|
|
|
2010-03-01
Helix 38 (H38) of the large ribosomal subunit, with a length of 110 Å, reaches the small subunit through intersubunit bridge B1a. Previous cryo-EM studies revealed that the tip of H38 moves...Full Text Available
2010-03-01
Full Text Available.Helix 38 (H38) of the large ribosomal subunit, with a length of 110 Å, reaches the small subunit through intersubunit bridge B1a. Previous cryo-EM studies revealed that the tip of H38 moves by more than 10 Å from the non-ratcheted to the ratcheted state of the ribosome while mutational studies implicated a key role of flexible H38 in attenuation of translocation and in dynamical signaling between ribosomal functional centers. We investigate a region including the elbow-shaped kink-turn (Kt-38) in the Haloarcula marismortui archaeal ribosome, and equivalently positioned elbows in three eubacterial species, located at the H38 base. We performed explicit solvent molecular dynamics simulations on the H38 elbows in all four species. They are formed by at first sight unrelated sequences resulting in diverse base interactions but built with the same overall topology, as shown by X-ray crystallography. The elbows display similar fluctuations and intrinsic flexibilities in simulations indicating that the eubacterial H38 elbows are structural and dynamical analogs of archaeal Kt-38. We suggest that this structural element plays a pivotal role in the large motions of H38 and may act as fulcrum for the abovementioned tip motion. The directional flexibility inferred from simulations correlates well with the cryo-EM results.
2010-01-01
Helix 38 (H38) of the large ribosomal subunit, with a length of 110 A, reaches the small subunit through intersubunit bridge B1a. Previous cryo-EM studies revealed that the tip of H38 moves by more than 10 A from the non-ratcheted to the ratcheted state of the ribosome while mutational studies implicated a key role of flexible H38 in attenuation of translocation and in dynamical signaling between ribosomal functional centers. We investigate a region including the elbow-shaped kink-turn (Kt-38) in the Haloarcula marismortui archaeal ribosome, and equivalently positioned elbows in three eubacterial species, located at the H38 base. We performed explicit solvent molecular dynamics simulations on the H38 elbows in all four species. They are formed by at first sight unrelated sequences resultin...
axion: Axion - Java Database - News
The Axion news feed is on hiatus, yet Axion is still being actively developed. ... Better late than never, it's the Axion database project's October 2003 ...
A small, fast, SQL and JDBC compliant relational database engine written in and for the Java programming language. [Open source, BSD License]
arXiv:hep-ph/9506229 v1 02 Jun 95
File Format: PDF/Adobe Acrobat - View as HTMLThe axion is the quantum of oscillation of the ? parameter of QCD. It is a particle ... ticle physics is the PQ mechanism with an ?invisible? axion. ...
VEZF1 Elements Mediate Protection from DNA Methylation
2010-01-01
There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier...Full Text Available
VEZF1 Elements Mediate Protection from DNA Methylation
2010-01-01
Full Text Available.There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm β-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin state.
Introduction ............................................................................................................................... 26 History of Media-Effects Research ............................................................................................. 27 Levels of Theory and Analysis .................................................................................................... 28 Summary .................................................................................................................................... 44 References ................................................................................................................................... 45 Part 2?Tobacco Marketing...................................................................................51 Chapter 3?Key Principles of Tobacco Promotion and Rationales for Regulation .....................53 Introduction ............................................................................................................................... 54 Key Principles of Tobacco Advertising and Promotion.
EDRN Breast and Gynecologic Cancers Collaborative Group Members Jeffrey Marks, Ph.D., Chair Duke University Medical Center Daniel Cramer, M.D., Sc.D., Co-chair Brigham and Women?s Hospital Karen Anderson, M.D., Ph.D. Harvard Institute of Proteomics Paul Cairns, Ph.D. Fox Chase Cancer Center David Chia, Ph.D. University of California, Los Angeles Miral Dizdar, Ph.D. National Institute of Standards and Technology Richard Drake, Ph.D. Eastern Virginia Medical School Paul Engstrom, M.D. Fox Chase Cancer Center Laura J.
1997-12-31
Full text: Pigments are minerals that provide the colour to paints and the pigments most commonly used by Aboriginal people are derived from red and yellow ochre and white minerals for example, gypsum and kaolin. During the early 1980s, the opportunity arose to collect pigments from many sources in South Australia. The sources included samples from known Aboriginal quarries and other outcrops. Pinhead-size samples of paint were collected from figures in some of the rock painting sites in the Olary District. These samples were analysed using Emission Spectrography with the aim of determining the nature of the pigments that is their constituent elements, and to investigate the possibility of finger-printing the sources of the pigments used by Aboriginal people. The ability of being able to source pigments found on the decorated surface of artefacts; pieces of ochre found in archaeological deposits or painted figures in a rock painting is important for understanding the trading and exchange network known to criss-cross Australia in the past. Facilities for Emission Spectrographic analyses were readily available and the capability to analyse (for twenty six elements) samples in milligram proportions suggested its use for the determination of the composition of material from unlimited sources and the compilation of a data-base detailing the results of the analyses in a form suitable for comparison. Examination of this database could then lead to further investigations with narrower and more specific aims. The results of the spectrographic analyses for red ochre from eighteen sources and yellow ochres from eight sources were tabulated as: strongly present >10%; present 1-10%; strong trace 0.1-1% ; trace 0.01-0.1%; faint trace <0.01%. Major elements, for example iron, aluminium, and silica showed in the Strongly Present and Present categories, while Trace and Faint Trace elements were variable. The results of the analyses of seventeen samples of red pigment and five samples of yellow pigment from five painting sites were tabulated as above. There is a possibility that trace elements in the samples from the painting sites may indicate their sources.
1994-09-01
The desmoplastic small round cell tumor (DSRCT) is a recently recognized aggressive type of primitive sarcoma occurring mainly in young males. Previous cytogenetic reports have identified a recurrent translocation in DSRCT, t(11;22)(p13;q12). We have recently shown that this translocation represents a rearrangement between the EWS and WT1 genes, normally located at 22q12 and 11p13, respectively, generating a fusion gene which encodes a chimeric RNA resulting from an in-frame junction of EWS exon 7 to WT1 exon 8. Thus, this chimeric RNA encodes a putative protein in which the RNA-binding domain of EWS is replaced by the three C-terminal zinc fingers of the WT1 DNA-binding domain. We have now assessed the molecular detection of this rearrangement in a panel of 7 DSRCTs and 38 other small round cell tumors, and we have examined the WT1 portion of the chimeric RNA for the presence of the previously reported splice variants of the zinc-finger DNA-binding domain of WT1. Reverse transcriptase PCR (RT-PCR) revealed a single identical product in 4/5 cases tested, including a case in which a t(11;22)(p13;q12) by karyotyping. By Southern blotting, rearrangement of both EWS and WT1 was detectable in 3/6 cases, EWS alone in 1/6, and neither in 2/6. Histologically, the sole sample negative by both methods contained very scanty viable tumor. EWS-WT1 RT-PCR was negative in 16 Wilms` tumors, 12 rhadomyosarcomas, and 10 Ewing`s sarcomas. RT-PCR with splice site-specific primers showed the chimeric EWS-WT1 transcripts to include both splice variants of the zinc-finger domain of WT1, {open_quotes}+KTS{close_quotes} and {open_quotes}-KTS{close_quotes}. The t(11;22)(p13;q12) of DSRCT is most reliably detected by RT-PCR, and results in a specific and structurally highly consistent EWS-WT1 chimeric transcript which may interact with the normal targets of both splice variants of WT1.
Most mitochondrial mRNAs in trypanosomes undergo uridine insertion/deletion editing that is catalyzed by ∼20S editosomes. The editosome component KREPA3 is essential for editosome structural...Full Text Available
Full Text Available.Most mitochondrial mRNAs in trypanosomes undergo uridine insertion/deletion editing that is catalyzed by ∼20S editosomes. The editosome component KREPA3 is essential for editosome structural integrity and its two zinc finger (ZF) motifs are essential for editing in vivo but not in vitro. KREPA3 function was further explored by examining the consequence of mutation of its N- and C- terminal ZFs (ZF1 and ZF2, respectively). Exclusively expressed myc-tagged KREPA3 with ZF2 mutation resulted in lower KREPA3 abundance and a relative increase in KREPA2 and KREL1 proteins. Detailed analysis of edited RNA products revealed the accumulation of partially edited mRNAs with less insertion editing compared to the partially edited mRNAs found in the cells with wild type KREPA3 expression. Mutation of ZF1 in TAP-tagged KREPA3 also resulted in accumulation of partially edited mRNAs that were shorter and only edited in the 3′-terminal editing region. Mutation of both ZFs essentially eliminated partially edited mRNA. The mutations did not affect gRNA abundance. These data indicate that both ZFs are essential for the progression of editing and perhaps its accuracy, which suggests that KREPA3 plays roles in the editing process via its ZFs interaction with editosome proteins and/or RNA substrates.
2005-01-01
Maturation of MC3T3-E1 osteoblast cells in vitro can be divided into three major stages, namely, proliferation, differentiation, and mineralization. Our microarray analysis identified genes differentially expressed between proliferating and differentiated MC3T3-E1 osteoblastic cells. Immunohistochemical analyses of RNF11 protein encoded by one of the differentially expressed genes revealed it as highly expressed in osteoblasts of multiple skeletal elements during embryonic bone formation in mice. In contrast, cartilage, undifferentiated mesenchymal tissue and osteocytes did not express detectable amounts of the RNF11 protein. The RNF11 mRNA was found to be abundant during the proliferation stage of MC3T3-E1 osteoblast development with a short second peak of expression during the mineralization phase. This pattern of expression is similar to that of the ... >>
The Nation's Investment in Cancer Research
SPOTLIGHTS ON RESEARCH Exciting progress has been made in harnessing the immune system to prevent and treat cancer, in developing new detection tools, and in using new technologies to improve understanding of specific cancers.
2005-01-01
During the translocation of tRNAs and mRNA relative to the ribosome, the B1a, B1b and B1c bridges undergo the most extensive conformational changes among the bridges between the large and the small ribosomal subunits. The B1a bridge, also called the "A-site finger" (ASF), is formed by the 23S rRNA helix 38, which is located right above the ribosomal A-site. Here, we deleted part of the ASF so that the B1a intersubunit bridge could not be formed (DB1a). The mutation led to a less efficient subunit association. A number of functional activities of the DB1a ribosomes, such as tRNA binding to the P and A-sites, translocation and EF-G-related GTPase reaction were preserved. A moderate decrease in EF-G-related GTPase stimulation by the P-site occupation by deacylated tRNA was observed. This sugg...
2000-12-01
Molecular dynamics simulations of the p21ras-p120GAP-GTP complex suggest that the local structure around the catalytic region can be different from that revealed by the x-ray crystal structure. We find that the carbonyl oxygen on the backbone of the arginine finger supplied in trans by p120GAP (Arg789) interacts with a water molecule in the active site that is forming a bridge between the NH2 group of the Gln61 and the g-phosphate of GTP. Thus Arg789 may play a dual role in generating the nucleophile as well as stabilizing the transition state for P-O bond cleavage.
Full Text Available.BackgroundPlants respond to abiotic stress through complex regulation of transcription, including both transcriptional activation and repression. Dehydration-responsive-element binding protein (DREB)-type transcription factors are well known to play important roles in adaptation to abiotic stress. The mechanisms by which DREB-type transcription factors activate stress-induced gene expression have been relatively well studied. However, little is known about how DREB-type transcriptional repressors modulate plant stress responses. In this study, we report the functional analysis of RAP2.1, a DREB-type transcriptional repressor.ResultsRAP2.1 possesses an APETALA2 (AP2) domain that binds to dehydration-responsive elements (DREs) and an ERF-associated amphiphilic repression (EAR) motif, as the repression domain located at the C-terminus of the protein. Expression of RAP2.1 is strongly induced by drought and cold stress via an ABA-independent pathway. Arabidopsis plants overexpressing RAP2.1 show enhanced sensitivity to cold and drought stresses, while rap2.1-1 and rap2.1-2 T-DNA insertion alleles result in reduced sensitivity to these stresses. The reduced stress sensitivity of the plant containing the rap2.1 allele can be genetically complemented by the expression of RAP2.1, but not by the expression of EAR-motif-mutated RAP2.1. Furthermore, chromatin immunoprecipitation (ChIP) analysis has identified Responsive to desiccation/Cold-regulated (RD/COR) genes as downstream targets of RAP2.1 in vivo. Stress-induced expression of the RD/COR genes is repressed by overexpression of RAP2.1 and is increased in plants expressing the rap2.1 allele. In addition, RAP2.1 can negatively regulate its own expression by binding to DREs present in its own promoter. Our data suggest that RAP2.1 acts as a negative transcriptional regulator in defence responses to cold and drought stress in Arabidopsis.ConclusionsA hypothetical model for the role of RAP2.1 in modulating plant responses to cold and drought is proposed in this study. It appears that RAP2.1 acts as a negative "subregulon" of DREB-type activators and is involved in the precise regulation of expression of stress-related genes, acting to keep stress responses under tight control.
BackgroundPlants respond to abiotic stress through complex regulation of transcription, including both transcriptional activation and repression. Dehydration-responsive-element binding...Full Text Available
Texas site selection and licensing status
1989-11-01
Texas has identified a potential site in Hudspeth County in far West Texas near the town of Fort Hancock. Over the past year the Texas Low-Level Radioactive Waste Disposal Authority has been conducting detailed geology, hydrology, meteorology, soils, and flora and fauna evaluations. An authorization by the Board of Directors of the Authority to proceed with a license application, assuming that the detailed evaluation indicates that the site is suitable, is expected by September. A prototype license has been prepared in anticipation of the order to proceed with licensing, and the formal license application is expected to be submitted to the Texas Department of Health-Bureau of Radiation Control in December, meeting the license application milestone. Although site selection processes in all siting areas across the country have experienced organized opposition, El Paso County has funded a particularly well-organized, well-financed program to legally and technically stop consideration of the Fort Hancock site prior to the licensing process. Many procedural, regulatory, and technical issues have been raised which have required responses from the Authority in order to proceed with licensing. This has provided a unique perspective of what to expect from well-organized opposition at the licensing stage. This paper presents an update on the Texas siting activity with detailed information on the site evaluation and license application. Experience of dealing with issues raised by opposition relating to NRC guidelines and rules is also discussed.
Sp1/Sp3 and the myeloid zinc finger gene MZF1 regulate the human N-cadherin promoter in osteoblasts
2005-01-01
To determine the molecular mechanisms by which N-cadherin transcription is regulated, we cloned and sequenced a 3681-bp of the 5'-flanking region of the human N-cadherin gene. Deletion analysis of the proximal region identified a minimal 318-bp region with strong promoter activity in human osteoblasts. The cryptic promoter is characterized by high GC content and a GA-rich binding core that may bind zing finger transcription factors. Electrophoretic mobility shift assays (EMSA), competition and supershift EMSA revealed that an Sp1/Sp3 binding site acts as a basal regulatory element of the promoter in osteoblasts. Incubation of osteoblast nuclear extracts with -163/-131 wild-type probe containing the GA-rich binding core revealed another specific complex, which was not formed with a -163/-131 probe mutated in the GA repeat. EMSA identified the nuclear factor involved ... >>
Slimhole drilling for geothermal exploration
1994-07-01
Sandia National Laboratories manages the US Department of Energy program for slimhole drilling. The principal objective of this program is to expand proven geothermal reserves through increased exploration, made possible by lower-cost slimhole drilling. For this to be a valid exploration method, however, it is necessary to demonstrate that slimholes yield enough data to evaluate a geothermal reservoir, and that is the focus of Sandia`s current research. Sandia negotiated an agreement with Far West Capital, which operates the Steamboat Hills geothermal field, to drill and test an exploratory slimhole on their lease. The principal objectives for the slimhole were development of slimhole testing methods, comparison of slimhole data with that from adjacent production-size wells, and definition of possible higher-temperature production zones lying deeper than the existing wells.
Site selection and licensing issues: Southwest Compact low-level radioactive waste disposal site
1989-11-01
The low-level radioactive waste disposal site in California is being selected through a three-phase program. Phase 1 is a systematic statewide, regional, and local screening study. This program was conducted during 1986 and 1987, and culminated in the selection of three candidate sites fur further study. The candidate sites are identified as the Panamint, Silurian, and Ward Valley sites. Phase 2 comprises site characterization and environmental and socio-economic impact study activities at the three candidate sites. Based upon the site characterization studies, the candidate sites are ranked according to the desirability and conformance with regulatory requirements. Phase 3 comprises preparation of a license application for the selected candidate site. The license application will include a detailed characterization of the site, detailed design and operations plans for the proposed facility, and assessments of potential impacts of the site upon the environment and the local communities. Five types of siting criteria were developed to govern the site selection process. These types are: technical suitability exclusionary criteria, high-avoidance criteria beyond technical suitability requirements, discretionary criteria, public acceptance, and schedule requirements of the LLWR Policy Act Amendments. This paper discusses the application of the hydrological and geotechnical criteria during the siting and licensing studies in California. These criteria address site location and performance, and the degree to which present and future site behavior can be predicted. Primary regulatory requirements governing the suitability of a site are that the site must be hydrologically and geologically simple enough for the confident prediction of future behavior, and that the site must be stable enough that frequent or intensive maintenance of the closed site will not be required. This paper addresses the methods to measure site suitability at each stage of the process, methods to gather data to address the criteria, and tradeoffs necessary to locate sites which conform to sometimes inconsistent requirements.
Sequence Ready Characterization of the Pericentromeric Region of 19p12
2006-08-31
Current mapping and sequencing strategies have been inadequate within the proximal portion of 19p12 due, in part, to the presence of a recently expanded ZNF (zinc-finger) gene family and the presence of large (25-50 kb) inverted beta-satellite repeat structures which bracket this tandemly duplicated gene family. The virtual of absence of classically defined “unique” sequence within the region has hampered efforts to identify and characterize a suitable minimal tiling path of clones which can be used as templates required for finished sequencing of the region. The goal of this proposal is to develop and implement a novel sequence-anchor strategy to generate a contiguous BAC map of the most proximal portion of chromosome 19p12 for the purpose of complete sequence characterization. The target region will be an estimated 4.5 Mb of DNA extending from STS marker D19S450 (the beginning of the ZNF gene cluster) to the centromeric (alpha-satellite) junction of 19p11. The approach will entail 1) pre-selection of 19p12 BAC and cosmid clones (NIH approved library) utilizing both 19p12 -unique and 19p12-SPECIFIC repeat probes (Eichler et al., 1998); 2) the generation of a BAC/cosmid end-sequence map across the region with a density of one marker every 8kb; 3) the development of a second-generation of STS (sequence tagged sites) which will be used to identify and verify clonal overlap at the level of the sequence; 4) incorporation of these sequence-anchored overlapping clones into existing cosmid/BAC restriction maps developed at Livermore National Laboratory; and 5) validation of the organization of this region utilizing high-resolution FISH techniques (extended chromatin analysis) on monochromosomal 19 somatic cell hybrids and parental cell lines of source material. The data generated will be used in the selection of the most parsimonious tiling path of BAC clones to be sequenced as part of the JGI effort on chromosome 19 and should serve as a model for the sequence characterization of other difficult regions of the human genome
Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage
Human immunodeficiency virus type 1 (HIV-1) has been shown to replicate productively in cells of the monocyte-macrophage lineage, although replication occurs to a lesser extent than in infected T cells....Full Text Available
Regulation of HIV-1 transcription in cells of the monocyte-macrophage lineage
Full Text Available.Human immunodeficiency virus type 1 (HIV-1) has been shown to replicate productively in cells of the monocyte-macrophage lineage, although replication occurs to a lesser extent than in infected T cells. As cells of the monocyte-macrophage lineage become differentiated and activated and subsequently travel to a variety of end organs, they become a source of infectious virus and secreted viral proteins and cellular products that likely initiate pathological consequences in a number of organ systems. During this process, alterations in a number of signaling pathways, including the level and functional properties of many cellular transcription factors, alter the course of HIV-1 long terminal repeat (LTR)-directed gene expression. This process ultimately results in events that contribute to the pathogenesis of HIV-1 infection. First, increased transcription leads to the upregulation of infectious virus production, and the increased production of viral proteins (gp120, Tat, Nef, and Vpr), which have additional activities as extracellular proteins. Increased viral production and the presence of toxic proteins lead to enhanced deregulation of cellular functions increasing the production of toxic cellular proteins and metabolites and the resulting organ-specific pathologic consequences such as neuroAIDS. This article reviews the structural and functional features of the cis-acting elements upstream and downstream of the transcriptional start site in the retroviral LTR. It also includes a discussion of the regulation of the retroviral LTR in the monocyte-macrophage lineage during virus infection of the bone marrow, the peripheral blood, the lymphoid tissues, and end organs such as the brain. The impact of genetic variation on LTR-directed transcription during the course of retrovirus disease is also reviewed.
Recombinant protein expression by targeting pre-selected chromosomal loci
Full Text Available.BackgroundRecombinant protein expression in mammalian cells is mostly achieved by stable integration of transgenes into the chromosomal DNA of established cell lines. The chromosomal surroundings have strong influences on the expression of transgenes. The exploitation of defined loci by targeting expression constructs with different regulatory elements is an approach to design high level expression systems. Further, this allows to evaluate the impact of chromosomal surroundings on distinct vector constructs.ResultsWe explored antibody expression upon targeting diverse expression constructs into previously tagged loci in CHO-K1 and HEK293 cells that exhibit high reporter gene expression. These loci were selected by random transfer of reporter cassettes and subsequent screening. Both, retroviral infection and plasmid transfection with eGFP or antibody expression cassettes were employed for tagging. The tagged cell clones were screened for expression and single copy integration. Cell clones producing > 20 pg/cell in 24 hours could be identified. Selected integration sites that had been flanked with heterologous recombinase target sites (FRTs) were targeted by Flp recombinase mediated cassette exchange (RMCE). The results give proof of principle for consistent protein expression upon RMCE. Upon targeting antibody expression cassettes 90-100% of all resulting cell clones showed correct integration. Antibody production was found to be highly consistent within the individual cell clones as expected from their isogenic nature. However, the nature and orientation of expression control elements revealed to be critical. The impact of different promoters was examined with the tag-and-targeting approach. For each of the chosen promoters high expression sites were identified. However, each site supported the chosen promoters to a different extent, indicating that the strength of a particular promoter is dominantly defined by its chromosomal context.ConclusionRMCE provides a powerful method to specifically design vectors for optimized gene expression with high accuracy. Upon considering the specific requirements of chromosomal sites this method provides a unique tool to exploit such sites for predictable expression of biotechnologically relevant proteins such as antibodies.
Recombinant protein expression by targeting pre-selected chromosomal loci
BackgroundRecombinant protein expression in mammalian cells is mostly achieved by stable integration of transgenes into the chromosomal DNA of established cell lines. The chromosomal...Full Text Available
Rapid evolution of a recently retroposed transcription factor YY2 in mammalian genomes
2005-11-11
YY2 was originally identified due to its unusual similarity to the evolutionarily well conserved, zinc-finger gene YY1. In this study, we have determined the evolutionary origin and conservation of YY2 using comparative genomic approaches. Our results indicate that YY2 is a retroposed copy of YY1 that has been inserted into another gene locus named Mbtps2 (membrane-bound transcription factor protease site 2). This retroposition is estimated to have occurred after the divergence of placental mammals from other vertebrates based on the detection of YY2 only in the placental mammals. The N-terminal and C-terminal regions of YY2 have evolved under different selection pressures. The N-terminal region has evolved at a very fast pace with very limited functional constraints whereas the DNA-binding, C-terminal region still maintains very similar sequence structure as YY1 and is also well conserved among placental mammals. In situ hybridizations using different adult mouse tissues indicate that mouse YY2 is expressed at relatively low levels in Purkinje and granular cells of cerebellum, and neuronal cells of cerebrum, but at very high levels in testis. The expression levels of YY2 is much lower than YY1, but the overall spatial expression patterns are similar to those of Mbtps2, suggesting a possible shared transcriptional control between YY2 and Mbtps2. Taken together, the formation and evolution of YY2 represent a very unusual case where a transcription factor was first retroposed into another gene locus encoding a protease and survived with different selection schemes and expression patterns.
2010-02-01
Full Text Available.AbstractIn this study we examined the potential for PAR2 and TNFα to synergise at the level of MAP kinase signalling in PAR2 expressing NCTC2544 cells. However, to our surprise we found that activation of PAR2 by trypsin or the specific activating peptide SLIGKV-OH strongly inhibited both the phosphorylation and activity of JNK. In contrast neither p38 MAP kinase nor ERK activation was affected although TNFα stimulated IκBα loss was partially reversed. The inhibitory effect was not observed in parental cells nor in cells expressing PAR4, however inhibition was reversed by pre-incubation with the novel PAR2 antagonist K14585, suggesting that the effect is specific for PAR2 activation. SLIGKV-OH was found to be more potent in inhibiting TNFα-induced JNK activation than in stimulating JNK alone, suggesting agonist-directed signalling. The PKC activator PMA, also mimicked the inhibitory effect of SLIGKV-OH, and the effects of both agents were reversed by pre-treatment with the PKC inhibitor, GF109203X. Furthermore, incubation with the novel Gq/11 inhibitor YM25480 also reversed PAR2 mediated inhibition. Activation of PAR2 was found to disrupt TNFR1 binding to RIP and TRADD and this was reversed by both GF109203X and YM25480. A similar mode of inhibition observed in HUVECs through PAR2 or P2Y2 receptors demonstrates the potential of a novel paradigm for GPCRs linked to Gq/11, in mediating inhibition of TNFα-stimulated JNK activation. This has important implications in assessing the role of GPCRs in inflammation and other conditions.
2010-02-01
AbstractIn this study we examined the potential for PAR2 and TNFα to synergise at the level of MAP kinase signalling in PAR2 expressing NCTC2544 cells. However,...Full Text Available
2001-08-01
The Area 12 Fleet Operations Steam Cleaning site is located in the southeast portion of the Area 12 Camp at the Nevada Test Site (Figure 1). This site is identified in the Federal Facility Agreement and Consent Order (FFACO, 1996) as Corrective Action Site (CAS) 12-19-01 and is the only CAS assigned to Corrective Action Unit (CAU) 339. Post-closure sampling and inspection of the site were completed on March 23, 2001. Because of questionable representativeness and precision of the results, the site was resampled on June 12, 2001. Post-closure monitoring activities were scheduled biennially (every two years) in the Post-Closure Monitoring Plan provided in the December 1997 Closure Report for CAU 339: Area 12 Fleet Operations Steam Cleaning Discharge Area, Nevada Test Site (U.S. Department of Energy, Nevada Operations Office [DOE/NV], 1997). If after six years the rate of degradation appears to be so slow that the greatest concentration of total petroleum hydrocarbons (TPH) present at the site would not decay within 30 years of the site closure, the site will be reevaluated with consideration to enriching the impacted soil at the site to enhance the degradation process. A baseline for the site was established by sampling in 1997. Based on the recommendations from the 1999 post-closure monitoring report, samples were collected in 2000, earlier than originally proposed, because the 1999 sample results did not provide the expected decrease in TPH concentrations at the site. Sampling results from 2000 revealed favorable conditions for natural degradation at the CAU 339 site, but because of differing sample methods and heterogeneity of the soil, the data results from 2000 were not directly correlated with previous results. Post-closure monitoring activities for 2001 consisted of the following: Soil sample collection from three undisturbed plots (Plots A, B, and C, Figure 2); Sample analysis for TPH as oil and bio-characterization parameters (Comparative Enumeration Assay [CEA] and Standard Nutrient Panel [SNP]); Site inspection to evaluate the condition of the fencing and signs; and Preparation and submittal of the Post-Closure Monitoring Report.
Full Text Available.BackgroundTristetraprolin (TTP) is the prototype member of a family of CCCH tandem zinc finger proteins and is considered to be an anti-inflammatory protein in mammals. TTP plays a critical role in the decay of tumor necrosis factor alpha (TNF) mRNA, among others, by binding AU-rich RNA elements in the 3′-untranslated regions of this transcript and promoting its deadenylation and degradation.Methodology/Principal FindingsWe used yeast two-hybrid analysis to identify potential protein binding partners for human TTP (hTTP). Various regions of hTTP recovered 31 proteins that fell into 12 categories based on sequence similarities. Among these, the interactions between hTTP and CIN85, cytoplasmic poly (A) binding protein (PABP), nucleolin and heat shock protein 70 were confirmed by co-immunoprecipitation experiments. CIN85 and hTTP co-localized in the cytoplasm of cells as determined by confocal microscopy. CIN85 contains three SH3 domains that specifically bind a unique proline-arginine motif (PXXXPR) found in several CIN85 effectors. We found that the SH3 domains of CIN85 bound to a PXXXPR motif located near the C-terminus of hTTP. Co-expression of CIN85 with hTTP resulted in the increased phosphorylation of hTTP at serine residues in positions 66 and 93, possibly due in part to the demonstrated association of mitogen-activated protein kinase kinase kinase 4 (MEKK4) to both proteins. The presence of CIN85 did not appear to alter hTTP's binding to RNA probes or its stimulated breakdown of TNF mRNA.Conclusions/SignificanceThese studies describe interactions between hTTP and nucleolin, cytoplasmic PABP, heat shock protein 70 and CIN85; these interactions were initially discovered by two-hybrid analysis, and confirmed by co-immunoprecipitation. We found that CIN85 binding to a C-terminal motif within hTTP led to the increased phosphorylation of hTTP, possibly through enhanced association with MEKK4. The functional consequences to each of the members of this putative complex remain to be determined.
BackgroundTristetraprolin (TTP) is the prototype member of a family of CCCH tandem zinc finger proteins and is considered to be an anti-inflammatory protein in mammals. TTP plays...Full Text Available
Phase diagram of the disordered Bose-Hubbard model
2009-01-01
We establish the phase diagram of the disordered three-dimensional Bose-Hubbard model at unity filling which has been controversial for many years. The theorem of inclusions, proven by Pollet et al. [Phys. Rev. Lett. 103, 140402 (2009)] states that the Bose-glass phase always intervenes between the Mott insulating and superfluid phases. Here, we note that assumptions on which the theorem is based exclude phase transitions between gapped (Mott insulator) and gapless phases (Bose glass). The apparent paradox is resolved through a unique mechanism: such transitions have to be of the Griffiths type when the vanishing of the gap at the critical point is due to a zero concentration of rare regions where extreme fluctuations of disorder mimic a regular gapless system. An exactly solvable random transverse field Ising model in one dimension is used to illustrate the point. A highly ... >>
Phase III Drilling Operations at the Long Valley Exploratory Well (LVF 51-20)
1999-06-01
During July-September, 1998, a jointly funded drilling operation deepened the Long Valley Exploratory Well from 7178 feet to 9832 feet. This was the third major drilling phase of a project that began in 1989, but had sporadic progress because of discontinuities in tiding. Support for Phase III came from the California Energy Commission (CEC), the International Continental Drilling Program (ICDP), the US Geological Survey (USGS), and DOE. Each of these agencies had a somewhat different agenda: the CEC wants to evaluate the energy potential (specifically energy extraction from magma) of Long Valley Caldera; the ICDP is studying the evolution and other characteristics of young, silicic calderas; the USGS will use this hole as an observatory in their Volcano Hazards program; and the DOE, through Sandia, has an opportunity to test new geothermal tools and techniques in a realistic field environment. This report gives a description of the equipment used in drilling and testing; a narrative of the drilling operations; compiled daily drilling reports; cost information on the project; and a brief summary of engineering results related to equipment performance and energy potential. Detailed description of the scientific results will appear in publications by the USGS and other researchers.
Penetration of liquid fingers into superheated fracturedrock
2002-11-14
Water infiltrating down a fracture in unsaturated rock experiences complex fluid-flow and heat-transfer phenomena when entering above-boiling rock temperature regions. Such conditions are expected, for example, after emplacement of heat-generating nuclear waste in underground repositories. A new, efficient semi-analytical method is proposed in this paper that simulates the flow processes of infiltration events subject to vigorous boiling from the adjacent hot rock. It is assumed that liquid flow forms in localized preferential flow paths, and that infiltration events are typically short in duration but large in magnitude relative to the average net infiltration. The new solution scheme is applied to several test cases studying sensitivity to a variety of input parameters. Sample simulations are performed for conditions representative of the potential nuclear waste repository at Yucca Mountain, Nevada. A characteristic parameter is introduced that provides a quick estimate of the relative significance of boiling at a given location of interest.
Pain (PDQ®) (Health Professional)
Expert-reviewed information summary about pain as a complication of cancer or its treatment. Approaches to the management and treatment of cancer-associated pain are discussed.
2009-12-01
Important regions of rRNA are rich in nucleotide modifications that can have strong effects on ribosome biogenesis and translation efficiency. Here, we examine the influence of pseudouridylation and...Full Text Available
2009-12-01
Full Text Available.Important regions of rRNA are rich in nucleotide modifications that can have strong effects on ribosome biogenesis and translation efficiency. Here, we examine the influence of pseudouridylation and 2′-O-methylation on translation accuracy in yeast, by deleting the corresponding guide snoRNAs. The regions analyzed were: the decoding centre (eight modifications), and two intersubunit bridge domains—the A-site finger and Helix 69 (six and five modifications). Results show that a number of modifications influence accuracy with effects ranging from 0.3- to 2.4-fold of wild-type activity. Blocking subsets of modifications, especially from the decoding region, impairs stop codon termination and reading frame maintenance. Unexpectedly, several Helix 69 mutants possess ribosomes with increased fidelity. Consistent with strong positional and synergistic effects is the finding that single deletions can have a more pronounced phenotype than multiple deficiencies in the same region. Altogether, the results demonstrate that rRNA modifications have significant roles in translation accuracy.
Montreal Axion - Wikipedia, the free encyclopedia
The Montreal Axion are a National Women's Hockey League team located in Montreal, Quebec, Canada. v ? d ? e · Sports teams based in the province of Quebec, ...
2001-02-28
If geologic formations are used to sequester carbon dioxide (CO{sub 2}), monitoring the CO{sub 2} injection will be required to confirm the performance of the reservoir system, assess leaks and flow paths, and understand the geophysical and geochemical interactions between the CO{sub 2} and the geologic minerals and fluids. Electrical methods are well suited for monitoring processes involving fluids, as electrical properties are sensitive to the presence and nature of the formation fluids. High resolution tomographs of electrical properties are now possible using it 3D technique called electrical resistance tomography (ERT). Surveys are commonly conducted utilizing vertical arrays of point electrodes in a cross-well configuration. Recent field results obtained using steel well casings as electrodes are promising. When 3D ERT imaging can be performed using existing well casings as long electrodes, the need for additional drilling of observation wells is minimized. Using a model patterned after an oil field undergoing CO{sub 2} flood, forward and inverse simulations of ERT surveys have been run to test the sensitivity of the method to changes resulting from CO{sub 2} migration. Factors considered include resistivity contrast, anomaly proximity to electrodes, anomaly size and shape, measurement noise, and the electrode configuration used to perform the measurements. Field data suggest that CO{sub 2} migration changes the resistivity of a layer, producing an anomalous region. In our numerical study, the anomalous region s resistivity ranges from 0.2 to 10 times that of the initial value. Its geometry ranges from a thin, horizontal finger to a planar, horizontal mass having vertical protrusions simulating leakage of CO{sub 2} through caprock. Results of simulations run assuming that well casings are used as long electrodes or with arrays of point electrodes (simulating high resolution surveys) show useful information for even the narrowest simulated CO{sub 2} fingers.
Microsoft Word - October2009.doc
To unsubscribe from this newsletter please send an email to Dr. Betty Tarnowski tarnowsb@mail.nih.gov Send meeting announcements and other information you would like to have included in this newsletter to Ulli Wagner: ulrike@mail.nih.gov M MM MH
2005-01-01
The MUC1 mucin is a large membrane-tethered glycoprotein that shows differential expression in many adenocarcinomas, where it contributes to their invasive and metastatic properties. We previously identified DNase I hypersensitive sites at -750 and -250 bp in the human MUC1 gene promoter and showed concordance between the -250 site and MUC1 mRNA levels in vivo. Transient expression assays using promoter constructs, in which the core DHS was deleted, to drive reporter gene expression revealed in vivo evidence for their activity. DNase I footprinting using nuclear extracts from HPAF human pancreatic carcinoma cells and MCF7 breast carcinoma cells identified three protein-binding elements in these regions (-250FP1, FP2 and -750FP). Electrophoretic mobility shift assays detected several complexes between HPAF nuclear proteins and labeled FP DNA probes. Southwestern ... >>
MEETING PARTICIPANTS President?s Cancer Panel Harold P. Freeman, M.D., Chairman Dennis J. Slamon, M.D. National Cancer Institute Maureen O. Wilson, Ph.D., Assistant Director, NCI, and Executive Secretary, President?s Cancer Panel Jon Kerner, Ph.D., Assistant Director, Research Dissemination and Diffusion, Division of Cancer Control and Population Sciences Speakers Ferdinand Addo, M.D., Medcenter One Health Care (North Dakota) Jeanne L.
2009-12-01
The appropriate development of conidia and appressoria is critical in the disease cycle of many fungal pathogens, including Magnaporthe oryzae. A total of eight genes (MoHOX1...Full Text Available
2009-12-01
Full Text Available.The appropriate development of conidia and appressoria is critical in the disease cycle of many fungal pathogens, including Magnaporthe oryzae. A total of eight genes (MoHOX1 to MoHOX8) encoding putative homeobox transcription factors (TFs) were identified from the M. oryzae genome. Knockout mutants for each MoHOX gene were obtained via homology-dependent gene replacement. Two mutants, ΔMohox3 and ΔMohox5, exhibited no difference to wild-type in growth, conidiation, conidium size, conidial germination, appressorium formation, and pathogenicity. However, the ΔMohox1 showed a dramatic reduction in hyphal growth and increase in melanin pigmentation, compared to those in wild-type. ΔMohox4 and ΔMohox6 showed significantly reduced conidium size and hyphal growth, respectively. ΔMohox8 formed normal appressoria, but failed in pathogenicity, probably due to defects in the development of penetration peg and invasive growth. It is most notable that asexual reproduction was completely abolished in ΔMohox2, in which no conidia formed. ΔMohox2 was still pathogenic through hypha-driven appressoria in a manner similar to that of the wild-type. However, ΔMohox7 was unable to form appressoria either on conidial germ tubes, or at hyphal tips, being non-pathogenic. These factors indicate that M. oryzae is able to cause foliar disease via hyphal appressorium-mediated penetration, and MoHOX7 is mutually required to drive appressorium formation from hyphae and germ tubes. Transcriptional analyses suggest that the functioning of M. oryzae homeobox TFs is mediated through the regulation of gene expression and is affected by cAMP and Ca2+ signaling and/or MAPK pathways. The divergent roles of this gene set may help reveal how the genome and regulatory pathways evolved within the rice blast pathogen and close relatives.
Genomic Hotspots for Adaptation: The Population Genetics of Müllerian Mimicry in Heliconius erato
2010-02-01
Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection. The genes controlling pattern variation are classic...Full Text Available
Genomic Hotspots for Adaptation: The Population Genetics of Müllerian Mimicry in Heliconius erato
2010-02-01
Full Text Available.Wing pattern evolution in Heliconius butterflies provides some of the most striking examples of adaptation by natural selection. The genes controlling pattern variation are classic examples of Mendelian loci of large effect, where allelic variation causes large and discrete phenotypic changes and is responsible for both convergent and highly divergent wing pattern evolution across the genus. We characterize nucleotide variation, genotype-by-phenotype associations, linkage disequilibrium (LD), and candidate gene expression patterns across two unlinked genomic intervals that control yellow and red wing pattern variation among mimetic forms of Heliconius erato. Despite very strong natural selection on color pattern, we see neither a strong reduction in genetic diversity nor evidence for extended LD across either patterning interval. This observation highlights the extent that recombination can erase the signature of selection in natural populations and is consistent with the hypothesis that either the adaptive radiation or the alleles controlling it are quite old. However, across both patterning intervals we identified SNPs clustered in several coding regions that were strongly associated with color pattern phenotype. Interestingly, coding regions with associated SNPs were widely separated, suggesting that color pattern alleles may be composed of multiple functional sites, conforming to previous descriptions of these loci as “supergenes.” Examination of gene expression levels of genes flanking these regions in both H. erato and its co-mimic, H. melpomene, implicate a gene with high sequence similarity to a kinesin as playing a key role in modulating pattern and provides convincing evidence for parallel changes in gene regulation across co-mimetic lineages. The complex genetic architecture at these color pattern loci stands in marked contrast to the single casual mutations often identified in genetic studies of adaptation, but may be more indicative of the type of genetic changes responsible for much of the adaptive variation found in natural populations.
Genetics of Prostate Cancer (PDQ®) (Health Professional)
Expert-reviewed information summary about the genetics of prostate cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for prostate cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary prostate cancer syndrome are also discussed.
Full Text Available.BackgroundAlthough the rat is extensively used as a laboratory model, the inability to utilize germ line-competent rat embryonic stem (ES) cells has been a major drawback for studies that aim to elucidate gene functions. Recently, zinc-finger nucleases (ZFNs) were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc.Methodology/Principal FindingsWe report here on ZFN-induced gene targeting of the rat interleukin 2 receptor gamma (Il2rg) locus, where orthologous human and mouse mutations cause X-linked severe combined immune deficiency (X-SCID). Co-injection of mRNAs encoding custom-designed ZFNs into the pronucleus of fertilized oocytes yielded genetically modified offspring at rates greater than 20%, which possessed a wide variety of deletion/insertion mutations. ZFN-modified founders faithfully transmitted their genetic changes to the next generation along with the severe combined immune deficiency phenotype.Conclusions and SignificanceThe efficient and rapid generation of gene knockout rats shows that using ZFN technology is a new strategy for creating gene-targeted rat models of human diseases. In addition, the X-SCID rats that were established in this study will be valuable in vivo tools for evaluating drug treatment or gene therapy as well as model systems for examining the treatment of xenotransplanted malignancies.
BackgroundAlthough the rat is extensively used as a laboratory model, the inability to utilize germ line-competent rat embryonic stem (ES) cells has been a major drawback for studies...Full Text Available
2010-01-01
We address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription...Full Text Available
2010-01-01
Full Text Available.We address the problem of finding statistically significant associations between cis-regulatory motifs and functional gene sets, in order to understand the biological roles of transcription factors. We develop a computational framework for this task, whose features include a new statistical score for motif scanning, the use of different scores for predicting targets of different motifs, and new ways to deal with redundancies among significant motif–function associations. This framework is applied to the recently sequenced genome of the jewel wasp, Nasonia vitripennis, making use of the existing knowledge of motifs and gene annotations in another insect genome, that of the fruitfly. The framework uses cross-species comparison to improve the specificity of its predictions, and does so without relying upon non-coding sequence alignment. It is therefore well suited for comparative genomics across large evolutionary divergences, where existing alignment-based methods are not applicable. We also apply the framework to find motifs associated with socially regulated gene sets in the honeybee, Apis mellifera, using comparisons with Nasonia, a solitary species, to identify honeybee-specific associations.
Full Text Available.BackgroundWhile traditionally quite distinct, functional neuroimaging (e.g. functional magnetic resonance imaging: fMRI) and functional interference techniques (e.g. transcranial magnetic stimulation: TMS) increasingly address similar questions of functional brain organization, including connectivity, interactions, and causality in the brain. Time-resolved TMS over multiple brain network nodes can elucidate the relative timings of functional relevance for behavior (“TMS chronometry”), while fMRI functional or effective connectivity (fMRI EC) can map task-specific interactions between brain regions based on the interrelation of measured signals. The current study empirically assessed the relation between these different methods.Methodology/Principal FindingsOne group of 15 participants took part in two experiments: one fMRI EC study, and one TMS chronometry study, both of which used an established cognitive paradigm involving one visuospatial judgment task and one color judgment control task. Granger causality mapping (GCM), a data-driven variant of fMRI EC analysis, revealed a frontal-to-parietal flow of information, from inferior/middle frontal gyrus (MFG) to posterior parietal cortex (PPC). FMRI EC-guided Neuronavigated TMS had behavioral effects when applied to both PPC and to MFG, but the temporal pattern of these effects was similar for both stimulation sites. At first glance, this would seem in contradiction to the fMRI EC results. However, we discuss how TMS chronometry and fMRI EC are conceptually different and show how they can be complementary and mutually constraining, rather than contradictory, on the basis of our data.Conclusions/SignificanceThe findings that fMRI EC could successfully localize functionally relevant TMS target regions on the single subject level, and conversely, that TMS confirmed an fMRI EC identified functional network to be behaviorally relevant, have important methodological and theoretical implications. Our results, in combination with data from earlier studies by our group (Sack et al., 2007, Cerebral Cortex), lead to informed speculations on complex brain mechanisms, and TMS disruption thereof, underlying visuospatial judgment. This first in-depth empirical and conceptual comparison of fMRI EC and TMS chronometry thereby shows the complementary insights offered by the two methods.
BackgroundWhile traditionally quite distinct, functional neuroimaging (e.g. functional magnetic resonance imaging: fMRI) and functional interference techniques (e.g. transcranial...Full Text Available
2005-09-28
Although most genes are conserved as one-to-one orthologs in different mammalian orders, certain gene families have evolved to comprise different numbers and types of protein-coding genes through independent series of gene duplications, divergence and gene loss in each evolutionary lineage. One such family encodes KRAB-zinc finger (KRAB-ZNF) genes, which are likely to function as transcriptional repressors. One KRAB-ZNF subfamily, the ZNF91 clade, has expanded specifically in primates to comprise more than 110 loci in the human genome, yielding large gene clusters in human chromosomes 19 and 7 and smaller clusters or isolated copies at other chromosomal locations. Although phylogenetic analysis indicates that many of these genes arose before the split between old world monkeys and new world monkeys, the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. The paralogous loci are distinguished by sequence divergence within their zinc finger arrays indicating a selection for proteins with different DNA binding specificities. RT-PCR and in situ hybridization data show that some of these ZNF genes can have tissue-specific expression patterns, however many KRAB-ZNFs that are near-ubiquitous could also be playing very specific roles in halting target pathways in all tissues except for a few, where the target is released by the absence of its repressor. The number of variant KRAB-ZNF proteins is increased not only because of the large number of loci, but also because many loci can produce multiple splice variants, which because of the modular structure of these genes may have separate and perhaps even conflicting regulatory roles. The lineage-specific duplication and rapid divergence of this family of transcription factor genes suggests a role in determining species-specific biological differences and the evolution of novel primate traits.
Electrostatic Discharge/Electrical Overstress Susceptibility in MEMS: A New Failure Mode
2000-09-12
No abstract prepared.
1997-12-31
Full text: The potential to examine prehistoric trade, exchange systems, social boundaries or regional interconnections through characterising the major ethnographic red ochre sources has long been recognised by Australian archaeologists. Recently several teams have made a start in characterising major ochre deposits and in attempting to source ochres recovered in archaeological contexts. Here we review prospects and progress with this line of research. We present case studies of the geochemistry of several major Australian ochre deposits - including Bookartoo, Karrku and Wilgie Mia -looking at their diagenesis, geochemistry and variability and explore the application of various analytical techniques, principally XRD, SEM/EDXA, ICP/MS and stable isotope analysis. We then explore an archaeological application at the Puritjarra shelter in central Australia where ochre sourcing has major implications for understanding prehistoric land use. Our results show that a systematic program of characterising ochre sources and archaeological ochres has great potential in Australia. Major ochre sources often have distinctive chemical fingerprints, particularly if a range of analytical techniques are used in conjunction to characterise ochres. Ochre is frequently found in both late Pleistocene and Holocene contexts, often in sufficient quantity to permit systematic study of temporal changes in prehistoric systems. To fully realize the potential of this research however it will be important to work collaboratively to build up centralized data files of compositional analyses of Australian ochres.
Development of an integrated strategy for the disposal of solid low level waste at BNFL`s Drigg site
1989-11-01
During the past 12 months, the first phase of a major upgrading of disposal operations at Drigg has been completed. This has involved the introduction of waste containerization and orderly emplacement in open concrete vaults. A further phase over the next few years will involve the introduction of compaction of all suitable waste. While the current upgrade has clearly resulted in a major improvement in the visual impact and management control of the site, the desire to implement such an improvement on a timescale consistent with the short term need for new facilities at Drigg has not allowed sufficient time for a detailed assessment of the full implications of the proposed system. This paper describes the development of the strategy for upgrading the Drigg site, highlights improvements that have been implemented as the project has progressed and outlines major outstanding concerns, particularly in relation to long term site management, that may eventually lead to a requirement for further optimization of the overall strategy. Progress under the Drigg Technical Development Programme is reviewed with specific emphasis on the preliminary results of engineering studies aimed at defining an integrated strategy that will meet the requirements of both acceptable visual impact and long term site stability and safety.
New Faces at NCI-Frederick 18 NCI-Frederick People 19 The Poster Puzzler 20 Poster Puzzler Winner 21 PALS? Celebrations 22 Technology Transfer Branch 23 Charles River Laboratories 24 Data Management Services 25 SAIC-Frederick, Inc.
December 2004 3 The NCI-Frederick Poster NCI-Frederick Welcomes New Staff New Faces at NCI-Frederick Sergei Grivennikov Eighty-fi ve people joined our Facility in May, June, July, and August 2004.
Conservation and divergence of known apicomplexan transcriptional regulons
Full Text Available.BackgroundThe apicomplexans are a diverse phylum of parasites causing an assortment of diseases including malaria in a wide variety of animals and lymphoproliferation in cattle. Little is known about how these varied parasites regulate their transcriptional regulons. Even less is known about how regulon systems, consisting of transcription factors and target genes together with their associated biological process, evolve in these diverse parasites.ResultsIn order to obtain insights into the differences in transcriptional regulation between these parasites we compared the orthology profiles of putative malaria transcription factors across species and examined the enrichment patterns of four binding sites across eleven apicomplexans.About three-fifths of the factors are broadly conserved in several phylogenetic orders of sequenced apicomplexans. This observation suggests the existence of regulons whose regulation is conserved across this ancient phylum. Transcription factors not broadly conserved across the phylum are possibly involved in regulon systems that have diverged between species. Examining binding site enrichment patterns in light of transcription factor conservation patterns suggests a second mode via which regulon systems may diverge - rewiring of existing transcription factors and their associated binding sites in specific ways. Integrating binding sites with transcription factor conservation patterns also facilitated prediction of putative regulators for one of the binding sites.ConclusionsEven though transcription factors are underrepresented in apicomplexans, the distribution of these factors and their associated regulons reflect common and family-specific transcriptional regulatory processes.
Conservation and divergence of known apicomplexan transcriptional regulons
BackgroundThe apicomplexans are a diverse phylum of parasites causing an assortment of diseases including malaria in a wide variety of animals and lymphoproliferation in cattle....Full Text Available
Full Text Available.BackgroundHealth record-based observations from several parts of Africa indicate a major decline in malaria, but up-to-date information on parasite prevalence in West-Africa is sparse. This study aims to provide parasite prevalence data from three sites in the Gambia and Guinea Bissau, respectively, and compares the usefulness of PCR, rapid diagnostic tests (RDT), serology and slide-microscopy for surveillance.MethodsCross-sectional surveys in 12 villages at three rural sites were carried out in the Gambia and Guinea Bissau in January/February 2008, shortly following the annual transmission season.ResultsA surprisingly low microscopically detectable parasite prevalence was detected in the Gambia (Farafenni: 10.9%, CI95%: 8.7-13.1%; Basse: 9.0%, CI95%: 7.2-10.8%), and Guinea Bissau (Caio: 4%, CI95%: 2.6-5.4%), with low parasite densities (geometric mean: 104 parasites/μl, CI95%: 76-143/μl). In comparison, PCR detected a more than three times higher proportion of parasite carriers, indicating its usefulness to sensitively identify foci where malaria declines, whereas the RDT had very low sensitivity. Estimates of force of infection using age sero-conversion rates were equivalent to an EIR of approximately 1 infectious bite/person/year, significantly less than previous estimates. The sero-prevalence profiles suggest a gradual decline of malaria transmission, confirming their usefulness in providing information on longer term trends of transmission. A greater variability in parasite prevalence among villages within a site than between sites was observed with all methods. The fact that serology equally captured the inter-village variability, indicates that the observed heterogeneity represents a stable pattern.ConclusionPCR and serology may be used as complementary tools to survey malaria in areas of declining malaria prevalence such as the Gambia and Guinea Bissau.
BackgroundHealth record-based observations from several parts of Africa indicate a major decline in malaria, but up-to-date information on parasite prevalence in West-Africa is sparse....Full Text Available
The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis. Prior work has demonstrated a role for Brn3a in the repression...Full Text Available
Full Text Available.The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis. Prior work has demonstrated a role for Brn3a in the repression of early neurogenic genes; here we describe a second major role for Brn3a in the specification of sensory subtypes in the trigeminal ganglion (TG). Sensory neurons initially co-express multiple Trk-family neurotrophin receptors, but are later marked by the unique expression of TrkA, TrkB or TrkC. Maturation of these sensory subtypes is known to depend on the expression of Runx transcription factors. Newborn Brn3a knockout mice fail to express TrkC, which is associated in the TG with mechanoreceptors, plus a set of functional genes associated with nociceptor subtypes. In embryonic Brn3a-/- ganglia, the normal expression of Runx3 is never initiated in TrkC+ neurons, and Runx1 expression is greatly attenuated in TrkA+ nociceptors. These changes are accompanied by expanded expression of TrkB in neurons that abnormally express multiple Trks, followed by the loss of TrkC and TrkA expression. In transgenic embryos expressing a Brn3a-VP16 dominant transactivator, Runx3 mRNA expression is increased, suggesting that it is a direct regulatory target of Brn3a. Chromatin immunoprecipitation confirms that Brn3a binds in vivo to a conserved upstream enhancer element within histone H3-acetylated chromatin in the Runx3 locus. Together these data show that Brn3a acts upstream of the Runx factors, which then repress TrkB expression to allow establishment of the non-overlapping Trk receptor profiles and correct terminally differentiated phenotypes.
Axiontv.com-Portable DVD Player, Handheld LCD TVs, LCD + DVD Combos
Axiontv.com-LCD,tv,televisions,portable,handheld,CRT,DVD,axion,action,HD,HDTV,digital,display,monitor,color,personal,video,audio,CE,OEM,ODM,monitor,computer ...
Best buy price Computer Parts, PC Components, notebook computer, computer desktop best price guarantee at Axiontech.com.
Axion Project Incubation Status - Apache Incubator
For general project status, see the Axion project website. ... The axion project never moved to the ASF from tigris.org. 2003-12-19: The Apache Incubator ...
We believe our PcB technology represents the first major advance in lead-acid battery technology in 30 years.
Axion - Wikipedia, the free encyclopedia
The axion is a hypothetical elementary particle postulated by Peccei-Quinn theory in 1977 to resolve the strong-CP problem in quantum chromodynamics (QCD). ...
Automated Sorting of Transuranic Waste
2001-03-01
The HANDSS-55 Transuranic Waste Sorting Module is designed to sort out items found in 55-gallon drums of waste as determined by an operator. Innovative imaging techniques coupled with fast linear motor-based motion systems and a flexible end-effector system allow the operator to remove items from the waste stream by a touch of the finger. When all desired items are removed from the waste stream, the remaining objects are automatically moved to a repackaging port for removal from the glovebox/cell. The Transuranic Waste Sorting Module consists of 1) a high accuracy XYZ Stereo Measurement and Imaging system, 2) a vibrating/tilting sorting table, 3) an XY Deployment System, 4) a ZR Deployment System, 5) several user-selectable end-effectors, 6) a waste bag opening system, 7) control and instrumentation, 8) a noncompliant waste load-out area, and 9) a Human/Machine Interface (HMI). The system is modular in design to accommodate database management tools, additional load-out ports, and other enhancements. Manually sorting the contents of a 55-gallon drum takes about one day per drum. The HANDSS-55 Waste Sorting Module is designed to significantly increase the throughput of this sorting process by automating those functions that are strenuous and tiresome for an operator to perform. The Waste Sorting Module uses the inherent ability of an operator to identify the items that need to be segregated from the waste stream and then, under computer control, picks that item out of the waste and deposits it in the appropriate location. The operator identifies the object by locating the visual image on a large color display and touches the image on the display with his finger. The computer then determines the location of the object, and performing a highspeed image analysis determines its size and orientation, so that a robotic gripper can be deployed to pick it up. Following operator verification by voice or function key, the object is deposited into a specified location.
Archaeological applications of naturally occurring nanomagnets
2005-01-01
The ubiquitous presence of iron minerals within the soils and sediments forming archaeological sites can often provide a valuable record of past human activity. These records are formed through the alteration of weakly magnetic minerals to fine grained iron oxides, such as magnetite or maghaemite, that leave an almost indelible magnetic 'finger print' on the landscape. Archaeologists have exploited these magnetic records at a variety of levels from geophysical survey to reveal the location of a site, to determining how old a particular excavated feature may be through archaeomagnetic dating. More recent studies have investigated the process of magnetic enhancement through the often complex interaction of pedogenic, microbial and anthropogenic mechanisms and pathways. This research has revealed many unique magnetic signatures within archaeological sediments that ... >>
Allosteric modulation of Ras positions Q61 for a direct role in catalysis
2010-03-16
Ras and its effector Raf are key mediators of the Ras/Raf/MEK/ERK signal transduction pathway. Mutants of residue Q61 impair the GTPase activity of Ras and are found prominently in human cancers. Yet...Full Text Available
Allosteric modulation of Ras positions Q61 for a direct role in catalysis
2010-03-16
Full Text Available.Ras and its effector Raf are key mediators of the Ras/Raf/MEK/ERK signal transduction pathway. Mutants of residue Q61 impair the GTPase activity of Ras and are found prominently in human cancers. Yet the mechanism through which Q61 contributes to catalysis has been elusive. It is thought to position the catalytic water molecule for nucleophilic attack on the γ-phosphate of GTP. However, we previously solved the structure of Ras from crystals with symmetry of the space group R32 in which switch II is disordered and found that the catalytic water molecule is present. Here we present a structure of wild-type Ras with calcium acetate from the crystallization mother liquor bound at a site remote from the active site and likely near the membrane. This results in a shift in helix 3/loop 7 and a network of H-bonding interactions that propagates across the molecule, culminating in the ordering of switch II and placement of Q61 in the active site in a previously unobserved conformation. This structure suggests a direct catalytic role for Q61 where it interacts with a water molecule that bridges one of the γ-phosphate oxygen atoms to the hydroxyl group of Y32 to stabilize the transition state of the hydrolysis reaction. We propose that Raf together with the binding of Ca2+ and a negatively charged group mimicked in our structure by the acetate molecule induces the ordering of switch I and switch II to complete the active site of Ras.
Accelerated Evolution of the Prdm9 Speciation Gene across Diverse Metazoan Taxa
2009-12-01
The onset of prezygotic and postzygotic barriers to gene flow between populations is a hallmark of speciation. One of the earliest postzygotic isolating barriers to arise between incipient species is...Full Text Available
Accelerated Evolution of the Prdm9 Speciation Gene across Diverse Metazoan Taxa
2009-12-01
Full Text Available.The onset of prezygotic and postzygotic barriers to gene flow between populations is a hallmark of speciation. One of the earliest postzygotic isolating barriers to arise between incipient species is the sterility of the heterogametic sex in interspecies' hybrids. Four genes that underlie hybrid sterility have been identified in animals: Odysseus, JYalpha, and Overdrive in Drosophila and Prdm9 (Meisetz) in mice. Mouse Prdm9 encodes a protein with a KRAB motif, a histone methyltransferase domain and several zinc fingers. The difference of a single zinc finger distinguishes Prdm9 alleles that cause hybrid sterility from those that do not. We find that concerted evolution and positive selection have rapidly altered the number and sequence of Prdm9 zinc fingers across 13 rodent genomes. The patterns of positive selection in Prdm9 zinc fingers imply that rapid evolution has acted on the interface between the Prdm9 protein and the DNA sequences to which it binds. Similar patterns are apparent for Prdm9 zinc fingers for diverse metazoans, including primates. Indeed, allelic variation at the DNA–binding positions of human PRDM9 zinc fingers show significant association with decreased risk of infertility. Prdm9 thus plays a role in determining male sterility both between species (mouse) and within species (human). The recurrent episodes of positive selection acting on Prdm9 suggest that the DNA sequences to which it binds must also be evolving rapidly. Our findings do not identify the nature of the underlying DNA sequences, but argue against the proposed role of Prdm9 as an essential transcription factor in mouse meiosis. We propose a hypothetical model in which incompatibilities between Prdm9-binding specificity and satellite DNAs provide the molecular basis for Prdm9-mediated hybrid sterility. We suggest that Prdm9 should be investigated as a candidate gene in other instances of hybrid sterility in metazoans.
A reproducible brain tumour model established from human glioblastoma biopsies
Full Text Available.BackgroundEstablishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates.MethodsIn this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features.ResultsThe tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms.ConclusionsIn vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.
A reproducible brain tumour model established from human glioblastoma biopsies
BackgroundEstablishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the...Full Text Available
2006-06-07
Homologous chromosome pairing and synapsis are prerequisitefor accurate chromosome segregation during meiosis. Here, we show that afamily of four related C2H2 zinc-finger proteins plays a central role inthese events in C. elegans. These proteins are encoded within a tandemgene cluster. In addition to the X-specific HIM-8 protein, threeadditional paralogs collectively mediate the behavior of the fiveautosomes. Each chromosome relies on a specific member of the family topair and synapse with its homolog. These "ZIM" proteins concentrate atspecial regions called meiotic pairing centers on the correspondingchromosomes. These sites are dispersed along the nuclear envelope duringearly meiotic prophase, suggesting a role analogous to thetelomere-mediated meiotic bouquet in other organisms. To gain insightinto the evolution of these components, wecharacterized homologs in C.briggsae and C. remanei, which revealed changes in copy number of thisgene family within the nematode lineage.
2005-09-30
Krueppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotic species. In mammals, most ZNF proteins comprise a single class of transcriptional repressors in which a chromatin interaction domain, called the Krueppel-associated box (KRAB) is attached to a tandem array of DNA-binding zinc-finger motifs. KRAB-ZNF loci are specific to tetrapod vertebrates, but have expanded dramatically in numbers through repeated rounds of segmental duplication to create a gene family with hundreds of members in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the human genome for key motifs and used them to construct and manually curate gene models. The resulting KRAB-ZNF gene catalog includes 326 known genes, 243 of which were structurally corrected by manual annotation, and 97 novel KRAB-ZNF genes; this single family therefore comprises 20% of all predicted human transcription factor genes. Many of the genes are alternatively spliced, yielding a total of 743 distinct predicted proteins. Although many human KRAB-ZNF genes are conserved in mammals, at least 136 and potentially more than 200 genes of this type are primate-specific including many recent segmental duplicates. KRAB-ZNF genes are active in a wide variety of human tissues suggesting roles in many key biological processes, but most member genes remain completely uncharacterized. Because of their sheer numbers, wide-ranging tissue-specific expression patterns, and remarkable evolutionary divergence we predict that KRAB-ZNF transcription factors have played critical roles in crafting many aspects of human biology, including both deeply conserved and primate-specific traits.
Website Policies and Important Links Comments
 |
 |
 |
WorldWideScience.org is maintained by the
U.S. Department of Energy's
Office of Scientific and Technical Information as the Operating Agent
for the WorldWideScience Alliance.