obligation Values and Family Assistance Behaviors: Protective and Risk Factors for Mexican-American Adolescents’ Substance Use

PubMed Central

2014-01-01

Adolescent substance use is one of today’s most important social concerns, with Latino youth exhibiting the highest overall rates of substance use. Recognizing the particular importance of family connection and support for families from Mexican backgrounds, the current study seeks to examine how family obligation values and family assistance behaviors may be a source of protection or risk for substance use among Mexican-American adolescents. Three hundred and eighty-five adolescents (51% female) from Mexican backgrounds completed a questionnaire and daily diary for 14 consecutive days. Results suggest that family obligation values are protective, relating to lower substance use, due, in part, to the links with less association with deviant peers and increased adolescent disclosure. In contrast, family assistance behaviors are a source of risk within high parent-child conflict homes, relating to higher levels of substance use. These findings suggest that cultural values are protective against substance use, but the translation of these values into behaviors can be a risk factor depending upon the relational context of the family. PMID:23532598

Family obligation values and family assistance behaviors: protective and risk factors for Mexican-American adolescents' substance use.

PubMed

Telzer, Eva H; Gonzales, Nancy; Fuligni, Andrew J

2014-02-01

Adolescent substance use is one of today's most important social concerns, with Latino youth exhibiting the highest overall rates of substance use. Recognizing the particular importance of family connection and support for families from Mexican backgrounds, the current study seeks to examine how family obligation values and family assistance behaviors may be a source of protection or risk for substance use among Mexican-American adolescents. Three hundred and eighty-five adolescents (51% female) from Mexican backgrounds completed a questionnaire and daily diary for 14 consecutive days. Results suggest that family obligation values are protective, relating to lower substance use, due, in part, to the links with less association with deviant peers and increased adolescent disclosure. In contrast, family assistance behaviors are a source of risk within high parent-child conflict homes, relating to higher levels of substance use. These findings suggest that cultural values are protective against substance use, but the translation of these values into behaviors can be a risk factor depending upon the relational context of the family.

ARF1·GTP, Tyrosine-based Signals, and Phosphatidylinositol 4,5-Bisphosphate Constitute a Minimal Machinery to Recruit the AP-1 Clathrin Adaptor to Membranes

PubMed Central

Crottet, Pascal; Meyer, Daniel M.; Rohrer, Jack; Spiess, Martin

2002-01-01

At the trans-Golgi network, clathrin coats containing AP-1 adaptor complexes are formed in an ARF1-dependent manner, generating vesicles transporting cargo proteins to endosomes. The mechanism of site-specific targeting of AP-1 and the role of cargo are poorly understood. We have developed an in vitro assay to study the recruitment of purified AP-1 adaptors to chemically defined liposomes presenting peptides corresponding to tyrosine-based sorting motifs. AP-1 recruitment was found to be dependent on myristoylated ARF1, GTP or nonhydrolyzable GTP-analogs, tyrosine signals, and small amounts of phosphoinositides, most prominently phosphatidylinositol 4,5-bisphosphate, in the absence of any additional cytosolic or membrane bound proteins. AP-1 from cytosol could be recruited to a tyrosine signal independently of the lipid composition, but the rate of recruitment was increased by phosphatidylinositol 4,5-bisphosphate. The results thus indicate that cargo proteins are involved in coat recruitment and that the local lipid composition contributes to specifying the site of vesicle formation. PMID:12388765

Dyadic confirmatory factor analysis of the inflammatory bowel disease family responsibility questionnaire.

PubMed

Greenley, Rachel Neff; Reed-Knight, Bonney; Blount, Ronald L; Wilson, Helen W

2013-09-01

Evaluate the factor structure of youth and maternal involvement ratings on the Inflammatory Bowel Disease Family Responsibility Questionnaire, a measure of family allocation of condition management responsibilities in pediatric inflammatory bowel disease. Participants included 251 youth aged 11-18 years with inflammatory bowel disease and their mothers. Item-level descriptive analyses, subscale internal consistency estimates, and confirmatory factor analyses of youth and maternal involvement were conducted using a dyadic data-analytic approach. Results supported the validity of 4 conceptually derived subscales including general health maintenance, social aspects, condition management tasks, and nutrition domains. Additionally, results indicated adequate support for the factor structure of a 21-item youth involvement measure and strong support for a 16-item maternal involvement measure. Additional empirical support for the validity of the Inflammatory Bowel Disease Family Responsibility Questionnaire was provided. Future research to replicate current findings and to examine the measure's clinical utility is warranted.

An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress.

PubMed

West, Junior J; Zulueta-Coarasa, Teresa; Maier, Janna A; Lee, Donghoon M; Bruce, Ashley E E; Fernandez-Gonzalez, Rodrigo; Harris, Tony J C

2017-08-07

In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress. We show that cytohesins, and their Arf small G protein guanine nucleotide exchange activity, are required for tissues to elongate under stress during both Drosophila dorsal closure (DC) and zebrafish epiboly. In Drosophila, protein localization, laser ablation, and genetic interaction studies indicate that the cytohesin Steppke reduces tissue tension by inhibiting actomyosin activity at adherens junctions. Without Steppke, embryogenesis fails, with epidermal distortions and tears resulting from myosin misregulation. Remarkably, actomyosin network assembly is necessary and sufficient for local Steppke accumulation, where live imaging shows Steppke recruitment within minutes. This rapid negative feedback loop provides a molecular mechanism for attenuating the main tension generator of animal tissues. Such attenuation relaxes tissues and allows orderly elongation under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of functional redundancies within the Arabidopsis TCP transcription factor family.

PubMed

Danisman, Selahattin; van Dijk, Aalt D J; Bimbo, Andrea; van der Wal, Froukje; Hennig, Lars; de Folter, Stefan; Angenent, Gerco C; Immink, Richard G H

2013-12-01

Analyses of the functions of TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1 (TCP) transcription factors have been hampered by functional redundancy between its individual members. In general, putative functionally redundant genes are predicted based on sequence similarity and confirmed by genetic analysis. In the TCP family, however, identification is impeded by relatively low overall sequence similarity. In a search for functionally redundant TCP pairs that control Arabidopsis leaf development, this work performed an integrative bioinformatics analysis, combining protein sequence similarities, gene expression data, and results of pair-wise protein-protein interaction studies for the 24 members of the Arabidopsis TCP transcription factor family. For this, the work completed any lacking gene expression and protein-protein interaction data experimentally and then performed a comprehensive prediction of potential functional redundant TCP pairs. Subsequently, redundant functions could be confirmed for selected predicted TCP pairs by genetic and molecular analyses. It is demonstrated that the previously uncharacterized class I TCP19 gene plays a role in the control of leaf senescence in a redundant fashion with TCP20. Altogether, this work shows the power of combining classical genetic and molecular approaches with bioinformatics predictions to unravel functional redundancies in the TCP transcription factor family.

Analysis of functional redundancies within the Arabidopsis TCP transcription factor family

PubMed Central

Danisman, Selahattin; de Folter, Stefan; Immink, Richard G. H.

2013-01-01

Analyses of the functions of TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1 (TCP) transcription factors have been hampered by functional redundancy between its individual members. In general, putative functionally redundant genes are predicted based on sequence similarity and confirmed by genetic analysis. In the TCP family, however, identification is impeded by relatively low overall sequence similarity. In a search for functionally redundant TCP pairs that control Arabidopsis leaf development, this work performed an integrative bioinformatics analysis, combining protein sequence similarities, gene expression data, and results of pair-wise protein–protein interaction studies for the 24 members of the Arabidopsis TCP transcription factor family. For this, the work completed any lacking gene expression and protein–protein interaction data experimentally and then performed a comprehensive prediction of potential functional redundant TCP pairs. Subsequently, redundant functions could be confirmed for selected predicted TCP pairs by genetic and molecular analyses. It is demonstrated that the previously uncharacterized class I TCP19 gene plays a role in the control of leaf senescence in a redundant fashion with TCP20. Altogether, this work shows the power of combining classical genetic and molecular approaches with bioinformatics predictions to unravel functional redundancies in the TCP transcription factor family. PMID:24129704

Controlled study of critical parent and family factors in the obesigenic environment.

PubMed

Zeller, Meg H; Reiter-Purtill, Jennifer; Modi, Avani C; Gutzwiller, Joeanne; Vannatta, Kathryn; Davies, W Hobart

2007-01-01

Critical gaps remain in our understanding of the obesigenic family environment. This study examines parent and family characteristics among obese youth presenting for treatment in a clinic setting. Families of 78 obese youth (BMI z-score = 2.4; age, 8 to 16 years; 59% girls; 49% African-American) were compared with 71 non-overweight (BMI z-score = -0.02) demographically matched comparisons. Parents completed measures assessing family demographics, psychological distress (Symptom Checklist 90-Revised), and family functioning both broadly (Family Environment Scale: Conflicted, Support, Control) and at mealtimes (About Your Child's Eating-Revised: Mealtime Challenges, Positive Mealtime Interaction). Height and weight were obtained from all participants. Compared with mothers and fathers of non-overweight youth, parents of obese youth had significantly higher BMIs (p < 0.001). Mothers of obese youth reported significantly greater psychological distress (p < 0.01), higher family conflict (p < 0.05), and more mealtime challenges (p < 0.01). Less positive family mealtime interactions were reported by both mothers (p < 0.01) and fathers (p < 0.05) of obese youth. These group differences did not vary by child sex or race. Logistic regression analyses indicated that maternal distress and mealtime challenges discriminated between obese and non-overweight youth after controlling for maternal BMI. Family conflict was explained, in part, by maternal distress. Obese youth who present for treatment in a clinic setting are characterized by psychosocial factors at the parent and family level that differ from non-overweight youth. These data are critical because they identify factors that may be serving as barriers to a family's or youth's ability to implement healthy lifestyle behaviors but that are potentially modifiable.

Factors influencing bereaved families' decisions about organ donation: an integrative literature review.

PubMed

Walker, Wendy; Broderick, Andrew; Sque, Magi

2013-11-01

This article reports on the process and outcomes of a systematic integrative literature review, designed to enhance understanding of the factors influencing bereaved families' decisions to agree or decline the donation of their deceased relative's organs for transplantation. Research originating from eight Western countries (N = 20 studies) provided an international perspective to the review. Thematic analysis and synthesis of textual data culminated in the development of three global themes (past, present, and future) that captured the temporal dimensions of family decision making. The review findings provide valuable insight into ways of increasing the rate of consent to organ donation through the development family-centered care interventions that reflect the needs of the bereaved. Further research to explore the pathway of donation after circulatory death and the experiences of bereaved families who decline organ donation is essential to providing a more complete understanding of the factors affecting donation decisions.

Factor Structure and Psychometric Properties of the Work-Family Balance Scale in an Urban Chinese Sample.

PubMed

Zhang, Huiping; Yip, Paul S F; Chi, Peilian; Chan, Kinsun; Cheung, Yee Tak; Zhang, Xiulan

2012-02-01

The purpose of this study was to explore the factor structure of the Work-Family Balance Scale (WFBS) and examine its reliability and validity in use in the urban Chinese population. The scale was validated using a sample of 605 urban Chinese residents from 7 cities. Exploratory factor analysis identified two factors: work-family conflict and work-family enrichment. The WFBS showed adequate reliability and concurrent validity. The WFBS is a reliable and valid instrument to measure work-family balance for Chinese working parents. However, further examination of the scale is needed.

Children's dental fear and anxiety: exploring family related factors.

PubMed

Wu, Lingli; Gao, Xiaoli

2018-06-04

Dental fear and anxiety (DFA) is a major issue affecting children's oral health and clinical management. This study investigates the association between children's DFA and family related factors, including parents' DFA, parenting styles, family structure (nuclear or single-parent family), and presence of siblings. A total of 405 children (9-13 years old) and their parents were recruited from 3 elementary schools in Hong Kong. Child's demographic and family-related information was collected through a questionnaire. Parents' and child's DFA were measured by using the Corah Dental Anxiety Scale (CDAS) and Children Fear Survey Schedule-Dental Subscale (CFSS-DS), respectively. Parenting styles were gauged by using the Parent Authority Questionnaire (PAQ). DFA was reported by 33.1% of children. The mean (SD) CFSS-DS score was 29.1 (11.0). Children with siblings tended to report DFA (37.0% vs. 24.1%; p = 0.034) and had a higher CFSS-DS score (29.9 vs. 27.4; p = 0.025) as compared with their counterpart. Children from single-parent families had lower CFSS-DS score as compared with children from nuclear families (β = - 9.177; p = 0.029). Subgroup analysis showed a higher CFSS-DS score among boys with siblings (β = 7.130; p = 0.010) as compared with their counterpart; girls' from single-parent families had a lower CFSS-DS score (β = - 13.933; p = 0.015) as compared with girls from nuclear families. Children's DFA was not associated with parents' DFA or parenting styles (p > 0.05). Family structure (nuclear or single-parent family) and presence of siblings are significant determinants for children's DFA. Parental DFA and parenting style do not affect children's DFA significantly.

[Protective factors for preventing the use of drugs in the families of a Colombia locality].

PubMed

Arias, Núbia Medina; Ferriani, Maria das Graças Carvalho

2010-01-01

The aim of this study was to analyze the protective factors that prevent drug use in the families of children who attend Community Homes of Family Well-being in a small Colombian locality. This was a quantitative, descriptive, transversal study, with 256 families constituting the sample. Data were collected through a self-applied questionnaire throughout March and April 2007. Protective factors found included demonstrations of affection toward the children, playing with them and talking to them about things they like, open communication, decision making as a couple, flexibility of the nursing process, and establishment of rules. However, some risk factors were also found, such as consumption of legal drugs such as cigarettes and alcohol, and in a low percentage, consumption of illicit drugs. A high percentage of families consider that drug use must be prevented in the first years of life, by the parents. The protective factors found require reinforcement as they are not very strong, and the risk factors must be controlled to turn them into protective factors.

Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors.

PubMed

Kjøllesdal, M K R; Ariansen, I; Mortensen, L H; Davey Smith, G; Næss, Ø

2016-12-01

To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

Factors influencing palliative care. Qualitative study of family physicians' practices.

PubMed Central

Brown, J. B.; Sangster, M.; Swift, J.

1998-01-01

OBJECTIVE: To examine factors that influence family physicians' decisions to practise palliative care. DESIGN: Qualitative method of in-depth interviews. SETTING: Southwestern Ontario. PARTICIPANTS: Family physicians who practise palliative care on a full-time basis, who practise on a part-time basis, or who have retired from active involvement in palliative care. METHOD: Eleven in-depth interviews were conducted to explore factors that influence family physicians' decisions to practise palliative care and factors that sustain their interest in palliative care. All interviews were audiotaped and transcribed verbatim. The analysis strategy used a phenomenological approach and occurred concurrently rather than sequentially. All interview transcriptions were read independently by the researchers, who then compared and combined their analyses. Final analysis involved examining all interviews collectively, thus permitting relationships between and among central themes to emerge. MAIN OUTCOME FINDINGS: The overriding theme was a common philosophy of palliative care focusing on acceptance of death, whole person care, compassion, communication, and teamwork. Participants' philosophies were shaped by their education and by professional and personal experiences. In addition, participants articulated personal and systemic factors currently affecting their practice of palliative care. CONCLUSIONS: Participants observed that primary care physicians should be responsible for their patients' palliative care within the context of interdisciplinary teams. For medical students to be knowledgeable and sensitive to the needs of dying patients, palliative care should be given higher priority in the curriculum. Finally, participants argued compellingly for transferring the philosophy of palliative care to the overall practice of medicine. PMID:9612588

Ethnic Differences for Developing Rheumatic Fever in a Low-Income Group Living in Hawaii

PubMed Central

Kurahara, David K.; Grandinetti, Andrew; Galario, Judith; Reddy, D. Venu; Tokuda, Angela; Langan, Susan; Tanabe, Brian; Yamamoto, Kara S.; Yamaga, Karen M.

2006-01-01

The risk factors responsible for acute rheumatic fever (ARF) are complex, in part, because group A streptococcus (GAS) infection is a prerequisite for this disease. We attempted to differentiate socioeconomic from genetic risk factors by studying subjects in a Hawaii pediatric cardiology clinic who qualified for Medicaid. This ethnically diverse group was unique because they maintained a low socioeconomic but generally healthy lifestyle with more limited risks than those living in extremely impoverished conditions. Methods Questionnaires were administered to consenting subjects in the clinic, who were divided into those diagnosed with ARF (n=26) and those with other (primarily congenital) heart diseases (n=41). Results The socioeconomic status of the ARF and non-ARF groups was lower than that of the Hawaii population in general, and little differences were noted between the groups. The ARF group, however, had slightly larger household sizes and more children than the non-ARF group. The greatest difference was in ethnicity. By the Fisher exact test, the number of Polynesians belonging to the ARF group was significantly greater than all other ethnicities (P=.005). Polynesians had an odds ratio >4.80 of developing ARF, which increased to 6.33 when number of children per household was considered. Conclusion The potential contribution of genetic predisposing factors for developing ARF was analyzed in subjects living in a homogeneously low socioeconomic level relative to the general Hawaii population. Polynesians were at highest risk when compared to other ethnicities living in similar socioeconomic conditions. PMID:17200684

Factors Influencing Active Family Engagement in Care Among Critical Care Nurses.

PubMed

Hetland, Breanna; Hickman, Ronald; McAndrew, Natalie; Daly, Barbara

2017-01-01

Critical care nurses are vital to promoting family engagement in the intensive care unit. However, nurses have varying perceptions about how much family members should be involved. The Questionnaire on Factors That Influence Family Engagement was given to a national sample of 433 critical care nurses. This correlational study explored the impact of nurse and organizational characteristics on barriers and facilitators to family engagement. Study results indicate that (1) nurses were most likely to invite family caregivers to provide simple daily care; (2) age, degree earned, critical care experience, hospital location, unit type, and staffing ratios influenced the scores; and (3) nursing work-flow partially mediated the relationships between the intensive care unit environment and nurses' attitudes and between patient acuity and nurses' attitudes. These results help inform nursing leaders on ways to promote nurse support of active family engagement in the intensive care unit. ©2017 American Association of Critical-Care Nurses.

Staff Factors Contributing to Family Satisfaction with Long-Term Dementia Care: A Systematic Review of the Literature.

PubMed

Law, Katharine; Patterson, Tom G; Muers, Jane

2017-01-01

The aim of the present review was to critically evaluate empirical evidence regarding staff factors that contribute to families' satisfaction with ongoing care provision for their relatives with dementia in long-term care. Four databases were systematically searched using search terms informed by the aim of the present systematic review. The resulting 14 relevant articles comprised both qualitative and quantitative studies. The findings highlighted three broad areas relating to staff factors that appeared to contribute to families' satisfaction with care provision: family related factors, relating to staff interaction with families; staffing related factors, focusing on staffing organization and composition; and client related factors, focusing on staff interaction with clients and the quality of care provided. The findings have important implications for care staff and managers working in such settings regarding staffing organization, staff training, recruitment and retention. Future research directions are discussed. Families want consistent, knowledgeable staff that interact well and respond appropriately to the needs of their relative as well as their own needs as family members. Staff training in such settings should therefore focus not only on staff education but also on the importance of establishing effective relationships with both clients and families.

Cognitive functioning and family risk factors in relation to symptom behaviors of ADHD and ODD in adolescents.

PubMed

Forssman, Linda; Eninger, Lilianne; Tillman, Carin M; Rodriguez, Alina; Bohlin, Gunilla

2012-05-01

In this study, the authors investigated whether ADHD and oppositional defiant disorder (ODD) behaviors share associations with problems in cognitive functioning and/or family risk factors in adolescence. This was done by examining independent as well as specific associations of cognitive functioning and family risk factors with ADHD and ODD behaviors. A sample of 120 adolescents from the general population was assessed on various cognitive tasks. ADHD and ODD behaviors were measured through parental and teacher ratings based on Diagnostic and Statistical Manual of Mental Disorders (4th edition) criteria. Parents and adolescents provided information regarding measures of family risk factors. The results show that only cognitive functioning was associated with ADHD behaviors, and family risk factors were, independent of cognitive functioning, associated with ODD behaviors. These results suggest that cognitive performance bears a specific significance for ADHD behaviors, whereas family risk factors have specific importance for ODD behaviors.

[Potential risk factors for children in the family diet].

PubMed

Pavlović, M; Bijelović, S; Berenji, K; Balać, D

2001-01-01

It has been proven that high-energy diet with predominance of saturated fatty acids, cholesterol, animal proteins and sugar increases disease incidence. The aim of this study was to determine the potential risk factors of family diet of schoolchildren in Subotica. Evaluation of energy and nutrient intake in family diet (n = 357 families with schoolchildren) was examined by a Food Consumption Questionnaire during 7 days in February-March 1998. Data were elaboreted using a software "NUTQ". The potential nutritive risk factors were determined according to Recommended Dietary Allowances (RDA) index of dietary adequacy, as well as Population Nutrition Goals. Mean energy intake was 2197 kcal, where proteins made 14.64%, fats 41.39% and carbohydrates 43.97%. Mean intake of dietary saturated fatty acids (S) was 11.17%, of polyunsaturated fatty acids (P) 14.39%, of monounsaturated fatty acids 15.82%, dietary cholesterol 82.68 g/1000 kcal, dietary fiber 10.67 g daily, while the P/S ratio was 1.28. Analytical questionnaire of schoolchildren family diet shows that daily about 7.5% of children take in more than 30% of fats, 7% of them over 300 mg of dietary cholesterol, 65% of them over 10% of refined sugars, 50% of them over 10% of saturated fatty acids and all of them more than 6 g of NaCl and less than 20 g of dietary fiber a day. According to WHO recommendations, the average daily energy intake values are appropriate for boys, but exceeding for girls aged ten. Domination of meat, meat products, fats, oils, sugars, as well as mean intake of total fats, saturated fatty acids, potassium and sodium, represent potential nutritive risk factors for developing cardiovascular diseases, which are at the first place of morbidity and the second cause of mortality. In regard to our data from 1998, which have shown that among schoolchildren (n = 478) 10.04% boys and 11.47% girls were obese, 8.55% boys and 6.42% girls were overweight, 9.15% had hypercholesterolemia, 14.83% had

Familial and Temperamental Risk Factors for Social Anxiety Disorder

ERIC Educational Resources Information Center

Hirshfeld-Becker, Dina R.

2010-01-01

Social anxiety disorder (SAD) is a common disorder that can lead to significant impairment. In this chapter, the author provides background on the disorder and reviews hypothesized familial and temperamental risk factors. In particular, it highlights the Massachusetts General Hospital (MGH) Longitudinal Study of Children at Risk for Anxiety, now…

Psychological, Family, and Social Factors Linked with Juvenile Theft in Korea

ERIC Educational Resources Information Center

Lee, DongHun; Han, Yoonsun; Park, ManSik; Roh, SeakZoon

2015-01-01

The absence of an approach which encompasses several micro-systems in Korea may leave important factors of youth risk behaviors undetected. Thus, an examination of a broad set of ecological factors within the micro-system--including individual characteristics as well as immediate family, peer, and school environments surrounding the youth--that is…

Developmental expression patterns of candidate co-factors for vertebrate Six family transcription factors

PubMed Central

Neilson, Karen M.; Pignoni, Francesca; Yan, Bo; Moody, Sally A.

2010-01-01

Six family transcription factors play important roles in craniofacial development. Their transcriptional activity can be modified by co-factor proteins. Two Six genes and one co-factor gene (Eya1) are involved in the human Branchio-otic (BO) and Branchio-otic-renal (BOR) syndromes. However, mutations in Six and Eya genes only account for about half of these patients. To discover potential new causative genes, we searched the Xenopus genome for orthologues of Drosophila co-factor proteins that interact with the fly Six-related factor, SO. We identified 33 Xenopus genes with high sequence identity to 20 of the 25 fly SO-interacting proteins. We provide the developmental expression patterns of the Xenopus orthologues for 11 of the fly genes, and demonstrate that all are expressed in developing craniofacial tissues with at least partial overlap with Six1/Six2. We speculate that these genes may function as Six-interacting partners with important roles in vertebrate craniofacial development and perhaps congenital syndromes. PMID:21089078

Involvement of Bmi-1 gene in the development of gastrointestinal stromal tumor by regulating p16Ink4A/p14ARF gene expressions: An in vivo and in vitro study.

PubMed

Wang, Jiang-Li; Wu, Jiang-Hong; Hong, Cai; Wang, Ya-Nong; Zhou, Ye; Long, Zi-Wen; Zhou, Ying; Qin, Hai-Shu

2017-12-01

This study was conducted in order to explore the role that Bmi-1 plays during the development of a gastrointestinal stromal tumor (GIST) by regulation of the p16 Ink4A and p14 ARF expressions. Eighty-six patients diagnosed with GIST were selected to take part in this experiment. The Bmi-1 protein expressions in GIST and adjacent normal tissues were detected using immunohistochemistry and further analyzed by using photodensitometry. To monitor and track the progression of the GIST, a 3-year follow-up was conducted for all affected patients. After cell transfection, the GIST cells were assigned into the control group (without transfection), the negative control (NC) group (transfected with Bmi-1-Scramble plasmid), and the Bmi-1 shRNA group (transfected with the pcDNA3.1-Bmi-1 shRNA plasmid). Protein and mRNA expressions collected from Bmi-1, p16 lnk4A , P14 ARF , cyclin D1, and CDK4 were measured using both the RT-qPCR and western blotting methods Cell senescence was assessed and obtained by using the β-Galactosidase (β-Gal) activity assay. The use of a Soft agar colony formation assay and CCK-8 assay were performed in order to detect the cell growth and subsequent proliferation. Cell invasion and migration were analyzed using the Transwell assay and scratch test. Bmi-1 in the GIST tissues was found to be significantly higher and the p16 lnk4A and P14 ARF expressions were lower than those in the adjacent normal tissues. Bmi-1 was negatively correlated with p16 lnk4A and P14 ARF expressions according to the correlation analysis. Bmi-1 expression was associated with the TNM stage, postoperative recurrence, metastasis, tumor size, and the 5-year survival rate. Area under ROC curve was calculated at 0.884, and sensitivity, specificity, and accuracy of Bmi-1 predicting the GIST were 67.44%, 97.67%, and 65.12%, respectively. Patients exhibiting a high Bmi-1 expression in the GIST tissues had lower survival rates than those with low Bmi-1 expression. In comparison with

Identification, cloning and characterization of the tomato TCP transcription factor family.

PubMed

Parapunova, Violeta; Busscher, Marco; Busscher-Lange, Jacqueline; Lammers, Michiel; Karlova, Rumyana; Bovy, Arnaud G; Angenent, Gerco C; de Maagd, Ruud A

2014-06-06

TCP proteins are plant-specific transcription factors, which are known to have a wide range of functions in different plant species such as in leaf development, flower symmetry, shoot branching, and senescence. Only a small number of TCP genes has been characterised from tomato (Solanum lycopersicum). Here we report several functional features of the members of the entire family present in the tomato genome. We have identified 30 Solanum lycopersicum SlTCP genes, most of which have not been described before. Phylogenetic analysis clearly distinguishes two homology classes of the SlTCP transcription factor family - class I and class II. Class II differentiates in two subclasses, the CIN-TCP subclass and the CYC/TB1 subclass, involved in leaf development and axillary shoots formation, respectively. The expression patterns of all members were determined by quantitative PCR. Several SlTCP genes, like SlTCP12, SlTCP15 and SlTCP18 are preferentially expressed in the tomato fruit, suggesting a role during fruit development or ripening. These genes are regulated by RIN (RIPENING INHIBITOR), CNR (COLORLESS NON-RIPENING) and SlAP2a (APETALA2a) proteins, which are transcription factors with key roles in ripening. With a yeast one-hybrid assay we demonstrated that RIN binds the promoter fragments of SlTCP12, SlTCP15 and SlTCP18, and that CNR binds the SlTCP18 promoter. This data strongly suggests that these class I SlTCP proteins are involved in ripening. Furthermore, we demonstrate that SlTCPs bind the promoter fragments of members of their own family, indicating that they regulate each other. Additional yeast one-hybrid studies performed with Arabidopsis transcription factors revealed binding of the promoter fragments by proteins involved in the ethylene signal transduction pathway, contributing to the idea that these SlTCP genes are involved in the ripening process. Yeast two-hybrid data shows that SlTCP proteins can form homo and heterodimers, suggesting that they act

Identification, cloning and characterization of the tomato TCP transcription factor family

PubMed Central

2014-01-01

Background TCP proteins are plant-specific transcription factors, which are known to have a wide range of functions in different plant species such as in leaf development, flower symmetry, shoot branching, and senescence. Only a small number of TCP genes has been characterised from tomato (Solanum lycopersicum). Here we report several functional features of the members of the entire family present in the tomato genome. Results We have identified 30 Solanum lycopersicum SlTCP genes, most of which have not been described before. Phylogenetic analysis clearly distinguishes two homology classes of the SlTCP transcription factor family - class I and class II. Class II differentiates in two subclasses, the CIN-TCP subclass and the CYC/TB1 subclass, involved in leaf development and axillary shoots formation, respectively. The expression patterns of all members were determined by quantitative PCR. Several SlTCP genes, like SlTCP12, SlTCP15 and SlTCP18 are preferentially expressed in the tomato fruit, suggesting a role during fruit development or ripening. These genes are regulated by RIN (RIPENING INHIBITOR), CNR (COLORLESS NON-RIPENING) and SlAP2a (APETALA2a) proteins, which are transcription factors with key roles in ripening. With a yeast one-hybrid assay we demonstrated that RIN binds the promoter fragments of SlTCP12, SlTCP15 and SlTCP18, and that CNR binds the SlTCP18 promoter. This data strongly suggests that these class I SlTCP proteins are involved in ripening. Furthermore, we demonstrate that SlTCPs bind the promoter fragments of members of their own family, indicating that they regulate each other. Additional yeast one-hybrid studies performed with Arabidopsis transcription factors revealed binding of the promoter fragments by proteins involved in the ethylene signal transduction pathway, contributing to the idea that these SlTCP genes are involved in the ripening process. Yeast two-hybrid data shows that SlTCP proteins can form homo and heterodimers, suggesting

[Factors affecting subjective satisfaction with verbal communication among the disabled elderly and their family caregivers].

PubMed

Miura, Hiroko; Arai, Yumiko; Yamasaki, Kiyoko

2005-05-01

The aims of the present study were to investigate satisfaction with verbal communication among the disabled elderly and their family caregivers; and to find the significantly influential factors of satisfaction with verbal communication. The subjects were 85 disabled elderly and 85 family caregivers. For the disabled elderly, satisfaction with verbal communication, demographic, and physical factors were examined using an interview survey. For the caregivers, satisfaction with verbal communication, demographic factors, and some factors related caregiving were examined using a self-administered questionnaire. In the disabled elderly, 82.4% were satisfied with their verbal communication while 55.3% of family caregivers were satisfied. Satisfaction with verbal communication between the disabled elderly and their caregivers showed low agreement (kappa = 0.17). Bivariate analysis revealed that satisfaction with verbal communication of the disabled elderly was significantly related to ADL (p < 0.01), dysphagia risk (p < 0.05), and ability of comprehension (p < 0.05) while satisfaction with verbal communication of caregivers was significantly related to the gender of the disabled elderly and caregivers' burden. Furthermore, multiple regression analysis showed that the factor most related to satisfaction with verbal communication for the disabled elderly was ability of comprehension (p value = 0.032, odds ratio = 2.960), and the most related factor for their caregivers was the burden evaluated by J-ZBI_8 (p value = 0.004, odds ratio = 0.842). These results suggest that satisfaction with verbal communication of the disabled elderly disagrees with that of the family caregivers, and that some related factors for the disabled elderly are different from those in their family caregivers.

Self-Reported Internalization Symptoms and Family Factors in Indigenous Sami and Non-Sami Adolescents in North Norway

ERIC Educational Resources Information Center

Bals, Margrethe; Turi, Anne Lene; Vitterso, Joar; Skre, Ingunn; Kvernmo, Siv

2011-01-01

Through differences in family socialization between indigenous and non-indigenous youth, there may be cultural differences in the impact of family factors on mental health outcome. Using structural equation modelling, this population-based study explored the relationship between symptoms of anxiety and depression and family factors in indigenous…

Inequality and adolescent violence: an exploration of community, family, and individual factors.

PubMed Central

Bruce, Marino A.

2004-01-01

PURPOSE: The study seeks to examine whether the relationships among community, family, individual factors, and violent behavior are parallel across race- and gender-specific segments of the adolescent population. METHODS: Data from the National Longitudinal Study of Adolescent Health are analyzed to highlight the complex relationships between inequality, community, family, individual behavior, and violence. RESULTS: The results from robust regression analysis provide evidence that social environmental factors can influence adolescent violence in race- and gender-specific ways. CONCLUSIONS: Findings from this study establish the plausibility of multidimensional models that specify a complex relationship between inequality and adolescent violence. PMID:15101669

Child, parent and family factors as predictors of adjustment for siblings of children with a disability.

PubMed

Giallo, R; Gavidia-Payne, S

2006-12-01

Siblings adjust to having a brother or sister with a disability in diverse ways. This study investigated a range of child, parent and family factors as predictors of sibling adjustment outcomes. Forty-nine siblings (aged 7-16 years) and parents provided information about (1) sibling daily hassles and uplifts; (2) sibling coping; (3) parent stress; (4) parenting; and (5) family resilience. Multiple regression techniques were used. It was found that parent and family factors were stronger predictors of sibling adjustment difficulties than siblings' own experiences of stress and coping. Specifically, socio-economic status, past attendance at a sibling support group, parent stress, family time and routines, family problem-solving and communication, and family hardiness-predicted sibling adjustment difficulties. Finally, siblings' perceived intensity of daily uplifts significantly predicted sibling prosocial behaviour. The results revealed that the family level of risk and resilience factors were better predictors of sibling adjustment than siblings' own experiences of stress and coping resources, highlighting the importance of familial and parental contributions to the sibling adjustment process. The implications of these results for the design of interventions and supports for siblings are discussed.

Factors Associated with the Empowerment of Japanese Families Raising a Child with Developmental Disorders

ERIC Educational Resources Information Center

Wakimizu, Rie; Fujioka, Hiroshi; Yoneyama, Akira; Iejima, Atsushi; Miyamoto, Shinya

2011-01-01

We identified factors associated with the empowerment of Japanese families using the Family Empowerment Scale (FES) to contribute to the improvement of empowerment in Japanese families raising a child with developmental disorders (DDs). The study was conducted in 350 caregivers who raised children aged 4-18 years with DDs in urban and suburban…

Factors Associated with Young Children's Opportunities for Maintaining Family Relationships during Maternal Incarceration

ERIC Educational Resources Information Center

Poehlmann, Julie; Shlafer, Rebecca J.; Maes, Elizabeth; Hanneman, Ashley

2008-01-01

Children affected by maternal incarceration experience challenges maintaining continuous family relationships because of changes in caregivers, separation from siblings, and limited contact with mothers. In this mixed-method study, we investigated maternal and contextual factors associated with continuity in family relationships of children living…

Impact of Health-Related Family Factors on School Enrollment in Bolivia: Implications for Health Education

ERIC Educational Resources Information Center

Madanat, Hala; Dearden, Kirk; Heaton, Tim; Forste, Renata

2005-01-01

This study identified the extent to which family factors increase school enrollment in Bolivia, after adjusting for human and financial capital. The sample was drawn from the 1998 Demographic and Health Survey. Logistic regression models were used to determine the effect of human capital, financial capital and family factors on school enrollment.…

Characterization of the activation of small GTPases by their GEFs on membranes using artificial membrane tethering.

PubMed

Peurois, François; Veyron, Simon; Ferrandez, Yann; Ladid, Ilham; Benabdi, Sarah; Zeghouf, Mahel; Peyroche, Gérald; Cherfils, Jacqueline

2017-03-23

Active, GTP-bound small GTPases need to be attached to membranes by post-translational lipid modifications in order to process and propagate information in cells. However, generating and manipulating lipidated GTPases has remained difficult, which has limited our quantitative understanding of their activation by guanine nucleotide exchange factors (GEFs) and their termination by GTPase-activating proteins. Here, we replaced the lipid modification by a histidine tag in 11 full-length, human small GTPases belonging to the Arf, Rho and Rab families, which allowed to tether them to nickel-lipid-containing membranes and characterize the kinetics of their activation by GEFs. Remarkably, this strategy uncovered large effects of membranes on the efficiency and/or specificity in all systems studied. Notably, it recapitulated the release of autoinhibition of Arf1, Arf3, Arf4, Arf5 and Arf6 GTPases by membranes and revealed that all isoforms are efficiently activated by two GEFs with different regulatory regimes, ARNO and Brag2. It demonstrated that membranes stimulate the GEF activity of Trio toward RhoG by ∼30 fold and Rac1 by ∼10 fold, and uncovered a previously unknown broader specificity toward RhoA and Cdc42 that was undetectable in solution. Finally, it demonstrated that the exceptional affinity of the bacterial RabGEF DrrA for the phosphoinositide PI(4)P delimits the activation of Rab1 to the immediate vicinity of the membrane-bound GEF. Our study thus validates the histidine-tag strategy as a potent and simple means to mimic small GTPase lipidation, which opens a variety of applications to uncover regulations brought about by membranes. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Factor Structure and Psychometric Properties of the Work-Family Balance Scale in an Urban Chinese Sample

ERIC Educational Resources Information Center

Zhang, Huiping; Yip, Paul S. F.; Chi, Peilian; Chan, Kinsun; Cheung, Yee Tak; Zhang, Xiulan

2012-01-01

The purpose of this study was to explore the factor structure of the Work-Family Balance Scale (WFBS) and examine its reliability and validity in use in the urban Chinese population. The scale was validated using a sample of 605 urban Chinese residents from 7 cities. Exploratory factor analysis identified two factors: work-family conflict and…

Family Risk Factors for Adolescent Drug Misuse in Spain

ERIC Educational Resources Information Center

Secades-Villa, Roberto; Fernandez-Hermida, Jose Ramon; Vallejo-Seco, Guillermo

2005-01-01

The main objective of this research was to analyze the influence and the differential weight of certain family factors in Spanish adolescent substance abuse. A representative sample of 1,680 students of both sexes from all over Spain took part in the study. The results show that the variables associated with drug consumption are: male,…

Family factors in adolescent problematic Internet gaming: A systematic review.

PubMed

Schneider, Luke A; King, Daniel L; Delfabbro, Paul H

2017-09-01

Background and aims Familial influences are known to affect the likelihood of an adolescent becoming a problem gamer. This systematic review examined some of the key findings in empirical research on family factors related to adolescent problem gaming. Methods A total of 14 studies in the past decade were evaluated. Family-related variables included: (a) parent status (e.g., socioeconomic status and mental health), (b) parent-child relationship (e.g., warmth, conflict, and abuse), (c) parental influence on gaming (e.g., supervision of gaming, modeling, and attitudes toward gaming), and (d) family environment (e.g., household composition). Results The majority of studies have focused on parent-child relationships, reporting that poorer quality relationships are associated with increased severity of problem gaming. The paternal relationship may be protective against problem gaming; therefore, prevention programs should leverage the support of cooperative fathers. Discussion The intergenerational effects of problem gaming require further attention, in light of adult gamers raising their children in a gaming-centric environment. Research has been limited by a reliance on adolescent self-report to understand family dynamics, without gathering corroborating information from parents and other family members. The very high rates of problem gaming (>10%) reported in general population samples raise concerns about the validity of current screening tools. Conclusions Interventions for adolescents may be more effective in some cases if they can address familial influences on problem gaming with the active co-participation of parents, rather than enrolling vulnerable adolescents in individual-based training or temporarily isolating adolescents from the family system.

Family factors in adolescent problematic Internet gaming: A systematic review

PubMed Central

Schneider, Luke A.; King, Daniel L.; Delfabbro, Paul H.

2017-01-01

Background and aims Familial influences are known to affect the likelihood of an adolescent becoming a problem gamer. This systematic review examined some of the key findings in empirical research on family factors related to adolescent problem gaming. Methods A total of 14 studies in the past decade were evaluated. Family-related variables included: (a) parent status (e.g., socioeconomic status and mental health), (b) parent–child relationship (e.g., warmth, conflict, and abuse), (c) parental influence on gaming (e.g., supervision of gaming, modeling, and attitudes toward gaming), and (d) family environment (e.g., household composition). Results The majority of studies have focused on parent–child relationships, reporting that poorer quality relationships are associated with increased severity of problem gaming. The paternal relationship may be protective against problem gaming; therefore, prevention programs should leverage the support of cooperative fathers. Discussion The intergenerational effects of problem gaming require further attention, in light of adult gamers raising their children in a gaming-centric environment. Research has been limited by a reliance on adolescent self-report to understand family dynamics, without gathering corroborating information from parents and other family members. The very high rates of problem gaming (>10%) reported in general population samples raise concerns about the validity of current screening tools. Conclusions Interventions for adolescents may be more effective in some cases if they can address familial influences on problem gaming with the active co-participation of parents, rather than enrolling vulnerable adolescents in individual-based training or temporarily isolating adolescents from the family system. PMID:28762279

Origin and Evolution of the Sponge Aggregation Factor Gene Family

PubMed Central

Grice, Laura F.; Gauthier, Marie E.A.; Roper, Kathrein E.; Fernàndez-Busquets, Xavier; Degnan, Sandie M.

2017-01-01

Although discriminating self from nonself is a cardinal animal trait, metazoan allorecognition genes do not appear to be homologous. Here, we characterize the Aggregation Factor (AF) gene family, which encodes putative allorecognition factors in the demosponge Amphimedon queenslandica, and trace its evolution across 24 sponge (Porifera) species. The AF locus in Amphimedon is comprised of a cluster of five similar genes that encode Calx-beta and Von Willebrand domains and a newly defined Wreath domain, and are highly polymorphic. Further AF variance appears to be generated through individualistic patterns of RNA editing. The AF gene family varies between poriferans, with protein sequences and domains diagnostic of the AF family being present in Amphimedon and other demosponges, but absent from other sponge classes. Within the demosponges, AFs vary widely with no two species having the same AF repertoire or domain organization. The evolution of AFs suggests that their diversification occurs via high allelism, and the continual and rapid gain, loss and shuffling of domains over evolutionary time. Given the marked differences in metazoan allorecognition genes, we propose the rapid evolution of AFs in sponges provides a model for understanding the extensive diversification of self–nonself recognition systems in the animal kingdom. PMID:28104746

Making time for family meals: Parental influences, home eating environments, barriers and protective factors.

PubMed

Jones, Blake L

2018-04-06

Frequent family mealtimes have been associated with numerous positive dietary, health, and behavioral outcomes for children and families. This review article summarizes some of the beneficial outcomes associated with having frequent family dinners. Current trends in family dinner frequency are discussed in the context of barriers that influence how often families eat dinner together, including time issues, work issues, and distractions in the home environment. Next, several parental influences and home environment factors that promote healthy and consistent family dinners are outlined. Finally, limitations are discussed and a few practical suggestions are mentioned to help encourage families, employers, and policy-makers to make family mealtimes a regular practice for as many families as possible. Copyright © 2018. Published by Elsevier Inc.

Repeat Pregnancy among Urban Adolescents: Sociodemographic, Family, and Health Factors.

ERIC Educational Resources Information Center

Coard, Stephanie Irby; Nitz, Katherine; Felice, Marianne E.

2000-01-01

Examines sociodemographic, family, and health factors associated with repeat pregnancy in a clinical sample of urban, first-time mothers. Results indicate that postpartum contraceptive method was associated with repeat pregnancy at year one; contraceptive use, maternal age, history of miscarriages, and postpartum contraceptive method were…

Familial and Institutional Factors: Job Satisfaction for Female Counselor Educators

ERIC Educational Resources Information Center

Alexander-Albritton, Carrie; Hill, Nicole R.

2015-01-01

Job satisfaction based on familial and institutional factors was explored for 157 female counselor educators. Results indicate that female associate professors had lower levels of intrinsic rewards domain after controlling for institutional type. Parental responsibility and partnership status were equivocal, with significant interaction effects…

Homicide in the western family and background factors of a perpetrator.

PubMed

Aho, Anna Liisa; Remahl, Anni; Paavilainen, Eija

2017-07-01

Familicide is a multiple-victim homicide incident in which the killer's spouse and one or more children are slain. A systematic review was conducted to reveal the background factors of western homicide perpetrators. The systematic search was performed in the Arto, Medic, Cinahl, Medline, EBSCOhost Academic Search Premier and Social Services abstracts databases. The keywords were familicide, family homicide, familicide-suicide, filicide-suicide, extended suicide, child, murder, family, filicide and infanticide. The searches revealed 4139 references from the databases. The references were filtered and 32 peer-reviewed research articles revealed in years 2004-2014 were selected as data. The articles were analysed using inductive content analysis, by finding all possible background factors related to homicide. The factors were described as percentages of the range. The background factors of familicide perpetrators were categorised as follows: perpetrators who had committed homicide of a child and intimate partner and possibly committed suicide; a father had who killed a child; a mother who had killed a child; a father who had committed a filicide-suicide; and a mother who had committed a filicide-suicide. Psychological instability, violence and crime were found in all these categories of familicides. Perpetrators who had committed a suicide in addition to the familicide had more often been diagnosed with depression, but they sought treatment for mental health problems less often and had violence and self-destructiveness less often in their background than in other familicide categories. Social and healthcare professionals should be more sensitive to emerging family problems and be prepared for intervention.

[Genome-wide identification and expression analysis of auxin-related gene families in grape].

PubMed

Yuan, Hua-zhao; Zhao, Mi-zhen; Wu, Wei-min; Yu, Hong-Mei; Qian, Ya-ming; Wang, Zhuang-wei; Wang, Xi-cheng

2015-07-01

The auxin response gene family adjusts the auxin balance and the growth hormone signaling pathways in plants. Using bioinformatics methods, the auxin-response genes from the grape genome database are identified and their chromosomal location, gene collinearity and phylogenetic analysis are performed. Probable genes include 25 AUX_IAA, 19 ARF, 9 GH3 and 42 LBD genes, which are unevenly distributed on all 19 chromosomes and some of them formed distinct tandem duplicate gene clusters. The available grape microarray databases show that all of the auxin-response genes are expressed in fruit and leaf buds, and significant overexpressed during fruit color-changing, bud break and bud dormancy periods. This paper provides a resource for functional studies of auxin-response genes in grape leaf and fruit development.

Quarrelsome family environment as an enhanced factor on child suicidal ideation.

PubMed

Lin, Fu-Gong; Lin, Jing-Ding; Hsieh, Yu-Hsin; Chang, Chien-Yi

2014-12-01

Suicide is a leading cause of death in adolescents, and develops through a process leading from depression to suicidal ideation and self-injury. In this study, we analyzed and compared suicidal ideation among elementary school children from distinct families and school-related backgrounds. We conducted a cross-sectional study to investigate suicidal ideation in elementary school children in Miaoli County of Western Taiwan. Our study included 979 eligible participants and collected data, including suicidal ideation, depression scores, demographic characteristics, and family and school variables. The results revealed that 175 students (17.9%) exhibited depression, and 146 students (14.9%) had contemplated suicide. A quarrelsome family environment was found to be an important independent factor in child suicidal ideation after controlling for depression status. Children living in quarrelsome families showed a 3.7-fold risk of suicidal ideation compared with children in a harmonious family. Among boys living in quarrelsome family environments, suicidal ideation risk was 7.4-fold higher than for girls living in harmonious families. A 27-fold high increased suicidal ideation risk was also observed among the depressed children who living in the quarrelsome family environment, compared with the non-depressed in the harmonious family environment. This study provides novel evidence indicating the enhanced effects of a quarrelsome family environment combined with depression symptoms and among boys on suicidal ideation. These findings suggest of quarrels in a family environment playing an important role on elementary school children's psychological development, and may help parents in improving their mental health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Family-based risk factors for non-suicidal self-injury: Considering influences of maltreatment, adverse family-life experiences, and parent-child relational risk.

PubMed

Martin, Jodi; Bureau, Jean-François; Yurkowski, Kim; Fournier, Tania Renaud; Lafontaine, Marie-France; Cloutier, Paula

2016-06-01

The current investigation addressed the potential for unique influences of perceived childhood maltreatment, adverse family-life events, and parent-child relational trauma on the lifetime occurrence and addictive features of non-suicidal self-injury (NSSI). Participants included 957 undergraduate students (747 females; M = 20.14 years, SD = 3.88) who completed online questionnaires regarding the key variables under study. Although self-injuring youth reported more experiences with each family-based risk factor, different patterns of association were found when lifetime engagement in NSSI or its addictive features were under study. Perceived parent-child relational trauma was uniquely linked with NSSI behavior after accounting for perceived childhood maltreatment; adverse family-life events had an additional unique association. In contrast, perceived paternal maltreatment was uniquely related with NSSI's addictive features. Findings underline the importance of studying inter-related family-based risk factors of NSSI simultaneously for a comprehensive understanding of familial correlates of NSSI behavior and its underlying features. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Genetic Selection of Peptide Aptamers That Interact and Inhibit Both Small Protein B and Alternative Ribosome-Rescue Factor A of Aeromonas veronii C4.

PubMed

Liu, Peng; Chen, Yong; Wang, Dan; Tang, Yanqiong; Tang, Hongqian; Song, Haichao; Sun, Qun; Zhang, Yueling; Liu, Zhu

2016-01-01

Aeromonas veronii is a pathogenic gram-negative bacterium, which infects a variety of animals and results in mass mortality. The stalled-ribosome rescues are reported to ensure viability and virulence under stress conditions, of which primarily include trans-translation and alternative ribosome-rescue factor A (ArfA) in A. veronii. For identification of specific peptides that interact and inhibit the stalled-ribosome rescues, peptide aptamer library (pTRG-SN-peptides) was constructed using pTRG as vector and Staphylococcus aureus nuclease (SN) as scaffold protein, in which 16 random amino acids were introduced to form an exposed surface loop. In the meantime both Small Protein B (SmpB) which acts as one of the key components in trans-translation, and ArfA were inserted to pBT to constitute pBT-SmpB and pBT-ArfA, respectively. The peptide aptamer PA-2 was selected from pTRG-SN-peptides by bacterial two-hybrid system (B2H) employing pBT-SmpB or pBT-ArfA as baits. The conserved sites G133K134 and D138K139R140 of C-terminal SmpB were identified by interacting with N-terminal SN, and concurrently the residue K62 of ArfA was recognized by interacting with the surface loop of the specific peptide aptamer PA-2. The expression plasmids pN-SN or pN-PA-2, which combined the duplication origin of pRE112 with the neokanamycin promoter expressing SN or PA-2, were created and transformed into A. veronii C4, separately. The engineered A. veronii C4 which endowing SN or PA-2 expression impaired growth capabilities under stress conditions including temperatures, sucrose, glucose, potassium chloride (KCl) and antibiotics, and the stress-related genes rpoS and nhaP were down-regulated significantly by Quantitative Real-time PCR (qRT-PCR) when treating in 2.0% KCl. Thus, the engineered A. veronii C4 conferring PA-2 expression might be potentially attenuated vaccine, and also the peptide aptamer PA-2 could develop as anti-microbial drugs targeted to the ribosome rescued factors in A

Genetic Selection of Peptide Aptamers That Interact and Inhibit Both Small Protein B and Alternative Ribosome-Rescue Factor A of Aeromonas veronii C4

PubMed Central

Liu, Peng; Chen, Yong; Wang, Dan; Tang, Yanqiong; Tang, Hongqian; Song, Haichao; Sun, Qun; Zhang, Yueling; Liu, Zhu

2016-01-01

Aeromonas veronii is a pathogenic gram-negative bacterium, which infects a variety of animals and results in mass mortality. The stalled-ribosome rescues are reported to ensure viability and virulence under stress conditions, of which primarily include trans-translation and alternative ribosome-rescue factor A (ArfA) in A. veronii. For identification of specific peptides that interact and inhibit the stalled-ribosome rescues, peptide aptamer library (pTRG-SN-peptides) was constructed using pTRG as vector and Staphylococcus aureus nuclease (SN) as scaffold protein, in which 16 random amino acids were introduced to form an exposed surface loop. In the meantime both Small Protein B (SmpB) which acts as one of the key components in trans-translation, and ArfA were inserted to pBT to constitute pBT-SmpB and pBT-ArfA, respectively. The peptide aptamer PA-2 was selected from pTRG-SN-peptides by bacterial two-hybrid system (B2H) employing pBT-SmpB or pBT-ArfA as baits. The conserved sites G133K134 and D138K139R140 of C-terminal SmpB were identified by interacting with N-terminal SN, and concurrently the residue K62 of ArfA was recognized by interacting with the surface loop of the specific peptide aptamer PA-2. The expression plasmids pN-SN or pN-PA-2, which combined the duplication origin of pRE112 with the neokanamycin promoter expressing SN or PA-2, were created and transformed into A. veronii C4, separately. The engineered A. veronii C4 which endowing SN or PA-2 expression impaired growth capabilities under stress conditions including temperatures, sucrose, glucose, potassium chloride (KCl) and antibiotics, and the stress-related genes rpoS and nhaP were down-regulated significantly by Quantitative Real-time PCR (qRT-PCR) when treating in 2.0% KCl. Thus, the engineered A. veronii C4 conferring PA-2 expression might be potentially attenuated vaccine, and also the peptide aptamer PA-2 could develop as anti-microbial drugs targeted to the ribosome rescued factors in A

Factors affecting public dissatisfaction with urban family physician plan: A general population based study in Fars Province.

PubMed

Imanieh, Mohammad Hadi; Mirahmadizadeh, Alireza; Imani, Bahareh

2017-11-01

Understanding the level of public satisfaction with a family physician plan as well as the relevant factors in this respect, can be employed as valuable tools in identifying quality of services. To determine the factors affecting public dissatisfaction with an urban family physician plan in Iran. This cross-sectional study was conducted from January 2014 through June 2015 on Fars Province residents in Iran, selected based on cluster sampling method. The data collection instrument was comprised of a two-part checklist including demographic information and items related to dissatisfaction with the family physician plan, specialists, para-clinic services, pharmacy, physicians on shift work, emergency services, and family physician assistants. Data were described by SPSS 20. In this study, 1,020 individuals (524 males, 496 females) were investigated. Based on the results, the most frequent factor affecting dissatisfaction with physicians was their single work shifts and unavailability (53%). In terms of dissatisfaction with family physicians' specialist colleagues and para-clinic services, the most common factors were related to difficulty in obtaining a referral form (41.5%) and making appointments (21.6%), respectively. Given the level of dissatisfaction with pharmacies, the significant factor was reported to be excessive delay in medication delivery (31.6%); and in terms of physicians on shift work and emergency services, the most important factor was lower work hours for family physicians (9.2%). It seems that, the most common causes of dissatisfaction with the urban family physician plan are due to the short duration of services, obtaining a referral form and making appointments, and providing prescribed medications.

Is Nonsuicidal Self-Injury Associated with Parenting and Family Factors?

ERIC Educational Resources Information Center

Baetens, Imke; Claes, Laurence; Martin, Graham; Onghena, Patrick; Grietens, Hans; Van Leeuwen, Karla; Pieters, Ciska; Wiersema, Jan R.; Griffith, James W.

2014-01-01

The present study investigates the association of parenting and family factors with nonsuicidal self-injury (NSSI) in preadolescents. A sample of 1,439 preadolescents and their parents were assessed by means of (a) adolescent-reported parenting behaviors (support and behavioral/psychological control), (b) parent-reported parenting behaviors…

[Family characteristics, organic risk factors, psychopathological picture and premorbid adjustment of hospitalized adolescent patients].

PubMed

Małkiewicz-Borkowska, M; Namysłowska, I; Siewierska, A; Puzyńska, E; Sredniawa, H; Zechowski, C; Iwanek, A; Ruszkowska, E

1996-01-01

The relation of some family characteristics such as cohesion and adaptability with organic risk factors, developmental psychopathology, clinical picture and premorbid adjustment was assessed in the group of 100 hospitalized adolescent patients and families. We found correlation between: some of organic risk factors (pathology of neonatal period, pathology of early childhood), some of indicators of developmental psychopathology (eating disorders, conduct disorders), some of clinical signs (mannerism, grandiosity, hostility, suspciousness, disturbances of content of thinking), premorbid adjustment, and variables related to families, described before. We think that biological variables characterizing child (pathology of neonatal period, pathology of early childhood) have an influence on some family characteristics as independent variable. General system theory and circular thinking support these conclusions. In order to verify them, it is necessary to undertake further investigations, based on other methodology, using this results as preliminary findings.

Whole-genome phylogenies of the family Bacillaceae and expansion of the sigma factor gene family in the Bacillus cereus species-group

PubMed Central

2011-01-01

Background The Bacillus cereus sensu lato group consists of six species (B. anthracis, B. cereus, B. mycoides, B. pseudomycoides, B. thuringiensis, and B. weihenstephanensis). While classical microbial taxonomy proposed these organisms as distinct species, newer molecular phylogenies and comparative genome sequencing suggests that these organisms should be classified as a single species (thus, we will refer to these organisms collectively as the Bc species-group). How do we account for the underlying similarity of these phenotypically diverse microbes? It has been established for some time that the most rapidly evolving and evolutionarily flexible portions of the bacterial genome are regulatory sequences and transcriptional networks. Other studies have suggested that the sigma factor gene family of these organisms has diverged and expanded significantly relative to their ancestors; sigma factors are those portions of the bacterial transcriptional apparatus that control RNA polymerase recognition for promoter selection. Thus, examining sigma factor divergence in these organisms would concurrently examine both regulatory sequences and transcriptional networks important for divergence. We began this examination by comparison to the sigma factor gene set of B. subtilis. Results Phylogenetic analysis of the Bc species-group utilizing 157 single-copy genes of the family Bacillaceae suggests that several taxonomic revisions of the genus Bacillus should be considered. Within the Bc species-group there is little indication that the currently recognized species form related sub-groupings, suggesting that they are members of the same species. The sigma factor gene family encoded by the Bc species-group appears to be the result of a dynamic gene-duplication and gene-loss process that in previous analyses underestimated the true heterogeneity of the sigma factor content in the Bc species-group. Conclusions Expansion of the sigma factor gene family appears to have preferentially

Heritabilities of Facial Measurements and Their Latent Factors in Korean Families

PubMed Central

Kim, Hyun-Jin; Im, Sun-Wha; Jargal, Ganchimeg; Lee, Siwoo; Yi, Jae-Hyuk; Park, Jeong-Yeon; Sung, Joohon; Cho, Sung-Il; Kim, Jong-Yeol; Kim, Jong-Il; Seo, Jeong-Sun

2013-01-01

Genetic studies on facial morphology targeting healthy populations are fundamental in understanding the specific genetic influences involved; yet, most studies to date, if not all, have been focused on congenital diseases accompanied by facial anomalies. To study the specific genetic cues determining facial morphology, we estimated familial correlations and heritabilities of 14 facial measurements and 3 latent factors inferred from a factor analysis in a subset of the Korean population. The study included a total of 229 individuals from 38 families. We evaluated a total of 14 facial measurements using 2D digital photographs. We performed factor analysis to infer common latent variables. The heritabilities of 13 facial measurements were statistically significant (p < 0.05) and ranged from 0.25 to 0.61. Of these, the heritability of intercanthal width in the orbital region was found to be the highest (h2 = 0.61, SE = 0.14). Three factors (lower face portion, orbital region, and vertical length) were obtained through factor analysis, where the heritability values ranged from 0.45 to 0.55. The heritability values for each factor were higher than the mean heritability value of individual original measurements. We have confirmed the genetic influence on facial anthropometric traits and suggest a potential way to categorize and analyze the facial portions into different groups. PMID:23843774

The association between family factors and child behaviour problems using dyadic data.

PubMed

Wang, Y; Pan, J; Zhang, X; Yi, C

2015-11-01

Parental psychopathology and family issues are key influence factors to child behaviour problems. This study aimed to investigate the dyadic impact of maternal and paternal depression and perceived family functioning on child behaviour problems. Both maternal and paternal depression, perceived family functioning and reported child behaviour problems were collected, respectively. Because of the interdependent characteristic of dyadic data, structural equation modelling was used to examine the relationship among all variables and the mutual influence between mother and father. Results showed that father-perceived family functioning mediated the relationship between parental depression and child behaviour problems, but mother-perceived family functioning did not show this mediation effect. Meanwhile, maternal and paternal depression influenced both of their own and their partner's perceived family functioning. The findings indicated that paternal psychopathology and family functioning should not be overlooked in child behaviour development. In addition, this study underscored the importance to investigate the different impact of father and mother on child development within a dyadic unit. © 2014 John Wiley & Sons Ltd.

Factors impacting the mental health of the caregivers of children with asthma in china: effects of family socioeconomic status, symptoms control, proneness to shame, and family functioning.

PubMed

Zhou, Ting; Yi, Chunli; Zhang, Xuxia; Wang, Yuyin

2014-12-01

Caregiver mental health is widely considered to be an important factor influencing children's asthma symptoms. The present study aimed to examine key factors that contribute to caregiver mental health in pediatric asthma with a Chinese sample. Two hundred participants reported their family socioeconomic status (SES), proneness to shame, asthma symptoms control of their child, family functioning, and their depression and anxiety symptoms. Results suggested that low family SES, low family functioning, and a high level of shame proneness were associated with high levels of anxiety and depression for caregivers. Family functioning mediated the effects of SES and shame on caregiver mental health and also moderated the effects of SES and shame on caregiver depression. This study highlights the importance of reducing experience of shame and enhancing family functioning in families affected by pediatric asthma. © 2014 Family Process Institute.

Bidirectional associations between family factors and Internet addiction among adolescents in a prospective investigation.

PubMed

Ko, Chih-Hung; Wang, Peng-Wei; Liu, Tai-Ling; Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu

2015-04-01

This study aimed at evaluating the effect of family factors on the occurrence of Internet addiction and determining whether Internet addiction could make any difference in the family function. A total of 2293 adolescents in grade 7 participated in the study. We assessed their Internet addiction, family function, and family factors with a 1-year follow up. In the prospective investigation, inter-parental conflict predicted the incidence of Internet addiction 1 year later in forward regression analysis, followed by not living with mother and allowance to use Internet more than 2 h per day by parents or caregiver. The inter-parental conflict and allowance to use Internet more than 2 h per day also predicted the incidence in girls. Not cared for by parents and family APGAR score predicted the incidence of Internet addiction among boys. The prospective investigation demonstrated that the incidence group had more decreased scores on family APGAR than did the non-addiction group in the 1-year follow-up. This effect was significant only among girls. Inter-parental conflict and inadequate regulation of unessential Internet use predicted risk of Internet addiction, particularly among adolescent girls. Family intervention to prevent inter-parental conflict and promote family function and Internet regulation were necessary to prevent Internet addiction. Among adolescents with Internet addiction, it is necessary to pay attention to deterioration of family function, particularly among girls. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Assessment of probabilistic areal reduction factors of precipitations for the entire French territory with gridded rainfall data.

NASA Astrophysics Data System (ADS)

Fouchier, Catherine; Maire, Alexis; Arnaud, Patrick; Cantet, Philippe; Odry, Jean

2016-04-01

The starting point of our study was the availability of maps of rainfall quantiles available for the entire French mainland territory at the spatial resolution of 1 km². These maps display the rainfall amounts estimated for different rainfall durations (from 15 minutes to 72 hours) and different return periods (from 2 years up to 1 000 years). They are provided by a regionalized stochastic hourly point rainfall generator, the SHYREG method which was previously developed by Irstea (Arnaud et al., 2007; Cantet and Arnaud, 2014). Being calibrated independently on numerous raingauges data (with an average density across the country of 1 raingauge per 200 km²), this method suffers from a limitation common to point-process rainfall generators: it can only reproduce point rainfall patterns and has no capacity to generate rainfall fields. It can't hence provide areal rainfall quantiles, the estimation of the latter being however needed for the construction of design rainfall or for the diagnostic of observed events. One means of bridging this gap between our local rainfall quantiles and areal rainfall quantiles is given by the concept of probabilistic areal reduction factors of rainfall (ARF) as defined by Omolayo (1993). This concept enables to estimate areal rainfall of a particular frequency within a certain amount of time from point rainfalls of the same frequency and duration. Assessing such ARF for the whole French territory is of particular interest since it should allow us to compute areal rainfall quantiles, and eventually watershed rainfall quantiles, by using the already available grids of statistical point rainfall of the SHYREG method. Our purpose was then to assess these ARF thanks to long time-series of spatial rainfall data. We have used two sets of rainfall fields: i) hourly rainfall fields from a 10-year reference database of Quantitative Precipitation Estimation (QPE) over France (Tabary et al., 2012), ii) daily rainfall fields resulting from a 53-year

Risk and Protective Factors for Family Violence among Low-Income Fathers: Implications for Violence Prevention and Fatherhood Programs.

PubMed

Hayward, R Anna; Honegger, Laura; Hammock, Amy Cristina

2018-01-01

Over the last decade there has been an increased focus on improving father engagement to improve child and family outcomes. Recent research suggests that child and family outcomes improve with increased fatherhood engagement. This exploratory study examined risk and protective factors associated with approval of family violence among a sample of low-income fathers (N = 686) enrolled in a responsible fatherhood program. The program goals include increasing father involvement and economic stability and encouraging healthy relationships-with a focus on preventing intimate partner violence. Toward these aims, this study explored factors associated with fathers' self-reported approval of family violence. Understanding the prevalence of risk and protective factors in this population and factors associated with fathers' potential for family violence is important in developing programs to address responsible fatherhood and healthy relationships. © 2017 National Association of Social Workers.

The Child Abusing Family: II. Child and Child-Rearing Variables, Environmental Factors and Typologies of Abusing Families.

ERIC Educational Resources Information Center

Berger, Audrey M.

1980-01-01

Characteristics such as prematurity, illegitimacy, handicaps, or behavior deviations have been found with high frequency in abused children. Aggressive/coercive behavior may be typical of child rearing techniques in abusing families who tend to be socially isolated and experience environmental stress. Investigators must interpret such factors with…

When there Seem to be No Predetermining Factors: Early Child and Proximal Family Risk Predicting Externalizing Behavior in Young Children Incurring No Distal Family Risk

ERIC Educational Resources Information Center

Roskam, I.; Meunier, J.-C.; Stievenart, M.; Noel, M.-P.

2013-01-01

The main objective of the current study was to examine the impact of two child risk factors, i.e. personality and inhibition, and two proximal family risk factors, i.e. parenting and attachment, and the impact of their cumulative effect on later externalizing behavior among young children incurring no distal family risk. Data were collected in a…

High-tensile strength sticking induced by ArF excimer laser surface treatment of poly(tetrafluoroethylene)

NASA Astrophysics Data System (ADS)

Hopp, Bela; Revesz, K.; Bor, Zsolt

1998-07-01

A successful enhancement of sticking of PTFE is demonstrated using ArF excimer laser irradiation in the presence of novel photoreagents. The applied laser fluence was very low at the sample - photoreagent liquid interface compared to the energy density applied in earlier investigations. After the treatment the PTFE films were glued by epoxy resin. It was found that at low doses the tensile strength of the sticking increased rapidly with the UV pulse number and the reached a saturation value, which was 6.66 MPa for triethylamine, 5.56 MPa in the case of 1,2-diaminoethane and 4.64 MPa for triethylene-tetramine. These are around two hundred times higher than the value of the untreated surface. It was found that this procedure makes the metallization and painting of PTFE surface also possible. A photoinduced electron transfer mechanism was suggested to describe the photoreaction, which is responsible for the increase of adhesion features on PTFE surface.

Origin and Evolution of the Sponge Aggregation Factor Gene Family.

PubMed

Grice, Laura F; Gauthier, Marie E A; Roper, Kathrein E; Fernàndez-Busquets, Xavier; Degnan, Sandie M; Degnan, Bernard M

2017-05-01

Although discriminating self from nonself is a cardinal animal trait, metazoan allorecognition genes do not appear to be homologous. Here, we characterize the Aggregation Factor (AF) gene family, which encodes putative allorecognition factors in the demosponge Amphimedon queenslandica, and trace its evolution across 24 sponge (Porifera) species. The AF locus in Amphimedon is comprised of a cluster of five similar genes that encode Calx-beta and Von Willebrand domains and a newly defined Wreath domain, and are highly polymorphic. Further AF variance appears to be generated through individualistic patterns of RNA editing. The AF gene family varies between poriferans, with protein sequences and domains diagnostic of the AF family being present in Amphimedon and other demosponges, but absent from other sponge classes. Within the demosponges, AFs vary widely with no two species having the same AF repertoire or domain organization. The evolution of AFs suggests that their diversification occurs via high allelism, and the continual and rapid gain, loss and shuffling of domains over evolutionary time. Given the marked differences in metazoan allorecognition genes, we propose the rapid evolution of AFs in sponges provides a model for understanding the extensive diversification of self-nonself recognition systems in the animal kingdom. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The Impact of Neighborhood, Family, and Individual Risk Factors on Toddlers’ Disruptive Behavior

PubMed Central

Heberle, Amy E.; Thomas, Yolanda M.; Wagmiller, Robert L.; Briggs-Gowan, Margaret J.; Carter, Alice S.

2014-01-01

Disadvantaged neighborhoods confer risk for behavior problems in school aged children but their impact in toddlerhood is unknown. Relations between toddlers’ disruptive behavior and neighborhood disadvantage, family disadvantage, violence or conflict exposure, parent depressive symptoms, and parenting behavior were examined using multilevel, multi-group (girl/boy) models. Participants were 1204 families (mean child age = 24.7 months). Unique associations between disruptive behavior and all risk factors were observed, but the effect of neighborhood disadvantage was negligible when all of the more proximal factors were accounted for. The results suggest both that children in disadvantaged neighborhoods are at greater risk of behavior problems than children in non-disadvantaged neighborhoods and that optimal prevention/intervention work with these children will attend to proximal risk factors. PMID:24773306

BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth

PubMed Central

Schneider, Pascal; MacKay, Fabienne; Steiner, Véronique; Hofmann, Kay; Bodmer, Jean-Luc; Holler, Nils; Ambrose, Christine; Lawton, Pornsri; Bixler, Sarah; Acha-Orbea, Hans; Valmori, Danila; Romero, Pedro; Werner-Favre, Christiane; Zubler, Rudolph H.; Browning, Jeffrey L.; Tschopp, Jürg

1999-01-01

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M–stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center–like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function. PMID:10359578

Factors Associated With Higher Caregiver Burden Among Family Caregivers of Elderly Cancer Patients: A Systematic Review.

PubMed

Ge, Lixia; Mordiffi, Siti Zubaidah

Caring for elderly cancer patients may cause multidimensional burden on family caregivers. Recognition of factors associated with caregiver burden is important for providing proactive support to caregivers at risk. The aim of this study was to identify factors associated with high caregiver burden among family caregivers of elderly cancer patients. A systematic search of 7 electronic databases was conducted from database inception to October 2014. The identified studies were screened, and full text was further assessed. The quality of included studies was assessed using a checklist, and relevant data were extracted using a predeveloped data extraction form. Best-evidence synthesis model was used for data synthesis. The search yielded a total of 3339 studies, and 7 studies involving 1233 family caregivers were included after screening and full assessment of 116 studies. Moderate evidence supported that younger caregivers, solid tumors, and assistance with patient's activities of daily living were significantly associated with high caregiver burden. Eighteen factors were supported by limited evidence, and 1 was a conflicting factor. The scientific literature to date proved that caregiver burden was commonly experienced by family caregivers of elderly cancer patients. The evidence indicated that family caregivers who were at younger age, caring for solid tumor patients, and providing assistance with patient's activities of daily living reported high caregiver burden. The data provide evidence in identifying family caregivers at high risk of high caregiver burden. More high-quality studies are needed to clarify and determine the estimates of the effects of individual factors.

Family factors related to children's intrinsic/extrinsic motivational orientation and academic performance.

PubMed

Ginsburg, G S; Bronstein, P

1993-10-01

This study examined 3 familial factors--parental surveillance of homework, parental reactions to grades, and general family style--in relation to children's motivational orientation and academic performance. Family, parent, and child measures were obtained in the home from 93 fifth graders and their parents. Teachers provided a measure of classroom motivational orientation, and grades and achievement scores were obtained from school records. Higher parental surveillance of homework, parental reactions to grades that included negative control, uninvolvement, or extrinsic reward, and over- and undercontrolling family styles were found to be related to an extrinsic motivational orientation and to lower academic performance. On the other hand, parental encouragement in response to grades children received was associated with an intrinsic motivational orientation, and autonomy-supporting family styles were associated with intrinsic motivation and higher academic performance. In addition, socioeconomic level was a significant predictor of motivational orientation and academic performance.

The APOBEC3 Family of Retroelement Restriction Factors

PubMed Central

Refsland, Eric W.; Harris, Reuben S.

2014-01-01

The ability to regulate and even target mutagenesis is an extremely valuable cellular asset. Enzyme-catalyzed DNA cytosine deamination is a molecular strategy employed by vertebrates to promote antibody diversity and defend against foreign nucleic acids. Ten years ago, a family of cellular enzymes was first described with several proving capable of deaminating DNA and inhibiting HIV-1 replication. Ensuing studies on the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) restriction factors have uncovered a broad-spectrum innate defense network that suppresses the replication of numerous endogenous and exogenous DNA-based parasites. Although many viruses possess equally elaborate counter-defense mechanisms, the APOBEC3 enzymes offer a tantalizing possibility of leveraging innate immunity to fend off viral infection. Here we focus on mechanisms of retroelement restriction by the APOBEC3 family of restriction enzymes and we consider the therapeutic benefits, as well as the possible pathological consequences, of arming cells with active DNA deaminases. PMID:23686230

Academic Failure and Child-to-Parent Violence: Family Protective Factors.

PubMed

Ibabe, Izaskun

2016-01-01

A reduction in academic achievement over the course of adolescence has been observed. School failure is characterized by difficulties to teaching school goals. A variety of other behavioral problems are often associated with school failure. Child-to-parent violence has been associated with different school problems. The main objective of current study was to examine the contribution of family variables (parental education level, family cohesion, and positive family discipline) on academic failure and child-to-parent violence of adolescents from a community sample. Moreover, a goal was to explore if academic failure was a valid predictor of child-to-parent violence. To this end, it has been developed a comprehensive statistical model through Structural Equation Modeling (SEM). Participants were 584 children from eight secondary schools in the Basque Country (Spain) and aged between 12 and 18. Among other scales Conflict Tactics Scale and Family Environment Scale were administrated for measuring child-to-parent violence and family cohesion environment, respectively. The structural model revealed that parental education level is a relevant protective factor against academic failure. Positive family discipline (inductive discipline, supervision, and penalty) show a significant association with child-to-parent violence and academic failure. Disciplinary practices could be more efficient to prevent child-to-parent violence or school failure if children perceive a positive environment in their home. However, these findings could be explained by inverse causality, because some parents respond to child-to-parent violence or academic failure with disciplinary strategies. School failure had indirect effects on child-to-parent violence through family cohesion. For all that, education policies should focus on parental education courses for disadvantaged families in order to generate appropriate learning environments at home and to foster improvement of parent

Academic Failure and Child-to-Parent Violence: Family Protective Factors

PubMed Central

Ibabe, Izaskun

2016-01-01

A reduction in academic achievement over the course of adolescence has been observed. School failure is characterized by difficulties to teaching school goals. A variety of other behavioral problems are often associated with school failure. Child-to-parent violence has been associated with different school problems. The main objective of current study was to examine the contribution of family variables (parental education level, family cohesion, and positive family discipline) on academic failure and child-to-parent violence of adolescents from a community sample. Moreover, a goal was to explore if academic failure was a valid predictor of child-to-parent violence. To this end, it has been developed a comprehensive statistical model through Structural Equation Modeling (SEM). Participants were 584 children from eight secondary schools in the Basque Country (Spain) and aged between 12 and 18. Among other scales Conflict Tactics Scale and Family Environment Scale were administrated for measuring child-to-parent violence and family cohesion environment, respectively. The structural model revealed that parental education level is a relevant protective factor against academic failure. Positive family discipline (inductive discipline, supervision, and penalty) show a significant association with child-to-parent violence and academic failure. Disciplinary practices could be more efficient to prevent child-to-parent violence or school failure if children perceive a positive environment in their home. However, these findings could be explained by inverse causality, because some parents respond to child-to-parent violence or academic failure with disciplinary strategies. School failure had indirect effects on child-to-parent violence through family cohesion. For all that, education policies should focus on parental education courses for disadvantaged families in order to generate appropriate learning environments at home and to foster improvement of parent

Transcription factor WRKY23 assists auxin distribution patterns during Arabidopsis root development through local control on flavonol biosynthesis.

PubMed

Grunewald, Wim; De Smet, Ive; Lewis, Daniel R; Löfke, Christian; Jansen, Leentje; Goeminne, Geert; Vanden Bossche, Robin; Karimi, Mansour; De Rybel, Bert; Vanholme, Bartel; Teichmann, Thomas; Boerjan, Wout; Van Montagu, Marc C E; Gheysen, Godelieve; Muday, Gloria K; Friml, Jirí; Beeckman, Tom

2012-01-31

Gradients of the plant hormone auxin, which depend on its active intercellular transport, are crucial for the maintenance of root meristematic activity. This directional transport is largely orchestrated by a complex interaction of specific influx and efflux carriers that mediate the auxin flow into and out of cells, respectively. Besides these transport proteins, plant-specific polyphenolic compounds known as flavonols have been shown to act as endogenous regulators of auxin transport. However, only limited information is available on how flavonol synthesis is developmentally regulated. Using reduction-of-function and overexpression approaches in parallel, we demonstrate that the WRKY23 transcription factor is needed for proper root growth and development by stimulating the local biosynthesis of flavonols. The expression of WRKY23 itself is controlled by auxin through the Auxin Response Factor 7 (ARF7) and ARF19 transcriptional response pathway. Our results suggest a model in which WRKY23 is part of a transcriptional feedback loop of auxin on its own transport through local regulation of flavonol biosynthesis.

Factor analysis of the Zarit Burden Interview in family caregivers of patients with amyotrophic lateral sclerosis.

PubMed

Oh, Juyeon; Kim, Jung A

2018-02-01

The Zarit Burden Interview has been used in many studies to assess caregiver burden in family caregivers of patients with amyotrophic lateral sclerosis, but the factor structure of the Zarit Burden Interview in the caregivers of amyotrophic lateral sclerosis patients is unknown. The aim of this study was to explore the factor structure of the Zarit Burden Interview in family caregivers of amyotrophic lateral sclerosis patients using exploratory factor analysis. The exploratory factor analysis was performed using generalized least squares with oblique rotation in a sample of 202 family caregivers. Three factors had an eigenvalue greater than 1 and accounted for 60.33% of the total variance. The three factors were named as follows: (factor 1) "Social restrictions" (items 2, 3, and 10-15); (factor 2) "Self-criticism" (items 20-21); and (factor 3) "Anger and frustration" (items 1, 4-6, 9, and 16-19). The correlation between factors 1 and 3 was much higher (r = 0.79) than that between factors 1 and 2 (r = 0.14) or factors 2 and 3 (r = 0.15). The findings of this study enriched our understanding of several meaningful dimensions of the caregiving burden in caregivers of an amyotrophic lateral sclerosis population and provided opportunities for future intervention.

An Examination of Educational and Familial Factors in Leadership Development

ERIC Educational Resources Information Center

Balikçi, Abdullah

2018-01-01

In this study, family attitudes and behaviours, along with educational factors during school years, which are believed to have an effect on the development of leadership, are researched. In the study, the qualitative research method and phenomenological model have been applied. The participants were identified as one female and one male student by…

Co-localization of endogenous Arf6 and its activator EFA6D in the granular convoluted tubule cells of mouse submandibular glands under normal conditions and when stimulated by isoproterenol, noradrenaline and carbachol.

PubMed

Tachow, Apussara; Thoungseabyoun, Wipawee; Phuapittayalert, Laorrat; Petcharat, Kanoktip; Sakagami, Hiroyuki; Kondo, Hisatake; Hipkaeo, Wiphawi

2017-10-01

This study proposed to investigate the localization at light and electron microscopic levels of Arf6 and its activator EFA6D in the mouse submandibular gland (SMG) under normal conditions and when stimulated by adrenergic or cholinergic agonists. SMGs of male adult mice were utilized for immunoblotting and immuno-light and -electron microscopic analyses. Isoproterenol and noradrenalin were used as adrenergics, while carbachol was used for the cholinergic stimulant. SMGs were examined at 15, 30, 60 and 120min after intraperitoneal injection of these agents. Immunoreactivities for both Arf6 and its activator EFA6D were similarly intense in the basolateral domain of GCTs, but no significant immunoreactivities were seen in the apical domain of GCT cells or any domain of acinar cells under normal conditions. In immuno-electron microscopy, the immunoreactive materials were mainly deposited on the basolateral plasma membranes and subjacent cytoplasm. Shortly after injection of isoproterenol and noradrenaline, but not carbachol, the immunoreactivities for both molecules were additionally seen on the apical plasmalemma of most, if not all, GCT cells, but not acinar cells. The present findings suggest that the direct involvement of Arf6/EFA6D in regulatory exocytosis at the apical plasma membrane of acinar and GCT cells is apparently to be smaller, if present, than that of endocytosis at the basolateral membranes of GCT cells under normal conditions. This also suggests that the two molecules function additionally at the apical membrane of GCT cells for modulation of saliva secretion under β-adrenoceptor stimulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Factors that influence clinicians' assessment and management of family violence.

PubMed Central

Tilden, V P; Schmidt, T A; Limandri, B J; Chiodo, G T; Garland, M J; Loveless, P A

1994-01-01

OBJECTIVES. High rates of family violence and low rates of detection, report, and therapeutic intervention by health professionals are well documented. This study was undertaken to determine what factors influence clinicians' decision making about identifying abuse and intervening with victims. METHODS. Survey data about clinicians' experiences with and attitudes toward family violence were gathered by mailed questionnaire from a random sample of practicing clinicians in six disciplines (n = 1521). RESULTS. Data showed similarities within and wide differences among three groups of subjects: dentists/dental hygienists, nurses/physicians, and psychologists/social workers. Overall, a third of subjects reported having received no educational content on child, spouse, or elder abuse in their professional training programs. Subjects with education on the topic more commonly suspected abuse in their patients than those without; among all subjects, spouse abuse was suspected more often than child abuse while elder abuse was suspected infrequently. Significant numbers of subjects did not view themselves as responsible for dealing with problems of family violence. Subjects indicated low confidence in and low compliance with mandatory reporting laws. CONCLUSIONS. There is a need for educators to expand curricula on family violence and for legislators to reexamine mandatory reporting laws. PMID:8154568

Familiality of factor analysis-derived YBOCS dimensions in OCD-affected sibling pairs from the OCD Collaborative Genetics Study.

PubMed

Hasler, Gregor; Pinto, Anthony; Greenberg, Benjamin D; Samuels, Jack; Fyer, Abby J; Pauls, David; Knowles, James A; McCracken, James T; Piacentini, John; Riddle, Mark A; Rauch, Scott L; Rasmussen, Steven A; Willour, Virginia L; Grados, Marco A; Cullen, Bernadette; Bienvenu, O Joseph; Shugart, Yin-Yao; Liang, Kung-Yee; Hoehn-Saric, Rudolf; Wang, Ying; Ronquillo, Jonne; Nestadt, Gerald; Murphy, Dennis L

2007-03-01

Identification of familial, more homogenous characteristics of obsessive-compulsive disorder (OCD) may help to define relevant subtypes and increase the power of genetic and neurobiological studies of OCD. While factor-analytic studies have found consistent, clinically meaningful OCD symptom dimensions, there have been only limited attempts to evaluate the familiality and potential genetic basis of such dimensions. Four hundred eighteen sibling pairs with OCD were evaluated using the Structured Clinical Interview for DSM-IV and the Yale-Brown Obsessive Compulsive Scale (YBOCS) Symptom Checklist and Severity scales. After controlling for sex, age, and age of onset, robust sib-sib intraclass correlations were found for two of the four YBOCS factors: Factor IV (hoarding obsessions and compulsions (p = .001) and Factor I (aggressive, sexual, and religious obsessions, and checking compulsions; p = .002). Smaller, but still significant, familiality was found for Factor III (contamination/cleaning; p = .02) and Factor II (symmetry/ordering/arranging; p = .04). Limiting the sample to female subjects more than doubled the familiality estimates for Factor II (p = .003). Among potentially relevant comorbid conditions for genetic studies, bipolar I/II and major depressive disorder were strongly associated with Factor I (p < .001), whereas ADHD, alcohol dependence, and bulimia were associated with Factor II (p < .01). Factor-analyzed OCD symptom dimensions in sibling pairs with OCD are familial with some gender-dependence, exhibit relatively specific relationships to comorbid psychiatric disorders and thus may be useful as refined phenotypes for molecular genetic studies of OCD.

Relation of family history and reversible risk factors to coronary heart disease prevalence in an Afrikaner community.

PubMed

Rossouw, J E; Thompson, M L; Jooste, P L; Swanepoel, A S; Jordaan, P C

1991-01-01

In a cross-sectional study of an Afrikaner community (n = 2,722 men and n = 3,173 women aged 25-64 years), family history of coronary heart disease (CHD) was associated with an adverse risk factor profile and with prevalent CHD. Men with myocardial infarction (MI) and a family history of CHD had higher total minus high density lipoprotein cholesterol (TC-HDLC) levels than men with MI but no CHD family history. In preliminary multiple regression analyses, family history of CHD appeared to exert its effect partly independently of known risk factors and partly dependently through age, TC minus HDLC, and HDLC. Even though their association with MI was weakened after entering family history into the models, the reversible risk factors (particularly TC minus HDLC, HDLC, and uric acid levels) continued to contribute to CHD. For MI in men, there was an interaction between family history of CHD and TC minus HDLC, to the extent that raised TC minus HDLC levels were adverse only in the presence of a positive CHD family history. The findings suggest coinheritance of high blood cholesterol and increased susceptibility to CHD. If confirmed in prospective studies, the interaction between family history and TC minus HDLC will have implications for cholesterol screening and management.

Proximity matching for ArF and KrF scanners

NASA Astrophysics Data System (ADS)

Kim, Young Ki; Pohling, Lua; Hwee, Ng Teng; Kim, Jeong Soo; Benyon, Peter; Depre, Jerome; Hong, Jongkyun; Serebriakov, Alexander

2009-03-01

There are many IC-manufacturers over the world that use various exposure systems and work with very high requirements in order to establish and maintain stable lithographic processes of 65 nm, 45 nm and below. Once the process is established, manufacturer desires to be able to run it on different tools that are available. This is why the proximity matching plays a key role to maximize tools utilization in terms of productivity for different types of exposure tools. In this paper, we investigate the source of errors that cause optical proximity mismatch and evaluate several approaches for proximity matching of different types of 193 nm and 248 nm scanner systems such as set-get sigma calibration, contrast adjustment, and, finally, tuning imaging parameters by optimization with Manual Scanner Matcher. First, to monitor the proximity mismatch, we collect CD measurement data for the reference tool and for the tool-to-be-matched. Normally, the measurement is performed for a set of line or space through pitch structures. Secondly, by simulation or experiment, we determine the sensitivity of the critical structures with respect to small adjustment of exposure settings such as NA, sigma inner, sigma outer, dose, focus scan range etc. that are called 'proximity tuning knobs'. Then, with the help of special optimization software, we compute the proximity knob adjustment that has to be applied to the tool-to-be-matched to match the reference tool. Finally, we verify successful matching by exposing on the tool-to-be-matched with tuned exposure settings. This procedure is applicable for inter- and intra scanner type matching, but possibly also for process transfers to the design targets. In order to illustrate the approach we show experimental data as well as results of imaging simulations. The set demonstrate successful matching of critical structures for ArF scanners of different tool generations.

Early life stage trimethyltin exposure induces ADP-ribosylation factor expression and perturbs the vascular system in zebrafish.

PubMed

Chen, Jiangfei; Huang, Changjiang; Truong, Lisa; La Du, Jane; Tilton, Susan C; Waters, Katrina M; Lin, Kuanfei; Tanguay, Robert L; Dong, Qiaoxiang

2012-12-16

Trimethyltin chloride (TMT) is an organotin contaminant, widely detected in aqueous environments, posing potential human and environmental risks. In this study, we utilized the zebrafish model to investigate the impact of transient TMT exposure on developmental progression, angiogenesis, and cardiovascular development. Embryos were waterborne exposed to a wide TMT concentration range from 8 to 96 h post fertilization (hpf). The TMT concentration that led to mortality in 50% of the embryos (LC(50)) at 96 hpf was 8.2 μM; malformations in 50% of the embryos (EC(50)) was 2.8 μM. The predominant response observed in surviving embryos was pericardial edema. Additionally, using the Tg (fli1a: EGFP) y1 transgenic zebrafish line to non-invasively monitor vascular development, TMT exposure led to distinct disarrangements in the vascular system. The most susceptible developmental stage to TMT exposure was between 48 and 72 hpf. High density whole genome microarrays were used to identify the early transcriptional changes following TMT exposure from 48 to 60 hpf or 72 hpf. In total, 459 transcripts were differentially expressed at least 2-fold (P<0.05) by TMT compared to control. Using Ingenuity Pathway Analysis (IPA) tools, it was revealed that the transcripts misregulated by TMT exposure were clustered in numerous categories including metabolic and cardiovascular disease, cellular function, cell death, molecular transport, and physiological development. In situ localization of highly elevated transcripts revealed intense staining of ADP-ribosylation factors arf3 and arf5 in the head, trunk, and tail regions. When arf5 expression was blocked by morpholinos, the zebrafish did not display the prototypical TMT-induced vascular deficits, indicating that the induction of arf5 was necessary for TMT-induced vascular toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Family Engagement in Literacy Activities: Revised Factor Structure for the Familia--An Instrument Examining Family Support for Early Literacy Development

ERIC Educational Resources Information Center

Buhs, Eric S.; Welch, Greg; Burt, Jennifer; Knoche, Lisa

2011-01-01

This study evaluated a data-set drawn using "The Familia"--a measure originally developed to evaluate shared-reading activities. A newly developed set of conceptual supports and a confirmatory factor analysis (CFA) were applied to a new factor structure/model. Data were drawn from 219 young children and their families (mean age = 43…

The association of psychosocial and familial factors with adolescent suicidal ideation: A population-based study.

PubMed

An, Hoyoung; Ahn, Joon-ho; Bhang, Soo-young

2010-05-30

We aimed to compare the influence of various parental factors on adolescent suicidal ideas from a population-based sample of 2965 adolescents between 15 to 18 years-old, and their parents. Among the subject variables, gender, satisfaction with one's health, having an illness, and satisfaction with family; and among parental variables, fathers' satisfaction with health; mothers' insufficient sleep; parents' history of suicidal ideation, and satisfaction with family were significantly different in adolescents who reported suicidal ideation compared to those who reported none. Odds ratios indicated increased risk of adolescent suicidal ideation was associated with the subject factors female gender, insufficient sleep, dissatisfaction with one's health, dissatisfaction with family, and with maternal data showing insufficient sleep and a positive history of suicidal impulse. A path analysis model (comparative fit index (CFI)=0.907; root mean square error of approximation (RMSEA)=0.047), indicated psychosocial factors (beta=0.232) had a greater influence on adolescent suicidal ideation than did genetic factors (beta=0.120). These results show psychosocial factors have an almost two-fold greater influence on adolescent suicidal ideation than genetic factors. Assessment and modification of these factors would greatly assist future interventions. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Risk factors for colorectal cancer in subjects with family history of the disease.

PubMed

Fernandez, E; La Vecchia, C; D'Avanzo, B; Negri, E; Franceschi, S

1997-01-01

The relationship between lifestyle factors, past medical conditions, daily meal frequency, diet and the risk of 'familial' colorectal cancer has been analysed using data from a case-control study conducted in northern Italy. A total of 1584 colorectal cancer patients and 2879 control subjects were admitted to a network of hospitals in the Greater Milan area and the Pordenone province. The subjects included for analysis were the 112 cases and the 108 control subjects who reported a family history of colorectal cancer in first-degree relatives. Colorectal cancer cases and control subjects with family history were similarly distributed according to sex, age, marital status, years of schooling and social class. Familial colorectal cancer was associated with meal frequency, medical history of diabetes (relative risk, RR = 4.6) and cholelithiasis (RR = 5.2). Significant positive trends of increasing risk with more frequent consumption were observed for pasta (RR = 2.5, for the highest vs the lowest intake tertile), pastries (RR = 2.4), red meat (RR = 2.9), canned meat (RR = 1.9), cheese (RR = 3.5) and butter (RR = 1.9). Significant inverse associations and trends in risk were observed for consumption of poultry (RR = 0.4), tomatoes (RR = 0.2), peppers (RR = 0.3) and lettuce (RR = 0.3). Significant inverse trends in risk with increasing consumption for beta-carotene and ascorbic acid were observed (RR = 0.5 and 0.4 respectively, highest vs lowest intake tertile). These results suggest that risk factors for subjects with a family history of colorectal cancer in first-degree relatives are not appreciably different from recognized risk factors of the disease in the general population.