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1

Early events in arenavirus replication are sensitive to lysosomotropic compounds  

Microsoft Academic Search

Summary Lysosomotropic compounds (ammonium chloride, chloroquine, amantadine, monensin) effectively inhibited the replication of Pichinde, Mopeia, and Lassa viruses in BHK-21 and Vero cells. The inhibitory effect was dependent upon the time of drug addition and was most effective when the drugs were added 1h before the viral adsorption. The drugs had no direct effect on the infectious viruses nor on

Svetlana E. Glushakova; I. S. Lukashevich

1989-01-01

2

Role of early and late replication events in induction of apoptosis by baculoviruses.  

PubMed Central

Autographa californica nuclear polyhedrosis virus (AcMNPV) mutants that lack the apoptotic suppressor gene p35 cause apoptosis in Spodoptera frugiperda SF21 cells. To identify a viral signal(s) that induces programmed cell death, we first defined the timing of apoptotic events during infection. Activation of a P35-inhibitable caspase, intracellular fragmentation of host and AcMNPV DNA, and cell membrane blebbing coincided with the initiation of viral DNA synthesis between 9 and 12 h after infection and thus suggested that apoptotic signaling begins at or before this time. Virus entry was required since binding of budded virus to host cell receptors alone was insufficient to induce apoptosis. To therefore determine the contribution of early and late replication events to apoptotic signaling, we used the AcMNPV mutant ts8 with a temperature-sensitive lesion in the putative helicase gene p143. At the nonpermissive temperature at which viral DNA synthesis was conditionally blocked, ts8 caused extensive apoptosis of the SF21 cell line p3576D, which dominantly interferes with anti-apoptotic function of viral P35. Confirming that apoptosis can be induced in the absence of normal viral DNA synthesis, parental SF21 cells also underwent apoptosis when infected with a ts8 p35 deletion mutant at the nonpermissive temperature. However, maximum levels of ts8 p35 deletion mutant-induced apoptosis required a temperature-sensitive event(s) that included the initiation of viral DNA synthesis. Collectively, these data suggested that baculovirus-induced apoptosis can be triggered by distinct early (pre-DNA synthesis) and late replicative events, including viral DNA synthesis or late gene expression.

LaCount, D J; Friesen, P D

1997-01-01

3

Inhibiting early-stage events in HIV-1 replication by small-molecule targeting of the HIV-1 capsid.  

PubMed

The HIV-1 capsid (CA) protein plays essential roles in both early and late stages of virl replication and has emerged as a novel drug target. We report hybrid structure-based virtual screening to identify small molecules with the potential to interact with the N-terminal domain (NTD) of HIV-1 CA and disrupt early, preintegration steps of the HIV-1 replication cycle. The small molecule 4,4'-[dibenzo[b,d]furan-2,8-diylbis(5-phenyl-1H-imidazole-4,2-diyl)]dibenzoic acid (CK026), which had anti-HIV-1 activity in single- and multiple-round infections but failed to inhibit viral replication in peripheral blood mononuclear cells (PBMCs), was identified. Three analogues of CK026 with reduced size and better drug-like properties were synthesized and assessed. Compound I-XW-053 (4-(4,5-diphenyl-1H-imidazol-2-yl)benzoic acid) retained all of the antiviral activity of the parental compound and inhibited the replication of a diverse panel of primary HIV-1 isolates in PBMCs, while displaying no appreciable cytotoxicity. This antiviral activity was specific to HIV-1, as I-XW-053 displayed no effect on the replication of SIV or against a panel of nonretroviruses. Direct interaction of I-XW-053 was quantified with wild-type and mutant CA protein using surface plasmon resonance and isothermal titration calorimetry. Mutation of Ile37 and Arg173, which are required for interaction with compound I-XW-053, crippled the virus at an early, preintegration step. Using quantitative PCR, we demonstrated that treatment with I-XW-053 inhibited HIV-1 reverse transcription in multiple cell types, indirectly pointing to dysfunction in the uncoating process. In summary, we have identified a CA-specific compound that targets and inhibits a novel region in the NTD-NTD interface, affects uncoating, and possesses broad-spectrum anti-HIV-1 activity. PMID:22647699

Kortagere, Sandhya; Madani, Navid; Mankowski, Marie K; Schön, Arne; Zentner, Isaac; Swaminathan, Gokul; Princiotto, Amy; Anthony, Kevin; Oza, Apara; Sierra, Luz-Jeannette; Passic, Shendra R; Wang, Xiaozhao; Jones, David M; Stavale, Eric; Krebs, Fred C; Martín-García, Julio; Freire, Ernesto; Ptak, Roger G; Sodroski, Joseph; Cocklin, Simon; Smith, Amos B

2012-05-30

4

Inhibition of early and late events of the HIV-1 replication cycle by cytoplasmic Fab intrabodies against the matrix protein, p17.  

PubMed Central

BACKGROUND: The HIV-1 matrix (MA) protein, p17, contains two subcellular localization signals that facilitate both nuclear import of the viral preintegration complex early during infection and virus particle assembly late in infection. The dual role of MA in both the afferent and efferent arms of the HIV-1 life cycle makes it an important target for intracellular immunization-based gene therapy strategies. MATERIALS AND METHODS: Here we report, using a new bicistronic vector, that an intracellular Fab antibody, or Fab intrabody, directed against a carboxy-terminal epitope of MA from the Clade B HIV-1 genotype, can inhibit HIV-1 infection when expressed in the cytoplasm of actively dividing CD4+ T cells. RESULTS: Marked inhibition of proviral gene expression occurred when single-round HIV-1 CAT virus was used for infections. In challenge experiments using both laboratory strains and syncytium-inducing primary isolates of HIV-1, a substantial reduction in the infectivity of virions released from the cells was also observed. CONCLUSIONS: This novel strategy of simultaneously blocking early and late events of the HIV-1 life cycle may prove useful in clinical gene therapy approaches for the treatment of HIV-1 infection and AIDS, particularly when combined with genetic or pharmacologic-based strategies that inhibit other HIV-1 target molecules simultaneously. Images FIG. 2 FIG. 3 FIG. 5 FIG. 6 FIG. 8

Levin, R.; Mhashilkar, A. M.; Dorfman, T.; Bukovsky, A.; Zani, C.; Bagley, J.; Hinkula, J.; Niedrig, M.; Albert, J.; Wahren, B.; GA?ttlinger, H. G.; Marasco, W. A.

1997-01-01

5

Early traumatic events in psychopaths.  

PubMed

The relationship between diverse early traumatic events and psychopathy was studied in 194 male inmates. Criminal history transcripts were revised, and clinical interviews were conducted to determine the level of psychopathy using the Psychopathy Checklist-Revised (PCL-R) Form, and the Early Trauma Inventory was applied to assess the incidence of abuse before 18 years of age. Psychopathic inmates presented a higher victimization level and were more exposed to certain types of intended abuse than sociopathic inmates, while the sum of events and emotional abuse were associated with the PCL-R score. Our studies support the influence of early adverse events in the development of psychopathic offenders. PMID:23550705

Borja, Karina; Ostrosky, Feggy

2013-03-28

6

Early events in ovarian oncogenesis  

PubMed Central

Ovarian cancer represents the most lethal of the gynecological neoplasms. The molecular and genetic events associated with early ovarian oncogenesis are still largely unknown, thus contributing to the lack of reliable biomarkers for disease detection. Since the majority of ovarian tumors are diagnosed at an advanced stage, the availability of early ovarian cancer tissue samples for molecular analyses is very limited. In this review, problems encountered in the study of early ovarian cancer are presented, along with the controversies concerning precursor lesions and stepwise progression towards ovarian malignancy. Experimental modeling in the development of ovarian cancer is also described, as well as genetic and epigenetic alterations associated with early ovarian cancer. Lastly, examples of technological advances in the study of early ovarian cancer are discussed. Hopefully, the increasing knowledge about molecular and genetic events involved in the early stages of ovarian tumorigenesis will provide the basis for management of ovarian cancer in the future.

Cvetkovic, Dusica

2003-01-01

7

Loss of heterozygosity preferentially occurs in early replicating regions in cancer genomes  

PubMed Central

Erroneous repair of DNA double-strand breaks by homologous recombination (HR) leads to loss of heterozygosity (LOH). Analysing 22 392 and 74 415 LOH events in 363 glioblastoma and 513 ovarian cancer samples, respectively, and using three different metrics, we report that LOH selectively occurs in early replicating regions; this pattern differs from the trends for point mutations and somatic deletions, which are biased toward late replicating regions. Our results are independent of BRCA1 and BRCA2 mutation status. The LOH events are significantly clustered near RNA polII-bound transcription start sites, consistent with the reports that slow replication near paused RNA polII might initiate HR-mediated repair. The frequency of LOH events is higher in the chromosomes with shorter inter-homolog distance inside the nucleus. We propose that during early replication, HR-mediated rescue of replication near paused RNA polII using homologous chromosomes as template leads to LOH. The difference in the preference for replication timing between different classes of genomic alterations in cancer genomes also provokes a testable hypothesis that replicating cells show changing preference between various DNA repair pathways, which have different levels of efficiency and fidelity, as the replication progresses.

Pedersen, Brent S.; De, Subhajyoti

2013-01-01

8

DNA replication origin of polyoma virus: early proximal boundary.  

PubMed Central

We constructed a series of deleted polyoma genomes by Bal 31 nuclease digestion from the unique Bg/I site at nucleotide 86 on the "early" side of the origin of DNA replication. The ability of the cloned deleted genomes to replicate was tested after transfection into mouse 3T6 fibroblasts or into the polyomatransformed C127 (COP5) mouse cell line (Tyndall et al., Nucleic Acids Res. 9:6231-6251, 1981). Deletions up to nucleotide 64-had no effect on the amount of replicated DNA accumulated, but larger deletions, extending up to nucleotide 42, decreased this amount 7- to 10-fold. By nucleotide 38, the quantity of detected DNA was down 100-fold, and by nucleotide 20, no replication could be detected. The minimum origin segment does not contain any known high-affinity, large tumor antigen binding site. Images

Katinka, M; Yaniv, M

1983-01-01

9

Early Events in RNA Folding  

NASA Astrophysics Data System (ADS)

We describe a conceptual framework for understanding the way large RNA molecules fold based on the notion that their free-energy landscape is rugged. A key prediction of our theory is that RNA folding can be described by the kinetic partitioning mechanism (KPM). According to KPM a small fraction of molecules folds rapidly to the native state whereas the remaining fraction is kinetically trapped in a low free-energy non-native state. This model provides a unified description of the way RNA and proteins fold. Single-molecule experiments on Tetrahymena ribozyme, which directly validate our theory, are analyzed using KPM. We also describe the earliest events that occur on microsecond time scales in RNA folding. These must involve collapse of RNA molecules that are mediated by counterion-condensation. Estimates of time scales for the initial events in RNA folding are provided for the Tetrahymena ribozyme.

Thirumalai, D.; Lee, Namkyung; Woodson, Sarah A.; Klimov, Dk

2001-10-01

10

Differential host response, rather than early viral replication efficiency, correlates with pathogenicity caused by influenza viruses.  

PubMed

Influenza viruses exhibit large, strain-dependent differences in pathogenicity in mammalian hosts. Although the characteristics of severe disease, including uncontrolled viral replication, infection of the lower airway, and highly inflammatory cytokine responses have been extensively documented, the specific virulence mechanisms that distinguish highly pathogenic strains remain elusive. In this study, we focused on the early events in influenza infection, measuring the growth rate of three strains of varying pathogenicity in the mouse airway epithelium and simultaneously examining the global host transcriptional response over the first 24 hours. Although all strains replicated equally rapidly over the first viral life-cycle, their growth rates in both lung and tracheal tissue strongly diverged at later times, resulting in nearly 10-fold differences in viral load by 24 hours following infection. We identified separate networks of genes in both the lung and tracheal tissues whose rapid up-regulation at early time points by specific strains correlated with a reduced viral replication rate of those strains. The set of early-induced genes in the lung that led to viral growth restriction is enriched for both NF-?B binding site motifs and members of the TREM1 and IL-17 signaling pathways, suggesting that rapid, NF-?B -mediated activation of these pathways may contribute to control of viral replication. Because influenza infection extending into the lung generally results in severe disease, early activation of these pathways may be one factor distinguishing high- and low-pathogenicity strains. PMID:24073225

Askovich, Peter S; Sanders, Catherine J; Rosenberger, Carrie M; Diercks, Alan H; Dash, Pradyot; Navarro, Garnet; Vogel, Peter; Doherty, Peter C; Thomas, Paul G; Aderem, Alan

2013-09-20

11

Differential Host Response, Rather Than Early Viral Replication Efficiency, Correlates with Pathogenicity Caused by Influenza Viruses  

PubMed Central

Influenza viruses exhibit large, strain-dependent differences in pathogenicity in mammalian hosts. Although the characteristics of severe disease, including uncontrolled viral replication, infection of the lower airway, and highly inflammatory cytokine responses have been extensively documented, the specific virulence mechanisms that distinguish highly pathogenic strains remain elusive. In this study, we focused on the early events in influenza infection, measuring the growth rate of three strains of varying pathogenicity in the mouse airway epithelium and simultaneously examining the global host transcriptional response over the first 24 hours. Although all strains replicated equally rapidly over the first viral life-cycle, their growth rates in both lung and tracheal tissue strongly diverged at later times, resulting in nearly 10-fold differences in viral load by 24 hours following infection. We identified separate networks of genes in both the lung and tracheal tissues whose rapid up-regulation at early time points by specific strains correlated with a reduced viral replication rate of those strains. The set of early-induced genes in the lung that led to viral growth restriction is enriched for both NF-?B binding site motifs and members of the TREM1 and IL-17 signaling pathways, suggesting that rapid, NF-?B –mediated activation of these pathways may contribute to control of viral replication. Because influenza infection extending into the lung generally results in severe disease, early activation of these pathways may be one factor distinguishing high- and low-pathogenicity strains.

Askovich, Peter S.; Sanders, Catherine J.; Rosenberger, Carrie M.; Diercks, Alan H.; Dash, Pradyot; Navarro, Garnet; Vogel, Peter; Doherty, Peter C.; Thomas, Paul G.; Aderem, Alan

2013-01-01

12

USF Binding Sequences from the HS4 Insulator Element Impose Early Replication Timing on a Vertebrate Replicator  

PubMed Central

The nuclear genomes of vertebrates show a highly organized program of DNA replication where GC-rich isochores are replicated early in S-phase, while AT-rich isochores are late replicating. GC-rich regions are gene dense and are enriched for active transcription, suggesting a connection between gene regulation and replication timing. Insulator elements can organize independent domains of gene transcription and are suitable candidates for being key regulators of replication timing. We have tested the impact of inserting a strong replication origin flanked by the ?-globin HS4 insulator on the replication timing of naturally late replicating regions in two different avian cell types, DT40 (lymphoid) and 6C2 (erythroid). We find that the HS4 insulator has the capacity to impose a shift to earlier replication. This shift requires the presence of HS4 on both sides of the replication origin and results in an advance of replication timing of the target locus from the second half of S-phase to the first half when a transcribed gene is positioned nearby. Moreover, we find that the USF transcription factor binding site is the key cis-element inside the HS4 insulator that controls replication timing. Taken together, our data identify a combination of cis-elements that might constitute the basic unit of multi-replicon megabase-sized early domains of DNA replication.

Cadoret, Jean-Charles; Ma, Meiji Kit-Wan; Boggetto, Nicole; West, Adam G.; Prioleau, Marie-Noelle

2012-01-01

13

What is remembered about early childhood events?  

Microsoft Academic Search

Almost 100 years ago, Freud identified infantile or childhood amnesia, the difficulty that most adults have remembering events from their first years of life. Recent research in cognitive psychology has in fact demonstrated a paucity of verbal memories of early life experiences. Although Freud believed that childhood memories are repressed, modern explanations for childhood amnesia focus instead on cognitive and

David B. Pillemer

1998-01-01

14

Modeling homopolymer self-replication: implications for early competition.  

PubMed

We start showing that the rate equation for a homopolymer self-replication may be written as being proportional to mbetapGamma with beta=1 and Gamma=1/2, where m is the monomer concentration and p is the homopolymer total concentration (double helices plus isolated strands). With such values for the exponents beta and Gamma, we examine analytically the asymptotic behavior of our model previously proposed for studying the early polymer evolution. In this model, polymers compete for activated monomers carried into the system under a constant flux. Time changes on their concentrations are determined by the reactions of: spontaneous generation of dimers through non-instructed junction of two monomers; ligation among free monomers and polymers at the end of their chains, so that they can extend their sizes; template-instructed synthesis by which polymers with lengths above a length threshold can catalyse the formation of other polymers; and decomposition of all species. We find out that if the monomer flux intensity is "low" (lesser than the decomposition rate constants), dimer is the dominant species. Under a "high" flux (greater than the template-instructed synthesis rate constant), the longest self-replicating species prevails. For a "middle" flux (between "low" and "high"), the shortest self-replicating polymer is the winner. Whatever the flux intensity, all polymer species ever coexist. PMID:9892555

Monteiro, L H; Piqueira, J R

1999-01-01

15

Mapping of early firing origins on a replication profile of budding yeast  

Microsoft Academic Search

Background : Understanding of the firing time deter- mination of replication origins in the entire genome will require a genome-wide survey of replication origins and their mapping on chromosomes. A micro- array technology was applied to obtain a genome- wide profile of DNA replication and to classify early firing origins. Results : A total of 260 potential replication origins (PROs)

Nami Yabuki; Hiromichi Terashima; Kunio Kitada

2002-01-01

16

Early Events in Ionic Liquid Radiation Chemistry  

SciTech Connect

Ionic liquids are interesting and useful materials whose solvation time scales are up to thousands of times longer than in conventional solvents. The extended lifetimes of pre-solvated electrons and other energetic species in ionic liquids has profound consequences for the radiolytic product distributions and reactivity patterns. We use a newly developed, multiplexed variation of pulse-probe spectroscopy to measure the kinetics of the early dynamical and reactive events in ionic liquids.

Wishart, J.F.; Cook, A.; Rimmer, R.D.; Gohdo, M.

2010-09-14

17

Initiation of baculovirus DNA replication: early promoter regions can function as infection-dependent replicating sequences in a plasmid-based replication assay.  

PubMed Central

From the results of transient plasmid-based replication assays, it has been postulated that homologous regions (hrs) of Autographa californica nuclear polyhedrosis virus (AcMNPV) function as origins of viral DNA replication. However, these assays vary in specificity according to the methodology used and may not be dependent solely on the presence of hr sequences. To determine the role that hrs and other sequences might play in the replication process, a series of plasmids containing specific deletions of various hrs was generated and tested in a standardized replication assay. Deletion of the AcMNPV hr2 and hr5 sequences abolished the ability of plasmids to replicate in the standard infection-dependent replication assay, while deletion of hr1, hr3, and hr4a sequences decreased but did not eliminate plasmid replication in this assay. Plasmids carrying the complete ie-2 and pe38 genes, the ie-1 gene upstream region, or a variety of baculovirus genes including 11 early promoter regions were also able to replicate in virus-infected cells, suggesting that early viral promoter sequences could also function as putative origins of replication. These data suggest that the standard infection-dependent replication assay may identify a broad range of infection-dependent replicating sequences, only one or a few of which may represent genuine viral origins used by the virus in vivo. We propose a model suggesting that the selection of replication initiation sites may be imposed directly by chromatin structure and indirectly by primary sequence and that the process of viral DNA replication may be linked with viral transcription.

Wu, Y; Carstens, E B

1996-01-01

18

Mouse STAT2 Restricts Early Dengue Virus Replication  

PubMed Central

Summary Dengue virus encodes several interferon antagonists. Among these the NS5 protein binds STAT2, a necessary component of the type-I interferon signaling pathway, and targets it for degradation. We now demonstrate that the ability of dengue NS5 to associate with and degrade STAT2 is species specific. Thus, NS5 is able to bind and degrade human STAT2 but not mouse STAT2. This difference was exploited to demonstrate, absent manipulation of the viral genome, that NS5 mediated IFN antagonism is essential for efficient virus replication. Moreover, we demonstrate that differences in NS5 mediated binding and degradation between human and mouse STAT2 maps to a region within the STAT2 coiled-coil domain. By using STAT2?/? mice, we also demonstrate that mouse STAT2 restricts early dengue virus replication in vivo. These results suggest that overcoming this restriction through transgenic mouse technology may help in the development of a long-sought immune-competent mouse model of dengue virus infection.

Ashour, Joseph; Morrison, Juliet; Laurent-Rolle, Maudry; Belicha-Villanueva, Alan; Plumlee, Courtney Ray; Bernal-Rubio, Dabeiba; Williams, Kate; Harris, Eva; Fernandez-Sesma, Ana; Schindler, Christian; Garcia-Sastre, Adolfo

2012-01-01

19

A post-entry role for CD63 in early HIV-1 replication  

SciTech Connect

Macrophages and CD4{sup +} lymphocytes are the major reservoirs for HIV-1 infection. CD63 is a tetraspanin transmembrane protein, which has been shown to play an essential role during HIV-1 replication in macrophages. In this study, we further confirm the requirement of CD63 in early HIV-1 replication events in both macrophages and a CD4{sup +} cell line. Further analysis revealed that viral attachment and cell-cell fusion were unaffected by CD63 silencing. However, CD63-depleted macrophages showed a significant decrease in the initiation and completion of HIV-1 reverse transcription, affecting subsequent events of the HIV-1 life cycle. Integration of HIV-1 cDNA as well as the formation of 2-LTR circles was notably reduced. Reporter assays showed that CD63 down regulation reduced production of the early HIV protein Tat. In agreement, CD63 silencing also inhibited production of the late protein p24. These findings suggest that CD63 plays an early post-entry role prior to or at the reverse transcription step.

Li Guangyu; Dziuba, Natallia; Friedrich, Brian [Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555-0435 (United States); Murray, James L. [Zirus, Inc., 1384 Buford Business Boulevard, Suite 700, Buford, GA 30518 (United States); Ferguson, Monique R., E-mail: mrfergus@utmb.ed [Department of Internal Medicine, Division of Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555-0435 (United States)

2011-04-10

20

Detection and early identification in bioterrorism events.  

PubMed

Syndromic surveillance, collecting and analyzing symptoms before diagnosis, has the potential to identify bioterrorist attacks in a timely, flexible, and specific manner. Nurses are important resources in collecting and interpreting surveillance data. Clinical skills in early diagnosis may identify a bioterrorist attack before surveillance systems and independently trigger investigations. Computerized syndromic surveillance systems are difficult to sustain and are not in use nationwide. Traditional public health surveillance is not replaced by syndromic surveillance. Weaknesses remain in surveillance related to bioterrorism preparedness. Bioterrorist events must be recognized in a timely manner, but this is dependent on sufficient funding for training, equipment, and personnel. PMID:18091080

Persell, Deborah J; Robinson, Carolyn H

21

Resolving Paradoxical Criteria for the Expansion and Replication of Early Childhood Care and Education Programs.  

ERIC Educational Resources Information Center

|Identifies underlying paradoxical bases for expansion and replication of early childhood care and education (ECCE) programs. Presents history of ECCE in the United States. Proposes typology of expansion and replication processes, and considers paradoxes associated with replication process. Offers recommendations for funders, policymakers, and…

Yoshikawa, Hirokazu; Rosman, Elisa Altman; Hsueh, JoAnn

2002-01-01

22

Replication of centromeric heterochromatin in mouse fibroblasts takes place in early, middle, and late S phase  

Microsoft Academic Search

The replication of eukaryotic chromosomes takes place throughout S phase, but little is known how this process is organized\\u000a in space and time. Early and late replicating chromosomal domains appear to localize to distinct spatial compartments of the\\u000a nucleus where DNA synthesis can take place at defined times during S phase. In general, transcriptionally active chromatin\\u000a replicates early in S

Stefanie Weidtkamp-Peters; Hans-Peter Rahn; M. Cristina Cardoso; Peter Hemmerich

2006-01-01

23

Giemsa staining of the sites replicating DNA early in human lymphocyte chromosomes  

Microsoft Academic Search

A timetable for the initiation of DNA replication in human lymphocyte chromosomes has been established by a technique which allows detection of areas of chromosomes replicating at a given interval of the S-phase. The resolution of the method, using 33258 Hoechst-Giemsa staining, is more refined than that obtained with 3H-thymidine autoradiography. Early replicating regions coincide with R-bands. The timetable is

My. A. Kim; R. Johannsmann; K.-H. Grzeschik

1975-01-01

24

Kinetochores coordinate pericentromeric cohesion and early DNA replication by Cdc7-Dbf4 kinase recruitment.  

PubMed

Centromeres play several important roles in ensuring proper chromosome segregation. Not only do they promote kinetochore assembly for microtubule attachment, but they also support robust sister chromatid cohesion at pericentromeres and facilitate replication of centromeric DNA early in S phase. However, it is still elusive how centromeres orchestrate all these functions at the same site. Here, we show that the budding yeast Dbf4-dependent kinase (DDK) accumulates at kinetochores in telophase, facilitated by the Ctf19 kinetochore complex. This promptly recruits Sld3-Sld7 replication initiator proteins to pericentromeric replication origins so that they initiate replication early in S phase. Furthermore, DDK at kinetochores independently recruits the Scc2-Scc4 cohesin loader to centromeres in G1 phase. This enhances cohesin loading and facilitates robust pericentromeric cohesion in S phase. Thus, we have found the central mechanism by which kinetochores orchestrate early S phase DNA replication and robust sister chromatid cohesion at microtubule attachment sites. PMID:23746350

Natsume, Toyoaki; Müller, Carolin A; Katou, Yuki; Retkute, Renata; Gierli?ski, Marek; Araki, Hiroyuki; Blow, J Julian; Shirahige, Katsuhiko; Nieduszynski, Conrad A; Tanaka, Tomoyuki U

2013-06-01

25

RELATIVE EFFICIENCY OF SPATIAL ANALYSES FOR NON-REPLICATED EARLY-STAGE SUGARCANE FIELD EXPERIMENTS  

Microsoft Academic Search

In the early stages of sugarcane (Saccharum spp.) selection programs, large numbers of clones are tested in non-replicated plots. Field trends are likely to affect the performance of these non-replicated experimental genotypes and mask their true genetic potential. The purpose of this study was to evaluate different spatial analyses for their relative efficiency in accounting for field trends in early-stage

S. J. Edmé; P. Y. P. Tai; J. D. Miller

26

Transcription and replication result in distinct epigenetic marks following repression of early gene expression.  

PubMed

Simian virus 40 (SV40) early transcription is repressed when the product of early transcription, T-antigen, binds to its cognate regulatory sequence, Site I, in the promoter of the SV40 minichromosome. Because SV40 minichromosomes undergo replication and transcription potentially repression could occur during active transcription or during DNA replication. Since repression is frequently epigenetically marked by the introduction of specific forms of methylated histone H3, we characterized the methylation of H3 tails during transcription and replication in wild-type SV40 minichromosomes and mutant minichromosomes which did not repress T-antigen expression. While repressed minichromosomes following replication were clearly marked with H3K9me1 and H3K4me1, minichromosomes repressed during early transcription were not similarly marked. Instead repression of early transcription was marked by a significant reduction in the level of H3K9me2. The replication dependent introduction of H3K9me1 and H3K4me1 into wild-type SV40 minichromosomes was also observed when replication was inhibited with aphidicolin. The results indicate that the histone modifications associated with repression can differ significantly depending upon whether the chromatin being repressed is undergoing transcription or replication. PMID:23914205

Kallestad, Les; Woods, Emily; Christensen, Kendra; Gefroh, Amanda; Balakrishnan, Lata; Milavetz, Barry

2013-07-30

27

Logistic regression applied to natural hazards: rare event logistic regression with replications  

NASA Astrophysics Data System (ADS)

Statistical analysis of natural hazards needs particular attention, as most of these phenomena are rare events. This study shows that the ordinary rare event logistic regression, as it is now commonly used in geomorphologic studies, does not always lead to a robust detection of controlling factors, as the results can be strongly sample-dependent. In this paper, we introduce some concepts of Monte Carlo simulations in rare event logistic regression. This technique, so-called rare event logistic regression with replications, combines the strength of probabilistic and statistical methods, and allows overcoming some of the limitations of previous developments through robust variable selection. This technique was here developed for the analyses of landslide controlling factors, but the concept is widely applicable for statistical analyses of natural hazards.

Guns, M.; Vanacker, V.

2012-06-01

28

Early events in geotropism of seedling shoots.  

PubMed

Developments during the first ten minutes of geotropic stimulation in plant seedling shoots are reviewed. Topics include induction and curvature; early processes; the relationship between auxin, electric field, calcium, and differential growth; gravity reception leading to Went-Cholodny transport; and comparison of root and shoot. Early processes reviewed are sedimentation of amyloplasts, release of ethylene, rise of electrical and auxin asymmetry, redistribution of calcium, asymmetric vascular transport, increase in tendency to deposit callose, and simulation of putative exocytotic voltage transients. PMID:11540829

Pickard, B G

1985-01-01

29

Early Reproductive Events and Breast Cancer  

Cancer.gov

The 11/25/2002 document below precedes an NCI workshop held in February 2003. This scientific workshop was held to present and review the available scientific data on reproductive events in a woman's life that may impact her subsequent risk of developing breast cancer. NCI has drawn on the outcomes of the February workshop to develop new, updated materials on this topic. See NCI's current fact sheet on Abortion, Miscarriage, and Breast Cancer Risk. Document posted: 11/25/2002

30

DNA replication origin interference increases the spacing between initiation events in human cells.  

PubMed

Mammalian DNA replication origins localize to sites that range from base pairs to tens of kilobases. A regular distribution of initiations in individual cell cycles suggests that only a limited number of these numerous potential start sites are converted into activated origins. Origin interference can silence redundant origins; however, it is currently unknown whether interference participates in spacing functional human initiation events. By using a novel hybridization strategy, genomic Morse code, on single combed DNA molecules from primary keratinocytes, we report the initiation sites present on 1.5 Mb of human chromosome 14q11.2. We confirm that initiation zones are widespread in human cells, map to intergenic regions, and contain sequence motifs found at other mammalian initiation zones. Origins used per cell cycle are less abundant than the potential sites of initiation, and their limited use increases the spacing between initiation events. Between-zone interference decreases in proportion to the distance from the active origin, whereas within-zone interference is 100% efficient. These results identify a hierarchical organization of origin activity in human cells. Functional origins govern the probability that nearby origins will fire in the context of multiple potential start sites of DNA replication, and this is mediated by origin interference. PMID:17005913

Lebofsky, Ronald; Heilig, Roland; Sonnleitner, Max; Weissenbach, Jean; Bensimon, Aaron

2006-09-27

31

DNA Replication Origin Interference Increases the Spacing between Initiation Events in Human Cells  

PubMed Central

Mammalian DNA replication origins localize to sites that range from base pairs to tens of kilobases. A regular distribution of initiations in individual cell cycles suggests that only a limited number of these numerous potential start sites are converted into activated origins. Origin interference can silence redundant origins; however, it is currently unknown whether interference participates in spacing functional human initiation events. By using a novel hybridization strategy, genomic Morse code, on single combed DNA molecules from primary keratinocytes, we report the initiation sites present on 1.5 Mb of human chromosome 14q11.2. We confirm that initiation zones are widespread in human cells, map to intergenic regions, and contain sequence motifs found at other mammalian initiation zones. Origins used per cell cycle are less abundant than the potential sites of initiation, and their limited use increases the spacing between initiation events. Between-zone interference decreases in proportion to the distance from the active origin, whereas within-zone interference is 100% efficient. These results identify a hierarchical organization of origin activity in human cells. Functional origins govern the probability that nearby origins will fire in the context of multiple potential start sites of DNA replication, and this is mediated by origin interference.

Lebofsky, Ronald; Heilig, Roland; Sonnleitner, Max; Weissenbach, Jean

2006-01-01

32

Role of the Proximal Enhancer of the Major Immediate-Early Promoter in Human Cytomegalovirus Replication  

Microsoft Academic Search

The human cytomegalovirus (CMV) enhancer has a distal component (positions 550 to 300) and a proximal component (300 to 39) relative to the transcription start site (1) of the major immediate-early (MIE) promoter. Without the distal enhancer, human CMV replicates slower and has a small-plaque pheno- type. We determined the sequence requirements of the proximal enhancer by making 5? -end

Hiroki Isomura; Tatsuya Tsurumi; Mark F. Stinski

2004-01-01

33

Impairment of Human Immunodeficiency Virus Type-1 Integrase SUMOylation Correlates with an Early Replication Defect*  

PubMed Central

HIV-1 integrase (IN) orchestrates the integration of the reverse transcribed viral cDNA into the host cell genome and participates also in other steps of HIV-1 replication. Cellular and viral factors assist IN in performing its multiple functions, and post-translational modifications contribute to modulate its activities. Here, we show that HIV-1 IN is modified by SUMO proteins and that phylogenetically conserved SUMOylation consensus motifs represent major SUMO acceptor sites. Viruses harboring SUMOylation site IN mutants displayed a replication defect that was mapped during the early stages of infection, before integration but after reverse transcription. Because SUMOylation-defective IN mutants retained WT catalytic activity, we hypothesize that SUMOylation might regulate the affinity of IN for co-factors, contributing to efficient HIV-1 replication.

Zamborlini, Alessia; Coiffic, Audrey; Beauclair, Guillaume; Delelis, Olivier; Paris, Joris; Koh, Yashuiro; Magne, Fabian; Giron, Marie-Lou; Tobaly-Tapiero, Joelle; Deprez, Eric; Emiliani, Stephane; Engelman, Alan; de The, Hugues; Saib, Ali

2011-01-01

34

Differential assembly of Cdc45p and DNA polymerases at early and late origins of DNA replication  

PubMed Central

Chromosomes are replicated in characteristic, temporal patterns during S phase. We have compared the timing of association of replication proteins at early- and late-replicating origins of replication. Minichromosome maintenance proteins assemble simultaneously at early- and late-replicating origins. In contrast, Cdc45p association with late origins is delayed relative to early origins. DNA polymerase ? association is similarly delayed at late origins and requires Cdc45p function. Activation of the S phase checkpoint inhibits association of Cdc45p with late-firing origins. These studies suggest that Cdc45p is poised to serve as a key regulatory target for both the temporal and checkpoint-mediated regulation of replication origins.

Aparicio, Oscar M.; Stout, Anita M.; Bell, Stephen P.

1999-01-01

35

Investigation of the Effects of G9a Knockout on Subnuclear Localization and Replication Timing of G9a Repressed Genes When Integrated into an Early Replicating Region  

Microsoft Academic Search

G9a is a histone methyltransferase that is responsible for dimethylation of histone 3 lysine 9 (H3K9me2) this chromatin marker is typically associated with transcriptional silencing. Following conditional knockout of G9a in mouse embryonic stem cells, genes that are regulated by G9a are strongly upregulated. Typically genes that replicate late in S-phase are transcriptionally repressed while genes that replicate early in

Kristina Poduch

2010-01-01

36

The early secretory pathway contributes to the growth of the Coxiella-replicative niche.  

PubMed

Coxiella burnetii is a Gram-negative obligate intracellular bacterium. After internalization, this bacterium replicates in a large parasitophorous vacuole that has features of both phagolysosomes and autophagosomal compartments. We have previously demonstrated that early after internalization Coxiella phagosomes interact with both the endocytic and the autophagic pathways. In this report, we present evidence that the Coxiella-replicative vacuoles (CRVs) also interact with the secretory pathway. Rab1b is a small GTPase responsible for the anterograde transport between the endoplasmic reticulum and the Golgi apparatus. We present evidence that Rab1b is recruited to the CRV at later infection times (i.e., after 6 h of infection). Interestingly, knockdown of Rab1b altered vacuole growth, indicating that this protein was required for the proper biogenesis of the CRV. In addition, overexpression of the active GTPase-defective mutant (GFP-Rab1b Q67L) affected the development of the Coxiella-replicative compartment inhibiting bacterial growth. On the other hand, disruption of the secretory pathway by brefeldin A treatment or by overexpression of Sar1 T39N, a defective dominant-negative mutant of Sar1, affected the typical spaciousness of the CRVs. Taken together, our results show for the first time that the Coxiella-replicative niche also intercepts the early secretory pathway. PMID:20937765

Campoy, Emanuel Martín; Zoppino, Felipe Carlos Martín; Colombo, María Isabel

2010-10-11

37

The Early Secretory Pathway Contributes to the Growth of the Coxiella-Replicative Niche? †  

PubMed Central

Coxiella burnetii is a Gram-negative obligate intracellular bacterium. After internalization, this bacterium replicates in a large parasitophorous vacuole that has features of both phagolysosomes and autophagosomal compartments. We have previously demonstrated that early after internalization Coxiella phagosomes interact with both the endocytic and the autophagic pathways. In this report, we present evidence that the Coxiella-replicative vacuoles (CRVs) also interact with the secretory pathway. Rab1b is a small GTPase responsible for the anterograde transport between the endoplasmic reticulum and the Golgi apparatus. We present evidence that Rab1b is recruited to the CRV at later infection times (i.e., after 6 h of infection). Interestingly, knockdown of Rab1b altered vacuole growth, indicating that this protein was required for the proper biogenesis of the CRV. In addition, overexpression of the active GTPase-defective mutant (GFP-Rab1b Q67L) affected the development of the Coxiella-replicative compartment inhibiting bacterial growth. On the other hand, disruption of the secretory pathway by brefeldin A treatment or by overexpression of Sar1 T39N, a defective dominant-negative mutant of Sar1, affected the typical spaciousness of the CRVs. Taken together, our results show for the first time that the Coxiella-replicative niche also intercepts the early secretory pathway.

Campoy, Emanuel Martin; Zoppino, Felipe Carlos Martin; Colombo, Maria Isabel

2011-01-01

38

Neurogenesis requires TopBP1 to prevent catastrophic replicative DNA damage in early progenitors  

PubMed Central

The rapid proliferation of progenitors during neurogenesis requires a stringent genomic maintenance program to ensure transmission of genetic fidelity. However the essential factors that govern neural progenitor genome integrity are unknown. Here we report that conditional inactivation of mouse TopBP1, a protein linked to DNA replication, and a key activator of the DNA damage response kinase ATR (ataxia telangiectasia and rad3 related) is critical for maintenance of early-born neural progenitors. During cortical development TopBP1 prevented replication-associated DNA damage in Emx1-progenitors which otherwise resulted in profound tissue ablation. Importantly, disrupted neurogenesis in TopBP1-depleted tissues was substantially rescued by p53- but not ATM-inactivation. Our data establish that TopBP1 is essential for preventing replication-associated DNA strand breaks, but is not essential per se for DNA replication. Thus, TopBP1 is crucial for maintaining genome integrity in the early progenitors that drive neurogenesis.

Lee, Youngsoo; Katyal, Sachin; Downing, Susanna M.; Zhao, Jingfeng; Russell, Helen R.; McKinnon, Peter J.

2012-01-01

39

On the Relativistic Electron Injection Event in Early April 2010  

NASA Astrophysics Data System (ADS)

Beginning in early 2008, the MeV electron population in the Earth's radiation belts began declining and reached an unprecedented low in the autumn. This minimum continued until early April 2010 when a large relativistic electron injection event occurred. An extraordinary feature of this event was that high intensities of multi-MeV electrons extended out to beyond L=7, and the energy spectrum was very hard, extending to several MeV. Observations are available from many spacecraft including HEO1 & HEO3, ICO-F2, SAMPEX, and GOES. Also data are available from several GOES spacecraft including observations with the HEPAD sensors that give clear evidence that the electron energies extended to above 10 MeV. These data and other information on the state of the magnetosphere suggest that loss processes were subdued during this time period, enabling the magnetospheric electron accelerator to operate effectively over an extended time period

Blake, J. B.; OBrien, P.; Rodriguez, J. V.; Green, J. C.

2011-12-01

40

Early events induced by chitosan on plant cells  

Microsoft Academic Search

Chitosan (a polymer of b-1,4-glucosamine residues) is a deacetylated derivative of chitin which presents antifungal properties and acts as a potent elicitor of plant resistance against fungal pathogens. Attention was focused in this study on the chitosan-induced early events in the elicitation chain. Thus, it was shown that chitosan triggered in a dose-dependent manner rapid membrane transient depolarization of Mimosa

Benigne-Ernest Amborabe; Janine Bonmort; Pierrette Fleurat-Lessard; Gabriel Roblin

2008-01-01

41

Nigericin is a potent inhibitor of the early stage of vaccinia virus replication.  

PubMed

Poxviruses remain a significant public health concern due to their potential use as bioterrorist agents and the spread of animal borne poxviruses, such as monkeypox virus, to humans. Thus, the identification of small molecule inhibitors of poxvirus replication is warranted. Vaccinia virus is the prototypic member of the Orthopoxvirus genus, which also includes variola and monkeypox virus. In this study, we demonstrate that the carboxylic ionophore nigericin is a potent inhibitor of vaccinia virus replication in several human cell lines. In HeLa cells, we found that the 50% inhibitory concentration of nigericin against vaccinia virus was 7.9 nM, with a selectivity index of 1038. We present data demonstrating that nigericin targets vaccinia virus replication at a post-entry stage. While nigericin moderately inhibits both early vaccinia gene transcription and translation, viral DNA replication and intermediate and late gene expression are severely compromised in the presence of nigericin. Our results demonstrate that nigericin has the potential to be further developed into an effective antiviral to treat poxvirus infections. PMID:20951746

Myskiw, Chad; Piper, Jessica; Huzarewich, Rhiannon; Booth, Tim F; Cao, Jingxin; He, Runtao

2010-10-15

42

Early events regulating immunity and pathogenesis during Listeria monocytogenes infection.  

PubMed

Listeria monocytogenes (Lm) is both a life-threatening pathogen of humans and a model organism that is widely used to dissect the mechanisms of innate and adaptive immune resistance to infection. Specific aspects of the immune response to systemic Lm infection can be protective, neutral, or in some cases deleterious. In this review, we seek to provide an overview of the early events during Lm infection that dictate or regulate host innate and adaptive immune responses. We highlight several recent developments that add to our understanding of the complex interplay between inflammatory responses, host susceptibility to infection, and the development of protective immunity. PMID:22677184

Williams, Matthew A; Schmidt, Rebecca L; Lenz, Laurel L

2012-06-05

43

Early events regulating immunity and pathogenesis during Listeria monocytogenes infection  

PubMed Central

Listeria monocytogenes is both a life-threatening pathogen of humans and a model organism that is widely used to dissect the mechanisms of innate and adaptive immune resistance to infection. Specific aspects of the immune response to systemic Lm infection can be protective, neutral, or in some cases deleterious. In this review, we seek to provide an overview of the early events during Lm infection that dictate or regulate host innate and adaptive immune responses. We highlight several recent developments that add to our understanding of the complex interplay between inflammatory responses, host susceptibility to infection, and the development of protective immunity.

Williams, Matthew A.; Schmidt, Rebecca L.

2012-01-01

44

The Hemagglutinin Protein of Highly Pathogenic H5N1 Influenza Viruses Overcomes an Early Block in the Replication Cycle To Promote Productive Replication in Macrophages  

PubMed Central

Macrophages are known to be one of the first lines of defense against influenza virus infection. However, they may also contribute to severe disease caused by the highly pathogenic avian (HPAI) H5N1 influenza viruses. One reason for this may be the ability of certain influenza virus strains to productively replicate in macrophages. However, studies investigating the productive replication of influenza viruses in macrophages have been contradictory, and the results may depend on both the type of macrophages used and the specific viral strain. In this work, we investigated the ability of H1 to H16 viruses to productively replicate in primary murine alveolar macrophages and RAW264.7 macrophages. We show that only a subset of HPAI H5N1 viruses, those that cause high morbidity and mortality in mammals, can productively replicate in macrophages, as measured by the release of newly synthesized virus particles into the cell supernatant. Mechanistically, we found that these H5 strains can overcome a block early in the viral life cycle leading to efficient nuclear entry, viral transcription, translation, and ultimately replication. Studies with reassortant viruses demonstrated that expression of the hemagglutinin gene from an H5N1 virus rescued replication of H1N1 influenza virus in macrophages. This study is the first to characterize H5N1 influenza viruses as the only subtype of influenza virus capable of productive replication in macrophages and establishes the viral gene that is required for this characteristic. The ability to productively replicate in macrophages is unique to H5N1 influenza viruses and may contribute to their increased pathogenesis.

Cline, Troy D.; Karlsson, Erik A.; Seufzer, Bradley J.

2013-01-01

45

DNA replication initiates at different sites in early and late S phase within human ribosomal RNA genes.  

PubMed

Metazoan replication origins often contain multiple potential initiation sites, and the selection of which of the potential sites are used appears to be dependent upon multiple factors, including the state of differentiation, cell metabolism, and local transcriptional activity. Numerous studies have shown that a replication origin exists within the non-transcribed spacer region of the human ribosomal RNA gene. We here analyze nascent leading strand DNA from S phase human lymphoid cells, and find that while the majority of rDNA replicates in mid- and late S phase and preferentially initiates replication 6 kbp from the transcription start site, in very early S phase the preferred initiation site is much closer to the transcription start site and may involve rDNA promoter sequences. This early site is coincident with a minimum GC skew value, diagnostic for replication origins in bacteria and yeast. These results suggest that replication timing can influence initiation site selection. The timing and nucleolar localization of rDNA further suggest that this site likely participates in the small number of perinucleolar initiation foci observed in very early S phase cells that represent the beginning of cellular DNA replication. PMID:16082215

Coffman, Frederick D; He, Mai; Diaz, Mai-Ling; Cohen, Stanley

2005-09-22

46

Astronomical forcing and chronology of the early Toarcian (Early Jurassic) oceanic anoxic event in Yorkshire, UK  

NASA Astrophysics Data System (ADS)

During the early Toarcian (˜183 Ma ago), a high rate of organic carbon burial globally over a brief interval of time has led to the recognition of a major oceanic anoxic event (OAE). A pronounced negative excursion in the carbon-isotope composition of marine organic matter, marine carbonate and terrestrial plant material is a key feature of this event but the precise timescale and cause(s) of this isotopic anomaly are debated. Associated with the negative carbon-isotope excursion is evidence for a coeval rise in seawater palaeotemperature, an increase in continental weathering rates, and the mass extinction of marine invertebrate species. The early Toarcian OAE provides evidence for the Earth's response during rapid climate change, and critical to our understanding of the event is a high-resolution timescale that allows us to quantify the rates, duration and lead/lag times of environmental processes. In this study, we present 2743 new high-resolution organic carbon, sulphur and carbonate concentration data from samples of well-preserved organic-rich mudrocks spanning the early Toarcian OAE in Yorkshire, UK. We have used these data to document the geochemical changes and significantly extend and refine the astronomical timescale across this event. Our detailed analysis of the relationship between astronomical forcing and carbon isotope changes in both Yorkshire and a section from Peniche, Portugal, indicates that astronomical forcing paced the timing of major shifts in ?13C and hence climate in both sections. Our analyses also demonstrate that there was a marked increase in the relative strength of astronomical forcing recorded at the onset of the OAE, and that the recorded nature of astronomical forcing changed during the event. Both the Yorkshire and Peniche cyclostratigraphies suggest that one astronomical forcing parameter paced environmental change through the ?13C event, and that this parameter was obliquity or precession.

Kemp, David B.; Coe, Angela L.; Cohen, Anthony S.; Weedon, Graham P.

2011-11-01

47

Early Low-Titer Neutralizing Antibodies Impede HIV-1 Replication and Select for Virus Escape  

PubMed Central

Single genome sequencing of early HIV-1 genomes provides a sensitive, dynamic assessment of virus evolution and insight into the earliest anti-viral immune responses in vivo. By using this approach, together with deep sequencing, site-directed mutagenesis, antibody adsorptions and virus-entry assays, we found evidence in three subjects of neutralizing antibody (Nab) responses as early as 2 weeks post-seroconversion, with Nab titers as low as 1?20 to 1?50 (IC50) selecting for virus escape. In each of the subjects, Nabs targeted different regions of the HIV-1 envelope (Env) in a strain-specific, conformationally sensitive manner. In subject CH40, virus escape was first mediated by mutations in the V1 region of the Env, followed by V3. HIV-1 specific monoclonal antibodies from this subject mapped to an immunodominant region at the base of V3 and exhibited neutralizing patterns indistinguishable from polyclonal antibody responses, indicating V1–V3 interactions within the Env trimer. In subject CH77, escape mutations mapped to the V2 region of Env, several of which selected for alterations of glycosylation. And in subject CH58, escape mutations mapped to the Env outer domain. In all three subjects, initial Nab recognition was followed by sequential rounds of virus escape and Nab elicitation, with Nab escape variants exhibiting variable costs to replication fitness. Although delayed in comparison with autologous CD8 T-cell responses, our findings show that Nabs appear earlier in HIV-1 infection than previously recognized, target diverse sites on HIV-1 Env, and impede virus replication at surprisingly low titers. The unexpected in vivo sensitivity of early transmitted/founder virus to Nabs raises the possibility that similarly low concentrations of vaccine-induced Nabs could impair virus acquisition in natural HIV-1 transmission, where the risk of infection is low and the number of viruses responsible for transmission and productive clinical infection is typically one.

Bar, Katharine J.; Tsao, Chun-yen; Iyer, Shilpa S.; Decker, Julie M.; Yang, Yongping; Bonsignori, Mattia; Chen, Xi; Hwang, Kwan-Ki; Montefiori, David C.; Liao, Hua-Xin; Hraber, Peter; Fischer, William; Li, Hui; Wang, Shuyi; Sterrett, Sarah; Keele, Brandon F.; Ganusov, Vitaly V.; Perelson, Alan S.; Korber, Bette T.; Georgiev, Ivelin; McLellan, Jason S.; Pavlicek, Jeffrey W.; Gao, Feng; Haynes, Barton F.; Hahn, Beatrice H.; Kwong, Peter D.; Shaw, George M.

2012-01-01

48

Early viral replication in lymph nodes provides HIV with a means by which to escape NK-cell-mediated control.  

PubMed

Acute HIV infection is marked by dramatic viral replication associated with preferential replication within secondary lymphoid tissues, such as lymph nodes (LNs), that is rapidly but incompletely contained to a viral setpoint. Accumulating evidence supports a role for natural killer (NK) cells in the early control of HIV infection; however, little is known about the location of their antiviral control. Given that HIV replicates profusely in LNs during early infection, we sought to define whether changes occurred in the NK cell infiltrate within these sites during the first year of HIV infection. Surprisingly, NK cell numbers and distribution were unaltered during early HIV infection. LN NK cells expressed decreased inhibitory receptors, were more highly activated, and expressed elevated TRAIL, potentially conferring a superior capacity for NK cells to become activated and control infection. Most noticeably, KIR(+) NK cells were rarely detected in the LN during HIV infection, associated with diminished migratory capacity in the setting of reduced expression of CX3CR1 and CXCR1. Thus, incomplete control of HIV viral replication during early disease may be due to the inefficient recruitment of KIR(+) NK cells to this vulnerable site, providing HIV a niche where it can replicate unabated by early NK-cell-mediated innate pressure. PMID:21630248

Luteijn, Rutger; Sciaranghella, Gaia; van Lunzen, Jan; Nolting, Anne; Dugast, Anne-Sophie; Ghebremichael, Musie S; Altfeld, Marcus; Alter, Galit

2011-08-12

49

Ant-based query processing for replicated events in wireless sensor networks  

Microsoft Academic Search

Wireless sensor networks are often deployed in diverse application specific contexts and one unifying view is to treat them essentially as distributed databases. The simplest mechanism to obtain information from this kind of database is to flood queries for named data within the network and obtain the relevant responses from sources. However, if the queries are issued for replicated data,

Jianping Yu; Yaping Lin; Jinhua Zheng

2008-01-01

50

Replicative mechanisms of CNV formation preferentially occur as intrachromosomal events: evidence from Potocki-Lupski duplication syndrome.  

PubMed

Copy number variations (CNVs) in the human genome contribute significantly to disease. De novo CNV mutations arise via genomic rearrangements, which can occur in 'trans', i.e. via interchromosomal events, or in 'cis', i.e. via intrachromosomal events. However, what molecular mechanisms occur between chromosomes versus between or within chromatids has not been systematically investigated. We hypothesized that distinct CNV mutational mechanisms, based on their intrinsic properties, may occur in a biased intrachromosomal versus interchromosomal manner. Here, we studied 62 genomic duplications observed in association with sporadic Potocki-Lupski syndrome (PTLS), in which multiple mutational mechanisms appear to be operative. Intriguingly, more interchromosomal than intrachromosomal events were identified in recurrent PTLS duplications mediated by non-allelic homologous recombination, whereas the reciprocal distribution was found for replicative mechanisms and non-homologous end-joining, likely reflecting the differences in spacial proximity of homologous chromosomes during different mutational processes. PMID:23161748

Sun, Zhe; Liu, Pengfei; Jia, Xueyuan; Withers, Marjorie A; Jin, Li; Lupski, James R; Zhang, Feng

2012-11-16

51

Early growth response 1 protein, an upstream gatekeeper of the p53 tumor suppressor, controls replicative senescence  

PubMed Central

The proliferation of most primary cells in culture is limited by replicative senescence and crisis, p53-dependent events. However, the regulation of p53 itself has not been defined. We find that deletion of the early growth response 1 (EGR1) transcription factor leads to a striking phenotype, including complete bypass of senescence and apparent immortal growth consistent with loss of a suppressor gene. EGR1-null mouse embryo fibroblasts (MEFs) exhibit decreased expression of p53, p21Cip1/Waf1, and other p53 “marker” proteins. Precrisis WT but not EGR1-null cells exhibit irradiation-induced arrest. WT MEFs that emerge from crisis exhibit a mutated p53 (sequence confirmed), colony formation, and tumorigenicity. In contrast, high-passage EGR1-null MEFs retain the WT p53 sequence but with much reduced expression, remain untransformed, and grow continuously. An EGR1-expressing retrovirus restores p53 expression and sencescence to EGR1-null but not p53-null MEFs or postcrisis WT cells. Taken together, the results establish EGR1 as a major regulator of cell senescence and previously undescribed upstream “gatekeeper” of the p53 tumor suppressor pathway.

Krones-Herzig, Anja; Adamson, Eileen; Mercola, Dan

2003-01-01

52

Early- and Intermediate-Stage Variants of Simian Immunodeficiency Virus Replicate Efficiently in Cells Lacking CCR5  

PubMed Central

Primate lentiviruses are thought to use the chemokine receptor CCR5 as the major coreceptor for entry into cells. Here we show that some variants of simian immunodeficiency virus (SIV) replicate efficiently in peripheral blood mononuclear cells (PBMCs) lacking a functional CCR5. There were differences in the replication patterns of sequential variants that evolved during SIVMne infection; the late-stage pathogenic variants were unable to replicate in PBMCs lacking CCR5, whereas the early- and intermediate-stage viruses replicated as well in PBMCs lacking CCR5 as they did in cells with wild-type CCR5. The coreceptor specificities of these sequential variants were compared using indicator cell lines expressing known SIV coreceptors. Among the known SIV coreceptors, there were none that were functional for the early and intermediate variants but not the late-stage variants, suggesting that the coreceptor used for replication in PBMCs may be a coreceptor that has not yet been described. Because some variants replicate with high efficiency in peripheral blood cells using this as yet uncharacterized cellular receptor, this coreceptor may be important for viral entry of some target cell populations in the host.

Forte, Serene; Harmon, Mary-Elizabeth; Pineda, Mario J.; Overbaugh, Julie

2003-01-01

53

The sperm centriole: its inheritance, replication and perpetuation in early human embryos.  

PubMed

The inheritance, replication and perpetuation of the sperm centriole in the early human embryo are reported. Both normal monospermic and abnormal dispermic embryos (n = 127) were examined by transmission electron microscopy. Centrioles were traced from fertilization to the hatching blastocyst stage. The sperm proximal centriole is introduced into the oocyte at fertilization and remains attached to the expanding spermhead during sperm nuclear decondensation, as it forms the male pronucleus. A sperm aster is initially formed after the centriole duplicates at the pronuclear stage. At syngamy, centrioles occupy a pivotal position on opposite spindle poles, when the first mitotic figure is formed. Bipolar spindles were found in the majority of embryos, while tripolar spindles were seen in four dispermic embryos at syngamy. Two single centrioles were detected at two poles of two tripolar spindles, while two additional centrioles were located on the sides of a bipolar spindle of a dispermic embryo. Sperm tails were detected near spindle poles at syngamy and in later embryos. Typical centrioles showing the characteristic pin-wheel organization of nine triplets of microtubules were evident. During centriolar replication, the daughter centriole grows laterally from the parent and gradually acquires pericentriolar material (PCM). The two centrioles are surrounded by a halo of electron-dense PCM, which nucleates microtubules, thus making it a typical centrosome. The usual alignment of diplosomes at right angles to each other was maintained. Centrioles were detected at all stages of embryonic cleavage from the 1-cell through 8-cell stages, right up to the hatching blastocyst stage. They were closely associated with nuclei at interphase, when they were often replicating, and were prominently located at spindle poles during the first four cell cycles. In blastocysts, they were detected in trophoblast, embryoblast and endoderm cells respectively. It is evident that the sperm centrosome is the functional active centrosome in human, while the female is inactive but may contribute some centrosomal material to the zygote centrosome. It is very likely that the paternal centriole is the ancestor of the centrioles in fetal and adult somatic cells. PMID:8671223

Sathananthan, A H; Ratnam, S S; Ng, S C; Tarín, J J; Gianaroli, L; Trounson, A

1996-02-01

54

Early arrival of Southern Source Water in the deep North Atlantic prior to Heinrich event 2  

Microsoft Academic Search

North Atlantic Deep Water ventilated the deep N Atlantic during early MIS 2Deep and intermediate water changes preceded Heinrich event 2Heinrich event 2 was the result and not the cause for AMOC changes

Marcus Gutjahr; Jörg Lippold

2011-01-01

55

Effect of deletions in adenovirus early region 1 genes upon replication of adeno-associated virus.  

PubMed Central

The growth of adeno-associated virus (AAV) is dependent upon helper functions provided by adenovirus. We investigated the role of adenovirus early gene region 1 in the AAV helper function by using six adenovirus type 5 (Ad5) host range mutants having deletions in early region 1. These mutants do not grow in human KB cells but are complemented by and grow in a line of adenovirus-transformed human embryonic kidney cells (293 cells); 293 cells contain and express the Ad5 early region 1 genes. Mutants having extensive deletions of adenovirus early region 1a (dl312) or regions 1a and 1b (dl313) helped AAV as efficiently as wild-type adenovirus in 293 cells, but neither mutant helped in KB cells. No AAV DNA, RNA, or protein synthesis was detected in KB cells in the presence of the mutant adenoviruses. Quantitative blotting experiments showed that at 20 h after infection with AAV and either dl312 or dl313 there was less than one AAV genome per cell. In KB cells infected with AAV alone, the unreplicated AAV genomes were detected readily. Apparently, infection with adenovirus mutant dl312 or dl313 results in degradation of most of the infecting AAV genomes. We suggest that at least an adenovirus region 1b product (and perhaps a region 1a product also) is required for AAV DNA replication. This putative region 1b function appears to protect AAV DNA from degradation by an adenovirus-induced DNase. We also tested additional Ad5 mutants (dl311, dl314, sub315, and sub316). All of these mutants were inefficient helpers, and they showed varying degrees of multiplicity leakiness. dl312 and dl313 complemented each other for the AAV helper function, and each was complemented by Ad5ts125 at the nonpermissive temperature. The defect in region 1 mutants for AAV helper function acts at a different stage of the AAV growth cycle than the defect in the region 2 mutant ts125. Images

Laughlin, C A; Jones, N; Carter, B J

1982-01-01

56

EXAMINING THE STRUCTURE OF THE SCHEDULE OF SEXIST EVENTS: REPLICATION AND EXTENSION  

Microsoft Academic Search

The current study reexamined the factor structure of the Lifetime and Recent scales of the Schedule of Sexist Events (SSE; Klonoff & Landrine, 1995) and conducted the first factor analysis of the SSE-Appraisal scale (Landrine & Klonoff, 1997). Factor analyses conducted with data from 245 women yielded, for SSE-Lifetime and SSE-Appraisal scales, two reliable factors that can be scored as

Alicia V. Matteson; Bonnie Moradi

2005-01-01

57

APOBEC3G restricts early HIV-1 replication in the cytoplasm of target cells  

SciTech Connect

Cellular APOBEC3G (A3G) protein is packaged into human immunodeficiency virus type 1 (HIV-1) virions in producer cells yet restricts viral replication in target cells. To characterize this restriction in target cells, the effect of A3G on generating various HIV-1 cDNA products was measured by quantitative real-time PCR. A3G decreased cDNA products from Vif-deficient HIV-1, with minor effects on early reverse transcripts and larger declines in late reverse transcripts. However, the greatest decline was typically observed in nuclear 2-LTR circles. Moreover, the magnitude of these declines varied with A3G dose. Adding integration inhibitor did not stop the A3G-mediated loss in 2-LTR circles. Moreover, obstructing HIV-1 nuclear entry using vesicular stomatitis virus matrix protein did not stop the A3G-mediated decline in late reverse transcripts. Collectively, these data suggest that A3G has important restriction activity in the cytoplasm and progressively diminishes viral cytoplasmic and nuclear cDNA forms with increasing magnitude during restriction.

Anderson, Jenny L. [Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (United States); Hope, Thomas J. [Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (United States)], E-mail: thope@northwestern.edu

2008-05-25

58

Inhibition of S-phase cyclin-dependent kinase activity blocks expression of Epstein-Barr virus immediate-early and early genes, preventing viral lytic replication.  

PubMed

The induction of lytic replication of the Epstein-Barr virus (EBV) completely arrests cell cycle progression, in spite of elevation of S-phase cyclin-dependent kinase (CDK) activity, thereby causing accumulation of hyperphosphorylated forms of retinoblastoma (Rb) protein (A. Kudoh, M. Fujita, T. Kiyono, K. Kuzushima, Y. Sugaya, S. Izuta, Y. Nishiyama, and T. Tsurumi, J. Virol. 77:851-861, 2003). Thus, the EBV lytic program appears to promote specific cell cycle-associated activity involved in the progression from G1 to S phase. We have proposed that this provides a cellular environment that is advantageous for EBV productive infection. Purvalanol A and roscovitine, inhibitors of S-phase CDKs, blocked the viral lytic replication when cells were treated at the early stage of lytic infection, while well-characterized inhibitors of enzymes, such as mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase C, known to be involved in BZLF1 gene expression did not. Inhibition of CDK activity resulted in the accumulation of the hypophosphorylated form of Rb protein and inhibition of expression of EBV immediate-early and early proteins. Cycloheximide block-and-release experiments clearly demonstrated that even in the presence of enough amounts of the BZLF1 protein, purvalanol A blocked expression of lytic viral proteins at transcription level. Furthermore, reporter gene experiments confirmed that BZLF1-induced activation of early EBV promoters was impaired in the presence of the CDK inhibitor. We conclude here that the EBV lytic program promotes specific cell cycle-associated activity involved in the progression from G1 to S phase because the S-phase-like cellular environment is essential for the expression of immediate-early and early genes supplying the viral replication proteins and hence for lytic viral replication. PMID:14671092

Kudoh, Ayumi; Daikoku, Tohru; Sugaya, Yutaka; Isomura, Hiroki; Fujita, Masatoshi; Kiyono, Tohru; Nishiyama, Yukihiro; Tsurumi, Tatsuya

2004-01-01

59

Human cytomegalovirus DNA replicates after early circularization by concatemer formation, and inversion occurs within the concatemer.  

PubMed Central

To determine the replicative mechanism for human cytomegalovirus (HCMV) DNA, field inversion gel electrophoresis was used to separate HCMV replicative DNAs during lytic infection. Unit-length circular HCMV genomes lacking terminal restriction fragments were detected starting 4 h after infection even when cells were treated with aphidicolin, phosphonoacetic acid, or cycloheximide. Viral DNA synthesis began 24 h after infection and produced large amounts of high-molecular-weight replicative DNA that was a precursor of progeny genomes. Replicative DNA contained rare terminal restriction fragments, and long-arm termini were much less frequent than short-arm termini. Replicative DNA was not composed of unit-length circles because low-dose gamma irradiation of replicative DNA generated numerous random high-molecular-weight fragments rather than unit-length molecules. PacI digestion of replicative DNA from a recombinant HCMV with two closely spaced PacI sites revealed that replicative DNA is concatemeric and genome segment inversion occurs after concatemer synthesis. These results show that after circularization of the parental genome, DNA synthesis produces concatemers and genomic inversion occurs within concatemeric DNA. The results further suggest that concatemers acquire genomic termini during the cleavage/packaging process which preferentially inserts short-arm termini into empty capsids, causing a predominance of short-arm termini on the concatemer. Images

McVoy, M A; Adler, S P

1994-01-01

60

An EAS event observed in the early stage of development  

NASA Astrophysics Data System (ADS)

Since 1969 the experiments of Brazil-Japan Collaboration showed the occurrence of a series of events, showing a region with a high concentration of electromagnetic particles, surrounded by isolated and/or groups of showers. These events were named “halo events” or “super-families”. Currently, we have more than a dozen of such events. The first of them, due to its aspect, was named “Andromeda”. We present here the main characteristics of a similar halo event, named C21S087I075. It has a halo region with many high energy showers in its border. Other small energy showers spread over the central and surrounding blocks (S088, S100, S101, I074). These isolated showers, classified as of hadronic or electromagnetic origin, present a fractional energy distribution compatible with that of a Centauro candidate event (C16S087I037), reported at this symposium [S.L.C. Barroso, P.C. Beggio, J.A. Chinellato, A.O. Carvalho, A. Mariano, R. Oliveira, E.H. Shibuya, in this issue of XIV ISVHECRI]. Moreover, the lateral distribution in the halo region is similar to that observed in other 3 halo events.

Brazil-JAPAN Collaboration Of Chacaltaya Emulsion Chamber Experiment; Beggio, P. C.; de Carvalho, A. O.; Chinellato, J. A.; Mariano, A.; de Oliveira, R.; Shibuya, E. H.

2008-01-01

61

Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages  

PubMed Central

Background Macrophages, which are CD4 and CCR5 positive, can sustain HIV-1 replication for long periods of time. Thus, these cells play critical roles in the transmission, dissemination and persistence of viral infection. Of note, current antiviral therapies do not target macrophages efficiently. Previously, it was demonstrated that interactions between CCR5 and gp120 stimulate PKC. However, the PKC isozymes involved were not identified. Results In this study, we identified PKC-delta as a major cellular cofactor for HIV-1 replication in macrophages. Indeed, PKC-delta was stimulated following the interaction between the virus and its target cell. Moreover, inhibition of PKC-delta blocked the replication of R5-tropic viruses in primary human macrophages. However, this inhibition did not have significant effects on receptor and co-receptor expression or fusion. Additionally, it did not affect the formation of the early reverse transcription product containing R/U5 sequences, but did inhibit the synthesis of subsequent cDNAs. Importantly, the inhibition of PKC-delta altered the redistribution of actin, a cellular cofactor whose requirement for the completion of reverse transcription was previously established. It also prevented the association of the reverse transcription complex with the cytoskeleton. Conclusion This work highlights the importance of PKC-delta during early steps of the replicative cycle of HIV-1 in human macrophages.

2012-01-01

62

Childhood amnesia: on answering questions about very early life events.  

PubMed

Twenty five young adults were asked about the events surrounding the birth of a younger sibling which took place when they were under the age of 2 years. Approximately 40% of the participants claimed to have significant memories of the events. The mothers of our participants verified that a majority of their answers were accurate. Comparing the pattern of data with those previously collected (Eacott & Crawley, 1998) suggests that the memories of those who were aged below 2:0 are qualitatively similar to the memories of those who were older at the time of events and dissimilar in type to those who are basing their reports on reconstructions from family knowledge. This finding may be evidence that memories of events that occurred before the age of 2 years are genuine but rare. This conclusion may be useful in assessing theories of childhood amnesia. PMID:10659078

Eacott, M J; Crawley, R A

1999-05-01

63

RNA Interference-Mediated Targeting of Human Cytomegalovirus Immediate-Early or Early Gene Products Inhibits Viral Replication with Differential Effects on Cellular Functions  

PubMed Central

Viral drug toxicity, resistance, and an increasing immunosuppressed population warrant continued research into new avenues for limiting diseases associated with human cytomegalovirus (HCMV). In this study, a small interfering RNA (siRNA), siX3, was designed to target coding sequences within shared exon 3 of UL123 and UL122 transcripts encoding IE1 and IE2 immediate-early proteins of HCMV. Pretreatment of cells with siX3 reduced the levels of viral protein expression, DNA replication, and progeny virus production compared to control siRNA. Two siRNAs against UL54 and overlapping transcripts (UL55-57) were compared to siX3 in HCMV infection and were also found to be effective at inhibiting HCMV replication. Further investigation into the effects of the siRNAs on viral replication showed that pretreatment with each of the siRNAs resulted in an inhibition in the formation of mature replication compartments. The ability of these siRNAs to prevent or reduce certain cytopathic effects associated with HCMV infection was also examined. Infected cells pretreated with siX3, but not siUL54, retained promyelocytic leukemia (PML) protein in cellular PML bodies, an essential component of this host intrinsic antiviral defense. DNA damage response proteins, which are localized in nuclear viral replication compartments, were reduced in the siX3- and siUL54-treated cells. siX3, but not siUL54, prevented DNA damage response signaling early after infection. Therapeutic efficacy was demonstrated by treating cells with siRNAs after HCMV replication had commenced. Together, these findings suggest that siRNAs targeting exon 3 of the major IE genes or the UL54-57 transcripts be further studied for their potential development into anti-HCMV therapeutics.

E, Xiaofei; Stadler, Bradford M.; Debatis, Michelle; Wang, Shixia; Lu, Shan

2012-01-01

64

An adenovirus early region 1A protein is required for maximal viral DNA replication in growth-arrested human cells.  

PubMed Central

Two closely related adenovirus early region 1A proteins are expressed in transformed cells. The smaller of these, which is 243 amino acids in length, is required for the transformation of primary rat cells and for the transformation of immortalized rat cells to anchorage-independent growth. This protein is not required for productive infection of exponentially growing HeLa cells but is required for maximal replication in growth (G0)-arrested human lung fibroblasts (WI-38 cells). To determine the function of this protein in viral replication in these G0-arrested cells, we compared viral early mRNA, early protein, and late protein synthesis after infection with wild type or a mutant which does not express the protein. No differences were found. However, viral DNA synthesis by the mutant was delayed and decreased to 20 to 30% that of wild type in these cells. Viral DNA synthesis was much less defective in growing WI-38 cells, and in the transformed human HeLa cell line it occurred at wild-type levels. Furthermore, the mutant which can express only the 243-amino-acid early region 1A protein induced cellular DNA synthesis in G0-arrested rat cells to the same level as wild-type virus. A mutant which can express only the 289-amino-acid early region 1A protein induced less cellular DNA synthesis in G0-arrested rat cells. We propose that the early region 1A 243-amino-acid protein alters the physiology of arrested permissive cells to allow maximal viral DNA replication. In nonpermissive rodent cells, the 243-amino-acid protein drives G0-arrested cells into S phase. This activity is probably important for the immortalization of primary cells. Images

Spindler, K R; Eng, C Y; Berk, A J

1985-01-01

65

The Human Cytomegalovirus Major Immediate-Early Enhancer Determines the Efficiency of Immediate-Early Gene Transcription and Viral Replication in Permissive Cells at Low Multiplicity of Infection  

Microsoft Academic Search

To determine the effect of the human cytomegalovirus (CMV) major immediate-early (MIE) enhancer or promoter on the efficiency of viral replication in permissive human cells, we constructed recombinant viruses with their human MIE promoter, enhancer, and promoter plus enhancer replaced with the murine CMV components. After a low multiplicity of infection (MOI) (0.01 PFU\\/cell), recombinant human CMV with the murine

Hiroki Isomura; Mark F. Stinski

2003-01-01

66

The Human Cytomegalovirus Major Immediate-Early Distal Enhancer Region Is Required for Efficient Viral Replication and Immediate-Early Gene Expression  

Microsoft Academic Search

The human cytomegalovirus (HCMV) major immediate-early (MIE) genes, encoding IE1 p72 and IE2 p86, are activated by a complex enhancer region (base positions -65 to -550) that operates in a cell type- and differentiation-dependent manner. The expression of MIE genes is required for HCMV replication. Previous studies analyzing functions of MIE promoter-enhancer segments suggest that the distal enhancer region vari-

JEFFERY L. MEIER; JONATHAN A. PRUESSNER

2000-01-01

67

A Search for an Early Holocene CACO3 Preservation Event  

Microsoft Academic Search

The CO2 record for air bubbles from the Byrd Station ice core suggest a drawdown in the ocean-atmosphere carbon reservoir during the early Holocene. Such a drawdown would require a corresponding increase in the CO3= ion concentration in the deep sea. We report here the results of a search in Atlantic sediments for evidence that the lysocline showed a corresponding

W. S. Broecker; Yong Lao; Mieczyslawa Klas; Elizabeth Clark; Georges Bonani; Susan Ivy; Chin Chen

1993-01-01

68

The Human Cytomegalovirus Major Immediate-Early Distal Enhancer Region Is Required for Efficient Viral Replication and Immediate-Early Gene Expression  

PubMed Central

The human cytomegalovirus (HCMV) major immediate-early (MIE) genes, encoding IE1 p72 and IE2 p86, are activated by a complex enhancer region (base positions -65 to -550) that operates in a cell type- and differentiation-dependent manner. The expression of MIE genes is required for HCMV replication. Previous studies analyzing functions of MIE promoter-enhancer segments suggest that the distal enhancer region variably modifies MIE promoter activity, depending on cell type, stimuli, or state of differentiation. To further understand the mechanism by which the MIE promoter is regulated, we constructed and analyzed several different recombinant HCMVs that lack the distal enhancer region (-300 to -582, -640, or -1108). In human fibroblasts, the HCMVs without the distal enhancer replicate normally at high multiplicity of infection (MOI) but replicate poorly at low MOI in comparison to wild-type virus (WT) or HCMVs that lack the neighboring upstream unique region and modulator (-582 or -640 to -1108). The growth aberrancy was normalized after restoring the distal enhancer in a virus lacking this region. For HCMVs without a distal enhancer, the impairment in replication at low MOI corresponds to a deficiency in production of MIE RNAs compared to WT or virus lacking the unique region and modulator. An underproduction of viral US3 RNA was also evident at low MOI. Whether lower production of IE1 p72 and IE2 p86 causes a reduction in expression of the immediate-early (IE) class US3 gene remains to be determined. We conclude that the MIE distal enhancer region possesses a mechanism for augmenting viral IE gene expression and genome replication at low MOI, but this regulatory function is unnecessary at high MOI.

Meier, Jeffery L.; Pruessner, Jonathan A.

2000-01-01

69

The p92 polymerase coding region contains an internal RNA element required at an early step in Tombusvirus genome replication.  

PubMed

The replication of positive-strand RNA viral genomes involves various cis-acting RNA sequences. Generally, regulatory RNA sequences are present at or near genomic termini; however, internal replication elements (IREs) also exist. Here we report the structural and functional characterization of an IRE present in the readthrough portion of the p92 polymerase gene of Tomato bushy stunt virus. Analysis of this element in the context of a noncoding defective interfering RNA revealed a functional core structure composed of two noncontiguous segments of sequence that interact with each other to form an extended helical conformation. IRE activity required maintenance of several base-paired sections as well as two distinct structural features: (i) a short, highly conserved segment that can potentially form two different and mutually exclusive structures and (ii) an internal loop that contains a critical CC mismatch. The IRE was also shown to play an essential role within the context of the viral genome. In vivo analysis with novel RNA-based temperature-sensitive genomic mutants and translationally active subgenomic viral replicons revealed the following about the IRE: (i) it is active in the positive strand, (ii) it is dispensable late in the viral RNA replication process, and (iii) it is functionally inhibited by active translation over its sequence. Together, these results suggest that IRE activity is required in the cytosol at an early step in the viral replication process, such as template recruitment and/or replicase complex assembly. PMID:15795270

Monkewich, Sandra; Lin, Han-Xin; Fabian, Marc R; Xu, Wei; Na, Hong; Ray, Debashish; Chernysheva, Olena A; Nagy, Peter D; White, K Andrew

2005-04-01

70

MAP kinase dependent cyclinE/cdk2 activity promotes DNA replication in early sea urchin embryos.  

PubMed

Sea urchins provide an excellent model for studying cell cycle control mechanisms governing DNA replication in vivo. Fertilization and cell cycle progression are tightly coordinated by Ca(2+) signals, but the mechanisms underlying the onset of DNA replication after fertilization remain less clear. In this study we demonstrate that calcium-dependent activation of ERK1 promotes accumulation of cyclinE/cdk2 into the male and female pronucleus and entry into first S-phase. We show that cdk2 activity rises quickly after fertilization to a maximum at 4 min, corresponding in timing to the early ERK1 activity peak. Abolishing MAP kinase activity after fertilization with MEK inhibitor, U0126, substantially reduces the early peak of cdk2 activity and prevents cyclinE and cdk2 accumulation in both sperm pronucleus and zygote nucleus in vivo. Both p27(kip1) and roscovitine, cdk2 inhibitors, prevented DNA replication suggesting cdk2 involvement in this process in sea urchin. Inhibition of cdk2 activity using p27(kip1) had no effect on the phosphorylation of MBP by ERK, but completely abolished phosphorylation of retinoblastoma protein, a cdk2 substrate, indicating that cdk2 activity is downstream of ERK1 activation. This pattern of regulation of DNA synthesis conforms to the pattern observed in mammalian somatic cells. PMID:19665013

Kisielewska, J; Philipova, R; Huang, J-Y; Whitaker, M

2009-08-06

71

National Cancer Institute Boards Accept Scientific Workshop Findings on Early Reproductive Events and Breast Cancer  

Cancer.gov

On March 3, 2003, the NCI's Board of Scientific Advisors and Board of Scientific Counselors reviewed and unanimously accepted the findings of an "Early Reproductive Events and Breast Cancer Workshop."

72

Early\\/fast VLF events produced by electron density changes associated with sprite halos  

Microsoft Academic Search

The magnitudes of scattered fields produced during early\\/fast very low frequency (VLF) events observed at 13 closely spaced (?65 km) sites are compared with those expected for sprite halo disturbances using a numerical model of wave propagation within the Earth-ionosphere waveguide. Three different early\\/fast events of varying magnitudes are analyzed using three different nighttime ambient lower ionospheric electron density profiles.

Robert C. Moore; Christopher P. Barrington-Leigh; Umran S. Inan; Timothy F. Bell

2003-01-01

73

Early\\/fast VLF events produced by electron density changes associated with sprite halos  

Microsoft Academic Search

The magnitudes of scattered fields produced during early\\/fast very low frequency (VLF) events observed at 13 closely spaced (~65 km) sites are compared with those expected for sprite halo disturbances using a numerical model of wave propagation within the Earth-ionosphere waveguide. Three different early\\/fast events of varying magnitudes are analyzed using three different nighttime ambient lower ionospheric electron density profiles.

Robert C. Moore; Christopher P. Barrington-Leigh; Umran S. Inan; Timothy F. Bell

2003-01-01

74

Emotional perception: correspondence of early and late event-related potentials with cortical and subcortical functional MRI.  

PubMed

This research examines the relationship between brain activity recorded with functional magnetic resonance imaging (fMRI) and event related potentials (ERP) as these responses varied over a series of emotionally evocative and neutral pictures. We investigate the relationship of early occipitotemporal and later centroparietal emotion-modulated ERPs in one sample to fMRI estimates of neural activity in another sample in a replicated experiment. Using this approach, we aimed to link effects found in time-resolved electrocortical measures to specific neural structures across individual emotional and nonemotional picture stimuli. The centroparietal late positive potential (LPP) showed covariation with emotion-modulated regions of hemodynamic activation across multiple dorsal and ventral visual cortical structures, while the early occipitotemporal potential was not reliably associated. Subcortical and corticolimbic structures involved in the perception of motivationally relevant stimuli also related to modulation of the LPP, and were modestly associated to the amplitude of the early occipitotemporal potential. These data suggest that early occipitotemporal potentials may reflect multiple sources of modulation including motivational relevance, and supports the perspective that the slow-wave LPP represents aggregate cortical and subcortical structures involved in emotional discrimination. PMID:22560889

Sabatinelli, Dean; Keil, Andreas; Frank, David W; Lang, Peter J

2012-04-26

75

Baculovirus resistance in codling moth (Cydia pomonella L.) caused by early block of virus replication.  

PubMed

An up to 10,000-fold resistance against the biocontrol agent Cydia pomonella granulovirus (CpGV) was observed in field populations of codling moth, C. pomonella, in Europe. Following different experimental approaches, a modified peritrophic membrane, a modified midgut receptor, or a change of the innate immune response could be excluded as possible resistance mechanisms. When CpGV replication was traced by quantitative PCR in different tissues of susceptible and resistant insects after oral and intra-hemocoelic infection, no virus replication could be detected in any of the tissues of resistant insects, suggesting a systemic block prior to viral DNA replication. This conclusion was corroborated by fluorescence microscopy using a modified CpGV (bacCpGV(hsp-eGFP)) carrying enhanced green fluorescent gene (eGFP), which showed that infection in resistant insects did not spread. In conclusion, the different lines of evidence indicate that CpGV can enter but not replicate in the cells of resistant codling moth larvae. PMID:21190707

Asser-Kaiser, Sabine; Radtke, Pit; El-Salamouny, Said; Winstanley, Doreen; Jehle, Johannes A

2010-12-28

76

Resolving database replication conflicts in the health care information system project early phase  

Microsoft Academic Search

Considering that any public health care information system is based on a distributed database management system that consists of many dozens distributed databases, and IS itself can consist of at least few dozens of applications, database replication conflicts can make significant problems to administrators in the system implementing phase. All world known database platforms (like Oracle or SQL Server) have

Tatjana N. Stankovi?; Dragan S. Jankovi?; S. N. Pesic

2009-01-01

77

Replication Study of the First Step to Success Early Intervention Program  

ERIC Educational Resources Information Center

This article describes a replication of the "First Step to Success" program (Walker, Stiller, Severson, & Golly, 1998) with at-risk students in the first and second grade to determine program effectiveness in decreasing inappropriate behaviors and increasing academic engagement time. This expands the "First Step to Success" program to (1) serve…

Lien-Thorne, Stephanie; Kamps, Debra

2005-01-01

78

Computational Prediction Models for Early Detection of Risk of Cardiovascular Events Using Mass Spectrometry Data  

Microsoft Academic Search

Early prediction of the risk of cardiovascular events in patients with chest pain is critical in order to provide appropriate medical care for those with positive diagnosis. This paper introduces a computational methodology for predicting such events in the context of robust computerized classification using mass spectrometry data of blood samples collected from patients in emergency departments. We applied the

Tuan D. Pham; Honghui Wang; Xiaobo Zhou; Dominik Beck; Miriam Brandl; Gerard Hoehn; Joseph Azok; Marie-luise Brennan; Stanley L. Hazen; King Li; Stephen T. C. Wong

2008-01-01

79

Early Interventions Following Exposure to Traumatic Events–Implications for Practice from Recent Research  

Microsoft Academic Search

It is has been argued that early interventions for individuals, groups or others affected by traumatic events should not be routinely offered as there is the danger of causing more harm. The notion of ‘watchful waiting’ has been espoused in clinical guidelines for the assessment and treatment of PTSD. Instead, a more proactive early intervention is suggested for potentially traumatic

Atle Dyregrov; Stephen Regel

2011-01-01

80

Early Interventions Following Exposure to Traumatic Events: Implications for Practice From Recent Research  

Microsoft Academic Search

It is has been argued that early interventions for individuals, groups or others affected by traumatic events should not be routinely offered as there is the danger of causing more harm. The notion of “watchful waiting” has been espoused in clinical guidelines for the assessment and treatment of posttraumatic stress disorder (PTSD). Instead, a more proactive early intervention is suggested

Atle Dyregrov; Stephen Regel

2012-01-01

81

Eclipse period during replication of plasmid R1: contributions from structural events and from the copy-number control system.  

PubMed

The eclipse period (the time period during which a newly replicated plasmid copy is not available for a new replication) of plasmid R1 in Escherichia coli was determined with the classic Meselson-Stahl density-shift experiment. A mini-plasmid with the wild-type R1 replicon and a mutant with a thermo-inducible runaway-replication phenotype were used in this work. The eclipses of the chromosome and of the wild-type plasmid were 0.6 and 0.2 generation times, respectively, at temperatures ranging from 30 degrees C to 42 degrees C. The mutant plasmid had a similar eclipse at temperatures up to 38 degrees C. At 42 degrees C, the plasmid copy number increased rapidly because of the absence of replication control and replication reached a rate of 350-400 plasmid replications per cell and cell generation. During uncontrolled replication, the eclipse was about 3 min compared with 10 min at controlled replication (the wild-type plasmid at 42 degrees C). Hence, the copy-number control system contributed significantly to the eclipse. The eclipse in the absence of copy-number control (3 min) presumably is caused by structural requirements: the covalently closed circular plasmid DNA has to regain the right degree of superhelicity needed for initiation of replication and it takes time to assemble the initiation factors. PMID:14507381

Olsson, Jan A; Berg, Otto G; Dasgupta, Santanu; Nordström, Kurt

2003-10-01

82

The Gammaretroviral p12 protein has multiple domains that function during the early stages of replication  

PubMed Central

Background The Moloney murine leukaemia virus (Mo-MLV) gag gene encodes three main structural proteins, matrix, capsid and nucleocapsid and a protein called p12. In addition to its role during the late stages of infection, p12 has an essential, but undefined, function during early post-entry events. As these stages of retroviral infection remain poorly understood, we set out to investigate the function of p12. Results Examination of the infectivity of Mo-MLV virus-like particles containing a mixture of wild type and mutant p12 revealed that the N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function, and that the N-terminal activity precedes the C-terminal activity in the viral life cycle. By creating a panel of p12 mutants in other gammaretroviruses, we showed that these domains are conserved in this retroviral genus. We also undertook a detailed mutational analysis of each domain, identifying residues essential for function. These data show that different regions of the N-terminal domain are necessary for infectivity in different gammaretroviruses, in stark contrast to the C-terminal domain where the same region is essential for all viruses. Moreover, chimeras between the p12 proteins of Mo-MLV and gibbon ape leukaemia virus revealed that the C-terminal domains are interchangeable whereas the N-terminal domains are not. Finally, we identified potential functions for each domain. We observed that particles with defects in the N-terminus of p12 were unable to abrogate restriction factors, implying that their cores were impaired. We further showed that defects in the C-terminal domain of p12 could be overcome by introducing a chromatin binding motif into the protein. Conclusions Based on these data, we propose a model for p12 function where the N-terminus of p12 interacts with, and stabilizes, the viral core, allowing the C-terminus of p12 to tether the preintegration complex to host chromatin during mitosis, facilitating integration.

2012-01-01

83

Organization of Early and Late Replicating DNA in Human Chromosome Territories  

Microsoft Academic Search

It has been suggested that DNA organized into replication foci during S-phase remains stably aggregated in non-S-phase cells and that these stable aggregates provide fundamental units of nuclear or chromosome architecture [C. Meng and R. Berezney (1991)J. Cell Biol.115, 95a; E. Sparvoliet al.(1994)J. Cell Sci.107, 3097–3103; D. A. Jackson and A. Pombo (1998)J. Cell Biol.140, 1285–1295; D. Zinket al.(1998)Hum. Genet.112,

Daniele Zink; Harald Bornfleth; Astrid Visser; Christoph Cremer; Thomas Cremer

1999-01-01

84

Reassociation kinetics of sequences replicated early in S phase and expression of a centriolar antigen  

SciTech Connect

This thesis addresses two aspects of the initiation of DNA replication in eucaryotic cells. The major part of this thesis is concerned with an attempt to identify and isolate DNA sequences that are replicated at the onset of S-phase. It was presumed that these sequences contain origins of DNA replication. Growth requirements and restrictions of the epithelial-like cell lines TC7 and COS-1, and the fibroblast-like cell lines 3T3, SV3T3, and CHO have been rigorously characterized. A serum deprivation protocol was adapted for the synchronization of the most useful of these, 3T3 cells. By stimulating a quiescent culture with serum in the presence of the DNA polymerase inhibitor, aphidicolin, the cells progress toward S phase but are held at the G1/S boundary. Upon removal of the drug, the cells, synchronously enter S phase. DNA sequences in 3T3 cells that replicate at entrance to S phase were labelled with /sup 3/H-thymidine and used as tracers in reassociation experiments that examined the complexity of these sequences. Approximately one third of the S-entry labelled sequences were driven to reassociate as sequences that are moderately reiterated in the 3T3 genome. In a separate study, the expression of an antigen located at the centrolar region of TC7 cells was investigated. The expression was dependent on both the position in the cell cycle and on the growth conditions. Within the cell cycle, expression of the centriolar antigen was observed just before and during the onset of S phase. The nature and function of the antigen remains unclear.

Segarini, P.R.

1986-01-01

85

Phosphoproteome Dynamics Upon Changes in Plant Water Status Reveal Early Events Associated With Rapid Growth Adjustment in Maize Leaves*  

PubMed Central

Plant growth adjustment during water deficit is a crucial adaptive response. The rapid fine-tuned control achieved at the post-translational level is believed to be of considerable importance for regulating early changes in plant growth reprogramming. Aiming at a better understanding of early responses to contrasting plant water statuses, we carried out a survey of the protein phosphorylation events in the growing zone of maize leaves upon a range of water regimes. In this study, the impact of mild and severe water deficits were evaluated in comparison with constant optimal watering and with recovery periods lasting 5, 10, 20, 30, 45, and 60 min. Using four biological replicates per treatment and a robust quantitative phosphoproteomic methodology based on stable-isotope labeling, we identified 3664 unique phosphorylation sites on 2496 proteins. The abundance of nearly 1250 phosphorylated peptides was reproducibly quantified and profiled with high confidence among treatments. A total of 138 phosphopeptides displayed highly significant changes according to water regimes and enabled to identify specific patterns of response to changing plant water statuses. Further quantification of protein amounts emphasized that most phosphorylation changes did not reflect protein abundance variation. During water deficit and recovery, extensive changes in phosphorylation status occurred in critical regulators directly or indirectly involved in plant growth and development. These included proteins influencing epigenetic control, gene expression, cell cycle-dependent processes and phytohormone-mediated responses. Some of the changes depended on stress intensity whereas others depended on rehydration duration, including rapid recoveries that occurred as early as 5 or 10 mins after rewatering. By combining a physiological approach and a quantitative phosphoproteomic analysis, this work provides new insights into the in vivo early phosphorylation events triggered by rapid changes in plant water status, and their possible involvement in plant growth-related processes.

Bonhomme, Ludovic; Valot, Benoit; Tardieu, Francois; Zivy, Michel

2012-01-01

86

An early Eocene transient warming ( ˜ 53 Ma): Implications for astronomically-paced early Eocene hyperthermal events.  

NASA Astrophysics Data System (ADS)

Here we report on a pronounced hyperthermal event approximately 2 Myrs after the Paleocene-Eocene thermal maximum (PETM) and place both events in a new orbitally-tuned framework. This previously unrecognized transient event and the underlying PETM were both recovered at five sites along a 2km depth transect on the Walvis Ridge (southeast Atlantic) during Ocean Drilling Program Leg 208. Similar to the PETM, this event, \\textit{Elmo}, is marked by a red clay layer, associated with severe drop in CaCO3 concentrations, suggesting a ˜ 2 km rise in the lysocline. High-resolution (1cm) bulk carbonate ? 13C measurements of the shallowest, and hence most complete Site 1263 revealed a ˜ 1.5% drop in ? 13C and ? 18O. The negative ? 13C excursion is composed of three steep steps of which the last one corresponds to the base of the red clay layer. The post-\\textit{Elmo} interval mirrors the typical PETM signature with an exponential recovery to pre-excursion ? 13C values. The planktonic foraminiferal ? 13C record (measured on single specimens of the surface dweller \\textit{Acaranina soldadoensis}) confirms the bulk pattern, although the amplitude of the excursion, ˜ -2.5, is larger. The planktonic foraminiferal ? 18O record shows the same ˜ -1% excursion as the bulk, suggesting a fast increase in sea surface temperature of ˜ 4 degrees C. The case of conditions similar to the PETM during the ELMO event is further strengthened by the occurrence of low diversity, diminutive benthic foraminifer assemblages, and a decrease in planktonic foraminifer diversity. Examination of published isotope, X-ray fluorescence and magnetic susceptibility records further indicates that this event is global in nature and recorded in other marine and terrestrial basins. Orbital tuning of the deepest Sites 1262 magnetic susceptibility and Sites 1262 and 1267 color reflectance records to the La2004 and R7 astronomical solutions shows that the \\textit{Elmo} is five 400-kyr eccentricity cycles younger than the PETM and that both events are linked to eccentricity-maxima. This, and the subtle resemblance between the \\textit{Elmo} and PETM mentioned above, suggests that similar, astronomically modulated, mechanisms are at the root of them. The leading hypothesis to explain the PETM climatic event and its ? 13C excursion is the dissociation of submarine methane hydrates. If the \\textit{Elmo} shares a similar origin, its less extreme appearance may be associated with the ability of the methane hydrate reservoir to recharge after the PETM, especially under the warm conditions that prevailed in the interval spanning the two events.

Sluijs, A.; Lourens, L. J.; Kroon, D.; Zachos, J. C.; Thomas, E.; Röhl, U.

2004-12-01

87

Stepwise atmospheric carbon-isotope excursion during the Toarcian Oceanic Anoxic Event (Early Jurassic, Polish Basin)  

Microsoft Academic Search

During the Mesozoic (250–64Ma) intervals of about 0.5Myr were subject to severe environmental changes, including high sea-surface temperature and very low oxygen content of marine water. These Oceanic Anoxic Events, or OAEs, occurred simultaneously with profound disturbance to the carbon cycle. The carbon-isotope anomaly in the Early Jurassic that marks the Toarcian Oceanic Anoxic Event (T-OAE) at ~182Ma is characterized

Stephen P. Hesselbo; Grzegorz Pienkowski

2011-01-01

88

Evidence for an early pliocene cold event in the southern oceans  

SciTech Connect

Although it is generally agreed that the early Pliocene witnessed the last great climate warming before the onset of Northern Hemisphere glaciation, it is generally not recognized that this time interval also witnessed what appear to be major glaciations in both northern and southern Hemispheres. This describes a study of brief, intense warm events in the early Pliocene as well as evidence for at least one major glaciation during this time interval. 13 refs.

Burckle, L.H.; Mortlock, R.A. (Columbia Univ., Palisades, NY (United States)); Rudolph, S. (State Univ. of New York, Oswego, NY (United States))

1993-01-01

89

Sequence analysis of Stx2-converting phage VT2-Sa shows a great divergence in early regulation and replication regions.  

PubMed

In enterohemorrhagic Escherichia coli, Shiga toxin is produced by lysogenic prophages. We have isolated the prophage VT2-Sa that is responsible for production of Shiga toxin type 2 protein, and determined the complete nucleotide sequence of this phage DNA. The entire DNA sequence consisted of 60,942 bp, exhibiting marked similarity to the 933W phage genome. However, several differences were observed in the immunity and replication regions, where cI, cII, cIII, N, cro, O, and P genes were present: Predicted amino acid sequences of N, cI, cro, O and P in the VT2-Sa genome did not show significant similarity to the counterparts of the 933W genome; however its cI showed higher similarity to lambda. Furthermore, O and P closely resembled those of phage HK022. These observations suggest that the various degrees of homology observed in the immunity and replication regions of VT2-Sa could have resulted from frequent recombination events among the lambdoid phages, and that these regions play a key role as a functional unit for phage propagation in competition with other lambdoid phages. PMID:10492170

Miyamoto, H; Nakai, W; Yajima, N; Fujibayashi, A; Higuchi, T; Sato, K; Matsushiro, A

1999-08-31

90

Replication Evidence in Support of the Psychometric Properties of the Devereux Early Childhood Assessment  

ERIC Educational Resources Information Center

|The Devereux Early Childhood Assessment (DECA) was developed to assess the social-emotional functioning of preschool children. The developers of the DECA report initial validity and reliability evidence in support of the use of the instrument with 2- to 5-year-old children across the United States. There is further need to collect independent…

Jaberg, Peter E.; Dixon, David J.; Weis, Glenna M.

2009-01-01

91

Replicating vaccines  

Technology Transfer Automated Retrieval System (TEKTRAN)

Early work on fish immunology and disease resistance demonstrated fish (like animals and humans) that survived infection were typically resistant to re-infection with the same pathogen. The concepts of resistance upon reinfection lead to the research and development of replicating (live) vaccines in...

92

Early snowmelt events: detection, distribution, and significance in a major sub-arctic watershed  

NASA Astrophysics Data System (ADS)

High latitude drainage basins are experiencing higher average temperatures, earlier snowmelt onset in spring, and an increase in rain on snow (ROS) events in winter, trends that climate models project into the future. Snowmelt-dominated basins are most sensitive to winter temperature increases that influence the frequency of ROS events and the timing and duration of snowmelt, resulting in changes to spring runoff. Of specific interest in this study are early melt events that occur in late winter preceding melt onset in the spring. The study focuses on satellite determination and characterization of these early melt events using the Yukon River Basin (Canada/USA) as a test domain. The timing of these events was estimated using data from passive (Advanced Microwave Scanning Radiometer—EOS (AMSR-E)) and active (SeaWinds on Quick Scatterometer (QuikSCAT)) microwave remote sensors, employing detection algorithms for brightness temperature (AMSR-E) and radar backscatter (QuikSCAT). The satellite detected events were validated with ground station meteorological and hydrological data, and the spatial and temporal variability of the events across the entire river basin was characterized. Possible causative factors for the detected events, including ROS, fog, and positive air temperatures, were determined by comparing the timing of the events to parameters from SnowModel and National Centers for Environmental Prediction North American Regional Reanalysis (NARR) outputs, and weather station data. All melt events coincided with above freezing temperatures, while a limited number corresponded to ROS (determined from SnowModel and ground data) and a majority to fog occurrence (determined from NARR). The results underscore the significant influence that warm air intrusions have on melt in some areas and demonstrate the large temporal and spatial variability over years and regions. The study provides a method for melt detection and a baseline from which to assess future change.

Alese Semmens, Kathryn; Ramage, Joan; Bartsch, Annett; Liston, Glen E.

2013-03-01

93

The Structure of The Extended Psychosis Phenotype in Early Adolescence--A Cross-sample Replication  

PubMed Central

The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and structure of the extended psychosis phenotype was investigated. Positive psychotic experiences, broadly defined, were reported by the majority of adolescents. Exploratory analysis with Structural Equation Modelling (Exploratory Factor Analysis followed by Confirmatory Factor Analysis [CFA]) in sample 1 suggested that psychotic experiences were best represented by 5 underlying dimensions; CFA in sample 2 provided a replication of this model. Dimensions were labeled Hallucinations, Delusions, Paranoia, Grandiosity, and Paranormal beliefs. Prevalences differed strongly, Hallucinations having the lowest and Paranoia having the highest rates. Girls reported more experiences on all dimensions, except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations, Delusions, and Paranoia, but not Grandiosity and Paranormal beliefs, were associated with distress and general measures of psychopathology. Thus, only some of the dimensions of the extended psychosis phenotype in young people may represent a continuum with more severe psychopathology and predict later psychiatric disorder.

Wigman, Johanna T. W.; Vollebergh, Wilma A. M.; Raaijmakers, Quinten A. W.; Iedema, Jurjen; van Dorsselaer, Saskia; Ormel, Johan; Verhulst, Frank C.; van Os, Jim

2011-01-01

94

Replication Evidence in Support of the Psychometric Properties of the Devereux Early Childhood Assessment  

Microsoft Academic Search

The Devereux Early Childhood Assessment (DECA) was developed to assess the social-emotional functioning of preschool children. The developers of the DECA report initial validity and reliability evidence in support of the use of the instrument with 2- to 5-year-old children across the United States. There is further need to collect independent validity and reliability evidence in support of the use

Peter E. Jaberg; David J. Dixon; Glenna M. Weis

2009-01-01

95

Pilot Evaluation of Early Juvenile Blue Crab Stock Enhancement Using a Replicated BACI Design  

Microsoft Academic Search

We quantified whether local populations of early juvenile blue crabs (J1–2) could be enhanced through the translocation of crabs to underutilized nursery habitats, and if enhancement success, survival, and potential impacts of stocked crabs on their benthic prey varied in a density-dependent manner. Using plankton nets, ?143,000 blue crab megalopae were collected as they ingressed into Pamlico Sound, NC. Of

David B. Eggleston; Eric G. Johnson; G. Todd Kellison; Gayle R. Plaia; Cynthia L. Huggett

2008-01-01

96

Palaeoceanographic and biotic response during early Eocene extreme global warming events  

Microsoft Academic Search

Studying past intervals of abrupt global warming and massive carbon release can improve our knowledge in ways relevant to understanding future climate change. Possible paleo-analogues for future climate change are the early Paleogene hyperthermal events, such as the Paleocene-Eocene Thermal Maximum (PETM; ~56 Ma), during which large amounts of carbon were released. More recently, another distinct period of global warming

H. L. Stap

2010-01-01

97

An ultrastructural analysis of early fertilization events in the giant scallop, Placopecten magellanicus (Mollusca, Pelecypoda)  

Microsoft Academic Search

We examined the ultrastuctural events occurring during early fertilization in the giant scallop, Placopecten magellanicus. The unfertilized oocytes had not completed their meiotic maturation and were blocked at the metaphase I stage. At fertilization, there was a local loss of microvilli, and a fertilization cone of 6 ?m in length by 4 ?m in diameter was produced. As the spermatozoon

JEAN DÉSILETS; CLAUDE GICQUAUD; FRANÇOIS DUBÉ

1995-01-01

98

How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt  

ERIC Educational Resources Information Center

Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…

National Scientific Council on the Developing Child, 2006

2006-01-01

99

G2 phase chromatin lacks determinants of replication timing  

PubMed Central

DNA replication in all eukaryotes follows a defined replication timing program, the molecular mechanism of which remains elusive. Using a Xenopus laevis egg extract replication system, we previously demonstrated that replication timing is established during early G1 phase of the cell cycle (timing decision point [TDP]), which is coincident with the repositioning and anchorage of chromatin in the newly formed nucleus. In this study, we use this same system to show that G2 phase chromatin lacks determinants of replication timing but maintains the overall spatial organization of chromatin domains, and we confirm this finding by genome-wide analysis of rereplication in vivo. In contrast, chromatin from quiescent cells retains replication timing but exhibits disrupted spatial organization. These data support a model in which events at the TDP, facilitated by chromatin spatial organization, establish determinants of replication timing that persist independent of spatial organization until the process of chromatin replication during S phase erases those determinants.

Lu, Junjie; Li, Feng; Murphy, Christopher S.; Davidson, Michael W.

2010-01-01

100

Identifying Early Events of Gene Expression in Breast Cancer with Systems Biology Phylogenetics  

PubMed Central

Advanced omics technologies such as deep sequencing and spectral karyotyping are revealing more of cancer heterogeneity at the genetic, genomic, gene expression, epigenetic, proteomic, and metabolomic levels. With this increasing body of emerging data, the task of data analysis becomes critical for mining and modeling to better understand the relevant underlying biological processes. However, the multiple levels of heterogeneity evident within and among populations, healthy and diseased, complicate the mining and interpretation of biological data, especially when dealing with hundreds to tens of thousands of variables. Heterogeneity occurs in many diseases, such as cancers, autism, macular degeneration, and others. In cancer, heterogeneity has hampered the search for validated biomarkers for early detection, and it has complicated the task of finding clonal (driver) and nonclonal (nonexpanded or passenger) aberrations. We show that subtyping of cancer (classification of specimens) should be an a priori step to the identification of early events of cancers. Studying early events in oncogenesis can be done on histologically normal tissues from diseased individuals (HNTDI), since they most likely have been exposed to the same mutagenic insults that caused the cancer in their neighboring tissues. Polarity assessment of HNTDI data variables by using healthy specimens as outgroup(s), followed by the application of parsimony phylogenetic analysis, produces a hierarchical classification of specimens that reveals the early events of the disease ontogeny within its subtypes as shared derived changes (abnormal changes) or synapomorphies in phylogenetic terminology.

Abu-Asab, M.S.; Abu-Asab, N.; Loffredo, C.A.; Clarke, R.; Amri, H.

2013-01-01

101

Energetic Particle Cross-field Propagation Early in a Solar Event  

NASA Astrophysics Data System (ADS)

Solar energetic particles (SEPs) have been observed to easily spread across heliographic longitudes, and the mechanisms responsible for this behavior remain unclear. We use full-orbit simulations of a 10 MeV proton beam in a turbulent magnetic field to study to what extent the spread across the mean field can be described as diffusion early in a particle event. We compare the full-orbit code results to solutions of a Fokker-Planck equation including spatial and pitch angle diffusion, and of one including also propagation of the particles along random-walking magnetic field lines. We find that propagation of the particles along meandering field lines is the key process determining their cross-field spread at 1 AU at the beginning of the simulated event. The mean square displacement of the particles an hour after injection is an order of magnitude larger than that given by the diffusion model, indicating that models employing spatial cross-field diffusion cannot be used to describe early evolution of an SEP event. On the other hand, the diffusion of the particles from their initial field lines is negligible during the first 5 hr, which is consistent with the observations of SEP intensity dropouts. We conclude that modeling SEP events must take into account the particle propagation along meandering field lines for the first 20 hr of the event.

Laitinen, T.; Dalla, S.; Marsh, M. S.

2013-08-01

102

Environmental change during the Late Berriasian - Early Valanginian: a prelude to the late Early Valanginian carbon-isotope event?  

NASA Astrophysics Data System (ADS)

The Valanginian period is well known for a positive excursion in marine and terrestrial ?13C records, which has been interpreted as the consequence of a major perturbation in the global carbon cycle (Lini et al., 1992; Erba et al., 2004). In contrast to the positive ?13C excursions of the Early Aptian and latest Cenomanian, marine organic-rich sediments have only been recognized from a few localities (van de Schootbrugge et al., 2003; Reboulet et al., 2003; Gröcke et al., 2005; Westermann et al., in press). The ?13C excursion began in the late Early Valanginian (campylotoxus ammonite zone) and gradually ended during the Late Valanginian. It is associated with a phase of widespread carbonate-platform drowning on the shelf (Föllmi et al., 1994) and a decline in calcareous nannofossils in the pelagic realm (Erba et al., 2004). As a triggering mechanism, numerous authors invoke the formation of the Parañà-Etendeka flood basalt. The correlation of this episode with the Valanginian ?13C event depends, however, on the absolute ages attributed to the Valanginian stage. The recent geological timescale by Ogg et al. (2008) shows that the major eruptional phase occurred during the Late Valanginian. This may imply that the late Early Valanginian ?13C event resulted from a combination of different factors. Important paleoenvironmental change occurred already in the latest Berriasian and earliest Valanginian, prior to the positive ?13C excursion. An increase in nutrient input near the onset of the ?13C excursion (campylotoxus ammonite zone), which may be considered as a trigger of the carbon cycle perturbation, has been identified in different studies, (Hennig, 2003; Duchamp-Alphonse et al., 2007; Bornemann & Mutterlose, 2008). Heterozoan faunal associations became dominant since the Early Valanginian on the northern Tethyan Helvetic platform and may indicate the beginning of sea-water eutrophication (Föllmi et al., 2007). Clay assemblages in the Tethys and Western European basins show that the climate became more humid during the Late Berriasian (Hallam et al., 1991, Schnyder et al., 2009). The aim of this project is to precisely characterize and date paleoenvironmental and paleoclimatic change during the latest Berriasian-Early Valanginian time interval in order to decipher if they can be viewed as precursor events, linked with the late Early Valanginian ?13C event. Three key sections have been studied: Capriolo (N Italy), Montclus (SE France) and Musfallen (E Switzerland) located in the Lombardian and Vocontian basins and on the Helvetic platform, respectively. Phosphorus and stable-isotope analyses have been performed, in addition to clay-mineralogy and facies determinations. The three sections show similar and comparable trends: The phosphorus content (in ppm) is higher in Late Berriasian sediments (compared to Early Berriasian and Valanginian deposits) and this period is also characterised by a decrease in ?13C values. This is interpreted as the result of enhanced continental weathering, which would be coeval with a change to a more humid climate during the Late Berriasian (Schnyder et al., 2009). References: Bornemann, A. and Mutterlose, J. (2008). "Calcareous nannofossil and d13C records from the Early Cretaceous of the Western Atlantic ocean: evidence of enhanced fertilization accross the Berriasian-Valanginian transition." palaios 23: 821-832. Duchamp-Alphonse, S., Gardin, S., Fiet, N., Bartolini, A., Blamart, D. and Pagel, M. (2007). "Fertilization of the northwestern Tethys (Vocontian basin, SE France) during the Valanginian carbon isotope perturbation: Evidence from calcareous nannofossils and trace element data." Palaeogeography, Palaeoclimatology, Palaeoecology 243(1-2): 132-151. Föllmi, K.B., Weissert, H., Bisping, M. & Funk, H. 1994: Phosphogenesis, carbon-isotope stratigraphy, and carbonate-platform evolution along the Lower Cretaceous northern tethyan margin. Geological Society of America, Bulletin 106, 729-746. F^llmi, K.B., Bodin, S., Godet, A., Linder, P. and Van de Scho

Morales, Chloé; Schnyder, Johann; Spangenberg, Jorge; Adatte, Thierry; Westermann, Stephane; Föllmi, Karl

2010-05-01

103

Carbonate platform evidence of ocean acidification at the onset of the early Toarcian oceanic anoxic event  

NASA Astrophysics Data System (ADS)

The early Toarcian oceanic anoxic event (Early Jurassic;˜183 Myr ago) is associated with one of the largest negative carbon isotope excursion (CIE) in the whole Phanerozoic (3-7‰). Estimates of the magnitude and rate of CO2 injection in the ocean-atmosphere system are compatible with a scenario of ocean acidification. Many carbonate platforms drowned in the Pliensbachian, well before the early Toarcian event. In this paper we test the hypothesis of surface water ocean acidification by presenting data from a resilient carbonate platform: the Apennine Carbonate Platform of southern Italy. The studied sections document a dramatic shift of the carbonate factory from massive biocalcification to chemical precipitation. Lithiotis bivalves and calcareous algae (Palaeodasycladus mediterraneus), which were the most prolific carbonate producers of Pliensbachian carbonate platforms, disappear during the first phase of the early Toarcian CIE, before the most depleted values are reached. We discuss the local versus supraregional significance of this shift and propose a scenario involving abrupt decline of carbonate saturation, forced by CO2 release at the beginning of the early Toarcian CIE, followed by a calcification overshoot, driven by the recovery of ocean alkalinity. Attribution of the demise of carbonate platform hypercalcifiers to ocean acidification is supported by palaeophysiology and reinforced by experimental data on the detrimental effects of ocean acidification on recent shellfishes and calcareous algae.

Trecalli, Alberto; Spangenberg, Jorge; Adatte, Thierry; Föllmi, Karl B.; Parente, Mariano

2012-12-01

104

HIV-protease inhibitors block the replication of both vesicular stomatitis and influenza viruses at an early post-entry replication step  

SciTech Connect

The inhibitors of HIV-1 protease (PIs) have been designed to block the activity of the viral aspartyl-protease. However, it is now accepted that this family of inhibitors can also affect the activity of cell proteases. Since the replication of many virus species requires the activity of host cell proteases, investigating the effects of PIs on the life cycle of viruses other than HIV would be of interest. Here, the potent inhibition induced by saquinavir and nelfinavir on the replication of both vesicular stomatitis and influenza viruses is described. These are unrelated enveloped RNA viruses infecting target cells upon endocytosis and intracellular fusion. The PI-induced inhibition was apparently a consequence of a block at the level of the fusion between viral envelope and endosomal membranes. These findings would open the way towards the therapeutic use of PIs against enveloped RNA viruses other than HIV.

Federico, Maurizio, E-mail: maurizio.federico@iss.it

2011-08-15

105

Tyrosine phosphorylation is an early and specific event involved in primary keratinocyte differentiation.  

PubMed Central

Very little is known about early molecular events triggering epithelial cell differentiation. We have examined the possible role of tyrosine phosphorylation in this process, as observed in cultures of primary mouse keratinocytes after exposure to calcium or 12-O-tetradecanoylphorbol-13-acetate (TPA). Immunoblotting with phosphotyrosine-specific antibodies as well as direct phosphoamino acid analysis revealed that induction of tyrosine phosphorylation occurs as a very early and specific event in keratinocyte differentiation. Very little or no induction of tyrosine phosphorylation was observed in a keratinocyte cell line resistant to the differentiating effects of calcium. Treatment of cells with tyrosine kinase inhibitors prevented induction of tyrosine phosphorylation by calcium and TPA and interfered with the differentiative effects of these agents. These results suggest that specific activation of tyrosine kinase(s) may play an important regulatory role in keratinocyte differentiation. Images

Filvaroff, E; Stern, D F; Dotto, G P

1990-01-01

106

Decreased delta event-related synchronization in patients with early vascular dementia.  

PubMed

Electroencephalogram (EEG) activity, recorded while performing an "odd ball" detection task, was compared between patients with early vascular dementia (VD), healthy young controls and healthy elderly controls performing the same task. The data were analyzed using the event-related synchronization/desynchronization (ERS/ERD) method. VD patients, compared with controls, showed decreased ERS effects in the delta frequency band (0.5-3.5Hz) of EEG after the target stimulus appeared in frontal, central and parietal regions. Similarly, elderly controls also showed a decreased ERS compared with young controls only in central and parietal regions. As part of this analysis, we introduce a novel quantitative index, the Event-related Energy Change Progression (EECP), which provides a reliable measure that distinguishes these groups and thereby provides a promising marker for early diagnosis of VD. PMID:21309443

Xu, Jin; Zhao, Songzhen; Zhang, Haoshi; Zheng, Chongxun

2011-01-01

107

Early events in natural resistance to bone marrow transplantation. Use of radiolabeled bone marrow cells  

Microsoft Academic Search

Natural resistance against the proliferation of splenic colony-forming units (CFU-S) is seen in certain combinations of bone marrow donors and irradiated hosts. In order to examine the early events following bone marrow transplantation and to determine whether genetically determined CFU-S repression is due to elimination of the transplanted cells from the spleen or to inhibition of their proliferation, we labeled

GEORGE A. CARLSON; SUSAN T. MARSHALL; AMY KIESCHE

1986-01-01

108

Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes  

Microsoft Academic Search

Early events leading to renal injury in obese Zucker (fatty) rats with type II diabetes.BackgroundMore than half of the new patients admitted to dialysis therapy in some centers are diagnosed with type IIb diabetes, that is, diabetes associated with obesity. This study searched for a common final pathway of renal damage in this progressive renal disease.MethodsThe evolution of biochemical and

Terezila Machado Coimbra; Ulf Janssen; Hermann Joseph Gröne; Tammo Ostendorf; Uta Kunter; Hartmut Schmidt; Georg Brabant; Jürgen Floege

2000-01-01

109

Brain event-related potentials: Diagnosing early-stage Alzheimer's disease  

Microsoft Academic Search

A pattern of components from brain event-related potentials (ERPs) (cognitive non-invasive electrical brain measures) performed well in separating early-stage Alzheimer's disease (AD) subjects from normal-aging control subjects and shows promise for developing a clinical diagnostic for probable AD. A Number–Letter task elicited brain activity related to cognitive processes. In response to the task stimuli, brain activity was recorded as ERPs,

Robert M. Chapman; Geoffrey H. Nowlis; John W. McCrary; John A. Chapman; Tiffany C. Sandoval; Maria D. Guillily; Margaret N. Gardner; Lindsey A. Reilly

2007-01-01

110

Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy  

PubMed Central

Polyomavirus JC (JCV) is the etiological agent of progressive multifocal leukoencephalopathy (PML), a demyelinating infection of oligodendrocytes in the brain. PML, a frequently fatal opportunistic infection in AIDS, has also emerged as a consequence of treatment with several new immunosuppressive therapeutic agents. Although nearly 80% of adults are seropositive, JCV attains an ability to infect glial cells in only a minority of people. Data suggest that JCV undergoes sequence alterations that accompany this ability, and these changes can be derived from an archetype strain by mutation, deletion, and duplication. While the introductory source and primary tissue reservoir of JCV remain unknown, lymphoid cells have been identified as potential intermediaries in progression of JCV to the brain. This review is focused on sequence changes in the noncoding control region (NCCR) of the virus. We propose an adaptive mechanism that involves a sequential series of DNA replication-driven NCCR recombination events involving stalled DNA replication forks at NCCR palindromic secondary structures. We shall describe how the NCCR sequence changes point to a model in which viral DNA replication drives NCCR recombination, allowing JCV adaptation to different cell types in its progression to neurovirulence.

Johnson, Edward M.; Wortman, Margaret J.; Dagdanova, Ayuna V.; Lundberg, Patric S.; Daniel, Dianne C.

2013-01-01

111

Early Events in Helix Unfolding Under External Forces: A Milestoning Analysis  

PubMed Central

Initial events of helix breakage as a function of load are considered using Molecular Dynamics simulations and Milestoning analysis. A helix length of ~100 amino acids is considered as a model for typical helices found in molecular machines and as a model that minimizes end effects for early events of unfolding. Transitions of individual amino acids (averaged over the helix’s interior residues) are examined and its surrounding hydrogen bonds are considered. Dense kinetic networks are constructed that, with Milestoning analysis, provide the overall kinetics of early breakage events. Network analysis and selection of MaxFlux pathways illustrate that load impacts unfolding mechanisms in addition to time scales. At relatively high (100pN) load levels, the principal intermediate is the 310-helix, while at relatively low (10pN) levels the ?-helix is significantly populated, albeit not as an unfolding intermediate. Coarse variables are examined at different levels of resolution; the rate of unfolding illustrates remarkable stability under changes in the coarsening. Consistent prediction of about ~5ns for the time of a single amino-acid unfolding event are obtained. Hydrogen bonds are much faster coarse variables (by about 2 orders of magnitude) compared to backbone torsional transition, which gates unfolding and thereby provides the appropriate coarse variable for the initiation of unfolding.

Kreuzer, Steven M; Elber, Ron; Moon, Tess J

2012-01-01

112

Exposure to potentially traumatic events in early childhood: differential links to emergent psychopathology  

PubMed Central

Objective To examine associations between exposure to potentially traumatic events (PTEs) and clinical patterns of symptoms and disorders in preschool children. Method Two hundred and thirteen referred and non-referred children, ages 24 to 48 months (MN = 34.9, SD = 6.7 months) were studied. Lifetime exposure to PTEs (family violence and non-interpersonal events) and recent stressful life events were assessed with the Preschool Age Psychiatric Assessment (PAPA) and Child Life Events Scale. Child psychiatric symptoms and disorders were assessed with parent-reports in the PAPA, a comprehensive, developmentally sensitive interview. Sociodemographic risk, parental anxiety and depressive symptoms (Center for Epidemiologic Studies Depression, Beck Anxiety Inventory), and child developmental level (Mullen Scales of Early Learning) also were assessed. Results Violence exposure was broadly associated with psychiatric status in the areas of depression, separation anxiety, posttraumatic stress, and conduct problems, whereas potentially traumatic non-interpersonal exposure was associated with phobic anxiety. The majority of the associations between violence exposure and preschoolers’ symptoms were significant even when other key factors, including economic disadvantage and parental mood and anxiety symptoms, were controlled statistically. However, parental depressive/anxious symptoms may have partially or fully mediated the relationships between violence exposure and depressive and conduct symptoms. Conclusions Evidence of robust associations between violence exposure and early childhood internalizing and externalizing disorders and symptoms highlights the need for longitudinal prospective research concerning neurodevelopmental mechanisms and pathways. Findings underscore the relevance of assessing trauma exposure, particularly interpersonal violence, to identify young children at risk.

Briggs-Gowan, Margaret J.; Carter, Alice S.; Clark, Roseanne; Augustyn, Marilyn; McCarthy, Kimberly J.; Ford, Julian D.

2011-01-01

113

Back to the origin: reconsidering replication, transcription, epigenetics, and cell cycle control.  

PubMed

In bacteria, replication is a carefully orchestrated event that unfolds the same way for each bacterium and each cell division. The process of DNA replication in bacteria optimizes cell growth and coordinates high levels of simultaneous replication and transcription. In metazoans, the organization of replication is more enigmatic. The lack of a specific sequence that defines origins of replication has, until recently, severely limited our ability to define the organizing principles of DNA replication. This question is of particular importance as emerging data suggest that replication stress is an important contributor to inherited genetic damage and the genomic instability in tumors. We consider here the replication program in several different organisms including recent genome-wide analyses of replication origins in humans. We review recent studies on the role of cytosine methylation in replication origins, the role of transcriptional looping and gene gating in DNA replication, and the role of chromatin's 3-dimensional structure in DNA replication. We use these new findings to consider several questions surrounding DNA replication in metazoans: How are origins selected? What is the relationship between replication and transcription? How do checkpoints inhibit origin firing? Why are there early and late firing origins? We then discuss whether oncogenes promote cancer through a role in DNA replication and whether errors in DNA replication are important contributors to the genomic alterations and gene fusion events observed in cancer. We conclude with some important areas for future experimentation. PMID:23634256

Evertts, Adam G; Coller, Hilary A

2012-11-01

114

Dramatic early event in chronic allograft nephropathy: increased but not decreased expression of MMP-9 gene  

PubMed Central

Objective The infiltration of mononuclear cells and replication and migration of smooth muscle cells (SMCs) from media into the intima in the vascular wall are the cardinal pathological changes in the early stage of chronic allograft nephropathy (CAN). But the mechanism is unclear. Therefore we investigated the role of matrix metalloproteinase 9 (MMP-9) and its interaction with TGF-beta1, tubulointerstitial mononuclear cells infiltration and migration of SMCs in the early stage of CAN. Methods Kidneys of Fisher (F334) rats were orthotopically transplanted into bilaterally nephrectomized Lewis (LEW) recipients. To suppress an initial episode of acute rejection, rats were briefly treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days. Animals were harvested at 12 weeks after transplantation for histological, immunohistochemistry and molecular biological analysis. Results The expression of MMP-9 was up-regulated in interstitium and vascular wall in the early stage of CAN, where there were interstitial mononuclear cells infiltration and SMCs migration and proliferation. Moreover the expression of MMP-9 were positively correlated with the degree of interstitial mononuclear cells infiltration, the quantity of SMCs in arteriolar wall, and also the increased TFG-beta1 expression in the tubulointerstitium and arteriolar wall. Conclusions MMP-9 may play an important role in the mechanism of pathological changes during the earlier period of CAN. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1582313332832700.

2013-01-01

115

Early Infection HIV-1 Envelope V1-V2 Genotypes Do Not Enhance Binding or Replication in Cells Expressing High Levels of ?4?7 Integrin.  

PubMed

: It has been postulated that HIV-1 envelope properties, such as shorter and less-glycosylated V1-V2 loops commonly observed among non-subtype B early-transmitted viruses, promote utilization of the gut homing integrin ?4?7. This property potentially confers an advantage to some HIV-1 variants early after acquisition. We found that replication-competent recombinant viruses incorporating HIV-1 subtype A compact and less-glycosylated early versus chronic phase V1-V2 loops demonstrated no significant difference in binding to ?4?7 high CD8 T cells or replication in ?4?7 high CD4 T cells. Integrin ?4?7 usage does not select for shorter less-glycosylated envelopes during transmission. PMID:23797693

Etemad, Behzad; Gonzalez, Oscar A; McDonough, Sean; Pena-Cruz, Victor; Sagar, Manish

2013-11-01

116

Rapid Determination of Event Source Parameters in Southern California for earthquake early warning  

NASA Astrophysics Data System (ADS)

The rapid increase in the number of seismic stations in earthquake prone regions, combined with the implementation of near real time data transmission technologies, provides the potential for earthquake early warning. In the absence of earthquake prediction methodologies in the foreseeable future, the rapid detection and analysis of a seismic event on its initiation, allowing the issuance of a ground motion warning of the order of seconds, is appealing. We present our efforts to design and implement such a system in southern California. The early warning systems currently operating in Mexico and Taiwan rely on significant distances (> 100 km) between the source and populated regions. In this scenario an early warning system can wait for several stations to detect an event, allowing the application of standard location and magnitude determination algorithms (a process that may take tens of seconds), and still issue a warning tens of seconds in advance of associated ground motion. The close proximity of fault zones to metropolitan areas in southern California precludes such an approach. Instead, we develop a system more similar to the UrEDAS warning system in Japan. The two event parameters needed are location and magnitude. The high density of seismic stations in southern California ( ~25 km spacing in populated areas) allows for an adequate location of events based solely on the first station to detect a P-arrival. The classical use of amplitude to determine magnitude is problematic due to its relatively high sensitivity to epicentral distance close to the source. Instead, we utilize the frequency dependence of the P-arrival to magnitude, which is less sensitive to epicentral distance. With this approach we estimate event magnitude with an accuracy of +/-1 magnitude unit using the P-arrival at one station only. As the P-arrival is recorded at additional stations, we average the magnitude estimates, which reduces the uncertainty. The event location and magnitude may then be used to estimate ground motion throughout the region using attenuation relations. Using the current TriNet infrastructure we expect to be able to reduce data transmission and analysis time sufficiently to be able to give zero to a few seconds warning prior to the onset of peak, damaging ground motion in the epicentral region. The warning time improves for locations further from the epicenter and, as the time-since-event initiation increases, the uncertainty in ground motion predictions decreases and warning messages can be updated.

Allen, R. M.; Kanamori, H.

2001-12-01

117

BioSense: implementation of a National Early Event Detection and Situational Awareness System.  

PubMed

BioSense is a CDC initiative to support enhanced early detection, quantification, and localization of possible biologic terrorism attacks and other events of public health concern on a national level. The goals of the BioSense initiative are to advance early detection by providing the standards, infrastructure, and data acquisition for near real-time reporting, analytic evaluation and implementation, and early event detection support for state and local public health officials. BioSense collects and analyzes Department of Defense and Department of Veterans Affairs ambulatory clinical diagnoses and procedures and Laboratory Corporation of America laboratory-test orders. The application summarizes and presents analytical results and data visualizations by source, day, and syndrome for each ZIP code, state, and metropolitan area through maps, graphs, and tables. An initial proof of a concept evaluation project was conducted before the system was made available to state and local users in April 2004. User recruitment involved identifying and training BioSense administrators and users from state and local health departments. User support has been an essential component of the implementation and enhancement process. CDC initiated the BioIntelligence Center (BIC) in June 2004 to conduct internal monitoring of BioSense national data daily. BIC staff have supported state and local system monitoring, conducted data anomaly inquiries, and communicated with state and local public health officials. Substantial investments will be made in providing regional, state, and local data for early event detection and situational awareness, test beds for data and algorithm evaluation, detection algorithm development, and data management technologies, while maintaining the focus on state and local public health needs. PMID:16177687

Bradley, Colleen A; Rolka, H; Walker, D; Loonsk, J

2005-08-26

118

``Early/slow'' events: A new category of VLF perturbations observed in relation with sprites  

NASA Astrophysics Data System (ADS)

Analysis of subionospheric VLF transmissions, observed in relation with sprites, has led to the identification of a new category of VLF perturbations caused by the direct effects of tropospheric lightning on the overlying lower ionosphere. They constitute a large subset of the so-called "early/fast" events where now the term "fast," which implies rapid onset durations less than ˜20 ms, does not apply. In contrast with early/fast, the perturbations have a gradual growth and thus "slow" onset durations ranging from about 0.5 to 2.5 s; thus these events are labeled herein as "early/slow." They are indicative of a new physical process at work which, following a sprite-causative cloud-to-ground discharge, leads to a gradual buildup of conductivity changes in the lower ionosphere which must be responsible for the long onset durations of the observed perturbations. Analysis of broadband VLF sferic recordings, made with a two-channel receiver near the sprite producing storms, shows that the growth phase of an early/slow event coincides with the occurrence of complex and dynamic lightning action. This is composed of a few sequential cloud-to-ground lightning strokes and clusters (bursts) of sferics which are attributable to intracloud lightning. We postulate that the long onset durations are due to secondary ionization buildup in the upper D region below the nighttime VLF reflection heights, caused mainly by the impact on sprite-produced electrons of sequential electromagnetic pulses radiated upward from horizontal in-cloud discharges.

Haldoupis, C.; Steiner, R. J.; Mika, Á.; Shalimov, S.; Marshall, R. A.; Inan, U. S.; BöSinger, T.; Neubert, T.

2006-11-01

119

Competing risks determining event-free survival in early breast cancer.  

PubMed Central

To evaluate the natural history of a disease and the effects of therapeutic interventions, it is important to determine which are the causes of treatment failure and to assess the extent to which each cause contributes to the total failure rate. The paper presents a new biostatistical technique to decompose the total event-free survival of a diseased population into cause-specific failure rates. The technique was based on a competing risk approach thereby avoiding biases related to assumptions of independence between different types of event. Such assumptions are inherent in the conventional Kaplan-Meier or actuarial methods. The competing risk method was used to analyse the pattern of failure among 2,850 pre- and postmenopausal patients with early-stage breast cancer and the results were compared to those obtained using conventional methods. The following events were analysed: loco-regional recurrence, distant metastasis, contralateral breast cancer, other new primary malignancies, and intercurrent deaths. The rate of new primary malignancies was found to be significantly higher in post- than in premenopausal patients (6% vs 3% at 10 years). In low-risk, node-negative postmenopausal patients the incidence of recurrences from breast cancer were found to be no greater than other types of events. This observation highlights the significance of the effect of different adjuvant therapies not only on the disease itself but also on the risk of second primary malignancies and other intercurrent diseases. In general, it was found that the conventional statistical methods tended to overestimate the event-specific rates. In conclusion, the method based on competing risks permits an unbiased analysis of all types of events determining the total event-free survival. It is thus useful for the description of the natural history of breast cancer as well as other diseases.

Arriagada, R.; Rutqvist, L. E.; Kramar, A.; Johansson, H.

1992-01-01

120

The hr5 transcriptional enhancer stimulates early expression from the Autographa californica nuclear polyhedrosis virus genome but is not required for virus replication.  

PubMed Central

Autographa californica nuclear polyhedrosis virus (AcMNPV) contains five homologous regions (hr1 through hr5) interspersed throughout its genome. Analysis of plasmid transfections indicates that the hrs function as transcriptional enhancers and possible origins of viral DNA replication. The role of these repetitive elements in regulating expression from the AcMNPV genome was examined by constructing a series of recombinant viruses that tested the effect of hr5 on expression of the adjacent p35 gene (p35). When embedded within the viral genome, hr5 stimulated transcription from the early p35 promoter in a position- and orientation-independent manner. Moreover, hr5 and the upstream activating region of p35 were functionally interchangeable. A 28-bp imperfect palindrome, repeated six times within hr5, was the minimal sequence required for p35 promoter activation. hr5 also stimulated another early AcMNPV promoter but not a late promoter or a host-derived promoter, suggesting that enhancement is promoter specific during infection. To investigate its role during AcMNPV replication, hr5 was deleted from its normal position within the viral genome. The resulting hr5 mutants exhibited no apparent defects in replication, as judged by production of budded virus and levels of very late gene expression, even though steady-state levels of p35 RNA were reduced. These results indicated for the first time that hr5 functions as a transcriptional enhancer within the viral genome. However, the element is not required for AcMNPV replication in cultured cells. Thus, loss of one of five possible origins of DNA replication is not deleterious to viral growth. Since p26 was removed from the hr5 deletion mutants, this gene is also nonessential for viral replication. Images

Rodems, S M; Friesen, P D

1993-01-01

121

Early events in helix unfolding under external forces: a milestoning analysis.  

PubMed

Initial events of helix breakage as a function of load are considered using molecular dynamics simulations and milestoning analysis. A helix length of ?100 amino acids is considered as a model for typical helices found in molecular machines and as a model that minimizes end effects for early events of unfolding. Transitions of individual amino acids (averaged over the helix's interior residues) are examined and its surrounding hydrogen bonds are considered. Dense kinetic networks are constructed that, with milestoning analysis, provide the overall kinetics of early breakage events. Network analysis and selection of MaxFlux pathways illustrate that load impacts unfolding mechanisms in addition to time scales. At relatively high (100 pN) load levels, the principal intermediate is the 3(10)-helix, while at relatively low (10 pN) levels the ?-helix is significantly populated, albeit not as an unfolding intermediate. Coarse variables are examined at different levels of resolution; the rate of unfolding illustrates remarkable stability under changes in the coarsening. Consistent prediction of about ?5 ns for the time of a single amino-acid unfolding event are obtained. Hydrogen bonds are much faster coarse variables (by about 2 orders of magnitude) compared to backbone torsional transition, which gates unfolding and thereby provides the appropriate coarse variable for the initiation of unfolding. Results provide an atomic description of "catch-bond" behavior, based on alternative pathways, in which unfolding of a simple protein structural element occurs over longer timescales for intermediate (10 pN) loads than for zero (0 pN) or large (100 pN) loads. PMID:22471347

Kreuzer, Steven M; Elber, Ron; Moon, Tess J

2012-05-29

122

Not Just the 8.2 event: Dynamic Early Holocene Climate in Arctic Canada  

NASA Astrophysics Data System (ADS)

Temperature reconstructions from a lake in the eastern Canadian Arctic indicate that peak warmth in the early Holocene was interrupted by two abrupt, short-lived temperature reversals at ~9.l and ~8.5 ka. Summer temperatures at Lake CF8, Baffin Island (~500 km west of Greenland) are inferred from subfossil midge (Chironomidae) assemblages. Our results indicate that the site, like others on Baffin Island, experienced exceptionally warm summers (almost 5°C warmer than present) through much of the early Holocene, presumably in response to enhanced summer insolation. After 1000 years of very warm, stable climate, warmth was interrupted by two discrete cold reversals at ~9.1 and ~8.5 ka, during which multiple cold-stenothermous midge taxa appeared in the lake and summer temperatures dropped more than 3°C. These two clearly-defined reversals, well beyond the range of background variability, were of similar amplitude and duration, and were separated by several centuries of near-peak warmth. The only Holocene events of comparable amplitude at this site are the rapid onset of Holocene warmth, and the more gradual Neoglacial cooling after 8 ka. Abrupt cooling events over the Baffin region are consistent with model simulations of the impacts of freshwater outbursts into the Labrador Sea, such as the Lake Agassiz outburst flood that occurred ~8.4 ka. That there are two discrete events recorded at this site indicates that the "8.2 event" was not uniquely significant in this region; rather, the period between approximately ~9.2 and 8 ka was characterized by repeated climate fluctuations forced by multiple outburst floods or other mechanisms. Thus global correlations among paleoclimate records need not assume that climate perturbations during this time period necessarily correlate with the draining of Lake Agassiz or the 8.2 ka cooling in central Greenland.

Axford, Y.; Briner, J. P.; Miller, G. H.; Francis, D. R.

2006-12-01

123

Association with positive outcome induces early effects in event-related brain potentials.  

PubMed

Emotional pictures, faces, or words elicit an early posterior negativity (EPN) in the event-related potential, starting around 200-400 ms, followed by a late positive complex (LPC). Occasionally, also very early effects of emotion (VEEEs) are seen prior to 200 ms. The present study examined whether VEEEs can be due to direct links established by reinforcement learning. In the learning session, participants learned to associate previously unknown Chinese words with monetary gain, loss, or neither. In the test session, they were required to distinguish the learned stimuli from novel distracters. Specific to stimuli associated with positive outcome a VEEE, consisting of a posterior positivity, appeared around 150 ms and an LPC between 550 and 700 ms, whereas an EPN was absent. These results show that previous association with reward can induce VEEEs, indicating that emotion effects in ERPs may arise in the absence of biologically preparedness and semantic meaning. PMID:22027086

Schacht, Annekathrin; Adler, Nele; Chen, Peiyao; Guo, Taomei; Sommer, Werner

2011-10-24

124

Early arrival of Southern Source Water in the deep North Atlantic prior to Heinrich event 2  

NASA Astrophysics Data System (ADS)

The Atlantic Meridional Overturning Circulation (AMOC) plays an important role in the Northern Hemisphere climate system. Significant interest went into the question of how excessive freshwater input through melting of continental ice can affect its overturning vigor and, hence, heat supply, to higher northern latitudes. Such forcing can be tested by investigating its behavior during extreme iceberg discharge events into the open North Atlantic during the last glacial period, the so-called Heinrich events (HE). Here we present neodymium (Nd) isotope compositions of past seawater, a sensitive chemical water mass tag, extracted from sediments of Ocean Drilling Program Site 1063 in the western North Atlantic (Bermuda Rise), covering the period surrounding HE 2, the Last Glacial Maximum, and the early deglaciation. These data are compared with a record of the kinematic circulation tracer (231Pa/230Th)xs extracted from the same sediment core. Both tracers indicate significant circulation changes preceding intense ice rafting during HE 2 by almost 2 kyr. Moreover, the Nd isotope record suggests the presence of deeply ventilating North Atlantic Deep Water early during Marine Isotope Stage 2 until it was replaced by Southern Source Water at ˜27 ka. The early switch to high (Pa/Th)xs and radiogenic ?Nd in relation to intensified ice rafting during HE 2 suggests that ice rafting into the open North Atlantic during major HE 2 was preceded by an early change of the AMOC. This opens the possibility that variations in AMOC contributed to or even triggered the ice sheet instability rather than merely responding to it.

Gutjahr, Marcus; Lippold, JöRg

2011-06-01

125

Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma.  

PubMed

Glaucoma is one of the most common neurodegenerative diseases. Despite this, the earliest stages of this complex disease are still unclear. This study was specifically designed to identify early stages of glaucoma in DBA/2J mice. To do this, we used genome-wide expression profiling of optic nerve head and retina and a series of computational methods. Eyes with no detectable glaucoma by conventional assays were grouped into molecularly defined stages of disease using unbiased hierarchical clustering. These stages represent a temporally ordered sequence of glaucoma states. We then determined networks and biological processes that were altered at these early stages. Early-stage expression changes included upregulation of both the complement cascade and the endothelin system, and so we tested the therapeutic value of separately inhibiting them. Mice with a mutation in complement component 1a (C1qa) were protected from glaucoma. Similarly, inhibition of the endothelin system with bosentan, an endothelin receptor antagonist, was strongly protective against glaucomatous damage. Since endothelin 2 is potently vasoconstrictive and was produced by microglia/macrophages, our data provide what we believe to be a novel link between these cell types and vascular dysfunction in glaucoma. Targeting early molecular events, such as complement and endothelin induction, may provide effective new treatments for human glaucoma. PMID:21383504

Howell, Gareth R; Macalinao, Danilo G; Sousa, Gregory L; Walden, Michael; Soto, Ileana; Kneeland, Stephen C; Barbay, Jessica M; King, Benjamin L; Marchant, Jeffrey K; Hibbs, Matthew; Stevens, Beth; Barres, Ben A; Clark, Abbot F; Libby, Richard T; John, Simon W M

2011-03-07

126

Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology  

PubMed Central

Neurofibrillary tangles (NFTs) are composed of abnormal aggregates of the cytoskeletal protein tau. Together with amyloid ? (A?) plaques and neuronal and synaptic loss, NFTs constitute the primary pathological hallmarks of Alzheimer disease (AD). Recent evidence also suggests that caspases are activated early in the progression of AD and may play a role in neuronal loss and NFT pathology. Here we demonstrate that tau is cleaved at D421 (?Tau) by executioner caspases. Following caspase-cleavage, ?Tau facilitates nucleation-dependent filament formation and readily adopts a conformational change recognized by the early pathological tau marker MC1. ?Tau can be phosphorylated by glycogen synthase kinase-3? and subsequently recognized by the NFT antibody PHF-1. In transgenic mice and AD brains, ?Tau associates with both early and late markers of NFTs and is correlated with cognitive decline. Additionally, ?Tau colocalizes with A?1–42 and is induced by A?1–42 in vitro. Collectively, our data imply that A? accumulation triggers caspase activation, leading to caspase-cleavage of tau, and that this is an early event that may precede hyperphosphorylation in the evolution of AD tangle pathology. These results suggest that therapeutics aimed at inhibiting tau caspase-cleavage may prove beneficial not only in preventing NFT formation, but also in slowing cognitive decline.

Rissman, Robert A.; Poon, Wayne W.; Blurton-Jones, Mathew; Oddo, Salvatore; Torp, Reidun; Vitek, Michael P.; LaFerla, Frank M.; Rohn, Troy T.; Cotman, Carl W.

2004-01-01

127

Early Events following Experimental Infection with Peste-Des-Petits Ruminants Virus Suggest Immune Cell Targeting  

PubMed Central

Peste-des-petits ruminants virus (PPRV) is a viral pathogen that causes a devastating plague of small ruminants. PPRV is an economically significant disease that continues to be a major obstacle to the development of sustainable agriculture across the developing world. The current understanding of PPRV pathogenesis has been heavily assumed from the closely related rinderpest virus (RPV) and other morbillivirus infections alongside data derived from field outbreaks. There have been few studies reported that have focused on the pathogenesis of PPRV and very little is known about the processes underlying the early stages of infection. In the present study, 15 goats were challenged by the intranasal route with a virulent PPRV isolate, Côte d’Ivoire ’89 (CI/89) and sacrificed at strategically defined time-points post infection to enable pre- and post-mortem sampling. This approach enabled precise monitoring of the progress and distribution of virus throughout the infection from the time of challenge, through peak viraemia and into a period of convalescence. Observations were then related to findings of previous field studies and experimental models of PPRV to develop a clinical scoring system for PPRV. Importantly, histopathological investigations demonstrated that the initial site for virus replication is not within the epithelial cells of the respiratory mucosa, as has been previously reported, but is within the tonsillar tissue and lymph nodes draining the site of inoculation. We propose that virus is taken up by immune cells within the respiratory mucosa which then transport virus to lymphoid tissues where primary virus replication occurs, and from where virus enters circulation. Based on these findings we propose a novel clinical scoring methodology for PPRV pathogenesis and suggest a fundamental shift away from the conventional model of PPRV pathogenesis.

Pope, Robert A.; Parida, Satya; Bailey, Dalan; Brownlie, Joe; Barrett, Thomas; Banyard, Ashley C.

2013-01-01

128

Chromatin signatures of the Drosophila replication program.  

PubMed

DNA replication initiates from thousands of start sites throughout the Drosophila genome and must be coordinated with other ongoing nuclear processes such as transcription to ensure genetic and epigenetic inheritance. Considerable progress has been made toward understanding how chromatin modifications regulate the transcription program; in contrast, we know relatively little about the role of the chromatin landscape in defining how start sites of DNA replication are selected and regulated. Here, we describe the Drosophila replication program in the context of the chromatin and transcription landscape for multiple cell lines using data generated by the modENCODE consortium. We find that while the cell lines exhibit similar replication programs, there are numerous cell line-specific differences that correlate with changes in the chromatin architecture. We identify chromatin features that are associated with replication timing, early origin usage, and ORC binding. Primary sequence, activating chromatin marks, and DNA-binding proteins (including chromatin remodelers) contribute in an additive manner to specify ORC-binding sites. We also generate accurate and predictive models from the chromatin data to describe origin usage and strength between cell lines. Multiple activating chromatin modifications contribute to the function and relative strength of replication origins, suggesting that the chromatin environment does not regulate origins of replication as a simple binary switch, but rather acts as a tunable rheostat to regulate replication initiation events. PMID:21177973

Eaton, Matthew L; Prinz, Joseph A; MacAlpine, Heather K; Tretyakov, George; Kharchenko, Peter V; MacAlpine, David M

2010-12-22

129

Chromatin signatures of the Drosophila replication program  

PubMed Central

DNA replication initiates from thousands of start sites throughout the Drosophila genome and must be coordinated with other ongoing nuclear processes such as transcription to ensure genetic and epigenetic inheritance. Considerable progress has been made toward understanding how chromatin modifications regulate the transcription program; in contrast, we know relatively little about the role of the chromatin landscape in defining how start sites of DNA replication are selected and regulated. Here, we describe the Drosophila replication program in the context of the chromatin and transcription landscape for multiple cell lines using data generated by the modENCODE consortium. We find that while the cell lines exhibit similar replication programs, there are numerous cell line-specific differences that correlate with changes in the chromatin architecture. We identify chromatin features that are associated with replication timing, early origin usage, and ORC binding. Primary sequence, activating chromatin marks, and DNA-binding proteins (including chromatin remodelers) contribute in an additive manner to specify ORC-binding sites. We also generate accurate and predictive models from the chromatin data to describe origin usage and strength between cell lines. Multiple activating chromatin modifications contribute to the function and relative strength of replication origins, suggesting that the chromatin environment does not regulate origins of replication as a simple binary switch, but rather acts as a tunable rheostat to regulate replication initiation events.

Eaton, Matthew L.; Prinz, Joseph A.; MacAlpine, Heather K.; Tretyakov, George; Kharchenko, Peter V.; MacAlpine, David M.

2011-01-01

130

Rat intestinal crypt-cell replication factor with homology to early S-phase proteins required for cell division  

Microsoft Academic Search

Cell proliferation requires inhibitory and permissive factors to monitor cell-cycle progression and control DNA replication. The small intestine has a high rate of proliferation and a very low incidence of cancer, suggestive of efficient mechanisms for control of the cell cycle and assuring fidelity of DNA replication. We have isolated a cDNA from a rat crypt-cell library which hybridized to

Donald E. Sykes; Milton M. Weiser

1995-01-01

131

Heterologous microarray experiments allow the identification of the early events associated with potato tuber cold sweetening  

PubMed Central

Background Since its discovery more than 100 years ago, potato (Solanum tuberosum) tuber cold-induced sweetening (CIS) has been extensively investigated. Several carbohydrate-associated genes would seem to be involved in the process. However, many uncertainties still exist, as the relative contribution of each gene to the process is often unclear, possibly as the consequence of the heterogeneity of experimental systems. Some enzymes associated with CIS, such as ?-amylases and invertases, have still to be identified at a sequence level. In addition, little is known about the early events that trigger CIS and on the involvement/association with CIS of genes different from carbohydrate-associated genes. Many of these uncertainties could be resolved by profiling experiments, but no GeneChip is available for the potato, and the production of the potato cDNA spotted array (TIGR) has recently been discontinued. In order to obtain an overall picture of early transcriptional events associated with CIS, we investigated whether the commercially-available tomato Affymetrix GeneChip could be used to identify which potato cold-responsive gene family members should be further studied in detail by Real-Time (RT)-PCR (qPCR). Results A tomato-potato Global Match File was generated for the interpretation of various aspects of the heterologous dataset, including the retrieval of best matching potato counterparts and annotation, and the establishment of a core set of highly homologous genes. Several cold-responsive genes were identified, and their expression pattern was studied in detail by qPCR over 26 days. We detected biphasic behaviour of mRNA accumulation for carbohydrate-associated genes and our combined GeneChip-qPCR data identified, at a sequence level, enzymatic activities such as ?-amylases and invertases previously reported as being involved in CIS. The GeneChip data also unveiled important processes accompanying CIS, such as the induction of redox- and ethylene-associated genes. Conclusion Our Global Match File strategy proved critical for accurately interpretating heterologous datasets, and suggests that similar approaches may be fruitful for other species. Transcript profiling of early events associated with CIS revealed a complex network of events involving sugars, redox and hormone signalling which may be either linked serially or act in parallel. The identification, at a sequence level, of various enzymes long known as having a role in CIS provides molecular tools for further understanding the phenomenon.

Bagnaresi, Paolo; Moschella, Anna; Beretta, Ottavio; Vitulli, Federico; Ranalli, Paolo; Perata, Pierdomenico

2008-01-01

132

Temporal attention enhances early visual processing: a review and new evidence from event-related potentials.  

PubMed

Two fundamental cognitive functions, selective attention and processing of time, have been simultaneously explored in recent studies of temporal orienting of attention. A temporal-orienting procedure may consist of a temporal analogue to the Posner's paradigm, such that symbolic cues indicate the most probable moment for target arrival. Behavioral measures suggest that performance is improved for events appearing at expected vs. unexpected moments. However, there is no agreement on the locus of stimulus processing at which temporal attention operates. Thus, it remains unclear whether early perceptual or just late motor processes can be modulated. This article reviews current ERP research on temporal orienting, with an emphasis on factors that might determine the modulation of temporal orienting at early stages of processing. We conclude that: First, late components (N2 and P300) are consistently modulated by temporal orienting, which suggests attentional preparation of decision and/or motor processes. Second, early components (e.g., N1) seem to be modulated only when the task is highly demanding in perceptual processing. Hence, we conducted an ERP experiment which aimed to observe a modulation of early visual processing by using a perceptually demanding task, such as letter discrimination. The results show, for the first time, that targets appearing at attended moments elicited a larger P1 component than unattended targets. Moreover, temporal attention modulated the amplitude and latency of N2 and P300 components. This suggests that temporal orienting of attention not only modulates late motor processing, but also early visual processing when perceptually demanding tasks are used. PMID:16516173

Correa, Angel; Lupiáñez, Juan; Madrid, Eduardo; Tudela, Pío

2006-03-03

133

Effects of Phenylethyl Isothiocyanate on Early Molecular Events in N-Nitrosomethylbenzylamine-Induced Cytotoxicity in Rat Esophagus  

Microsoft Academic Search

There is little information on early molecular events in the development of N -nitrosomethylbenzylamine (NMBA)- induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-term NMBA treatment and modulated by cotreatment with phenylethyl isothiocyanate (PEITC). Rats were fed AIN-76A

Alan A. Dombkowski; Laura A. Kresty; Daniela Cukovic; Jennifer M. Mele; Sridevi Salagrama; Ronald Nines; Gary D. Stoner

134

Novel three-dimensional organotypic liver bioreactor to directly visualize early events in metastatic progression.  

PubMed

Metastatic seeding leads to most of the morbidity from carcinomas. However, little is known of this key event as current methods to study the cellular behaviors utilize nonrepresentative in vitro models or follow indirect subsequent developments in vivo. Therefore, we developed a system to visualize over a multiday to multiweek period the interactions between tumor cells and target organ parenchyma. We employ an ex vivo microscale perfusion culture system that provides a tissue-relevant environment to assess metastatic seeding behavior. The bioreactor recreates many features of the fluid flow, scale, and biological functionality of a hepatic parenchyma, a common site of metastatic spread for a wide range of carcinomas. As a test of this model, prostate and breast carcinoma cells were introduced. Tumor cell invasion and expansion could be observed by two-photon microscopy of red fluorescent protein (RFP)- and CellTracker-labeled carcinoma cells against a green fluorescent protein (GFP)-labeled hepatic tissue bed over a 14-day period. Tumors visible to the naked eye could be formed by day 25, without evident necrosis in the >0.3-mm tumor mass. These tumor cells failed to grow in the absence of the supporting three-dimensional (3D) hepatic microtissue, suggesting paracrine or stromal support function for the liver structure in tumor progression. Initial ultrastructural studies suggest that early during the tumor-parenchyma interactions, there are extensive interactions between and accommodations of the cancer and host cells, suggesting that the tumor-related epithelial-mesenchymal transition (EMT) reverts, at least transiently, to promote metastatic seeding. In sum, our 3D ex vivo organotypic liver tissue system presents a critical vehicle to examine tumor-host interactions during cancer metastasis and/or invasion. It also circumvents current limitations in assays to assess early events in metastasis, and provides new approaches to study molecular events during tumor progression. PMID:17419948

Yates, Clayton; Shepard, Chistopher R; Papworth, Glenn; Dash, Ajit; Beer Stolz, Donna; Tannenbaum, Steven; Griffith, Linda; Wells, Alan

2007-01-01

135

Assemblage level and intraspecific response of calcareous nannofossils during early Eocene hyperthermal events.  

NASA Astrophysics Data System (ADS)

The composition of calcareous nannofossils across the early Eocene has been investigated at the equatorial Atlantic (Demerara Rise; ODP Site 1260A, 277.17 - 227.04 mbsf & 1260B, 256.16 - 235.10 mbsf), including the Paleocene - Eocene Thermal Maximum (PETM), Eocene thermal maximum 2 (ETM2) = Eocene layer of mysterious origin (Elmo) and ETM3 ("X"-event). These hyperthermal events are marked by a substantial input of isotopically light carbon into the oceans, related to a general warming trend, which led to ocean acidification. Perturbations of the carbon system are thought to have caused significant changes in the composition of marine biota. The PETM interval of Site 1260, defined by the onset and the termination of a negative carbon isotope anomaly with a value of ~ - 2 ‰, is 1.39 m thick (1260A, 276.87 - 275.48 mbsf). The lowermost 65 cm thick interval (1260A, 276.87 - 276.22 mbsf) with a carbonate content lower than 20 % includes a distinctive basal clay layer of approximately 40 cm thickness. The ETM2 is 78 cm thick (1260B, 238.93 - 238.15 mbsf) and marked by a negative carbon isotope excursion of ~ - 1 ‰. The final ETM3 is 17cm thick (1260A, 227.06 - 226.89 mbsf) and shows a negative shift of the carbon isotopes of - 1.2 ‰. The PETM is preceded by two short eutrophic events, where the nannofossil-based productivity index shows very high values, with concomitant low temperatures, the latter eutrophic event is directly preceding the onset of the carbon isotope excursion. The PETM excursion flora can be divided in three groups: 1) Small taxa - or taxa with a big aperture, like Coccolithus minimus, Coccolithus latus and Coccolithus foraminis, which are regarded as stress forms of Coccolithus pelagicus, reacting to possible surface water acidification during the initial phase of the PETM. 2) The large sized Coccolithus bownii, which appears as an acme during the body and early recovery, may profit from increasing pH and decreasing DIC conditions. 3) Teratoid ("malformed") discoasters are not restricted to the PETM and are therefore rather related to higher temperatures then to changes of the oceans carbonate system. Size measurements in the common species of C. pelagicus, including several ecophenotypes like C. minimus and C. latus, show marked changes during the events.

Joachim, C.; Mutterlose, J.

2012-04-01

136

Characteristics of long recovery early VLF events observed by the North African AWESOME Network  

NASA Astrophysics Data System (ADS)

Lightning strokes are capable of initiating disturbances in the lower ionosphere, whose recoveries persist for many minutes. These events are remotely sensed via monitoring subionospherically propagating very low frequency (VLF) transmitter signals, which are perturbed as they pass through the region above the lightning stroke. In this paper we describe the properties and characteristics of the early VLF signal perturbations, which exhibit long recovery times using subionospheric VLF transmitter data from three identical receivers located at Algiers (Algeria), Tunis (Tunisia), and Sebha (Libya). The results indicate that the observation of long recovery events depends strongly on the modal structure of the signal electromagnetic field and the distance from the disturbed region and the receiver or transmitter locations. Comparison of simultaneously collected data at the three sites indicates that the role of the causative lightning stroke properties (e.g., peak current and polarity), or that of transient luminous events may be much less important. The dominant parameter which determines the duration of the recovery time and amplitude appears to be the modal structure of the subionospheric VLF probe signal at the ionospheric disturbance, where scattering occurs, and the subsequent modal structure that propagates to the receiver location.

Naitamor, S.; Cohen, M. B.; Cotts, B. R. T.; Ghalila, H.; Alabdoadaim, M. A.; Graf, K.

2013-08-01

137

Early events in protein folding: Is there something more than hydrophobic burst?  

PubMed Central

The presence of native contacts in the denatured state of many proteins suggests that elements of the biologically active structure of these molecules are formed during the initial stage of the folding process. The rapidity with which these events take place makes it difficult to study them in vitro, but, by the same token, suitable for studies in silico. With the help of all-atom, explicit solvent, molecular dynamics simulations we have followed in time, starting from elongated structureless conformations, the early events in the folding of src-SH3 domain and of proteins G, L, and CI2. It is observed that within the first 50 ns two important events take place, essentially independent of each other: hydrophobic collapse and formation of a few selected native contacts. The same contacts are also found in simulations carried out in the presence of guanidinium chloride in order to reproduce the conditions used to characterize experimentally the denatured state and testify to the fact that these contacts are to be considered a resilient characterizing property of the denaturated state.

Camilloni, Carlo; Sutto, Ludovico; Provasi, Davide; Tiana, Guido; Broglia, Ricardo A.

2008-01-01

138

Early Adverse Events and Attrition in SSRI Treatment: A Suicide Assessment Methodology Study (SAMS) Report  

PubMed Central

Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and may lead to premature treatment discontinuation. If attrition is associated with early worsening of side effects or the frequency, intensity, or burden of side effects, interventions to maximize retention could be focused on patients with these events. Outpatient participants (n=265) with nonpsychotic major depressive disorder entered an 8-week trial with an SSRI. At baseline and week 2, specific side effects were evaluated with the Systematic Assessment for Treatment Emergent Events – Systematic Inquiry, and at week 2 the Frequency, Intensity, and Burden of Side Effects Rating globally assessed side effects. Attrition was defined by those participants who left treatment after week 2 but before week 8. No specific week 2 side effect, either treatment emergent or with worsening intensity, was independently associated with attrition. Global ratings of side effect frequency, intensity, or burden at week 2 were also not associated with subsequent attrition. Neither global ratings nor specific side effects at week 2 were related to patient attrition during SSRI treatment. Other factors appear to contribute to patient decisions about continuing with treatment.

Warden, Diane; Trivedi, Madhukar H.; Wisniewski, Stephen R.; Kurian, Benji; Zisook, Sidney; Kornstein, Susan G.; Friedman, Edward S.; Miyahara, Sachiko; Leuchter, Andrew F.; Fava, Maurizio; Rush, John

2011-01-01

139

Irregularities in Early Seismic Rupture Propagation for Large Events in a Crustal Earthquake Model  

NASA Astrophysics Data System (ADS)

We study early seismic propagation of model earthquakes in a 2-D model of a vertical strike-slip fault with depth-variable rate and state friction properties. Our model earthquakes are obtained in fully dynamic simulations of sequences of instabilities on a fault subjected to realistically slow tectonic loading (Lapusta et al., JGR, 2000). This work is motivated by results of Ellsworth and Beroza (Science, 1995), who observe that for many earthquakes, far-field velocity seismograms during initial stages of dynamic rupture propagation have irregular fluctuations which constitute a "seismic nucleation phase". In our simulations, we find that such irregularities in velocity seismograms can be caused by two factors: (1) rupture propagation over regions of stress concentrations and (2) partial arrest of rupture in neighboring creeping regions. As rupture approaches a region of stress concentration, it sees increasing background stress and its moment acceleration (to which velocity seismographs in the far field are proportional) increases. After the peak in stress concentration, the rupture sees decreasing background stress and moment acceleration decreases. Hence a fluctuation in moment acceleration is created. If rupture starts sufficiently far from a creeping region, then partial arrest of rupture in the creeping region causes a decrease in moment acceleration. As the other parts of rupture continue to develop, moment acceleration then starts to grow again, and a fluctuation again results. Other factors may cause the irregularities in moment acceleration, e.g., phenomena such as branching and/or intermittent rupture propagation (Poliakov et al., submitted to JGR, 2001) which we have not studied here. Regions of stress concentration are created in our model by arrest of previous smaller events as well as by interactions with creeping regions. One such region is deep in the fault zone, and is caused by the temperature-induced transition from seismogenic to creeping behavior at depth. Small events appear in our model at that transition as we decrease the characteristic slip distance for evolution of frictional strength (but not if that distance is unrealistically large). Such clustering of small events at transitions from seismogenic to creeping behavior seems to occur on real faults as well, as we show in examples. To compute moment acceleration that can be compared with data, we translate the results of our 2-D fault model to a 3-D model with essentially radial symmetry on the fault plane. We will discuss limitations of that interpretation; in particular, it may overestimate the effect of partial arrest of rupture in creeping regions. Our present work cannot resolve whether there are any differences in the early phases of seismic moment release, i.e. in the seismic nucleation phase, that would make the beginning of larger events look different from smaller ones that are about to arrest. We have shown that the aseismic nucleation phase and the earliest phases of dynamic breakout are virtually identical for small and large events in our simulations. If early moment release is mostly affected by stress heterogeneities left by previous small events and by creep processes, as our present study suggests, then any such differences would have to be related to as yet unidentified properties of the pre-stress field that might determine the ultimate event size. See http://esag.harvard.edu/lapusta/Lapusta_Rice_Jun01.pdf, Lapusta and Rice, submitted to JGR, 2001.

Lapusta, N.; Rice, J. R.; Rice, J. R.

2001-12-01

140

Frontal genesis of moisture atmosphere during the early 2008 persistent freezing-rain event in southern China  

Microsoft Academic Search

From January 10 to February 2, 2008, a severe and persistent freezing-rain event occurred in southern and southwestern China.\\u000a Here we use an observational analysis to compare the persistent freezing-rain event in the early 2008 with the winter precipitation\\u000a in the late 2007 over south of the Yangtze River (Jiangnan). The persistent freezing-rain event was directly linked to the\\u000a activity

WeiHong Qian; JiaoLan Fu

2010-01-01

141

The regulation of arbuscular mycorrhizal symbiosis by phosphate in pea involves early and systemic signalling events  

PubMed Central

Most plants form root symbioses with arbuscular mycorrhizal (AM) fungi, which provide them with phosphate and other nutrients. High soil phosphate levels are known to affect AM symbiosis negatively, but the underlying mechanisms are not understood. This report describes experimental conditions which triggered a novel mycorrhizal phenotype under high phosphate supply: the interaction between pea and two different AM fungi was almost completely abolished at a very early stage, prior to the formation of hyphopodia. As demonstrated by split-root experiments, down-regulation of AM symbiosis occurred at least partly in response to plant-derived signals. Early signalling events were examined with a focus on strigolactones, compounds which stimulate pre-symbiotic fungal growth and metabolism. Strigolactones were also recently identified as novel plant hormones contributing to the control of shoot branching. Root exudates of plants grown under high phosphate lost their ability to stimulate AM fungi and lacked strigolactones. In addition, a systemic down-regulation of strigolactone release by high phosphate supply was demonstrated using split-root systems. Nevertheless, supplementation with exogenous strigolactones failed to restore root colonization under high phosphate. This observation does not exclude a contribution of strigolactones to the regulation of AM symbiosis by phosphate, but indicates that they are not the only factor involved. Together, the results suggest the existence of additional early signals that may control the differentiation of hyphopodia.

Balzergue, Coline; Puech-Pages, Virginie; Becard, Guillaume; Rochange, Soizic F.

2011-01-01

142

Immunological and Virological Events in Early HIV Infection Predict Subsequent Rate of Progression  

PubMed Central

Background Variability in HIV disease progression cannot fully be predicted by CD4 T-cell counts or viral load. Because central memory T cells (TCM) play a critical role in the pathogenesis of SIV disease, we hypothesized that quantifying these cells in early HIV-infection could provide prognostic information. Methods We measured expression of CD45RO, CCR5, CCR7, CD27, and CD28 to enumerate naïve and memory subsets in samples from recently-infected individuals. We also quantified proliferation, CD127 expression, and cell-associated viral load. Disease progression was compared across subgroups defined by these measurements, using Kaplan-Meier survival curves and multivariate Cox proportional hazards regression. Results 466 subjects contributed 101 events. The proportion or absolute count of TCM did not correlate with disease progression, defined as the time to AIDS or death. However, significant associations were observed for: proliferation within CD4 or CD8 T cells, loss of naïve or CD127+ CD8 T cells, and CD4 cell-associated proviral load. Conclusion Our results demonstrate that the extent of the immunopathogenesis established early in HIV infection predicts the course of future disease. Since antiretroviral drug treatment reverses such defects in part, our study provides mechanistic clues to why early use of antiretrovirals may prove beneficial.

Ganesan, Anuradha; Chattopadhyay, Pratip K.; Brodie, Tess M.; Qin, Jing; Gu, Wenjuan; Mascola, John R.; Michael, Nelson L.; Follmann, Dean A.; Roederer, Mario

2009-01-01

143

Fission yeast cdc21+ belongs to a family of proteins involved in an early step of chromosome replication.  

PubMed Central

The cdc21+ gene of Schizosaccharomyces pombe was originally identified in a screen for cdc mutants affecting S phase and nuclear division. Here we show that the cdc21+ gene product belongs to a family of proteins implicated in DNA replication. These include the Saccharomyces cerevisiae MCM2 and MCM3 proteins, which are needed for the efficient function of certain replication origins, and S.cerevisiae CDC46, which is required for the initiation of chromosome replication. The cdc21 mutant is defective in the mitotic maintenance of some plasmids, like mcm2 and mcm3. The mutant arrests with a single nucleus containing two genome equivalents of DNA, and maintains a cytoplasmic microtubular configuration. Activation of most, but not all, replication origins in the mutant may result in failure to replicate a small proportion of the genome, and this could explain the arrest phenotypes. Using the polymerase chain reaction technique, we have identified new cdc21(+)-related genes in S.cerevisiae, S.pombe and Xenopus laevis. Our results suggest that individual members of the cdc21(+)-related family are highly conserved in evolution. Images

Coxon, A; Maundrell, K; Kearsey, S E

1992-01-01

144

Paleoceanographic change associated with the Early Aptian Oceanic Anoxic Event in the western Tethys  

NASA Astrophysics Data System (ADS)

The Cretaceous oceanic anoxic events (OAEs) provide a good opportunity to study the biogeochemical pathways and feedbacks linked to environmental change. The early Aptian OAE, labelled OAE 1a, corresponds to one of the most studied anoxic events within the Cretaceous. This event is characterized by a positive excursion in ?13C, preceded by a pronounced negative spike. Here, we propose to improve our understanding of palaeoceanographic change leading to this event and test the proposed models by investigating phosphorus (P) and redox-sensitive trace-element (RSTE) contents in sections through lower Aptian sediments along a basin-shelf transect in the western Tethys. We complement our geochemical analysis by the analysis of organic matter contents. We selected three representative sections: Gorgo a Cerbara (central Italy) in the Umbria Marche basin, Glaise l’Ermitage (SE France) located in the Vocontian Trough and Cassis/La Bédoule (SE France) located along the Provencal platform. The general trend in P accumulation shows an increase at the onset of the early Aptian event followed by a rapid decrease. This suggests an increase in nutrient input, whereas the return to lower values through the first part of the anoxic event may be related to a weakened capacity to retain P in the sedimentary reservoir due to bottom-water oxygen depletion. This general pattern is contrasted by the data of Gorgo a Cerbara, which also show P-enrichments at the top of the Livello Selli. We compared these enrichments to the total organic carbon (TOC) values. The shales with the maximum TOC values correspond also to those with the highest P content. We calculated Corg:Ptot ratios and observed that the highest values correspond to the top of the Selli level. This is interpreted as a reflection of the decreased capacity of storing and preserving phosphorus in oxygen-depleted sediments. RSTE show similar behaviour in the basinal settings. In the section of Gorgo a Cerbara, the data for U, V, Mo, Co, As show a low background level, constrasted by different maxima in concentrations near the top of the Selli level. In the Glaise section, a weak increase is observed just after the negative spike in ?13C whereas in the Cassis/La Bédoule section, no significant enrichments have been observed in sediments equivalent to the Selli level. The different behaviour of the RSTE in the studied sections may be related to the palaeogeographic setting of the studied sections. These data seem to indicate anoxic conditions in the basin. In shallower-water environments, conditions may have been less reducing. Moreover, in Gorgo a Cerbara, three distinct enrichments have been observed. This seems to indicate fluctuations in the intensity of water-column anoxia during the shift in ?13C. Our results show that the expression of the OAE 1a is different following the palaeogeographic setting. The stratigraphic evolution of P contents suggests an increase in nutrient input at the onset of the anoxic event, just after the negative spike in ?13C. RSTE and high C:P values may indicate anoxia conditions in the deep environment characterized by several anoxic phases with intermittent return to less oxygen-depleted conditions.

Westermann, S.; Matera, V.; Fiet, N.; Thierry, A.; Follmi, K. B.

2009-12-01

145

Early event of protein folding studied by time-resolved photoacoustic calorimetry  

NASA Astrophysics Data System (ADS)

Recently, various methods including temperature jump and hydro-dynamics focusing have been used to study early event of protein folding. In this paper, we propose to use time-resolved photoacoustic (PAC) to study protein folding from nanoseconds to microseconds. The experiment use photolabile linkers to "cage" proteins or peptide systems that differ from their native equilibrium structures. Pulse laser was used to break the photolabile linker and initiate the refolding of the protein toward its native state. This novel method is very different from denature and temperature jump experiments because folding can start from a well-defined initial state. An acoustic microphone was used to detect the folding induced heat and volume changes of b-sheet peptides and mutants. Time-resolved PAC provides a new method to directly probe the folding funnel energy landscape.

Fann, Wunshain; Chen, Hsin-Liang; Huang, Jen-Tse; Chen, Pei-Yeh R.; Tien Lee, Chung; Chan, Sunney I.

2003-03-01

146

Respiratory defect as an early event in preservation-reoxygenation injury of endothelial cells.  

PubMed

Characterization of preservation injury in endothelial cells has been primarily accomplished by measurement of cell viability. To analyze early events and cellular mechanisms of preservation-reoxygenation injury, we developed high-resolution respirometry for the study of mitochondrial function in endothelial cells, to provide a quantitative marker for sublethal stress. Cultured human umbilical vein endothelial cells were stored for 4 and 8 hr at 4 degrees C under an atmosphere of 95% N2 and 5% CO2 in University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions. Respiration of suspended cells, measured after reoxygenation in growth medium at 37 degrees C, was significantly reduced in all treatments in comparison to controls not subjected to cold preservation. In contrast, trypan blue staining was unchanged after 4 hr of preservation and was significant only after 8 hr. After 8 hr of cold storage in UW and HTK solutions, respiration was 64+/-5% and 49+/-6%, respectively, of controls (46.5+/-3.3 pmol O2 x s(-1 x 10(-6) cells), indicating significantly better protection by UW solution than HTK solution. A titration regimen with substrate (succinate), uncoupler (carbonyl cyanide p-trifluoromethoxyphenylhydrazone), and inhibitors of complexes I and III (rotenone and antimycin A) resulted in identical respiratory response patterns in all treatments. The plasma membrane remained impermeable to succinate. Inner mitochondrial membrane function was preserved as indicated by a constant relative increase of respiration after uncoupling. These results demonstrate that loss of catalytic capacity for respiration constitutes an early event in preservation-reoxygenation injury, whereas membrane damage is not a primary defect. Respirometric evaluation of sublethal cell injury and localization of cell damage may provide selective guidelines for further optimization of strategies in organ preservation. PMID:9000675

Steinlechner-Maran, R; Eberl, T; Kunc, M; Schröcksnadel, H; Margreiter, R; Gnaiger, E

1997-01-15

147

Dephosphorylation of ezrin as an early event in renal microvillar breakdown and anoxic injury.  

PubMed Central

Disruption of the renal proximal tubule (PT) brush border is a prominent early event during ischemic injury to the kidney. The molecular basis for this event is unknown. Within the brush border, ezrin may normally link the cytoskeleton to the cell plasma membrane. Anoxia causes ezrin to dissociate from the cytoskeleton and also causes many cell proteins to become dephosphorylated in renal PTs. This study examines the hypothesis that ezrin dephosphorylation accompanies and may mediate the anoxic disruption of the rabbit renal PT. During normoxia, 73 +/- 3% of the cytoskeleton-associated (Triton-insoluble) ezrin was phosphorylated, but 88 +/- 6% of dissociated (Triton-soluble) ezrin was dephosphorylated. Phosphorylation was on serine/threonine resides, since ezrin was not detectable by an antibody against phosphotyrosine. After 60 min of anoxia, phosphorylation of total intracellular ezrin significantly decreased from 72 +/- 2% to 21 +/- 9%, and ezrin associated with the cytoskeleton decreased from 91 +/- 2% to 58 +/- 2%. Calyculin A (1 microM), the serine/threonine phosphatase inhibitor, inhibited the dephosphorylation of ezrin during anoxia by 57% and also blocked the dissociation of ezrin from the cytoskeleton by 53%. Our results demonstrate that (i) the association of ezrin with the renal microvillar cytoskeleton is correlated with phosphorylation of ezrin serine/threonine residues and (ii) anoxia may cause disruption of the renal brush border by dephosphorylating ezrin and thereby dissociating the brush border membrane from the cytoskeleton. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4

Chen, J; Cohn, J A; Mandel, L J

1995-01-01

148

Earthquake Early Warning for Large Events using Probabilistic Models for Seismic Rupture Prediction  

NASA Astrophysics Data System (ADS)

Earthquake Early Warning (EEW) requires a rapid determination of source and ground motion parameters before strong shaking occurs. The potential warning time to heavily shaken areas are greatest for infrequent large earthquakes (Mw>7.5) with rupture expansions of hundreds of kilometers. However, these long rupture-length events pose a major challenge; that is how to recognize that an ongoing rupture is likely to propagate for a long distance. We determine the posterior probabilities of remaining rupture length Lr as a function of current slip amplitude uc from simulated slip pulses using calibrated stochastic 1-D models. We find that (1) large current slip amplitudes usually indicate that a rupture will continue, although the uncertainty is significant which underlines the need for a probabilistic description; and (2) the relationship between uc and Lr is strongly controlled by fault characteristics, such as the spatial roughness of slip along the fault, which may be a function of the maturity of the fault system. For a practical application this means that one of the most important challenges in EEW for large events is the rapid recognition of the characteristics of the fault, along which the rupture propagates. For example, a critical question is, "is this ongoing rupture on the San Andreas fault?"" Our findings also support the hypothesis (with the above constraints) that seismic ruptures are to some degree deterministic, that is magnitudes are statistically predictable within the first few seconds after rupture initiation, provided that the hypocenter is in a patch of large slip.

Heaton, T. H.; Böse, M.

2008-12-01

149

Reflections on some early events related to behavior analysis of child development  

PubMed Central

A series of events related to the early application of behavioral principles to child behavior and development is described. The events began in the 1930s at Columbia University with a solicited letter from John B. Watson suggesting a master's degree thesis problem, and continued through the 1950s and 1960s at the University of Washington. Specifically, these happenings resulted in (a) research demonstrating that Skinner's laboratory method for studying nonhuman organisms could be profitably applied to the laboratory study of young normal children; (b) a demonstration that by successive approximations, a normal child can be operantly conditioned to respond to an arbitrary situation; (c) research showing that the effects of simple schedules of reinforcement obtained with nonhuman organisms could be duplicated in young normal and retarded children; (d) the demonstration that Skinner's operant laboratory method could be adapted to study young children in field situations; (e) research showing that operant principles can be successfully applied to the treatment of a young autistic boy with a serious visual handicap; (f) laboratory studies showing that mothers can be trained to treat their own young children who have behavior problems; (g) an in-home study demonstrating that a mother can treat her own child who has behavior problems; (h) a demonstration that operant principles can be applied effectively to teaching reading, writing, and arithmetic to children with retardation; and (i) publication of a book, Child Development: A Systematic and Empirical Theory, in collaboration with Donald M. Baer, by Prentice Hall in their Century Psychological Series.

Bijou, Sidney W.

1996-01-01

150

Constraints on early events in Martian history as derived from the cratering record  

SciTech Connect

The shapes and densities of crater size-frequency distribution curves are used to constrain two major events early in Martian history: termination of high obliteration rates and viability of the multiple impact origin of the crustal dichotomy. Distribution curves of fresh craters superposed on uplands, intercrater plains, and ridged plains display shapes and densities indicative of formation prior to the end of heavy bombardment. This observation correlates with other geologic evidence, suggesting a major change in the erosional regime following the last major basin size impact (i.e., Argrye). In addition, the multisloped nature of the curves supports the idea that the downturn in the crater size-frequency distribution curves reflects the size-frequency distribution of the impactors rather than being the result of erosion. The crustal dichotomy formed prior to the heavy bombardment intermediate epoch based on distribution curves of knobby terrain; if the dichotomy resulted from a single gigantic impact, this observation places constraints on when this event happened. An alternate theory for dichotomy formation, the multiple-impact basin idea, is questioned: since distribution curves of large basins as well as heavy bombardment era units are not represented by a {minus}3 differential power law function, this study finds fewer basins missing on Mars compare to the Moon and Mercury than previously reported. The area covered by these missing basins is less than that covered the northern plains.

Barlow, N.G. (Lunar and Planetary Institute, Houston, TX (USA))

1990-08-30

151

Latest Jurassic-early Cretaceous events and the ''late Cimmerian unconformity'' in North Sea area  

SciTech Connect

Several regional or local unconformities occur in the latest Jurassic-Early Cretaceous sequences of the North Sea and adjacent areas. Each may have been identified locally as the ''late Cimmerian unconformity,'' a supposed major break at the base of the Valhall Formation (or Rodby Formation where the Valhall is locally absent). Although a major hiatus (or a condensed sequence) may occur at basin margins or above structural highs, over most of the North Sea the base of the Valhall Formation is isochronous, and conformable with underlying sediments. It is detected on seismic reflection profiles because it represents a widespread facies change marking the late Ryazanian transgression. Most of the unconformities and associated sedimentary and/or biologic events are of eustatic origin and, even in the tectonically active areas of the North Sea, the effects of eustatic sea level changes were never completely masked by local tectonics. Thus, in the modeling of individual oil fields, the possibility of sedimentary breaks occurring can be predicted in part by reference to regional or eustatic events.

Rawson, P.F. (Queen Mary College, London, United Kingdom); Riley, L.A.

1982-12-01

152

Discourse-based emotional consistency modulates early and middle components of event-related potentials.  

PubMed

In this study, participants read stories describing emotional episodes with either a positive or negative valence (Experiment 1). Following each story, participants were exposed to short sentences referring to the protagonist, and the event-related potential (ERP) for each sentence's last word was recorded. Some sentences described the protagonist's emotion, either consistent or inconsistent with the story; others were neutral; and others involved a semantically anomalous word. Inconsistent emotions were found to elicit larger N100/P200 and N400 than consistent emotions. However, when participants were exposed to the same critical sentences in a control experiment (Experiment 2) in which the stories had been removed, emotional consistency effects disappeared in all ERP components, demonstrating that these effects were discourse-level phenomena. By contrast, the ordinary N400 effect for locally anomalous words in the sentence was obtained both with and without story context. In conclusion, reading stories describing events with emotional significance determines strong and very early anticipations of an emotional word. PMID:21171758

León, Inmaculada; Díaz, José M; de Vega, Manuel; Hernández, Juan A

2010-12-01

153

Diagnosis of second breast cancer events after initial diagnosis of early stage breast cancer.  

PubMed

To examine whether there are any characteristics of women or their initial tumors that might be useful for tailoring surveillance recommendations to optimize outcomes. We followed 17,286 women for up to 5 years after an initial diagnosis of ductal carcinoma in situ (DCIS) or early stage (I/II) invasive breast cancer diagnosed between 1996 and 2006. We calculated rates per 1,000 women years of recurrences and second breast primaries relative to demographics, risk factors, and characteristics of initial diagnosis: stage, treatment, mode of initial diagnosis. Nearly 4% had a second breast cancer event (314 recurrences and 344 second breast primaries). Women who used adjuvant hormonal therapy or were ? 80 years had the lowest rates of second events. Factors associated with higher recurrence and second primary rates included: initial DCIS or stage IIB, estrogen/progesterone receptor-negative, younger women (<50 years). Women with a family history or greater breast density had higher second primary rates, and women who received breast conserving surgery without radiation had higher recurrence rates. Roughly one-third of recurrences (37.6%) and second primaries (36.3%) were not screen-detected. Initial mode of diagnosis was a predictor of second events after adjusting for age, stage, primary treatment, and breast density. A recent negative mammogram should not falsely reassure physicians or women with new breast symptoms or changes because one-third of second cancers were interval cancers. This study does not provide any evidence in support of changing surveillance intervals for different subgroups. PMID:20700648

Buist, Diana S M; Abraham, Linn A; Barlow, William E; Krishnaraj, Arun; Holdridge, Regan C; Sickles, Edward A; Carney, Patricia A; Kerlikowske, Karla; Geller, Berta M

2010-08-11

154

Diagnosis of second breast cancer events after initial diagnosis of early stage breast cancer  

PubMed Central

To examine whether there are any characteristics of women or their initial tumors that might be useful for tailoring surveillance recommendations to optimize outcomes. We followed 17,286 women for up to 5 years after an initial diagnosis of ductal carcinoma in situ (DCIS) or early stage (I/II) invasive breast cancer diagnosed between 1996 and 2006. We calculated rates per 1,000 women years of recurrences and second breast primaries relative to demographics, risk factors, and characteristics of initial diagnosis: stage, treatment, mode of initial diagnosis. Nearly 4% had a second breast cancer event (314 recurrences and 344 second breast primaries). Women who used adjuvant hormonal therapy or were ?80 years had the lowest rates of second events. Factors associated with higher recurrence and second primary rates included: initial DCIS or stage IIB, estrogen/progesterone receptor-negative, younger women (<50 years). Women with a family history or greater breast density had higher second primary rates, and women who received breast conserving surgery without radiation had higher recurrence rates. Roughly one-third of recurrences (37.6%) and second primaries (36.3%) were not screen-detected. Initial mode of diagnosis was a predictor of second events after adjusting for age, stage, primary treatment, and breast density. A recent negative mammogram should not falsely reassure physicians or women with new breast symptoms or changes because one-third of second cancers were interval cancers. This study does not provide any evidence in support of changing surveillance intervals for different subgroups.

Abraham, Linn A.; Barlow, William E.; Krishnaraj, Arun; Holdridge, Regan C.; Sickles, Edward A.; Carney, Patricia A.; Kerlikowske, Karla; Geller, Berta M.

2010-01-01

155

Membrane remodeling, an early event in benzo[alpha]pyrene-induced apoptosis  

SciTech Connect

Benzo[alpha]pyrene (B[alpha]P) often serves as a model for mutagenic and carcinogenic polycyclic aromatic hydrocarbons (PAHs). Our previous work suggested a role of membrane fluidity in B[alpha]P-induced apoptotic process. In this study, we report that B[alpha]P modifies the composition of cholesterol-rich microdomains (lipid rafts) in rat liver F258 epithelial cells. The cellular distribution of the ganglioside-GM1 was markedly changed following B[alpha]P exposure. B[alpha]P also modified fatty acid composition and decreased the cholesterol content of cholesterol-rich microdomains. B[alpha]P-induced depletion of cholesterol in lipid rafts was linked to a reduced expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). Aryl hydrocarbon receptor (AhR) and B[alpha]P-related H{sub 2}O{sub 2} formation were involved in the reduced expression of HMG-CoA reductase and in the remodeling of membrane microdomains. The B[alpha]P-induced membrane remodeling resulted in an intracellular alkalinization observed during the early phase of apoptosis. In conclusion, B[alpha]P altered the composition of plasma membrane microstructures through AhR and H{sub 2}O{sub 2} dependent-regulation of lipid biosynthesis. In F258 cells, the B[alpha]P-induced membrane remodeling was identified as an early apoptotic event leading to an intracellular alkalinization.

Tekpli, Xavier; Rissel, Mary; Huc, Laurence [EA 4427 SeRAIC, Equipe labellisee Ligue contre le Cancer, Universite de Rennes 1, IFR 140, 35043 Rennes cedex (France); Catheline, Daniel [Laboratoire de Biochimie, INRA-Agrocampus Rennes, 35042 Rennes (France); Sergent, Odile [EA 4427 SeRAIC, Equipe labellisee Ligue contre le Cancer, Universite de Rennes 1, IFR 140, 35043 Rennes cedex (France); Rioux, Vincent; Legrand, Philippe [Laboratoire de Biochimie, INRA-Agrocampus Rennes, 35042 Rennes (France); Holme, Jorn A. [Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 404 Torshov, N-4303 Oslo (Norway); Dimanche-Boitrel, Marie-Therese [EA 4427 SeRAIC, Equipe labellisee Ligue contre le Cancer, Universite de Rennes 1, IFR 140, 35043 Rennes cedex (France); Lagadic-Gossmann, Dominique, E-mail: dominique.lagadic@univ-rennes1.f [EA 4427 SeRAIC, Equipe labellisee Ligue contre le Cancer, Universite de Rennes 1, IFR 140, 35043 Rennes cedex (France)

2010-02-15

156

Aberrant Methylation of the Maspin Promoter Is an Early Event in Human Breast Cancer1  

PubMed Central

Abstract The maspin gene functions as a tumor suppressor in human breasts, and its expression is frequently lost during breast cancer progression. In vitro models of human breast cancer indicate that the loss of maspin expression is closely linked to aberrant methylation of the maspin promoter. We conducted a study on 30 archival ductal carcinoma in situ (DCIS) specimens to determine if aberrant methylation of the maspin promoter occurred in vivo, and whether it occurred early in breast cancer evolution. Healthy tissue obtained from reduction mammoplasty was used as normal control. Results from immunohistochemical analysis indicate that maspin expression is lost in a substantial fraction of DCIS specimens (57%). Bisulfite sequencing of DNA isolated from laser capture-microdissected normal and neoplastic ducts showed that loss of maspin expression was often, but not always, linked to aberrant methylation of the maspin promoter, suggesting that other mechanisms, in addition to aberrant methylation, participate and/or cooperate to silence maspin gene expression. Taken together, these results indicate that aberrant methylation of the maspin promoter is an early event in human breast cancer.

Futscher, Bernard W.; O'Meara, Megan M.; Kim, Christina J.; Rennels, Margaret A.; Lu, Di; Gruman, Lynn M.; Seftor, Richard E. B.; Hendrix, Mary J. C.; Domann, Frederick E.

2004-01-01

157

Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei  

Microsoft Academic Search

Summary We have used immunofluorescent detection of 5- bromo-2-deoxyuridine-substituted DNA in order to determine the timing of initiation and the duration of nuclear and kinetoplast S-phases within the procyclic stage of the Trypanosoma brucei cell cycle. Both nuclear and kinetoplast S-phases were shown to be periodic, occupying 0.18 and 0.12 of the unit cell cycle, respectively. In addition, initiation of

R. WOODWARD

158

Involuntary attention impairment in early Parkinson's disease: an event-related potential study.  

PubMed

Dopaminergic nigro-striatal depletion interferes with the detection of novel stimuli. This suggests that Parkinson's disease (PD) may generate from the initial stages a failure in involuntary attention (IA), which can be studied through the distraction potential, composed by the mismatch negativity (MMN), the P3a and the reorientation negativity (RON). This study analyzed IA using event-related potentials (ERPs) in patients with early PD with and without dopaminergic replacement therapy. Twenty-five medicated, and 17 non-medicated patients with early PD were studied, as well as 20 healthy control subjects. All subjects performed an auditory distraction task while a digital EEG was being recorded. The distraction potential was obtained by averaging methodology. Each wave was analyzed with a Repeated Measures ANOVA test. The MMN was obtained in all subjects and no significant differences in mean amplitude were found among the groups. There was a main effect of group for the amplitude of P3a (F(2,59)=4.8, p=0.01, ?=0.411), with a significant lower amplitude in the medicated group compared to the control group (MD=-1.03, p=0.003). RON also showed a main effect of group (F(2,59)=4.8, p=0.01, ?=0.467), with significantly lower amplitudes in non-medicated patients with respect to both the control and medicated groups (MD=1.19, p=0.01, MD=1.27, p=0.005, respectively). There were no significant differences in the latencies of any of the waves among the groups. The main finding of this study was the reduction in the IA in early PD. Reorientation of attention (RON) showed a dopaminergic modulation in these patients. These results represent the basis for future in depth studies on the involvement of IA in executive impairments in PD. PMID:21443924

Solís-Vivanco, Rodolfo; Ricardo-Garcell, Josefina; Rodríguez-Camacho, Mario; Prado-Alcalá, Roberto A; Rodríguez, Ulises; Rodríguez-Violante, Mayela; Rodríguez-Agudelo, Yaneth

2011-04-02

159

Modulation of in vitro transformation and the early and late modes of DNA replication of uv-irradiation Syrian hamster cells by caffeine  

SciTech Connect

The effect of caffeine on post-uv DNA replication was studied to determine its relevance to carcinogenesis. The level of uv-induced transformed colonies of Syrian hamster embryo cells (HEC) was increased up to fivefold when caffeine was added to cells between 0 and 6 h post-uv. The greatest increase was observed when the interval between uv irradiation and caffeine addition was 4 h. Two modes of DNA replication occurred after uv irradiation. During the early mode (0 to 3 h post-uv) the size of nascent strands, as measured by alkaline sucrose sedimentation, was smaller than those in nonirradiated cells, whereas during the late mode they recovered to normal size. Caffeine inhibited the rate of elongation of nascent strands during the early mode. When caffeine was added immediately after uv irradiation, the conversion of the early mode to the late mode was inhibited. Studies on the effects of caffeine have now been extended to the late mode. While caffeine has little effect with the fd elements beginning from the 10th day after irradiation is connected with their proliferation but not with the migration out from lymphoid organs.

Doniger, J.; DiPaolo, J.A.

1981-09-01

160

Effects of 60 Hz electromagnetic fields on early growth in three plant species and a replication of previous results  

Microsoft Academic Search

In an attempt to replicate the findings of Smith et al., seeds of Raphanus sativus L. (radish), Sinapsis alba L. (mustard), and Hordeum vulgare L. (barley) were grown for between 9 and 21 days in continuous electromagnetic fields (EMFs) at ion-cyclotron resonance conditions for stimulation of Ca{sup 2+} (B{sub H} = 78.3 μT, B{sub HAC} = 40 μT peak-peak at

1996-01-01

161

Protein-mediated Selective Enclosure of Early Replicators Inside of Membranous Vesicles: First Step Towards Cell Membranes  

Microsoft Academic Search

Containment in cell membranes is essential for all contemporary life, and apparently even the earliest life forms had to be\\u000a somehow contained. It has been postulated that random enclosure of replicating molecules inside of spontaneously assembled\\u000a vesicles would have formed the initial cellular ancestors. However, completely random re-formation or division of such primitive\\u000a vesicles would have abolished the heritability of

Tiina Laiterä; Kirsi Lehto

2009-01-01

162

The glutathione transferase of Nicotiana benthamiana NbGSTU4 plays a role in regulating the early replication of Bamboo mosaic virus.  

PubMed

Bamboo mosaic virus (BaMV) is a single-stranded positive-sense RNA virus. One of the plant glutathione S-transferase (GST) genes, NbGSTU4, responds as an upregulated gene in Nicotiana benthamiana post BaMV infection. In order to identify the role of NbGSTU4 in BaMV infection, the expression of NbGSTU4 was knocked down using a virus-induced gene silencing technique or was transiently expressed in N. benthamiana in BaMV inoculation. The results show a significant decrease in BaMV RNA accumulation when the expression level of NbGSTU4 is reduced; whereas the viral RNA accumulation increases when NbGSTU4 is transiently expressed. Furthermore, this study identified that the involvement of NbGSTU4 in viral RNA accumulation occurs by its participation in the viral early replication step. The findings show that the NbGSTU4 protein expressed from Escherichia coli can interact with the 3' untranslated region (UTR) of the BaMV RNA in vitro in the presence of glutathione (GSH). The addition of GSH in the in vitro replication assay shows an enhancement of minus-strand but not plus-strand RNA synthesis. The results suggest that the plant GST protein plays a role in binding viral RNA and delivering GSH to the replication complex to create a reduced condition for BaMV minus-strand RNA synthesis. PMID:23701112

Chen, I-Hsuan; Chiu, Meng-Hsuen; Cheng, Shun-Fang; Hsu, Yau-Heiu; Tsai, Ching-Hsiu

2013-05-23

163

Herpes Simplex Virus Type 1 Latency-Associated Transcripts Suppress Viral Replication and Reduce Immediate-Early Gene mRNA Levels in a Neuronal Cell Line  

PubMed Central

During herpes simplex virus type 1 (HSV-1) latent infection in human dorsal root ganglia, limited viral transcription, which has been linked to HSV-1 reactivation ability, takes place. To study the involvement of this transcription in HSV-1 replication in neuronal cells and consequently in viral latency, we constructed stably transfected neuronal cell lines containing (i) the entire HSV-1 latency transcriptionally active DNA fragment, (ii) the same DNA sequence with deletions of the latency-associated transcript (LAT) promoters, or (iii) the DNA coding sequence of the LAT domain. Replication of HSV-1 or a LAT-negative mutant was markedly repressed in the LAT-expressing cells, a phenomenon mediated by the LATs. To study the mechanism responsible for this effect, we examined LAT influence upon expression of HSV-1 immediate-early (IE) genes ICP0, ICP4, and ICP27, by Northern blot analysis. Following infection of a LAT-expressing neuronal cell line with a LAT-negative mutant, the steady-state levels of all three IE mRNAs were reduced compared to those for control cells. Transient transfections into a neuronal cell line indicated that the LAT suppressive effect upon ICP0 mRNA was mediated directly and was not due to the LAT effect upon the ICP0 promoter. We therefore propose that the LATs may repress viral replication in neuronal cells by reducing IE gene mRNA levels and thus facilitate the establishment of HSV-1 latency in nervous tissue.

Mador, Nurith; Goldenberg, Daniel; Cohen, Oren; Panet, Amos; Steiner, Israel

1998-01-01

164

The glutathione transferase of Nicotiana benthamiana NbGSTU4 plays a role in regulating the early replication of Bamboo mosaic virus  

PubMed Central

Bamboo mosaic virus (BaMV) is a single-stranded positive-sense RNA virus. One of the plant glutathione S-transferase (GST) genes, NbGSTU4, responds as an upregulated gene in Nicotiana benthamiana post BaMV infection. In order to identify the role of NbGSTU4 in BaMV infection, the expression of NbGSTU4 was knocked down using a virus-induced gene silencing technique or was transiently expressed in N. benthamiana in BaMV inoculation. The results show a significant decrease in BaMV RNA accumulation when the expression level of NbGSTU4 is reduced; whereas the viral RNA accumulation increases when NbGSTU4 is transiently expressed. Furthermore, this study identified that the involvement of NbGSTU4 in viral RNA accumulation occurs by its participation in the viral early replication step. The findings show that the NbGSTU4 protein expressed from Escherichia coli can interact with the 3? untranslated region (UTR) of the BaMV RNA in vitro in the presence of glutathione (GSH). The addition of GSH in the in vitro replication assay shows an enhancement of minus-strand but not plus-strand RNA synthesis. The results suggest that the plant GST protein plays a role in binding viral RNA and delivering GSH to the replication complex to create a reduced condition for BaMV minus-strand RNA synthesis.

Chen, I-Hsuan; Chiu, Meng-Hsuen; Cheng, Shun-Fang; Hsu, Yau-Heiu; Tsai, Ching-Hsiu

2013-01-01

165

Evaluation of Radar Rainfall Estimation in Widespread Early Spring Rainfall Events  

NASA Astrophysics Data System (ADS)

Significant discrepancies can exist between actual and estimated rainfall with the interaction of biases and random error being documented in a number of studies. Numerous reports have demonstrated strong scale dependence in the uncertainties or errors in radar rainfall estimation strategies. This study addresses issues of scale, radar-range and uncertainty of weather radar rainfall measurements under early spring conditions. Rainfall measurement analysis is focused on XPOL (mobile X-band dual polarization weather radar) retrievals from late March through early May 2002 in Northeastern Connecticut, US. The applicable XPOL dataset has been refined through attenuation correction, considerations of contamination and vertical profiles adjustment and noise to twelve rainfall events at a base resolution of 300-meter grids every five minutes. XPOL measurements are validated with sixteen raingauges dispersed in the representative 424 km2 Mansfield Watershed at a maximum range of 23 km. The comparison dataset is taken from the NEXRAD stage-III bias adjusted hourly rainfall rates. This specific data is drawn from the most proximal National Weather Service radars in Upton, NY and Boston, MA each over 100 km away, demonstrating gridded rainfall on a 4-kilometer scale. Several statistical evaluations are employed to study the scale effects and cross-platform radar differences. XPOL radar observations are aggregated to coarser spatial grids; in successive aggregations we test the relative error of selected points against raingauge validation. Spatial XPOL data can be matched directly to NEXRAD stage III data thereby giving an indication of the internal variance of NEXRAD pixels. The assimilated internal variability of NEXRAD rain retrievals may offer insight into the bias and uncertainty of the system and information on the radar-gauge comparison uncertainty.

Knox, R. G.; Anagnostou, E. N.

2004-05-01

166

Matrix Metalloproteinases Limit Functional Recovery after Spinal Cord Injury by Modulation of Early Vascular Events  

PubMed Central

Inflammation in general and proteinases generated as a result are likely mediators of early secondary pathogenesis after spinal cord injury. We report that matrix metalloproteinase-9 (MMP-9) plays an important role in blood–spinal cord barrier dysfunction, inflammation, and locomotor recovery. MMP-9 was present in the meninges and neurons of the uninjured cord. MMP-9 increased rapidly after a moderate contusion spinal cord injury, reaching a maximum at 24 hr, becoming markedly reduced by 72 hr, and not detectable at 7 d after injury. It was seen in glia, macrophages, neutrophils, and vascular elements in the injured spinal cord at 24 hr after injury. The natural tissue inhibitors of MMPs were unchanged over this time course. MMP-9-null mice exhibited significantly less disruption of the blood–spinal cord barrier, attenuation of neutrophil infiltration, and significant locomotor recovery compared with wild-type mice. Similar findings were observed in mice treated with a hydroxamic acid MMP inhibitor from 3 hr to 3 d after injury, compared with the vehicle controls. Moreover, the area of residual white matter at the lesion epicenter was significantly greater in the inhibitor-treated group. This study provides evidence that MMP-9 plays a key role in abnormal vascular permeability and inflammation within the first 3 d after spinal cord injury, and that blockade of MMPs during this critical period attenuates these vascular events and leads to improved locomotor recovery. Our findings suggest that early inhibition of MMPs may be an efficacious strategy for the spinal cord-injured patient.

Noble, Linda J.; Donovan, Frances; Igarashi, Takuji; Goussev, Staci; Werb, Zena

2009-01-01

167

Molecular aspects of retinoic-acid-induced cellular differentiation: early events in differentiating F9 teratocarcinoma cells  

SciTech Connect

This thesis examines molecular aspects of retinoic acid induced differentiation of murine F9 teratocarcinoma cells which occur very early after induction. The author has studied the molecular response of F9 cells to retinoic acid on three levels: expression of various cellular oncogenes at the nRNA level; influence of retinoic acid on DNA replication patterns; and modulation of protein biosynthesis. The c-myc gene was chosen as a specific gene to study because of its association with regulation of cell proliferation and/or differentiation. Down-regulation of a c-myc expression by 50% at 3 hours after induction was demonstrated by Northern blot analysis. The gene is found to be normal copy number relative to control liver and differentiated teratocarcinoma DNA and does not show any of the common rearrangements found in hematopoietic tumors. A genomic library of F9 cell DNA in bacteriophage lambda was constructed to examine in greater detail the genomic organization of the c-myc gene in F9 DNA and to derive probes for study of the 5' end and flanking regions of the gene. Inhibition of DNA replication by high thymidine during the early stages of S-phase was found to induce differentiation in F9 cells without retinoic acid. Using partially synchronized cultures of F9 cells, it was found that retinoic acid alters the pattern of DNA replication as measured by /sup 3/H-thymidine incorporation at the time in the cell cycle which corresponds to high thymidine inhibition of replication. Using a highly sensitive computerized analysis of label autoradiography of two dimensional polyacrylamide gels, changes in the biosynthesis of specific proteins from 3 hours to 48 hours after induction of differentiation have been identified.

Griep, A.E.

1985-01-01

168

Global correlations of mid Early Triassic events: The Induan/Olenekian boundary in the Dolomites (Italy)  

NASA Astrophysics Data System (ADS)

The Dolomites (Southern Alps, Italy) are a reference-area for research on the end-Permian mass extinction and its Early Triassic aftermath. The effects on shallow marine benthic biota are recorded in the Werfen Formation, a thick mixed carbonate-siliciclastic sedimentary succession. Only in its lower (Griesbachian) and upper (Spathian) parts, this formation is bio-chronologically constrained by means of conodonts and ammonoids, whilst no significant bioevent occurs in its middle part. This represents an impediment to the biochronologic recognition of the Induan/Olenekian boundary (IOB). The Bulla/Pufels (Val Gardena) succession is a key-section for the P/T boundary and Early Triassic for global correlation due to the abundance of studies on biostratigraphy (mostly on conodonts), magnetostratigraphy and chemostratigraphy carried out there by stratigraphers of various nationalities. Recent chemostratigraphic studies have permitted the recognition of some carbon isotope positive peaks, the strongest of which is considered to approximate the IOB. However, various authors have reached different conclusions on the position of the maximum peak and thus on the IOB location. This leads to important stratigraphic consequences for the calibration of conodont biostratigraphy. The critical revision of the traditional stratigraphic units (litho- and biostratigraphy), under-evaluated in most of the recent literature, and magneto-, chemo- and sequence stratigraphic units allowed herein an integrated stratigraphic scale for the Bulla/Pufels section to be proposed. This contribution highlights the mid Early Triassic Dolomites record for regional and global correlations. The most significant results attained herein regard the different lithostratigraphic subdivisions of the middle Werfen Formation and its consequences on the position of the IOB with respect to the conodont and bivalve biostratigraphy and sequence stratigraphic units. The upper part of the section is attributed herein to the Gastropod Oolite Member, which is represented by the lithozone A, a predominant supratidal episode, and the lower part of the subtidal lithozone B. Between the lithozones A and B, a sequence boundary of 3th order (Sc2/Sc3) is located. The maximum carbon isotope excursion is near this boundary, which therefore approximates the IOB in the Dolomites. This proposal suggests a Dienerian age for the FO of the conodont Pachycladina obliqua, which occurs about 60 m below the stage boundary. No significant biotic event, either for molluscs or conodonts, occurred across this stage boundary.

Posenato, Renato

2008-12-01

169

Effects of 60 Hz electromagnetic fields on early growth in three plant species and a replication of previous results  

SciTech Connect

In an attempt to replicate the findings of Smith et al., seeds of Raphanus sativus L. (radish), Sinapsis alba L. (mustard), and Hordeum vulgare L. (barley) were grown for between 9 and 21 days in continuous electromagnetic fields (EMFs) at ion-cyclotron resonance conditions for stimulation of Ca{sup 2+} (B{sub H} = 78.3 {micro}T, B{sub HAC} = 40 {micro}T peak-peak at 60 Hz, B{sub v} = 0). On harvesting, radish showed results similar to those of Smith et al. Dry stem weight and plant height were both significantly greater (Mann-Whitney tests, Ps < 0.05) in EMF-exposed plants than in control plants in each EMF experiment. Wet root weight was significantly greater in EMF-exposed plants in two out of three experiments, as were dry leaf weight, dry whole weight, and stem diameter. Dry root weight, wet leaf weight, and wet whole weight were significantly greater in EMF-exposed plants in one of three experiments. All significant differences indicated an increase in weight or size in the EMF-exposed plants. In each of the sham experiments, no differences between exposed and control plants were evident. Mustard plants failed to respond to the EMFs in any of the plant parameters measured. In one experiment, barley similarly failed to respond; but in another showed significantly greater wet root weight and significantly smaller stem diameter and dry seed weight at the end of the experiment in exposed plants compared to control plants. Although these results give no clue about the underlying bioelectromagnetic mechanism, they demonstrate that, at least for one EMF-sensitive biosystem, results can be independently replicated in another laboratory. Such replication is crucial in establishing the validity of bioelectromagnetic science.

Davis, M.S. [Univ. of Sunderland (United Kingdom). Ecology Centre

1996-05-01

170

Visualization of Early Events in Acetic Acid Denaturation of HIV-1 Protease: A Molecular Dynamics Study  

PubMed Central

Protein denaturation plays a crucial role in cellular processes. In this study, denaturation of HIV-1 Protease (PR) was investigated by all-atom MD simulations in explicit solvent. The PR dimer and monomer were simulated separately in 9 M acetic acid (9 M AcOH) solution and water to study the denaturation process of PR in acetic acid environment. Direct visualization of the denaturation dynamics that is readily available from such simulations has been presented. Our simulations in 9 M AcOH reveal that the PR denaturation begins by separation of dimer into intact monomers and it is only after this separation that the monomer units start denaturing. The denaturation of the monomers is flagged off by the loss of crucial interactions between the ?-helix at C-terminal and surrounding ?-strands. This causes the structure to transit from the equilibrium dynamics to random non-equilibrating dynamics. Residence time calculations indicate that denaturation occurs via direct interaction of the acetic acid molecules with certain regions of the protein in 9 M AcOH. All these observations have helped to decipher a picture of the early events in acetic acid denaturation of PR and have illustrated that the ?-helix and the ?-sheet at the C-terminus of a native and functional PR dimer should maintain both the stability and the function of the enzyme and thus present newer targets for blocking PR function.

Borkar, Aditi Narendra; Rout, Manoj Kumar; Hosur, Ramakrishna V.

2011-01-01

171

Impact of early and late winter icing events on sub-arctic dwarf shrubs.  

PubMed

Polar regions are predicted to undergo large increases in winter temperature and an increased frequency of freeze-thaw cycles, which can cause ice layers in the snow pack and ice encasement of vegetation. Early or late winter timing of ice encasement could, however, modify the extent of damage caused to plants. To determine impacts of the date of ice encasement, a novel field experiment was established in sub-arctic Sweden, with icing events simulated in January and March 2008 and 2009. In the subsequent summers, reproduction, phenology, growth and mortality, as well as physiological indicators of leaf damage were measured in the three dominant dwarf shrubs: Vaccinium uliginosum, Vaccinium vitis-idaea and Empetrum nigrum. It was hypothesised that January icing would be more damaging compared to March icing due to the longer duration of ice encasement. Following 2 years of icing, E. nigrum berry production was 83% lower in January-iced plots compared to controls, and V. vitis-idaea electrolyte leakage was increased by 69%. Conversely, electrolyte leakage of E. nigrum was 25% lower and leaf emergence of V. vitis-idaea commenced 11 days earlier in March-iced plots compared to control plots in 2009. There was no effect of icing on any of the other parameters measured, indicating that overall these study species have moderate to high tolerance to ice encasement. Even much longer exposure under the January icing treatment does not clearly increase damage. PMID:23574610

Preece, C; Phoenix, G K

2013-04-10

172

Polarization of the endomembrane system is an early event in fucoid zygote development  

PubMed Central

Background Fucoid zygotes are excellent experimental organisms for investigating mechanisms that establish cell polarity and determine the site of tip growth. A common feature of polarity establishment is targeting endocytosis and exocytosis (secretion) to localized cortical domains. We have investigated the spatiotemporal development of endomembrane asymmetry in photopolarizing zygotes, and examined the underlying cellular physiology. Results The vital dye FM4-64 was used to visualize endomembranes. The endomembrane system preferentially accumulated at the rhizoid (growth) pole within 4 h of fertilization. The polarized endomembrane array was initially labile and reoriented when the developmental axis changed direction in response to changing light cues. Pharmacological studies indicated that vesicle trafficking, actin and microtubules were needed to maintain endomembrane polarity. In addition, endocytosis required a functional cortical actin cytoskeleton. Conclusion Endomembrane polarization is an early event in polarity establishment, beginning very soon after photolocalization of cortical actin to the presumptive rhizoid site. Targeting of endocytosis and secretion to the rhizoid cortex contributes to membrane asymmetry. We suggest that microtubule-actin interactions, possibly involving microtubule capture and stabilization at actin-rich sites in the rhizoid, may organize the endomembrane array.

Hadley, Rhett; Hable, Whitney E; Kropf, Darryl L

2006-01-01

173

Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension  

PubMed Central

Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II) promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnf? and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.

Hartono, Stella P.; Knudsen, Bruce E.; Zubair, Adeel S.; Nath, Karl A.; Textor, Stephen J.; Lerman, Lilach O.; Grande, Joseph P.

2013-01-01

174

Choline acetyltransferase expression does not identify early pathogenic events in fetal SMA spinal cord.  

PubMed

We investigated the expression of choline acetyltransferase, a specific marker for cholinergic neurons, in control and spinal muscular atrophy fetuses and newborns. By immunoblot we observed at 12 and 15 weeks a similar pattern of choline acetyltransferase expression in spinal muscular atrophy with respect to controls, although at 22 weeks this expression was reduced, probably due to a smaller number of motor neurons in the spinal muscular atrophy spinal cord. By immunohistochemistry, the counting of positive and negative motor neurons for choline acetyltransferase immunostaining in control and spinal muscular atrophy fetuses showed a similar proportion at all stages analyzed. The choline acetyltransferase-negative motor neurons were of similar appearance in both groups. After birth, chromatolytic motor neurons were detected in spinal muscular atrophy, all of which were choline acetyltransferase-negative. Our results in spinal muscular atrophy fetuses indicate that choline acetyltransferase immunostaining does not identify early events in neuronal pathogenesis and suggest that the spinal muscular atrophy surviving motor neurons may not be dysfunctional during this period. Furthermore, spinal muscular atrophy choline acetyltransferase-negative motor neurons showed detectable pathological changes only after birth, indicating that choline acetyltransferase is a late marker for motor neuron degeneration and not a primary contributing factor in this process. PMID:15725587

Soler-Botija, Carolina; Cuscó, Ivón; López, Eva; Clua, Agustín; Gich, Ignasi; Baiget, Montserrat; Ferrer, Isidre; Tizzano, Eduardo F

2005-01-28

175

Gender, facial attractiveness, and early and late event-related potential components.  

PubMed

Facial attractiveness has been an interesting topic in cognitive psychology due to its key role in human communication and experience. The evaluation of attractiveness is adjusted by many factors including gender differences and cultural biases. In this paper, event-related potential (ERP) activity was recorded in an oddball paradigm from 10 Chinese men and 10 Chinese women who judged attractiveness of faces. Participants were told to detect faces with neutral expression and judge their attractiveness among a train of neutral objects that were presented more frequently than the faces. The ERP analyses showed that there was enhanced detection over early (P1, N170, P2, N300) and late (P3b) components in both genders. This suggests that a biased electrophysiological response to attractive faces compared to unattractive faces could indicate the involvement of emotion and reward pathways in judging facial attractiveness. Specifically, there were delayed P1 and P3b latencies in response to attractive faces with slower response times in men compared to women. From an evolutionary perspective, this may suggest that men attribute more value to facial appearances, especially attractive features, than women do, as evidenced by their cognitive load while processing attractive faces compared to unattractive faces. PMID:23351053

Zhang, Zimu; Deng, Zhidong

2013-01-07

176

Early Events During Avian Skin Appendage Regeneration: Dependence on Epithelial-Mesenchymal Interaction and order of Molecular Reappearance  

Microsoft Academic Search

Early molecular events during the development and regeneration of skin appendages were studied using cultured chicken skin explants with epithelial-mesenchymal recombination, The explant epithelium was separated from the mesenchyme, rotated 90° or 180°, recombined with the niesenchyme, and cultured. After this procedure, existing feather buds disappeared and new buds were regenerated. The location of the new buds is determined by

Cheng-Ming Chuong; Randall B. Widelitz; Sheree Ting-Berreth; Ting-Xin Jiang

1996-01-01

177

Agreement of Parent and Child Reports of Trauma Exposure and Symptoms in the Early Aftermath of a Traumatic Event  

Microsoft Academic Search

Exposure to violence and potentially traumatic events (PTEs) is a common experience among children and youth. The assessment of necessary intervention relies upon parental acknowledgment of exposure and recognition of their child's distress. Early interventions and treatment are most effective when parents are aware of the nature of the traumatic exposure, understand their child's symptomatic response, and are intimately involved

Carla Smith Stover; Hilary Hahn; Steven Berkowitz; Jamie J. Y. Im

2010-01-01

178

EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.  

EPA Science Inventory

Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes. Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711. Environmental exposure to arsenic is a m...

179

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children  

Microsoft Academic Search

ObjectiveThis study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children.

L. M Jonkman; J. L Kenemans; C Kemner; M. N Verbaten; H van Engeland

2004-01-01

180

Early Event-Related Potential Changes During Working Memory Activation Predict Rapid Decline in Mild Cognitive Impairment  

Microsoft Academic Search

Background. The conversion of mild cognitive impairment (MCI) to Alzheimer's disease is associated with substantial compromise of neocortical circuits subserving rapid cognitive functions such as working memory. Event-related potential (ERP) analysis is a powerful tool to identify early impairment of these circuits, yet research for an electrophysiological marker of cognitive deterioration in MCI is scarce. Using a ''2-back'' activation paradigm,

Pascal Missonnier; Gabriel Gold; Lara Fazio-Costa; Jean-Pierre Michel; Reinhild Mulligan; Agnes Michon; Vicente Ibanez; Panteleimon Giannakopoulos

2005-01-01

181

Effects of musical expertise on the early right anterior negativity: An event-related brain potential study  

Microsoft Academic Search

Event-related brain potentials in response to harmonically inappropriate chords were compared for musical experts and novices. Similar to previous studies, these chords elicited an early right anterior negativity ~ERAN!. The amplitude of the ERAN was clearly larger for musical experts than for novices, presumably because experts had more specific musical expectancies than novices. Chords with a physically deviant timbre elicited

STEFAN KOELSCH; JULIA KANSOK

2002-01-01

182

A comparison of early family life events amongst monozygotic twin women with lifetime anorexia nervosa, bulimia nervosa, or major depression  

Microsoft Academic Search

Objectives: To investigate the differen- tial profile of early family life events asso- ciated with lifetime anorexia nervosa (AN), bulimia nervosa (BN), and major depression (MD). Method: Only data from the monozy- gotic twins (n 5 622) were examined from a community sample of female twins who had participated in three waves of data collection. Eating disorder and MD diagnoses

Tracey D. Wade; Nathan Gillespie; Nicholas G. Martin

2007-01-01

183

Space-time clusters of adverse health events as a means of early detection of departure from planned containment  

Microsoft Academic Search

Studies of rare health events offer a novel means for assessing community health impacts from excursions of hazardous contaminants into the ambient environment. Clusters of these infrequent, adverse health occurrences provide sentinel phenomena to epidemiologists for the purpose of formulating preventive strategies and decision rules. The goal of early identification and interpretation of these case clusters has led to the

T. E. Aldrich; C. E. Easterly

1987-01-01

184

The profile of lysosomal exoglycosidases in replicative and stress-induced senescence in early passage human fibroblasts.  

PubMed

The aim of the present study was to assess the profiles of the exoglycosidases: N-acetyl-?-hexosoaminidase, ? glucuronidase and ? galactosidase, ? mannosidase and ? fucosidase in fibroblast culture undergoing replicative and stress-induced senescence. Half of the cell culture was grown in normal conditions, without the stressor, and the other half of the cell was treated with 0.15 mM tert-butylhydroperoxide. The activities of total N-acetyl-?-hexosoaminidase as well as ? glucuronidase in the cell lysate were determined in duplicates using the method of Marciniak et al. The activities of ? galactosidase, ? mannosidase and ? fucosidase in the cell lysate were determined in duplicates using the method of Chatteriee et al. with the modification by Zwierz et al. The activities of the exoglycosidases examined, with the exception of ? glucuronidase, showed a significant increase between individual days of the experiment in both non-stressed and stressed fibroblast cell culture. On each day of the experiment, in the cell lysate of stressed fibroblasts, the activities of exoglycosidases were significantly higher compared to the non-stressed cells. There were very strong correlations between SA-?-GAL staining and b galactosidase activity on individual days of the experiment in both non-stressed and stressed fibroblast cell culture. Replicative and stress-induced senescence results in significant changes to the level of lysosomal exoglycosidases, and results in enhanced lysosomal degradative capacity. PMID:22763978

Kna?, Ma?gorzata; Zalewska, Anna; Kr?towski, Rafa?; Niczyporuk, Marek; Waszkiewicz, Napoleon; Cechowska-Pasko, Marzanna; Waszkiel, Danuta; Zwierz, Krzysztof

2012-07-05

185

Stepwise atmospheric carbon-isotope excursion during the Toarcian Oceanic Anoxic Event (Early Jurassic, Polish Basin)  

NASA Astrophysics Data System (ADS)

During the Mesozoic (250-64 Ma) intervals of about 0.5 Myr were subject to severe environmental changes, including high sea-surface temperature and very low oxygen content of marine water. These Oceanic Anoxic Events, or OAEs, occurred simultaneously with profound disturbance to the carbon cycle. The carbon-isotope anomaly in the Early Jurassic that marks the Toarcian Oceanic Anoxic Event (T-OAE) at ~ 182 Ma is characterized in marine sections by a series of dramatic steps towards lighter values. Herein we present new carbon-isotope data from terrestrial organic matter (phytoclast separates), collected through a Late Pliensbachian-Middle Toarcian coastal and marginal marine succession in the Polish Basin, a setting where hinterland climate and sea-level change are well recorded. The results show that the shift to light carbon-isotope values in the woody organic matter, and therefore also in atmospheric carbon dioxide, similarly occurred in major steps. The steps are here correlated with those identified from marine organic matter, where they have previously been attributed to 100 kyr eccentricity forcing of climate. The results provide strong support for orbitally and climatically controlled release of isotopically light carbon from gas hydrates into the ocean-atmosphere system in a series of rapid bursts. Additionally, a link between the carbon-isotope steps and shoreline movements can be demonstrated. Individual peaks of the negative excursion are mostly associated with facies indicative of sea-level rise (flooding surfaces). However, at the same time inferred higher atmospheric carbon-dioxide content may be expected to have resulted in increased rainfall and temperature, leading to accelerated weathering and erosion, and consequently increased sediment supply, progradation and regression, causing some mismatches between isotope shifts and inferred sea-level changes. Enhanced abundance of megaspores derived from hydrophilic plant groups, and marked increase in kaolinite, are coincident with the overall development of the negative isotope excursion. The combined data suggest that each 100-kyr cycle in carbon-isotope values was characterized by increasingly severe palaeoclimatic change, culminating in extremely hot and humid conditions co-incident with the peak of the final most negative carbon-isotope excursion. The chemostratigraphic correlation allows very precise dating of the Late Pliensbachian-Middle Toarcian coastal and marginal marine sedimentary succession in the Polish Basin.

Hesselbo, Stephen P.; Pie?kowski, Grzegorz

2011-01-01

186

Effect of metallic cations on the efficiency of DNA amplification. Implications for nucleic acid replication during early stages of life  

NASA Astrophysics Data System (ADS)

The process of catalysis of biochemical reactions has been essential since the first organic molecules appeared on Earth. As the complexity of the ensemble of primitive biomolecules was very low, primitive catalysts had necessarily to be very simple molecules or ions. The evolution of catalysts had to be in parallel with the evolution of the molecular species reacting. An example of this parallel evolution is nucleic acid polymerization. Synthesis of primitive short oligonucleotides could have been catalysed by metal ions either in solution or on the surface of minerals such as montmorillonite clays. Some oligonucleotides could start to function as templates for the synthesis of complementary copies and there is experimental evidence supporting the role also played by metal ions in this process. In later stages of evolution, a group of enzymatic proteins, nucleic acid polymerases, has been selected to catalyse nucleic acid replication. The presence of Mg2+ in the active centre of these enzymes suggests that evolution has preserved some of the primitive catalysts, including them as cofactors of more complex molecules. However, the reasons why Mg2+ was selected among other ions that possibly were present in primitive environments are unknown. In this paper we try to approach this question by analysing the amplification efficiency of the polymerase chain reaction of a DNA fragment in the presence of different metal ions. In some cases the conditions of the reaction have been displaced from optimum (by the presence of nucleotide imbalances and a suboptimal Mg2+concentration). The results obtained permit one to draw interesting conclusions about how some metallic cations can help replication to proceed in conditions of limited substrate availability, a circumstance that could have been frequent at prebiotic stages, when nucleic acid synthesis was dependent on the physico-chemical conditions of the environment.

Arribas, María; de Vicente, Aránzazu; Arias, Armando; Lázaro, Ester

2005-04-01

187

Nitric oxide participates in early events associated with NNMU-induced acute lung injury in rats.  

PubMed

In this study, the biochemical mechanisms by which N-nitroso-N-methylurethane (NNMU) induces acute lung injury are examined. Polymorphonuclear neutrophil infiltration into the lungs first appears in the bronchoalveolar lavage (BAL) fluid 24 h after NNMU injection (10.58 +/- 3.00% of total cells; P < 0.05 vs. control animals). However, NNMU-induced elevation of the alveolar-arterial O2 difference requires 72 h to develop. Daily intraperitoneal injections of the inducible nitric oxide (. NO) synthase (iNOS)-selective inhibitor aminoguanidine (AG) initiated 24 h after NNMU administration improve the survival of NNMU-treated animals. However, AG administration initiated 48 or 72 h after NNMU injection does not significantly improve the survival of NNMU-treated animals. These results suggest that. NO participates in events that occur early in NNMU-induced acute lung injury. BAL cells isolated from rats 24 and 48 h after NNMU injection produce elevated. NO and express iNOS during a 24-h ex vivo culture. AG attenuates. NO production but does not affect iNOS expression, whereas actinomycin D prevents iNOS expression and attenuates. NO production by BAL cells during this ex vivo culture. These results suggest that NNMU-derived BAL cells can stimulate iNOS expression and. NO production during culture. In 48-h NNMU-exposed rats, iNOS expression is elevated in homogenates of whole lavaged lungs but not in BAL cells derived from the same lung. These findings suggest that the pathogenic mechanism by which NNMU induces acute lung injury involves BAL cell stimulation of iNOS expression and. NO production in lung tissue. PMID:9950888

Cruz, W S; Corbett, J A; Longmore, W J; Moxley, M A

1999-02-01

188

Toward an orbital chronology for the early Aptian Oceanic Anoxic Event (OAE1a, ~ 120 Ma)  

NASA Astrophysics Data System (ADS)

The early Aptian Oceanic Anoxic Event (OAE1a, 120 Ma) represents a geologically brief time interval in the mid-Cretaceous greenhouse world that is characterized by increased organic carbon accumulation in marine sediments, sudden biotic changes, and abrupt carbon-isotope excursions indicative of significant perturbations to global carbon cycling. The brevity of these drastic environmental changes (< 106 year) and the typically 106 year temporal resolution of the available chronologies, however, represent a critical gap in our knowledge of OAE1a. We have conducted a high-resolution investigation of three widely distributed sections, including the Cismon APTICORE in Italy, Santa Rosa Canyon in northeastern Mexico, and Deep Sea Drilling Project (DSDP) Site 398 off the Iberian margin in the North Atlantic Ocean, which represent a range of depositional environments where condensed and moderately expanded OAE1a intervals are recorded. The objectives of this study are to establish orbital chronologies for these sections and to construct a common, high-resolution timescale for OAE1a. Spectral analyses of the closely-spaced (corresponding to ~ 5 to 10 kyr) measurements of calcium carbonate content of the APTICORE, magnetic susceptibility (MS) and anhysteretic remanent magnetization (ARM) of the Santa Rosa samples, and MS, ARM and ARM/IRM, where IRM is isothermal remanent magnetization, of Site 398 samples reveal statistically significant cycles. These cycles exhibit periodicity ratios and modulation patterns similar to those of the mid-Cretaceous orbital cycles, suggesting that orbital variations may have modulated depositional processes. Orbital control allows us to estimate the duration of unique, globally identifiable stages of OAE1a. Although OAE1a had a duration of ~ 1.0 to 1.3 Myr, the initial perturbation represented by the negative carbon-isotope excursion was rapid, lasting for ~ 27 44 kyr. This estimate could serve as a basis for constraining triggering mechanisms for OAE1a.

Li, Yong-Xiang; Bralower, Timothy J.; Montañez, Isabel P.; Osleger, David A.; Arthur, Michael A.; Bice, David M.; Herbert, Timothy D.; Erba, Elisabetta; Premoli Silva, Isabella

2008-07-01

189

A Concept of Word in Text: A Pivotal Event in Early Reading Acquisition  

Microsoft Academic Search

The purpose of this study was to examine a model of early reading acquisition that hinged on a phenomenon seldom explored in beginning reading research: a child's concept of word in text. Previous research in early literacy acquisition has centered on the role phonological awareness—the ability to consciously attend to and manipulate the sound structure of spoken language—plays in early

Kevin Flanigan

2007-01-01

190

Pronounced climate warming during early Middle Pleistocene interglacials: investigating the mid-Brunhes event in the British terrestrial sequence  

NASA Astrophysics Data System (ADS)

The mid-Brunhes event is a climatic transition that occurs between MIS 13 and 11 (ca 450,000 yrs B.P.) and is primarily characterised by an increase in the amount of warming received by interglacial episodes over the last 450,000 yrs relative to that experienced during interglacials of the early Middle Pleistocene (780,000 - 450,000 yrs B.P.). This event is observable within a range of long climate records (e.g. SPECMAP, EPICA etc) but its effect on terrestrial systems is poorly understood. The impact of this event in northwest Europe is tested through the British terrestrial sequence by the comparison of multi-proxy climate reconstructions for interglacials of the early Middle Pleistocene with climate reconstructions from the late Middle and Late Pleistocene (<500,000 B.P.). This comparison reveals that interglacial climates during the early Middle Pleistocene in Britain were, in fact, as warm as, and in some cases warmer than, those that occurred during the late Middle and Late Pleistocene. This suggestion is supported by sea surface temperature records in the North Atlantic which show that temperatures during the early Middle Pleistocene interglacials were at least as warm as the Holocene. There is therefore no evidence, in climate records of northwest Europe and the North Atlantic, for a mid-Brunhes event. This suggests that the mid-Brunhes event is not a global climatic transition but only impacts certain regions of the world, however, further work is needed to understand the extent of this significant transition and the reason for this regional variation.

Candy, I.; Rose, J.; Silva, B.; Lee, J.

2009-04-01

191

Suicidal Ideation and its Recurrence in Boys and Men From Early Adolescence to Early Adulthood: An Event History Analysis  

Microsoft Academic Search

Occurrence and recurrences of suicidal ideation (SI) were modeled among boys\\/men assessed annually from ages 12 to 29 years. Multiple-spell discrete-time event-history analyses permitted (a) determination of whether risk for SI escalates with prior experiences of SI (spell effects), while (b) accounting for changes in risk with time (period effects) and (c) controlling for vulnerability factors. Self-reported SI (presence\\/absence in

David C. R. Kerr; Lee D. Owen; Deborah M. Capaldi

2008-01-01

192

Impact of Viral Factors on Very Early In Vivo Replication Profiles in Simian Immunodeficiency Virus SIVagm-Infected African Green Monkeys  

PubMed Central

To better understand which factors govern the levels of viral loads in early lentiviral infections of primates, we developed a model that allows distinguishing between the influences of host and viral factors on viremia. Herein we report that two species of African green monkeys (Chlorocebus sabaeus and C. pygerythrus) infected with their respective wild-type simian immunodeficiency virus SIVagm viruses (SIVagm.sab92018 and SIVagm.ver644) consistently showed reproducible differences in viremia during primary infection but not at later stages of infection. Cross-infections of SIVagm.sab92018 and SIVagm.ver644 into, respectively, C. pygerythrus and C. sabaeus revealed that the dynamics of viral replication during primary infection were dependent on the viral strain used for the infection but not on the host. Hence, the kinetics of SIVagm.sab92018 and SIVagm.ver644 were similar in both sabaeus and vervet animals, indicating that the difference in viremia levels between the two groups during the early phase of infection was not associated with the host. Coreceptor usage for these two strains showed a larger coreceptor repertoire for SIVagm.sab92018, which is able to efficiently use CXCR4 in addition to CCR5, than for SIVagm.ver644, which showed a classical CCR5 coreceptor usage pattern. These differences could not be explained by different charges of the V3 loop for SIVagm.sab92018 and for SIVagm.ver644. In conclusion, our study showed that the extent of virus replication during the primary infection is primarily dependent on viral determinants.

Pandrea, Ivona; Kornfeld, Christopher; Ploquin, Mickael J.-Y.; Apetrei, Cristian; Faye, Abdourahmane; Rouquet, Pierre; Roques, Pierre; Simon, Francois; Barre-Sinoussi, Francoise; Muller-Trutwin, Michaela C.; Diop, Ousmane M.

2005-01-01

193

Transient expression of the vaccinia virus DNA polymerase is an intrinsic feature of the early phase of infection and is unlinked to DNA replication and late gene expression.  

PubMed Central

We have studied the expression pattern of the vaccinia virus DNA polymerase during the viral replicative cycle. To monitor polymerase synthesis, a polyclonal antiserum was raised against a TrpE-DNA polymerase fusion protein. Immunoprecipitation and S1 analyses revealed that polymerase synthesis and mRNA levels peak by 2 to 3.5 h postinfection during wild-type infections and then decline, becoming barely detectable by 5 to 6.5 h postinfection. Blocking viral DNA replication by performing infections with temperature-sensitive DNA- mutants at the nonpermissive temperature or by performing wild-type infections in the presence of cytosine beta-D-arabinofuranoside had no effect on polymerase expression. These results indicate that the transient expression of the DNA polymerase is regulated independently of intermediate and late viral gene expression. Cycloheximide, which inhibits protein synthesis and prevents secondary uncoating, caused prolonged and elevated levels of polymerase transcription. Early viral proteins and uncoating, rather than exhaustion of the encapsidated transcription machinery, are presumed to mediate the cessation of polymerase transcription. In the presence of aphidicolin, the polymerase transcripts were maintained at maximal levels rather than exhibiting their normal decline. This inhibition of RNA decay was seen even in infections performed with isolates encoding aphidicolin-resistant DNA polymerases, suggesting that aphidicolin may interfere directly with the process of RNA degradation. Under these conditions, polymerase synthesis remained transient and was not prolonged, despite the continuing presence of available mRNA. These observations suggest that early mRNAs may experience a loss in translation efficiency as infection progresses. Images

McDonald, W F; Crozel-Goudot, V; Traktman, P

1992-01-01

194

Early events in the perception of lipopolysaccharides in the brown alga Laminaria digitata include an oxidative burst and activation of fatty acid oxidation cascades  

Microsoft Academic Search

This study provides evidence that bacterial lipopoly- saccharides can be strong triggers of early events of defence reactions in the brown algal kelp Laminaria digitata, constituting the first report of a biological activity of this class of macromolecules in a marine alga. The early events include an oxidative burst, re- lease of free saturated and unsaturated fatty acids (FFAs) and

Frithjof C. Kupper; Emmanuel Gaquerel; Eva-Maria Boneberg; Siegfried Morath; Jean-Pierre Salaun; Philippe Potin

2006-01-01

195

Decreased replication origin activity in temporal transition regions.  

PubMed

In the mammalian genome, early- and late-replicating domains are often separated by temporal transition regions (TTRs) with novel properties and unknown functions. We identified a TTR in the mouse immunoglobulin heavy chain (Igh) locus, which contains replication origins that are silent in embryonic stem cells but activated during B cell development. To investigate which factors contribute to origin activation during B cell development, we systematically modified the genetic and epigenetic status of the endogenous Igh TTR and used a single-molecule approach to analyze DNA replication. Introduction of a transcription unit into the Igh TTR, activation of gene transcription, and enhancement of local histone modifications characteristic of active chromatin did not lead to origin activation. Moreover, very few replication initiation events were observed when two ectopic replication origin sequences were inserted into the TTR. These findings indicate that the Igh TTR represents a repressive compartment that inhibits replication initiation, thus maintaining the boundaries between early and late replication domains. PMID:19951913

Guan, Zeqiang; Hughes, Christina M; Kosiyatrakul, Settapong; Norio, Paolo; Sen, Ranjan; Fiering, Steven; Allis, C David; Bouhassira, Eric E; Schildkraut, Carl L

2009-11-30

196

Inhibition of Rho Kinase Regulates Specification of Early Differentiation Events in P19 Embryonal Carcinoma Stem Cells  

Microsoft Academic Search

BackgroundThe Rho kinase pathway plays a key role in many early cell\\/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis (membrane blebbing), cell proliferation\\/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma

Roman J. Krawetz; Jaymi Taiani; Alexis Greene; Gregory M. Kelly; Derrick E. Rancourt

2011-01-01

197

Real-Time Cross-Correlation Image Analysis of Early Events in IgE Receptor Signaling  

Microsoft Academic Search

Signaling in mast cells and basophils is mediated through IgE and its high affinity cell surface receptor, Fc?RI. Crosslinking of the receptors by a cognate multivalent antigen leads to degranulation and release of mediators of the allergic immune response. Using multicolor fluorescence confocal microscopy, we probed the spatio-temporal dynamics of early events in the IgE receptor signal cascade. We monitored

Raibatak Das; Stephanie Hammond; David Holowka; Barbara Baird

2008-01-01

198

Strontium isotope profile of the early Toarcian (Jurassic) oceanic anoxic event, the duration of ammonite biozones, and belemnite palaeotemperatures  

Microsoft Academic Search

We profile 87Sr\\/86Sr, ?13C, ?18O, Sr\\/Ca, Mg\\/Ca, and Na\\/Ca in belemnites through Pliensbachian and Toarcian strata on the Yorkshire coast, UK, which include the early Jurassic oceanic anoxic event. The 87Sr\\/86Sr profile shows that the relative duration of ammonite subzones differ by a factor of up to 30: the Lower Jurassic exaratum subzone is 30 times longer than the clevelandicum

J. M. McArthur; D. T Donovan; M. F. Thirlwall; B. W. Fouke; D. Mattey

2000-01-01

199

Interrelationships between Yeast Ribosomal Protein Assembly Events and Transient Ribosome Biogenesis Factors Interactions in Early Pre-Ribosomes  

PubMed Central

Early steps of eukaryotic ribosome biogenesis require a large set of ribosome biogenesis factors which transiently interact with nascent rRNA precursors (pre-rRNA). Most likely, concomitant with that initial contacts between ribosomal proteins (r-proteins) and ribosome precursors (pre-ribosomes) are established which are converted into robust interactions between pre-rRNA and r-proteins during the course of ribosome maturation. Here we analysed the interrelationship between r-protein assembly events and the transient interactions of ribosome biogenesis factors with early pre-ribosomal intermediates termed 90S pre-ribosomes or small ribosomal subunit (SSU) processome in yeast cells. We observed that components of the SSU processome UTP-A and UTP-B sub-modules were recruited to early pre-ribosomes independently of all tested r-proteins. On the other hand, groups of SSU processome components were identified whose association with early pre-ribosomes was affected by specific r-protein assembly events in the head-platform interface of the SSU. One of these components, Noc4p, appeared to be itself required for robust incorporation of r-proteins into the SSU head domain. Altogether, the data reveal an emerging network of specific interrelationships between local r-protein assembly events and the functional interactions of SSU processome components with early pre-ribosomes. They point towards some of these components being transient primary pre-rRNA in vivo binders and towards a role for others in coordinating the assembly of major SSU domains.

Jakob, Steffen; Ohmayer, Uli; Neueder, Andreas; Hierlmeier, Thomas; Perez-Fernandez, Jorge; Hochmuth, Eduard; Deutzmann, Rainer; Griesenbeck, Joachim; Tschochner, Herbert; Milkereit, Philipp

2012-01-01

200

Huntingtin Aggregate-Associated Axonal Degeneration is an Early Pathological Event in Huntington's Disease Mice  

Microsoft Academic Search

Huntington's disease (HD) is characterized by the selective loss of striatal projection neurons. In early stages of HD, neurode- generation preferentially occurs in the lateral globus pallidus (LGP) and substantia nigra (SN), two regions in which the axons of striatal neurons terminate. Here we report that in mice ex- pressing full-length mutant huntingtin and modeling early stages of HD, neuropil

He Li; Shi-Hua Li; Zhao-Xue Yu; Peggy Shelbourne; Xiao-Jiang Li

2001-01-01

201

Archean and Early Proterozoic Events Along the Snowbird Tectonic Zone in Northern Saskatchewan, Canada  

Microsoft Academic Search

The Snowbird tectonic zone is a major boundary structure in the Canadian shield, separating rocks of the Rae and Hearne lithostructural domains. Field investigations along portions of the Snowbird tectonic zone exposed in Northern Saskatchewan have revealed a major granulite facies mylonite belt that records deformation and metamorphism at several intervals in the Archean and early Proterozoic. Early assemblages are

Christopher F. Kopf

2002-01-01

202

Childhood amnesia and the beginnings of memory for four early life events  

Microsoft Academic Search

Childhood amnesia was examined in a between-groups study of adults' memories of 4 datable target events—the birth of a younger sibling, a hospitalization, the death of a family member, and making a family move. College students (N = 222) answered questions about events that had occurred when they were 1,2,3,4, or 5 years old and also about external information sources,

JoNell Adair Usher; Ulric Neisser

1993-01-01

203

[Eventful life stories. Members of student fraternities persecuted in Silesia in the early 19th century].  

PubMed

This study supplemented by three charts and a list of biographies, is, for the first time, encompassing their life-data, their resumés and even their professional careers as well as political commitments shown by more than 200 Silesian students. They, at the University of Breslau, but also at other German universities, had joined the student fraternities in the 20-ies and early 30-ies of the 19th century and, in consequence, were persecuted by state authorities, notably in Prussia and, in the majority of cases, had been sentenced to prison terms of varying degrees. The first demagogic persecution, which happened in the first half of the twenties, culminating in 1822 in the Breslau Arminen Trail and ending up with the staging of the Youth-Association-Trail in 1826, had implicated about 100 Silesians, with a smaller portion of them - apart from teh three Youth-Association Silesians who were sentenced to five years imprisonment in a fortress - getting away with a relatively short "political fortress imprisonment". Later a considerable part of them made a career in the prussian judicial authority, in the institutions of higher learning, as parish priests, physicians and scientists, whereas any political engagement remained a rare exception. Out of the 137 Silesian members of the student fraternities affected by the second wave of persecution, the overwhelming majority of them being Protestants and originating partly from the middle classes, mostly artisans, and from intellectual background, with about a hundred of them being given essentially higher sentences ranging from six years up to capital punishment and, in the event of reprieves, they had to serve their sentences between six months and four-to-six years in a fortress. The majority of them made a medium-level professional career, never exceeding the medium ranks, as judicial officers, lawyers in state or communal services, parish priests, teachers or physicians. However, from this group of persecuted persons, a far greater number became active in politics, especially during the 1848/49 revolution in their capacities as Deputies in the German National parliament, or in the Prussian Constitutional Assembly. But they became even active as leading figures on the level of local and regional societies. While conservative executive personalities emerged only rarely from the group of persecuted Silesian student fraternities - the highest office attainable was head of a county administration - a greater number of proponents and elites emerged from these circles in favour of liberalism and, even far more, in favour of the German Democracy. In isolated instances, the socialist movement obtained its protagonists from Silesian fraternities. A biographical study has confirmed the finding that in the first half of the 19th century student fraternities were a political institution which since 1848 had been at the service of the political parties in Germany with a view to recruiting from them their supporters and their party executives. PMID:15648115

Schmidt, Walter

2003-01-01

204

Massive Expansion of Marine Archaea During The Early Albian Oceanic Anoxic Event 1B  

NASA Astrophysics Data System (ADS)

Oceanic anoxic events (OAEs), periods of globally enhanced burial of organic matter (OM) in the marine realm, played an important role in the mid-Cretaceous `greenhouse climate' by effectively reducing atmospheric carbon dioxide concentrations. It is generally believed that these OAEs were caused either by decreased remineralisation or increased production of phytoplanktonic OM. Here we show that enhanced organic carbon (OC) burial during the early Albian OAE1b (~112 My) was caused by a different process. Combined biogeochemical and stable carbon isotopic analyses indicate that black shales from this period contain up to 80% of OC derived from archaea. Archaea-derived isoprenoidal tetraether membrane lipids and free and macromolecularly bound isoprenoid alkanes are abundantly present in these black shales. More specifically the presence of certain ether lipids (cyclic biphytane tetraethers) indicates representatives of the pelagic archaea. To the best of our knowledge this is the earliest fossil evidence for marine planktonic archaea, extending their geological record by more than 60 million years. The diversity of archaeal lipids recovered from the OAE1b black shales suggests that they derive from a multitude of archaeal species. However, the specific 13C enrichment of all such lipids indicates a common `heavy' (13C-rich) carbon source for the archaea and/or a common pathway of carbon-fixation with a reduced 13C fractionation effect compared to the Calvin cycle used by algae, cyanobacteria and higher plants. The large differences (up to 12%) in 13C/12C ratios between the algal biomarkers and the much more abundant archaeal molecular fossils suggest that the latter were not living heterotrophically on photoautotrophic biomass. It seems likely that the archaea present during OAE1b used a chemical energy source (possibly ammonium) for carbon fixation since photoautotrophy within the domain of the Archaea is restricted to only a few species from hypersaline environments. We can only speculate about the causes of this unprecedented massive expansion of marine planktonic archaea during the mid-Cretaceous OAE1b. Prolonged periods of enhanced hydrothermal activity would have significantly altered the ocean chemistry during the mid-Cretaceous, providing the necessary reduced compounds like ammonium to sustain a large community of chemoautotrophic archaea. In addition pronounced water stratification and anoxic conditions such as existed during the OAE1b could have provided a competitive advantage for archaea over phytoplankton utilising ammonium, allowing a diverse community of nitrifying non-thermophilic archaea to evolve. In any case our data show that there seems to be no unifying mechanism for black shale deposition during the mid-Cretaceous OAEs. Although there are apparent similarities (distinct lamination, 13C-enrichment of OC) between the black shales of OAE1b and other OAEs, our detailed molecular work shows that the origin of the OM (archaeal versus phytoplanktonic) and causes for 13C-enrichment of OC are completely different.

Kuypers, M. M.; Kuypers, M. M.; Blokker, P.; Erbacher, J.; Kinkel, H.; Pancost, R. D.; Pancost, R. D.; Schouten, S.; Sinninghe Damsté, J. S.

2001-12-01

205

Exposure to traumatic events and the behavioral health of children enrolled in an early childhood system of care.  

PubMed

Children may be exposed to numerous types of traumatic events that can negatively affect their development. The scope to which studies have examined an array of events among young children has been limited, thereby restricting our understanding of exposure and its relationship to behavioral functioning. The current cross-sectional study describes traumatic event exposure in detail and its relationship to behavioral health among an at-risk sample of young children (N = 184), under 6 years of age, upon enrollment into an early childhood, family-based, mental health system of care. Caregivers completed home-based semistructured interviews that covered children's exposure to 24 different types of traumatic events and behavioral and emotional functioning. Findings indicated that nearly 72% of young children experienced 1 or more types of traumatic events. Multiple regression model results showed that exposure was significantly associated with greater behavioral and emotional challenges with children's age, gender, race/ethnicity, household income, and caregiver's education in the model. These findings highlight the prevalence of traumatic exposures among an at-risk sample of young children in a system of care and suggest that this exposure is associated with behavioral and emotional challenges at a young age. PMID:23225035

Snyder, Frank J; Roberts, Yvonne Humenay; Crusto, Cindy A; Connell, Christian M; Griffin, Amy; Finley, Meghan K; Radway, Susan; Marshall, Tim; Kaufman, Joy S

2012-12-01

206

UTeach Replication  

NSDL National Science Digital Library

UTeach is a program for the preparation of secondary science and mathematics teachers at The University of Texas at Austin. It is currently being replicated at universities across the United States with funding sources that include grants from the National Math and Science Initiative and state sources in Texas and Tennessee. This website discusses the design and implementation of the replication process.

Marder, Michael

2010-02-25

207

High Levels of Viral Replication Contrast with Only Transient Changes in CD4+ and CD8+ Cell Numbers during the Early Phase of Experimental Infection with Simian Immunodeficiency Virus SIVmnd-1 in Mandrillus sphinx  

Microsoft Academic Search

Early events during human immunodeficiency virus infections are considered to reflect the capacity of the host to control infection. We have studied early virus and host parameters during the early phase of simian immunodeficiency virus SIVmnd-1 nonpathogenic infection in its natural host, Mandrillus sphinx. Four man- drills were experimentally infected with a primary SIVmnd-1 strain derived from a naturally infected

Richard Onanga; Christopher Kornfeld; Ivona Pandrea; Jerome Estaquier; Sandrine Souquiere; Pierre Rouquet; Virginie Poaty Mavoungou; Olivier Bourry; Souleymane M'Boup; F. Barre-Sinoussi; Francois Simon; Cristian Apetrei; Pierre Roques; Michaela C. Muller-Trutwin

2002-01-01

208

Suicidal Ideation and Its Recurrence in Boys and Men from Early Adolescence to Early Adulthood: An Event History Analysis  

PubMed Central

Occurrence and recurrences of suicidal ideation (SI) were modeled among boys/men assessed annually from ages 12 to 29 years. Multiple-spell discrete-time event history analyses permitted (a) determination of whether risk for SI escalates with prior experiences of SI (Spell effects), (b) while accounting for changes in risk with time (Period effects), and (c) controlling for vulnerability factors. Self-reported SI (presence/absence in past week), depressive symptoms, alcohol/substance use, and antisocial behavior, and official arrest records were collected annually from 205 boys recruited on the basis of community risk for delinquency. Parents’ self-reported psychopathology and SES were collected in childhood. Period effects supported decreasing risk for SI over time. Spell and time-varying, 1-year lagged substance use and depressive symptoms independently predicted increased risk for SI. Models involving SI with intent were explored. Consistent with interpersonal psychological theory, risk for young men’s SI increases with past experience of SI, even with key propensities controlled; however, risk also decays over time. Targeting conditions that confer risk for SI is essential. Preventing and delaying SI occurrence and recurrence may represent independent mechanisms by which prevention efforts operate.

Kerr, David C. R.; Owen, Lee. D.; Capaldi, Deborah M.

2008-01-01

209

Suicidal ideation and its recurrence in boys and men from early adolescence to early adulthood: an event history analysis.  

PubMed

Occurrence and recurrences of suicidal ideation (SI) were modeled among boys/men assessed annually from ages 12 to 29 years. Multiple-spell discrete-time event-history analyses permitted (a) determination of whether risk for SI escalates with prior experiences of SI (spell effects), while (b) accounting for changes in risk with time (period effects) and (c) controlling for vulnerability factors. Self-reported SI (presence/absence in past week), depressive symptoms, alcohol/substance use, antisocial behavior, and official arrest records were collected annually from 205 boys recruited on the basis of community risk for delinquency. Parents' self-reported psychopathology and SES were collected in childhood. Period effects supported decreasing risk for SI over time. Spell and time-varying 1-year lagged substance use and depressive symptoms independently predicted increased risk for SI. Models involving SI with intent were explored. Consistent with interpersonal psychological theory, risk for young men's SI increases with past experience of SI, even with key propensities controlled. However, risk also decays over time. Targeting conditions that confer risk for SI is essential. Preventing and delaying SI occurrence and recurrence may represent independent mechanisms by which prevention efforts operate. PMID:18729614

Kerr, David C R; Owen, Lee D; Capaldi, Deborah M

2008-08-01

210

Administrative Data Algorithms to Identify Second Breast Cancer Events Following Early-Stage Invasive Breast Cancer  

PubMed Central

Background Studies of breast cancer outcomes rely on the identification of second breast cancer events (recurrences and second breast primary tumors). Cancer registries often do not capture recurrences, and chart abstraction can be infeasible or expensive. An alternative is using administrative health-care data to identify second breast cancer events; however, these algorithms must be validated against a gold standard. Methods We developed algorithms using data from 3152 women in an integrated health-care system who were diagnosed with stage I or II breast cancer in 1993–2006. Medical record review served as the gold standard for second breast cancer events. Administrative data used in algorithm development included procedures, diagnoses, prescription fills, and cancer registry records. We randomly divided the cohort into training and testing samples and used a classification and regression tree analysis to build algorithms for classifying women as having or not having a second breast cancer event. We created several algorithms for researchers to use based on the relative importance of sensitivity, specificity, and positive predictive value (PPV) in future studies. Results The algorithm with high specificity and PPV had 89% sensitivity (95% confidence interval [CI] = 84% to 92%), 99% specificity (95% CI = 98% to 99%), and 90% PPV (95% CI = 86% to 94%); the high-sensitivity algorithm had 96% sensitivity (95% CI = 93% to 98%), 95% specificity (95% CI = 94% to 96%), and 74% PPV (95% CI = 68% to 78%). Conclusions Algorithms based on administrative data can identify second breast cancer events with high sensitivity, specificity, and PPV. The algorithms presented here promote efficient outcomes research, allowing researchers to prioritize sensitivity, specificity, or PPV in identifying second breast cancer events.

Yu, Onchee; Pocobelli, Gaia; Lamerato, Lois; Webster, Joe; Prout, Marianne N.; Ulcickas Yood, Marianne; Barlow, William E.; Buist, Diana S. M.

2012-01-01

211

Modeling and analysis of early events in T-lymphocyte antigen-activated intracellular-signaling pathways  

NASA Astrophysics Data System (ADS)

The T-cell antigen-activated signaling pathway is a highly regulated intracellular biochemical system that is crucial for initiating an appropriate adaptive immune response. To improve the understanding of the complex regulatory mechanisms controlling the early events in T-cell signaling, a detailed mathematical model was developed that utilizes ordinary differential equations to describe chemical reactions of the signaling pathway. The model parameter values were constrained by experimental data on the activation of a specific signaling intermediate and indicated an initial rapid cascade of phosphorylation events followed by a comparatively slow signal downregulation. Nonlinear analysis of the model suggested that thresholding and bistability occur as a result of the embedded positive and negative feedback loops within the model. These nonlinear system properties may enhance the T-cell receptor specificity and provide sub-threshold noise filtering with switch-like behavior to ensure proper cell response. Additional analysis using a reduced second-order model led to further understanding of the observed system behavior. Moreover, the interactions between the positive and negative feedback loops enabled the model to exhibit, among a variety of other feasible dynamics, a sustained oscillation that corresponds to a stable limit cycle in the two-dimensional phase plane. Quantitative analysis in this paper has helped identify potential regulatory mechanisms in the early T-cell signaling events. This integrated approach provides a framework to quantify and discover the ensemble of interconnected T-cell antigen-activated signaling pathways from limited experimental data.

Zheng, Yanan; Balakrishnan, Venkataramanan; Buzzard, Greg; Geahlen, Robert; Harrison, Marietta; Rundell, Ann

2005-12-01

212

Early Processing of Emotional Faces in Children with Autism: An Event-Related Potential Study  

ERIC Educational Resources Information Center

|Social deficits are one of the most striking manifestations of autism spectrum disorders (ASDs). Among these social deficits, the recognition and understanding of emotional facial expressions has been widely reported to be affected in ASDs. We investigated emotional face processing in children with and without autism using event-related…

Batty, Magali; Meaux, Emilie; Wittemeyer, Kerstin; Roge, Bernadette; Taylor, Margot J.

2011-01-01

213

Early Perception of Written Syllables in French: An Event-Related Potential Study  

ERIC Educational Resources Information Center

|The present study examined whether written syllable units are perceived in first steps of letter string processing. An illusory conjunction experiment was conducted while event-related potentials were recorded. Colored pseudowords were presented such that there was a match or mismatch between the syllable boundaries and the color boundaries. The…

Doignon-Camus, Nadege; Bonnefond, Anne; Touzalin-Chretien, Pascale; Dufour, Andre

2009-01-01

214

Traumatic and Stressful Events in Early Childhood: Can Treatment Help Those at Highest Risk?  

ERIC Educational Resources Information Center

Objective: This study involves a reanalysis of data from a randomized controlled trial to examine whether child-parent psychotherapy (CPP), an empirically based treatment focusing on the parent-child relationship as the vehicle for child improvement, is efficacious for children who experienced multiple traumatic and stressful life events (TSEs).…

Ippen, Chandra Ghosh; Harris, William W.; Van Horn, Patricia; Lieberman, Alicia F.

2011-01-01

215

The use of inhibitors to identify early events during Bacillus megaterium KM spore germination.  

PubMed Central

The germination response of spores of Bacillus megaterium KM, as measured by loss of A600, is more than 95% inhibited by 1 mM-HgCl2. Two Hg2+-sensitive sites (referred to as 'sites I and II') have been identified during germination. Site I represents a pre-commitment event and can be protected from HgCl2 by 50 mM-D-alanine, whereas site II represents a post-commitment event and is not D-alanine-protectable. At 1 mM-HgCl2, 25% of the spore population becomes committed to germinate, but an A600 loss of less than 5% occurs. In this system, loss of heat resistance was associated with commitment, whereas selective cortex hydrolysis, release of pyridine-2,6-dicarboxylic acid, Zn2+ and soluble peptidoglycan, as well as loss of refractility, were identified as post-commitment events. The commitment event was reversibly inhibited by several proteinase inhibitors and a membrane bulking agent. A model of spore germination based on these results is presented.

Foster, S J; Johnstone, K

1986-01-01

216

Early Referential Context Effects in Sentence Processing: Evidence from Event-Related Brain Potentials  

Microsoft Academic Search

An event-related brain potentials experiment was carried out to examine the interplay of referential and structural factors during sentence processing in discourse. Subjects read (Dutch) sentences beginning like “David told the girl that … ” in short story contexts that had introduced either one or two referents for a critical singular noun phrase (“the girl”). The waveforms showed that within

Jos J. A. van Berkum; Colin M. Brown; Peter Hagoort

1999-01-01

217

Early Echocardiography Can Predict Cardiac Events in Emergency Department Patients With Chest Pain  

Microsoft Academic Search

Study Objective: Accurate diagnosis in emergency department patients with possible myocardial ischemia is problematic. Two-dimensional echocardiography has a high sensitivity for identifying patients with myocardial infarction (MI); however, few studies have investigated its diagnostic ability when used acutely in ED patients with possible myocardial ischemia. Therefore we investigated the ability of ED echocardiography for predicting cardiac events in patients with

Michael C Kontos; James A Arrowood; Walter HJ Paulsen; JV Nixon

1998-01-01

218

Early psychosocial interventions after disasters, terrorism, and other shocking events: guideline development  

Microsoft Academic Search

Although most victims of disasters, terrorism, or other shocking events recover on their own, a sizable amount of these victims develops long-term disaster-related problems. These victims should receive timely and appropriate psychosocial help. This article describes the development of guidelines on psychosocial interventions during the first 6 weeks after a major incident. Scientific literature, expert opinions, and consensus among relevant

Hans Te Brake; M. Dückers; Maaike De Vries; Magda Rooze; Cor Spreeuwenberg

2009-01-01

219

Early psychosocial interventions after disasters, terrorism, and other shocking events: Guideline development  

Microsoft Academic Search

Although most victims of disasters, terrorism, or other shocking events recover on their own, a sizable amount of these victims develops long-term disaster-related problems. These victims should receive timely and appro- priate psychosocial help. This article describes the development of guidelines on psychosocial interventions during the first 6 weeks after a major incident. Scientific literature, expert opinions, and consensus among

Michel Dückers

220

Perturbation of membrane dynamics in nerve cells as an early event during bilirubin-induced apoptosis  

Microsoft Academic Search

Increased levels of unconjugated bilirubin, the end product of heme catabolism, impair crucial aspects of nerve cell function. In previous studies, we demonstrated that bilirubin toxicity may be due to cell death by apoptosis. To characterize the sequence of events leading to neurotox- icity, we exposed developing rat brain astrocytes and neu- rons to unconjugated bilirubin and investigated whether changes

Cecília M. P. Rodrigues; Susana Solá; Rui E. Castro; Pedro A. Laires; Dora Brites; José J. G. Moura

221

Riding the Wave to Reach the Masses: Natural Events in Early Twentieth Century Portuguese Daily Press  

ERIC Educational Resources Information Center

|This paper brings together science communicated in newspapers in Portugal by looking at how news on natural events were communicated in two different newspapers--the capital newspaper "Diario de Noticias" ("Daily News") and the "Diario dos Acores" ("Azores Daily"). In particular, we look at how the 1900 solar eclipse, a hot topic throughout…

Simoes, Ana; Carneiro, Ana; Diogo, Maria Paula

2012-01-01

222

Early Perception of Written Syllables in French: An Event-Related Potential Study  

ERIC Educational Resources Information Center

The present study examined whether written syllable units are perceived in first steps of letter string processing. An illusory conjunction experiment was conducted while event-related potentials were recorded. Colored pseudowords were presented such that there was a match or mismatch between the syllable boundaries and the color boundaries. The…

Doignon-Camus, Nadege; Bonnefond, Anne; Touzalin-Chretien, Pascale; Dufour, Andre

2009-01-01

223

Early Processing of Emotional Faces in Children with Autism: An Event-Related Potential Study  

ERIC Educational Resources Information Center

Social deficits are one of the most striking manifestations of autism spectrum disorders (ASDs). Among these social deficits, the recognition and understanding of emotional facial expressions has been widely reported to be affected in ASDs. We investigated emotional face processing in children with and without autism using event-related potentials…

Batty, Magali; Meaux, Emilie; Wittemeyer, Kerstin; Roge, Bernadette; Taylor, Margot J.

2011-01-01

224

Massive Expansion of Marine Archaea During The Early Albian Oceanic Anoxic Event 1B  

Microsoft Academic Search

Oceanic anoxic events (OAEs), periods of globally enhanced burial of organic matter (OM) in the marine realm, played an important role in the mid-Cretaceous `greenhouse climate' by effectively reducing atmospheric carbon dioxide concentrations. It is generally believed that these OAEs were caused either by decreased remineralisation or increased production of phytoplanktonic OM. Here we show that enhanced organic carbon (OC)

M. M. Kuypers; P. Blokker; J. Erbacher; H. Kinkel; R. D. Pancost; S. Schouten; J. S. Sinninghe Damsté

2001-01-01

225

Perceptual load interacts with involuntary attention at early processing stages: Event-related potential studies  

Microsoft Academic Search

Perceptual load is known to influence the locus of attentional selection in the brain but through an unknown underlying mechanism. We used event-related potentials (ERPs) to investigate how perceptual load interacts with cue-driven involuntary attention. Perceptual load was manipulated in a line orientation discrimination task in which target location was cued involuntarily by means of peripheral cues. Attentional modulation was

Shimin Fu; Yuxia Huang; Yuejia Luo; Yan Wang; John Fedota; Pamela M. Greenwood; Raja Parasuraman

2009-01-01

226

Facial attractiveness modulates early and late event-related brain potentials  

Microsoft Academic Search

Facial attractiveness is of high importance for human interaction and communication, and everyday experience suggests that the mere aspect of a face elicits spontaneous appraisal of attractiveness. However, little is known about the time course of brain responses related to this process. In the present study, event-related brain potentials were recorded during attractiveness classification of facial portraits that were standardized

Katja Werheid; Annekathrin Schacht; Werner Sommer

2007-01-01

227

Mood Reactivity to Daily Negative Events in Early Adolescence: Relationship to Risk for Psychopathology  

ERIC Educational Resources Information Center

|Emotional responses to negative daily experiences in young adolescents may provide important clues to the development of psychopathology, but research is lacking. This study assessed momentary mood reactivity to daily events as a function of risk profile in a school sample, ages 11-14. High-risk (HR, n = 25) and low-risk (LR, n = 106) subgroups…

Schneiders, Josien; Nicolson, Nancy A.; Berkhof, Johannes; Feron, Frans J.; van Os, Jim; deVries, Marten W.

2006-01-01

228

[Stressful life events, health symptoms, social support and coping in early adolescents].  

PubMed

Numerous research reports have substantiated the role of stressful life events in relation to the onset of health changes. The relationship tends to hold across different age groups. Theoretically, adolescence has been considered a developmental crisis period of great stress, impoverished coping skills and high vulnerability to biological, social and psychological demands. The research problem addressed by this study was to examine the relationships between stressful life events and health symptom patterns, and the effect of two variables, coping and social support, theoretically considered to mediate the relationship between stress and health symptoms in adolescents. The following five hypotheses were tested in this research: 1. Health symptoms are positively related to stressful life events in adolescents, 2. Health symptoms are negatively related to coping in adolescents, 3. Health symptoms are negatively related to social support in adolescents, 4. When coping is controlled, the relationship between health symptoms and stressful life events will decrease, and 5. When social support is controlled, the relationship between health symptoms and stressful life events will increase. The study subjects consisted of 1090 high school students of the metropolitan city of Seoul. The following sampling procedure was used: 1. Of the 169 high schools in nine school administrative districts in the city, a proportional sample of ten schools was selected. 2. One class from each of the freshman and sophomore was randomly selected and all the students who were in the sampled class were used as the study sample. The study was limited to freshman and sophomore adolescents, aged 15 to 18 (mean = 16.6). Of the 1090 subjects 688 (63%) were boys and 402 (37%) were girls. An Adolescent Inventory of Stressful Life Events, a Health Symptom Questionnaire and an Adolescent Coping Inventory were adapted for this study. The Norbeck Social Support Questionnaire was utilized to collect the data on perceived social support. Five high school teachers in the areas of school health and counselling reviewed the items of each questionnaire for content validity. A pilot study was undertaken to ascertain reliability. Fifty three high school students responded to the questionnaires and gave their opinions on the items. For stressful life events, health symptoms, coping, and social support, the Cronbach's alpha's on the study were .70, .94, .77, and .76, respectively. Research assistants attended all the sampled classes with the school proctor to explain the purpose and procedures of the study to the students. The questionnaires along with a ballpoint pen were distributed to the students who were asked to complete each item.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2290252

Oh, K; Han, J S

1990-12-01

229

Latest Jurassic-early Cretaceous events and the ''late Cimmerian unconformity'' in North Sea area  

Microsoft Academic Search

Several regional or local unconformities occur in the latest Jurassic-Early Cretaceous sequences of the North Sea and adjacent areas. Each may have been identified locally as the ''late Cimmerian unconformity,'' a supposed major break at the base of the Valhall Formation (or Rodby Formation where the Valhall is locally absent). Although a major hiatus (or a condensed sequence) may occur

P. F. Rawson; L. A. Riley

1982-01-01

230

The initiation of blood flow and flow induced events in early vascular development  

Microsoft Academic Search

Within a day of gastrulation, the embryonic heart begins to beat and creates blood flow in the developing cardiovascular system. The onset of blood flow completely changes the environment in which the cardiovascular system is forming. Flow provides physiological feedback such that the developing network adapts to cue provided by the flow. Targeted inactivation of genes that alter early blood

Elizabeth A. V. Jones

231

Methylation of homeobox genes is a frequent and early epigenetic event in breast cancer  

Microsoft Academic Search

INTRODUCTION: Aberrant methylation of CpG islands is a hallmark of cancer and occurs at an early stage in breast tumorigenesis. However, its impact on tumor development is not fully determined, and its potential as a diagnostic biomarker remains to be validated. Methylation profiling of invasive breast carcinoma has been largely explored. Conversely, very little and sparse information is available on

Stella Tommasi; Deborah L Karm; Xiwei Wu; Yun Yen; Gerd P Pfeifer

2009-01-01

232

Modeling evidences for global warming, Arctic seawater freshening, and sluggish oceanic circulation during the Early Toarcian anoxic event  

NASA Astrophysics Data System (ADS)

The paleoecological disturbances recorded during the Early Toarcian warming event (183 Myr ago), including marine anoxia, sea level rise, seawater acidification, carbonate production crisis, and species extinctions, are often regarded as past examples of Earth's possible responses to the rapid emergence of super greenhouse conditions. However, physical mechanisms explaining both the global and local expressions of paleoenvironmental events are still highly debated. Here we analyze the paleoclimatic and paleoceanographic consequences of increases in atmospheric pCO2 levels at a multiscale resolution using a fully coupled ocean-atmosphere model (FOAM). We show that, in association with stronger high-latitude precipitation rates and enhanced continental runoff, the demise of polar sea ice due to the global warming event involved a regional freshening of Arctic surface seawaters. These disturbances lead to progressive slowdowns of the global oceanic circulation accountable for widespread ocean stratification and bottom anoxia processes in deep oceanic settings and epicontinental basins. In agreement with very negative oxygen isotope values measured on fossil shells from the NW Tethys, our simulations also show that recurrent discharges of brackish and nutrient-rich Arctic surface waters through the Viking Corridor could have led to both vertical and geographical gradients in salinity and seawater ?18O in the NW Tethyan seas. Locally contrasted conditions in water mass density and rises in productivity rates due to strong nutrient supplies could partly explain the regional severity of the anoxic event in the restricted Euro-boreal domains, as it has been previously suggested and modeled regionally.

Dera, Guillaume; Donnadieu, Yannick

2012-06-01

233

Early childhood behavior trajectories and the likelihood of experiencing a traumatic event and PTSD by young adulthood.  

PubMed

This study modeled children's trajectories of teacher rated aggressive-disruptive behavior problems assessed at six time points between the ages of 6 and 11 and explored the likelihood of being exposed to DSM-IV qualifying traumatic events and posttraumatic stress disorder (PTSD) in 837 urban first graders (71% African American) followed-up for 15 years. Childhood trajectories of chronic high or increasing aggressive-disruptive behavior distinguished males more likely to be exposed to an assaultive violence event as compared to males with a constant course of low behavior problems (OR(chronic high) = 2.8, 95% CI = 1.3, 6.1 and OR(increasing) = 4.5, 95% CI = 2.3, 9.1, respectively). Among females, exposure to traumatic events and vulnerability to PTSD did not vary by behavioral trajectory. The findings illustrate that repeated assessments of disruptive classroom behavior during early school years identifies more fully males at increased risk for PTSD-level traumatic events, than a single measure at school entry does. PMID:19139797

Storr, Carla L; Schaeffer, Cindy M; Petras, Hanno; Ialongo, Nicholas S; Breslau, Naomi

2009-01-12

234

Paleomagnetic and Geochronologic Data from Central Asia: Inferences for Early Paleozoic Tectonic Evolution and Timing of Worldwide Glacial Events  

NASA Astrophysics Data System (ADS)

The Neoproterozoic to early Paleozoic Ural-Mongol belt that runs through Central Asia is crucial for determining the enigmatic amalgamation of microcontinents that make up the Eurasian subcontinent. Two unique models have been proposed for the evolution of Ural-Mongol belt. One involves a complex assemblage of cratonic blocks that have collided and rifted apart during diachronous opening and closing of Neoproterozoic to Devonian aged ocean basins. The opposing model of Sengor and Natal"in proposes a long-standing volcanic arc system that connected Central Asian blocks with the Baltica continent. The Aktau-Mointy and Dzabkhan microcontinents in Kazakhstan and Central Mongolia make up the central section of the Ural-Mongol belt, and both contain glacial sequences characteristic of the hypothesized snowball earth event. These worldwide glaciations are currently under considerable debate, and paleomagnetic data from these microcontients are a useful contribution to the snowball controversy. We have sampled volcanic and sedimentary sequences in Central Mongolia, Kazakhstan and Kyrgyzstan for paleomagnetic and geochronologic study. U-Pb data, 13C curves and abundant fossil records place age constraints on sequences that contain glacial deposits of the hypothesized snowball earth events. Carbonates in the Zavkhan Basin in Mongolia are likely remagnetized, but fossil evidence within the sequence suggests a readjusted age control on two glacial events that were previously labeled as Sturtian and Marinoan. U-Pb ages from both Kazakhstan and Mongolian volcanic sequences imply a similar evolution history of the areas as part of the Ural-Mongol fold belt, and these ages paired with paleomagnetic and 13C records have important tectonic implications. We will present these data in order to place better constraints on the Precambrian to early Paleozoic tectonic evolution of Central Asia and the timing of glacial events recorded in the area.

Gregory, L. C.; Meert, J. G.; Levashova, N.; Grice, W. C.; Gibsher, A.; Rybanin, A.

2007-12-01

235

Influence of inactivated Sendai virus on early events in polyomavirus infection of permissive and nonpermissive host cells.  

PubMed

Quantitative radiochemical investigations have been performed regarding the influence of betapropiolactone-inactivated Sendai virus on the early events of interaction of polyomavirus with permissive and nonpermissive cells. These experiments have shown: (i) Sendai virus did not increase polyomavirus adsorption on permissive or nonpermissive cells; (ii) Sendai virus induced polyomavirus elution from permissive and nonpermissive cells during the first 40 min and 6 h postinfection, respectively; and (iii) Sendai virus promoted the penetration of polyomavirus into lysosomes only in nonpermissive cells. The maximal amounts of radioactively labeled virion DNA and viral coat proteins were found in lysosomes at 2--3 h postinfection. PMID:227809

Artamonova, V; Shevliaghin, V

1979-01-01

236

Early trimpi events from lightning-induced electric fields in the ionosphere: An alternative explanation. (Reannouncement with new availability information)  

SciTech Connect

Two classes of Trimpi modulation of VLF signals in the Earth-ionosphere waveguide have been identified in the literature. The more common type occurs 1 s or more after causative lightning strokes, the second in less than 100 ms. The authors explore the possibility that these early Trimpi events result from lightning-generated, electric field impulses lowering the mirror altitudes of trapped electrons. To overcome the mirror force on energetic electrons, upward-directed electric fields with strength of a few tens of mV/m are required. This is well within the range of electric field observed on sounding rockets above thunderstorms.

Burke, W.J.

1992-12-31

237

Better Control of Early Viral Replication Is Associated with Slower Rate of Elicited Antiviral Antibodies in the Detuned EIA during Primary HIV-1C Infection  

PubMed Central

Background Estimation of HIV incidence rates is important for timing interventions, planning prevention studies, and monitoring the epidemic. This requires accurate estimation of the “recency period” (also known as the “window period”) between seroconversion and achievement of specific detectable levels of anti-HIV antibody titers, such as the standardized optical density (SOD) in the early phase of HIV-1 infection. Methods To obtain a better understanding of inter-patient variation of the recency period, prospective measurements of anti-viral antibody titers in the early phase of HIV-1 subtype C infection were quantified by Vironostika-LS. Time of seroconversion was estimated by Fiebig staging. Results The profiles of SOD values during the first year of infection commonly showed slow initial increase followed by a more rapid increase, though in some patients SOD values increased rapidly soon after seroconversion. Using an SOD cutoff of 1.0, the average duration of the recency period in subtype C infection in the local epidemic in Botswana was estimated to be 151 days (95% CI from 130 to 172 days) post-seroconversion. The recency period was significantly associated (p=0.007) with the level of viral replication during the first 2–3 months post-seroconversion. Reduction of SOD values after initiation of antiretroviral therapy (ART) was a dominant pattern in antiretroviral drug (ARV)-treated subjects. Conclusions Our data suggest that HIV incidence estimation based on sensitive/less sensitive EIA cross-sectional testing could be potentially improved by incorporation of viral load levels at the time of detection of a recent infection.

Novitsky, Vladimir; Wang, Rui; Kebaabetswe, Lemme; Greenwald, Jamieson; Rossenkhan, Raabya; Moyo, Sikhulile; Musonda, Rosemary; Woldegabriel, Elias; Lagakos, Stephen; Essex, M.

2009-01-01

238

Changes in intramitochondrial and cytosolic pH: early events that modulate caspase activation during apoptosis  

Microsoft Academic Search

Mitochondria trigger apoptosis by releasing caspase activators, including cytochrome c (cytC). Here we show, using a pH-sensitive green fluorescent protein (GFP), that mitochondria-dependent apoptotic stimuli (such as Bax, staurosporine and ultraviolet irradiation) induce rapid, Bcl-2-inhibitable mitochondrial alkalinization and cytosol acidification, followed by cytC release, caspase activation and mitochondrial swelling and depolarization. These events are not induced by mitochondria-independent apoptotic stimuli,

Shigemi Matsuyama; Juan Llopis; Quinn L. Deveraux; Roger Y. Tsien; John C. Reed

2000-01-01

239

Early processing of emotional faces in children with autism: An event-related potential study  

Microsoft Academic Search

Social deficits are one of the most striking manifestations of autism spectrum disorders (ASDs). Among these social deficits, the recognition and understanding of emotional facial expressions has been widely reported to be affected in ASDs. We investigated emotional face processing in children with and without autism using event-related potentials (ERPs). High-functioning children with autism (n=15, mean age=10.5±3.3 years) completed an

Magali Batty; Emilie Meaux; Kerstin Wittemeyer; Bernadette Rogé; Margot J. Taylor

2011-01-01

240

Impact of Prior Traumatic Life Events on Parental Early Stage Reactions following a Child's Cancer  

PubMed Central

Background In pediatric oncology, effective clinic–based management of acute and long–term distress in families calls for investigation of determinants of parents' psychological response to the child's cancer. We examined the relationship between parents' prior exposure to traumatic life events (TLE) and the occurrence of posttraumatic stress symptoms (PTSS) following their child's cancer diagnosis. Factors mediating the TLE–PTSS relationship were analyzed. Methodology The study comprised 169 parents (97 mothers, 72 fathers) of 103 cancer diagnosed children (median age: 5,9 years; range 0.1–19.7 years). Thirty five parents were of immigrant origin (20.7%). Prior TLE were collated using a standardized questionnaire, PTSS was assessed using the Impact of Events–Revised (IES–R) questionnaire covering intrusion, avoidance and hyperarousal symptoms. The predictive significance of prior TLE on PTSS was tested in adjusted regression models. Results Mothers demonstrated more severe PTSS across all symptom dimensions. TLE were associated with significantly increased hyperarousal symptoms. Parents' gender, age and immigrant status did not significantly influence the TLE–PTSS relationship. Conclusions Prior traumatic life–events aggravate posttraumatic hyperarousal symptoms. In clinic–based psychological care of parents of high–risk pediatric patients, attention needs to be paid to life history, and to heightened vulnerability to PTSS associated with female gender.

Boman, Krister K.; Kjallander, Ylva; Eksborg, Staffan; Becker, Jeremy

2013-01-01

241

Quantitative In Vivo Redox Sensors Uncover Oxidative Stress as an Early Event in Life  

PubMed Central

SUMMARY Obstacles in elucidating the role of oxidative stress in aging include difficulties in 1) tracking in vivo oxidants, in 2) identifying affected proteins, and in 3) correlating changes in oxidant levels with lifespan. Here, we used quantitative redox proteomics to determine the onset and the cellular targets of oxidative stress during Caenorhabditis elegans’ lifespan. In parallel, we used genetically encoded sensor proteins to determine peroxide levels in live animals in real time. We discovered that C. elegans encounters significant levels of oxidants as early as during larval development. Oxidant levels drop rapidly as animals mature and reducing conditions prevail throughout the reproductive age, after which age-accompanied protein oxidation sets in. Long-lived daf-2 mutants transition faster to reducing conditions, whereas short-lived daf-16 mutants retain higher oxidant levels throughout their mature life. These results suggest that animals with improved capacity to recover from early oxidative stress have significant advantages later in life.

Knoefler, Daniela; Thamsen, Maike; Koniczek, Martin; Niemuth, Nicholas J.; Diederich, Ann-Kristin; Jakob, Ursula

2012-01-01

242

Early events in speciation: polymorphism for hybrid male sterility in Drosophila.  

PubMed

Capturing the process of speciation early enough to determine the initial genetic causes of reproductive isolation remains a major challenge in evolutionary biology. We have found, to our knowledge, the first example of substantial intraspecific polymorphism for genetic factors contributing to hybrid male sterility. Specifically, we show that the occurrence of hybrid male sterility in crosses between Drosophila mojavensis and its sister species, Drosophila arizonae, is controlled by factors present at different frequencies in different populations of D. mojavensis. In addition, we show that hybrid male sterility is a complex phenotype; some hybrid males with motile sperm still cannot sire offspring. Because male sterility factors in hybrids between these species are not yet fixed within D. mojavensis, this system provides an invaluable opportunity to characterize the genetics of reproductive isolation at an early stage. PMID:15184657

Reed, Laura K; Markow, Therese A

2004-06-07

243

Early Events in Foamy Virus--Host Interaction and Intracellular Trafficking  

PubMed Central

Here we review viral and cellular requirements for entry and intracellular trafficking of foamy viruses (FVs) resulting in integration of viral sequences into the host cell genome. The virus encoded glycoprotein harbors all essential viral determinants, which are involved in absorption to the host membrane and triggering the uptake of virus particles. However, only recently light was shed on some details of FV’s interaction with its host cell receptor(s). Latest studies indicate glycosaminoglycans of cellular proteoglycans, particularly heparan sulfate, to be of utmost importance. In a species-specific manner FVs encounter endogenous machineries of the target cell, which are in some cases exploited for fusion and further egress into the cytosol. Mostly triggered by pH-dependent endocytosis, viral and cellular membranes fuse and release naked FV capsids into the cytoplasm. Intact FV capsids are then shuttled along microtubules and are found to accumulate nearby the centrosome where they can remain in a latent state for extended time periods. Depending on the host cell cycle status, FV capsids finally disassemble and, by still poorly characterized mechanisms, the preintegration complex gets access to the host cell chromatin. Host cell mitosis finally allows for viral genome integration, ultimately starting a new round of viral replication.

Berka, Ursula; Hamann, Martin Volker; Lindemann, Dirk

2013-01-01

244

MINI REVIEW Early life events and conditions and breast cancer risk: From epidemiology to etiology  

Microsoft Academic Search

Risk factors for breast cancer—documented by intensive epidemi- ological investigations and viewed in the context of general princi- ples of carcinogenesis—can be integrated to an etiologic model comprising 3 principal components: the likelihood of breast can- cer occurrence depends on the number of mammary tissue-specific stem cells, which is determined in early life; all growth-enhancing mammotropic hormones affect the rate

Dimitrios Trichopoulos; Hans-Olov Adami; Anders Ekbom; Chung-Cheng Hsieh; Pagona Lagiou

2008-01-01

245

Irregularities in Early Seismic Rupture Propagation for Large Events in a Crustal Earthquake Model  

Microsoft Academic Search

We study early seismic propagation of model earthquakes in a 2-D model of a vertical strike-slip fault with depth-variable rate and state friction properties. Our model earthquakes are obtained in fully dynamic simulations of sequences of instabilities on a fault subjected to realistically slow tectonic loading (Lapusta et al., JGR, 2000). This work is motivated by results of Ellsworth and

N. Lapusta; J. R. Rice

2001-01-01

246

Not Just the 8.2 event: Dynamic Early Holocene Climate in Arctic Canada  

Microsoft Academic Search

Temperature reconstructions from a lake in the eastern Canadian Arctic indicate that peak warmth in the early Holocene was interrupted by two abrupt, short-lived temperature reversals at ~9.l and ~8.5 ka. Summer temperatures at Lake CF8, Baffin Island (~500 km west of Greenland) are inferred from subfossil midge (Chironomidae) assemblages. Our results indicate that the site, like others on Baffin

Y. Axford; J. P. Briner; G. H. Miller; D. R. Francis

2006-01-01

247

Diagnosis of second breast cancer events after initial diagnosis of early stage breast cancer  

Microsoft Academic Search

To examine whether there are any characteristics of women or their initial tumors that might be useful for tailoring surveillance\\u000a recommendations to optimize outcomes. We followed 17,286 women for up to 5 years after an initial diagnosis of ductal carcinoma\\u000a in situ (DCIS) or early stage (I\\/II) invasive breast cancer diagnosed between 1996 and 2006. We calculated rates per 1,000\\u000a women

Diana S. M. Buist; Linn A. Abraham; William E. Barlow; Arun Krishnaraj; Regan C. Holdridge; Edward A. Sickles; Patricia A. Carney; Karla Kerlikowske; Berta M. Geller

2010-01-01

248

Strong El Niño events during the early Holocene: stable isotope evidence from Peruvian sea shells  

Microsoft Academic Search

Intrashell oxygen and carbon stable isotope profiles (?18O,?13C) were established for Mesodesma donacium shells from the preceramic archaeological site, Quebrada de los Burros in coastal southern Peru, to reconstruct the sea-surface temperature (SST) variations and to estimate changes of the El Niño-Southem Oscillation (ENSO) interannual variability from the early Holocene to the present. Very strong oxygen isotopic excursions attributed to

Matthieu Carrè; Ilhem Bentaleb; Michel Fontugne; Daniele Lavallee

2005-01-01

249

Interactions of MCP1 with components of the replication machinery in mammalian cells.  

PubMed

Eukaryotic DNA replication starts with the assembly of a pre-replication complex (pre-RC) at replication origins. We have previously demonstrated that Metaphase Chromosome Protein 1 (MCP1) is involved in the early events of DNA replication. Here we show that MCP1 associates with proteins that are required for the establishment of the pre-replication complex. Reciprocal immunoprecipitation analysis showed that MCP1 interacted with Cdc6, ORC2, ORC4, MCM2, MCM3 and MCM7, with Cdc45 and PCNA. Immunofluorescence studies demonstrated the co-localization of MCP1 with some of those proteins. Moreover, biochemical studies utilizing chromatin-immunoprecipitation (ChIP) revealed that MCP1 preferentially binds replication initiation sites in human cells. Interestingly, although members of the pre-RC are known to interact with some hallmarks of heterochromatin, our co-immunoprecipitation and immunofluorescence analyses showed that MCP1 did not interact and did not co-localize with heterochromatic proteins including HP1? and MetH3K9. These observations suggest that MCP1 is associated with replication factors required for the initiation of DNA replication and binds to the initiation sites in loci that replicate early in S-phase. In addition, immunological assays revealed the association of MCP1 forms with histone H1 variants and mass spectrometry analysis confirmed that MCP1 peptides share common sequences with H1.2 and H1.5 subtypes. PMID:21383955

Bronze-da-Rocha, Elsa; Lin, Chii-Mei; Shimura, Tsutomu; Aladjem, Mirit I

2011-02-17

250

Interactions of MCP1 with Components of the Replication Machinery in Mammalian Cells  

PubMed Central

Eukaryotic DNA replication starts with the assembly of a pre-replication complex (pre-RC) at replication origins. We have previously demonstrated that Metaphase Chromosome Protein 1 (MCP1) is involved in the early events of DNA replication. Here we show that MCP1 associates with proteins that are required for the establishment of the pre-replication complex. Reciprocal immunoprecipitation analysis showed that MCP1 interacted with Cdc6, ORC2, ORC4, MCM2, MCM3 and MCM7, with Cdc45 and PCNA. Immunofluorescence studies demonstrated the co-localization of MCP1 with some of those proteins. Moreover, biochemical studies utilizing chromatin-immunoprecipitation (ChIP) revealed that MCP1 preferentially binds replication initiation sites in human cells. Interestingly, although members of the pre-RC are known to interact with some hallmarks of heterochromatin, our co-immunoprecipitation and immunofluorescence analyses showed that MCP1 did not interact and did not co-localize with heterochromatic proteins including HP1? and MetH3K9. These observations suggest that MCP1 is associated with replication factors required for the initiation of DNA replication and binds to the initiation sites in loci that replicate early in S-phase. In addition, immunological assays revealed the association of MCP1 forms with histone H1 variants and mass spectrometry analysis confirmed that MCP1 peptides share common sequences with H1.2 and H1.5 subtypes.

Bronze-da-Rocha, Elsa; Lin, Chii-Mei; Shimura, Tsutomu; Aladjem, Mirit I.

2011-01-01

251

Targeted Deletion of FGL2 Leads to Increased Early Viral Replication and Enhanced Adaptive Immunity in a Murine Model of Acute Viral Hepatitis Caused by LCMV WE  

PubMed Central

Mounting effective innate and adaptive immune responses are critical for viral clearance and the generation of long lasting immunity. It is known that production of inhibitory factors may result in the inability of the host to clear viruses, resulting in chronic viral persistence. Fibrinogen-like protein 2 (FGL2) has been identified as a novel effector molecule of CD4+CD25+ Foxp3+ regulatory T (Treg) cells that inhibits immune activity by binding to FC?RIIB expressed primarily on antigen presenting cells (APC). In this study, we show that infection of mice with Lymphocytic Choriomeningitis Virus WE (LCMV WE) leads to increased plasma levels of FGL2, which were detected as early as 2 days post-infection (pi) and persisted until day 50 pi. Mice deficient in FGL2 (fgl2?/?) had increased viral titers of LCMV WE in the liver early p.i but cleared the virus by day 12 similar to wild type mice. Dendritic cells (DC) isolated from the spleens of LCMV WE infected fgl2?/? had increased expression of the DC maturation markers CD80 and MHC Class II compared to wild type (fgl2+/+). Frequencies of CD8+ and CD4+ T cells producing IFN? in response to ex vivo peptide re-stimulation isolated from the spleen and lymph nodes were also increased in LCMV WE infected fgl2 ?/? mice. Increased frequencies of CD8+ T cells specific for LCMV tetramers GP33 and NP396 were detected within the liver of fgl2?/? mice. Plasma from fgl2?/? mice contained higher titers of total and neutralizing anti-LCMV antibody. Enhanced anti-viral immunity in fgl2?/? mice was associated with increased levels of serum alanine transaminase (ALT), hepatic necrosis and inflammation following LCMV WE infection. These data demonstrate that targeting FGL2 leads to early increased viral replication but enhanced anti-viral adaptive T & B cell responses. Targeting FGL2 may enhance the efficacy of current anti-viral therapies for hepatotropic viruses.

Khattar, Ramzi; Luft, Olga; Yavorska, Nataliya; Shalev, Itay; Phillips, M. James; Adeyi, Oyedele; Gao, Darrin; Bartczak, Agata; Urbanellis, Peter; Shyu, Wendy; Zhang, Jianhua; Manuel, Justin; Levy, Gary A.; Selzner, Nazia

2013-01-01

252

The interplay of turn formation and hydrophobic interactions on the early kinetic events in protein folding.  

PubMed

While both turn formation and hydrophobic interactions play dominant roles in the initiation of protein folding, their individual contributions to the folding kinetics and to the structural stability of the protein still remain poorly understood. Here, we applied a photolabile linker to "cage" some important structural motifs, including both ?-helices and ?-sheets, into their non-native states. These "caged" structural motifs are then relaxed by laser-flash photolysis and their refolding events followed by photoacoustic calorimetry (PAC) and photothermal beam deflection (PBD). These experiments, combined with our previous results, revealed that spontaneous ?-helix formation can occur extremely rapidly (10(8)-10(9) s(-1)) if the process is driven solely by turn formation followed by helix propagation. However, if sequestering of the side chains of hydrophobic amino acid residues participates in the refolding process, which may provide additional driving force beyond that afforded by turn formation alone, the refolding rate will be retarded, often by many orders of magnitude. This is usually the case in the formation of three-stranded ?-sheets (10(7)-10(8) s(-1)) and ?-hairpins (10(5)-10(6) s(-1)). Thus, we propose that proteins take advantage of the hierarchy of timescales associated with either turn formation, hydrophobic interactions, or global collapse of tertiary structure to accomplish the folding process in an orderly fashion, as these events are sufficiently separated in time and do not interfere with one another. PMID:22053320

Huang, Joseph Jen-Tse; Larsen, Randy W; Chan, Sunney I

2011-11-04

253

Stressful life events and depressive problems in early adolescent boys and girls: The influence of parental depression, temperament and family environment  

Microsoft Academic Search

BackgroundStressful life events increase the probability of depressive problems in early adolescence. Several genetic and environmental risk factors may change individual sensitivity to the depressogenic effect of these events. We examined modification by parental depression and gender, and mediation of the former by temperament and family environment.

Esther M. C. Bouma; Johan Ormel; Frank C. Verhulst; Albertine J. Oldehinkel

2008-01-01

254

Research report Stressful life events and depressive problems in early adolescent boys and girls: The influence of parental depression, temperament and family environment  

Microsoft Academic Search

Background: Stressful life events increase the probability of depressive problems in early adolescence. Several genetic and environmental risk factors may change individual sensitivity to the depressogenic effect of these events. We examined modification by parental depression and gender, and mediation of the former by temperament and family environment. Methods: Data were collected as part of a longitudinal cohort study of

Esther M. C. Bouma; Johan Ormel; Frank C. Verhulst; Albertine J. Oldehinkel

255

Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver  

PubMed Central

Aberrant DNA methylation is a common feature of neoplastic lesions, and early detection of such changes may provide powerful mechanistic insights and biomarkers for carcinogenesis. Here, we investigate dynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen, phenobarbital (PB). We find that the distribution of 5mC/5hmC is highly consistent between untreated individuals of a similar age; yet, changes during liver maturation in a transcriptionally dependent manner. Following drug treatment, we identify and validate a series of differentially methylated or hydroxymethylated regions: exposure results in staged transcriptional responses with distinct kinetic profiles that strongly correlate with promoter proximal region 5hmC levels. Furthermore, reciprocal changes for both 5mC and 5hmC in response to PB suggest that active demethylation may be taking place at each set of these loci via a 5hmC intermediate. Finally, we identify potential early biomarkers for non-genotoxic carcinogenesis, including several genes aberrantly expressed in liver cancer. Our work suggests that 5hmC profiling can be used as an indicator of cell states during organ maturation and drug-induced responses and provides novel epigenetic signatures for non-genotoxic carcinogen exposure.

Thomson, John P.; Hunter, Jennifer M.; Lempiainen, Harri; Muller, Arne; Terranova, Remi; Moggs, Jonathan G.; Meehan, Richard R.

2013-01-01

256

Early folding events protect aggregation-prone regions of a ?-rich protein.  

PubMed

Protein folding and aggregation inevitably compete with one another. This competition is even keener for proteins with frustrated landscapes, such as those rich in ? structure. It is interesting that, despite their rugged energy landscapes and high ? sheet content, intracellular lipid-binding proteins (iLBPs) appear to successfully avoid aggregation, as they are not implicated in aggregation diseases. In this study, we used a canonical iLBP, cellular retinoic acid-binding protein 1 (CRABP1), to understand better how folding is favored over aggregation. Analysis of folding kinetics of point mutants reveals that the folding pathway of CRABP1 involves early barrel closure. This folding mechanism protects sequences in CRABP1 that comprise cores of aggregates as identified by nuclear magnetic resonance. The amino acid conservation pattern in other iLBPs suggests that early barrel closure may be a general strategy for successful folding and minimization of aggregation. We suggest that folding mechanisms in general may incorporate steps that disfavor aggregation. PMID:23454187

Budyak, Ivan L; Krishnan, Beena; Marcelino-Cruz, Anna M; Ferrolino, Mylene C; Zhuravleva, Anastasia; Gierasch, Lila M

2013-03-01

257

The influence of surface energy on early adherent events of osteoblast on titanium substrates.  

PubMed

Surface energy of implant material is one of the important factors in the process of osseointegration. How surface energy regulates the signaling pathway of osteoblasts, however, is not well understood. Cell adhesion is one of the first steps essential to subsequent proliferation and differentiation of bone cells before tissue formation. Our present study was designed to investigate how surface energy may influence the early adhesion of human alveolar osteoblasts (AOBs). Substrates applied were two groups of titanium disks: (1) hydrophobic sandblasted and acid-etched (SLA) surfaces; (2) chemically modified hydrophilic SLA (modSLA) ones. Cell morphology and cell attachment were examined by scanning electron microscopy (SEM). Defined cytoskeletal actin organization was immunohistochemically examined using confocal laser scanning microscopy. RT-PCR was applied to detect and to compare the expression of focal adhesion kinase (FAK) of osteoblasts cultured on the two groups of substrates. The attachment rates of AOBs cultured on modSLA substrates were significantly higher than the cells on SLA ones within 3 h. AOBs on modSLA developed more defined actin stress fibers after 6 h of attachment. FAK expression was comparably higher on modSLA after 6 h. Within the limitation of the current study, higher surface energy of titanium surfaces enhanced the cell adhesion in the early stage of cell response and may work through influencing the expression of adhesion-associated molecules. PMID:19562750

Lai, Hong-Chang; Zhuang, Long-Fei; Liu, Xin; Wieland, Marco; Zhang, Zhi-Yong; Zhang, Zhi-Yuan

2010-04-01

258

Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver.  

PubMed

Aberrant DNA methylation is a common feature of neoplastic lesions, and early detection of such changes may provide powerful mechanistic insights and biomarkers for carcinogenesis. Here, we investigate dynamic changes in the mouse liver DNA methylome associated with short (1 day) and prolonged (7, 28 and 91 days) exposure to the rodent liver non-genotoxic carcinogen, phenobarbital (PB). We find that the distribution of 5mC/5hmC is highly consistent between untreated individuals of a similar age; yet, changes during liver maturation in a transcriptionally dependent manner. Following drug treatment, we identify and validate a series of differentially methylated or hydroxymethylated regions: exposure results in staged transcriptional responses with distinct kinetic profiles that strongly correlate with promoter proximal region 5hmC levels. Furthermore, reciprocal changes for both 5mC and 5hmC in response to PB suggest that active demethylation may be taking place at each set of these loci via a 5hmC intermediate. Finally, we identify potential early biomarkers for non-genotoxic carcinogenesis, including several genes aberrantly expressed in liver cancer. Our work suggests that 5hmC profiling can be used as an indicator of cell states during organ maturation and drug-induced responses and provides novel epigenetic signatures for non-genotoxic carcinogen exposure. PMID:23598998

Thomson, John P; Hunter, Jennifer M; Lempiäinen, Harri; Müller, Arne; Terranova, Rémi; Moggs, Jonathan G; Meehan, Richard R

2013-04-17

259

Astrochronology of the Valanginian Stage (Early Cretaceous) : implications for the origin of the Weissert Event  

NASA Astrophysics Data System (ADS)

Due to the scarcity of available radioisotopic ages in the Lower Cretaceous, the Geologic Time Scale presents uncertainties that impact palaeoceanographic and palaeoclimatic reconstructions. Particularly, the chronological relationship between the Mid-Valanginian carbon-isotope excursion (namely the 'Weissert Event') and the activity of the Paraná-Etendeka Large Igneous Province is debated. To better constrain this relationship, an astrochronology of the Valanginian Stage is proposed based on high-resolution gamma-ray spectrometry measurements performed on five biostratigraphically well-constrained sections throughout the Vocontian Basin (SE France). The Valanginian sediments of the Vocontian Basin are composed of decimetric hemipelagic marl-limestone alternations. These lithologic cycles are attributed to orbital forcing because marls and limestones display significant differences within clay mineralogy, geochemistry and faunal assemblages and these marl-limestone alternations are correlated throughout the Western Tethys and the Atlantic Ocean. Among the analyzed sections, Vergol (GSSP candidate for the Berriasian-Valanginian boundary), La Charce (GSSP candidate for the Valanginian-Hauterivian boundary) and Angles (Valanginian Hypostratotype) are standard sections for the Valanginian Stage since all ammonite zones and subzones are precisely identified and bounded. Spectral analyses were performed using the multi-taper method and amplitude spectrograms on the gamma-ray signals. The comparison between sedimentary frequency ratios derived from the spectral analyses and orbital frequency ratios calculated from astronomical solutions allows the identification of a pervasive dominance of the precession and the 405 kyr-eccentricity cycles throughout the Valanginian Stage. A duration of 5.1 myr is proposed for the Valanginian Stage on the base of the recognition of the 405 kyr-eccentricity cycles. This duration is in agreement with the orbital calibration proposed from ?13C measurements in the Maiolica Formation (Central Italy). By anchoring this proposed astrochronology with available radioisotopic ages for the Berriasian-Hauterivian interval, it appears that the Paraná-Etendeka activity started ~2 myr after the onset of the Weissert Event and therefore can not have induced the carbon-isotope excursion. Instead, following Westermann et al. (2010), we propose that continental carbon organic storage accompanied by carbonate-platform drownings are responsible for the first major carbon-isotope shift of the Cretaceous. Bibliography : Westermann, S., Föllmi, K.B., Adatte, T., Matera, V., Schnyder, J., Fleitmann, D., Fiet, N., Ploch, I., Duchamp-Alphonse, S., 2010. The Valanginian ?13C excrusion may no be an expression of a global oceanic anoxic event. EPSL 290, 118-131.

Martinez, Mathieu; Deconinck, Jean-François; Pellenard, Pierre; Reboulet, Stéphane; Riquier, Laurent

2013-04-01

260

HIV-1 Transmission during Early Antiretroviral Therapy: Evaluation of Two HIV-1 Transmission Events in the HPTN 052 Prevention Study  

PubMed Central

In the HPTN 052 study, transmission between HIV-discordant couples was reduced by 96% when the HIV-infected partner received suppressive antiretroviral therapy (ART). We examined two transmission events where the newly infected partner was diagnosed after the HIV-infected partner (index) initiated therapy. We evaluated the sequence complexity of the viral populations and antibody reactivity in the newly infected partner to estimate the dates of transmission to the newly infected partners. In both cases, transmission most likely occurred significantly before HIV-1 diagnosis of the newly infected partner, and either just before the initiation of therapy or before viral replication was adequately suppressed by therapy of the index. This study further strengthens the conclusion about the efficacy of blocking transmission by treating the infected partner of discordant couples. However, this study does not rule out the potential for HIV-1 transmission to occur shortly after initiation of ART, and this should be recognized when antiretroviral therapy is used for HIV-1 prevention.

Rodrigo, Allen G.; Hudelson, Sarah E.; Piwowar-Manning, Estelle; Wang, Lei; Eshleman, Susan H.; Cohen, Myron S.; Swanstrom, Ronald

2013-01-01

261

Early age-related changes in episodic memory retrieval as revealed by event-related potentials.  

PubMed

Familiarity is better preserved than recollection in ageing. The age at which changes first occur and the slope of the subsequent decline, however, remain unclear. In this study, we investigated changes in episodic memory, by using event-related potentials (ERPs) in young (m=24), middle-aged (m=58) and older (m=70) adults. Although behavioural performance did not change before the age of 65 years, changes in ERP correlates were already present in the middle-aged adults. The ERP correlates of recollection and monitoring processes were the first to be affected by ageing, with a linear decrease as age increased. Conversely, the ERP correlate of familiarity remained unchanged, at least up to the age of 65 years. These results suggest a differential time course for the age effects on episodic retrieval. PMID:19104457

Guillaume, Cécile; Clochon, Patrice; Denise, Pierre; Rauchs, Géraldine; Guillery-Girard, Bérengère; Eustache, Francis; Desgranges, Béatrice

2009-01-28

262

Age influences the early events of skeletal muscle regeneration: Studies of whole muscle grafts transplanted between young (8 weeks) and old (13–21 months) mice  

Microsoft Academic Search

Injured skeletal muscle generally regenerates less efficiently with age, but little is understood about the effects of ageing on the very early inflammatory and neovascular events in the muscle repair process. This study used a total of 174 whole muscle grafts transplanted within and between young and old mice to analyse the effects of ageing on the early inflammatory response

Gail Smythe; Thea Shavlakadze; Peter Roberts; Marilyn Davies; John McGeachie; Miranda Grounds

2008-01-01

263

Lung Transplant Acceptance is Facilitated by Early Events in the Graft and is Associated with Lymphoid Neogenesis  

PubMed Central

Early immune responses are important in shaping long-term outcomes of human lung transplants. To examine the role of early immune responses in lung rejection and acceptance we developed a method to retransplant mouse lungs. Retransplantation into T cell-deficient hosts showed that for lungs and hearts alloimmune responses occurring within 72 hours of transplantation are reversible. In contrast to hearts, a 72-hour period of immunosuppression with costimulation blockade in primary allogeneic recipients suffices to prevent rejection of lungs upon retransplantation into untreated allogeneic hosts. Long-term lung acceptance is associated with induction of bronchus-associated lymphoid tissue, where Foxp3+ cells accumulate and recipient T cells interact with CD11c+ dendritic cells. Acceptance of retransplanted lung allografts is abrogated by treatment of immunosuppressed primary recipients with anti-CD25 antibodies. Thus, events contributing to lung transplant acceptance are established early in the graft and induction of bronchus-associated lymphoid tissue can be associated with an immune quiescent state.

Li, Wenjun; Bribriesco, Alejandro C.; Nava, Ruben G.; Brescia, Alexander A.; Ibricevic, Aida; Spahn, Jessica H.; Brody, Steven L.; Ritter, Jon H.; Gelman, Andrew E.; Krupnick, Alexander S.; Miller, Mark J.; Kreisel, Daniel

2012-01-01

264

Early events in the evolution of the Silene latifolia Y chromosome: male specialization and recombination arrest.  

PubMed

Understanding the origin and evolution of sex chromosomes requires studying recently evolved X-Y chromosome systems such as those in some flowering plants. We describe Y chromosome deletion mutants of Silene latifolia, a dioecious plant with heteromorphic sex chromosomes. The combination of results from new and previously described deletions with histological descriptions of their stamen development defects indicates the presence of two distinct Y regions containing loci with indispensable roles in male reproduction. We determined their positions relative to the two main sex determination functions (female suppressing and the other male promoting). A region proximal to the centromere on the Y p arm containing the putative stamen promoting sex determination locus includes additional early stamen developmental factors. A medial region of the Y q arm carries late pollen fertility factors. Cytological analysis of meiotic X-Y pairing in one of the male-sterile mutants indicates that the Y carries sequences or functions specifically affecting sex chromosome pairing. PMID:17603119

Zluvova, Jitka; Georgiev, Sevdalin; Janousek, Bohuslav; Charlesworth, Deborah; Vyskot, Boris; Negrutiu, Ioan

2007-07-01

265

Early Events in the Evolution of the Silene latifolia Y Chromosome: Male Specialization and Recombination Arrest  

PubMed Central

Understanding the origin and evolution of sex chromosomes requires studying recently evolved X–Y chromosome systems such as those in some flowering plants. We describe Y chromosome deletion mutants of Silene latifolia, a dioecious plant with heteromorphic sex chromosomes. The combination of results from new and previously described deletions with histological descriptions of their stamen development defects indicates the presence of two distinct Y regions containing loci with indispensable roles in male reproduction. We determined their positions relative to the two main sex determination functions (female suppressing and the other male promoting). A region proximal to the centromere on the Y p arm containing the putative stamen promoting sex determination locus includes additional early stamen developmental factors. A medial region of the Y q arm carries late pollen fertility factors. Cytological analysis of meiotic X–Y pairing in one of the male-sterile mutants indicates that the Y carries sequences or functions specifically affecting sex chromosome pairing.

Zluvova, Jitka; Georgiev, Sevdalin; Janousek, Bohuslav; Charlesworth, Deborah; Vyskot, Boris; Negrutiu, Ioan

2007-01-01

266

Rotaviruses induce an early membrane permeabilization of MA104 cells and do not require a low intracellular Ca2+ concentration to initiate their replication cycle.  

PubMed Central

In this work, we found that rotavirus infection induces an early membrane permeabilization of MA104 cells and promotes the coentry of toxins, such as alpha-sarcin, into the cell. This cell permeability was shown to depend on infectious virus and was also shown to be virus dose dependent, with 10 infectious particles per cell being sufficient to achieve maximum permeability; transient, lasting no more than 15 min after virus entry and probably occurring concomitantly with virus penetration; and specific, since cells that are poorly permissive for rotavirus were not permeabilized. The rotavirus-mediated coentry of toxins was not blocked by the endocytosis inhibitors dansylcadaverine and cytochalasin D or by the vacuolar proton-ATPase inhibitor bafilomycin A1, suggesting that neither endocytocis nor an intraendosomal acidic pH or a proton gradient is required for permeabilization of the cells. Compounds that raise the intracellular concentration of calcium ([Ca2+]i) by different mechanisms, such as the calcium ionophores A23187 and ionomycin and the endoplasmic reticulum calcium-ATPase inhibitor thapsigargin, did not block the coentry of alpha-sarcin or affect the onset of viral protein synthesis, suggesting that a low [Ca2+]i is not essential for the initial steps of the virus life cycle. Since the entry of alpha-sarcin correlates with virus penetration in all parameters tested, the assay for permeabilization to toxins might be a useful tool for studying and characterizing the route of entry and the mechanism used by rotaviruses to traverse the cell membrane and initiate a productive replication cycle.

Cuadras, M A; Arias, C F; Lopez, S

1997-01-01

267

Hypermethylation of the nel-like 1 gene is a common and early event and is associated with poor prognosis in early-stage esophageal adenocarcinoma.  

PubMed

The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (P<0.001). NELL1 normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's (D) and EAC than in NE (P<0.0000001). NELL1 hypermethylation frequency was zero in NE but increased early during neoplastic progression, to 41.7% in BE from patients with Barrett's alone, 52.5% in D and 47.8% in EAC. There was a significant correlation between NELL1 hypermethylation and BE segment length. Three (11.5%) of 26 ESCCs exhibited NELL1 hypermethylation. Survival correlated inversely with NELL1 hypermethylation in patients with stages I-II (P=0.0264) but not in stages III-IV (P=0.68) EAC. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2'-deoxycytidine reduced NELL1 methylation and increased NELL1 mRNA expression. NELL1 mRNA levels in EACs with an unmethylated NELL1 promoter were significantly higher than those in EACs with a methylated promoter (P=0.02). Promoter hypermethylation of NELL1 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC. PMID:17452981

Jin, Z; Mori, Y; Yang, J; Sato, F; Ito, T; Cheng, Y; Paun, B; Hamilton, J P; Kan, T; Olaru, A; David, S; Agarwal, R; Abraham, J M; Beer, D; Montgomery, E; Meltzer, S J

2007-04-23

268

Phosphoacceptor Site S173 in the Regulatory Domain of Epstein-Barr Virus ZEBRA Protein Is Required for Lytic DNA Replication but Not for Activation of Viral Early Genes?  

PubMed Central

The Epstein-Barr virus ZEBRA protein controls the viral lytic cycle. ZEBRA activates the transcription of viral genes required for replication. ZEBRA also binds to oriLyt and interacts with components of the viral replication machinery. The mechanism that differentiates the roles of ZEBRA in regulation of transcription and initiation of lytic replication is unknown. Here we show that S173, a residue in the regulatory domain, is obligatory for ZEBRA to function as an origin binding protein but is dispensable for its role as a transcriptional activator of early genes. Serine-to-alanine substitution of this residue, which prevents phosphorylation of S173, resulted in a threefold reduction in the DNA binding affinity of ZEBRA for oriLyt, as assessed by chromatin immunoprecipitation. An independent assay based on ZEBRA solubility demonstrated a marked defect in DNA binding by the Z(S173A) mutant. The phenotype of a phosphomimetic mutant, the Z(S173D) mutant, was similar to that of wild-type ZEBRA. Our findings suggest that phosphorylation of S173 promotes viral replication by enhancing ZEBRA's affinity for DNA. The results imply that stronger DNA binding is required for ZEBRA to activate replication than that required to activate transcription.

El-Guindy, Ayman; Heston, Lee; Delecluse, Henri-Jacques; Miller, George

2007-01-01

269

Repression of early lateral root initiation events by transient water deficit in barley and maize.  

PubMed

The formation of lateral roots (LRs) is a key driver of root system architecture and developmental plasticity. The first stage of LR formation, which leads to the acquisition of founder cell identity in the pericycle, is the primary determinant of root branching patterns. The fact that initiation events occur asynchronously in a very small number of cells inside the parent root has been a major difficulty in the study of the molecular regulation of branching patterns. Inducible systems that trigger synchronous lateral formation at predictable sites have proven extremely valuable in Arabidopsis to decipher the first steps of LR formation. Here, we present a LR repression system for cereals that relies on a transient water-deficit treatment, which blocks LR initiation before the first formative divisions. Using a time-lapse approach, we analysed the dynamics of this repression along growing roots and were able to show that it targets a very narrow developmental window of the initiation process. Interestingly, the repression can be exploited to obtain negative control root samples where LR initiation is absent. This system could be instrumental in the analysis of the molecular basis of drought-responsive as well as intrinsic pathways of LR formation in cereals. PMID:22527396

Babé, Aurélie; Lavigne, Tristan; Séverin, Jean-Philippe; Nagel, Kerstin A; Walter, Achim; Chaumont, François; Batoko, Henri; Beeckman, Tom; Draye, Xavier

2012-06-01

270

Riding the Wave to Reach the Masses: Natural Events in Early Twentieth Century Portuguese Daily Press  

NASA Astrophysics Data System (ADS)

This paper brings together science communicated in newspapers in Portugal by looking at how news on natural events were communicated in two different newspapers—the capital newspaper Diário de Notícias (Daily News) and the Diário dos Açores (Azores Daily). In particular, we look at how the 1900 solar eclipse, a hot topic throughout Europe, was reported by the capital newspaper, and how news on seismology were conveyed in the period 1907-1910 in the newspaper published in Azores, an archipelago with a significant seismic and volcanic activity. We argue that the importance conceded to these scientific news was related to their overwhelming features, that their dissimilar presentation stemmed from their local relevance allied to their different nature, predictable in the case of eclipses, and unpredictable in the case of earthquakes, and that behind these two instances of science journalism laid an attempt by the scientific and political communities to gain the support of the general public to such an extent that these two specific instances of science journalism transcended their usual features to become successful forms of expository science.

Simões, Ana; Carneiro, Ana; Diogo, Maria Paula

2010-09-01

271

Riding the Wave to Reach the Masses: Natural Events in Early Twentieth Century Portuguese Daily Press  

NASA Astrophysics Data System (ADS)

This paper brings together science communicated in newspapers in Portugal by looking at how news on natural events were communicated in two different newspapers—the capital newspaper Diário de Notícias ( Daily News) and the Diário dos Açores ( Azores Daily). In particular, we look at how the 1900 solar eclipse, a hot topic throughout Europe, was reported by the capital newspaper, and how news on seismology were conveyed in the period 1907-1910 in the newspaper published in Azores, an archipelago with a significant seismic and volcanic activity. We argue that the importance conceded to these scientific news was related to their overwhelming features, that their dissimilar presentation stemmed from their local relevance allied to their different nature, predictable in the case of eclipses, and unpredictable in the case of earthquakes, and that behind these two instances of science journalism laid an attempt by the scientific and political communities to gain the support of the general public to such an extent that these two specific instances of science journalism transcended their usual features to become successful forms of expository science.

Simões, Ana; Carneiro, Ana; Diogo, Maria Paula

2012-03-01

272

Fast temporal event integration in the visual domain demonstrated by event-related potentials.  

PubMed

Four experiments are reported that investigated visual event integration by using a variant of the missing element paradigm. Good performance on this task depends on whether two brief successive stimulus displays are perceived as (or integrated into) one single event. We replicated the classic finding of greater accuracy with shorter duration of the first stimulus and ruled out an attention-related account thereof. In a subsequent electrophysiological experiment we found that successful event integration increased the amplitude of the N1, N2, and late P3 components of the event-related potential and decreased early P3 amplitude. No effect on the P1 was observed. The results provided evidence for an early onset of event integration in time and demonstrated the existence of electrophysiological markers of episodic integration. The implications of these results are related to studies on feature-specific integration and early attentional processes. PMID:20136735

Akyürek, Elkan G; Schubö, Anna; Hommel, Bernhard

2010-02-02

273

Database replication  

US Patent & Trademark Office Database

A new database design is implemented in which everything in the database is modeled with primitives, including the links and nodes for a graph tuple store. A query syntax provides a nested tree of constraints with a single global schema. Various optimization techniques for queries and replication techniques are also described.

2012-06-19

274

Characterization of the early ultrastructural and biochemical events occurring in dichloromethane diphosphonate nephrotoxicity.  

PubMed

A chelator, dichloromethane diphosphonate (Cl2MDP), used to treat for malignancy-induced hypercalcemia, has nephrotoxic potential. An acute animal model developed to examine the mechanism was used to further characterize the renal effects. NAG enzymuria appears to be an early premonitor of injury. Ultrastructurally, an increase in size and number of protein-containing phagolysosomal reabsorption droplets in proximal convoluted tubules associated with proteinuria precedes advent of tubular cell necrosis indicating these organelles to be a potential target site for Cl2MDP in the kidney. In vitro studies using rabbit cortical tubules and rat brush border membrane vesicle preparations suggest that the renal toxicity is not due to perturbation of phosphate transport or oxidative metabolism. An operational hypothesis emerges indicating that Cl2MDP may be protein bound affecting carrier protein charge facilitating glomerular leakage with tubular accumulation via protein transport. Cl2MDP may induce critical cation perturbation at the subcellular level as the mechanism of cell death. PMID:2151201

Alden, C L; Burns, J L; Parker, R D; Englehart, J L; Dennis, V W

1990-01-01

275

hESC derived neuro-epithelial rosettes recapitulate early mammalian neurulation events; an in vitro model.  

PubMed

The in vitro neuralization of hESCs has been widely used to generate central and peripheral nervous system components from neural precursors (Bajpai et al., 2009; Curchoe et al., 2010), most often through an intermediate "rosette" stage. Here we confirm that hESC derived neuro-epithelial rosettes express many characteristics of the developing embryonic neural plate (Aaku-Saraste et al., 1996), characterized by expression of the tight junction proteins ZO-1 and N-Cadherin. Moreover, neuro-epithelial rosettes display a characteristic acetylated alpha tubulin cytoskeletal arrangement (similar to that observed in the developing embryonic neural plate) (Bhattacharyya et al., 1994). Demonstrated here for the first time MKLP was observed in a hESC model system. We found MKLP expression in small particles in between mitotic spindles, large particles aggregating in the lumen of neuroepithelial rosettes, and we did not observe MKLP in the nucleus of hESC derived neural precursors as previously described in the HeLa cell line. We observed MKLP+ particles in aggregations in the lumen of "early" rosette structures. Furthermore, we observed that MKLP+ particle aggregations can also be lost from the lumens of hESC derived neuro-epithelial rosettes, similar to a phenomenon observed in the developing neural tube in vivo (Marzesco et al., 2005). We determined that this loss of MKLP+ particles occurs from "late" as opposed to "early" stage neuro-epithelial rosettes (characterized by junction type). Disrupting the apical-basal polarization of "early" stage rosettes with a 1% Matrigel overlay (Krtolica et al., 2007) nearly ablates MKLP particle aggregation in the lumen of rosettes, demonstrating that the apical-basal polarity of early NE cells is necessary for lumenal MKLP particle aggregation. We conclude that early hESC derived neuro-epithelial rosettes can model early neurulation events, such as the transition from neural plate like cells to neural tube like cells (i.e., symmetric to asymmetric NE cell division) demonstrated by polarized MKLP particle inheritance and distribution using junction type as a measure of stage. PMID:22265743

Curchoe, Carol Lynn; Russo, Joseph; Terskikh, Alexey V

2011-11-20

276

Transcriptional Program of Early Sporulation and Stationary-Phase Events in Clostridium acetobutylicum†  

PubMed Central

DNA microarray analysis of Clostridium acetobutylicum was used to examine the genomic-scale gene expression changes during the shift from exponential-phase growth and acidogenesis to stationary phase and solventogenesis. Self-organizing maps were used to identify novel expression patterns of functional gene classes, including aromatic and branched-chain amino acid synthesis, ribosomal proteins, cobalt and iron transporters, cobalamin biosynthesis, and lipid biosynthesis. The majority of pSOL1 megaplasmid genes (in addition to the solventogenic genes aad-ctfA-ctfB and adc) had increased expression at the onset of solventogenesis, suggesting that other megaplasmid genes may play a role in stationary-phase phenomena. Analysis of sporulation genes and comparison with published Bacillus subtilis results indicated conserved expression patterns of early sporulation genes, including spo0A, the sigF operon, and putative canonical genes of the ?H and ?F regulons. However, sigE expression could not be detected within 7.5 h of initial spo0A expression, consistent with the observed extended time between the appearance of clostridial forms and endospore formation. The results were compared with microarray comparisons of the wild-type strain and the nonsolventogenic, asporogenous M5 strain, which lacks the pSOL1 megaplasmid. While some results were similar, the expression of primary metabolism genes and heat shock proteins was higher in M5, suggesting a difference in metabolic regulation or a butyrate stress response in M5. The results of this microarray platform and analysis were further validated by comparing gene expression patterns to previously published Northern analyses, reporter assays, and two-dimensional protein electrophoresis data of metabolic genes (including all major solventogenesis genes), sporulation genes, heat shock proteins, and other solventogenesis-induced gene expression.

Alsaker, Keith V.; Papoutsakis, Eleftherios T.

2005-01-01

277

High-Content Analysis of Sequential Events during the Early Phase of Influenza A Virus Infection  

PubMed Central

Influenza A virus (IAV) represents a worldwide threat to public health by causing severe morbidity and mortality every year. Due to high mutation rate, new strains of IAV emerge frequently. These IAVs are often drug-resistant and require vaccine reformulation. A promising approach to circumvent this problem is to target host cell determinants crucial for IAV infection, but dispensable for the cell. Several RNAi-based screens have identified about one thousand cellular factors that promote IAV infection. However, systematic analyses to determine their specific functions are lacking. To address this issue, we developed quantitative, imaging-based assays to dissect seven consecutive steps in the early phases of IAV infection in tissue culture cells. The entry steps for which we developed the assays were: virus binding to the cell membrane, endocytosis, exposure to low pH in endocytic vacuoles, acid-activated fusion of viral envelope with the vacuolar membrane, nucleocapsid uncoating in the cytosol, nuclear import of viral ribonucleoproteins, and expression of the viral nucleoprotein. We adapted the assays to automated microscopy and optimized them for high-content screening. To quantify the image data, we performed both single and multi-parametric analyses, in combination with machine learning. By time-course experiments, we determined the optimal time points for each assay. Our quality control experiments showed that the assays were sufficiently robust for high-content analysis. The methods we describe in this study provide a powerful high-throughput platform to understand the host cell processes, which can eventually lead to the discovery of novel anti-pathogen strategies.

Banerjee, Indranil; Yamauchi, Yohei; Helenius, Ari; Horvath, Peter

2013-01-01

278

Petrography and carbonate isotope stratigraphy from MIS AND-1B core, Antarctica: Evidence of the early Pliocene warming event  

NASA Astrophysics Data System (ADS)

A large portion of ANDRILL (ANtarctic geological DRILLing) core AND-1B recovered in the Western Ross Sea and spanning the early Pliocene has been investigated in order to obtain a detailed carbonate isotope record from Antarctic margin sediments through the early Pliocene warming event. Petrographic observations and mineralogical analyses reveal the authigenic nature of the carbonate and small proportions of Fe and Mg incorporated within the calcite lattice. High productivity conditions testified by ~ 80 m-thick diatomite interval (383 to 460 mbsf) well fit with the composite nature of the authigenic carbonate generally characterizing organic matter-rich sediments. As is known, sediments from the Polar Region are generally poor in carbonate. Although in the investigated portion of AND-1B core the carbonate seldom exceeds 5% in content, an automated Carbonate Preparation Device was used to obtain a high-resolution stable isotope dataset. Paleoenvironmental conditions characterized by high organic matter flux are supported by negative ? 13C values suggesting a contribution of isotopically light biogenic CO 2 during the carbonate precipitation. As to ? 18O, even if melting glaciers are thought to be responsible for depletion in 18O composition, the isotope record exhibits long- and short-term trends. Analysis of the long-term trend constrains the Pliocene warming climax in an interval between 400-450 mbsf highlighting that most of the event is not documented because of a 800 kyr hiatus. The short-term trend documents the influence of obliquity controlling the annual insolation, but also that of precession-linked cyclicity seldom documented at high latitude.

Scopelliti, G.; Bellanca, A.; Neri, R.

2011-03-01

279

Antibody-mediated osseous regeneration: the early events in the healing response.  

PubMed

Bone engineering strategies often exploit modulation of the extracellular environment, including delivery of cell and growth factors to repair and regenerate damaged tissues. During bone healing, the expression of endogenous bone morphogenetic proteins is an essential component of the healing response. However, in some situations, the inherent reparative capacity available in the local microenvironment is exceeded by the requirements of the defects. We have recently reported on a novel strategy, that exploits the specificity of antibodies to capture and make available endogenous osteogenic growth factors, referred to as "antibody-mediated osseous regeneration" (AMOR). The objective of the present study was to identify some of the cellular and molecular events involved in AMOR in an effort to begin to elucidate the mechanism of AMOR. The rat critical-sized calvarial defect model was used, where anti-bone morphogenetic protein (BMP)-2 monoclonal antibody (mAb), isotype-control mAb, or recombinant human (rh)BMP-2 were immobilized on absorbable collagen calvarial sponge (ACS) by adsorption, and then implanted into calvarial defects. The results demonstrated persistence of implanted mAbs for short term from 1 to 2 weeks after implantation. Increased cell infiltration was found in defects treated with anti-BMP-2?mAb. Examination of proteins on ACS scaffolds retrieved from defect sites demonstration increased levels of BMP-2, BMP-4, and BMP-7 proteins in sites implanted with anti-BMP-2?mAb. Moreover, BMP-2, BMP-4, and BMP-7 gene expression levels were increased in sites implanted with anti-BMP-2?mAb. Micro-computed tomography and histological analysis demonstrated that the bone within calvarial defects was fully regenerated in sites implanted with either anti-BMP-2?mAb or rhBMP-2. However, rhBMP-2-regenerated bone exhibited aberrant histomorphology with dystrophic calcification and invasion of subjacent areas. Altogether, the results revealed evidence for anti-BMP-2?mAbs to form an immune complex with BMP-2, BMP-4, and BMP-7, and bind to cells to mediate osteogenesis bone regeneration in vivo. This approach suggests a significant role for antibodies in regenerative orthopedic medicine. PMID:23190409

Freire, Marcelo O; Kim, Hak Kyun; Kook, Joong-Ki; Nguyen, Anthony; Zadeh, Homayoun H

2013-01-08

280

Binding sites for the herpes simplex virus immediate-early protein ICP4 impose an increased dependence on viral DNA replication on simple model promoters located in the viral genome.  

PubMed Central

We examined the ability of binding sites for the herpes simplex virus immediate-early protein ICP4 to alter the regulation of closely linked promoters by placing strong ICP4 binding sites upstream or downstream of simple TATA promoters in the intact viral genome. We found that binding sites strongly reduced the levels of expression at early times postinfection and that this effect was partially overcome after the onset of viral DNA replication. These data confirm that DNA-bound ICP4 can inhibit the activity of a closely linked promoter and raise the possibility that ICP4 binding sites contribute to temporal regulation during infection. Images

Koop, K E; Duncan, J; Smiley, J R

1993-01-01

281

Co-ordination of early and late ripening events in apples is regulated through differential sensitivities to ethylene  

PubMed Central

In this study, it is shown that anti-sense suppression of Malus domestica 1-AMINO-CYCLOPROPANE-CARBOXYLASE OXIDASE (MdACO1) resulted in fruit with an ethylene production sufficiently low to be able to assess ripening in the absence of ethylene. Exposure of these fruit to different concentrations of exogenous ethylene showed that flesh softening, volatile biosynthesis, and starch degradation, had differing ethylene sensitivity and dependency. Early ripening events such as the conversion of starch to sugars showed a low dependency for ethylene, but a high sensitivity to low concentrations of ethylene (0.01 ?l l?1). By contrast, later ripening events such as flesh softening and ester volatile production showed a high dependency for ethylene but were less sensitive to low concentrations (needing 0.1 ?l l?1 for a response). A sustained exposure to ethylene was required to maintain ripening, indicating that the role of ethylene may go beyond that of ripening initiation. These results suggest a conceptual model for the control of individual ripening characters in apple, based on both ethylene dependency and sensitivity.

Johnston, Jason W.; Gunaseelan, Kularajathaven; Pidakala, Paul; Wang, Mindy; Schaffer, Robert J.

2009-01-01

282

Early event-related potentials indicate context-specific target processing for eye and hand motor systems.  

PubMed

Concurrent eye and hand movements toward a common visual target require different motor programs based on identical visual input. We used event-related brain potentials (ERP) to determine if and when the processing of the visual target differs for the two motor systems. The N2, an index for target evaluation, was more negative for the target of a hand than of an eye movement in two experiments. A possible interpretation for this finding is different visual target processing. Targets for hand movements require a different weighting of visual information, for example concerning features such as surface structure which are important for hand but not for eye movements. In experiment 2, the early C1-component, which had an average maximum at 67ms following target onset, was significantly more negative when subjects pointed at the stimuli. Traditionally, the C1 has been regarded as a sensory component, but recent studies have linked it to higher order processing, such as attention and expectations. Thus, the present data indicate that target processing for eye or hand movements is already context-specific during early visual information processing. We suggest that differences in a target's relevance for upcoming movements modify target processing as well as sensory expectations. PMID:23968690

Wehrspaun, Claudia C; Pfabigan, Daniela M; Sailer, Uta

2013-08-19

283

Elemental Enrichment in Sediments Corresponding to the Early Aptian Oceanic Anoxic Event at Shatsky Rise (Site 1207)  

NASA Astrophysics Data System (ADS)

During ODP Leg 198 a pelagic organic-rich sedimentary sequence deposited during the Early Aptian Oceanic Anoxic Event (OAE1a) was recovered at SIte 1207 on Shatsky Rise in the NW Pacific. This 45 cm continuous sequence includes samples with extremely high organic carbon contents (i.e. 40 percent Corg), and provides molecular evidence from TEX86 measurements for cooler intervals during OAE1a, associated with this episode of enhanced carbon sequestration. Investigation of the major and trace element concentrations within the organic-rich sequence reveals enrichments in many constituents relative to average shale, although comparable with values observed in sediments from other OAE. Nutrient- and organic matter-related elements (e.g., P, Ni, and Cu) suggest that these sediments were deposited during a period of increased, albeit variable, primary production, an interpretation consistent with evidence from molecular and isotopic data. The depositional environment also appears to have experienced fluctuating redox conditions based on the concentrations of specific elements (e.g. U, V, Mo) and indices (e.g. Ni/Co, V/Cr), confirming the importance of productivity in carbon accumulation. In addition, metal enrichments suggest that magmatic degassing associated with the emplacement of Ontong-Java and Manihiki Plateaus and water-rock exchange at spreading centers introduced large quantities of trace metals into the ocean during the Early Aptian that may have promoted biological productivity.

Dumitrescu, M.; Brassell, S. C.

2006-12-01

284

Human Papillomavirus Type 31 Replication Modes during the Early Phases of the Viral Life Cycle Depend on Transcriptional and Posttranscriptional Regulation of E1 and E2 Expression  

PubMed Central

The E1 and E2 proteins are both required for papillomavirus DNA replication, and replication efficiency is controlled by the abundance of these factors. In human papillomaviruses (HPVs), the regulation of E1 and E2 expression and its effect on viral replication are not well understood. In particular, it is not known if E1 and E2 modulate their own expression and how posttranscriptional mechanisms may affect the levels of the replication proteins. Previous studies have implicated splicing within the E6 open reading frame (ORF) as being important for modulating replication of HPV type 31 (HPV31) through altered expression of E1 and E2. To analyze the function of the E6 intron in viral replication more specifically, we examined the effects of E6 splicing mutations in the context of entire viral genomes in transient assays. HPV31 genomes which had mutations in the splice donor site (E6SD) or the splice acceptor site (E6SA), a deletion of the intron (E6ID), or substituted heterologous intron sequences (E6IS) were constructed. Compared to wild-type (wt) HPV31, pHPV31-E6SD, -E6SA, and -E6IS replicated inefficiently while pHPV31-E6ID replicated at an intermediate level. Cotransfection of the E6 mutant genomes with an E1 expression vector strongly activated their replication levels, indicating that efficient expression of E1 requires E6 internal splicing. In contrast, replication was activated only moderately with an E2 expression vector. Replacing the wt E6 intron in HPV31 with a heterologous intron from simian virus 40 (E6SR2) resulted in replication levels similar to that of the wt in the absence of expression vectors, suggesting that mRNA splicing upstream of the E1 ORF is important for high-level replication. To examine the effects of E6 intron splicing on E1 and E2 expression directly, we constructed reporter DNAs in which the luciferase coding sequences were fused in frame to the E1 (E1Luc) or E2 (E2Luc) gene. Reporter activities were then analyzed in transient assays with cotransfected E1 or E2 expression vectors. Both reporters were moderately activated by E1 in a dose-dependent manner. In addition, E1Luc was activated by low doses of E2 but was repressed at high doses. In contrast, E2 had little effect on E2Luc activity. These data indicate that E1 expression and that of E2 are interdependent and regulated differentially. When the E6 splicing mutations were analyzed in both reporter backgrounds, only E1Luc activities correlated with splicing competence in the E6 ORF. These findings support the hypothesis that the E6 intron primarily regulates expression of E1. Finally, in long-term replication assays, none of the E6 mutant genomes could be stably maintained. However, cotransfection of the E6 splicing mutant genomes with pHPV31-E7NS, which contains a nonsense mutation in the E7 coding sequence, restored stable replication of some mutants. Our observations indicate that E1 expression and that of E2 are differentially regulated at multiple levels and that efficient expression of E1 is required for transient and stable viral replication. These regulatory mechanisms likely act to control HPV copy number during the various phases of the viral life cycle.

Hubert, Walter G.; Laimins, Laimonis A.

2002-01-01

285

Inhibition of Rho Kinase Regulates Specification of Early Differentiation Events in P19 Embryonal Carcinoma Stem Cells  

PubMed Central

Background The Rho kinase pathway plays a key role in many early cell/tissue determination events that take place in embryogenesis. Rho and its downstream effector Rho kinase (ROCK) play pivotal roles in cell migration, apoptosis (membrane blebbing), cell proliferation/cell cycle, cell-cell adhesion and gene regulation. We and others have previously demonstrated that inhibition of ROCK blocks endoderm differentiation in embryonal carcinoma stem cells, however, the effect of ROCK inhibition on mesoderm and ectoderm specification has not been fully examined. In this study, the role of ROCK within the specification and differentiation of all three germ layers was examined. Methodology/Principal Findings P19 cells were treated with the specific ROCK inhibitor Y-27623, and increase in differentiation efficiency into neuro-ectodermal and mesodermal lineages was observed. However, as expected a dramatic decrease in early endodermal markers was observed when ROCK was inhibited. Interestingly, within these ROCK-inhibited RA treated cultures, increased levels of mesodermal or ectodermal markers were not observed, instead it was found that the pluripotent markers SSEA-1 and Oct-4 remained up-regulated similar to that seen in undifferentiated cultures. Using standard and widely accepted methods for reproducible P19 differentiation into all three germ layers, an enhancement of mesoderm and ectoderm differentiation with a concurrent loss of endoderm lineage specification was observed with Y-27632 treatment. Evidence would suggest that this effect is in part mediated through TGF-? and SMAD signaling as ROCK-inhibited cells displayed aberrant SMAD activation and did not return to a ‘ground’ state after the inhibition had been removed. Conclusions/Significance Given this data and the fact that only a partial rescue of normal differentiation capacity occurred when ROCK inhibition was alleviated, the effect of ROCK inhibition on the differentiation capacity of pluripotent cell populations should be further examined to elucidate the role of the Rho-ROCK pathway in early cellular ‘fate’ decision making processes.

Krawetz, Roman J.; Taiani, Jaymi; Greene, Alexis; Kelly, Gregory M.; Rancourt, Derrick E.

2011-01-01

286

Impact of the large-scale dynamics on the ARM Arctic cloud and radiation measurements and early snowmelt events  

NASA Astrophysics Data System (ADS)

In the last 3 decades the average temperature over the Northern Alaska has increased by about 2.3 °C with the maximum during the spring (3.9 °C) and the minimum during the summer (1.5 °C). This warming has resulted in an average 8-day advance in snowmelt date over Northern Alaska, and a 10% decrease in the extent of snow cover observed from satellites. Therefore it is necessary to identify the factors influencing this trend, especially during the spring because changes in the spring snowmelt date will significantly affect the surface radiation budget. In this study, we use 10 years (1998-2007) of surface observations collected from the Atmospheric Radiation Measurement (ARM) North Slope of Alaska (NSA) site and NCEP reanalysis, and find that there are more clouds in the warm season (May-October) than in the cold season (November - April), which exhibits a strong association with the large-scale dynamics. The net surface radiation budget indicates that the Arctic surface loses radiative energy during October - April and gains radiative energy during May-September, and clouds tend to enhance snow melting in spring and impede the solidification of permafrost in autumn. We have identified the years of 2002, 2005, and 2007 as years with abnormally early snowmelt, where the date of the spring snowmelt is approximately 10 days earlier than average. Large-scale dynamics and previous winter snow fall are certainly two of the factors affecting the snowmelt over this region. Using NCEP reanalysis data, we have developed a pattern which positions the Aleutian Low (AL) in the center of the Bering Sea and a ridge building over eastern Alaska during the early snowmelt events. This large-scale pattern supports warm moist air advection over northern Alaska, increasing the areal clouds and thus supporting early snowmelt. We will use the integrated ARM NSA radiation and cloud, snow depth and accumulation, and NCEP reanalysis data over the Western Arctic to investigate the 2002, 2005 and 2007 spring snowmelt events.

Crosby, K. M.; Dong, X.; Xi, B.; Long, C. N.

2008-05-01

287

Differences in cell-type-specific blocks to immediate early gene expression and DNA replication of human, simian and murine cytomegalovirus.  

PubMed

We have previously described blocks to the viral lytic cycle at two different levels in cytomegalovirus (CMV)-infected non-permissive cells. BALB/c-3T3 cells express only the predominant immediate early (IE) nuclear phosphoproteins (IE68 or IE94) of human CMV (HCMV) or simian CMV (SCMV) and do not replicate the input viral genomes. However, in human teratocarcinoma stem cells and 293 cells, expression of the HCMV IE68 gene (but not the SCMV IE94 gene) is blocked at the transcriptional level. Here we report the results of an extensive comparison of the level of permissiveness for HCMV, SCMV and murine CMV (MCMV) in a variety of additional cell types of human, monkey and mouse origin. We also describe a subtle change in the tryptic peptide pattern of the IE68 polypeptide produced in BALB/c-3T3 cells compared to permissive human foreskin fibroblasts. Neither the IE68 nor IE94 proteins could be detected by biochemical labelling procedures in infected mouse Ltk- or F9 teratocarcinoma stem cells, although IE94 was synthesized after retinoic acid-induced differentiation of the F9 cells. Synthesis of [35S]methionine-labelled IE94 protein, but not that of HCMV IE68, was detected in infected Vero cells and in human peripheral blood leukocyte cultures. The failure to synthesize detectable IE68 protein in infected Vero cells appeared to be unrelated to a lack of entry of viral DNA and to a lack of appropriate transcription factors. Indeed, immunofluorescence assays showed that the IE68 antigen was expressed efficiently in DNA-transfected Vero cells and in a small fraction of infected Vero cells. Overall, two clear host range trends emerged. First, whilst all three viruses showed a tendency for repression of IE expression in transformed cell lines, the effect was severe for HCMV and only minimal for SCMV. Secondly, progression of infection to the viral DNA synthesis level in non-transformed fibroblast cell types occurred in a much wider range of host species cell types for SCMV and MCMV than for HCMV. PMID:2828515

Lafemina, R L; Hayward, G S

1988-02-01

288

Early pathogenic events associated with Sjögren's syndrome (SjS)-like disease of the NOD mouse using microarray analysis.  

PubMed

Recently, we reported development of the C57BL/6.NOD-Aec1Aec2 mouse carrying two genetic intervals derived from the NOD mouse. These two genetic regions confer full Sjögren's syndrome (SjS)-like disease in SjS-non-susceptible C57BL/6 mice. The current study was undertaken to apply microarray technology to define the molecular basis underlying onset of SjS-disease in C57BL/6.NOD-Aec1Aec2 mice. Using oligonucleotide microarrays, gene expression profiles of submandibular glands derived from 8- to 12-week-old C57BL/6.NOD-Aec1Aec2 mice and 8-week-old C57BL/6 mice were performed for comparison. Significant differential expressions were determined using the Mann-Whitney U test. Hybridizations using submandibular cDNA probes revealed 75 differentially expressed genes at 8 weeks and 105 differentially expressed genes at 12 weeks of age in C57BL/6.NOD-Aec1Aec2 mice compared to 8-week-old C57BL/6 mice. These genes were related generally to basic cellular activities such as transcription, translation, DNA replication, and protein folding. During the predisease phase, genes upregulated encode proteins associated with the IFN-gamma signal-transduction-pathway (Jak/Stat1), TLR-3 (Irf3 and Traf6) and apoptosis (casp11 and casp3), indicative of chronic proinflammatory stimuli, especially IL-1. Between 8 and 12 weeks of age, sets of clustered genes were upregulated that are associated with adaptive immune responses, especially B cell activation, proliferation and differentiation (Baffr, Taci, Bcma, Blys, April, CD70, CD40L, Traf1, Traf3, Pax5, c-Jun, Elk1 and Nf-kB), and neural receptors (Taj/Troy). Altered gene expressions of TLR3 and TNF-superfamily-receptors and ligands during this early phase of SjS suggest a possible viral etiology in the altered glandular homeostasis with an upregulated, possibly overstimulated, B-lymphocyte activation in the early autoimmune response present in the submandibular glands. The importance of NF-kappaB as a critical signal transduction pathway is also suggested but its link is not yet clear. PMID:17075579

Killedar, Smruti J; Killedar, Smruti Y; Eckenrode, Sarah E; McIndoe, Richard A; She, Jin-Xiong; Nguyen, Cuong Q; Peck, Ammon B; Cha, Seunghee R; Cha, Seunghee

2006-10-30

289

Metastasis is an early event in mouse mammary carcinomas and is associated with cells bearing stem cell markers  

PubMed Central

Introduction It is still uncertain whether metastasis is predominantly an early or late event in tumor progression. The detection of early metastases and cells responsible for the dissemination may therefore have significant clinical implications. Methods Lung dissemination and/or metastasis were investigated in mice carrying the polyomavirus middle-T oncogene (PyMT) during different stages of mammary tumorigenesis using the colony forming assay. Immunocytochemical or immunohistochemical staining was used to identify subpopulations of cells responsible for lung dissemination and metastasis. Histological examination was used to show primary and metastatic tumors. The tumor-initiating and metastatic capacity of cells expressing stem cell markers was assessed in syngeneic wild-type (WT) mice whose mammary fat pads were injected with these cells. Results Metastatic mammary epithelial cells were detected in the lungs of mice carrying the PyMT oncogene (MMT mice). These cells were observed early in breast tumorigenesis when the mammary tree appeared by histological inspection to be normal (or at a premalignant stage), suggesting the possession of disseminating and metastatic capacity even before full malignant transformation. Some of the disseminated cells and lung metastases displayed surface stem cell markers. These findings suggest that stem cells from apparently precancerous primary lesions could be a source of metastasis. Indeed, injection of lung tissue cells from MMT mice into syngeneic WT mice resulted in the formation of mammary tumors. These tumors resembled their parent mammary tumors in the MMT donors as well as grafted tumors derived from mammary tumor cells. Furthermore, when we injected lung tissue cells from GFP MMT mice into the fat pads of recipient WT mice, disseminated or metastatic GFP-expressing cells were detected in the lungs, lymph nodes and blood of the recipient WT mice. We finally identified a subpopulation of mammary epithelial/tumor cells expressing CD44 and Sca1 that was largely responsible for dissemination and metastasis in MMT mice. Conclusions The tumorigenic and metastatic potential of a subpopulation of mammary epithelial/tumor cells in MMT mice is endowed relatively early in mammary neoplasms and suggests a potential role for cancer stem cell sub-populations in metastasis.

2012-01-01

290

Effects of Phenylethyl Isothiocyanate on Early Molecular Events in N-Nitrosomethylbenzylamine-Induced Cytotoxicity in Rat Esophagus  

PubMed Central

There is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA)–induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-term NMBA treatment and modulated by cotreatment with phenylethyl isothiocyanate (PEITC). Rats were fed AIN-76A diet or AIN-76A diet containing PEITC for 3 weeks. During the 3rd week of dietary treatment, they were administered three s.c. doses of NMBA (0.5 mg/kg body weight). Rats were sacrificed 24 h after the last treatment; esophagi were excised and processed for histologic grading, microarray and real-time PCR analysis. Histopathologic analysis showed that treatment of rats with PEITC had a protective effect on NMBA-induced preneoplastic lesions in the rat esophagus. We identified 2,261 genes that were differentially expressed in the NMBA-treated versus control esophagi and 1,936 genes in the PEITC + NMBA versus NMBA-treated esophagi. The intersection of these two sets resulted in the identification of 1,323 genes in NMBA-treated esophagus, the vast majority of which were modulated by PEITC to near-normal levels of expression. Measured changes in the expression levels of eight selected genes were validated using real-time PCR. Results from 12 microarrays indicated that PEITC treatment had a genome-wide modulating effect on NMBA-induced gene expression. Samples obtained from animals treated with PEITC alone or cotreated with PEITC + NMBA were more similar to controls than to samples treated with NMBA alone.

Reen, Rashmeet K.; Dombkowski, Alan A.; Kresty, Laura A.; Cukovic, Daniela; Mele, Jennifer M.; Salagrama, Sridevi; Nines, Ronald; Stoner, Gary D.

2010-01-01

291

Effects of phenylethyl isothiocyanate on early molecular events in N-nitrosomethylbenzylamine-induced cytotoxicity in rat esophagus.  

PubMed

There is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-term NMBA treatment and modulated by cotreatment with phenylethyl isothiocyanate (PEITC). Rats were fed AIN-76A diet or AIN-76A diet containing PEITC for 3 weeks. During the 3rd week of dietary treatment, they were administered three s.c. doses of NMBA (0.5 mg/kg body weight). Rats were sacrificed 24 h after the last treatment; esophagi were excised and processed for histologic grading, microarray and real-time PCR analysis. Histopathologic analysis showed that treatment of rats with PEITC had a protective effect on NMBA-induced preneoplastic lesions in the rat esophagus. We identified 2,261 genes that were differentially expressed in the NMBA-treated versus control esophagi and 1,936 genes in the PEITC + NMBA versus NMBA-treated esophagi. The intersection of these two sets resulted in the identification of 1,323 genes in NMBA-treated esophagus, the vast majority of which were modulated by PEITC to near-normal levels of expression. Measured changes in the expression levels of eight selected genes were validated using real-time PCR. Results from 12 microarrays indicated that PEITC treatment had a genome-wide modulating effect on NMBA-induced gene expression. Samples obtained from animals treated with PEITC alone or cotreated with PEITC + NMBA were more similar to controls than to samples treated with NMBA alone. PMID:17616710

Reen, Rashmeet K; Dombkowski, Alan A; Kresty, Laura A; Cukovic, Daniela; Mele, Jennifer M; Salagrama, Sridevi; Nines, Ronald; Stoner, Gary D

2007-07-01

292

Using Simcyp to project human oral pharmacokinetic variability in early drug research to mitigate mechanism-based adverse events.  

PubMed

Positive allosteric modulators ('potentiators') of the ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) have been shown to display a mechanism-based exposure-response continuum in preclinical species with procognitive electrophysiological and behavioral effects ('efficacy') at low exposures and motor coordination disruptions at progressively higher exposures. Due to the dose-capping nature of such motor coordination deficits, an exposure threshold-mediated adverse event (C(AE) ), the adequacy of separation between the maximal total plasma compound concentration (C(max) ) at a predicted clinically efficacious oral dose and this adverse event (AE) was explored in early drug research with three AMPAR potentiators considered potential candidates for clinical trials. In vitro metabolism studies in human liver microsomes and human hepatocytes demonstrated the metabolic clearance for each compound was predominately due to cytochromes P450 (CYP). Thus, for each compound's anticipated clinically efficacious dose, human C(max) variability following oral administration was assessed using Simcyp software, which combines its virtual human populations database using extensive demographic, physiological and genomic information with routinely collected compound-specific in vitro biochemical data to simulate and predict drug disposition. Using a combination of experimentally determined recombinant human CYP intrinsic clearances for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, human binding factors, expected fraction absorbed and estimated steady-state volume of distribution, Simcyp simulations demonstrated that two of the three potentiators had acceptable projected C(max) variability (i.e. the 95th percentile C(max) did not breach C(AE) ). This evaluation aided in the selection of compounds for preclinical progression, and represents a novel application of pharmacologically based pharmacokinetic (PBPK) software approaches to predict interpatient variability. PMID:22213407

Shaffer, Christopher L; Scialis, Renato J; Rong, Haojing; Obach, R Scott

2012-01-17

293

Rapid changes in the redox conditions of the western Tethys Ocean during the early Aptian oceanic anoxic event  

NASA Astrophysics Data System (ADS)

The early Aptian (125 to 121 Ma) records an episode of severe environmental change including a major perturbation of the carbon cycle, an oceanic anoxic event (OAE 1a, 122.5 Ma), a platform drowning episode and a biocalcification crisis. We propose to trace changes in the oxygenation state of the ocean during the early Aptian anoxic event using the redox-sensitive trace-element (RSTE) distribution, phosphorus accumulation rates (PARs) and organic-matter characterization in three different basins of the western Tethys. The following sections have been investigated: Gorgo a Cerbara (central Italy) in the Umbria Marche basin, Glaise (SE France) in the Vocontian basin and Cassis/La Bédoule (SE France) located in the Provencal basin. In the Gorgo a Cerbara section, RSTE distributions show a low background level along the main part of the section, contrasted by different maxima in concentrations within the Selli level. In the Glaise section, the Goguel level displays a weak increase in RSTE contents coeval with moderate TOC values. At Cassis/La Bédoule, no significant RSTE enrichments have been observed in sediments equivalent to the Selli level. These differences in the records of the geochemical proxies of the Selli level or its equivalent indicate the deposition under different redox conditions, probably related to the paleogeography. Our data indicate the development of anoxic-euxinic conditions in the deeper part of the Tethys during OAE 1a, whereas in the shallower environments, conditions were less reducing. Moreover, at Gorgo a Cerbara, the Selli level is characterized by rapid changes in the intensity of reducing conditions in the water column. Ocean eutrophication seems to be a major factor in the development and the persistence of anoxia as suggested by the PAR evolution. Higher PAR values at the onset of OAE 1a suggest an increase in nutrient input, whereas the return to lower values through the first part of the OAE 1a interval may be related to the weakened capacity to retain P in the sedimentary reservoir due to bottom-water oxygen depletion. This general pattern is contrasted by the data of Gorgo a Cerbara, where the sediments deposited during the OAE 1a interval show P-enrichments (mainly authigenic P). This is associated with maxima in TOC values and Corg:Ptot ratios, suggesting that a part of the remobilized P was trapped in the sediments and as such prevented from returning to the water column.

Westermann, Stéphane; Stein, Melody; Matera, Virginie; Fiet, Nicolas; Fleitmann, Dominik; Adatte, Thierry; Föllmi, Karl B.

2013-11-01

294

Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: a five year prospective study  

PubMed Central

Introduction Co-morbidity and mortality due to cardiovascular disease (CVD) are increased in patients with rheumatoid arthritis (RA). Most published studies in this field are retrospective or cross sectional. We investigated the presence of traditional and disease related risk factors for CVD at the onset of RA and during the first five years following diagnosis. We also evaluated their potential for predicting a new cardiovascular event (CVE) during the five-year follow-up period and the modulatory effect of pharmacological treatment. Methods All patients from the four northern-most counties of Sweden with early RA are, since December 1995, consecutively recruited at diagnosis (T0) into a large survey on the progress of the disease. Information regarding cardiovascular co-morbidity and related predictors was collected from clinical records and supplemented with questionnaires. By April 2008, 700 patients had been included of whom 442 patients had reached the five-year follow-up (T5). Results Among the 442 patients who reached T5 during the follow-up period, treatment for hypertension increased from 24.5 to 37.4% (P < 0.001)), diagnosis of diabetes mellitus (DM) from 7.1 to 9.5% (P < 0.01) whilst smoking decreased from 29.8 to 22.4% (P < 0.001) and the BMI from 26.3 to 25.8 (P < 0.05), respectively. By T5, 48 patients had suffered a new CVE of which 12 were fatal. A total of 23 patients died during the follow-up period. Age at disease onset, male sex, a previous CVE, DM, treatment for hypertension, triglyceride level, cumulative disease activity (area under the curve (AUC) disease activity score (DAS28)), extra-articular disease, corticosteroid use, shorter duration of treatment with disease modifying anti-rheumatic drugs (DMARDs) and use of COX-2 inhibitors increased the hazard rate for a new CVE. A raised erythrocyte sedimentation rate (ESR) at inclusion and AUC DAS28 at six months increased the hazard rate of CVE independently whilst DMARD treatment was protective in multiple Cox extended models adjusted for sex and CV risk factors. The risk of a CVE due to inflammation was potentiated by traditional CV risk factors. Conclusions The occurrence of new CV events in very early RA was explained by traditional CV risk factors and was potentiated by high disease activity. Treatment with DMARDs decreased the risk. The results may have implications for cardio-protective strategies in RA.

2011-01-01

295

Mutations in NA that induced low pH-stability and enhanced the replication of pandemic (H1N1) 2009 influenza A virus at an early stage of the pandemic.  

PubMed

An influenza A virus that originated in pigs caused a pandemic in 2009. The sialidase activity of the neuraminidase (NA) of previous pandemic influenza A viruses are stable at low pH (?5). Here, we identified the amino acids responsible for this property. We found differences in low-pH stability at pH 5.0 among pandemic (H1N1) 2009 viruses, which enhanced the replication of these viruses. Low-pH-stable NA enhancement of virus replication may have contributed to the rapid worldwide spread and adaptation to humans of pandemic (H1N1) 2009 viruses during the early stages of the 2009 pandemic. PMID:23696893

Takahashi, Tadanobu; Song, Jiasheng; Suzuki, Takashi; Kawaoka, Yoshihiro

2013-05-16

296

Oceanic Anoxic Events in the Early Cretaceous Pacific Ocean: Unique Records From the Calera Limestone of Central California  

NASA Astrophysics Data System (ADS)

Our understanding of Early Cretaceous palaeoceanography relies heavily on observations from the then narrow ocean basins of the Tethys and Atlantic Oceans, and we have only fragmentary evidence from the largest contiguous Cretaceous marine environment, the Pacific Ocean. This fragmentary record results from loss of much of the Pacific sea floor to subduction but, additionally, ocean drilling has struggled to core continuous sections due to the ubiquitous presence of `unrecoverable' chert-rich sediments. However, the record as it stands still provides a tantalising glimpse of Cretaceous climates and environments in the Pacific Ocean, including evidence for `oceanic anoxic events' (OAEs) and associated biotic change. In order to improve our understanding of Pacific Ocean palaeoceanography we have exploited the little studied, but virtually unique, sections of the Calera Limestone, part of an accreted terrane (the Franciscan Complex) exposed in central California, USA. These calcareous sediments were deposited in pelagic environments in the Pacific Ocean on either seamounts or oceanic plateaus of the, now-subducted, Farallon plate, analogous to present-day plateaus on the Pacific plate such as Shatsky Rise and Hess Rise. Previous work on the Pacifica Quarry has shown that the Calera Limestone is Aptian-Cenomanian in age and includes Aptian-age organic-rich sediments that are Pacific Ocean expressions of OAEs. We present the results of lithological, palaeontological and geochemical studies of samples collected in the Permanente Quarry. We document two stratigraphic intervals of increased organic-carbon burial that we date, on the basis of carbon-isotope and foraminiferal stratigraphy, as Early Aptian and Late Albian-Early Cenomanian. These time intervals correspond to OAE1a and OAE1d, respectively. The sediments associated with OAE1a are rich in silica, consistent with an origin analogous to organic-rich porcellanites recovered by the ODP on Shatsky Rise. Although it has been previously suggested that during OAE1d organic-carbon burial rates increased in the Pacific Ocean, this was based upon poorly recovered, poorly dated DSDP sediments. The Calera Limestone provides the first clear evidence that OAE1d may have led to environmental changes in the Pacific Ocean, resulting in the deposition of organic-carbon-rich sediments in some areas. The organic-carbon-rich sediments of OAE1d in the Calera Limestone are associated with ash-rich lithologies, suggesting a possible (local) connection between organic carbon production, volcanism and oceanic fertilization.

Robinson, S. A.; Clarke, L. J.; Nederbragt, A.; Wood, I. G.; Brassell, S. C.

2006-12-01

297

DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability.  

PubMed

Normal cellular division requires that the genome be faithfully replicated to ensure that unaltered genomic information is passed from one generation to the next. DNA replication initiates from thousands of origins scattered throughout the genome every cell cycle; however, not all origins initiate replication at the same time. A vast amount of work over the years indicates that different origins along each eukaryotic chromosome are activated in early, middle or late S phase. This temporal control of DNA replication is referred to as the replication-timing program. The replication-timing program represents a very stable epigenetic feature of chromosomes. Recent evidence has indicated that the replication-timing program can influence the spatial distribution of mutagenic events such that certain regions of the genome experience increased spontaneous mutagenesis compared to surrounding regions. This influence has helped shape the genomes of humans and other multicellular organisms and can affect the distribution of mutations in somatic cells. It is also becoming clear that the replication-timing program is deregulated in many disease states, including cancer. Aberrant DNA replication timing is associated with changes in gene expression, changes in epigenetic modifications and an increased frequency of structural rearrangements. Furthermore, certain replication timing changes can directly lead to overt genomic instability and may explain unique mutational signatures that are present in cells that have undergone the recently described processes of "chromothripsis" and "kataegis". In this review, we will discuss how the normal replication timing program, as well as how alterations to this program, can contribute to the evolution of the genomic landscape in normal and cancerous cells. PMID:23327985

Donley, Nathan; Thayer, Mathew J

2013-01-14

298

A computational model for early events in B cell antigen receptor signaling: analysis of the roles of Lyn and Fyn  

PubMed Central

B cell antigen receptor (BCR) signaling regulates the activities and fates of B cells. BCR signaling encompasses two feedback loops emanating from Lyn and Fyn, which are Src-family protein tyrosine kinases (SFKs). Positive feedback arises from SFK-mediated trans phosphorylation of BCR and receptor-bound Lyn and Fyn, which increases the kinase activities of Lyn and Fyn. Negative feedback arises from SFK-mediated cis phosphorylation of the transmembrane adapter protein PAG1, which recruits the cytosolic protein tyrosine kinase Csk to the plasma membrane, where it acts to decrease the kinase activities of Lyn and Fyn. To study the effects of the positive and negative feedback loops on the dynamical stability of BCR signaling and the relative contributions of Lyn and Fyn to BCR signaling, we consider here a rule-based model for early events in BCR signaling that encompasses membrane-proximal interactions of six proteins: BCR, Lyn, Fyn, Csk, PAG1 and Syk, a cytosolic protein tyrosine kinase that is activated as a result of SFK-mediated phosphorylation of BCR. The model is consistent with known effects of Lyn and Fyn deletions. We find that BCR signaling can generate a single pulse or oscillations of Syk activation depending on the strength of antigen signal and the relative levels of Lyn and Fyn. We also show that bistability can arise in Lyn or Csk deficient cells.

Barua, Dipak; Hlavacek, William S.; Lipniacki, Tomasz

2012-01-01

299

High-resolution late Maastrichtian early Danian oceanic 87Sr/86Sr record: Implications for Cretaceous-Tertiary boundary events  

NASA Astrophysics Data System (ADS)

A high-resolution late Maastrichtian early Danian seawater 87Sr/86Sr reference curve is constructed from two Cretaceous-Tertiary boundary (K-T boundary) sections: Bidart (France) and El Kef (Tunisia). The 87Sr/86Sr curve shows maxima at 0.3 0.4 Ma before the K-T boundary and at the K-T boundary. The first maximum could mark the onset of a major outflow of the Deccan Traps. The second maximum, a rapid 0.000 06 87Sr/86Sr, shift, extends from ˜3 4 m below to ˜1 m above the K-T boundary. This profile probably results from diagenetic smoothing of an originally sharp K-T boundary 87Sr/86Sr anomaly, rather than from a gradual process. The sharp shift could result from (1) the vaporization of the Chicxulub target rocks, (2) global wildfires, and (3) acid-rain leaching of soils and sialic surface rocks. Of these three possibilities, only Sr release by soil leaching combined with increased rainfall associated with the K-T event appears to be sufficiently large to produce the observed K-T 87Sr/86Sr anomaly.

Vonhof, H. B.; Smit, J.

1997-04-01

300

Model selection for prognostic time-to-event gene signature discovery with applications in early breast cancer data.  

PubMed

Abstract Model selection between competing models is a key consideration in the discovery of prognostic multigene signatures. The use of appropriate statistical performance measures as well as verification of biological significance of the signatures is imperative to maximise the chance of external validation of the generated signatures. Current approaches in time-to-event studies often use only a single measure of performance in model selection, such as logrank test p-values, or dichotomise the follow-up times at some phase of the study to facilitate signature discovery. In this study we improve the prognostic signature discovery process through the application of the multivariate partial Cox model combined with the concordance index, hazard ratio of predictions, independence from available clinical covariates and biological enrichment as measures of signature performance. The proposed framework was applied to discover prognostic multigene signatures from early breast cancer data. The partial Cox model combined with the multiple performance measures were used in both guiding the selection of the optimal panel of prognostic genes and prediction of risk within cross validation without dichotomising the follow-up times at any stage. The signatures were successfully externally cross validated in independent breast cancer datasets, yielding a hazard ratio of 2.55 [1.44, 4.51] for the top ranking signature. PMID:24077567

Ahdesmäki, Miika; Lancashire, Lee; Proutski, Vitali; Wilson, Claire; Davison, Timothy S; Harkin, D Paul; Kennedy, Richard D

2013-10-01

301

Abnormal Mitochondrial Dynamics and Synaptic Degeneration as Early Events in Alzheimer's Disease: Implications to Mitochondria-Targeted Antioxidant Therapeutics  

PubMed Central

Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer’s disease (AD) progression. Loss of synapses and synaptic damage are the best correlate of cognitive deficits found in AD patients. Recent research on amyloid bet (A?) and mitochondria in AD revealed that A? accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (A?PP) transgenic mice revealed that reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that A? is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in A?-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD.

Reddy, P. Hemachandra; Tripathy, Raghav; Troung, Quang; Thirumala, Karuna; Reddy, Tejaswini P.; Anekonda, Vishwanath; Shirendeb, Ulziibat P.; Calkins, Marcus J.; Reddy, Arubala P.; Mao, Peizhong; Manczak, Maria

2011-01-01

302

Time-resolved human kinome RNAi screen identifies a network regulating mitotic-events as early regulators of cell proliferation.  

PubMed

Analysis of biological processes is frequently performed with the help of phenotypic assays where data is mostly acquired in single end-point analysis. Alternative phenotypic profiling techniques are desired where time-series information is essential to the biological question, for instance to differentiate early and late regulators of cell proliferation in loss-of-function studies. So far there is no study addressing this question despite of high unmet interests, mostly due to the limitation of conventional end-point assaying technologies. We present the first human kinome screen with a real-time cell analysis system (RTCA) to capture dynamic RNAi phenotypes, employing time-resolved monitoring of cell proliferation via electrical impedance. RTCA allowed us to investigate the dynamics of phenotypes of cell proliferation instead of using conventional end-point analysis. By introducing data transformation with first-order derivative, i.e. the cell-index growth rate, we demonstrate this system suitable for high-throughput screenings (HTS). The screen validated previously identified inhibitor genes and, additionally, identified activators of cell proliferation. With the information of time kinetics available, we could establish a network of mitotic-event related genes to be among the first displaying inhibiting effects after RNAi knockdown. The time-resolved screen captured kinetics of cell proliferation caused by RNAi targeting human kinome, serving as a resource for researchers. Our work establishes RTCA technology as a novel robust tool with biological and pharmacological relevance amenable for high-throughput screening. PMID:21765947

Zhang, Jitao David; Koerner, Cindy; Bechtel, Stephanie; Bender, Christian; Keklikoglou, Ioanna; Schmidt, Christian; Irsigler, Anja; Ernst, Ute; Sahin, Ozgür; Wiemann, Stefan; Tschulena, Ulrich

2011-07-13

303

Cognitive and behavioral development of at risk infants and toddlers exposed to stressful life events: The effects of trauma in early childhood  

Microsoft Academic Search

The present study examined the relations between traumatic life events and cognitive, behavioral, and relational competence in an at-risk sample of children between the ages of 11 and 41 months. As part of a larger, ongoing investigation, participants for the current study were 53 children enrolled in Early Head Start programs and their primary caregivers. The children participated in a

Zachary E. Warren

2005-01-01

304

Genetic and Functional Analysis of DD44, a Sex-Linked Gene From the Dioecious Plant Silene latifolia, Provides Clues to Early Events in Sex Chromosome Evolution  

Microsoft Academic Search

Silene latifolia is a dioecious plant with heteromorphic sex chromosomes. The sex chromosomes of S. latifolia provide an opportunity to study the early events in sex chromosome evolution because of their relatively recent emergence. In this article, we present the genetic and physical mapping, expression analysis, and molecular evolutionary analysis of a sex-linked gene from S. latifolia, DD44 (Differential Display

Richard C. Moore; Olga Kozyreva; Sabine Lebel-Hardenack; Jiri Siroky; Roman Hobza; Boris Vyskot; Sarah R. Grant

305

Abnormal developmental control of replication-timing domains in pediatric acute lymphoblastic leukemia  

PubMed Central

Abnormal replication timing has been observed in cancer but no study has comprehensively evaluated this misregulation. We generated genome-wide replication-timing profiles for pediatric leukemias from 17 patients and three cell lines, as well as normal B and T cells. Nonleukemic EBV-transformed lymphoblastoid cell lines displayed highly stable replication-timing profiles that were more similar to normal T cells than to leukemias. Leukemias were more similar to each other than to B and T cells but were considerably more heterogeneous than nonleukemic controls. Some differences were patient specific, while others were found in all leukemic samples, potentially representing early epigenetic events. Differences encompassed large segments of chromosomes and included genes implicated in other types of cancer. Remarkably, differences that distinguished leukemias aligned in register to the boundaries of developmentally regulated replication-timing domains that distinguish normal cell types. Most changes did not coincide with copy-number variation or translocations. However, many of the changes that were associated with translocations in some leukemias were also shared between all leukemic samples independent of the genetic lesion, suggesting that they precede and possibly predispose chromosomes to the translocation. Altogether, our results identify sites of abnormal developmental control of DNA replication in cancer that reveal the significance of replication-timing boundaries to chromosome structure and function and support the replication domain model of replication-timing regulation. They also open new avenues of investigation into the chromosomal basis of cancer and provide a potential novel source of epigenetic cancer biomarkers.

Ryba, Tyrone; Battaglia, Dana; Chang, Bill H.; Shirley, James W.; Buckley, Quinton; Pope, Benjamin D.; Devidas, Meenakshi; Druker, Brian J.; Gilbert, David M.

2012-01-01

306

Downregulation of varicella-zoster virus (VZV) immediate-early ORF62 transcription by VZV ORF63 correlates with virus replication in vitro and with latency.  

PubMed

Varicella-zoster virus (VZV) open reading frame 63 (ORF63) protein is expressed during latency in human sensory ganglia. Deletion of ORF63 impairs virus replication in cell culture and establishment of latency in cotton rats. We found that cells infected with a VZV ORF63 deletion mutant yielded low titers of cell-free virus and produced very few enveloped virions detectable by electron microscopy compared with those infected with parental virus. Microarray analysis of cells infected with a recombinant adenovirus expressing ORF63 showed that transcription of few human genes was affected by ORF63; a heat shock 70-kDa protein gene was downregulated, and several histone genes were upregulated. In experiments using VZV transcription arrays, deletion of ORF63 from VZV resulted in a fourfold increase in expression of ORF62, the major viral transcriptional activator. A threefold increase in ORF62 protein was observed in cells infected with the ORF63 deletion mutant compared with those infected with parental virus. Cells infected with ORF63 mutants impaired for replication and latency (J. I. Cohen, T. Krogmann, S. Bontems, C. Sadzot-Delvaux, and L. Pesnicak, J. Virol. 79:5069-5077, 2005) showed an increase in ORF62 transcription compared with those infected with parental virus. In contrast, cells infected with an ORF63 mutant that is not impaired for replication or latency showed ORF62 RNA levels equivalent to those in cells infected with parental virus. The ability of ORF63 to downregulate ORF62 transcription may play an important role in virus replication and latency. PMID:16537613

Hoover, Susan E; Cohrs, Randall J; Rangel, Zoila G; Gilden, Donald H; Munson, Peter; Cohen, Jeffrey I

2006-04-01

307

Human cytomegalovirus function inhibits replication of herpes simplex virus  

SciTech Connect

Human embryonic lung (HEL) cells infected with human cytomegalovirus (HCMV) restricted the replication of herpes simplex virus type 1 (HSV-1). A delay in HSV replication of 15 h as well as a consistent, almost 3 log inhibition of HSV replication in HCMV-infected cell cultures harvested 24 to 72 h after superinfection were observed compared with controls infected with HSV alone. Treatment of HCMV-infected HEL cells with cycloheximide (100 ..mu..g/ml) for 3 or 24 h was demonstrated effective in blocking HCMV protein synthesis, as shown by immunoprecipitation with HCMV antibody-positive polyvalent serum. Cycloheximide treatment of HCMV-infected HEL cells and removal of the cycloheximide block before superinfection inhibited HSV-1 replication more efficiently than non-drug-treated superinfected controls. HCMV DNA-negative temperature-sensitive mutants restricted HSV as efficiently as wild-type HCMV suggesting that immediate-early and/or early events which occur before viral DNA synthesis are sufficient for inhibition of HSV. Inhibition of HSV-1 in HCMV-infected HEL cells was unaffected by elevated temperature (40.5/sup 0/C). However, prior UV irradiation of HCMV removed the block to HSV replication, demonstrating the requirement for an active HCMV genome. HSV-2 replication was similarly inhibited in HCMV-infected HEL cells. Superinfection of HCMV-infected HEL cells with HSV-1 labeled with (/sup 3/H)thymidine provided evidence that the labeled virus could penetrate to the nucleus of cells after superinfection. Evidence for penetration of superinfecting HSV into HCMV-infected cells was also provided by blot hybridization of HSV DNA synthesized in cells infected with HSV alone versus superinfected cell cultures at 0 and 48 h after superinfection.

Cockley, K.D.; Shiraki, K.; Rapp, F.

1988-01-01

308

The replication licensing system  

PubMed Central

The replication licensing system acts to ensure that the no section of the genome is replicated more than once in a single cell cycle. Experiments using Xenopus egg extracts have revealed that the licensing system consists of two components, named RLF-M and RLF-B. Whereas the function of RLF-B is still unclear, RLF-M has been shown to consist of all six members of MCM/P1 family proteins, which appear to be the structural component of the licensing system. The origin recognition complex (ORC) and Cdc6/Cdc18 are needed on chromatin before the licensing reaction can take place, although they are not themselves components of the licensing system. Cell cycle events and cyclin-dependent protein kinases (Cdks) also seem to involved in controlling the licensing system to ensure once per cell cycle DNA replication. The subject of this review is to detail our current understanding of the licensing system and the way that it interacts with other components of the cell cycle machinery.

Tada, Shusuke; Blow, J. Julian

2013-01-01

309

Strong alkalinization of Chara cell surface in the area of cell wall incision as an early event in mechanoperception.  

PubMed

Mechanical wounding of cell walls occurring in plants under the impact of pathogens or herbivores can be mimicked by cell wall incision with a glass micropipette. Measurements of pH at the surface of Chara corallina internodes following microperforation of cell wall revealed a rapid (10-30s) localized alkalinization of the apoplast after a lag period of 10-20s. The pH increase induced by incision could be as large as 3 pH units and relaxed slowly, with a halftime up to 20min. The axial pH profile around the incision zone was bell-shaped and localized to a small area, extending over a distance of about 100?m. The pH response was suppressed by lowering cell turgor upon the replacement of artificial pond water (APW) with APW containing 50mM sorbitol. Stretching of the plasma membrane during its impression into the cell wall defect is likely to activate the Ca(2+) channels, as evidenced from sensitivity of the incision-induced alkalinization to the external calcium concentration and to the addition of Ca(2+)-channel blockers, such as La(3+), Gd(3+), and Zn(2+). The maximal pH values attained at the incision site (~10.0) were close to pH in light-dependent alkaline zones of Chara cells. The involvement of cytoskeleton in the origin of alkaline patch was documented by observations that the incision-induced pH transients were suppressed by the inhibitors of microtubules (oryzalin and taxol) and, to a lesser extent, by the actin inhibitor (cytochalasin B). The results indicate that the localized increase in apoplastic pH is an early event in mechanoperception and depends on light, cytoskeleton, and intracellular calcium. PMID:23850637

Bulychev, Alexander A; Alova, Anna V; Bibikova, Tatiana N

2013-07-10

310

A selective requirement for elevated calcium in DNA degradation, but not early events in anti-Fas-induced apoptosis.  

PubMed

Jurkat cells undergo apoptosis in response to anti-Fas antibody through a caspase-dependent death cascade in which calcium signaling has been implicated. We have now evaluated the role of calcium during this death cascade at the single cell level in real time utilizing flow cytometric analysis and confocal microscopy. Fluo-3 and propidium iodide were employed to evaluate calcium fluxes and to discriminate between viable and non-viable cells, respectively. Anti-Fas treatment of Jurkat cells resulted in a sustained increase in intracellular calcium commencing between 1 and 2 h after treatment and persisting until subsequent loss of cell membrane integrity. The significance of this rise in calcium was evaluated by buffering intracellular calcium with BAPTA and/or removing calcium from the extracellular medium and monitoring the effects of these manipulations on calcium signaling and components of the apoptotic process. Complete inhibition of the anti-Fas induced rise in intracellular calcium required both chelation of [Ca(2+)](i) and removal of extracellular calcium. Interestingly, this condition did not abrogate several events in Fas-induced apoptosis including cell shrinkage, mitochondrial depolarization, annexin binding, caspase activation, and nuclear poly(A)DP-ribose polymerase cleavage. Furthermore, calcium-free conditions in the absence of anti-Fas antibody weakly induced these apoptotic components. In marked contrast, calcium depletion did not induce DNA degradation in control cells, and inhibited apoptotic DNA degradation in response to anti-Fas. These data support the concept that the rise in intracellular calcium is not a necessary component for the early signal transduction pathways in anti-Fas-induced apoptosis in Jurkat cells, but rather is necessary for the final degradation of chromatin via nuclease activation. PMID:10859318

Scoltock, A B; Bortner, C D; St J Bird, G; Putney, J W; Cidlowski, J A

2000-09-29

311

Plate tectonics hiati as the cause of global glaciations: 1. Early Proterozoic events and the rise of oxygen  

NASA Astrophysics Data System (ADS)

Plate tectonics is the main way in which the Earth's internal heat is brought to the surface and lost, so it seems that global tectonics should not stop and start. Consequently the long-standing fact that, globally, no orogenic granitoid or greenstone U-Pb ages have been found in the 2.45--2.22 Ga interval has been attributed to defective sampling. Here I argue that this interval was indeed a prolonged hiatus in plate tectonics, being the first of two. The other, but differently caused, was in the late Proterozoic and is the topic of Part 2. The feature common to both hiati, and relevant to global glaciation, is that mid-ocean ridges (MORs) die and subside, potentially lowering sea-level by several kilometres, causing loss of atmospheric CO2 by weathering and an increase in planetary albedo. For the origin of the first hiatus we must first go back to formation of the core. The current iron-percolation model is invalidated by the fact that its corollary, the arrival of a water and siderophile-rich "late veneer" at the end of percolation, would be required to arrive some 60 Ma after the Moon, which never had a late veneer, was already in Earth orbit. The available alternative [1] would have given the early Earth a wet and low-viscosity convecting mantle able to dispose of the early heat with high efficiency; so that by 2.8 Ga MORs began to deepen, exposing cratons to massive weathering which lowered atmospheric CO2. The well-documented late Archaean acceleration of crustal addition to cratons, or, more precisely, of TTG-granitoid intrusion of greenstone belts, is also, paradoxically, evidence of waning mantle heat. Such wide-belt intrusion, grouped into quasi-coeval 'events', are examples of post-subduction magmatism (PSM), marking interruption of flat-slab subduction under a greenstone belt when a microcraton arrived [2]. On each occasion the TTG, derived from the subducted and reheated oceanic crust, advected subducting-plate heat to the surface that would otherwise have been returned to the mantle heat budget. This worsened the heat-budget problem, finally precipitating a collapse of mantle convection and the ensuing Huronian global glaciations at ˜2.35 Ga. The unparalleled deposition of banded iron-formation (BIF) during the early part of this hiatus supports this picture. Throughout the Archaean, Fe2+ had accumulated in the deep ocean, stabilized by acidic input from MORs, despite the efforts of oxygenic life (OL) in shallow water. Removal of this input enabled OL to "win its battle", the BIF was deposited and the ocean largely oxygenated. ?13C rose as OL really flowered at ˜2.22 Ga, when MORs resumed, patchily at first, and sea-level rose and flooded planated cratons. [1] Osmaston, M.F. (Goldschmidt 2002) GCA 66 (15A) A571.

Osmaston, M. F.

2003-04-01

312

Helicase loading at chromosomal origins of replication.  

PubMed

Loading of the replicative DNA helicase at origins of replication is of central importance in DNA replication. As the first of the replication fork proteins assemble at chromosomal origins of replication, the loaded helicase is required for the recruitment of the rest of the replication machinery. In this work, we review the current knowledge of helicase loading at Escherichia coli and eukaryotic origins of replication. In each case, this process requires both an origin recognition protein as well as one or more additional proteins. Comparison of these events shows intriguing similarities that suggest a similar underlying mechanism, as well as critical differences that likely reflect the distinct processes that regulate helicase loading in bacterial and eukaryotic cells. PMID:23613349

Bell, Stephen P; Kaguni, Jon M

2013-06-01

313

Reactivation of the Human Cytomegalovirus Major Immediate-Early Regulatory Region and Viral Replication in Embryonal NTera2 Cells: Role of Trichostatin A, Retinoic Acid, and Deletion of the 21-Base-Pair Repeats and Modulator  

PubMed Central

Inactivity of the human cytomegalovirus (HCMV) major immediate-early regulatory region (MIERR), which is composed of promoter, enhancer, unique region, and modulator, is linked to lack of HCMV replication in latently infected cells and in other nonpermissive cell types, including human embryonal NTera2 carcinoma (NT2) cells. I refined the embryonal NT2 cell model to enable characterization of the unknown mechanistic basis for silencing of HCMV MIERR-dependent transcription and viral replication in nonpermissive cells. These infected NT2 cells contain nonreplicating viral genomes with electrophoretic mobility equivalent to a supercoiled, bacterial artificial chromosome of comparable molecular weight. MIERR-dependent transcription is minimal to negligible. Increasing the availability of positive-acting transcription factors by retinoic acid (RA) treatment after infection is largely insufficient in reactivating the MIERR. In contrast, trichostatin A (TSA), a histone deacetylase inhibitor, reactivates MIERR-dependent transcription. Contrary to prior findings produced from transfected MIERR segments, deletion of the 21-bp repeats and modulator from the MIERR in the viral genome does not relieve MIERR silencing. To demonstrate that MIERR silencing likely results from enhancer inactivity, I examined an HCMV with a heterologous MIERR promoter that is enhancer dependent but exempt from IE2 p86-mediated negative autoregulation. This heterologous promoter, like its neighboring native MIERR promoter, exhibits immediate-early transcriptional kinetics in fibroblasts. In embryonal NT2 cells, the heterologous MIERR promoter is transcriptionally inactive. This silence is relieved by TSA but not by RA. Remarkably, TSA-induced reactivation of MIERR-dependent transcription from quiescent viral genomes is followed by release of infectious virus. I conclude that a mechanism of active repression imposes a block to MIERR-dependent transcription and viral replication in embryonal NT2 cells. Because TSA overcomes the block, viral gene silencing may involve histone deacetylase-based modification of viral chromatin, which might account for the covalently closed circular conformation of quiescent HCMV genomes.

Meier, Jeffery L.

2001-01-01

314

Inhibition of iridovirus protein synthesis and virus replication by antisense morpholino oligonucleotides targeted to the major capsid protein, the 18 kDa immediate-early protein, and a viral homolog of RNA polymerase II  

SciTech Connect

Frog virus 3 (FV3) is a large DNA virus that encodes {approx} 100 proteins. Although the general features of FV3 replication are known, the specific roles that most viral proteins play in the virus life cycle have not yet been elucidated. To address the question of viral gene function, antisense morpholino oligonucleotides (asMOs) were used to transiently knock-down expression of specific viral genes and thus infer their role in virus replication. We designed asMOs directed against the major capsid protein (MCP), an 18 kDa immediate-early protein (18K) that was thought to be a viral regulatory protein, and the viral homologue of the largest subunit of RNA polymerase II (vPol-II{alpha}). All three asMOs successfully inhibited translation of the targeted protein, and two of the three asMOs resulted in marked phenotypic changes. Knock-down of the MCP resulted in a marked reduction in viral titer without a corresponding drop in the synthesis of other late viral proteins. Transmission electron microscopy (TEM) showed that in cells treated with the anti-MCP MO assembly sites were devoid of viral particles and contained numerous aberrant structures. In contrast, inhibition of 18K synthesis did not block virion formation, suggesting that the 18K protein was not essential for replication of FV3 in fathead minnow (FHM) cells. Finally, consistent with the view that late viral gene expression is catalyzed by a virus-encoded or virus-modified Pol-II-like protein, knock-down of vPol-II{alpha} triggered a global decline in late gene expression and virus yields without affecting the synthesis of early viral genes. Collectively, these results demonstrate the utility of using asMOs to elucidate the function of FV3 proteins.

Sample, Robert [Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216 (United States); Bryan, Locke [Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216 (United States); Long, Scott [Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216 (United States); Majji, Sai [Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216 (United States); Hoskins, Glenn [Department of Anatomy, University of Mississippi Medical Center, Jackson, MS 39216 (United States); Sinning, Allan [Department of Anatomy, University of Mississippi Medical Center, Jackson, MS 39216 (United States); Olivier, Jake [Department of Preventive Medicine, University of Mississippi Medical Center, Jackson, MS 39216 (United States); Chinchar, V. Gregory [Department of Microbiology, University of Mississippi Medical Center, Jackson, MS 39216 (United States)]. E-mail: vchinchar@microbio.umsmed.edu

2007-02-20

315

The early region 1B 55-kilodalton oncoprotein of adenovirus relieves growth restrictions imposed on viral replication by the cell cycle.  

PubMed Central

The E1B 55-kDa oncoprotein of adenovirus enables the virus to overcome restrictions imposed on viral replication by the cell cycle. Approximately 20% of HeLa cells infected with an E1B 55-kDa mutant adenovirus produced virus when evaluated by electron microscopy or by assays for infectious centers. By contrast, all HeLa cells infected with a wild-type adenovirus produced virus. The yield of E1B mutant virus from randomly cycling HeLa cells correlated with the fraction of cells in S phase at the time of infection. In synchronously growing HeLa cells, approximately 75% of the cells infected during S phase with the E1B mutant virus produced virus, whereas only 10% of the cells infected during G1 produced virus. The yield of E1B mutant virus from HeLa cells infected during S phase was sevenfold greater than that of cells infected during G1 and threefold greater than that of cells infected during asynchronous growth. Cells infected during S phase with the E1B mutant virus exhibited severe cytopathic effects, whereas cells infected with the E1B mutant virus during G1 exhibited a mild cytopathic effect. Viral DNA synthesis appeared independent of the cell cycle because equivalent amounts of viral DNA were synthesized in cells infected with either wild-type or E1B mutant virus. The inability of the E1B mutant virus to replicate was not mediated by the status of p53. These results define a novel property of the large tumor antigen of adenovirus in relieving growth restrictions imposed on viral replication by the cell cycle.

Goodrum, F D; Ornelles, D A

1997-01-01

316

Antiretroviral Treatment Start-Time during Primary SIVmac Infection in Macaques Exerts a Different Impact on Early Viral Replication and Dissemination  

PubMed Central

Background The time of infection is rarely known in human cases; thus, the effects of delaying the initiation of antiretroviral therapy (ART) on the peripheral viral load and the establishment of viral reservoirs are poorly understood. Methodology/Principal Findings Six groups of macaques, infected intravenously with SIVmac251, were given placebo or antiretroviral therapy to explore reservoir establishment; macaques were treated for 2 weeks, with treatment starting 4 hours, 7 or 14 days after infection. Viral replication and dissemination were measured in the gut (rectum), in the lung and in blood and lymphoid tissues (peripheral lymph nodes), by quantifying viral RNA, DNA and 2LTR circles. We used immunohistochemistry (CD4 and CD68) to assess the impact of these treatments on the relative amount of virus target cells in tissue. Treatment that was started 4 hours post-infection (pi) decreased viral replication and dissemination in blood and tissue samples, which were assessed on day 14 (RNA/DNA/2LTR circles). The virus remained detectable and lymphoid tissues were activated in LN and the gut in both placebo- and ART-treated animals. Viral RNA in plasma continued to be lower in macaques treated seven days after infection; however, this was not the case for viral DNA in peripheral blood mononuclear cells. There was a small but significant difference in RNA and DNA levels in tissues between placebo- and ART-treated animals on day 21. When started 14 days after infection, treatment resulted in a limited decrease in the plasma viral load. Conclusions Treatment that was started 4 hours after infection significantly reduced viral replication and dissemination. When started 7 days after infection, it was of slight virological benefit in peripheral blood and in tissues, and treatment was even less effective if started 14 days pi. These data favor starting ART no longer than one week after intravenous SIVmac251 exposure.

Sellier, Pierre; Mannioui, Abdelkrim; Bourry, Olivier; Dereuddre-Bosquet, Nathalie; Delache, Benoit; Brochard, Patricia; Calvo, Julien; Prevot, Sophie; Roques, Pierre

2010-01-01

317

The Evolution of Diversity in Replicator Networks  

Microsoft Academic Search

Novel species are introduced into a network of interacting replicators either (i) as mutants of members of the network (ii) as unrelated immigrants. We consider the meta-population dynamics of such a system. In the first case the appearance of mutants leads to a slow growth of the replicator network, proportional to the logarithm of the number of mutation events. Surprisingly,

Robert Happel; Peter F. Stadler

1998-01-01

318

The Evolution of Diversity in Replicator Networks  

Microsoft Academic Search

Novel species are introduced into a network of interacting replicators either (i) as mutants of members of the network or (ii) as unrelated immigrants. We consider the meta-population dynamics of such a system. In the first case, the appearance of mutants leads to a slow growth of the replicator network, proportional to the logarithm of the number of mutation events.

Robert Happel; Peter F. Stadler

1997-01-01

319

The checkpoint response to replication stress.  

PubMed

Genome instability is a hallmark of cancer cells, and defective DNA replication, repair and recombination have been linked to its etiology. Increasing evidence suggests that proteins influencing S-phase processes such as replication fork movement and stability, repair events and replication completion, have significant roles in maintaining genome stability. DNA damage and replication stress activate a signal transduction cascade, often referred to as the checkpoint response. A central goal of the replication checkpoint is to maintain the integrity of the replication forks while facilitating replication completion and DNA repair and coordinating these events with cell cycle transitions. Progression through the cell cycle in spite of defective or incomplete DNA synthesis or unrepaired DNA lesions may result in broken chromosomes, genome aberrations, and an accumulation of mutations. In this review we discuss the multiple roles of the replication checkpoint during replication and in response to replication stress, as well as the enzymatic activities that cooperate with the checkpoint pathway to promote fork resumption and repair of DNA lesions thereby contributing to genome integrity. PMID:19482564

Branzei, Dana; Foiani, Marco

2009-05-23

320

Evolution of GHF5 endoglucanase gene structure in plant-parasitic nematodes: no evidence for an early domain shuffling event  

PubMed Central

Background Endo-1,4-beta-glucanases or cellulases from the glycosyl hydrolase family 5 (GHF5) have been found in numerous bacteria and fungi, and recently also in higher eukaryotes, particularly in plant-parasitic nematodes (PPN). The origin of these genes has been attributed to horizontal gene transfer from bacteria, although there still is a lot of uncertainty about the origin and structure of the ancestral GHF5 PPN endoglucanase. It is not clear whether this ancestral endoglucanase consisted of the whole gene cassette, containing a catalytic domain and a carbohydrate-binding module (CBM, type 2 in PPN and bacteria) or only of the catalytic domain while the CBM2 was retrieved by domain shuffling later in evolution. Previous studies on the evolution of these genes have focused primarily on data of sedentary nematodes, while in this study, extra data from migratory nematodes were included. Results Two new endoglucanases from the migratory nematodes Pratylenchus coffeae and Ditylenchus africanus were included in this study. The latter one is the first gene isolated from a PPN of a different superfamily (Sphaerularioidea); all previously known nematode endoglucanases belong to the superfamily Tylenchoidea (order Rhabditida). Phylogenetic analyses were conducted with the PPN GHF5 endoglucanases and homologous endoglucanases from bacterial and other eukaryotic lineages such as beetles, fungi and plants. No statistical incongruence between the phylogenetic trees deduced from the catalytic domain and the CBM2 was found, which could suggest that both domains have evolved together. Furthermore, based on gene structure data, we inferred a model for the evolution of the GHF5 endoglucanase gene structure in plant-parasitic nematodes. Our data confirm a close relationship between Pratylenchus spp. and the root knot nematodes, while some Radopholus similis endoglucanases are more similar to cyst nematode genes. Conclusion We conclude that the ancestral PPN GHF5 endoglucanase gene most probably consisted of the whole gene cassette, i.e. the GHF5 catalytic domain and the CBM2, rather than that it evolved by domain shuffling. Our evolutionary model for the gene structure in PPN GHF5 endoglucanases implies the occurrence of an early duplication event, and more recent gene duplications at genus or species level.

2008-01-01

321

A computational model of gene expression reveals early transcriptional events at the subtelomeric regions of the malaria parasite, Plasmodium falciparum  

Microsoft Academic Search

BACKGROUND: The malaria parasite, Plasmodium falciparum, replicates asexually in a well-defined infection cycle within human erythrocytes (red blood cells). The intra-erythrocytic developmental cycle (IDC) proceeds with a 48 hour periodicity. RESULTS: Based on available malaria microarray data, which monitored gene expression over one complete IDC in one-hour time intervals, we built a mathematical model of the IDC using a circular

Matthias Scholz; Martin J Fraunholz

2008-01-01

322

The VP1 subunit of JC polyomavirus recapitulates early events in viral trafficking and is a novel tool to study polyomavirus entry  

PubMed Central

JC polyomavirus (JCV) is an important human pathogen that causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In this study we further delineate the early events of JCV entry in human glial cells and demonstrate that a pentameric subunit of the viral capsid is able to recapitulate early events in viral trafficking. We show that JCV traffics to the endoplasmic reticulum (ER) by 6 h post infection, and that VP1 pentamers arrive at the ER with similar kinetics. Further, this JCV localization to the ER is critical for infection, as treatment of cells with agents that prevent ER trafficking, ER function, or ER quality control reduce JCV infectivity. These pentamers represent a new tool to study polyomavirus entry, and will be particularly useful in studying recently identified polyomaviruses that are difficult to propagate.

Nelson, Christian D.S.; Derdowski, Aaron; Maginnis, Melissa S.; O'Hara, Bethany A.; Atwood, Walter J.

2013-01-01

323

The VP1 subunit of JC polyomavirus recapitulates early events in viral trafficking and is a novel tool to study polyomavirus entry.  

PubMed

JC polyomavirus (JCV) is an important human pathogen that causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). In this study we further delineate the early events of JCV entry in human glial cells and demonstrate that a pentameric subunit of the viral capsid is able to recapitulate early events in viral trafficking. We show that JCV traffics to the endoplasmic reticulum (ER) by 6h post infection, and that VP1 pentamers arrive at the ER with similar kinetics. Further, this JCV localization to the ER is critical for infection, as treatment of cells with agents that prevent ER trafficking, ER function, or ER quality control reduce JCV infectivity. These pentamers represent a new tool to study polyomavirus entry, and will be particularly useful in studying recently identified polyomaviruses that are difficult to propagate. PMID:22516137

Nelson, Christian D S; Derdowski, Aaron; Maginnis, Melissa S; O'Hara, Bethany A; Atwood, Walter J

2012-04-18

324

Temporal Order is Coded Temporally in the Brain: Early Event-related Potential Latency Shifts Underlying Prior Entry in a Cross-modal Temporal Order Judgment Task  

Microsoft Academic Search

The speeding-up of neural processing associated with at- tended events (i.e., the prior-entry effect) has long been proposed as a viable mechanism by which attention can pri- oritize our perception and action. In the brain, this has been thought to be regulated through a sensory gating mechanism, increasing the amplitudes of early evoked potentials while leaving their latencies unaffected. However,

J. Vibell; C. Klinge; M. Zampini; C. Spence; A. C. Nobre

2007-01-01

325

Early sensory information processes are enhanced on visual oddball and S1–S2 tasks in Parkinson's disease: a visual event-related potentials study  

Microsoft Academic Search

To observe sensory and cognitive information processing in Parkinson's disease (PD), 34 PD patients and 26 controls were investigated. A visual oddball paradigm and an S1–S2 paradigm were employed to record the early (P1, N1, P2) and late (N2, P3) event-related potentials (ERPs) at Cz, Pz and Oz. Results showed: (1) enlarged P1 amplitude at all electrode locations on both

Mei Li; Yoshiyuki Kuroiwa; Lihong Wang; Toshiaki Kamitani; Tatsuya Takahashi; Yume Suzuki; Shu Omoto

2003-01-01

326

Cerebral Activation Areas with Respect to Word and Sentence Production by Early and Late Korean-English Bilinguals: Event-Related fMRI Study  

Microsoft Academic Search

\\u000a This study was conducted to investigate the cerebral areas related with word and sentence production shown in event-related\\u000a fMRI. Specifically the current study has an intention to enlighten the difference between native and foreign language processing\\u000a by early and late Korean-English bilinguals. Two experiments were performed to confirm the areas related with each level of\\u000a word and sentence generation. The

Choong-myung Kim; Donghoon Lee; Kichun Nam

2004-01-01

327

The record of Tethyan planktonic foraminifera at the early Paleogene hyperthermal events and Middle Eocene Climatic Optimum in northeastern Italy: are they comparable?  

NASA Astrophysics Data System (ADS)

The early Paleogene is one of the more climatically and evolutionary dynamic periods in the Earth history that records a pronounced warming trend peaking in the Early Eocene, and a successive composite transition towards the modern icehouse world. Ever increasingly scientific attention is dedicated to definitely comprehend timing, nature and characters of the complex, non-linear evolution of the Paleogene climate. Several complete and expanded Paleogene successions (Forada, Possagno, Alano, Farra), with a sound magneto-biochronostratigraphic and stable isotope record crop out in the Venetian Southern Alps (Northeast Italy). Recent studies (Giusberti et. al., 2007; Luciani et al., 2007; Agnini et al., 2008) and unpublished data document the presence in these section of the main short-lived warming events (hyperthermals) of the Eocene (Paleocene-Eocene Thermal Maximum, PETM, ca 55 Ma, Eocene Layer of Mysterious Origin (ELMO, ca 53,6 Ma), X-event (ca 52.5 Ma), of the Early Eocene Climatic Optimum (EECO, ca 50-52 Ma) and of the Middle Eocene Climatic Optimum (MECO, ca 40 Ma; Zachos et al., 2001. 2008). All these events are typified by marked negative shifts in ?13C curves that correspond to carbonate decrease related to rise of the carbonate compensation depth in turn induced by large introduction in the ocean-atmosphere system of CO2. Common features to the warming events are pronounced and complex changes in planktonic foraminiferal assemblages, indicating strong environmental perturbations that perfectly parallel the variations of the stable isotope curves in all the examined events. These strict correspondences indicate close cause-effect relationships between changes in environmental conditions and modifications of the assemblages. Our analysis shows that the most striking variations are recorded by the PETM and MECO assemblages that reflect highly perturbed environments. The ELMO, X-event and EECO exhibit planktic foraminiferal responses that are similar to, though less intense than, those observed across the PETM and the MECO. In addition, sedimentological and quantitative micropaleontological data from the hyperthermal events from the Venetian Southern Alps essentially suggest as the main response to the pronounced warmth, increased weathering and runoff as well as sea surface eutrophication. A pronounced shift from relatively oligotrophic to eutrophic, opportunist planktonic foraminiferal assemblages was observed at the MECO as well, thus showing analogies with the hyperthermal events recorded in the same area. The taxa indicating eutrophic environmental conditions are however different at the MECO from the Alano section; on the other hand we can expect that the planktonic foraminiferal taxa indicating analogous scenarios might be different in different Eocene time-intervals. Remarkably, the PETM and MECO events record a significant occurrence of giant and malformed foraminifera, evidence of transient alteration in the ocean chemistry, including possible pH oscillations and increase in trace metal content. Our data suggests therefore that a major threshold in the photic zone ocean chemistry has been passed only for those prominent events. In conclusion, from the biotic response to the hyperthermal events, to the EECO and MECO we deduce that the most important effect of pronounced warming, that is the aspect common to all these events, has been the eutrophication of surface waters, as a consequence of modification in the hydrological cycle. The location adjacent to land masses of the studied Tethyan setting evidently facilitated the terrigenous input that was apparently the main responsible for the increase in nutrient availability during the cited Paleogene warming events. Finally, several lines of evidence indicate that PETM, EECO and MECO were linked to permanent changes in planktonic foraminiferal evolution beside the transient, ecologically controlled variations. Even though the true mechanisms forcing evolution of life on Earth are still unexplained, our record of the major climatic Paleogene events suggests a

Luciani, Valeria; Giusberti, Luca; Agnini, Claudia; Fornaciari, Eliana; Rio, Domenico

2010-05-01

328

Relative proportion of ethical teaching versus historical events concerning Jesus in early Islamic and Christian historical documents.  

PubMed

The relative proportion of reports of events in the life of Jesus versus reports of his teachings are compared across the Qur'an and a sample of the New Testament (Luke 2-21). A much larger number of teachings (74) appear to be mentioned in the New Testament; at the same time, there are more teachings than events (52) reported, while the opposite is true (15 events, 3 teachings) in the Qur'an. The difference is significant statistically (p < .002). More research is needed to assess the sources of such differences. PMID:15217047

Schumm, Walter R

2004-06-01

329

Effects of temporal trial-by-trial cuing on early and late stages of auditory processing: evidence from event-related potentials.  

PubMed

Temporal-cuing studies show faster responding to stimuli at an attended versus unattended time point. Whether the mechanisms involved in this temporal orienting of attention are located early or late in the processing stream has not been answered unequivocally. To address this question, we measured event-related potentials in two versions of an auditory temporal cuing task: Stimuli at the uncued time point either required a response (Experiment 1) or did not (Experiment 2). In both tasks, attention was oriented to the cued time point, but attention could be selectively focused on the cued time point only in Experiment 2. In both experiments, temporal orienting was associated with a late positivity in the timerange of the P3. An early enhancement in the timerange of the auditory N1 was observed only in Experiment 2. Thus, temporal attention improves auditory processing at early sensory levels only when it can be focused selectively. PMID:21590512

Lampar, Alexa; Lange, Kathrin

2011-08-01

330

Evidence for a Dual Antiviral Role of the Major Nuclear Domain 10 Component Sp100 during the Immediate-Early and Late Phases of the Human Cytomegalovirus Replication Cycle ?  

PubMed Central

In recent studies, the nuclear domain 10 (ND10) components PML and hDaxx were identified as cellular restriction factors that inhibit the initiation of human cytomegalovirus (HCMV) replication. The antiviral function of ND10, however, is antagonized by the IE1 protein, which induces ND10 disruption. Here we show that IE1 not only de-SUMOylates PML immediately upon infection but also directly targets Sp100. IE1 expression alone was sufficient to downregulate endogenous Sp100 independently of the presence of PML. Moreover, cotransfection experiments revealed that IE1 negatively interferes with the SUMOylation of all Sp100 isoforms. The modulation of Sp100 at immediate-early (IE) times of infection, indeed, seemed to have an in vivo relevance for HCMV replication, since knockdown of Sp100 resulted in more cells initiating the viral gene expression program. In addition, we observed that Sp100 was degraded in a proteasome-dependent manner at late times postinfection, suggesting that Sp100 may play an additional antiviral role during the late phase. Infection experiments conducted with Sp100 knockdown human foreskin fibroblasts (HFFs) confirmed this hypothesis: depletion of Sp100 resulted in augmented release of progeny virus particles compared to that from control cells. Consistent with this observation, we noted increased amounts of viral late gene products in the absence of Sp100. Importantly, this elevated late gene expression was not dependent on enhanced viral IE gene expression. Taken together, our data provide evidence that Sp100 is the first ND10-related factor identified that not only possesses the potential to restrict the initial stage of infection but also inhibits HCMV replication during the late phase.

Tavalai, Nina; Adler, Martina; Scherer, Myriam; Riedl, Yvonne; Stamminger, Thomas

2011-01-01

331

The use of an E1-deleted, replication-defective adenovirus recombinant expressing the rabies virus glycoprotein for early vaccination of mice against rabies virus.  

PubMed Central

An E1-deleted, replication-defective adenovirus recombinant of the human strain 5 expressing the rabies virus glycoprotein, termed Adrab.gp, was tested in young mice. Mice immunized at birth with the Adrab.gp construct developed antibodies to rabies virus and cytokine-secreting lymphocytes and were protected against subsequent challenge. Maternal immunity to rabies virus strongly interferes with vaccination of the offspring with a traditional inactivated rabies virus vaccine. The immune response to the rabies virus glycoprotein, as presented by the Adrab.gp vaccine, on the other hand, was not impaired by maternal immunity. Even neonatal immunization of mice born to rabies virus-immune dams with Adrab.gp construct resulted in a long-lasting protective immune response to rabies virus, suggesting that this type of vaccine could be useful for immunization shortly after birth. Nevertheless, pups born to Adrab.gp virus-immune dams showed an impaired immune response to the rabies virus glycoprotein upon vaccination with the Adrab.gp virus, indicating that maternal immunity to the vaccine carrier affected the offspring's immune response to rabies virus.

Wang, Y; Xiang, Z; Pasquini, S; Ertl, H C

1997-01-01

332

IQGAP1 translocates to the nucleus in early S-phase and contributes to cell cycle progression after DNA replication arrest  

Microsoft Academic Search

IQGAP1 is a plasma membrane-associated protein and an important regulator of the actin cytoskeleton, contributing to cell migration, polarity and adhesion. In this study, we demonstrate the nuclear translocation of IQGAP1 using confocal microscopy and cell fractionation. Moreover, we identify a specific pool of IQGAP1 that accumulates in the nucleus during late G1-early S phase of the cell cycle. The

Michael Johnson; Manisha Sharma; Mariana G. Brocardo; Beric R. Henderson

2011-01-01

333

Impact of Viral Factors on Very Early In Vivo Replication Profiles in Simian Immunodeficiency Virus SIVagm-Infected African Green Monkeys  

Microsoft Academic Search

To better understand which factors govern the levels of viral loads in early lentiviral infections of primates, we developed a model that allows distinguishing between the influences of host and viral factors on viremia. Herein we report that two species of African green monkeys (Chlorocebus sabaeus and C. pygerythrus) infected with their respective wild-type simian immunodeficiency virus SIVagm viruses (SIVagm.sab92018

Ivona Pandrea; Christopher Kornfeld; Mickael J.-Y. Ploquin; Cristian Apetrei; Abdourahmane Faye; Pierre Rouquet; Pierre Roques; Francois Simon; F. Barre-Sinoussi; Michaela C. Muller-Trutwin; Ousmane M. Diop

2005-01-01

334

Activation of the PI3K/Akt Pathway Early during Vaccinia and Cowpox Virus Infections Is Required for both Host Survival and Viral Replication?  

PubMed Central

Viral manipulation of the transduction pathways associated with key cellular functions such as actin remodeling, microtubule stabilization, and survival may favor a productive viral infection. Here we show that consistent with the vaccinia virus (VACV) and cowpox virus (CPXV) requirement for cytoskeleton alterations early during the infection cycle, PBK/Akt was phosphorylated at S473 [Akt(S473-P)], a modification associated with the mammalian target of rapamycin complex 2 (mTORC2), which was paralleled by phosphorylation at T308 [Akt(T308-P)] by PI3K/PDK1, which is required for host survival. Notably, while VACV stimulated Akt(S473-P/T308-P) at early (1 h postinfection [p.i.]) and late (24 h p.i.) times during the infective cycle, CPXV stimulated Akt at early times only. Pharmacological and genetic inhibition of PI3K (LY294002) or Akt (Akt-X and a dominant-negative form of Akt-K179M) resulted in a significant decline in virus yield (from 80% to ?90%). This decline was secondary to the inhibition of late viral gene expression, which in turn led to an arrest of virion morphogenesis at the immature-virion stage of the viral growth cycle. Furthermore, the cleavage of both caspase-3 and poly(ADP-ribose) polymerase and terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end labeling assays confirmed that permissive, spontaneously immortalized cells such as A31 cells and mouse embryonic fibroblasts (MEFs) underwent apoptosis upon orthopoxvirus infection plus LY294002 treatment. Thus, in A31 cells and MEFs, early viral receptor-mediated signals transmitted via the PI3K/Akt pathway are required and precede the expression of viral antiapoptotic genes. Additionally, the inhibition of these signals resulted in the apoptosis of the infected cells and a significant decline in viral titers.

Soares, Jamaria A. P.; Leite, Flavia G. G.; Andrade, Luciana G.; Torres, Alice A.; De Sousa, Lirlandia P.; Barcelos, Luciola S.; Teixeira, Mauro M.; Ferreira, Paulo C. P.; Kroon, Erna G.; Souto-Padron, Thais; Bonjardim, Claudio A.

2009-01-01

335

Brachial-Ankle Pulse Wave Velocity Predicts Decline in Renal Function and Cardiovascular Events in Early Stages of Chronic Kidney Disease  

PubMed Central

Objective: In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). Method: Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ? eGFR < 90 ml/min/1.73m2, eGFR < 90 group; n=117) and those with eGFR ? 90 ml/min/1.73 m2 (eGFR ? 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. Results: baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (?=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (?=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ? 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03) Conclusions: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.

Yoon, Hye Eun; Shin, Dong Il; Kim, Sung Jun; Koh, Eun Sil; Hwang, Hyeon Seok; Chung, Sungjin; Shin, Seok Joon

2013-01-01

336

PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection  

PubMed Central

Background Although gene exchange is not likely to occur freely, reassortment between the H5N1 highly pathogenic avian influenza virus (HPAIV) and currently circulating human viruses is a serious concern. The PA polymerase subunit of H5N1 HPAIV was recently reported to activate the influenza replicon activity. Methods The replicon activities of PR8 and WSN strains (H1N1) of influenza containing PA from HPAIV A/Cambodia/P0322095/2005 (H5N1) and the activity of the chimeric RNA polymerase were analyzed. A reassortant WSN virus containing the H5N1 Cambodia PA (C-PA) was then reconstituted and its growth in cells and pathogenicity in mice examined. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities of C-PA-infected cells were compared with those of WSN-infected cells. Results The activity of the chimeric RNA polymerase was slightly higher than that of WSN, and C-PA replicated better than WSN in cells. However, the multi-step growth of C-PA and its pathogenicity in mice were lower than those of WSN. The interferon promoter, TUNEL, and caspase 3, 8, and 9 activities were strongly induced in early infection in C-PA-infected cells but not in WSN-infected cells. Conclusions Apoptosis and interferon were strongly induced early in C-PA infection, which protected the uninfected cells from expansion of viral infection. In this case, these classical host-virus interactions contributed to the attenuation of this strongly replicating virus.

2012-01-01

337

Modeling the Control of DNA Replication in Fission Yeast  

Microsoft Academic Search

A central event in the eukaryotic cell cycle is the decision to commence DNA replication (S phase). Strict controls normally operate to prevent repeated rounds of DNA replication without intervening mitoses (``endoreplication'') or initiation of mitosis before DNA is fully replicated (``mitotic catastrophe''). Some of the genetic interactions involved in these controls have recently been identified in yeast. From this

Bela Novak; John J. Tyson

1997-01-01

338

Combined oxygen- and carbon-isotope records through the Early Jurassic: multiple global events and two modes of carbon-cycle/temperature coupling  

NASA Astrophysics Data System (ADS)

The Jurassic comprises some 55 million years of Earth history. However, within the Jurassic, only one major environmental change (hyperthermal) event is really well known - the Early Toarcian Oceanic Anoxic Event (OAE) at ~183 Ma - and until very recently the extent to which the accompanying environmental changes were global has been strongly debated. Nevertheless, partly as a result of the international effort to define Global Stratotype Sections and Points (GSSPs), much more is now being discovered about environmental changes taking place at and around the other Jurassic Age (Stage) boundaries, to the extent that meaningful comparisons between these events can begin to be made. Here we present new carbon and oxygen isotope data from mollusks (bivalves and belemnites) and brachiopods collected through the marine Early Jurassic succession of NE England, including the Sinemurian-Plienbachian boundary GSSP. All materials have been screened by chemical analysis and scanning electron microscopy to check for diagenetic alteration. Analysis of carbon isotopes from marine calcite is supplemented by analysis of carbon-isotope values from fossil wood collected through the same section. It is demonstrated that both long-term and short-term carbon-isotope shifts from the UK Early Jurassic represent global changes in carbon cycle balances. The Sinemurian-Pliensbachian boundary event is an event of global significance and shows several similarities to the Toarcian OAE (relative sea-level change, carbon-isotope signature), but also some significant contrasts (oxygen-isotope based paleotemperatures which provide no evidence for warming). Significant contrast in oxygen- and carbon-isotope co-variation also occurs on a long timescale. There appear to be two modes in the co-variation of carbon and oxygen isotopes through this time interval: mode 1 shows positive correlation and may be explained by conventional sources and sinks for carbon-dioxide; mode 2, representing negative correlation, is more difficult to explain but appears to dominate. Additionally, we show that estimates of carbon dioxide change through the Early Jurassic based on ??13C values from the stratigraphically extended Mochras Farm core are unlikely to be correct.

Hesselbo, S. P.; Korte, C.

2010-12-01

339

Early and Mid Term Histological Events During Single Level Posterolateral Intertransverse Process Fusion With Rhbmp-2/Collagen Carrier and a Ceramic Bulking Agent In a Non-Human Primate Model: Implications for Bone Graft Preparation.  

PubMed

STUDY DESIGN:: We used a non-human primate lumbar intertransverse process arthrodesis model to evaluate biological cascade of bone formation using different carrier preparation methods with a single dose of recombinant human bone morphogenetic protein-2 (rhBMP-2) at early time points. OBJECTIVE:: To examine early/mid-term descriptive histological and computerized tomographic events in single-level uninstrumented posterolateral non-human primate spinal fusions using rhBMP-2/ACS combined with ceramic bulking agents in three different configurations. SUMMARY OF BACKGROUND DATA:: rhBMP-2 on an absorbable collagen sponge carrier (ACS) alone leads to consistent posterolateral lumbar spine fusions in lower-order animals; however, these results have been difficult to replicate in non-human primates. METHODS:: Twelve skeletally mature, rhesus macaque monkeys underwent single-level posterolateral arthrodesis at L4-L5. A hydroxyapatite (HA)/tricalcium phosphate (?-TCP) ceramic bulking agent in three formulations was used in the treatment groups (n=3). When used, rhBMP-2/ACS at 1.5?mg/cc (3.0?mg rhBMP-2) was combined with 2.5?cc of ceramic bulking agent per side. Animals were killed at 4 weeks and 12 weeks postoperative. Computerized tomography scans were performed immediately post-op and every 4 weeks until sacrifice. Sagittal histologic sections were evaluated for bone histogenesis and location, cellular infiltration of the graft/substitute, and bone remodeling activity. RESULTS:: Significant histological differences in the developing fusion appeared between the three rhBMP-2/ACS treatment groups at 4 and 12 weeks. At 4 weeks, bone formation appeared to originate at the transverse process and the intertransverse membrane. Cellular infiltration was greatest in granular ceramic groups compared with matrix ceramic group. Minimal to no residual ACS was identified at the early time point. At 12 weeks, marked ceramic remodeling was observed with continued bone formation noted in all carrier groups. CONCLUSIONS:: At the early time period, histology showed that bone formation appeared to originate at the transverse processes and the intertransverse membrane, indicating that the dorsal muscle bed may not be the only location for bone formation. Histology also showed that the collagen carrier for rhBMP-2 is mostly resorbed by 4 weeks. Our results as well as previous literature indicate that ceramic bulking agents are needed to provide resistance to compression caused by paraspinal muscles on the fusion bed in the posterolateral environment. Histology showed that ceramic bulking agents may offer long-term scaffolding as well as a structure to supporting bone formation of the developing fusion mass. PMID:23073151

Khan, Safdar N; Toth, Jeffrey M; Gupta, Kavita; Glassman, Steven D; Gupta, Munish C

2012-10-15

340

Sea-ice melt onset associated with ice deformation events during early summer near the North Pole in the Arctic Ocean  

NASA Astrophysics Data System (ADS)

In the central Arctic Ocean, autonomous observations of ocean mixed layer and ice documented the transition from cold spring to early summer. Our ice motion measurements using GPS drifters captured three events of lead opening and ice ridge formation in May and June. We clarify how these ice deformation events are linked with the onset of sea ice melt. In early June, the buoy array detected a shear deformation coincident with a temperature peak at 6 m below the ice bottom. At this time, an autonomous profiler shows there was a slow decrease of temperature with depth and nearly homogeneous salinity profiles, with persistently stable mixed layer. We use a one-dimensional numerical simulation incorporating the Local Turbulence Closure (LTC) scheme to investigate the mechanisms controlling basal melt onset. According to the simulation, a combination of the extremely slow ice motion and incoming solar energy input at the open lead, followed by a transient low pressure system, produced a thin, low density surface layer by advection of warm lead water under the ice. This enhanced stratification near the surface facilitates storage of solar radiation within the thin layer, instead of exchange with deeper layers, leading to early onset of basal ice melt preceding the upper surface melt.

Kawaguchi, Yusuke; Huthchings, Jennifer; Vivire, Frederic; Kikuchi, Takashi; Morison, James; Noguchi, Tomohide; Lourenco, Antonio

2013-04-01

341

Impacts of a water stress followed by an early frost event on beech (Fagus sylvatica L.) susceptibility to Scolytine ambrosia beetles - Research strategy and first results  

NASA Astrophysics Data System (ADS)

Climate change tends to induce more frequent abiotic and biotic extreme events, having large impacts on tree vitality. Weakened trees are then more susceptible to secondary insect outbreaks, as it happened in Belgium in the early 2000s: after an early frost event, secondary Scolytine ambrosia beetles attacks were observed on beech trees. In this study, we test if a combination of stress, i.e. a soil water deficit preceding an early frost, could render trees more attractive to beetles. An experimental study was set in autumn 2008. Two parcels of a beech forest were covered with plastic tents to induce a water stress by rain interception. The parcels were surrounded by 2-meters depth trenches to avoid water supply by streaming. Soil water content and different indicators of tree water use (sap flow, predawn leaf water potential, tree radial growth) were followed. In autumn 2010, artificial frost injuries will be inflicted to trees using dry ice. Trees attractivity for Scolytine insects, and the success of insect colonization will then be studied. The poster will focus on experiment setting and first results (impacts of soil water deficit on trees).

La Spina, Sylvie; de Cannière, Charles; Molenberg, Jean-Marc; Vincke, Caroline; Deman, Déborah; Grégoire, Jean-Claude

2010-05-01

342

The Madotz Urgonian platform (Aralar, northern Spain): Paleoecological changes in response to Early Aptian global environmental events  

Microsoft Academic Search

Sudden addition of carbon dioxide to the atmosphere can reduce the CaCO3 saturation and weaken the biocalcification potential of marine organisms in shallow water and in open marine settings. In this study, the response of an Aptian neritic carbonate environment to sudden addition of carbon dioxide at the beginning of Oceanic Anoxic Event 1a is investigated. The beginning of the

M. I. Millán; H. J. Weissert; H. Owen; P. A. Fernández-Mendiola; J. García-Mondéjar

343

Rab4b controls an early endosome sorting event by interacting with the ?-subunit of the clathrin adaptor complex 1.  

PubMed

The endocytic pathway is essential for cell homeostasis and numerous small Rab GTPases are involved in its control. The endocytic trafficking step controlled by Rab4b has not been elucidated, although recent data suggested it could be important for glucose homeostasis, synaptic homeostasis or adaptive immunity. Here, we show that Rab4b is required for early endosome sorting of transferrin receptors (TfRs) to the recycling endosomes, and we identified the AP1? subunit of the clathrin adaptor AP-1 as a Rab4b effector and key component of the machinery of early endosome sorting. We show that internalised transferrin (Tf) does not reach Vamp3/Rab11 recycling endosomes in the absence of Rab4b, whereas it is rapidly recycled back to the plasma membrane. By contrast, overexpression of Rab4b leads to the accumulation of internalised Tf within AP-1- and clathrin-coated vesicles. These vesicles are poor in early and recycling endocytic markers except for TfR and require AP1? for their formation. Furthermore, the targeted overexpression of the Rab4b-binding domain of AP1? to early endosome upon its fusion with FYVE domains inhibited the interaction between Rab4b and endogenous AP1?, and perturbed Tf traffic. We thus proposed that the interaction between early endocytic Rab4b and AP1? could allow the budding of clathrin-coated vesicles for subsequent traffic to recycling endosomes. The data also uncover a novel type of endosomes, characterised by low abundance of either early or recycling endocytic markers, which could potentially be generated in cell types that naturally express high level of Rab4b. PMID:24006255

Laura, Perrin; Sandra, Lacas-Gervais; Jérôme, Gilleron; Franck, Ceppo; François, Prodon; Alexandre, Benmerah; Jean-François, Tanti; Mireille, Cormont

2013-09-04

344

40Ar/39Ar chronology of Late Pliocene and Early Pleistocene geomagnetic and glacial events in southern Argentina  

NASA Astrophysics Data System (ADS)

K-Ar dating and paleomagnetic directions from the lava sequence atop Cerro del Fraile, Argentina, contributed to the nascent Geomagnetic Polarity Time Scale (GPTS), recording the Réunion event, and the Olduvai and Jaramillo subchrons [Fleck et al., 1972]. New stratigraphy, paleomagnetic analyses, 40Ar/39Ar incremental heating ages, and unspiked K-Ar dating of 10 lava flows on Cerro del Fraile place these eruptions between 2.181±0.097 and 1.073±0.036 Ma and enhance this unique record, which includes seven tills interbedded with the lavas. The Réunion event is recorded by three lavas with transitional, normal, and reversed polarity that yielded identical 40Ar/39Ar isochron ages and a weighted mean age of 2.136±0.019 Ma. When combined with 40Ar/39Ar ages from lavas on Réunion Island and a normal tuff in the Massif Central, the age of the Réunion event is 2.137±0.016 Ma and is older by ˜50 kyr than the 2.086±0.016 Ma Huckleberry Ridge event. The onset and termination of the Olduvai are similarly constrained to 1.922±0.066 Ma and 1.775±0.015 Ma, whereas the onset of the Jaramillo occurred 1.069±0.011 Ma. A discordant age spectrum from another transitional lava gave a total fusion age of 1.61 Ma and an unspiked K-Ar age of 1.43 Ma. It is uncertain whether this corresponds to the Gilsa, Gardar, Stage 54, or Sangiran events, or represents an unrecognized period of geomagnetic instability. Deposition of till on the piedmont surface prior to 2.186 Ma and six subsequent tills between 2.186 Ma and ˜1.073 Ma mark frequent glaciations of southern South America during marine oxygen isotope stages 82 to 48.

Singer, Brad S.; Brown, Laurie L.; Rabassa, Jorge O.; Guillou, Hervé

345

Rumination as a mechanism linking stressful life events to symptoms of depression and anxiety: longitudinal evidence in early adolescents and adults.  

PubMed

Rumination is a well-established risk factor for the onset of major depression and anxiety symptomatology in both adolescents and adults. Despite the robust associations between rumination and internalizing psychopathology, there is a dearth of research examining factors that might lead to a ruminative response style. In the current study, we examined whether social environmental experiences were associated with rumination. Specifically, we evaluated whether self-reported exposure to stressful life events predicted subsequent increases in rumination. We also investigated whether rumination served as a mechanism underlying the longitudinal association between self-reported stressful life events and internalizing symptoms. Self-reported stressful life events, rumination, and symptoms of depression and anxiety were assessed in 2 separate longitudinal samples. A sample of early adolescents (N = 1,065) was assessed at 3 time points spanning 7 months. A sample of adults (N = 1,132) was assessed at 2 time points spanning 12 months. In both samples, self-reported exposure to stressful life events was associated longitudinally with increased engagement in rumination. In addition, rumination mediated the longitudinal relationship between self-reported stressors and symptoms of anxiety in both samples and the relationship between self-reported life events and symptoms of depression in the adult sample. Identifying the psychological and neurobiological mechanisms that explain a greater propensity for rumination following stressors remains an important goal for future research. This study provides novel evidence for the role of stressful life events in shaping characteristic responses to distress, specifically engagement in rumination, highlighting potentially useful targets for interventions aimed at preventing the onset of depression and anxiety. PMID:23713497

Michl, Louisa C; McLaughlin, Katie A; Shepherd, Kathrine; Nolen-Hoeksema, Susan

2013-05-01

346

Loss of chloroplast transcripts for proteins associated with photosystem II: an early event during heat-bleaching in Euglena gracilis  

Microsoft Academic Search

A shift in the ratio of chlorophyll (Chl) a and Chl b is an early indicator of heat bleaching in Euglena gracilis. This observation prompted us to consider whether or not changes in steady-state levels of chloroplast transcripts and in transcriptional activity could limit the synthesis of Chl a-binding proteins in bleaching plastids. We found that the mature transcripts for

Eric J. Thomas; William Ortiz

1995-01-01

347

Geochemistry of oceanic anoxic events  

Microsoft Academic Search

Oceanic anoxic events (OAEs) record profound changes in the climatic and paleoceanographic state of the planet and represent major disturbances in the global carbon cycle. OAEs that manifestly caused major chemical change in the Mesozoic Ocean include those of the early Toarcian (Posidonienschiefer event, T-OAE, ?183 Ma), early Aptian (Selli event, OAE 1a, ?120 Ma), early Albian (Paquier event, OAE

Hugh C. Jenkyns

2010-01-01

348

Geochemistry of oceanic anoxic events  

Microsoft Academic Search

Oceanic anoxic events (OAEs) record profound changes in the climatic and paleoceanographic state of the planet and represent major disturbances in the global carbon cycle. OAEs that manifestly caused major chemical change in the Mesozoic Ocean include those of the early Toarcian (Posidonienschiefer event, T-OAE, ˜183 Ma), early Aptian (Selli event, OAE 1a, ˜120 Ma), early Albian (Paquier event, OAE

Hugh C. Jenkyns

2010-01-01

349

QTc dispersion is prolonged in patients with early postoperative adverse cardiovascular events and those with silent myocardial ischemia  

Microsoft Academic Search

Objective: To determine if increased QT interval dispersion (corrected and not corrected for heart rate) is associated with perioperative silent myocardial ischemia or postoperative adverse cardiovascular events.Design: Blinded retrospective observational study.Setting: University hospital.Participants: One hundred eighty-one perioperative patients receiving general anesthesia for elective major vascular or orthopedic surgery.Interventions: None.Measurements and main results: QT dispersion, corrected and uncorrected for heart rate,

Keith J Anderson; John W Sear

2004-01-01

350

Early childhood behavior trajectories and the likelihood of experiencing a traumatic event and PTSD by young adulthood  

Microsoft Academic Search

This study modeled children’s trajectories of teacher rated aggressive-disruptive behavior problems assessed at six time points\\u000a between the ages of 6 and 11 and explored the likelihood of being exposed to DSM-IV qualifying traumatic events and posttraumatic\\u000a stress disorder (PTSD) in 837 urban first graders (71% African American) followed-up for 15 years. Childhood trajectories\\u000a of chronic high or increasing aggressive-disruptive behavior

Carla L. Storr; Cindy M. Schaeffer; Hanno Petras; Nicholas S. Ialongo; Naomi Breslau

2009-01-01

351

Replication Fork Polarity Gradients Revealed by Megabase-Sized U-Shaped Replication Timing Domains in Human Cell Lines  

Microsoft Academic Search

In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell

Antoine Baker; Benjamin Audit; Chun-Long Chen; Benoit Moindrot; Antoine Leleu; Guillaume Guilbaud; Aurélien Rappailles; Cédric Vaillant; Arach Goldar; Fabien Mongelard; Yves dAubenton-Carafa; Olivier Hyrien; Claude Thermes; Alain Arneodo

2012-01-01

352

High-resolution late Maastrichtian early Danian oceanic 87Sr\\/86Sr record: Implications for Cretaceous-Tertiary boundary events  

Microsoft Academic Search

A high-resolution late Maastrichtian early Danian seawater 87Sr\\/86Sr reference curve is constructed from two Cretaceous-Tertiary boundary (K-T boundary) sections: Bidart (France) and El Kef (Tunisia). The 87Sr\\/86Sr curve shows maxima at 0.3 0.4 Ma before the K-T boundary and at the K-T boundary. The first maximum could mark the onset of a major outflow of the Deccan Traps. The second

H. B. Vonhof; J. Smit

1997-01-01

353

Linkage Replication for Chromosomal Region 13q32 in Schizophrenia: Evidence from a Brazilian Pilot Study on Early Onset Schizophrenia Families  

PubMed Central

We report analyses of a Brazilian study of early onset schizophrenia (BEOS) families. We genotyped 22 members of 4 families on a linkage SNP array and report here non-parametric linkage analyses using MERLIN® software. We found suggestive evidence for linkage on two chromosomal regions, 13q32 and 11p15.4. A LOD score of 2.71 was observed at 13q32 with a one LOD interval extending from 60.63–92.35 cM. From simulations, this LOD score gave a genome-wide empirical corrected p?=?0.33, after accounting for all markers tested. Similarly 11p15.4 showed the same maximum LOD of 2.71 and a narrower one LOD interval of 4–14 cM. Of these, 13q32 has been reported to be linked to schizophrenia by multiple different studies. Thus, our study provides additional supporting evidence for an aetiological role of variants at 13q32 in schizophrenia.

Gadelha, Ary; Ota, Vanessa Kiyomi; Cano, Jose Paya; Melaragno, Maria Isabel; Smith, Marilia A. C.; de Jesus Mari, Jair; Bressan, Rodrigo A.; Belangero, Sintia Iole; Breen, Gerome

2012-01-01

354

Reversible Inhibition of Murine Cytomegalovirus Replication by Gamma Interferon (IFN-?) in Primary Macrophages Involves a Primed Type I IFN-Signaling Subnetwork for Full Establishment of an Immediate-Early Antiviral State ? †  

PubMed Central

Activated macrophages play a central role in controlling inflammatory responses to infection and are tightly regulated to rapidly mount responses to infectious challenge. Type I interferon (alpha/beta interferon [IFN-?/?]) and type II interferon (IFN-?) play a crucial role in activating macrophages and subsequently restricting viral infections. Both types of IFNs signal through related but distinct signaling pathways, inducing a vast number of interferon-stimulated genes that are overlapping but distinguishable. The exact mechanism by which IFNs, particularly IFN-?, inhibit DNA viruses such as cytomegalovirus (CMV) is still not fully understood. Here, we investigate the antiviral state developed in macrophages upon reversible inhibition of murine CMV by IFN-?. On the basis of molecular profiling of the reversible inhibition, we identify a significant contribution of a restricted type I IFN subnetwork linked with IFN-? activation. Genetic knockout of the type I-signaling pathway, in the context of IFN-? stimulation, revealed an essential requirement for a primed type I-signaling process in developing a full refractory state in macrophages. A minimal transient induction of IFN-? upon macrophage activation with IFN-? is also detectable. In dose and kinetic viral replication inhibition experiments with IFN-?, the establishment of an antiviral effect is demonstrated to occur within the first hours of infection. We show that the inhibitory mechanisms at these very early times involve a blockade of the viral major immediate-early promoter activity. Altogether our results show that a primed type I IFN subnetwork contributes to an immediate-early antiviral state induced by type II IFN activation of macrophages, with a potential further amplification loop contributed by transient induction of IFN-?.

Kropp, Kai A.; Robertson, Kevin A.; Sing, Garwin; Rodriguez-Martin, Sara; Blanc, Mathieu; Lacaze, Paul; Hassim, Muhamad F. B. Noor; Khondoker, Mizanur R.; Busche, Andreas; Dickinson, Paul; Forster, Thorsten; Strobl, Birgit; Mueller, Mathias; Jonjic, Stipan; Angulo, Ana; Ghazal, Peter

2011-01-01

355

Physical activity, additional breast cancer events, and mortality among early-stage breast cancer survivors: findings from the WHEL Study  

Microsoft Academic Search

Objective  Research suggests that physical activity is associated with improved breast cancer survival, yet no studies have examined\\u000a the association between post-diagnosis changes in physical activity and breast cancer outcomes. The aim of this study was\\u000a to determine whether baseline activity and 1-year change in activity are associated with breast cancer events or mortality.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A total of 2,361 post-treatment breast cancer

Lisa A. Cadmus Bertram; Marcia L. Stefanick; Nazmus Saquib; Loki Natarajan; Ruth E. Patterson; Wayne Bardwell; Shirley W. Flatt; Vicky A. Newman; Cheryl L. Rock; Cynthia A. Thomson; John P. Pierce

2011-01-01

356

Proteomic analysis of early reprogramming events in murine somatic cells incubated with Xenopus laevis oocyte extracts demonstrates network associations with induced pluripotency markers.  

PubMed

The reprogramming of somatic cells into a pluripotent/embryonic-like state holds great potential for regenerative medicine, bypassing ethical issues associated with embryonic stem cells (ESCs). Numerous methods, including somatic cell nuclear transfer (SCNT), fusion to pluripotent cells, the use of cell extracts, and expression of transcription factors, have been used to reprogram cells into ES-like cells [termed induced pluripotent stem cells (iPSCs)]. This study investigated early events in the nuclei of permeabilized murine somatic cells incubated in cytoplasmic extract prepared from Xenopus laevis germinal vesicle-stage oocytes by identifying proteins that showed significant quantitative changes using proteomic techniques. A total of 69 protein spots from two-dimensional electrophoresis were identified as being significantly altered in expression after treatment, and 38 proteins were identified by tandem mass spectrometry. Network analysis was used to highlight pathway connections and interactions between these identified proteins, which were found to be involved in many functions--primarily nuclear structure and dynamics, transcription, and translation. The pluripotency markers Klf4, c-Myc, Nanog, and POU5F1 were highlighted by the interaction network analysis, as well as other compounds/proteins known to be repressed in pluripotent cells [e.g., protein kinase C (PRKC)] or enhanced during differentiation of ESCs (e.g., retinoic acid). The network analysis also indicated additional proteins and pathways potentially involved in early reprogramming events. PMID:23768116

Rathbone, Alex J; Liddell, Susan; Campbell, Keith H S

2013-06-15

357

The Neuronal Replicator Hypothesis  

Microsoft Academic Search

We propose that replication (with mutation) of patterns of neuronal activity can occur within the brain using known neurophysiological processes. Thereby evolutionary algorithms implemented by neuro- nal circuits can play a role in cognition. Replication of structured neuronal representations is assumed in several cognitive architectures. Replicators overcome some limitations of selectionist models of neuronal search. Hebbian learning is combined with

Chrisantha Fernando; Richard Goldstein; Eörs Szathmáry

2010-01-01

358

Non-Verbal Reasoning Ability and Academic Achievement as Moderators of the Relation between Adverse Life Events and Emotional and Behavioural Problems in Early Adolescence: The Importance of Moderator and Outcome Specificity  

ERIC Educational Resources Information Center

|This study was carried out to model the functional form of the effect of contextual risk (number of adverse life events) on emotional and behavioural problems in early adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life events on emotional and behavioural…

Flouri, Eirini; Tzavidis, Nikos

2011-01-01

359

Non-Verbal Reasoning Ability and Academic Achievement as Moderators of the Relation between Adverse Life Events and Emotional and Behavioural Problems in Early Adolescence: The Importance of Moderator and Outcome Specificity  

ERIC Educational Resources Information Center

This study was carried out to model the functional form of the effect of contextual risk (number of adverse life events) on emotional and behavioural problems in early adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life events on emotional and behavioural…

Flouri, Eirini; Tzavidis, Nikos

2011-01-01

360

Fragile Site Instability in Saccharomyces cerevisiae Causes Loss of Heterozygosity by Mitotic Crossovers and Break-Induced Replication  

PubMed Central

Loss of heterozygosity (LOH) at tumor suppressor loci is a major contributor to cancer initiation and progression. Both deletions and mitotic recombination can lead to LOH. Certain chromosomal loci known as common fragile sites are susceptible to DNA lesions under replication stress, and replication stress is prevalent in early stage tumor cells. There is extensive evidence for deletions stimulated by common fragile sites in tumors, but the role of fragile sites in stimulating mitotic recombination that causes LOH is unknown. Here, we have used the yeast model system to study the relationship between fragile site instability and mitotic recombination that results in LOH. A naturally occurring fragile site, FS2, exists on the right arm of yeast chromosome III, and we have analyzed LOH on this chromosome. We report that the frequency of spontaneous mitotic BIR events resulting in LOH on the right arm of yeast chromosome III is higher than expected, and that replication stress by low levels of polymerase alpha increases mitotic recombination 12-fold. Using single-nucleotide polymorphisms between the two chromosome III homologs, we mapped the locations of recombination events and determined that FS2 is a strong hotspot for both mitotic reciprocal crossovers and break-induced replication events under conditions of replication stress.

Miller, Shaylynn D.; Casper, Anne M.

2013-01-01

361

Bio- and chemostratigraphy of the Early Aptian Oceanic Anoxic Event 1a within the mid-latitudes of northwest Europe (Germany, Lower Saxony Basin)  

NASA Astrophysics Data System (ADS)

The Mid-Cretaceous period was characterised by a series of prominent anoxic events, one of these was the late Early Aptian Oceanic Anoxic Event 1a (OAE 1a). The Fischschiefer horizon is the regional sedimentary expression of this event in a small epicontinental sea in northwest Europe (Germany, Lower Saxony Basin). In the present study, two sediment cores of Lower to Upper Aptian age (Hoheneggelsen KB 9 and 40) from the Brunswick area, north Germany, have been investigated in detail with respect to their lithostratigraphy, geochemistry (CaCO3, TOC), biostratigraphy (coccoliths, nannoliths) and high-resolution chemostratigraphy (^13Ccarb and ^13Corg). Together with separately published new planktonic foraminifer data of the cores it was possible to establish a detailed time frame and to recognise the OAE 1a. The ^13C data enabled us to subdivide the deposits into isotope segments (C2-C7), which are commonly used as stratigraphic markers in coeval sediments around the world. The carbon isotope curves are compared to recently published Aptian curves from other parts of the Lower Saxony Basin, all of which record the prominent carbon isotope anomaly of the OAE 1a. A high-resolution correlation of the typical isotope trends of OAE 1a (segments C3-6) across the Lower Saxony Basin appears difficult due to an early diagenetic overprint of the primary isotope signal. These alterations can be explained by the temporary establishment of euxinic conditions the Lower Saxony Basin during OAE 1a as consequence of an interplay of different factors, such as global warming, restricted palaeogeography, increased fluvial input and intensified stable water stratification, which is supported by several lines of regional evidence.

Heldt, Matthias; Mutterlose, Joerg; Berner, Uli; Erbacher, Jochen

2013-04-01

362

Carcinogen-induced early molecular events and its implication in the initiation of chemical hepatocarcinogenesis in rats: chemopreventive role of vanadium on this process.  

PubMed

Carcinogen-induced formation of DNA adducts and other types of DNA lesions are the critical molecular events in the initiation of chemical carcinogenesis and modulation of such events by chemopreventive agents could be an important step in limiting neoplastic transformation in vivo. Vanadium, a dietary micronutrient has been found to be effective in several types of cancers both in vivo and in vitro and also possesses profound anticarcinogenicity against rat models of mammary, colon and hepatocarcinogenesis. Presently, we report the chemopreventive potential of vanadium on diethylnitrosamine (DEN)-induced early DNA damages in rat liver. Hepatocarcinogenesis was induced in male Sprague-Dawley rats with a single, necrogenic, intraperitoneal (i.p.) injection of DEN (200 mg/kg body weight) at week 4. There was a significant induction of tissue-specific ethylguanines, steady elevation of modified DNA bases 8-hydroxy-2'-deoxyguanosines (8-OHdGs) (P<0.0001; 89.93%) along with substantial increment of the extent of single-strand breaks (SSBs) (P<0.0001) following DEN exposure. Supplementation of 0.5 ppm of vanadium throughout the experiment abated the formations of O(6)-ethylguanines and 7-ethylguanines (P<0.0001; 48.71% and 67.54% respectively), 8-OHdGs (P<0.0001; 81.37%), length:width (L:W) of DNA mass (P<0.01; 62.12%) and the mean frequency of tailed DNA (P<0.001; 53.58%), and hepatic nodulogenesis in preneoplastic rat liver. The study indicates that 0.5 ppm vanadium is potentially and optimally effective, as derived from dose-response studies, in limiting early molecular events and preneoplastic lesions, thereby modulating the initiation stage of hepatocarcinogenesis. Vanadium is chemopreventive against DEN-induced genotoxicity and resulting hepatocellular transformation in rats. PMID:17174075

Chakraborty, Tridib; Chatterjee, Amrita; Rana, Ajay; Dhachinamoorthi, Duraisami; Kumar P, Ashok; Chatterjee, Malay

2006-11-10

363

Ability to delay neuropathological events associated with astrocytic MAO-B increase in a Parkinsonian mouse model: Implications for early intervention on disease progression  

PubMed Central

We previously demonstrated that elevation of astrocytic monoamine oxidase B (MAO-B) levels in a doxycycline (dox)-inducible transgenic mouse model following 14 days of dox induction results in several neuropathologic features similar to those observed in the Parkinsonian midbrain (Mallajosyula et al., 2008). These include a specific, selective and progressive loss of dopaminergic neurons of the substantia nigra (SN), selective decreases in mitochondrial complex I (CI) activity and increased oxidative stress. Here, we report that the temporal sequence of events following MAO-B elevation initially involves increased oxidative stress followed by CI inhibition and finally neurodegeneration. Furthermore, dox removal (DR) at days 3 and 5 of MAO-B induction was sufficient to arrest further increases in oxidative stress as well as subsequent neurodegenerative events. In order to assess the contribution of MAO-B-induced oxidative stress to later events, we compared the impact of DR which reverses the MAO-B increase with treatment of animals with the lipophilic antioxidant compound EUK-189. EUK-189 was found to be as effective as DR in halting downstream CI inhibition and also significantly attenuated SN DA cell loss as a result of astrocytic MAO-B induction. This suggests that MAO-B-mediated ROS contributes to neuropathology associated with this model and that antioxidant treatment can arrest further progression of dopaminergic cell death. This has implications for early intervention therapies.

Siddiqui, Almas; Mallajosyula, Jyothi K.; Rane, Anand; Andersen, Julie K.

2010-01-01

364

Diffusion MRI detects early events in the response of a glioma model to the yeast cytosine deaminase gene therapy strategy.  

PubMed

Detection of a therapeutic response early in the course of cancer treatment, before tumor growth delay or regression, is not currently possible in experimental models or clinical medicine. New interim measures of therapeutic response would be particularly useful in the development of cancer chemosensitization gene therapy by facilitating optimization of gene transfer protocols and prodrug dosing schedules. Diffusion MRI is a sensitive technique producing quantitative and noninvasive images of the apparent mobility of water within a tissue. We investigated the utility of diffusion MRI for detecting early changes associated with a refined cytosine deaminase (CD)/5-fluorocytosine (5FC) chemosensitization gene therapy paradigm in orthotopic 9L gliomas stably expressing the recently cloned S. cerevisiae CD gene. Mean tumor diffusion increased 31% within 8 days of initiating 5-FC treatment, preceding tumor growth arrest and regression. Complete regression of the intracranial tumor was observed in four of five treated animals, and recurrent tumor in the remaining animal exhibited water diffusion behavior similar to primary, untreated tumors. These results demonstrate the efficacy of the yCD/5FC strategy for glioma and suggest that increased tumor water diffusion is an indicator of active therapeutic intervention. PMID:10871748

Stegman, L D; Rehemtulla, A; Hamstra, D A; Rice, D J; Jonas, S J; Stout, K L; Chenevert, T L; Ross, B D

2000-06-01

365

Early events in development of electrical activity and contraction in embryonic rat heart assessed by optical recording.  

PubMed Central

Spontaneous action potential and contraction in the early embryonic heart of the rat have been monitored optically using a voltage-sensitive merocyanine-rhodanine dye together with a multiple-element photodiode matrix array, and the onset of rhythmical action-potential activity in the early phases of rat cardiogenesis was conclusively determined for the first time. Spontaneous rhythmical action potentials were first generated in the central part of the embryonic heart at the middle period of the 3-somite stage of development, at 91/2 days after copulation. Subsequently, contractions coupled with the action potential also appeared at the end of the 3-somite stage. Usually, at the 3-somite stage, spontaneous action signals were synchronized among the different areas in the heart. From this result, it is evident that the paired right and left cardiac primordia are fused completely at the time of initiation of spontaneous electrical activity. In the 3-somite embryonic heart, excitatory waves were conducted radially over the heart, at a uniform rate (0.4-0.8 mm/s), from the pace-making area. However, the regional priority of pace-making activity is not rigid but is flexible. Images Fig. 8 Plate 1

Hirota, A; Kamino, K; Komuro, H; Sakai, T; Yada, T

1985-01-01

366

The inter-specific hybrid Silene latifolia x S. viscosa reveals early events of sex chromosome evolution.  

PubMed

The dioecious plant species Silene latifolia has a sex determination mechanism based on an active Y chromosome. Here, we used inter-specific hybrids in the genus Silene to study the effects of gene complexes on the Y chromosome. If the function of Y-linked genes has been maintained in the same state as in the hermaphrodite progenitor species, it should be possible to substitute such genes by genes coming from a related hermaphrodite species. In the inter-specific hybrid, S. latifolia x S. viscosa, anthers indeed develop far beyond the early bilobal stage characteristic of XX S. latifolia female plants. The S. viscosa genome can thus replace the key sex determination gene whose absence abolishes early stamen development in females (loss of the stamen-promoting function, SPF), so that hybrid plants are morphologically hermaphrodite. However, the hybrids have two anther development defects, loss of adhesion of the tapetum to the endothecium, and precocious endothecium maturation. Both these defects were also found in independent Y-chromosome deletion mutants of S. latifolia. The data support the hypothesis that the evolution of complete gender dimorphism from hermaphroditism involved a major largely recessive male-sterility factor that created females, and the appearance of new, dominant genes on the Y chromosome, including both the well-documented gynoecium-suppressing factor, and two other Y specific genes promoting anther development. PMID:15982369

Zluvova, Jitka; Lengerova, Martina; Markova, Michaela; Hobza, Roman; Nicolas, Michael; Vyskot, Boris; Charlesworth, Deborah; Negrutiu, Ioan; Janousek, Bohuslav

367

Amino acids in the basic domain of Epstein-Barr virus ZEBRA protein play distinct roles in DNA binding, activation of early lytic gene expression, and promotion of viral DNA replication.  

PubMed

The ZEBRA protein of Epstein-Barr virus (EBV) drives the viral lytic cycle cascade. The capacity of ZEBRA to recognize specific DNA sequences resides in amino acids 178 to 194, a region in which 9 of 17 residues are either lysine or arginine. To define the basic domain residues essential for activity, a series of 46 single-amino-acid-substitution mutants were examined for their ability to bind ZIIIB DNA, a high-affinity ZEBRA binding site, and for their capacity to activate early and late EBV lytic cycle gene expression. DNA binding was obligatory for the protein to activate the lytic cascade. Nineteen mutants that failed to bind DNA were unable to disrupt latency. A single acidic replacement of a basic amino acid destroyed DNA binding and the biologic activity of the protein. Four mutants that bound weakly to DNA were defective at stimulating the expression of Rta, the essential first target of ZEBRA in lytic cycle activation. Four amino acids, R183, A185, C189, and R190, are likely to contact ZIIIB DNA specifically, since alanine or valine substitutions at these positions drastically weakened or eliminated DNA binding. Twenty-three mutants were proficient in binding to ZIIIB DNA. Some DNA binding-proficient mutants were refractory to supershift by BZ-1 monoclonal antibody (epitope amino acids 214 to 230), likely as the result of the increased solubility of the mutants. Mutants competent to bind DNA could be separated into four functional groups: the wild-type group (eight mutants), a group defective at activating Rta (five mutants, all with mutations at the S186 site), a group defective at activating EA-D (three mutants with the R179A, S186T, and K192A mutations), and a group specifically defective at activating late gene expression (seven mutants). Three late mutants, with a Y180A, Y180E, or K188A mutation, were defective at stimulating EBV DNA replication. This catalogue of point mutants reveals that basic domain amino acids play distinct functions in binding to DNA, in activating Rta, in stimulating early lytic gene expression, and in promoting viral DNA replication and viral late gene expression. These results are discussed in relationship to the recently solved crystal structure of ZEBRA bound to an AP-1 site. PMID:16940523

Heston, Lee; El-Guindy, Ayman; Countryman, Jill; Dela Cruz, Charles; Delecluse, Henri-Jacques; Miller, George

2006-09-01

368

Unraveling the Early Events of Amyloid-? Protein (A?) Aggregation: Techniques for the Determination of A? Aggregate Size  

PubMed Central

The aggregation of proteins into insoluble amyloid fibrils coincides with the onset of numerous diseases. An array of techniques is available to study the different stages of the amyloid aggregation process. Recently, emphasis has been placed upon the analysis of oligomeric amyloid species, which have been hypothesized to play a key role in disease progression. This paper reviews techniques utilized to study aggregation of the amyloid-? protein (A?) associated with Alzheimer’s disease. In particular, the review focuses on techniques that provide information about the size or quantity of oligomeric A? species formed during the early stages of aggregation, including native-PAGE, SDS-PAGE, Western blotting, capillary electrophoresis, mass spectrometry, fluorescence correlation spectroscopy, light scattering, size exclusion chromatography, centrifugation, enzyme-linked immunosorbent assay, and dot blotting.

Pryor, N. Elizabeth; Moss, Melissa A.; Hestekin, Christa N.

2012-01-01

369

Patch dynamics and the timing of colonization-abandonment events by male Kirtland's Warblers in an early succession habitat  

USGS Publications Warehouse

Habitat colonization and abandonment affects the distribution of a species in space and time, ultimately influencing the duration of time habitat is used and the total area of habitat occupied in any given year. Both aspects have important implications to long-term conservation planning. The importance of patch isolation and area to colonization-extinction events is well studied, but little information exists on how changing regional landscape structure and population dynamics influences the variability in the timing of patch colonization and abandonment events. We used 26 years of Kirtland's Warbler (Dendroica kirtlandii) population data taken during a habitat restoration program (1979-2004) across its historical breeding range to examine the influence of patch attributes and temporal large-scale processes, specifically the rate of habitat turnover and fraction of occupied patches, on the year-to-year timing of patch colonization and abandonment since patch origin. We found the timing of patch colonization and abandonment was influenced by patch and large-scale regional factors. In this system, larger patches were typically colonized earlier (i.e., at a younger age) and abandoned later than smaller patches. Isolated patches (i.e., patches farther from another occupied patch) were generally colonized later and abandoned earlier. Patch habitat type affected colonization and abandonment; colonization occurred at similar patch ages between plantation and wildfire areas (9 and 8.5 years, respectively), but plantations were abandoned at earlier ages (13.9 years) than wildfire areas (16.4 years) resulting in shorter use. As the fraction of occupied patches increased, patches were colonized and abandoned at earlier ages. Patches were abandoned at older ages when the influx of new habitat patches was at low and high rates. Our results provide empirical support for the temporal influence of patch dynamics (i.e., patch destruction, creation, and succession) on local colonization and extinction processes that help explain large-scale patterns of habitat occupancy. Results highlight the need for practitioners to consider the timing of habitat restoration as well as total amount and spatial arrangement of habitat to sustain populations.

Donner, D. M.; Ribic, C. A.; Probst, J. R.

2010-01-01

370

Early emotional processing deficits in depersonalization: an exploration with event-related potentials in an undergraduate sample.  

PubMed

Emotional stimuli may draw attention to such an extent that they hamper the processing of subsequent signals, a phenomenon termed emotion-induced blindness (EIB). As depersonalization is associated with self-reported attenuated emotional responses, the present study explored whether individuals scoring high on the Cambridge Depersonalization Scale (CDS; n=15) exhibit a diminished EIB effect relative to low CDS scoring individuals (n=15), and whether attentional processes reflected in event-related potentials (ERPs) are implicated in this effect. We obtained an EIB effect such that emotional distractors that preceded targets with a lag of 200ms reduced correct detection of targets. Although the magnitude of this effect was similar for high and low CDS participants, high CDS participants exhibited a significantly lower ERP amplitude at the frontal lead in the 200-300ms window than did low CDS individuals to targets that followed emotional versus neutral distractors. This latter effect was significantly related to the Alienation factor of the CDS. This pattern suggests that difficulties in the discrimination between emotional and neutral stimuli relate to the feeling of unreality in depersonalization. PMID:23149021

Quaedflieg, Conny W E M; Giesbrecht, Timo; Meijer, Ewout; Merckelbach, Harald; de Jong, Peter J; Thorsteinsson, Haraldur; Smeets, Tom; Simeon, Daphne

2012-11-10

371

E-cadherin inactivation in lobular carcinoma in situ of the breast: an early event in tumorigenesis.  

PubMed Central

In breast cancer, inactivating point mutations in the E-cadherin gene are frequently found in invasive lobular carcinoma (ILC) but never in invasive ductal carcinoma (IDC). Lobular carcinoma in situ (LCIS) adjacent to ILC has previously been shown to lack E-cadherin expression, but whether LCIS without adjacent invasive carcinoma also lacks E-cadherin expression and whether the gene mutations present in ILC are already present in LCIS is not known. We report here that E-cadherin expression is absent in six cases of LCIS and present in 150 cases of ductal carcinoma in situ (DCIS), both without an adjacent invasive component. Furthermore, using mutation analysis, we could demonstrate the presence of the same truncating mutations and loss of heterozygosity (LOH) of the wild-type E-cadherin in the LCIS component and in the adjacent ILC. Our results indicate that E-cadherin is a very early target gene in lobular breast carcinogenesis and plays a tumour-suppressive role, additional to the previously suggested invasion-suppressive role. Images Figure 1 Figure 2 Figure 3

Vos, C. B.; Cleton-Jansen, A. M.; Berx, G.; de Leeuw, W. J.; ter Haar, N. T.; van Roy, F.; Cornelisse, C. J.; Peterse, J. L.; van de Vijver, M. J.

1997-01-01

372

Event-related potential evidence for the early activation of literal meaning during comprehension of conventional lexical metaphors.  

PubMed

Among different types of metaphors, lexical metaphors are special in that they have been highly lexicalized and often suggested to be processed like non-metaphorical words. The present study examined two types of Chinese metaphorical words which are conceptualized through body parts. One has both a metaphorical meaning and a literal meaning actively in use, with the former dominant over the latter, referred to as the Met+Lit words. The other has only metaphorical meaning, referred to as Met-only words. In two experiments, lexical metaphor words were presented following a body-related picture and participants judged whether the picture and word were semantically related (Experiment 1) or made lexical decision on the word ignoring the picture (Experiment 2). The N400 ERP responses showed a clear semantic priming effect for the Met+Lit words compared with the non-ambiguous neutral words, with latencies comparable to that in Met-only words in both experiments. The results were interpreted to indicate that the literal meaning as a subordinate meaning was activated during the early comprehension of conventional lexical metaphors, supporting the notion of dual access to metaphorical meaning and literal meaning in metaphor processing. PMID:22561889

Lu, Aitao; Zhang, John X

2012-04-25

373

Endocytosis of beta1 integrins is an early event in migration promoted by the cell adhesion molecule L1.  

PubMed

Directional cell motility is a complex process requiring orchestration of signals from diverse cell adhesion receptors for proper organization of neuronal groups in the brain. The L1 cell adhesion molecule potentiates integrin-dependent migration of neuronal cells and stimulates integrin endocytosis but its mechanism of action is unclear. The hypothesis was investigated that L1 stimulates cell motility by modulating surface levels of integrins through intracellular trafficking using a model cell system. Antibody-induced clustering of L1, which mimics ligand binding, induced formation of cell surface complexes of L1 and beta1 integrins in L1-expressing HEK293 cells. L1 formed cell surface complexes with integrin beta1 and alpha3 subunits but not with integrin alpha1. Following cell surface clustering, beta1 integrins and L1 became rapidly internalized into Rab5+ early endosomes. Internalization of L1 and beta1 integrins was prevented by treatment with monodansyl cadaverine (MDC), an inhibitor of clathrin-dependent endocytosis, and by deletion of the AP2/clathrin binding motif (RSLE) from the L1 cytoplasmic domain. MDC treatment coordinately inhibited L1-potentiated haptotactic migration of HEK293 cells to fibronectin in Transwell assays. These results suggested that downregulation of adhesive complexes of L1 and beta1 integrin at the plasma membrane by clathrin-mediated endocytosis is a potential mechanism for enhancing cell motility. PMID:16330023

Panicker, Anitha K; Buhusi, Mona; Erickson, Ann; Maness, Patricia F

2005-12-05

374

The icy highlands scenario for early Mars: modeling of transient melting events and comparison with the geological evidence  

NASA Astrophysics Data System (ADS)

Explaining the geological evidence for fluvial erosion on Mars’ most ancient terrain remains a key challenge to planetary science despite decades of research. Previously, we performed 3D simulations of the global climate and water cycle in the Noachian under a thicker (0.1-2 bar) primitive atmosphere and faint young Sun (75% of present flux). These simulations revealed a possible mechanism for replenishing valley network sources: because of altitude-dependent adiabatic surface cooling, net transport of ice to the equatorial and southern Noachian highlands occurs via precipitation (snowfall) over long timescales. Here we investigate potential mechanisms for episodic melting of the highland ice deposits once they have formed. We present simulations of the melting and runoff rates induced by volcanic SO2/H2S emissions and the resulting formation of sulphate aerosols. Through modeling and basic theory, we evaluate recent suggestions that early Mars could have been warmed above freezing by water ice clouds or forced into a long-lived runaway greenhouse state by impacts. Finally, we discuss how large-scale variations in the VN distribution may inform us about the varying state of the atmosphere during the Noachian era.

Wordsworth, Robin; Kerber, L.; Forget, F.; Head, J. W.; Madeleine, J.; Millour, E.; Scanlon, K.

2013-10-01

375

Antioxidant and hepatoprotective potential of Aegle marmelos Correa. against CCl4-induced oxidative stress and early tumor events.  

PubMed

The antioxidant properties and inhibitory effect on early tumor promoter markers of A. marmelos (25 and 50 mg/Kg b. wt. orally) have been evaluated. Male Wistar rats were pre-treated for seven consecutive days with A. marmelos prior to CCl4 (1 mL Kg(- 1) body weight p. o., in corn oil [1:1 v/v]) treatment. Pre-treatment with A. marmelos suppressed lipid peroxidation (LPO), xanthine oxidase (XO) and release of serum toxicity marker enzymes viz, SGOT, LDH, SGPT dose-dependently and significantly (p < 0.001). Hepatic antioxidant status viz, reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), quinone reductase (QR), catalase (CAT) were concomitantly restored in A. marmelos-treated groups (p < 0.001). In addition, A. marmelos pretreatment also prevented the CCl4-enhanced ornithine decarboxylase (ODC) and hepatic DNA synthesis significantly (p < 0.001). In conclusion, carbon tetrachloride-induced liver toxicity was strikingly attenuated by A. marmelos treatment and the study gives some insight into the mechanisms involved in diminution of free radical generating toxicants and enhancement of the antioxidant armory, hence preventing further tissue damage, injury and hyperproliferation. Thus, these findings indicate that A. marmelos attenuates CCl4-mediated hepatic oxidative stress, toxicity, tumor promotion and subsequent cell proliferation response in Wistar rats. PMID:18830880

Khan, Tajdar Hussain; Sultana, Sarwat

2009-04-01

376

Defining the replication program through the chromatin landscape.  

PubMed

DNA replication is an essential cell cycle event required for the accurate and timely duplication of the chromosomes. It is essential that the genome is replicated accurately and completely within the confines of S-phase. Failure to completely copy the genome has the potential to result in catastrophic genomic instability. Replication initiates in a coordinated manner from multiple locations, termed origins of replication, distributed across each of the chromosomes. The selection of these origins of replication is a dynamic process responding to both developmental and tissue-specific signals. In this review, we explore the role of the local chromatin environment in regulating the DNA replication program at the level of origin selection and activation. Finally, there is increasing molecular evidence that the DNA replication program itself affects the chromatin landscape, suggesting that DNA replication is critical for both genetic and epigenetic inheritance. PMID:21417598

Ding, Queying; MacAlpine, David M

2011-04-01

377

An examination of backgrounds to early-run minimum-bias events in ATLAS at the LHC  

NASA Astrophysics Data System (ADS)

The initial stages of the Large Hadron Collider (LHC) run will be a source of critical information---about the ATLAS detector and about the physics of pp collisions at s = 14 TeV, including parton distribution evolution and the cross-section of sigmapp. The accelerator itself will be the source of some detector interest, as we have a first look at what have so far been speculations on the quality of the vacuum in the experimental insertion, and the cleanliness of the beam from the accelerator. The shakedown period, with its low beam squeeze, low luminosity, and undemanding trigger menus, will be very useful in addressing some of these questions, as it lacks the pileup and radiation levels that will arrive with higher luminosity---making it an important opportunity to investigate minimum-bias events in relative isolation. For the short lifetime of the Minimum Bias Trigger Scintillators (MBTS), which are expected to fail within a few months of running, they will aid in discriminating the minimum bias signal of inelastic non-single-diffractive pp collisions. Using single- or double-coincidence signatures, the MBTS system and other trigger and analysis strategies attempt to avoid triggering on otherwise empty bunch crossings and eliminate the effects of beam-gas collisions and beam-halo effects which would lead these spurious triggers and reduce the general minimum-bias trigger efficiency. An examination of the effects of beam halo and beam-gas interactions on the minimum-bias trigger response is made. The signatures of the beam halo and beam gas are examined from the standard ATLAS tracking reconstruction.

Stradling, Alden Reid

378

Di-Cysteine S,S-Tetrazine: A Potential Ultra-fast Photochemical Trigger to Explore the Early Events of Peptide/Protein Folding  

PubMed Central

The tetrazine chromophore holds promise as an effective photochemical trigger to achieve structural release, directed at the determination of peptide/protein motions that occur early in the folding processes. The photochemistry of 3,6-di-cysteine-S,S-tetrazines was examined by femtosecond IR transient absorption spectroscopy. Excitation of the tetrazine chromophore by visible and near UV light in the end yields chemically inert, structurally unobtrusive photoproducts that are not expected to interfere with the conformational dynamics of peptides and proteins. Dicysteine S,S-tetrazine is suggested to undergo photocleavage via a photochemical pathway different than the parent molecule s-tetrazine, based on kinetic measurements that reveal a stepwise reaction pathway of photofragmentation, whereby the initial ring cleavage event occurs prior to the formation of the SCN groups.

Tucker, Matthew J.; Abdo, Mohannad; Courter, Joel R.; Chen, Jianxin; Smith, Amos B.; Hochstrasser, Robin M.

2012-01-01

379

Evidence for Proterozoic and late Cretaceous-early Tertiary ore-forming events in the Coeur d'Alene district, Idaho and Montana  

USGS Publications Warehouse

New 40Ar/39Ar age spectra on sericite and lead isotope data on tetrahedrite, siderite, galena, bournonite, and stibnite, together with previously published isotopic, geochemical, and geologic studies provide evidence for two major vein-forming events in the Coeur d'Alene district and surrounding area of the Belt basin. The data suggest that the zinc- and lead-rich veins (e.g., Bunker Hill and Star-Morning mines) formed in the Proterozoic (1.0 Ga), whereas the silver-rich veins (e.g., Silver belt mines), antimony veins (e.g., US Antimony mine), and gold-bearing quartz veins (Murry subdistrict) formed in Late Cretaceous to early Tertiary time.

Leach, D. L.; Hofstra, A. H.; Church, S. E.; Snee, L. W.; Vaughn, R. B.; Zartman, R. E.

1998-01-01

380

Modulation of key regulators of mitosis linked to chromosomal instability is an early event in ochratoxin A carcinogenicity.  

PubMed

Ochratoxin A (OTA) is a potent renal carcinogen, but little is known regarding the mechanism of OTA carcinogenicity. Early histopathological alterations induced by OTA in rat kidney include single cell death, stimulation of cell proliferation and prominent karyomegaly indicative of blocked nuclear division during mitosis. Based on these observations, it has been suggested that disruption of mitosis by OTA may be the principal cause of cell death and subsequent trigger for cell proliferation to compensate for cell loss. To gain further insight into the molecular mechanism of OTA toxicity, we used targeted quantitative real-time polymerase chain reaction arrays to investigate the expression of genes involved in cell cycle control and mitosis in kidneys of male F344 rats treated with 0, 21, 70 and 210 microg/kg body wt OTA for up to 90 days. Treatment with OTA resulted in overexpression of key regulators of mitosis, including the mitotic protein kinases Polo-like kinase 1, Aurora B and cyclin-dependent kinase 1 (Cdk1Cdc2), several cyclins and cyclin-dependent kinase inhibitors, topoisomerase II and survivin. Immunohistochemical analysis confirmed upregulation of Cdk1, p21(WAF1/CIP1), topoisomerase II and survivin in S3 proximal tubule cells, from which OTA-induced tumors in rats arise, and demonstrated increased phosphorylation of histone H3, a target of Aurora B. Importantly, many of the genes found to be deregulated in response to OTA have been linked to chromosomal instability and malignant transformation, supporting the hypothesis that aberrant mitosis, resulting in blocked or asymmetric cell division, accompanied by an increased risk o