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Sample records for hic-5 regulates anchorage

  1. 77 FR 43514 - Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI

    Science.gov (United States)

    2012-07-25

    ...-AA01 Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI AGENCY: Coast Guard, DHS... Narragansett Bay, Rhode Island, and adding an offshore anchorage in Rhode Island Sound south of Brenton Point... rulemaking (NPRM) entitled ``Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI,'' in the...

  2. HIC1 links retinoic acid signalling to group 3 innate lymphoid cell-dependent regulation of intestinal immunity and homeostasis

    Science.gov (United States)

    Antignano, Frann; Korinek, Vladimir; Underhill, T. Michael

    2018-01-01

    The intestinal immune system must be able to respond to a wide variety of infectious organisms while maintaining tolerance to non-pathogenic microbes and food antigens. The Vitamin A metabolite all-trans-retinoic acid (atRA) has been implicated in the regulation of this balance, partially by regulating innate lymphoid cell (ILC) responses in the intestine. However, the molecular mechanisms of atRA-dependent intestinal immunity and homeostasis remain elusive. Here we define a role for the transcriptional repressor Hypermethylated in cancer 1 (HIC1, ZBTB29) in the regulation of ILC responses in the intestine. Intestinal ILCs express HIC1 in a vitamin A-dependent manner. In the absence of HIC1, group 3 ILCs (ILC3s) that produce IL-22 are lost, resulting in increased susceptibility to infection with the bacterial pathogen Citrobacter rodentium. Thus, atRA-dependent expression of HIC1 in ILC3s regulates intestinal homeostasis and protective immunity. PMID:29470558

  3. Coronal Heating Observed with Hi-C

    Science.gov (United States)

    Winebarger, Amy R.

    2013-01-01

    The recent launch of the High-Resolution Coronal Imager (Hi-C) as a sounding rocket has offered a new, different view of the Sun. With approx 0.3" resolution and 5 second cadence, Hi-C reveals dynamic, small-scale structure within a complicated active region, including coronal braiding, reconnection regions, Alfven waves, and flows along active region fans. By combining the Hi-C data with other available data, we have compiled a rich data set that can be used to address many outstanding questions in solar physics. Though the Hi-C rocket flight was short (only 5 minutes), the added insight of the small-scale structure gained from the Hi-C data allows us to look at this active region and other active regions with new understanding. In this talk, I will review the first results from the Hi-C sounding rocket and discuss the impact of these results on the coronal heating problem.

  4. 76 FR 15246 - Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI

    Science.gov (United States)

    2011-03-21

    ...-AA01 Anchorage Regulations; Narragansett Bay and Rhode Island Sound, RI AGENCY: Coast Guard, DHS... Rhode Island Sound south of Brenton Point, Rhode Island, for use by vessels waiting to enter... Sound that under current informal practice is routinely used by mariners as an anchorage while waiting...

  5. diffHic: a Bioconductor package to detect differential genomic interactions in Hi-C data.

    Science.gov (United States)

    Lun, Aaron T L; Smyth, Gordon K

    2015-08-19

    Chromatin conformation capture with high-throughput sequencing (Hi-C) is a technique that measures the in vivo intensity of interactions between all pairs of loci in the genome. Most conventional analyses of Hi-C data focus on the detection of statistically significant interactions. However, an alternative strategy involves identifying significant changes in the interaction intensity (i.e., differential interactions) between two or more biological conditions. This is more statistically rigorous and may provide more biologically relevant results. Here, we present the diffHic software package for the detection of differential interactions from Hi-C data. diffHic provides methods for read pair alignment and processing, counting into bin pairs, filtering out low-abundance events and normalization of trended or CNV-driven biases. It uses the statistical framework of the edgeR package to model biological variability and to test for significant differences between conditions. Several options for the visualization of results are also included. The use of diffHic is demonstrated with real Hi-C data sets. Performance against existing methods is also evaluated with simulated data. On real data, diffHic is able to successfully detect interactions with significant differences in intensity between biological conditions. It also compares favourably to existing software tools on simulated data sets. These results suggest that diffHic is a viable approach for differential analyses of Hi-C data.

  6. Hi-C First Results

    Science.gov (United States)

    Cirtain, Jonathan

    2013-01-01

    Hi-C obtained the highest spatial and temporal resolution observatoins ever taken in the solar corona. Hi-C reveals dynamics and structure at the limit of its temporal and spatial resolution. Hi-C observed ubiquitous fine-scale flows consistent with the local sound speed.

  7. 78 FR 44917 - Anchorage Regulations; Port of New York

    Science.gov (United States)

    2013-07-25

    ...-AA01 Anchorage Regulations; Port of New York AGENCY: Coast Guard, DHS. ACTION: Notice of proposed... New York. This action is necessary to facilitate safe navigation and provide safe and secure... this rule, call or email Mr. Jeff Yunker, Sector New York, Waterways Management Division, U.S. Coast...

  8. 75 FR 22323 - Anchorage Regulations; Port of New York

    Science.gov (United States)

    2010-04-28

    ...-AA01 Anchorage Regulations; Port of New York AGENCY: Coast Guard, DHS. ACTION: Supplemental notice of..., Coast Guard Sector New York, Waterways Management Division; telephone 718-354-4195, e-mail Jeff.M.Yunker... Purpose The Hudson River Pilots Association, through the Port of New York/ New Jersey Harbor Safety...

  9. Understanding spatial organizations of chromosomes via statistical analysis of Hi-C data

    Science.gov (United States)

    Hu, Ming; Deng, Ke; Qin, Zhaohui; Liu, Jun S.

    2015-01-01

    Understanding how chromosomes fold provides insights into the transcription regulation, hence, the functional state of the cell. Using the next generation sequencing technology, the recently developed Hi-C approach enables a global view of spatial chromatin organization in the nucleus, which substantially expands our knowledge about genome organization and function. However, due to multiple layers of biases, noises and uncertainties buried in the protocol of Hi-C experiments, analyzing and interpreting Hi-C data poses great challenges, and requires novel statistical methods to be developed. This article provides an overview of recent Hi-C studies and their impacts on biomedical research, describes major challenges in statistical analysis of Hi-C data, and discusses some perspectives for future research. PMID:26124977

  10. 76 FR 20524 - Anchorage Regulations; Port of New York

    Science.gov (United States)

    2011-04-13

    ...-AA01 Anchorage Regulations; Port of New York AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: The... Yunker, Coast Guard Sector New York, Waterways Management Division; telephone 718-354-4195, e-mail Jeff.M... New York in the Federal Register (74 FR 47906). We received one comment on the NPRM. No public meeting...

  11. Dynamic Moss Observed with Hi-C

    Science.gov (United States)

    Alexander, Caroline; Winebarger, Amy; Morton, Richard; Savage, Sabrina

    2014-01-01

    The High-resolution Coronal Imager (Hi-C), flown on 11 July 2012, has revealed an unprecedented level of detail and substructure within the solar corona. Hi-C imaged a large active region (AR11520) with 0.2-0.3'' spatial resolution and 5.5s cadence over a 5 minute period. An additional dataset with a smaller FOV, the same resolution, but with a higher temporal cadence (1s) was also taken during the rocket flight. This dataset was centered on a large patch of 'moss' emission that initially seemed to show very little variability. Image processing revealed this region to be much more dynamic than first thought with numerous bright and dark features observed to appear, move and disappear over the 5 minute observation. Moss is thought to be emission from the upper transition region component of hot loops so studying its dynamics and the relation between the bright/dark features and underlying magnetic features is important to tie the interaction of the different atmospheric layers together. Hi-C allows us to study the coronal emission of the moss at the smallest scales while data from SDO/AIA and HMI is used to give information on these structures at different heights/temperatures. Using the high temporal and spatial resolution of Hi-C the observed moss features were tracked and the distribution of displacements, speeds, and sizes were measured. This allows us to comment on both the physical processes occurring within the dynamic moss and the scales at which these changes are occurring.

  12. Hi-C Observations of Penumbral Bright Dots

    Science.gov (United States)

    Alpert, S. E.; Tiwari, S. K.; Moore, R. L.; Savage, S. L.; Winebarger, A. R.

    2014-01-01

    We use high-quality data obtained by the High Resolution Coronal Imager (Hi-C) to examine bright dots (BDs) in a sunspot's penumbra. The sizes of these BDs are on the order of 1 arcsecond (1") and are therefore hard to identify using the Atmospheric Imaging Assembly's (AIA) 0.6" pixel(exp -1) resolution. These BD become readily apparent with Hi-C's 0.1" pixel(exp -1) resolution. Tian et al. (2014) found penumbral BDs in the transition region (TR) by using the Interface Region Imaging Spectrograph (IRIS). However, only a few of their dots could be associated with any enhanced brightness in AIA channels. In this work, we examine the characteristics of the penumbral BDs observed by Hi-C in a sunspot penumbra, including their sizes, lifetimes, speeds, and intensity. We also attempt to find any association of these BDs to the IRIS BDs. There are fewer Hi-C BDs in the penumbra than seen by IRIS, though different sunspots were studied. We use 193 Angstroms Hi-C data from July 11, 2012 which observed from approximately 18:52:00 UT- 18:56:00 UT and supplement it with data from AIA's 193 Angstrom passband to see the complete lifetime of the dots that were born before and/or lasted longer than Hi- C's 5-minute observation period. We use additional AIA passbands and compare the light curves of the BDs at different temperatures to test whether the Hi-C BDs are TR BDs. We find that most Hi-C BDs show clear movement, and of those that do, they move in a radial direction, toward or away from the sunspot umbra. Single BDs interact with other BDs, combining to fade away or brighten. The BDs that do not interact with other BDs tend to move less. Many of the properties of our BDs are similar to the extreme values of the IRIS BDs, e.g., they move slower on average and their sizes and lifetimes are on the higher end of the IRIS BDs. We infer that our penumbral BDs are the large-scale end of the distribution of BDs observed by IRIS.

  13. Distinct HIC1-SIRT1-p53 Loop Deregulation in Lung Squamous Carcinoma and Adenocarcinoma Patients

    Directory of Open Access Journals (Sweden)

    Ruo-Chia Tseng

    2009-08-01

    Full Text Available A HIC1-SIRT1-p53 circular loop in which hypermethylation in cancer 1 (HIC1 represses the transcription of SIRT1 that deacetylates and inactivates p53 thus leading to HIC1 inactivation has been identified in cell and animal models. However, the alteration and prognostic effects of HIC1-SIRT1-p53 circular loop have never been demonstrated in human cancer patients. We examine the HIC1-SIRT1-p53 alterations in 118 lung cancer patients to define their etiological roles in tumorigenesis. We found that patients with lung squamous cell carcinoma with low p53 acetylation and SIRT1 expression mostly showed low HIC1 expression, confirming deregulation of HIC1-SIRT1-p53 circular loop in the clinical model. Interestingly, the expression of deleted in breast cancer 1 (DBC1, which blocks the interaction between SIRT1 deacetylase and p53, led to acetylated p53 in patients with lung adenocarcinoma. However, epigenetic alteration of HIC1 promoter by posttranslational modifications of histones and promoter hypermethylation favoring the compacted chromatin production attenuated the transcriptional induction by acetylated p53. Importantly, lung cancer patients with altered HIC1-SIRT1-p53 circular regulation showed poor prognosis. Our data show the first valid clinical evidence of the deregulation of HIC1-SIRT1-p53 loop in lung tumorigenesis and prognosis. Distinct status of p53 acetylation/deacetylation and HIC1 alteration mechanism result from different SIRT1-DBC1 control and epigenetic alteration in lung squamous cell carcinoma and lung adenocarcinoma.

  14. Transcriptional Repressor HIC1 Contributes to Suppressive Function of Human Induced Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Ubaid Ullah

    2018-02-01

    Full Text Available Regulatory T (Treg cells are critical in regulating the immune response. In vitro induced Treg (iTreg cells have significant potential in clinical medicine. However, applying iTreg cells as therapeutics is complicated by the poor stability of human iTreg cells and their variable suppressive activity. Therefore, it is important to understand the molecular mechanisms of human iTreg cell specification. We identified hypermethylated in cancer 1 (HIC1 as a transcription factor upregulated early during the differentiation of human iTreg cells. Although FOXP3 expression was unaffected, HIC1 deficiency led to a considerable loss of suppression by iTreg cells with a concomitant increase in the expression of effector T cell associated genes. SNPs linked to several immune-mediated disorders were enriched around HIC1 binding sites, and in vitro binding assays indicated that these SNPs may alter the binding of HIC1. Our results suggest that HIC1 is an important contributor to iTreg cell development and function.

  15. Sparkling extreme-ultraviolet bright dots observed with Hi-C

    International Nuclear Information System (INIS)

    Régnier, S.; Alexander, C. E.; Walsh, R. W.; Winebarger, A. R.; Cirtain, J.; Golub, L.; Korreck, K. E.; Weber, M.; Mitchell, N.; Platt, S.; De Pontieu, B.; Title, A.; Kobayashi, K.; Kuzin, S.; DeForest, C. E.

    2014-01-01

    Observing the Sun at high time and spatial scales is a step toward understanding the finest and fundamental scales of heating events in the solar corona. The high-resolution coronal (Hi-C) instrument has provided the highest spatial and temporal resolution images of the solar corona in the EUV wavelength range to date. Hi-C observed an active region on 2012 July 11 that exhibits several interesting features in the EUV line at 193 Å. One of them is the existence of short, small brightenings 'sparkling' at the edge of the active region; we call these EUV bright dots (EBDs). Individual EBDs have a characteristic duration of 25 s with a characteristic length of 680 km. These brightenings are not fully resolved by the SDO/AIA instrument at the same wavelength; however, they can be identified with respect to the Hi-C location of the EBDs. In addition, EBDs are seen in other chromospheric/coronal channels of SDO/AIA, which suggests a temperature between 0.5 and 1.5 MK. Based on their frequency in the Hi-C time series, we define four different categories of EBDs: single peak, double peak, long duration, and bursty. Based on a potential field extrapolation from an SDO/HMI magnetogram, the EBDs appear at the footpoints of large-scale, trans-equatorial coronal loops. The Hi-C observations provide the first evidence of small-scale EUV heating events at the base of these coronal loops, which have a free magnetic energy of the order of 10 26 erg.

  16. The Substructure of the Solar Corona Observed in the Hi-C Telescope

    Science.gov (United States)

    Winebarger, A.; Cirtain, J.; Golub, L.; DeLuca, E.; Savage, S.; Alexander, C.; Schuler, T.

    2014-01-01

    In the summer of 2012, the High-resolution Coronal Imager (Hi-C) flew aboard a NASA sounding rocket and collected the highest spatial resolution images ever obtained of the solar corona. One of the goals of the Hi-C flight was to characterize the substructure of the solar corona. We therefore calculate how the intensity scales from a low-resolution (AIA) pixels to high-resolution (Hi-C) pixels for both the dynamic events and "background" emission (meaning, the steady emission over the 5 minutes of data acquisition time). We find there is no evidence of substructure in the background corona; the intensity scales smoothly from low-resolution to high-resolution Hi-C pixels. In transient events, however, the intensity observed with Hi-C is, on average, 2.6 times larger than observed with AIA. This increase in intensity suggests that AIA is not resolving these events. This result suggests a finely structured dynamic corona embedded in a smoothly varying background.

  17. 29 CFR 1926.755 - Column anchorage.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 8 2010-07-01 2010-07-01 false Column anchorage. 1926.755 Section 1926.755 Labor... (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Steel Erection § 1926.755 Column anchorage. (a) General requirements for erection stability. (1) All columns shall be anchored by a minimum of 4 anchor...

  18. Loop Evolution Observed with AIA and Hi-C

    Science.gov (United States)

    Mulu-Moore, Fana; Winebarger, Amy R.; Cirtain, Jonathan W.; Kobayashi, Ken; Korreck, Kelly E.; Golub, Leon; Kuzin, Sergei; Walsh, Robert William; DeForest, Craig E.; De Pontieu, Bart; hide

    2012-01-01

    In the past decade, the evolution of EUV loops has been used to infer the loop substructure. With the recent launch of High Resolution Coronal Imager (Hi-C), this inference can be validated. In this presentation we discuss the first results of loop analysis comparing AIA and Hi-C data. In the past decade, the evolution of EUV loops has been used to infer the loop substructure. With the recent launch of High Resolution Coronal Imager (Hi-C), this inference can be validated. In this presentation we discuss the first results of loop analysis comparing AIA and Hi-C data.

  19. Iteratively improving Hi-C experiments one step at a time.

    Science.gov (United States)

    Golloshi, Rosela; Sanders, Jacob T; McCord, Rachel Patton

    2018-04-30

    The 3D organization of eukaryotic chromosomes affects key processes such as gene expression, DNA replication, cell division, and response to DNA damage. The genome-wide chromosome conformation capture (Hi-C) approach can characterize the landscape of 3D genome organization by measuring interaction frequencies between all genomic regions. Hi-C protocol improvements and rapid advances in DNA sequencing power have made Hi-C useful to study diverse biological systems, not only to elucidate the role of 3D genome structure in proper cellular function, but also to characterize genomic rearrangements, assemble new genomes, and consider chromatin interactions as potential biomarkers for diseases. Yet, the Hi-C protocol is still complex and subject to variations at numerous steps that can affect the resulting data. Thus, there is still a need for better understanding and control of factors that contribute to Hi-C experiment success and data quality. Here, we evaluate recently proposed Hi-C protocol modifications as well as often overlooked variables in sample preparation and examine their effects on Hi-C data quality. We examine artifacts that can occur during Hi-C library preparation, including microhomology-based artificial template copying and chimera formation that can add noise to the downstream data. Exploring the mechanisms underlying Hi-C artifacts pinpoints steps that should be further optimized in the future. To improve the utility of Hi-C in characterizing the 3D genome of specialized populations of cells or small samples of primary tissue, we identify steps prone to DNA loss which should be considered to adapt Hi-C to lower cell numbers. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Impact of a new gasoline benzene regulation on ambient air pollutants in Anchorage, Alaska

    Science.gov (United States)

    Yano, Yuriko; Morris, Stephen S.; Salerno, Christopher; Schlapia, Anne M.; Stichick, Mathew

    2016-05-01

    The purpose of this study was to quantify the impact of a new U.S. Environmental Protection Agency (EPA) standard that limits the amount of benzene allowed in gasoline on ambient benzene concentrations. This new standard, together with two companion regulations that limit cold-temperature automotive emissions and the permeability of portable fuel containers, was expected to lower the levels of ambient benzene and other volatile organic compounds (VOCs) nationwide. In this study the impact of the gasoline benzene standard was evaluated in Anchorage, Alaska in a two-phase ambient air monitoring study conducted before and after the new gasoline standard was implemented. Gasoline sold by Anchorage retailers was also evaluated in each phase to determine the content of benzene and other gasoline components. The average benzene content in Anchorage gasoline was reduced by 70%, from 5.05% (w/w) to 1.53% (w/w) following the implementation of the standard. The annual mean ambient benzene concentration fell by 51%, from 0.99 ppbv in Phase 1 to 0.49 ppbv in Phase 2. Analysis suggests the change in gasoline benzene content alone reduced benzene emissions by 46%. The changes in toluene, ethylbenzene, and xylene content in gasoline between Phase 1 and 2 were relatively small and the differences in the mean ambient concentrations of these compounds between phases were modest. Our results suggest that cold winter communities in high latitude and mountainous regions may benefit more from the gasoline benzene standard because of high benzene emissions resulting from vehicle cold start and a tendency to develop atmospheric stagnation conditions in the winter.

  1. 76 FR 59596 - Anchorage Regulations; Newport, RI

    Science.gov (United States)

    2011-09-27

    ... up to three cruise ships simultaneously in anchorage ``D''. For the convenience and safety of... standards (e.g., specifications of materials, performance, design, or operation; test methods; sampling...

  2. Promoter-enhancer interactions identified from Hi-C data using probabilistic models and hierarchical topological domains.

    Science.gov (United States)

    Ron, Gil; Globerson, Yuval; Moran, Dror; Kaplan, Tommy

    2017-12-21

    Proximity-ligation methods such as Hi-C allow us to map physical DNA-DNA interactions along the genome, and reveal its organization into topologically associating domains (TADs). As the Hi-C data accumulate, computational methods were developed for identifying domain borders in multiple cell types and organisms. Here, we present PSYCHIC, a computational approach for analyzing Hi-C data and identifying promoter-enhancer interactions. We use a unified probabilistic model to segment the genome into domains, which we then merge hierarchically and fit using a local background model, allowing us to identify over-represented DNA-DNA interactions across the genome. By analyzing the published Hi-C data sets in human and mouse, we identify hundreds of thousands of putative enhancers and their target genes, and compile an extensive genome-wide catalog of gene regulation in human and mouse. As we show, our predictions are highly enriched for ChIP-seq and DNA accessibility data, evolutionary conservation, eQTLs and other DNA-DNA interaction data.

  3. 77 FR 6010 - Anchorage Regulations; Newport, RI

    Science.gov (United States)

    2012-02-07

    ... anchor up to three cruise ships simultaneously in anchorage ``D''. For the convenience and safety of..., design, or operation; test methods; sampling procedures; and related management systems practices) that...

  4. OneD: increasing reproducibility of Hi-C samples with abnormal karyotypes.

    Science.gov (United States)

    Vidal, Enrique; le Dily, François; Quilez, Javier; Stadhouders, Ralph; Cuartero, Yasmina; Graf, Thomas; Marti-Renom, Marc A; Beato, Miguel; Filion, Guillaume J

    2018-05-04

    The three-dimensional conformation of genomes is an essential component of their biological activity. The advent of the Hi-C technology enabled an unprecedented progress in our understanding of genome structures. However, Hi-C is subject to systematic biases that can compromise downstream analyses. Several strategies have been proposed to remove those biases, but the issue of abnormal karyotypes received little attention. Many experiments are performed in cancer cell lines, which typically harbor large-scale copy number variations that create visible defects on the raw Hi-C maps. The consequences of these widespread artifacts on the normalized maps are mostly unexplored. We observed that current normalization methods are not robust to the presence of large-scale copy number variations, potentially obscuring biological differences and enhancing batch effects. To address this issue, we developed an alternative approach designed to take into account chromosomal abnormalities. The method, called OneD, increases reproducibility among replicates of Hi-C samples with abnormal karyotype, outperforming previous methods significantly. On normal karyotypes, OneD fared equally well as state-of-the-art methods, making it a safe choice for Hi-C normalization. OneD is fast and scales well in terms of computing resources for resolutions up to 5 kb.

  5. Digestion-ligation-only Hi-C is an efficient and cost-effective method for chromosome conformation capture.

    Science.gov (United States)

    Lin, Da; Hong, Ping; Zhang, Siheng; Xu, Weize; Jamal, Muhammad; Yan, Keji; Lei, Yingying; Li, Liang; Ruan, Yijun; Fu, Zhen F; Li, Guoliang; Cao, Gang

    2018-05-01

    Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome. This method requires only two rounds of digestion and ligation, without the need for biotin labeling and pulldown. Non-ligated DNA was efficiently removed in a cost-effective step by purifying specific linker-ligated DNA fragments. Notably, random ligation could be quickly evaluated in an early quality-control step before sequencing. Moreover, an in situ version of DLO Hi-C using a four-cutter restriction enzyme has been developed. We applied DLO Hi-C to delineate the genomic architecture of THP-1 and K562 cells and uncovered chromosomal translocations. This technology may facilitate investigation of genomic organization, gene regulation, and (meta)genome assembly.

  6. Capturing Three-Dimensional Genome Organization in Individual Cells by Single-Cell Hi-C.

    Science.gov (United States)

    Nagano, Takashi; Wingett, Steven W; Fraser, Peter

    2017-01-01

    Hi-C is a powerful method to investigate genome-wide, higher-order chromatin and chromosome conformations averaged from a population of cells. To expand the potential of Hi-C for single-cell analysis, we developed single-cell Hi-C. Similar to the existing "ensemble" Hi-C method, single-cell Hi-C detects proximity-dependent ligation events between cross-linked and restriction-digested chromatin fragments in cells. A major difference between the single-cell Hi-C and ensemble Hi-C protocol is that the proximity-dependent ligation is carried out in the nucleus. This allows the isolation of individual cells in which nearly the entire Hi-C procedure has been carried out, enabling the production of a Hi-C library and data from individual cells. With this new method, we studied genome conformations and found evidence for conserved topological domain organization from cell to cell, but highly variable interdomain contacts and chromosome folding genome wide. In addition, we found that the single-cell Hi-C protocol provided cleaner results with less technical noise suggesting it could be used to improve the ensemble Hi-C technique.

  7. Hyriopsis cumingii Hic52-A novel nacreous layer matrix protein with a collagen-like structure.

    Science.gov (United States)

    Liu, Xiaojun; Pu, Jingwen; Zeng, Shimei; Jin, Can; Dong, Shaojian; Li, Jiale

    2017-09-01

    Nacre is a product of a precisely regulated biomineralization process and a major contributor to the luster of pearls. Nacre is composed of calcium carbonate and an organic matrix of proteins that is secreted from mollusc mantle tissue and is exclusively associated with shell formation. In this study, hic52, a novel matrix protein gene from mantle of Hyriopsis cumingii, was cloned and functionally analyzed. The full-length cDNA of hic52 encoded 542 amino acids and contained a signal peptide of 18 amino acids. Excluding the signal peptide, the theoretical molecular mass of the polypeptide was 52.2kDa. The predicted isoelectric point was 10.37, indicating a basic shell protein. The amino acid sequence of hic52 featured high proportion of Gly (28.8%) and Gln (12.4%) residues. The predicted tertiary structure was characterized as having similarities to collagen I, alpha 1 and alpha 2 in the structure. The polypeptide sequence shared no homology with collagen. The hic52 expression pattern by quantitative real-time PCR and in situ hybridization exhibits at the dorsal epithelial cells of the mantle. Expression increased during the stages of pearl sac development. The data showed that hic52 is probably a framework shell protein that mediates and controls the nacreous biomineralization process. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Coronal Fine Structure in Dynamic Events Observed by Hi-C

    Science.gov (United States)

    Winebarger, Amy; Schuler, Timothy

    2013-01-01

    The High-Resolution Coronal Imager (Hi-C) flew aboard a NASA sounding rocket on 2012 July 11 and captured roughly 345 s of high spatial and temporal resolution images of the solar corona in a narrowband 193 Angstrom channel. We have analyzed the fluctuations in intensity of Active Region 11520. We selected events based on a lifetime greater than 11 s (two Hi-C frames) and intensities greater than a threshold determined from the photon and readout noise. We compare the Hi-C events with those determined from AIA. We find that HI-C detects shorter and smaller events than AIA. We also find that the intensity increase in the Hi-C events is approx. 3 times greater than the intensity increase in the AIA events we conclude the events are related to linear sub-structure that is unresolved by AIA

  9. Down-regulation of Rab5 decreases characteristics associated with maintenance of cell transformation

    International Nuclear Information System (INIS)

    Silva, Patricio; Soto, Nicolás; Díaz, Jorge; Mendoza, Pablo; Díaz, Natalia; Quest, Andrew F.G.; Torres, Vicente A.

    2015-01-01

    The early endosomal protein Rab5 is highly expressed in tumor samples, although a causal relationship between Rab5 expression and cell transformation has not been established. Here, we report the functional effects of targeting endogenous Rab5 with specific shRNA sequences in different tumor cell lines. Rab5 down-regulation in B16-F10 cells decreased tumor formation by subcutaneous injection into C57/BL6 mice. Accordingly, Rab5 targeting in B16-F10 and A549, but not MDA-MB-231 cells was followed by decreased cell proliferation, increased apoptosis and decreased anchorage-independent growth. These findings suggest that Rab5 expression is required to maintain characteristics associated with cell transformation. - Highlights: • Rab5 is important to the maintenance of cell transformation characteristics. • Down-regulation of Rab5 decreases cell proliferation and increases apoptosis in different cancer cells. • Rab5 is required for anchorage-independent growth and tumorigenicity in-vivo

  10. Hi-C 2.0: An optimized Hi-C procedure for high-resolution genome-wide mapping of chromosome conformation.

    Science.gov (United States)

    Belaghzal, Houda; Dekker, Job; Gibcus, Johan H

    2017-07-01

    Chromosome conformation capture-based methods such as Hi-C have become mainstream techniques for the study of the 3D organization of genomes. These methods convert chromatin interactions reflecting topological chromatin structures into digital information (counts of pair-wise interactions). Here, we describe an updated protocol for Hi-C (Hi-C 2.0) that integrates recent improvements into a single protocol for efficient and high-resolution capture of chromatin interactions. This protocol combines chromatin digestion and frequently cutting enzymes to obtain kilobase (kb) resolution. It also includes steps to reduce random ligation and the generation of uninformative molecules, such as unligated ends, to improve the amount of valid intra-chromosomal read pairs. This protocol allows for obtaining information on conformational structures such as compartment and topologically associating domains, as well as high-resolution conformational features such as DNA loops. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Quantification of DNA cleavage specificity in Hi-C experiments.

    Science.gov (United States)

    Meluzzi, Dario; Arya, Gaurav

    2016-01-08

    Hi-C experiments produce large numbers of DNA sequence read pairs that are typically analyzed to deduce genomewide interactions between arbitrary loci. A key step in these experiments is the cleavage of cross-linked chromatin with a restriction endonuclease. Although this cleavage should happen specifically at the enzyme's recognition sequence, an unknown proportion of cleavage events may involve other sequences, owing to the enzyme's star activity or to random DNA breakage. A quantitative estimation of these non-specific cleavages may enable simulating realistic Hi-C read pairs for validation of downstream analyses, monitoring the reproducibility of experimental conditions and investigating biophysical properties that correlate with DNA cleavage patterns. Here we describe a computational method for analyzing Hi-C read pairs to estimate the fractions of cleavages at different possible targets. The method relies on expressing an observed local target distribution downstream of aligned reads as a linear combination of known conditional local target distributions. We validated this method using Hi-C read pairs obtained by computer simulation. Application of the method to experimental Hi-C datasets from murine cells revealed interesting similarities and differences in patterns of cleavage across the various experiments considered. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Comparison of Hi-C results using in-solution versus in-nucleus ligation.

    Science.gov (United States)

    Nagano, Takashi; Várnai, Csilla; Schoenfelder, Stefan; Javierre, Biola-Maria; Wingett, Steven W; Fraser, Peter

    2015-08-26

    Chromosome conformation capture and various derivative methods such as 4C, 5C and Hi-C have emerged as standard tools to analyze the three-dimensional organization of the genome in the nucleus. These methods employ ligation of diluted cross-linked chromatin complexes, intended to favor proximity-dependent, intra-complex ligation. During development of single-cell Hi-C, we devised an alternative Hi-C protocol with ligation in preserved nuclei rather than in solution. Here we directly compare Hi-C methods employing in-nucleus ligation with the standard in-solution ligation. We show in-nucleus ligation results in consistently lower levels of inter-chromosomal contacts. Through chromatin mixing experiments we show that a significantly large fraction of inter-chromosomal contacts are the result of spurious ligation events formed during in-solution ligation. In-nucleus ligation significantly reduces this source of experimental noise, and results in improved reproducibility between replicates. We also find that in-nucleus ligation eliminates restriction fragment length bias found with in-solution ligation. These improvements result in greater reproducibility of long-range intra-chromosomal and inter-chromosomal contacts, as well as enhanced detection of structural features such as topologically associated domain boundaries. We conclude that in-nucleus ligation captures chromatin interactions more consistently over a wider range of distances, and significantly reduces both experimental noise and bias. In-nucleus ligation creates higher quality Hi-C libraries while simplifying the experimental procedure. We suggest that the entire range of 3C applications are likely to show similar benefits from in-nucleus ligation.

  13. Effect of Microstructure on HIC Susceptibility of API X70MS Linepipe Steel

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Joon-Ho; Sim, Ho-Seop; Park, Byung-Gyu [Dongkuk Steel R and D Center, Pohang (Korea, Republic of); Cho, Kyung-Mox [Pusan National University, Busan (Korea, Republic of)

    2017-06-15

    The resistance of hydrogen induced cracking (HIC) was investigated with different microstructures of API X70MS steel. Ferrite/acicular ferrite (F/AF), deformed ferrite/acicular ferrite, ferrite/bainite (F/B) and single acicular ferrite (AF) were obtained by thermo-mechanical controlled process (TMCP) with changing rolling and cooling conditions. HIC resistance was found to be affected by the type as well as morphology of the microstructure, and thus the behavior of crack initiation and propagation could be analyzed. It was found that single AF and deformed F/AF with uniformly distributed dislocation reduced HIC initiation. Banded microstructure with a hardness value below 250 HV, such as AF, showed good HIC propagation resistance due to high toughness. AF generally exhibited excellent crack initiation and propagation resistance, namely the best HIC susceptibility performance. AF might redeem the HIC resistance for the banded microstructure also.

  14. Mapping 3D genome architecture through in situ DNase Hi-C.

    Science.gov (United States)

    Ramani, Vijay; Cusanovich, Darren A; Hause, Ronald J; Ma, Wenxiu; Qiu, Ruolan; Deng, Xinxian; Blau, C Anthony; Disteche, Christine M; Noble, William S; Shendure, Jay; Duan, Zhijun

    2016-11-01

    With the advent of massively parallel sequencing, considerable work has gone into adapting chromosome conformation capture (3C) techniques to study chromosomal architecture at a genome-wide scale. We recently demonstrated that the inactive murine X chromosome adopts a bipartite structure using a novel 3C protocol, termed in situ DNase Hi-C. Like traditional Hi-C protocols, in situ DNase Hi-C requires that chromatin be chemically cross-linked, digested, end-repaired, and proximity-ligated with a biotinylated bridge adaptor. The resulting ligation products are optionally sheared, affinity-purified via streptavidin bead immobilization, and subjected to traditional next-generation library preparation for Illumina paired-end sequencing. Importantly, in situ DNase Hi-C obviates the dependence on a restriction enzyme to digest chromatin, instead relying on the endonuclease DNase I. Libraries generated by in situ DNase Hi-C have a higher effective resolution than traditional Hi-C libraries, which makes them valuable in cases in which high sequencing depth is allowed for, or when hybrid capture technologies are expected to be used. The protocol described here, which involves ∼4 d of bench work, is optimized for the study of mammalian cells, but it can be broadly applicable to any cell or tissue of interest, given experimental parameter optimization.

  15. Bone anchorage: When and why?

    Directory of Open Access Journals (Sweden)

    Ahmet Nejat Erverdi

    2015-01-01

    Full Text Available Anchorage is the most important concept in biomechanics of orthodontics. In contemporary orthodontics, bone anchorage is a magic tool, which decreased the indication for extraoral appliances greatly and at the same time achieving stationary anchorage became possible. However, the indication for bone anchorage has to be clarified carefully. Skeletal open-bite treatment, effective molar distalization, Class III treatment by using chin anchorage, and space closure in severe minimal anchorage cases are some examples for bone anchorage supported orthodontic treatment. Here, we discussed three necessary usages of bone anchorage for different treatment modalities.

  16. Principles of Chromosome Architecture Revealed by Hi-C.

    Science.gov (United States)

    Eagen, Kyle P

    2018-06-01

    Chromosomes are folded and compacted in interphase nuclei, but the molecular basis of this folding is poorly understood. Chromosome conformation capture methods, such as Hi-C, combine chemical crosslinking of chromatin with fragmentation, DNA ligation, and high-throughput DNA sequencing to detect neighboring loci genome-wide. Hi-C has revealed the segregation of chromatin into active and inactive compartments and the folding of DNA into self-associating domains and loops. Depletion of CTCF, cohesin, or cohesin-associated proteins was recently shown to affect the majority of domains and loops in a manner that is consistent with a model of DNA folding through extrusion of chromatin loops. Compartmentation was not dependent on CTCF or cohesin. Hi-C contact maps represent the superimposition of CTCF/cohesin-dependent and -independent folding states. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. HiCUP: pipeline for mapping and processing Hi-C data.

    Science.gov (United States)

    Wingett, Steven; Ewels, Philip; Furlan-Magaril, Mayra; Nagano, Takashi; Schoenfelder, Stefan; Fraser, Peter; Andrews, Simon

    2015-01-01

    HiCUP is a pipeline for processing sequence data generated by Hi-C and Capture Hi-C (CHi-C) experiments, which are techniques used to investigate three-dimensional genomic organisation. The pipeline maps data to a specified reference genome and removes artefacts that would otherwise hinder subsequent analysis. HiCUP also produces an easy-to-interpret yet detailed quality control (QC) report that assists in refining experimental protocols for future studies. The software is freely available and has already been used for processing Hi-C and CHi-C data in several recently published peer-reviewed studies.

  18. Optimization and quality control of genome-wide Hi-C library preparation.

    Science.gov (United States)

    Zhang, Xiang-Yuan; He, Chao; Ye, Bing-Yu; Xie, De-Jian; Shi, Ming-Lei; Zhang, Yan; Shen, Wen-Long; Li, Ping; Zhao, Zhi-Hu

    2017-09-20

    Highest-throughput chromosome conformation capture (Hi-C) is one of the key assays for genome- wide chromatin interaction studies. It is a time-consuming process that involves many steps and many different kinds of reagents, consumables, and equipments. At present, the reproducibility is unsatisfactory. By optimizing the key steps of the Hi-C experiment, such as crosslinking, pretreatment of digestion, inactivation of restriction enzyme, and in situ ligation etc., we established a robust Hi-C procedure and prepared two biological replicates of Hi-C libraries from the GM12878 cells. After preliminary quality control by Sanger sequencing, the two replicates were high-throughput sequenced. The bioinformatics analysis of the raw sequencing data revealed the mapping-ability and pair-mate rate of the raw data were around 90% and 72%, respectively. Additionally, after removal of self-circular ligations and dangling-end products, more than 96% of the valid pairs were reached. Genome-wide interactome profiling shows clear topological associated domains (TADs), which is consistent with previous reports. Further correlation analysis showed that the two biological replicates strongly correlate with each other in terms of both bin coverage and all bin pairs. All these results indicated that the optimized Hi-C procedure is robust and stable, which will be very helpful for the wide applications of the Hi-C assay.

  19. Enhancing Hi-C data resolution with deep convolutional neural network HiCPlus.

    Science.gov (United States)

    Zhang, Yan; An, Lin; Xu, Jie; Zhang, Bo; Zheng, W Jim; Hu, Ming; Tang, Jijun; Yue, Feng

    2018-02-21

    Although Hi-C technology is one of the most popular tools for studying 3D genome organization, due to sequencing cost, the resolution of most Hi-C datasets are coarse and cannot be used to link distal regulatory elements to their target genes. Here we develop HiCPlus, a computational approach based on deep convolutional neural network, to infer high-resolution Hi-C interaction matrices from low-resolution Hi-C data. We demonstrate that HiCPlus can impute interaction matrices highly similar to the original ones, while only using 1/16 of the original sequencing reads. We show that the models learned from one cell type can be applied to make predictions in other cell or tissue types. Our work not only provides a computational framework to enhance Hi-C data resolution but also reveals features underlying the formation of 3D chromatin interactions.

  20. Discovery of Finely Structured Dynamic Solar Corona Observed in the Hi-C Telescope

    Science.gov (United States)

    Winebarger, A.; Cirtain, J.; Golub, L.; DeLuca, E.; Savage, S.; Alexander, C.; Schuler, T.

    2014-01-01

    In the summer of 2012, the High-resolution Coronal Imager (Hi-C) flew aboard a NASA sounding rocket and collected the highest spatial resolution images ever obtained of the solar corona. One of the goals of the Hi-C flight was to characterize the substructure of the solar corona. We therefore examine how the intensity scales from AIA resolution to Hi-C resolution. For each low-resolution pixel, we calculate the standard deviation in the contributing high-resolution pixel intensities and compare that to the expected standard deviation calculated from the noise. If these numbers are approximately equal, the corona can be assumed to be smoothly varying, i.e. have no evidence of substructure in the Hi-C image to within Hi-C's ability to measure it given its throughput and readout noise. A standard deviation much larger than the noise value indicates the presence of substructure. We calculate these values for each low-resolution pixel for each frame of the Hi-C data. On average, 70 percent of the pixels in each Hi-C image show no evidence of substructure. The locations where substructure is prevalent is in the moss regions and in regions of sheared magnetic field. We also find that the level of substructure varies significantly over the roughly 160 s of the Hi-C data analyzed here. This result indicates that the finely structured corona is concentrated in regions of heating and is highly time dependent.

  1. Structural Evaluation on HIC Transport Packaging under Accident Conditions

    International Nuclear Information System (INIS)

    Chung, Sung Hwan; Kim, Duck Hoi; Jung, Jin Se; Yang, Ke Hyung; Lee, Heung Young

    2005-01-01

    HIC transport packaging to transport a high integrity container(HIC) containing dry spent resin generated from nuclear power plants is to comply with the regulatory requirements of Korea and IAEA for Type B packaging due to the high radioactivity of the content, and to maintain the structural integrity under normal and accident conditions. It must withstand 9 m free drop impact onto an unyielding surface and 1 m drop impact onto a mild steel bar in a position causing maximum damage. For the conceptual design of a cylindrical HIC transport package, three dimensional dynamic structural analysis to ensure that the integrity of the package is maintained under all credible loads for 9 m free drop and 1 m puncture conditions were carried out using ABAQUS code.

  2. Bone anchorage: When and why?

    OpenAIRE

    Ahmet Nejat Erverdi

    2015-01-01

    Anchorage is the most important concept in biomechanics of orthodontics. In contemporary orthodontics, bone anchorage is a magic tool, which decreased the indication for extraoral appliances greatly and at the same time achieving stationary anchorage became possible. However, the indication for bone anchorage has to be clarified carefully. Skeletal open-bite treatment, effective molar distalization, Class III treatment by using chin anchorage, and space closure in severe minimal anchorage cas...

  3. HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea

    DEFF Research Database (Denmark)

    Jørgensen, Mikkel G; Pandey, Deo P; Jaskolska, Milena

    2009-01-01

    . Expression of HicB (145 aa) prevented HicA-mediated inhibition of cell growth. These results suggest that HicB neutralizes HicA and therefore functions as an antitoxin. As with other antitoxins (RelB and MazF), HicB could resuscitate cells inhibited by HicA, indicating that ectopic production of HicA induces...

  4. Tandem repeat variation near the HIC1 (hypermethylated in cancer 1) promoter predicts outcome of oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.

    Science.gov (United States)

    Okazaki, Satoshi; Schirripa, Marta; Loupakis, Fotios; Cao, Shu; Zhang, Wu; Yang, Dongyun; Ning, Yan; Berger, Martin D; Miyamoto, Yuji; Suenaga, Mitsukuni; Iqubal, Syma; Barzi, Afsaneh; Cremolini, Chiara; Falcone, Alfredo; Battaglin, Francesca; Salvatore, Lisa; Borelli, Beatrice; Helentjaris, Timothy G; Lenz, Heinz-Josef

    2017-11-15

    The hypermethylated in cancer 1/sirtuin 1 (HIC1/SIRT1) axis plays an important role in regulating the nucleotide excision repair pathway, which is the main oxaliplatin-induced damage-repair system. On the basis of prior evidence that the variable number of tandem repeat (VNTR) sequence located near the promoter lesion of HIC1 is associated with HIC1 gene expression, the authors tested the hypothesis that this VNTR is associated with clinical outcome in patients with metastatic colorectal cancer who receive oxaliplatin-based chemotherapy. Four independent cohorts were tested. Patients who received oxaliplatin-based chemotherapy served as the training cohort (n = 218), and those who received treatment without oxaliplatin served as the control cohort (n = 215). Two cohorts of patients who received oxaliplatin-based chemotherapy were used for validation studies (n = 176 and n = 73). The VNTR sequence near HIC1 was analyzed by polymerase chain reaction analysis and gel electrophoresis and was tested for associations with the response rate, progression-free survival, and overall survival. In the training cohort, patients who harbored at least 5 tandem repeats (TRs) in both alleles had a significantly shorter PFS compared with those who had fewer than 4 TRs in at least 1 allele (9.5 vs 11.6 months; hazard ratio, 1.93; P = .012), and these findings remained statistically significant after multivariate analysis (hazard ratio, 2.00; 95% confidence interval, 1.13-3.54; P = .018). This preliminary association was confirmed in the validation cohort, and patients who had at least 5 TRs in both alleles had a worse PFS compared with the other cohort (7.9 vs 9.8 months; hazard ratio, 1.85; P = .044). The current findings suggest that the VNTR sequence near HIC1 could be a predictive marker for oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Cancer 2017;123:4506-14. © 2017 American Cancer Society. © 2017 American Cancer Society.

  5. DISCOVERY OF FINELY STRUCTURED DYNAMIC SOLAR CORONA OBSERVED IN THE Hi-C TELESCOPE

    Energy Technology Data Exchange (ETDEWEB)

    Winebarger, Amy R.; Cirtain, Jonathan; Savage, Sabrina; Alexander, Caroline [NASA Marshall Space Flight Center, ZP 13, Huntsville, AL 35812 (United States); Golub, Leon; DeLuca, Edward [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Schuler, Timothy, E-mail: amy.r.winebarger@nasa.gov [State University of New York College at Buffalo, 1300 Elmwood Avenue, Buffalo, NY 14222 (United States)

    2014-05-20

    In the Summer of 2012, the High-resolution Coronal Imager (Hi-C) flew on board a NASA sounding rocket and collected the highest spatial resolution images ever obtained of the solar corona. One of the goals of the Hi-C flight was to characterize the substructure of the solar corona. We therefore examine how the intensity scales from AIA resolution to Hi-C resolution. For each low-resolution pixel, we calculate the standard deviation in the contributing high-resolution pixel intensities and compare that to the expected standard deviation calculated from the noise. If these numbers are approximately equal, the corona can be assumed to be smoothly varying, i.e., have no evidence of substructure in the Hi-C image to within Hi-C's ability to measure it given its throughput and readout noise. A standard deviation much larger than the noise value indicates the presence of substructure. We calculate these values for each low-resolution pixel for each frame of the Hi-C data. On average, 70% of the pixels in each Hi-C image show no evidence of substructure. The locations where substructure is prevalent is in the moss regions and in regions of sheared magnetic field. We also find that the level of substructure varies significantly over the roughly 160 s of the Hi-C data analyzed here. This result indicates that the finely structured corona is concentrated in regions of heating and is highly time dependent.

  6. DISCOVERY OF FINELY STRUCTURED DYNAMIC SOLAR CORONA OBSERVED IN THE Hi-C TELESCOPE

    International Nuclear Information System (INIS)

    Winebarger, Amy R.; Cirtain, Jonathan; Savage, Sabrina; Alexander, Caroline; Golub, Leon; DeLuca, Edward; Schuler, Timothy

    2014-01-01

    In the Summer of 2012, the High-resolution Coronal Imager (Hi-C) flew on board a NASA sounding rocket and collected the highest spatial resolution images ever obtained of the solar corona. One of the goals of the Hi-C flight was to characterize the substructure of the solar corona. We therefore examine how the intensity scales from AIA resolution to Hi-C resolution. For each low-resolution pixel, we calculate the standard deviation in the contributing high-resolution pixel intensities and compare that to the expected standard deviation calculated from the noise. If these numbers are approximately equal, the corona can be assumed to be smoothly varying, i.e., have no evidence of substructure in the Hi-C image to within Hi-C's ability to measure it given its throughput and readout noise. A standard deviation much larger than the noise value indicates the presence of substructure. We calculate these values for each low-resolution pixel for each frame of the Hi-C data. On average, 70% of the pixels in each Hi-C image show no evidence of substructure. The locations where substructure is prevalent is in the moss regions and in regions of sheared magnetic field. We also find that the level of substructure varies significantly over the roughly 160 s of the Hi-C data analyzed here. This result indicates that the finely structured corona is concentrated in regions of heating and is highly time dependent

  7. Hi-C Observations of an Active Region Corona, and Investigation of the Underlying Magnetic Structure

    Science.gov (United States)

    Tiwari, S. K.; Alexander, C. E.; Winebarger, A.; Moore, R. L.

    2014-01-01

    The solar corona is much hotter (>=10(exp 6) K) than its surface (approx 6000 K), puzzling astrophysicists for several decades. Active region (AR) corona is again hotter than the quiet Sun (QS) corona by a factor of 4-10. The most widely accepted mechanism that could heat the active region corona is the energy release by current dissipation via reconnection of braided magnetic field structure, first proposed by E. N. Parker three decades ago. The first observational evidence for this mechanism has only recently been presented by Cirtain et al. by using High-resolution Coronal Imager (Hi-C) observations of an AR corona at a spatial resolution of 0.2 arcsec, which is required to resolve the coronal loops, and was not available before the rocket flight of Hi-C in July 2012. The Hi-C project is led by NASA/MSFC. In the case of the QS, work done by convection/granulation on the inter-granular feet of the coronal field lines translates into the heat observed in the corona. In the case of the AR, as here, there could be flux emergence, cancellation/submergence, or shear flows generating large stress and tension in coronal field loops which is released as heat in the corona. We are currently investigating the changes taking place in photospheric feet of the magnetic field involved with brightenings in the Hi-C AR corona. For this purpose, we are also using SDO/AIA data of +/- 2 hours around the 5 minutes Hi-C flight. In the present talk, I will first summarize some of the results of the Hi-C observations and then present some results from our recent analysis on what photospheric processes feed the magnetic energy that dissipates into heat in coronal loops.

  8. Hospital incident command system (HICS performance in Iran; decision making during disasters

    Directory of Open Access Journals (Sweden)

    Djalali Ahmadreza

    2012-02-01

    Full Text Available Abstract Background Hospitals are cornerstones for health care in a community and must continue to function in the face of a disaster. The Hospital Incident Command System (HICS is a method by which the hospital operates when an emergency is declared. Hospitals are often ill equipped to evaluate the strengths and vulnerabilities of their own management systems before the occurrence of an actual disaster. The main objective of this study was to measure the decision making performance according to HICS job actions sheets using tabletop exercises. Methods This observational study was conducted between May 1st 2008 and August 31st 2009. Twenty three Iranian hospitals were included. A tabletop exercise was developed for each hospital which in turn was based on the highest probable risk. The job action sheets of the HICS were used as measurements of performance. Each indicator was considered as 1, 2 or 3 in accordance with the HICS. Fair performance was determined as Results None of the participating hospitals had a hospital disaster management plan. The performance according to HICS was intermediate for 83% (n = 19 of the participating hospitals. No hospital had a high level of performance. The performance level for the individual sections was intermediate or fair, except for the logistic and finance sections which demonstrated a higher level of performance. The public hospitals had overall higher performances than university hospitals (P = 0.04. Conclusions The decision making performance in the Iranian hospitals, as measured during table top exercises and using the indicators proposed by HICS was intermediate to poor. In addition, this study demonstrates that the HICS job action sheets can be used as a template for measuring the hospital response. Simulations can be used to assess preparedness, but the correlation with outcome remains to be studied.

  9. Procedures adopted by orthodontists for space closure and anchorage control.

    Science.gov (United States)

    Monini, André da Costa; Gandini Júnior, Luiz Gonzaga; dos Santos-Pinto, Ary; Maia, Luiz Guilherme Martins; Rodrigues, Willian Caetano

    2013-01-01

    The aim of this study was to identify the procedures adopted by Brazilian orthodontists in the following situations: extraction space closure, anchorage control in case of necessary anchorage for group A and frequency of skeletal anchorage use, especially in the upper jaw. A questionnaire was sent to the e-mail address of all dentists registered in the Brazilian Federal Council of Dentistry. The results showed that most Brazilian orthodontists usually perform extraction space closure by means of sliding mechanics. The use of palatal bar, inclusion of second molars in the archwire and space closure performed in two phases are the most used techniques for anchorage control in the upper jaw. The skeletal anchorage is referenced by 36.5% of specialists as a routine practice for the upper arch anchorage. There is a wide variety of procedures adopted by Brazilian orthodontists for orthodontic space closure and anchorage control.

  10. Serotype 3 pneumococci sequester platelet-derived human thrombospondin-1 via the adhesin and immune evasion protein Hic.

    Science.gov (United States)

    Binsker, Ulrike; Kohler, Thomas P; Krauel, Krystin; Kohler, Sylvia; Habermeyer, Johanna; Schwertz, Hansjörg; Hammerschmidt, Sven

    2017-04-07

    Streptococcus pneumoniae serotype 3 strains emerge frequently within clinical isolates of invasive diseases. Bacterial invasion into deeper tissues is associated with colonization and immune evasion mechanisms. Thus, pneumococci express a versatile repertoire of surface proteins sequestering and interacting specifically with components of the human extracellular matrix and serum. Hic, a PspC-like pneumococcal surface protein, possesses vitronectin and factor H binding activity. Here, we show that heterologously expressed Hic domains interact, similar to the classical PspC molecule, with human matricellular thrombospondin-1 (hTSP-1). Binding studies with isolated human thrombospondin-1 and various Hic domains suggest that the interaction between hTSP-1 and Hic differs from binding to vitronectin and factor H. Binding of Hic to hTSP-1 is inhibited by heparin and chondroitin sulfate A, indicating binding to the N-terminal globular domain or type I repeats of hTSP-1. Competitive inhibition experiments with other pneumococcal hTSP-1 adhesins demonstrated that PspC and PspC-like Hic recognize similar domains, whereas PavB and Hic can bind simultaneously to hTSP-1. In conclusion, Hic binds specifically hTSP-1; however, truncation in the N-terminal part of Hic decreases the binding activity, suggesting that the full length of the α-helical regions of Hic is required for an optimal interaction. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. ClusterTAD: an unsupervised machine learning approach to detecting topologically associated domains of chromosomes from Hi-C data.

    Science.gov (United States)

    Oluwadare, Oluwatosin; Cheng, Jianlin

    2017-11-14

    With the development of chromosomal conformation capturing techniques, particularly, the Hi-C technique, the study of the spatial conformation of a genome is becoming an important topic in bioinformatics and computational biology. The Hi-C technique can generate genome-wide chromosomal interaction (contact) data, which can be used to investigate the higher-level organization of chromosomes, such as Topologically Associated Domains (TAD), i.e., locally packed chromosome regions bounded together by intra chromosomal contacts. The identification of the TADs for a genome is useful for studying gene regulation, genomic interaction, and genome function. Here, we formulate the TAD identification problem as an unsupervised machine learning (clustering) problem, and develop a new TAD identification method called ClusterTAD. We introduce a novel method to represent chromosomal contacts as features to be used by the clustering algorithm. Our results show that ClusterTAD can accurately predict the TADs on a simulated Hi-C data. Our method is also largely complementary and consistent with existing methods on the real Hi-C datasets of two mouse cells. The validation with the chromatin immunoprecipitation (ChIP) sequencing (ChIP-Seq) data shows that the domain boundaries identified by ClusterTAD have a high enrichment of CTCF binding sites, promoter-related marks, and enhancer-related histone modifications. As ClusterTAD is based on a proven clustering approach, it opens a new avenue to apply a large array of clustering methods developed in the machine learning field to the TAD identification problem. The source code, the results, and the TADs generated for the simulated and real Hi-C datasets are available here: https://github.com/BDM-Lab/ClusterTAD .

  12. S/HIC: Robust Identification of Soft and Hard Sweeps Using Machine Learning.

    Directory of Open Access Journals (Sweden)

    Daniel R Schrider

    2016-03-01

    Full Text Available Detecting the targets of adaptive natural selection from whole genome sequencing data is a central problem for population genetics. However, to date most methods have shown sub-optimal performance under realistic demographic scenarios. Moreover, over the past decade there has been a renewed interest in determining the importance of selection from standing variation in adaptation of natural populations, yet very few methods for inferring this model of adaptation at the genome scale have been introduced. Here we introduce a new method, S/HIC, which uses supervised machine learning to precisely infer the location of both hard and soft selective sweeps. We show that S/HIC has unrivaled accuracy for detecting sweeps under demographic histories that are relevant to human populations, and distinguishing sweeps from linked as well as neutrally evolving regions. Moreover, we show that S/HIC is uniquely robust among its competitors to model misspecification. Thus, even if the true demographic model of a population differs catastrophically from that specified by the user, S/HIC still retains impressive discriminatory power. Finally, we apply S/HIC to the case of resequencing data from human chromosome 18 in a European population sample, and demonstrate that we can reliably recover selective sweeps that have been identified earlier using less specific and sensitive methods.

  13. Procedures adopted by orthodontists for space closure and anchorage control

    Directory of Open Access Journals (Sweden)

    André da Costa Monini

    2013-12-01

    Full Text Available OBJECTIVE: The aim of this study was to identify the procedures adopted by Brazilian orthodontists in the following situations: extraction space closure, anchorage control in case of necessary anchorage for group A and frequency of skeletal anchorage use, especially in the upper jaw. METHOD: A questionnaire was sent to the e-mail address of all dentists registered in the Brazilian Federal Council of Dentistry. RESULTS: The results showed that most Brazilian orthodontists usually perform extraction space closure by means of sliding mechanics. The use of palatal bar, inclusion of second molars in the archwire and space closure performed in two phases are the most used techniques for anchorage control in the upper jaw. The skeletal anchorage is referenced by 36.5% of specialists as a routine practice for the upper jaw anchorage. CONCLUSIONS: There is a wide variety of procedures adopted by Brazilian orthodontists for orthodontic space closure and anchorage control.

  14. Inter-chromosomal Contact Properties in Live-Cell Imaging and in Hi-C.

    Science.gov (United States)

    Maass, Philipp G; Barutcu, A Rasim; Weiner, Catherine L; Rinn, John L

    2018-03-15

    Imaging (fluorescence in situ hybridization [FISH]) and genome-wide chromosome conformation capture (Hi-C) are two major approaches to the study of higher-order genome organization in the nucleus. Intra-chromosomal and inter-chromosomal interactions (referred to as non-homologous chromosomal contacts [NHCCs]) have been observed by several FISH-based studies, but locus-specific NHCCs have not been detected by Hi-C. Due to crosslinking, neither of these approaches assesses spatiotemporal properties. Toward resolving the discrepancies between imaging and Hi-C, we sought to understand the spatiotemporal properties of NHCCs in living cells by CRISPR/Cas9 live-cell imaging (CLING). In mammalian cells, we find that NHCCs are stable and occur as frequently as intra-chromosomal interactions, but NHCCs occur at farther spatial distance that could explain their lack of detection in Hi-C. By revealing the spatiotemporal properties in living cells, our study provides fundamental insights into the biology of NHCCs. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. DETECTING NANOFLARE HEATING EVENTS IN SUBARCSECOND INTER-MOSS LOOPS USING Hi-C

    International Nuclear Information System (INIS)

    Winebarger, Amy R.; Moore, Ronald; Cirtain, Jonathan; Walsh, Robert W.; De Pontieu, Bart; Title, Alan; Hansteen, Viggo; Golub, Leon; Korreck, Kelly; Weber, Mark; Kobayashi, Ken; DeForest, Craig; Kuzin, Sergey

    2013-01-01

    The High-resolution Coronal Imager (Hi-C) flew aboard a NASA sounding rocket on 2012 July 11 and captured roughly 345 s of high-spatial and temporal resolution images of the solar corona in a narrowband 193 Å channel. In this paper, we analyze a set of rapidly evolving loops that appear in an inter-moss region. We select six loops that both appear in and fade out of the Hi-C images during the short flight. From the Hi-C data, we determine the size and lifetimes of the loops and characterize whether these loops appear simultaneously along their length or first appear at one footpoint before appearing at the other. Using co-aligned, co-temporal data from multiple channels of the Atmospheric Imaging Assembly on the Solar Dynamics Observatory, we determine the temperature and density of the loops. We find the loops consist of cool (∼10 5 K), dense (∼10 10 cm –3 ) plasma. Their required thermal energy and their observed evolution suggest they result from impulsive heating similar in magnitude to nanoflares. Comparisons with advanced numerical simulations indicate that such dense, cold and short-lived loops are a natural consequence of impulsive magnetic energy release by reconnection of braided magnetic field at low heights in the solar atmosphere.

  16. Single-nucleus Hi-C of mammalian oocytes and zygotes.

    Science.gov (United States)

    Gassler, Johanna; Flyamer, Ilya M; Tachibana, Kikuë

    2018-01-01

    The 3D folding of the genome is linked to essential nuclear processes including gene expression, DNA repair, and replication. Chromatin conformation capture assays such as Hi-C are providing unprecedented insights into higher-order chromatin structure. Bulk Hi-C of millions of cells enables detection of average chromatin features at high resolution but is challenging to apply to rare cell types. This chapter describes our recently developed single-nucleus Hi-C (snHi-C) approach for detection of chromatin contacts in single nuclei of murine oocytes and one-cell embryos (zygotes). The step-by-step protocol includes isolation of these cells, extraction of nuclei, fixation, restriction digestion, ligation, and whole genome amplification. Contacts obtained by snHi-C allow detection of chromatin features including loops, topologically associating domains, and compartments when averaged over the genome. The combination of snHi-C with other single-cell techniques in these and other rare cell types will likely provide a comprehensive picture of how chromatin architecture shapes cell identity. © 2018 Elsevier Inc. All rights reserved.

  17. HiCRep: assessing the reproducibility of Hi-C data using a stratum-adjusted correlation coefficient.

    Science.gov (United States)

    Yang, Tao; Zhang, Feipeng; Yardımcı, Galip Gürkan; Song, Fan; Hardison, Ross C; Noble, William Stafford; Yue, Feng; Li, Qunhua

    2017-11-01

    Hi-C is a powerful technology for studying genome-wide chromatin interactions. However, current methods for assessing Hi-C data reproducibility can produce misleading results because they ignore spatial features in Hi-C data, such as domain structure and distance dependence. We present HiCRep, a framework for assessing the reproducibility of Hi-C data that systematically accounts for these features. In particular, we introduce a novel similarity measure, the stratum adjusted correlation coefficient (SCC), for quantifying the similarity between Hi-C interaction matrices. Not only does it provide a statistically sound and reliable evaluation of reproducibility, SCC can also be used to quantify differences between Hi-C contact matrices and to determine the optimal sequencing depth for a desired resolution. The measure consistently shows higher accuracy than existing approaches in distinguishing subtle differences in reproducibility and depicting interrelationships of cell lineages. The proposed measure is straightforward to interpret and easy to compute, making it well-suited for providing standardized, interpretable, automatable, and scalable quality control. The freely available R package HiCRep implements our approach. © 2017 Yang et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import.

    LENUS (Irish Health Repository)

    Gu, Lili

    2011-03-14

    Abstract Background The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS) by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s) predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein) as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.

  19. Three invariant Hi-C interaction patterns: Applications to genome assembly.

    Science.gov (United States)

    Oddes, Sivan; Zelig, Aviv; Kaplan, Noam

    2018-06-01

    Assembly of reference-quality genomes from next-generation sequencing data is a key challenge in genomics. Recently, we and others have shown that Hi-C data can be used to address several outstanding challenges in the field of genome assembly. This principle has since been developed in academia and industry, and has been used in the assembly of several major genomes. In this paper, we explore the central principles underlying Hi-C-based assembly approaches, by quantitatively defining and characterizing three invariant Hi-C interaction patterns on which these approaches can build: Intrachromosomal interaction enrichment, distance-dependent interaction decay and local interaction smoothness. Specifically, we evaluate to what degree each invariant pattern holds on a single locus level in different species, cell types and Hi-C map resolutions. We find that these patterns are generally consistent across species and cell types but are affected by sequencing depth, and that matrix balancing improves consistency of loci with all three invariant patterns. Finally, we overview current Hi-C-based assembly approaches in light of these invariant patterns and demonstrate how local interaction smoothness can be used to easily detect scaffolding errors in extremely sparse Hi-C maps. We suggest that simultaneously considering all three invariant patterns may lead to better Hi-C-based genome assembly methods. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. 78 FR 11099 - Safety Zone Within the Lower Portion of Anchorage #9, Mantua Creek Anchorage; Paulsboro, NJ

    Science.gov (United States)

    2013-02-15

    ... 1625-AA00 Safety Zone Within the Lower Portion of Anchorage 9, Mantua Creek Anchorage; Paulsboro, NJ... temporary safety zone around the southern one-third of Anchorage 9 (Mantua Creek Anchorage), below position 39[deg] 51.573 N-075[deg] 13.557 W due to dredging operations. The Dredge Florida will be working...

  1. 33 CFR 162.136 - Connecting waters from Lake Huron to Lake Erie; anchorage grounds.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Connecting waters from Lake Huron to Lake Erie; anchorage grounds. 162.136 Section 162.136 Navigation and Navigable Waters COAST GUARD... REGULATIONS § 162.136 Connecting waters from Lake Huron to Lake Erie; anchorage grounds. (a) In the Detroit...

  2. Using DNase Hi-C techniques to map global and local three-dimensional genome architecture at high resolution.

    Science.gov (United States)

    Ma, Wenxiu; Ay, Ferhat; Lee, Choli; Gulsoy, Gunhan; Deng, Xinxian; Cook, Savannah; Hesson, Jennifer; Cavanaugh, Christopher; Ware, Carol B; Krumm, Anton; Shendure, Jay; Blau, C Anthony; Disteche, Christine M; Noble, William S; Duan, ZhiJun

    2018-06-01

    The folding and three-dimensional (3D) organization of chromatin in the nucleus critically impacts genome function. The past decade has witnessed rapid advances in genomic tools for delineating 3D genome architecture. Among them, chromosome conformation capture (3C)-based methods such as Hi-C are the most widely used techniques for mapping chromatin interactions. However, traditional Hi-C protocols rely on restriction enzymes (REs) to fragment chromatin and are therefore limited in resolution. We recently developed DNase Hi-C for mapping 3D genome organization, which uses DNase I for chromatin fragmentation. DNase Hi-C overcomes RE-related limitations associated with traditional Hi-C methods, leading to improved methodological resolution. Furthermore, combining this method with DNA capture technology provides a high-throughput approach (targeted DNase Hi-C) that allows for mapping fine-scale chromatin architecture at exceptionally high resolution. Hence, targeted DNase Hi-C will be valuable for delineating the physical landscapes of cis-regulatory networks that control gene expression and for characterizing phenotype-associated chromatin 3D signatures. Here, we provide a detailed description of method design and step-by-step working protocols for these two methods. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import

    Directory of Open Access Journals (Sweden)

    Sheehy Noreen

    2011-03-01

    Full Text Available Abstract Background The HIV-1 regulatory protein Rev, which is essential for viral replication, mediates the nuclear export of unspliced viral transcripts. Rev nuclear function requires active nucleocytoplasmic shuttling, and Rev nuclear import is mediated by the recognition of its Nuclear Localisation Signal (NLS by multiple import factors, which include transportin and importin β. However, it remains unclear which nuclear import pathway(s predominate in vivo, and the cellular environment that modulates Rev nucleocytoplasmic shuttling remains to be characterised. Results In our study, we have identified the cellular protein HIC (Human I-mfa domain-Containing protein as a novel interactor of HIV-1 Rev. We demonstrate that HIC selectively interferes with Rev NLS interaction with importin β and impedes its nuclear import and function, but does not affect Rev nuclear import mediated by transportin. Hence, the molecular determinants mediating Rev-NLS recognition by importin β and transportin appear to be distinct. Furthermore, we have employed HIC and M9 M, a peptide specifically designed to inhibit the transportin-mediated nuclear import pathway, to characterise Rev nuclear import pathways within different cellular environments. Remarkably, we could show that in 293T, HeLa, COS7, Jurkat, U937, THP-1 and CEM cells, Rev nuclear import is cell type specific and alternatively mediated by transportin or importin β, in a mutually exclusive fashion. Conclusions Rev cytoplasmic sequestration by HIC may represent a novel mechanism for the control of Rev function. These studies highlight that the multivalent nature of the Rev NLS for different import receptors enables Rev to adapt its nuclear trafficking strategy.

  4. Magnetic Structure of Sites of Braiding in Hi-C Active Region

    Science.gov (United States)

    Tiwari, S. K.; Alexander, C. E.; Winebarger, A.; Moore, R. L.

    2014-01-01

    High-resolution Coronal Imager (Hi-C) observations of an active region (AR) corona, at a spatial resolution of 0.2 arcsec, have offered the first direct evidence of field lines braiding, which could deliver sufficient energy to heat the AR corona by current dissipation via magnetic reconnection, a proposal given by Parker three decades ago. The energy required to heat the corona must be transported from the photosphere along the field lines. The mechanism that drives the energy transport to the corona is not yet fully understood. To investigate simultaneous magnetic and intensity structure in and around the AR in detail, we use SDO/HMI+AIA data of + / - 2 hours around the 5 minute Hi-C flight. In the case of the QS, work done by convection/granulation on the inter-granular feet of the coronal field lines probably translates into the heat observed in the corona. In the case of the AR, as here, there could be flux emergence, cancellation/submergence, or shear flows generating large stress and tension in coronal field loops which is released as heat in the corona. However, to the best of our knowledge, there is no observational evidence available to these processes. We investigate the changes taking place in the photospheric feet of the magnetic field involved with brightenings in the Hi-C AR corona. Using HMI 45s magnetograms of four hours we find that, out of the two Hi-C sub-regions where the braiding of field lines were recently detected, flux emergence takes place in one region and flux cancellation in the other. The field in these sub-regions are highly sheared and have apparent high speed plasma flows at their feet. Therefore, shearing flows plausibly power much of the coronal and transition region heating in these areas of the AR. In addition, the presence of large flux emergence/cancellation strongly suggests that the work done by these processes on the pre-existing field also drives much of the observed heating.

  5. A Novel Matrix Protein Hic31 from the Prismatic Layer of Hyriopsis Cumingii Displays a Collagen-Like Structure.

    Science.gov (United States)

    Liu, Xiaojun; Zeng, Shimei; Dong, Shaojian; Jin, Can; Li, Jiale

    2015-01-01

    In this study, we clone and characterize a novel matrix protein, hic31, from the mantle of Hyriopsis cumingii. The amino acid composition of hic31 consists of a high proportion of Glycine residues (26.67%). Tissue expression detection by RT-PCR indicates that hic31 is expressed specifically at the mantle edge. In situ hybridization results reveals strong signals from the dorsal epithelial cells of the outer fold at the mantle edge, and weak signals from inner epithelial cells of the same fold, indicating that hic31 is a prismatic-layer matrix protein. Although BLASTP results identify no shared homology with other shell-matrix proteins or any other known proteins, the hic31 tertiary structure is similar to that of collagen I, alpha 1 and alpha 2. It has been well proved that collagen forms the basic organic frameworks in way of collagen fibrils and minerals present within or outside of these fibrils. Therefore, hic31 might be a framework-matrix protein involved in the prismatic-layer biomineralization. Besides, the gene expression of hic31 increase in the early stages of pearl sac development, indicating that hic31 may play important roles in biomineralization of the pearl prismatic layer.

  6. A Novel Matrix Protein Hic31 from the Prismatic Layer of Hyriopsis Cumingii Displays a Collagen-Like Structure.

    Directory of Open Access Journals (Sweden)

    Xiaojun Liu

    Full Text Available In this study, we clone and characterize a novel matrix protein, hic31, from the mantle of Hyriopsis cumingii. The amino acid composition of hic31 consists of a high proportion of Glycine residues (26.67%. Tissue expression detection by RT-PCR indicates that hic31 is expressed specifically at the mantle edge. In situ hybridization results reveals strong signals from the dorsal epithelial cells of the outer fold at the mantle edge, and weak signals from inner epithelial cells of the same fold, indicating that hic31 is a prismatic-layer matrix protein. Although BLASTP results identify no shared homology with other shell-matrix proteins or any other known proteins, the hic31 tertiary structure is similar to that of collagen I, alpha 1 and alpha 2. It has been well proved that collagen forms the basic organic frameworks in way of collagen fibrils and minerals present within or outside of these fibrils. Therefore, hic31 might be a framework-matrix protein involved in the prismatic-layer biomineralization. Besides, the gene expression of hic31 increase in the early stages of pearl sac development, indicating that hic31 may play important roles in biomineralization of the pearl prismatic layer.

  7. DETECTING NANOFLARE HEATING EVENTS IN SUBARCSECOND INTER-MOSS LOOPS USING Hi-C

    Energy Technology Data Exchange (ETDEWEB)

    Winebarger, Amy R.; Moore, Ronald; Cirtain, Jonathan [NASA Marshall Space Flight Center, ZP 13, Huntsville, AL 35812 (United States); Walsh, Robert W. [University of Central Lancashire, Preston, Lancashire PR1 2HE (United Kingdom); De Pontieu, Bart; Title, Alan [Lockheed Martin Solar and Astrophysics Lab, 3251 Hanover St., Org. A0215, Bldg. 252, Palo Alto, CA 94304 (United States); Hansteen, Viggo [Institute of Theoretical Astrophysics, University of Oslo, P.O. Box 1029 Blindern, N-0315 Oslo (Norway); Golub, Leon; Korreck, Kelly; Weber, Mark [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Kobayashi, Ken [Center for Space Plasma and Aeronomic Research, University of Alabama in Huntsville, 320 Sparkman Dr, Huntsville, AL 35805 (United States); DeForest, Craig [Southwest Research Institute, 1050 Walnut Street, Suite 300, Boulder, CO 80302 (United States); Kuzin, Sergey, E-mail: amy.r.winebarger@nasa.gov [P.N. Lebedev Physical institute of the Russian Academy of Sciences, Leninskii prospekt 53 119991, Moscow (Russian Federation)

    2013-07-01

    The High-resolution Coronal Imager (Hi-C) flew aboard a NASA sounding rocket on 2012 July 11 and captured roughly 345 s of high-spatial and temporal resolution images of the solar corona in a narrowband 193 A channel. In this paper, we analyze a set of rapidly evolving loops that appear in an inter-moss region. We select six loops that both appear in and fade out of the Hi-C images during the short flight. From the Hi-C data, we determine the size and lifetimes of the loops and characterize whether these loops appear simultaneously along their length or first appear at one footpoint before appearing at the other. Using co-aligned, co-temporal data from multiple channels of the Atmospheric Imaging Assembly on the Solar Dynamics Observatory, we determine the temperature and density of the loops. We find the loops consist of cool ({approx}10{sup 5} K), dense ({approx}10{sup 10} cm{sup -3}) plasma. Their required thermal energy and their observed evolution suggest they result from impulsive heating similar in magnitude to nanoflares. Comparisons with advanced numerical simulations indicate that such dense, cold and short-lived loops are a natural consequence of impulsive magnetic energy release by reconnection of braided magnetic field at low heights in the solar atmosphere.

  8. Efficacy of the Nance appliance as an anchorage-reinforcement method.

    Science.gov (United States)

    Al-Awadhi, Ebrahim A; Garvey, Therese M; Alhag, Mohamed; Claffey, Noel M; O'Connell, Brian

    2015-03-01

    The Nance appliance is widely considered to be an efficient method of anchorage reinforcement; however, much of the perceived advantage is based on clinical judgment. The aim of this study was to assess the amounts of anchorage loss and desired tooth movement associated with the Nance appliance. The mandibular arches of 7 beagle dogs were used. The first and third premolars were extracted. Reference miniscrews were placed at the first premolar sites as stable references to measure the amounts of anchorage loss and desired tooth movement. Four beagles were fitted with custom-made Nance appliances on the fourth premolars and orthodontic bands on the second premolars (Nance group). Three beagles were fitted with orthodontic bands on the second and fourth premolars with no anchorage reinforcement (control group). The second premolars were retracted over 15 weeks in both groups. The amounts of second premolar movement (desired tooth movement) and fourth premolar movement (anchorage loss) were recorded at 5, 10, and 15 weeks. The percentages of desired tooth movement and anchorage loss to the total space closure were calculated. The mean desired tooth movement was significantly more in the Nance group than in the control group at 10 weeks (P appliance did not provide absolute anchorage, but there was significantly less anchorage loss with it than in the control group. The majority of anchorage loss occurred during the first 10 weeks in the Nance group. Copyright © 2015 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  9. Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase.

    Science.gov (United States)

    Thang, Nguyen Dinh; Yajima, Ichiro; Kumasaka, Mayuko Y; Ohnuma, Shoko; Yanagishita, Takeshi; Hayashi, Rumiko; Shekhar, Hossain U; Watanabe, Daisuke; Kato, Masashi

    2011-01-01

    Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl(2)) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5-50 µM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 µM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5-5 µM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro.

  10. Is skeletal anchorage changing the limit of orthodontics?

    DEFF Research Database (Denmark)

    Melsen, Birte

    2007-01-01

    The limits for orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied; not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... and can be loaded immediately. The course will be addressed the following topics: Are the mini-implants replacing conventional anchorage? Why are orthodontic mini-implants necessary? The development of the skeletal anchorage systems The biological basis for the skeletal anchorage systems...... The characteristics of the different skeletal anchorage systems The insertion procedure The indications for the use of orthodontic mini-implants Treatment planning in relation to the use of mini-implants Case presentations...

  11. [Skeletal anchorage in the past, today and tomorrow].

    Science.gov (United States)

    Melsen, Birte; Dalstra, Michel

    2017-03-01

    Skeletal anchorage was not introduced as an alternative to conventional anchorage modalities. The first skeletal anchorage was a ligature through a hole in the infrazygomatic crest. This was replaced by surgical screws and finally the TADs, which were optimized with respect to the material and morphology, were developed. A bracket-like head allows for the use of the mini-implant as indirect anchorage, but should not be a tool for lost control resulting from badly planned biomechanics or failing compliance. Skeletal anchorage should serve as an adjunct to correct biomechanics, to enable treatments that could not be performed prior to the introduction of skeletal anchorage. The aim of this study was to test the hypothesis that temporary anchorage mini-screws help maintain bone density, height and width of alveolar processes in the extraction sites, and thus prevent the thinning of the alveolar ridge usually observed. In adult patients with degenerated dentitions the application of skeletal anchorage can allow for the displacement of teeth where no anchorage units are present, but also for the redevelopment and maintenance of atrophic alveolar bone. The basis for the optimal use of skeletal anchorage is that the correct line of action for the desired tooth displacement is defined and the necessary force system constructed either with the skeletal anchorage as direct or as indirect anchorage. After a period, during which osseointegrated implants were used as anchorage for tooth movement and bone maintenance, it was accepted that the mini-implants could serve also as anchorage for skeletal displacements avoiding loading of teeth. © EDP Sciences, SFODF, 2017.

  12. Single-cell Hi-C for genome-wide detection of chromatin interactions that occur simultaneously in a single cell.

    Science.gov (United States)

    Nagano, Takashi; Lubling, Yaniv; Yaffe, Eitan; Wingett, Steven W; Dean, Wendy; Tanay, Amos; Fraser, Peter

    2015-12-01

    Hi-C is a powerful method that provides pairwise information on genomic regions in spatial proximity in the nucleus. Hi-C requires millions of cells as input and, as genome organization varies from cell to cell, a limitation of Hi-C is that it only provides a population average of genome conformations. We developed single-cell Hi-C to create snapshots of thousands of chromatin interactions that occur simultaneously in a single cell. To adapt Hi-C to single-cell analysis, we modified the protocol to include in-nucleus ligation. This enables the isolation of single nuclei carrying Hi-C-ligated DNA into separate tubes, followed by reversal of cross-links, capture of biotinylated ligation junctions on streptavidin-coated magnetic beads and PCR amplification of single-cell Hi-C libraries. The entire laboratory protocol can be carried out in 1 week, and although we have demonstrated its use in mouse T helper (TH1) cells, it should be applicable to any cell type or species for which standard Hi-C has been successful. We also developed an analysis pipeline to filter noise and assess the quality of data sets in a few hours. Although the interactome maps produced by single-cell Hi-C are sparse, the data provide useful information to understand cellular variability in nuclear genome organization and chromosome structure. Standard wet and dry laboratory skills in molecular biology and computational analysis are required.

  13. Orthodontic Anchorage Implants: State-of-the-art

    DEFF Research Database (Denmark)

    Melsen, Birte

    2007-01-01

    The limits of an orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied and not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... will improve the reconstruction possibilities. The mini-implant has widened the orthodontic possibilities....

  14. Sim3C: simulation of Hi-C and Meta3C proximity ligation sequencing technologies.

    Science.gov (United States)

    DeMaere, Matthew Z; Darling, Aaron E

    2018-02-01

    Chromosome conformation capture (3C) and Hi-C DNA sequencing methods have rapidly advanced our understanding of the spatial organization of genomes and metagenomes. Many variants of these protocols have been developed, each with their own strengths. Currently there is no systematic means for simulating sequence data from this family of sequencing protocols, potentially hindering the advancement of algorithms to exploit this new datatype. We describe a computational simulator that, given simple parameters and reference genome sequences, will simulate Hi-C sequencing on those sequences. The simulator models the basic spatial structure in genomes that is commonly observed in Hi-C and 3C datasets, including the distance-decay relationship in proximity ligation, differences in the frequency of interaction within and across chromosomes, and the structure imposed by cells. A means to model the 3D structure of randomly generated topologically associating domains is provided. The simulator considers several sources of error common to 3C and Hi-C library preparation and sequencing methods, including spurious proximity ligation events and sequencing error. We have introduced the first comprehensive simulator for 3C and Hi-C sequencing protocols. We expect the simulator to have use in testing of Hi-C data analysis algorithms, as well as more general value for experimental design, where questions such as the required depth of sequencing, enzyme choice, and other decisions can be made in advance in order to ensure adequate statistical power with respect to experimental hypothesis testing.

  15. Disposal demonstration of a high integrity container (HIC) containing an EPICOR-II prefilter from Three Mile Island

    International Nuclear Information System (INIS)

    McConnell, J.W. Jr.; Tyacke, M.J.; Schmitt, R.C.; Reno, H.W.

    1985-02-01

    A high integrity container (HIC) was developed, tested, and certified for use in disposing of unusual low-level radioactive waste from Three Mile Island Unit 2 (TMI-2). The work was coordinated by EG and G Idaho, Inc. and funded by the US Department of Energy. A disposal demonstration using an HIC containing an EPICOR-II prefilter from TMI-2 was completed at the commercial disposal facility in the State of Washington. A Certification of Compliance was issued by the Department of Social and Health Services of the State of Washington to use the HIC in disposing of up to 50 EPICOR-II prefilters. That Certification of Compliance was issued after rigorous review of the HIC design and test program by the State and by the US Nuclear Regulatory Commission. This report describes the processes of loading, transporting, and disposing of the demonstration HIC and briefly describes the design, testing, and approval effort leading up to the demonstration

  16. HIC1 interacts with a specific subunit of SWI/SNF complexes, ARID1A/BAF250A

    International Nuclear Information System (INIS)

    Van Rechem, Capucine; Boulay, Gaylor; Leprince, Dominique

    2009-01-01

    HIC1, a tumor suppressor gene epigenetically silenced in many human cancers encodes a transcriptional repressor involved in regulatory loops modulating p53-dependent and E2F1-dependent cell survival and stress responses. HIC1 is also implicated in growth control since it recruits BRG1, one of the two alternative ATPases (BRM or BRG1) of SWI/SNF chromatin-remodeling complexes to repress transcription of E2F1 in quiescent fibroblasts. Here, through yeast two-hybrid screening, we identify ARID1A/BAF250A, as a new HIC1 partner. ARID1A/BAF250A is one of the two mutually exclusive ARID1-containing subunits of SWI/SNF complexes which define subsets of complexes endowed with anti-proliferative properties. Co-immunoprecipitation assays in WI38 fibroblasts and in BRG1-/- SW13 cells showed that endogenous HIC1 and ARID1A proteins interact in a BRG1-dependent manner. Furthermore, we demonstrate that HIC1 does not interact with BRM. Finally, sequential chromatin immunoprecipitation (ChIP-reChIP) experiments demonstrated that HIC1 represses E2F1 through the recruitment of anti-proliferative SWI/SNF complexes containing ARID1A.

  17. Coronal Loop Evolution Observed with AIA and Hi-C

    Science.gov (United States)

    Mulu-Moore, Fana; Winebarger, A.; Cirtain, J.; Kobayashi, K.; Korreck, K.; Golub, L.; Kuzin. S.; Walsh, R.; DeForest, C.; DePontieu, B.; hide

    2012-01-01

    Despite much progress toward understanding the dynamics of the solar corona, the physical properties of coronal loops are not yet fully understood. Recent investigations and observations from different instruments have yielded contradictory results about the true physical properties of coronal loops. In the past, the evolution of loops has been used to infer the loop substructure. With the recent launch of High Resolution Coronal Imager (Hi-C), this inference can be validated. In this poster we discuss the first results of loop analysis comparing AIA and Hi-C data. We find signatures of cooling in a pixel selected along a loop structure in the AIA multi-filter observations. However, unlike previous studies, we find that the cooling time is much longer than the draining time. This is inconsistent with previous cooling models.

  18. Friction and anchorage loading revisited.

    Science.gov (United States)

    Dholakia, Kartik D

    2012-01-01

    Contemporary concepts of sliding mechanics explain that friction is inevitable. To overcome this frictional resistance, excess force is required to retract the tooth along the archwire (ie, individual retraction of canines, en masse retraction of anterior teeth), in addition to the amount of force required for tooth movement. The anterior tooth retraction force, in addition to excess force (to overcome friction), produces reciprocal protraction force on molars, thereby leading to increased anchorage loading. However, this traditional concept was challenged in recent literature, which was based on the finite element model, but did not bear correlation to the clinical scenario. This article will reinforce the fact that clinically, friction increases anchorage loading in all three planes of space, considering the fact that tooth movement is a quasistatic process rather than a purely continuous or static one, and that conventional ways of determining the effects of static or dynamic friction on anchorage load cannot be applied to clinical situations (which consist of anatomical resistance units and a complex muscular force system). The article does not aim to quantify friction and its effect on the amount of anchorage load. Rather, a new perspective regarding the role of various additional factors (which is not explained by contemporary concept) that may influence friction and anchorage loading is provided..

  19. Beyond the Flipped Classroom: A Highly Interactive Cloud-Classroom (HIC) Embedded into Basic Materials Science Courses

    Science.gov (United States)

    Liou, Wei-Kai; Bhagat, Kaushal Kumar; Chang, Chun-Yen

    2016-06-01

    The present study compares the highly interactive cloud-classroom (HIC) system with traditional methods of teaching materials science that utilize crystal structure picture or real crystal structure model, in order to examine its learning effectiveness across three dimensions: knowledge, comprehension and application. The aim of this study was to evaluate the (HIC) system, which incorporates augmented reality, virtual reality and cloud-classroom to teach basic materials science courses. The study followed a pretest-posttest quasi-experimental research design. A total of 92 students (aged 19-20 years), in a second-year undergraduate program, participated in this 18-week-long experiment. The students were divided into an experimental group and a control group. The experimental group (36 males and 10 females) was instructed utilizing the HIC system, while the control group (34 males and 12 females) was led through traditional teaching methods. Pretest, posttest, and delayed posttest scores were evaluated by multivariate analysis of covariance. The results indicated that participants in the experimental group who used the HIC system outperformed the control group, in the both posttest and delayed posttest, across three learning dimensions. Based on these results, the HIC system is recommended to be incorporated in formal materials science learning settings.

  20. Identification of copy number variations and translocations in cancer cells from Hi-C data.

    Science.gov (United States)

    Chakraborty, Abhijit; Ay, Ferhat

    2017-10-18

    Eukaryotic chromosomes adapt a complex and highly dynamic three-dimensional (3D) structure, which profoundly affects different cellular functions and outcomes including changes in epigenetic landscape and in gene expression. Making the scenario even more complex, cancer cells harbor chromosomal abnormalities (e.g., copy number variations (CNVs) and translocations) altering their genomes both at the sequence level and at the level of 3D organization. High-throughput chromosome conformation capture techniques (e.g., Hi-C), which are originally developed for decoding the 3D structure of the chromatin, provide a great opportunity to simultaneously identify the locations of genomic rearrangements and to investigate the 3D genome organization in cancer cells. Even though Hi-C data has been used for validating known rearrangements, computational methods that can distinguish rearrangement signals from the inherent biases of Hi-C data and from the actual 3D conformation of chromatin, and can precisely detect rearrangement locations de novo have been missing. In this work, we characterize how intra and inter-chromosomal Hi-C contacts are distributed for normal and rearranged chromosomes to devise a new set of algorithms (i) to identify genomic segments that correspond to CNV regions such as amplifications and deletions (HiCnv), (Nurtdinov et al.) to call inter-chromosomal translocations and their boundaries (HiCtrans) from Hi-C experiments, and (iii) to simulate Hi-C data from genomes with desired rearrangements and abnormalities (AveSim) in order to select optimal parameters for and to benchmark the accuracy of our methods. Our results on 10 different cancer cell lines with Hi-C data show that we identify a total number of 105 amplifications and 45 deletions together with 90 translocations, whereas we identify virtually no such events for two karyotypically normal cell lines. Our CNV predictions correlate very well with whole genome sequencing (WGS) data among chromosomes

  1. HiC-spector: a matrix library for spectral and reproducibility analysis of Hi-C contact maps.

    Science.gov (United States)

    Yan, Koon-Kiu; Yardimci, Galip Gürkan; Yan, Chengfei; Noble, William S; Gerstein, Mark

    2017-07-15

    Genome-wide proximity ligation based assays like Hi-C have opened a window to the 3D organization of the genome. In so doing, they present data structures that are different from conventional 1D signal tracks. To exploit the 2D nature of Hi-C contact maps, matrix techniques like spectral analysis are particularly useful. Here, we present HiC-spector, a collection of matrix-related functions for analyzing Hi-C contact maps. In particular, we introduce a novel reproducibility metric for quantifying the similarity between contact maps based on spectral decomposition. The metric successfully separates contact maps mapped from Hi-C data coming from biological replicates, pseudo-replicates and different cell types. Source code in Julia and Python, and detailed documentation is available at https://github.com/gersteinlab/HiC-spector . koonkiu.yan@gmail.com or mark@gersteinlab.org. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

  2. SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Feng; Jordan, Ashley; Kluz, Thomas [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States); Shen, Steven [Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY 10016 (United States); Sun, Hong; Cartularo, Laura A. [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States); Costa, Max, E-mail: Max.Costa@nyumc.org [Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

    2016-02-15

    The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.

  3. SATB2 expression increased anchorage-independent growth and cell migration in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Wu, Feng; Jordan, Ashley; Kluz, Thomas; Shen, Steven; Sun, Hong; Cartularo, Laura A.; Costa, Max

    2016-01-01

    The special AT-rich sequence-binding protein 2 (SATB2) is a protein that binds to the nuclear matrix attachment region of the cell and regulates gene expression by altering chromatin structure. In our previous study, we reported that SATB2 gene expression was induced in human bronchial epithelial BEAS-2B cells transformed by arsenic, chromium, nickel and vanadium. In this study, we show that ectopic expression of SATB2 in the normal human bronchial epithelial cell-line BEAS-2B increased anchorage-independent growth and cell migration, meanwhile, shRNA-mediated knockdown of SATB2 significantly decreased anchorage-independent growth in Ni transformed BEAS-2B cells. RNA sequencing analyses of SATB2 regulated genes revealed the enrichment of those involved in cytoskeleton, cell adhesion and cell-movement pathways. Our evidence supports the hypothesis that SATB2 plays an important role in BEAS-2B cell transformation. - Highlights: • We performed SATB2 overexpression in the BEAS-2B cell line. • We performed SATB2 knockdown in a Ni transformed BEAS-2B cell line. • SATB2 induced anchorage-independent growth and increased cell migration. • SATB2 knockdown significantly decreased anchorage-independent growth. • We identified alterations in gene involved in cytoskeleton, cell adhesion.

  4. The pipeline fracture behavior and pressure assessment under HIC (Hydrogen induced cracking) environment

    Energy Technology Data Exchange (ETDEWEB)

    Shaohua, Dong [China National Petroleum Corporation (CNPC), Beijing (China); Lianwei, Wang [University of Science and Technology Beijing (USTB), Beijing (China)

    2009-07-01

    As Hydrogen's transmit and diffuse, after gestating for a while, the density of hydrogen around crack tip of pipeline will get to the critical density, and the pipeline material will descend, make critical stress factor, the reason of pipeline Hydrogen Induced Cracking is Hydrogen's transmit and diffuse. The stress factor of Hydrogen Induced Cracking under surroundings-condition of stress is the key that estimate material's rupture behavior. The paper study the relationship among hydrogen concentrate, crack tip stress, stain field, hydrogen diffusion and inner pressure for crack tip process zone, then determined the length of HIC (hydrogen induced cracking) process zone. Based on the theory of propagation which reason micro-crack making core, dislocation model is produced for fracture criteria of HIC, the influence between material and environments under the HIC is analyzed, step by step pipeline maximum load pressure and threshold of J-integrity ( J{sub ISCC} ) is calculated, which is very significant for pipeline safety operation. (author)

  5. Performance of Sequoyah Containment Anchorage System

    International Nuclear Information System (INIS)

    Fanous, F.; Greimann, L.; Wassef, W.; Bluhm, D.

    1993-01-01

    Deformation of a steel containment anchorage system during a severe accident may result in a leakage path at the containment boundaries. Current design criteria are based on either ductile or brittle failure modes of headed bolts that do not account for factors such as cracking of the containment basemat or deformation of the anchor bolt that may affect the behavior of the containment anchorage system. The purpose of this study was to investigate the performance of a typical ice condenser containment's anchorage system. This was accomplished by analyzing the Sequoyah Containment Anchorage System. Based on a strength of materials approach and assuming that the anchor bolts are resisting the uplift caused by the internal pressure, one can estimate that the failure of the anchor bolts would occur at a containment pressure of 79 psig. To verify these results and to calibrate the strength of materials equation, the Sequoyah containment anchorage system was analyzed with the ABAQUS program using a three-dimensional, finite-element model. The model included portions of the steel containment building, shield building, anchor bolt assembly, reinforced concrete mat and soil foundation material

  6. Anchorage Areas

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — An anchorage area is a place where boats and ships can safely drop anchor. These areas are created in navigable waterways when ships and vessels require them for...

  7. GraphTeams: a method for discovering spatial gene clusters in Hi-C sequencing data.

    Science.gov (United States)

    Schulz, Tizian; Stoye, Jens; Doerr, Daniel

    2018-05-08

    Hi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species. We present the first gene cluster model capable of handling spatial data. Our model generalizes a popular computational model for gene cluster prediction, called δ-teams, from sequences to graphs. Following previous lines of research, we subsequently extend our model to allow for several vertices being associated with the same label. The model, called δ-teams with families, is particular suitable for our application as it enables handling of gene duplicates. We develop algorithmic solutions for both models. We implemented the algorithm for discovering δ-teams with families and integrated it into a fully automated workflow for discovering gene clusters in Hi-C data, called GraphTeams. We applied it to human and mouse data to find intra- and interchromosomal gene cluster candidates. The results include intrachromosomal clusters that seem to exhibit a closer proximity in space than on their chromosomal DNA sequence. We further discovered interchromosomal gene clusters that contain genes from different chromosomes within the human genome, but are located on a single chromosome in mouse. By identifying δ-teams with families, we provide a flexible model to discover gene cluster candidates in Hi-C data. Our analysis of Hi-C data from human and mouse reveals several known gene clusters (thus validating our approach), but also few sparsely studied or possibly unknown gene cluster candidates that could be the source of further experimental investigations.

  8. Hi-Corrector: a fast, scalable and memory-efficient package for normalizing large-scale Hi-C data.

    Science.gov (United States)

    Li, Wenyuan; Gong, Ke; Li, Qingjiao; Alber, Frank; Zhou, Xianghong Jasmine

    2015-03-15

    Genome-wide proximity ligation assays, e.g. Hi-C and its variant TCC, have recently become important tools to study spatial genome organization. Removing biases from chromatin contact matrices generated by such techniques is a critical preprocessing step of subsequent analyses. The continuing decline of sequencing costs has led to an ever-improving resolution of the Hi-C data, resulting in very large matrices of chromatin contacts. Such large-size matrices, however, pose a great challenge on the memory usage and speed of its normalization. Therefore, there is an urgent need for fast and memory-efficient methods for normalization of Hi-C data. We developed Hi-Corrector, an easy-to-use, open source implementation of the Hi-C data normalization algorithm. Its salient features are (i) scalability-the software is capable of normalizing Hi-C data of any size in reasonable times; (ii) memory efficiency-the sequential version can run on any single computer with very limited memory, no matter how little; (iii) fast speed-the parallel version can run very fast on multiple computing nodes with limited local memory. The sequential version is implemented in ANSI C and can be easily compiled on any system; the parallel version is implemented in ANSI C with the MPI library (a standardized and portable parallel environment designed for solving large-scale scientific problems). The package is freely available at http://zhoulab.usc.edu/Hi-Corrector/. © The Author 2014. Published by Oxford University Press.

  9. Effectiveness of 3 methods of anchorage reinforcement for maximum anchorage in adolescents: A 3-arm multicenter randomized clinical trial.

    Science.gov (United States)

    Sandler, Jonathan; Murray, Alison; Thiruvenkatachari, Badri; Gutierrez, Rodrigo; Speight, Paul; O'Brien, Kevin

    2014-07-01

    The objective of this 3-arm parallel randomized clinical trial was to compare the effectiveness of temporary anchorage devices (TADs), Nance button palatal arches, and headgear for anchorage supplementation in the treatment of patients with malocclusions that required maximum anchorage. This trial was conducted between August 2008 and February 2013 in 2 orthodontic departments in the United Kingdom. The study included 78 patients (ages, 12-18 years; mean age, 14.2 years) who needed maximum anchorage. Eligibility criteria included no active caries, exemplary oral hygiene, and maximum anchorage required. The primary outcome was mesial molar movement during the period in which anchorage supplementation was required. The secondary outcomes were duration of anchorage reinforcement, number of treatment visits, number of casual and failed appointments, total treatment time, dento-occlusal change, and patients' perceptions of the method of anchorage supplementation. Treatment allocation was implemented by contacting via the Internet the randomization center at the University of Nottingham, Clinical Trials Unit. The randomization was based on a computer-generated pseudo-random code with random permuted blocks of randomly varying size. A research assistant who was blinded to the group allocation recorded all data. The patients were randomly allocated to receive anchorage supplementation with TADs, a Nance button on a palatal arch, or headgear. They were all treated with maxillary and mandibular preadjusted edgewise fixed appliances with 0.022-in slot prescription brackets. They were followed until orthodontic treatment was complete. Seventy-eight patients were randomized in a 1:1:1 ratio among the 3 groups. The baseline characteristics were similar in the groups, and they were treated for an average of 27.4 months (SD, 7.1 months); 71 completed orthodontic treatment. The data were analyzed on a per-protocol basis and showed no differences in the effectiveness of anchorage

  10. HiView: an integrative genome browser to leverage Hi-C results for the interpretation of GWAS variants.

    Science.gov (United States)

    Xu, Zheng; Zhang, Guosheng; Duan, Qing; Chai, Shengjie; Zhang, Baqun; Wu, Cong; Jin, Fulai; Yue, Feng; Li, Yun; Hu, Ming

    2016-03-11

    Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex traits and diseases. However, most of them are located in the non-protein coding regions, and therefore it is challenging to hypothesize the functions of these non-coding GWAS variants. Recent large efforts such as the ENCODE and Roadmap Epigenomics projects have predicted a large number of regulatory elements. However, the target genes of these regulatory elements remain largely unknown. Chromatin conformation capture based technologies such as Hi-C can directly measure the chromatin interactions and have generated an increasingly comprehensive catalog of the interactome between the distal regulatory elements and their potential target genes. Leveraging such information revealed by Hi-C holds the promise of elucidating the functions of genetic variants in human diseases. In this work, we present HiView, the first integrative genome browser to leverage Hi-C results for the interpretation of GWAS variants. HiView is able to display Hi-C data and statistical evidence for chromatin interactions in genomic regions surrounding any given GWAS variant, enabling straightforward visualization and interpretation. We believe that as the first GWAS variants-centered Hi-C genome browser, HiView is a useful tool guiding post-GWAS functional genomics studies. HiView is freely accessible at: http://www.unc.edu/~yunmli/HiView .

  11. TERRAIN, Anchorage, Alaska

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Anchorage AOI consists of seven areas. These areas were to be collected to the 'highest' accuracy requirement. Ground Control is collected throughout the AOI for...

  12. On decisive factors of liner anchorage behaviour

    International Nuclear Information System (INIS)

    Bucchardt, F.; Weber, M.; Yazdi, F.

    1984-01-01

    Design of reinforced and prestressed containments for nuclear power plants in the FRG shall be guided by DIN 25459; this also includes the structural behaviour of the liner. While the containment safety analysis is a more global matter, the liner and especially the liner anchorage behaviour concentrates on local effects which need a more refined local area description. Due to the predominant stiffness of the concrete structure liner failure analysis are performed by decoupling the steel membrane which is then only supported by anchorage springs. A comprehensive nonlinear analytical study is carried out to examine the anchorage behaviour. (Author) [pt

  13. Paradigm shifts in orthodontic treatment with mini-implant anchorage

    Directory of Open Access Journals (Sweden)

    Johnny Joung-Lin Liaw

    2015-01-01

    Full Text Available After the applications of mini-implant anchorage, the envelope of orthodontic treatment was expanded and some treatment modes were changed because of more predictable tooth movement with empowered anchorage. The author tried to share his experience of TADs applications for clarifying the paradigm shifts of orthodontic treatment assisted with the mini-implant anchorage.

  14. Cell cycle control by components of cell anchorage

    OpenAIRE

    Gad, Annica

    2005-01-01

    Extracellular factors, such as growth factors and cell anchorage to the extracellular matrix, control when and where cells may proliferate. This control is abolished when a normal cell transforms into a tumour cell. The control of cell proliferation by cell anchorage was elusive and less well studied than the control by growth factors. Therefore, we aimed to clarify at what points in the cell cycle and through which molecular mechanisms cell anchorage controls cell cycle pro...

  15. 75 FR 3641 - Television Broadcasting Services; Anchorage, AK

    Science.gov (United States)

    2010-01-22

    ... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [DA 10-40; MB Docket No. 09-210; RM-11583] Television Broadcasting Services; Anchorage, AK AGENCY: Federal Communications Commission. ACTION: Final rule... review Act, see 5 U.S.C. 801(a)(1)(A). List of Subjects in 47 CFR Part 73 Television, Television...

  16. Application of a bus seat buffer to mitigate frontal crash effects

    Science.gov (United States)

    Stanisławek, Sebastian; Dziewulski, Paweł; Sławiński, Grzegorz

    2018-01-01

    The paper considers the problem of coach occupant safety during crash events. The authors present a simple low-cost seat buffer concept which may mitigate the effects of frontal impact. The method of computer simulation was chosen to solve the problem efficiently. The Finite Element Method (FEM) implemented in the LS-DYNA commercial code was used. The testing procedure was based on European Commission regulations, under which vehicles move at a defined speed. Simulations have shown that seat occupants suffer serious trauma during a crash, with the head experiencing relatively high acceleration, thus resulting in an HIC36 of 1490. The installation of a protective buffer mounted on the upper part of the seat reduced the HIC36 to only 510. However, in its current form it does not meet the requirements of the regulations. Further modifications to the overlay shape and structure are essential in order to better improve the deceleration of passengers' bodies. Moreover, a detailed model of seats and their anchorage should be taken into account. A more flexible structure should provide more positive and more accurate results.

  17. Comparative photoelastic study of dental and skeletal anchorages in the canine retraction

    Directory of Open Access Journals (Sweden)

    Cristiane Aparecida de Assis Claro

    2014-01-01

    Full Text Available OBJECTIVE: To compare dental and skeletal anchorages in mandibular canine retraction by means of a stress distribution analysis. METHODS: A photoelastic model was produced from second molar to canine, without the first premolar, and mandibular canine retraction was simulated by a rubber band tied to two types of anchorage: dental anchorage, in the first molar attached to adjacent teeth, and skeletal anchorage with a hook simulating the mini-implant. The forces were applied 10 times and observed in a circular polariscope. The stresses located in the mandibular canine were recorded in 7 regions. The Mann-Whitney test was employed to compare the stress in each region and between both anchorage systems. The stresses in the mandibular canine periradicular regions were compared by the Kruskal-Wallis test. RESULTS: Stresses were similar in the cervical region and the middle third. In the apical third, the stresses associated with skeletal anchorage were higher than the stresses associated with dental anchorage. The results of the Kruskal-Wallis test showed that the highest stresses were identified in the cervical-distal, apical-distal, and apex regions with the use of dental anchorage, and in the apical-distal, apical-mesial, cervical-distal, and apex regions with the use of skeletal anchorage. CONCLUSIONS: The use of skeletal anchorage in canine retraction caused greater stress in the apical third than the use of dental anchorage, which indicates an intrusive component resulting from the direction of the force due to the position of the mini-implant and the bracket hook of the canine.

  18. FRP tendon anchorage in post-tensioned concrete structures

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Täljsten, Björn; Bennitz, Anders

    2008-01-01

    effective Young´s modulus and the high stress capacity in the linear elastic range of the material. The use of external tendons increases the requirements on the anchorage systems. This is in particular important when using un-bonded tendon systems, where the anchorage and deviators are the only force...... transfer points. The demand for high capacity anchorage tendons is fulfilled for steel tendons, but no competitive mechanical anchor has yet been developed for FRP tendon. A new small, reliable and more user friendly anchor has to be developed, before FRP tendons can be utilized with all of its capacity...

  19. Single cell Hi-C reveals cell-to-cell variability in chromosome structure

    Science.gov (United States)

    Schoenfelder, Stefan; Yaffe, Eitan; Dean, Wendy; Laue, Ernest D.; Tanay, Amos; Fraser, Peter

    2013-01-01

    Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single cell Hi-C, combined with genome-wide statistical analysis and structural modeling of single copy X chromosomes, to show that individual chromosomes maintain domain organisation at the megabase scale, but show variable cell-to-cell chromosome territory structures at larger scales. Despite this structural stochasticity, localisation of active gene domains to boundaries of territories is a hallmark of chromosomal conformation. Single cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organisation underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns. PMID:24067610

  20. HIC1 Expression Distinguishes Intestinal Carcinomas Sensitive to Chemotherapy

    Czech Academy of Sciences Publication Activity Database

    Janečková, Lucie; Kolář, Michal; Švec, Jiří; Láníková, Lucie; Pospíchalová, Vendula; Baloghová, Nikol; Vojtěchová, Martina; Šloncová, Eva; Strnad, Hynek; Kořínek, Vladimír

    2016-01-01

    Roč. 9, č. 2 (2016), s. 99-107 ISSN 1944-7124 R&D Projects: GA ČR GAP305/12/2347; GA MŠk LO1419; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:68378050 Keywords : direct target gene * cancer 1 hic1 * colorectal-cancer * breast-cancer * lung-cancer * tgf-beta * methylation * hypermethylation * subtypes * cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.077, year: 2015

  1. A new non-metallic anchorage system for post-tensioning applications using CFRP tendons

    Science.gov (United States)

    Taha, Mahmoud Reda

    The objective of the work described in this thesis is to design, develop and test a new non-metallic anchorage system for post-tensioning applications using CFRP tendons. The use of a non-metallic anchorage system should eliminate corrosion and deterioration concerns in the anchorage zone. The development of a reliable non-metallic anchorage would provide an important contribution to this field of knowledge. The idea of the new anchorage is to hold the tendon through mechanical gripping. The anchorage consists of a barrel with a conical housing and four wedges. The anchorage components are made of ultra high performance concrete (UHPC) specially developed for the anchorage. Sixteen concrete mixtures with different casting and curing regimes were examined to develop four UHPC mixtures with compressive strengths in excess of 200 MPa. The UHPC mixtures showed very dense microstructures with some unique characteristics. To enhance the fracture toughness of the newly developed UHPC, analytical and experimental analyses were performed. Using 3 mm chopped carbon fibres, a significant increase in the fracture toughness of UHPC was achieved. The non-metallic anchorage was developed with the UHPC with enhanced fracture toughness. The barrel required careful wrapping with CFRP sheets to provide the confinement required to utilize the strength and toughness of the UHPC. Thirty-three anchorages were tested under both static and dynamic loading conditions. The non-metallic anchorage showed excellent mechanical performance and fulfilled the different requirements of a post-tensioning anchorage system. The development of the new non-metallic anchorage will widen the inclusion of CFRP tendons in post-tensioned concrete/masonry structures. The new system will offer the opportunity to exploit CFRP tendons effectively creating an innovative generation of corrosion-free, smart structures.

  2. Finite element simulation and testing of ISW CFRP anchorage

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Goltermann, Per; Hertz, Kristian Dahl

    2013-01-01

    is modelled in the 3D finite Element program ABAQUS, just as digital image correlation (DIC) testing was performed to verify the finite element simulation. Also a new optimized design was produced to ensure that the finite element simulation and anchorage behaviour correlated well. It is seen....... This paper presents a novel mechanical integrated sleeve wedge anchorage which seem very promising when perusing the scope of ultimate utilization of CFRP 8mm rods (with a tension capacity of approximately 140kN). Compression transverse to the CFRP is evaluated to prevent premature failure. The anchorage...

  3. Comparison of anchorage reinforcement with temporary anchorage devices or a Herbst appliance during lingual orthodontic protraction of mandibular molars without maxillary counterbalance extraction.

    Science.gov (United States)

    Metzner, Rebecca; Schwestka-Polly, Rainer; Helms, Hans-Joachim; Wiechmann, Dirk

    2015-06-20

    Orthodontic protraction of mandibular molars without maxillary counterbalance extraction in cases of aplasia or extraction requires stable anchorage. Reinforcement may be achieved by using either temporary anchorage devices (TAD) or a fixed, functional appliance. The objective was to compare the clinical effectiveness of both methods by testing the null-hypothesis of no significant difference in velocity of space closure (in mm/month) between them. In addition, we set out to describe the quality of posterior space management and treatment-related factors, such as loss of anchorage (assessed in terms of proportions of gap closure by posterior protraction or anterior retraction), frequencies of incomplete space closure, and potential improvement in the sagittal canine relationship. Twenty-seven subjects (15 male/12 female) with a total of 36 sites treated with a lingual multi-bracket appliance were available for retrospective evaluation of the effects of anchorage reinforcement achieved with either a Herbst appliance (n(subjects) = 15; 7 both-sided/8 single-sided Herbst appliances; n(sites) = 22) or TADs (n(subjects )= 12; 2 both-sided; 10 single-sided; n(sites) = 14). Descriptive analysis was based on measurements using intra-oral photographs which were individually scaled to corresponding plaster casts and taken on insertion of anchorage mechanics (T1), following removal of anchorage mechanics (T2), and at the end of multi-bracket treatment (T3). The null-hypothesis was rejected: The rate of mean molar protraction was significantly faster in the Herbst-reinforced group (0.51 mm/month) than in the TAD group (0.35). While complete space closure by sheer protraction of posterior teeth was achieved in all Herbst-treated cases, space closure in the TAD group was achieved in 76.9% of subjects by sheer protraction of molars, and it was incomplete in 50% of cases (mean gap residues: 1 mm). Whilst there was a deterioration in the canine relationship towards

  4. Seismic verification of nuclear plant equipment anchorage

    International Nuclear Information System (INIS)

    Lepiece, M.; Van Vyve, J.

    1991-01-01

    More than 60% of the electrical power of Belgium is generated by seven PWR nuclear power plants. For three of them, the electro-mechanical equipment had to be reassessed after ten years of operation, because the seismic requirements were upgraded from 0.1 g to 0.17 g free field ground acceleration. The seismic requalification of the active equipment was a critical problem as the classical methods were too conservative. The approach based on the use of the past experience on the seismic behavior of nonnuclear equipment, chosen and developed by the SQUG, had to be transposed to the Belgian N.P.P. The decision of the accept-ability of equipment relies heavily on the aseismatic capacity of anchorage. The Electrical Power Research Institute (EPRI) developed the procedure and guideline for the demonstration of the aseismatic adequacy of equipment anchorage in a cost-effective and consistent manner, to support the decision by Seismic Review Team. The field inspection procedure to identify the type of fasteners and detect their possible defects and the verification procedure developed to calculate the aseismatic capacity of equipment anchorage on the strength of fasteners, the aseismatic capacity of anchorage and the comparison of the capacity with the demand are reported. (K.I.)

  5. Juicebox.js Provides a Cloud-Based Visualization System for Hi-C Data.

    Science.gov (United States)

    Robinson, James T; Turner, Douglass; Durand, Neva C; Thorvaldsdóttir, Helga; Mesirov, Jill P; Aiden, Erez Lieberman

    2018-02-28

    Contact mapping experiments such as Hi-C explore how genomes fold in 3D. Here, we introduce Juicebox.js, a cloud-based web application for exploring the resulting datasets. Like the original Juicebox application, Juicebox.js allows users to zoom in and out of such datasets using an interface similar to Google Earth. Juicebox.js also has many features designed to facilitate data reproducibility and sharing. Furthermore, Juicebox.js encodes the exact state of the browser in a shareable URL. Creating a public browser for a new Hi-C dataset does not require coding and can be accomplished in under a minute. The web app also makes it possible to create interactive figures online that can complement or replace ordinary journal figures. When combined with Juicer, this makes the entire process of data analysis transparent, insofar as every step from raw reads to published figure is publicly available as open source code. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Research on the Bond Anchorage Properties of Alkali-Activated Slag Cementitious Material

    Science.gov (United States)

    Zhu, J.; Zheng, W. Z.; Leng, Y. F.; Qin, C. Z.; Xu, Z. Z.

    2017-12-01

    By bond-anchorage property tests at 20°C ∼500°C, the distribution of shear stress between carbon fiber sheets and concrete at all levels of loading and anchorage lengths were measured, which means the bond lengths during CFRP sheets are pulled off at the same time when the concrete is torn and stripped were gotten. The failure modes were obtained. In addition, the failure loads were measured, and the calculated formulas of anchorage lengths were identified by fitting at high temperature. It can be seen that the anchorage lengths of carbon fiber sheets increase with increasing temperature at 20°C ∼100°C, the anchorage lengths of carbon fiber sheets decrease with increasing temperature at 100°C ∼500°C. Tests prove that AASCM has favorable high-temperature resistant and bond anchorage properties.

  7. Procedures adopted by orthodontists for space closure and anchorage control

    OpenAIRE

    Monini,André da Costa; Gandini Júnior,Luiz Gonzaga; Santos-Pinto,Ary dos; Maia,Luiz Guilherme Martins; Rodrigues,Willian Caetano

    2013-01-01

    OBJECTIVE: The aim of this study was to identify the procedures adopted by Brazilian orthodontists in the following situations: extraction space closure, anchorage control in case of necessary anchorage for group A and frequency of skeletal anchorage use, especially in the upper jaw. METHOD: A questionnaire was sent to the e-mail address of all dentists registered in the Brazilian Federal Council of Dentistry. RESULTS: The results showed that most Brazilian orthodontists usually perform extra...

  8. Forward modeling transient brightenings and microflares around an active region observed with Hi-C

    Energy Technology Data Exchange (ETDEWEB)

    Kobelski, Adam R. [Now at National Radio Astronomy Observatory, P.O. Box 2, Green Bank, WV 24944 (United States); McKenzie, David E., E-mail: kobelski@solar.physics.montana.edu [Department of Physics, P.O. Box 173840, Montana State University, Bozeman, MT 59717-3840 (United States)

    2014-10-20

    Small-scale flare-like brightenings around active regions are among the smallest and most fundamental of energetic transient events in the corona, providing a testbed for models of heating and active region dynamics. In a previous study, we modeled a large collection of these microflares observed with Hinode/X-Ray Telescope (XRT) using EBTEL and found that they required multiple heating events, but could not distinguish between multiple heating events on a single strand, or multiple strands each experiencing a single heating event. We present here a similar study, but with extreme-ultraviolet data of Active Region 11520 from the High Resolution Coronal Imager (Hi-C) sounding rocket. Hi-C provides an order of magnitude improvement to the spatial resolution of XRT, and a cooler temperature sensitivity, which combine to provide significant improvements to our ability to detect and model microflare activity around active regions. We have found that at the spatial resolution of Hi-C (≈0.''3), the events occur much more frequently than expected (57 events detected, only 1 or 2 expected), and are most likely made from strands of the order of 100 km wide, each of which is impulsively heated with multiple heating events. These findings tend to support bursty reconnection as the cause of the energy release responsible for the brightenings.

  9. HIC1 loss promotes prostate cancer metastasis by triggering epithelial mesenchymal transition

    Czech Academy of Sciences Publication Activity Database

    Hao, M.; Li, Y.; Wang, J.; Qin, J.; Wang, Y.; Ding, Y.; Jiang, M.; Sun, X.; Zu, L.; Chang, K.; Lin, G.; Du, J.; Kořínek, Vladimír; Ye, D.W.; Wang, J.

    2017-01-01

    Roč. 242, č. 4 (2017), s. 409-420 ISSN 0022-3417 R&D Projects: GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : HIC * prostate cancer * EMT * metastasis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 6.894, year: 2016

  10. Mini-Implants in the Anchorage Armamentarium: New Paradigms in the Orthodontics

    Directory of Open Access Journals (Sweden)

    Masaru Yamaguchi

    2012-01-01

    Full Text Available Paradigms have started to shift in the orthodontic world since the introduction of mini-implants in the anchorage armamentarium. Various forms of skeletal anchorage, including miniscrews and miniplates, have been reported in the literature. Recently, great emphasis has been placed on the miniscrew type of temporary anchorage device (TAD. These devices are small, are implanted with a relatively simple surgical procedure, and increase the potential for better orthodontic results. Therefore, miniscrews not only free orthodontists from anchorage-demanding cases, but they also enable clinicians to have good control over tooth movement in 3 dimensions. The miniplate type also produces significant improvements in treatment outcomes and has widened the spectrum of orthodontics. The purpose of this paper is to update clinicians on the current concepts and versatile uses and clinical applications of skeletal anchorage in orthodontics.

  11. GOTHiC, a probabilistic model to resolve complex biases and to identify real interactions in Hi-C data.

    Directory of Open Access Journals (Sweden)

    Borbala Mifsud

    Full Text Available Hi-C is one of the main methods for investigating spatial co-localisation of DNA in the nucleus. However, the raw sequencing data obtained from Hi-C experiments suffer from large biases and spurious contacts, making it difficult to identify true interactions. Existing methods use complex models to account for biases and do not provide a significance threshold for detecting interactions. Here we introduce a simple binomial probabilistic model that resolves complex biases and distinguishes between true and false interactions. The model corrects biases of known and unknown origin and yields a p-value for each interaction, providing a reliable threshold based on significance. We demonstrate this experimentally by testing the method against a random ligation dataset. Our method outperforms previous methods and provides a statistical framework for further data analysis, such as comparisons of Hi-C interactions between different conditions. GOTHiC is available as a BioConductor package (http://www.bioconductor.org/packages/release/bioc/html/GOTHiC.html.

  12. GOTHiC, a probabilistic model to resolve complex biases and to identify real interactions in Hi-C data.

    Science.gov (United States)

    Mifsud, Borbala; Martincorena, Inigo; Darbo, Elodie; Sugar, Robert; Schoenfelder, Stefan; Fraser, Peter; Luscombe, Nicholas M

    2017-01-01

    Hi-C is one of the main methods for investigating spatial co-localisation of DNA in the nucleus. However, the raw sequencing data obtained from Hi-C experiments suffer from large biases and spurious contacts, making it difficult to identify true interactions. Existing methods use complex models to account for biases and do not provide a significance threshold for detecting interactions. Here we introduce a simple binomial probabilistic model that resolves complex biases and distinguishes between true and false interactions. The model corrects biases of known and unknown origin and yields a p-value for each interaction, providing a reliable threshold based on significance. We demonstrate this experimentally by testing the method against a random ligation dataset. Our method outperforms previous methods and provides a statistical framework for further data analysis, such as comparisons of Hi-C interactions between different conditions. GOTHiC is available as a BioConductor package (http://www.bioconductor.org/packages/release/bioc/html/GOTHiC.html).

  13. Calculation of 3D genome structures for comparison of chromosome conformation capture experiments with microscopy: An evaluation of single-cell Hi-C protocols.

    Science.gov (United States)

    Lando, David; Stevens, Tim J; Basu, Srinjan; Laue, Ernest D

    2018-01-01

    Single-cell chromosome conformation capture approaches are revealing the extent of cell-to-cell variability in the organization and packaging of genomes. These single-cell methods, unlike their multi-cell counterparts, allow straightforward computation of realistic chromosome conformations that may be compared and combined with other, independent, techniques to study 3D structure. Here we discuss how single-cell Hi-C and subsequent 3D genome structure determination allows comparison with data from microscopy. We then carry out a systematic evaluation of recently published single-cell Hi-C datasets to establish a computational approach for the evaluation of single-cell Hi-C protocols. We show that the calculation of genome structures provides a useful tool for assessing the quality of single-cell Hi-C data because it requires a self-consistent network of interactions, relating to the underlying 3D conformation, with few errors, as well as sufficient longer-range cis- and trans-chromosomal contacts.

  14. [Clinical effects of micro-implant and traditional anchorage in orthodontic treatments].

    Science.gov (United States)

    Qian, Yi; Zhou, Hua-Jie; Wu, Jian-Hua

    2017-06-01

    To analyze the value of micro-implant and traditional anchorage in the treatment of malocclusion. From Jan 2015 to Jan 2016, 20 cases with malocclusion were randomly divided into control group(10) and experimental group (10). A comparison was conducted between the control group, in which traditional anchorage was used and the experimental group, in which micro-implant anchorage was adopted. The data were analyzed with SPSS 17.0 software package. There was significant difference of U1-NA, L1-NB, U1-APg, U6-PtPNS between the 2 groups(PMicro-implant anchorage can improve overjet relation of the anterior teeth and effect of orthodontic treatment.

  15. Factors predisposing to maxillary anchorage loss: a retrospective study of 1403 cases.

    Directory of Open Access Journals (Sweden)

    Hong Su

    Full Text Available Anchorage loss is very disturbing for orthodontists and patients during orthodontic treatment, which usually results in bad treatment effects. Despite the same treatment strategy, different patients show different tendencies toward anchorage loss, which influences the treatment results and should preferably be predicted before the treatment is begun. However, relatively little research has been conducted on which patients are more likely to lose anchorage. The mesial tipping of the first molar marks the onset of anchorage loss, and changes in the angulation of the first molar are closely related to anchorage loss. This cross-sectional study aimed to determine how the mesiodistal angulation of the upper first molars changes during general orthodontic treatment and to identify the individual physiologic factors leading to these changes in a large sample of 1403 patients with malocclusion. The data indicate that the upper first molars tend to be tipped mesially during orthodontic treatment, and this constitutes a type of anchorage loss that orthodontists should consider carefully. Compared to treatment-related factors, patients' physiologic characteristics have a greater influence on changes in the angulation of the upper first molars during orthodontic treatment. The more distally tipped the upper first molars are before treatment, the more they will tip mesially during treatment. Mesial tipping of the upper first molars, and therefore, anchorage loss, is more likely to occur in adolescents, males, patients with class II malocclusion and patients who have undergone maxillary premolar extraction. This finding is of clinical significance to orthodontists who wish to prevent iatrogenic anchorage loss by tipping originally distally tipped upper molars forward, and provides a new perspective on anchorage during orthodontic treatment planning.

  16. Research on Anchorage Performance of Grouting Anchor Connection of Precast Concrete Structure

    Science.gov (United States)

    Wang, Donghui; Liu, Xudong; Wang, Sheng; Cao, Xixi

    2018-03-01

    The bonding of grouted anchor bars is one of the vertical connection forms of steel bars in fabricated concrete structures. The performance of grouted connection is mainly affected by the anchorage length and lap length of steel bars. The mechanisms of bond and anchorage between steel bar and concrete are analyzed, and the factors that influence the anchorage performance of steel bar are systematically summarized. Results show that the bond and anchorage performance of steel and concrete have been studied widely, but there are still shortcomings, and the connection forms need to be further improved.

  17. Application and Curative Effect of Micro-implant Anchorage in ...

    African Journals Online (AJOL)

    research hot spot in the Department of. Stomatology. Instead of taking teeth as the basis, as was previously the case, this new anchorage exerts the counteracting force of orthodontics on the jaw, thus completely avoiding the displacement of teeth. It solves a lot of problems existing in clinical anchorage. Micro - implant.

  18. Flexural Strengthening of RC Slabs with Prestressed CFRP Strips Using Different Anchorage Systems

    Directory of Open Access Journals (Sweden)

    José Sena-Cruz

    2015-10-01

    Full Text Available Externally Bonded Reinforcement (EBR technique has been widely used for flexural strengthening of concrete structures by using carbon fiber-reinforced polymers (CFRP. EBR technique offers several structural advantages when the CFRP material is prestressed. This paper presents an experimental and numerical study on reinforced (RC slabs strengthened in flexure with prestressed CFRP strips as a structural strengthening system. The strips are applied as an externally bonded reinforcement (EBR and anchored with either a mechanical or a gradient anchorage. The former foresees metallic anchorage plates fixed to the concrete substrate, while the latter is based on an accelerated epoxy resin curing followed by a segment-wise prestress force decrease at the strip ends. Both anchorage systems, in combination with different CFRP strip geometries, were subjected to static loading tests. It could be demonstrated that the composite strip’s performance is better exploited when prestressing is used, with slightly higher overall load carrying capacities for mechanical anchorages than for the gradient anchorage. The performed investigations by means of a cross-section analysis supported the experimental observation that in case a mechanical anchorage is used, progressive strip debonding changes the fully bonded configuration to an unbonded end-anchored system. The inclusion of defined debonding criteria for both the anchorage zones and free length between the anchorage regions allowed to precisely capture the ultimate loading forces.

  19. Commercial disposal of High Integrity Containers (HICs) containing EPICOR-II prefilters from Three Mile Island

    International Nuclear Information System (INIS)

    McConnell, J.W. Jr.; Lynch, R.J.; Tyacke, M.J.

    1985-09-01

    This report describes the processes of loading, transporting, and commercially disposing of 45 High Integrity Containers (HICs), each containing an EPICOR-II prefilter. Also described are the improvements that were applied in the disposition of the 45 commercial EPICOR-II prefilters at the Idaho National Engineering Laboratory (INEL), versus those used for the demonstration unit. The significance of this effort was that the commercial disposal campaign involved the first-of-a-kind production use of a reinforced concrete HIC at the US Ecology, Inc. facility in the State of Washington. This allowed for safe disposal of high-specific-activity ion exchange material in EPICOR-II prefilters generated during the cleanup of the Unit-2 Auxiliary and Fuel Handling Building of the Three Mile Island Nuclear Power Station. 26 figs

  20. Commercial disposal of high integrity containers (HICs) containing EPICOR-II prefilters from Three Mile Island: Reflections and projections

    International Nuclear Information System (INIS)

    McConnell, J.W. Jr.; Schmitt, R.C.

    1986-09-01

    The processes of loading, transporting, and commerically disposing of 46 EPICOR-II prefilters, each contained in a High Integrity Container (HIC), are described. Also described are participation of the regulatory agencies and industrial organizations in combining their efforts to accomplish this task. The significant aspect of the task was that the commerical disposal involved the first-of-a-kind production use of a reinforced concrete HIC at the US Ecology, Inc., facility in the State of Washington. The same type of container probably can be used in below- or above-ground disposal of other types of high specific activity, low-level nuclear wastes. 14 refs., 4 figs

  1. 33 CFR 110.236 - Pacific Ocean off Barbers Point, Island of Oahu, Hawaii: Offshore pipeline terminal anchorages.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Pacific Ocean off Barbers Point... Grounds § 110.236 Pacific Ocean off Barbers Point, Island of Oahu, Hawaii: Offshore pipeline terminal... regulations. (1) No vessels may anchor, moor, or navigate in anchorages A, B, C, or D except: (i) Vessels...

  2. 77 FR 60081 - Anchorages; Captain of the Port Puget Sound Zone, WA

    Science.gov (United States)

    2012-10-02

    ...'31'' W. Thorndike Bay Emergency Explosives Anchorage. Coordinates would be revised to read: All... 048[deg]T to point of origin. (6) Thorndike Bay Emergency Explosives Anchorage. All waters in a...

  3. 78 FR 59914 - Foreign-Trade Zone 160-Anchorage, Alaska; Application for Reorganization Under Alternative Site...

    Science.gov (United States)

    2013-09-30

    ...: Site 1 (56.89 acres)--the Port of Anchorage and Port of Anchorage Industrial Park, 1075 Dock Rd., 1076... acres)--619 East Ship Creek Ave., Anchorage; Site 6 (12.2 acres)-- Douglas Management Company, 660...

  4. PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth of melanoma cells.

    Directory of Open Access Journals (Sweden)

    Sophia Boyoung Lee

    Full Text Available PAX transcription factors play an important role during development and carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes and melanoma cells by Western Blot and immunofluorescence analysis and characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found weak PAX2 protein expression in keratinocytes and melanocytes. Compared to melanocytes increased PAX2 protein levels were detectable in melanoma cell lines. Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression strongly correlated with nuclear atypia and the degree of prominent nucleoli, indicating an association of PAX2 with a more atypical cellular phenotype. In addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2 siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a metalloproteinase known to play important roles in melanoma metastasis. In human tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign nevi and in melanoma cells of patients with malignant melanoma. Importantly, the downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell growth and decreased the migratory and invasive capacity of melanoma cells. Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma cells against cisplatin, indicating that PAX2 expression mediates cell survival and plays important roles during melanoma progression.

  5. Evaluating School Wellness Policy in Curbing Childhood Obesity in Anchorage, Alaska

    Science.gov (United States)

    Parsons, Wendy G.; Garcia, Gabriel M.; Hoffman, Pamela K.

    2014-01-01

    In 2006, the Anchorage School District implemented a school wellness policy to address the problem of obesity among its elementary-aged students. We assessed whether the addition of this policy is effective in protecting or preventing students from becoming overweight/obese over time. The methods involved following two cohorts of students for 5

  6. Anchorage Behaviors of Frictional Tieback Anchors in Silty Sand

    Science.gov (United States)

    Hsu, Shih-Tsung; Hsiao, Wen-Ta; Chen, Ke-Ting; Hu, Wen-Chi; Wu, Ssu-Yi

    2017-06-01

    Soil anchors are extensively used in geotechnical applications, most commonly serve as tieback walls in deep excavations. To investigate the anchorage mechanisms of this tieback anchor, a constitutive model that considers both strain hardening and softening and volume dilatancy entitled SHASOVOD model, and FLAC3D software are used to perform 3-D numerical analyses. The results from field anchor tests are compared with those calculated by numerical analyses to enhance the applicability of the numerical method. After the calibration, this research carried out the parameter studies by numerical analyses. The numerical results reveal that whether the yield of soil around an anchor develops to ground surface and/or touches the diaphragm wall depending on the overburden depth H and the embedded depth Z of an anchor, this study suggests the minimum overburden and embedded depths to avoid the yield of soils develop to ground surface and/or touch the diaphragm wall. When the embedded depth, overburden depth or fixed length of an anchor increases, the anchorage capacity also increases. Increasing fixed length should be the optimum method to increase the anchorage capacity for fixed length less than 20m. However, when the fixed length of an anchor exceeds 30 m, the increasing rate of anchorage capacity per fixed length decreases, and progressive yield occurs obviously between the fixed length and surrounding soil.

  7. Generation of two modified mouse alleles of the Hic1 tumor suppressor gene

    Czech Academy of Sciences Publication Activity Database

    Pospíchalová, Vendula; Turečková, Jolana; Fafílek, Bohumil; Vojtěchová, Martina; Krausová, Michaela; Lukáš, Jan; Šloncová, Eva; Takacova, S.; Divoký, V.; Leprince, D.; Plachý, Jiří; Kořínek, Vladimír

    2011-01-01

    Roč. 49, č. 3 (2011), s. 142-151 ISSN 1526-954X R&D Projects: GA ČR(CZ) GA204/07/1567; GA ČR(CZ) GD204/09/H058 Institutional research plan: CEZ:AV0Z50520514 Keywords : Hypermethylated In Cancer 1 * Hic1 tumor suppressor * gene targeting Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.527, year: 2011

  8. Inspection Mechanism and Experimental Study of Prestressed Reverse Tension Method under PC Beam Bridge Anchorage

    Science.gov (United States)

    Peng, Zhang

    2018-03-01

    the prestress under anchorage is directly related to the structural security and performance of PC beam bridge. The reverse tension method is a kind of inspection which confirms the prestress by exerting reversed tension load on the exposed prestressing tendon of beam bridge anchoring system. The thesis elaborately expounds the inspection mechanism and mechanical effect of reverse tension method, theoretically analyzes the influential elements of inspection like tool anchorage deformation, compression of conjuncture, device glide, friction of anchorage loop mouth and elastic compression of concrete, and then presents the following formula to calculate prestress under anchorage. On the basis of model experiment, the thesis systematically studies some key issues during the reverse tension process of PC beam bridge anchorage system like the formation of stress-elongation curve, influential factors, judgment method of prestress under anchorage, variation trend and compensation scale, verifies the accuracy of mechanism analysis and demonstrates: the prestress under anchorage is less than or equal to 75% of the ultimate strength of prestressing tendon, the error of inspect result is less than 1%, which can meet with the demands of construction. The research result has provided theoretical basis and technical foundation for the promotion and application of reverse tension in bridge construction.

  9. Local application of zoledronate for maximum anchorage during space closure.

    Science.gov (United States)

    Ortega, Adam J A J; Campbell, Phillip M; Hinton, Robert; Naidu, Aparna; Buschang, Peter H

    2012-12-01

    Orthodontists have used various compliance-dependent physical means such as headgears and intraoral appliances to prevent anchorage loss. The aim of this study was to determine whether 1 local application of the bisphosphonate zoledronate could be used to prevent anchorage loss during extraction space closure in rats. Thirty rats had their maxillary left first molars extracted and their maxillary left second molars protracted into the extraction space with a 10-g nickel-titanium closing coil for 21 days. Fifteen control rats received a local injection of phosphate-buffered saline solution, and 15 experimental rats received 16 μg of the bisphosphonate zoledronate. Bisphosphonate was also delivered directly into the extraction site and left undisturbed for 5 minutes. Cephalograms and incremental thickness gauges were used to measure tooth movements. Tissues were analyzed by microcomputed tomography and histology. The control group demonstrated significant (P <0.05) tooth movements throughout the 21-day period. They showed significantly greater tooth movements than the experimental group beginning in the second week. The experimental group showed no significant tooth movement after the first week. The microcomputed tomography and histologic observations showed significant bone loss in the extraction sites and around the second molars of the controls. In contrast, the experimental group had bone preservation and bone fill. There was no evidence of bisphosphonate-associated osteonecrosis in any sample. A single small, locally applied dose of zoledronate provided maximum anchorage and prevented significant bone loss. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  10. Quantification of temperature effect on impedance monitoring via PZT interface for prestressed tendon anchorage

    Science.gov (United States)

    Huynh, Thanh-Canh; Kim, Jeong-Tae

    2017-12-01

    In this study, the quantification of temperature effect on impedance monitoring via a PZT interface for prestressed tendon-anchorage is presented. Firstly, a PZT interface-based impedance monitoring technique is selected to monitor impedance signatures by predetermining sensitive frequency bands. An analytical model is designed to represent coupled dynamic responses of the PZT interface-tendon anchorage system. Secondly, experiments on a lab-scaled tendon anchorage are described. Impedance signatures are measured via the PZT interface for a series of temperature and prestress-force changes. Thirdly, temperature effects on measured impedance responses of the tendon anchorage are estimated by quantifying relative changes in impedance features (such as RMSD and CCD indices) induced by temperature variation and prestress-force change. Finally, finite element analyses are conducted to investigate the mechanism of temperature variation and prestress-loss effects on the impedance responses of prestressed tendon anchorage. Temperature effects on impedance monitoring are filtered by effective frequency shift-based algorithm for distinguishing prestress-loss effects on impedance signatures.

  11. The anchorage capacity of reinforcing bars at normal and high temperatures

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl

    1982-01-01

    of the cross-section. A simple method for calculating the resistance to splitting is proposed, and a test method for determining the bond strength is presented. Test results are shown from a series of 280 specimens exposed to various maximum temperatures, and a relation between the bond strength......The anchorage failure of reinforcing bars is analysed, and it is shown that two modes of failures are possible: splitting or bond failure. It is concluded that the anchorage capacity cannot be estimated by means of a standard specimen, since splitting failure is dependent upon the geometry...... and the ultimate limit stress of concrete under plane strain conditions is indicated. The influence of high temperatures upon the anchorage resistance is explained, and the theory is illustrated by examples....

  12. Improved anchorage of steel linings at WWER nuclear power plants

    International Nuclear Information System (INIS)

    Bouda, M.; Cepicky, J.

    1987-01-01

    Three variants were tested of anchoring the steel lining of special structures of nuclear power plants with WWER reactors, such as the containment, viz.: point anchorage with pins according to a Czechoslovak design, and two methods of linear anchorage according to a Soviet design and a design by the Institute for Industrial Construction of the GDR. Graphically shown are some results of the tests of the point anchorage with pins that showed the reliability of the method with respect to deformation and strain of the lining and of the anchoring elements at a lining temperature of up to 300 degC, which significantly exceeded the design-basis accident temperature of 150 degC. The advantages of the variant include a lower content of labour and an increased quality of welding jobs thanks to the application of the Nelson semi-automatic welding technique. (Z.M.). 10 figs., 7 refs

  13. Modification of evaluation response spectrum by ductility of equipment anchorage

    International Nuclear Information System (INIS)

    Choi, I. G.; Jun, Y. S.; Su, J. M.

    2003-01-01

    The failure mode of welded anchorage is assumed as brittle in the seismic capacity evaluation of nuclear power plant equipments. But the welded anchorage has some ductile capacity. This limited displacement capacity can cause the reduction of the effective frequency of high frequency equipments and the increase of the inelastic energy absorption capacity due to the nonlinear behavior. In this study, the uniform hazard spectrum for Korean nuclear power plant site was modified using the response spectrum reduction factor developed by EPRI. The spectral acceleration for various damping ratio was determined by the theoretical method based on the random vibration theory. In conclusion, the high frequency components of evaluation response spectra were greatly reduced due to the consideration of welded anchorage ductility. This reduced response spectra can be used for the development of in-structure response spectra used in the seismic capacity evaluation of high frequency equipments

  14. Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast.

    Science.gov (United States)

    Swayne, Theresa C; Zhou, Chun; Boldogh, Istvan R; Charalel, Joseph K; McFaline-Figueroa, José Ricardo; Thoms, Sven; Yang, Christine; Leung, Galen; McInnes, Joseph; Erdmann, Ralf; Pon, Liza A

    2011-12-06

    Mitochondria accumulate at neuronal and immunological synapses and yeast bud tips and associate with the ER during phospholipid biosynthesis, calcium homeostasis, and mitochondrial fission. Here we show that mitochondria are associated with cortical ER (cER) sheets underlying the plasma membrane in the bud tip and confirm that a deletion in YPT11, which inhibits cER accumulation in the bud tip, also inhibits bud tip anchorage of mitochondria. Time-lapse imaging reveals that mitochondria are anchored at specific sites in the bud tip. Mmr1p, a member of the DSL1 family of tethering proteins, localizes to punctate structures on opposing surfaces of mitochondria and cER sheets underlying the bud tip and is recovered with isolated mitochondria and ER. Deletion of MMR1 impairs bud tip anchorage of mitochondria without affecting mitochondrial velocity or cER distribution. Deletion of the phosphatase PTC1 results in increased Mmr1p phosphorylation, mislocalization of Mmr1p, defects in association of Mmr1p with mitochondria and ER, and defects in bud tip anchorage of mitochondria. These findings indicate that Mmr1p contributes to mitochondrial inheritance as a mediator of anchorage of mitochondria to cER sheets in the yeast bud tip and that Ptc1p regulates Mmr1p phosphorylation, localization, and function. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Beyond the Flipped Classroom: A Highly Interactive Cloud-Classroom (HIC) Embedded into Basic Materials Science Courses

    Science.gov (United States)

    Liou, Wei-Kai; Bhagat, Kaushal Kumar; Chang, Chun-Yen

    2016-01-01

    The present study compares the highly interactive cloud-classroom (HIC) system with traditional methods of teaching materials science that utilize crystal structure picture or real crystal structure model, in order to examine its learning effectiveness across three dimensions: knowledge, comprehension and application. The aim of this study was to…

  16. Implants for orthodontic anchorage

    Science.gov (United States)

    Zheng, Xiaowen; Sun, Yannan; Zhang, Yimei; Cai, Ting; Sun, Feng; Lin, Jiuxiang

    2018-01-01

    Abstract Implantanchorage continues to receive much attention as an important orthodontic anchorage. Since the development of orthodontic implants, the scope of applications has continued to increase. Although multiple reviews detailing implants have been published, no comprehensive evaluations have been performed. Thus, the purpose of this study was to comprehensively evaluate the effects of implants based on data published in review articles. An electronic search of the Cochrane Library, Medline, Embase, Ebsco and Sicencedirect for reviews with “orthodontic” and “systematic review or meta analysis” in the title, abstract, keywords, or full text was performed. A subsequent manual search was then performed to identify reviews concerning orthodontic implants. A manual search of the orthodontic journals American Journal of Orthodontics and Dentofacial Orthopedics (AJODO), European Journal of Orthodontics (EJO), and Angle Othodontist was also performed. Such systematic reviews that evaluated the efficacy and safety of orthodontic implants were used to indicate success rates and molar movements. A total of 23 reviews were included in the analysis. The quality of each review was assessed using a measurement tool for Assessment of Multiple Systematic Reviews (AMSTAR), and the review chosen to summarize outcomes had a quality score of >6. Most reviews were less than moderate quality. Success rates of implants ranged in a broad scope, and movement of the maxillary first molar was superior with implants compared with traditional anchorage. PMID:29595673

  17. Calculation of absorbed dose of anchorage-dependent cells from internal beta-rays irradiation

    International Nuclear Information System (INIS)

    Chen Jianwei; Huang Gang; Li Shijun

    2001-01-01

    Objective: To elicit the formula of internal dosimetry in anchorage-dependent cells by beta-emitting radionuclides from uniformly distributed volume sources. Methods: By means of the definition of absorbed dose and the MIRD (Medical International Radiation Dose) scheme the formula of internal dosimetry was reasonably deduced. Firstly, studying the systems of suspension culture cells. Then, taking account of the speciality of the systems of the anchorage-dependent cells and the directions of irradiation, the absorbed dose of anchorage -dependent cells was calculated by the accumulated radioactivity, beta-ray energy, and the volume of the cultured systems. Results: The formula of internal dosimetry of suspension culture cells and anchorage-dependent cells were achieved. At the same time, the formula of internal dosimetry of suspension culture cells was compared with that of MIRD and was confirmed accurate. Conclusion: The formula of internal dosimetry is concise, reliable and accurate

  18. Water quality and bathymetry of Sand Lake, Anchorage, Alaska

    Science.gov (United States)

    Donaldson, Donald E.

    1976-01-01

    Sand Lake, a dimictic lowland lake in Anchorage, Alaska, has recently become as urban lake. Analyses indicate that the lake is oligotrophic, having low dissolved solids and nutrient concentrations. Snowmelt runoff from an adjacent residential area, however, has a dissolved-solids concentration 10 times that of the main body of Sand Lake. Lead concentrations in the runoff exceed known values from other water in the ANchorage area, including water samples taken beneath landfills. The volume of the snowmelt runoff has not been measured. The data presented can be used as a baseline for water-resource management. (Woodard-USGS)

  19. Guidelines for evaluation of anchorage adequacy for safety-related equipment typically used on WWER-type NPPs

    International Nuclear Information System (INIS)

    Masopust, R.

    1999-01-01

    This report describes the criteria which should be met when the capacity evaluation of anchorage of safety related equipment is performed for the WWER type NPPs. It should be noted that these criteria were developed specifically for anchorage of WWER type equipment and components to the concrete or steel building structures and they cover different types of anchor bolts and other anchorage details which are typical just for the existing, constructed or reconstructed WWER type NPPs. The screening approach for verifying of equipment anchorage presented in this report is based on a combination of inspections, calculations, and engineering judgement

  20. Single-cell Hi-C bridges microscopy and genome-wide sequencing approaches to study 3D chromatin organization.

    Science.gov (United States)

    Ulianov, Sergey V; Tachibana-Konwalski, Kikue; Razin, Sergey V

    2017-10-01

    Recent years have witnessed an explosion of the single-cell biochemical toolbox including chromosome conformation capture (3C)-based methods that provide novel insights into chromatin spatial organization in individual cells. The observations made with these techniques revealed that topologically associating domains emerge from cell population averages and do not exist as static structures in individual cells. Stochastic nature of the genome folding is likely to be biologically relevant and may reflect the ability of chromatin fibers to adopt a number of alternative configurations, some of which could be transiently stabilized and serve regulatory purposes. Single-cell Hi-C approaches provide an opportunity to analyze chromatin folding in rare cell types such as stem cells, tumor progenitors, oocytes, and totipotent cells, contributing to a deeper understanding of basic mechanisms in development and disease. Here, we review key findings of single-cell Hi-C and discuss possible biological reasons and consequences of the inferred dynamic chromatin spatial organization. © 2017 WILEY Periodicals, Inc.

  1. Feasibility Verification of Mountable PZT-Interface for Impedance Monitoring in Tendon-Anchorage

    Directory of Open Access Journals (Sweden)

    Thanh-Canh Huynh

    2015-01-01

    Full Text Available This study has been motivated to numerically evaluate the performance of the mountable PZT-interface for impedance monitoring in tendon-anchorage. Firstly, electromechanical impedance monitoring and feature classification methods are outlined. Secondly, a structural model of tendon-anchorage subsystem with mountable PZT-interface is designed for impedance monitoring. Finally, the feasibility of the mountable PZT-interface is numerically examined. A finite element (FE model is designed for the lab-scaled tendon-anchorage. The FE model of the PZT-interface is tuned as its impedance signatures meet the experimental test results at the same frequency ranges and also with identical patterns. Equivalent model properties of the FE model corresponding to prestress forces inflicted on the lab-tested structure are identified from the fine-tuning practice.

  2. 33 CFR 166.200 - Shipping safety fairways and anchorage areas, Gulf of Mexico.

    Science.gov (United States)

    2010-07-01

    ... anchorage areas, Gulf of Mexico. 166.200 Section 166.200 Navigation and Navigable Waters COAST GUARD... the erection of structures therein to provide safe approaches through oil fields in the Gulf of Mexico... for Fairway Anchorages in the Gulf of Mexico. Structures may be placed within an area designated as a...

  3. Numerical Simulation and Experimental Validation of an Integrated Sleeve-Wedge Anchorage for CFRP Rods

    DEFF Research Database (Denmark)

    Schmidt, Jacob Wittrup; Smith, Scott T.; Täljsten, Björn

    2011-01-01

    . Recently, an integrated sleeve-wedge anchorage has been successfully developed specifically for CFRP rods. This paper in turn presents a numerical simulation of the newly developed anchorage using ABAQUS. The three-dimensional finite element (FE) model, which considers material non-linearity, uses...

  4. Image guided placement of temporary anchorage devices for tooth movement

    Energy Technology Data Exchange (ETDEWEB)

    Bahl-Palomo, L.; Bissada, N. [Case Western Reserve Univ. School of Dental Medicine, Dept. of Periodontics, Cleveland, OH (United States); Palomo, J.M.; Hans, M.G. [Case Western Reserve Univ. School of Dental Medicine, Dept. of Orthodontics, Cleveland, OH (United States)

    2007-06-15

    The aim of this project is to develop an image guided protocol for placement of a temporary anchorage device without surgically reflecting a mucoperiosteal flap. Eighteen orthodontic cases were selected for skeletal anchorage from the department of orthodontics at Case University. CBCT images of the subjects were taken using the Hitachi CB MercuRay system set at 15 mA, 120 kVp. CBCT images evaluated the ideal location for TAD placement in three dimensions. Horizontal and vertical linear measurements were taken from fixed dental landmarks to clearly define the location for placement. Transverse slices were used to evaluate the thickness of the buccal plate. Using the transverse view, the angle of insertion was determined such that the maximum buccal plate surface area would contact the screw. TADs were placed in the optimum location, with the most appropriate angle of insertion using a closed approach and with minimal local anesthesia and without flap elevation. Results: All TADs were placed without anatomic encroachment and enabled fixed orthodontic anchorage. (orig.)

  5. Image guided placement of temporary anchorage devices for tooth movement

    International Nuclear Information System (INIS)

    Bahl-Palomo, L.; Bissada, N.; Palomo, J.M.; Hans, M.G.

    2007-01-01

    The aim of this project is to develop an image guided protocol for placement of a temporary anchorage device without surgically reflecting a mucoperiosteal flap. Eighteen orthodontic cases were selected for skeletal anchorage from the department of orthodontics at Case University. CBCT images of the subjects were taken using the Hitachi CB MercuRay system set at 15 mA, 120 kVp. CBCT images evaluated the ideal location for TAD placement in three dimensions. Horizontal and vertical linear measurements were taken from fixed dental landmarks to clearly define the location for placement. Transverse slices were used to evaluate the thickness of the buccal plate. Using the transverse view, the angle of insertion was determined such that the maximum buccal plate surface area would contact the screw. TADs were placed in the optimum location, with the most appropriate angle of insertion using a closed approach and with minimal local anesthesia and without flap elevation. Results: All TADs were placed without anatomic encroachment and enabled fixed orthodontic anchorage. (orig.)

  6. Thick-Walled Cylinder Theory Applied on a Conical Wedge Anchorage

    DEFF Research Database (Denmark)

    Bennitz, Anders; Grip, Niklas; Schmidt, Jacob Wittrup

    2011-01-01

    for further development of the anchorage.In this paper, we derive and examine an analytical model for the internal stresses and strains within the anchorage for a prescribed presetting distance. This model is derived from the theory of thick walled cylinders under the assumptions regarding plane stress...... and axial symmetry. We simplify the resulting system of ten nonlinear equations and derive a method for solving them numerically. A comparison of plotted results for three different angles on the wedge’s outer surface and six different presetting distances follows.These results are also compared to both axi...

  7. EBSD study of hydrogen-induced cracking in API-5 L-X46 pipeline steel

    International Nuclear Information System (INIS)

    Venegas, V.; Caleyo, F.; Gonzalez, J.L.; Baudin, T.; Hallen, J.M.; Penelle, R.

    2005-01-01

    The spatial distribution of plastic deformation and grain orientation surrounding hydrogen-induced cracks (HIC) is investigated in samples of API-5L-X46 pipeline steel using scanning electron microscopy and electron backscattering diffraction (EBSD). This work shows direct experimental evidence of the influence of microstructure, microtexture and mesotexture on HIC crack path

  8. Orthodontic treatment with skeletal anchorage system

    Directory of Open Access Journals (Sweden)

    Arya Brahmanta

    2011-06-01

    Full Text Available Background: Correction of class I malocclusion with bimaxillary dental protrusion and unilateral free end right upper ridge in adult patient is one of difficult biomechanical case in orthodontics. Due to this case that needs proper anchorage for upper incisor retraction with missing teeth in the right posterior segment. Purpose: The aim of this study to find an effective therapy for correction of bimaxillary protrusion with unilateral free and ridge. Case: A female patient, 36 year old complaining for the difficulty of lip closure due to severe bimaxillary protrusion with incompetence lip. Case management: Firstly correction of the maxillary and mandibular incisor proclination were done by extraction of the mandibular first premolar, the maxillary second premolar on left side and finally placement of miniplates implant in the zygomatic process on right side as an absolut anchorage. Conclusion: Skeletal anchorage system (SAS can be considered as an effective therapy for corection of bimaxillary protrusion with unilateral free end ridge.Latar belakang: Koreksi dari maloklusi klas I dari penderita dewasa yang disertai protrusi bimaksiler dengan kehilangan gigi posterior pada regio kanan atas merupakan salah satu kasus sulit untuk dikerjakan terutama berhubungan dengan biomekanik pergerakan giginya dalam perawatan ortodonti. Tujuan: Tujuan dari penulisan artikel ini adalah untuk menemukan terapi yang efektif untuk perbaikan protrusi bimaksiler dan kehilangan gigi posterior pada satu sisi. Kasus: Seorang penderita wanita usia 35 tahun datang dengan keluhan utama kesulitan untuk menutup mulut oleh karena gigi rahang atas dan rahang bawahnya maju dan bibirnya tidak kompeten. Tatalaksana kasus: Koreksi pada gigi insisivus rahang atas dan insisivus rahang bawah yang protrusi dilakukan dengan melakukan pencabutan terlebih dahulu pada gigi premolar pertama dirahang bawah sisi kanan dan sisi kiri serta pencabutan pada gigi premolar kedua di rahang atas sisi

  9. Behaviour of Prestressed CFRP Anchorages during and after Freeze-Thaw Cycle Exposure

    Directory of Open Access Journals (Sweden)

    Yunus Emre Harmanci

    2018-05-01

    Full Text Available The long-term performance of externally-bonded reinforcements (EBR on reinforced concrete (RC structures highly depends on the behavior of constituent materials and their interfaces to various environmental loads, such as temperature and humidity exposure. Although significant efforts have been devoted to understanding the effect of such conditions on the anchorage resistance of unstressed EBR, with or without sustained loading, the effect of a released prestressing has not been thoroughly investigated. For this purpose, a series of experiments has been carried out herein, with concrete blocks strengthened with carbon fiber-reinforced polymer (CFRP strips, both unstressed, as well as prestressed using the gradient anchorage. The gradient anchorage is a non-mechanical technique to anchor prestressed CFRP by exploiting the accelerated curing property of epoxy under higher temperatures and segment-wise prestress-force releasing. Subsequently, strengthened blocks are transferred into a chamber for exposure in dry freeze-thaw cycles (FTC. Following FTC exposure, the blocks are tested in a conventional lap-shear test setup to determine their residual anchorage resistance and then compared with reference specimens. Blocks were monitored during FTC by conventional and Fabry–Pérot-based fiber optic strain (FOS sensors and a 3D-digital image correlation (3D-DIC system during gradient application and lap-shear testing. Results indicate a reduction of residual anchorage resistance, stiffness and deformation capacity of the system after FTC and a change in the failure mode from concrete substrate to epoxy-concrete interface failure. It was further observed that all of these properties experienced a more significant reduction for prestressed specimens. These findings are presented with a complementary finite element model to shed more light onto the durability of such systems.

  10. A genetic screen for anchorage-independent proliferation in mammalian cells identifies a membrane-bound neuregulin.

    Directory of Open Access Journals (Sweden)

    Davide Danovi

    2010-07-01

    Full Text Available Anchorage-independent proliferation is a hallmark of oncogenic transformation and is thought to be conducive to proliferation of cancer cells away from their site of origin. We have previously reported that primary Schwann cells expressing the SV40 Large T antigen (LT are not fully transformed in that they maintain a strict requirement for attachment, requiring a further genetic change, such as oncogenic Ras, to gain anchorage-independence. Using the LT-expressing cells, we performed a genetic screen for anchorage-independent proliferation and identified Sensory and Motor Neuron Derived Factor (SMDF, a transmembrane class III isoform of Neuregulin 1. In contrast to oncogenic Ras, SMDF induced enhanced proliferation in normal primary Schwann cells but did not trigger cellular senescence. In cooperation with LT, SMDF drove anchorage-independent proliferation, loss of contact inhibition and tumourigenicity. This transforming ability was shared with membrane-bound class III but not secreted class I isoforms of Neuregulin, indicating a distinct mechanism of action. Importantly, we show that despite being membrane-bound signalling molecules, class III neuregulins transform via a cell intrinsic mechanism, as a result of constitutive, elevated levels of ErbB signalling at high cell density and in anchorage-free conditions. This novel transforming mechanism may provide new targets for cancer therapy.

  11. Human I-mfa domain proteins specifically interact with KSHV LANA and affect its regulation of Wnt signaling-dependent transcription

    Energy Technology Data Exchange (ETDEWEB)

    Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Eizuru, Yoshito [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2010-06-04

    Kaposi's sarcoma-associated herpes virus (KSHV)-encoded latency-associated nuclear antigen (LANA) protein has been reported to interact with glycogen synthase kinase 3{beta} (GSK-3{beta}) and to negatively regulate its activity, leading to stimulation of GSK-3{beta}-dependent {beta}-catenin degradation. We show here that the I-mfa domain proteins, HIC (human I-mfa domain-containing protein) and I-mfa (inhibitor of MyoD family a), interacted in vivo with LANA through their C-terminal I-mfa domains. This interaction affected the intracellular localization of HIC, inhibited the LANA-dependent transactivation of a {beta}-catenin-regulated reporter construct, and decreased the level of the LANA.GSK-3{beta} complex. These data reveal for the first time that I-mfa domain proteins interact with LANA and negatively regulate LANA-mediated activation of Wnt signaling-dependent transcription by inhibiting the formation of the LANA.GSK-3{beta} complex.

  12. Ground Water in the Anchorage Area, Alaska--Meeting the Challenges of Ground-Water Sustainability

    Science.gov (United States)

    Moran, Edward H.; Galloway, Devin L.

    2006-01-01

    Ground water is an important component of Anchorage's water supply. During the 1970s and early 80s when ground water extracted from aquifers near Ship Creek was the principal source of supply, area-wide declines in ground-water levels resulted in near record low streamflows in Ship Creek. Since the importation of Eklutna Lake water in the late 1980s, ground-water use has been reduced and ground water has contributed 14-30 percent of the annual supply. As Anchorage grows, given the current constraints on the Eklutna Lake water availability, the increasing demand for water could place an increasing reliance on local ground-water resources. The sustainability of Anchorage's ground-water resources challenges stakeholders to develop a comprehensive water-resources management strategy.

  13. Maxillary incisors changes during space closure with conventional and skeletal anchorage methods: a systematic review.

    Science.gov (United States)

    Jayaratne, Yasas Shri Nalaka; Uribe, Flavio; Janakiraman, Nandakumar

    2017-01-01

    The objective of this systematic review was to compare the antero-posterior, vertical and angular changes of maxillary incisors with conventional anchorage control techniques and mini-implant based space closure methods. The electronic databases Pubmed, Scopus, ISI Web of knowledge, Cochrane Library and Open Grey were searched for potentially eligible studies using a set of predetermined keywords. Full texts meeting the inclusion criteria as well as their references were manually searched. The primary outcome data (linear, angular, and vertical maxillary incisor changes) and secondary outcome data (overbite changes, soft tissue changes, biomechanical factors, root resorption and treatment duration) were extracted from the selected articles and entered into spreadsheets based on the type of anchorage used. The methodological quality of each study was assessed. Six studies met the inclusion criteria. The amount of incisor retraction was greater with buccally placed mini-implants than conventional anchorage techniques. The incisor retraction with indirect anchorage from palatal mini-implants was less when compared with buccally placed mini-implants. Incisor intrusion occurred with buccal mini-implants, whereas extrusion was seen with conventional anchorage. Limited data on the biomechanical variables or adverse effects such as root resorption were reported in these studies. More RCT's that take in to account relevant biomechanical variables and employ three-dimensional quantification of tooth movements are required to provide information on incisor changes during space closure.

  14. Experimental evidence of pharmacological management of anchorage in Orthodontics: A systematic review

    Science.gov (United States)

    Fernández-González, Felipe José; Cañigral, Aránzazu; Balbontín-Ayala, Felipe; Gonzalo-Orden, José Manuel; de Carlos, Felix; Cobo, Teresa; Fernández-Vázquez, Jose Pedro; Sánchez-Lasheras, Fernando; Vega, José Antonio

    2015-01-01

    Introduction: Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed. Objectives: The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage. Methods: The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed. Results: Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs). Conclusions: Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements. PMID:26560822

  15. Modified Miniplates for Temporary Skeletal Anchorage in Orthodontics: Placement and Removal Surgeries

    Science.gov (United States)

    Cornelis, Marie A.; Scheffler, Nicole R.; Mahy, Pierre; Siciliano, Sergio; De Clerck, Hugo J.; Tulloch, J.F. Camilla

    2009-01-01

    Purpose Skeletal anchorage systems are increasingly used in orthodontics. This article describes the techniques of placement and removal of modified surgical miniplates used for temporary orthodontic anchorage and reports surgeons’ perceptions of their use. Patients and Methods We enrolled 97 consecutive orthodontic patients having miniplates placed as an adjunct to treatment. A total of 200 miniplates were placed by 9 oral surgeons. Patients and surgeons completed questionnaires after placement and removal surgeries. Results Fifteen miniplates needed to be removed prematurely. Antibiotics and anti-inflammatories were generally prescribed after placement but not after removal surgery. Most surgeries were performed with the patient under local anesthesia. Placement surgery lasted on average between 15 and 30 minutes per plate and was considered by the surgeons to be very easy to moderately easy. The surgery to remove the miniplates was considered easier and took less time. The patients’ chief complaint was swelling, lasting on average 5.3 ± 2.8 days after placement and 4.5 ± 2.6 days after removal. Conclusions Although miniplate placement/removal surgery requires the elevation of a flap, this was considered an easy and relatively short surgical procedure that can typically be performed with the patient under local anesthesia without complications, and it may be considered a safe and effective adjunct for orthodontic treatment. PMID:18571028

  16. 1964 Great Alaska Earthquake: a photographic tour of Anchorage, Alaska

    Science.gov (United States)

    Thoms, Evan E.; Haeussler, Peter J.; Anderson, Rebecca D.; McGimsey, Robert G.

    2014-01-01

    On March 27, 1964, at 5:36 p.m., a magnitude 9.2 earthquake, the largest recorded earthquake in U.S. history, struck southcentral Alaska (fig. 1). The Great Alaska Earthquake (also known as the Good Friday Earthquake) occurred at a pivotal time in the history of earth science, and helped lead to the acceptance of plate tectonic theory (Cox, 1973; Brocher and others, 2014). All large subduction zone earthquakes are understood through insights learned from the 1964 event, and observations and interpretations of the earthquake have influenced the design of infrastructure and seismic monitoring systems now in place. The earthquake caused extensive damage across the State, and triggered local tsunamis that devastated the Alaskan towns of Whittier, Valdez, and Seward. In Anchorage, the main cause of damage was ground shaking, which lasted approximately 4.5 minutes. Many buildings could not withstand this motion and were damaged or collapsed even though their foundations remained intact. More significantly, ground shaking triggered a number of landslides along coastal and drainage valley bluffs underlain by the Bootlegger Cove Formation, a composite of facies containing variably mixed gravel, sand, silt, and clay which were deposited over much of upper Cook Inlet during the Late Pleistocene (Ulery and others, 1983). Cyclic (or strain) softening of the more sensitive clay facies caused overlying blocks of soil to slide sideways along surfaces dipping by only a few degrees. This guide is the document version of an interactive web map that was created as part of the commemoration events for the 50th anniversary of the 1964 Great Alaska Earthquake. It is accessible at the U.S. Geological Survey (USGS) Alaska Science Center website: http://alaska.usgs.gov/announcements/news/1964Earthquake/. The website features a map display with suggested tour stops in Anchorage, historical photographs taken shortly after the earthquake, repeat photography of selected sites, scanned documents

  17. Use of miniplates as a method for orthodontic anchorage: a case report.

    Science.gov (United States)

    Peres, Fernando Gianzanti; Padovan, Luis Eduardo Marques; Kluppel, Leandro Eduardo; Albuquerque, Gustavo Calvalcanti; Souza, Paulo Cesar Ulson de; Claudino, Marcela

    2016-01-01

    Temporary anchorage devices (TADs) have been developed to be used as direct adjuncts in orthodontic treatment and have facilitated treatment of more complex orthodontic cases, including patients with dental impaction. This clinical case reports the applicability of TADs in the orthodontic treatment of a patient with impacted mandibular second molars. Surgical and orthodontic procedures related to the use of miniplates were also discussed in this study. The use of temporary anchorage devices, such as miniplates, can be suggested as an alternative to treat patients with impacted mandibular second molars.

  18. Electromechanical impedance-based health diagnosis for tendon and anchorage zone in a nuclear containment structure

    Science.gov (United States)

    Min, Jiyoung; Shim, Hyojin; Yun, Chung-Bang

    2012-04-01

    For a nuclear containment structure, the structural health monitoring is essential because of its high potential risk and grave social impact. In particular, the tendon and anchorage zone are to be monitored because they are under high tensile or compressive stress. In this paper, a method to monitor the tendon force and the condition of the anchorage zone is presented by using the impedance-based health diagnosis system. First, numerical simulations were conducted for cases with various loose tensile forces on the tendon as well as damages on the bearing plate and concrete structure. Then, experimental studies were carried out on a scaled model of the anchorage system. The relationship between the loose tensile force and the impedance-based damage index was analyzed by a regression analysis. When a structure gets damaged, the damage index increases so that the status of damage can be identified. The results of the numerical and experimental studies indicate a big potential of the proposed impedance-based method for monitoring the tendon and anchorage system.

  19. Comparative evaluation of sagittal anchorage loss in lingual and labial appliances during space closure: A pilot study

    Directory of Open Access Journals (Sweden)

    Shivanand Venkatesh

    2015-01-01

    Full Text Available Aim: The purpose of this investigation was to assess and compare the anchorage loss between labial and lingual appliance systems during space closure. Materials and Methods: Twenty subjects were part of the study among which 10 subjects (mean age 21 ± 3.6 years were treated using lingual appliance system (0.018" slot-STb™ and 10 subjects (mean age 19 ± 6.1 years were treated using labial preadjusted edgewise appliance system (0.018" slot-MBT™ . First premolar extractions were performed to enable retraction of anterior teeth. Lateral cephalometric radiographs were taken at two intervals, before starting space closure and after space closure that were connoted as T0 and T1 and were analyzed using the method described by Pancherz to measure anchorage loss. Intraclass correlation coefficient (ICC was used to evaluate intraexaminer reliability of the measurements. Student′s t-test was performed to verify any statistical significant correlation between the labial and lingual appliance systems. Statistical differences were determined at the 95% confidence level (P < 0.05. Results: The results showed that all ICC for lingual and labial group were ≥0.90 showing good repeatability of the measurements. Mean anchorage loss of 1.238 ± 0.17 mm in lingual appliance system and an anchorage loss of 2.06 ± 0.39 mm occurred with the labial appliance system. On the comparison between the two appliance systems, lingual appliance demonstrated a significantly lesser anchorage loss than did the labial appliance. Interpretation and Conclusion: This prospective study concludes with the fact that lingual appliance provided better anchorage control than labial appliance during space closure. Use of lingual appliance could be considered in critical anchorage cases when compared with labial appliance.

  20. Defining process design space for a hydrophobic interaction chromatography (HIC) purification step: application of quality by design (QbD) principles.

    Science.gov (United States)

    Jiang, Canping; Flansburg, Lisa; Ghose, Sanchayita; Jorjorian, Paul; Shukla, Abhinav A

    2010-12-15

    The concept of design space has been taking root under the quality by design paradigm as a foundation of in-process control strategies for biopharmaceutical manufacturing processes. This paper outlines the development of a design space for a hydrophobic interaction chromatography (HIC) process step. The design space included the impact of raw material lot-to-lot variability and variations in the feed stream from cell culture. A failure modes and effects analysis was employed as the basis for the process characterization exercise. During mapping of the process design space, the multi-dimensional combination of operational variables were studied to quantify the impact on process performance in terms of yield and product quality. Variability in resin hydrophobicity was found to have a significant influence on step yield and high-molecular weight aggregate clearance through the HIC step. A robust operating window was identified for this process step that enabled a higher step yield while ensuring acceptable product quality. © 2010 Wiley Periodicals, Inc.

  1. MAXILLARY INCISORS CHANGES DURING SPACE CLOSURE WITH CONVENTIONAL AND SKELETAL ANCHORAGE METHODS: A SYSTEMATIC REVIEW

    Directory of Open Access Journals (Sweden)

    Yasas Shri Nalaka JAYARATNE

    2017-12-01

    Full Text Available Purpose: The objective of this systematic review was to compare the antero-posterior, vertical and angular changes of maxillary incisors with conventional anchorage control techniques and mini-implant based space closure methods. Materials and Methods: The electronic databases Pubmed, Scopus, ISI Web of knowledge, Cochrane Library and Open Grey were searched for potentially eligible studies using a set of predetermined keywords. Full texts meeting the inclusion criteria as well as their references were manually searched. The primary outcome data (linear, angular, and vertical maxillary incisor changes and secondary outcome data (overbite changes, soft tissue changes, biomechanical factors, root resorption and treatment duration were extracted from the selected articles and entered into spreadsheets based on the type of anchorage used. The methodological quality of each study was assessed. Results: Six studies met the inclusion criteria. The amount of incisor retraction was greater with buccally placed mini-implants than conventional anchorage techniques. The incisor retraction with indirect anchorage from palatal mini-implants was less when compared with buccally placed mini-implants. Incisor intrusion occurred with buccal mini-implants, whereas extrusion was seen with conventional anchorage. Limited data on the biomechanical variables or adverse effects such as root resorption were reported in these studies. Conclusion: More RCT’s that take in to account relevant biomechanical variables and employ three-dimensional quantification of tooth movements are required to provide information on incisor changes during space closure.

  2. The Plurality of Harbors at Caesarea: The Southern Anchorage in Late Antiquity

    Science.gov (United States)

    Ratzlaff, Alexandra; Galili, Ehud; Waiman-Barak, Paula; Yasur-Landau, Assaf

    2017-08-01

    The engineering marvel of Sebastos, or Portus Augusti as it was called in Late Antiquity (284-638 CE), dominated Caesarea's harbor center along modern Israel's central coast but it was only one part of a larger maritime complex. The Southern Anchorage provides a case study as one portion of the Caesarea complex, as well as a node within the regional network of anchorages and small harbors. Ceramics recovered from here show a high percentage of locally, and provincially, produced storage jars engaged in maritime trade. The ceramic evidence points towards an intensified regional trade or cabotage rather than favouring long distance trade from large port to port. Working out of these small harbors, opportunities arose for greater flexibility in specialization of commodities and materials passing through the network of subsidiary ports, contributing to a more diversified market economy. This analysis provides another example in the growing focus on how these simple and semi-modified anchorages in the Eastern Mediterranean were often the predominant economic networks connecting hinterland and coastal trade.

  3. Success rates of a skeletal anchorage system in orthodontics: A retrospective analysis.

    Science.gov (United States)

    Lam, Raymond; Goonewardene, Mithran S; Allan, Brent P; Sugawara, Junji

    2018-01-01

    To evaluate the premise that skeletal anchorage with SAS miniplates are highly successful and predictable for a range of complex orthodontic movements. This retrospective cross-sectional analysis consisted of 421 bone plates placed by one clinician in 163 patients (95 female, 68 male, mean age 29.4 years ± 12.02). Simple descriptive statistics were performed for a wide range of malocclusions and desired movements to obtain success, complication, and failure rates. The success rate of skeletal anchorage system miniplates was 98.6%, where approximately 40% of cases experienced mild complications. The most common complication was soft tissue inflammation, which was amenable to focused oral hygiene and antiseptic rinses. Infection occurred in approximately 15% of patients where there was a statistically significant correlation with poor oral hygiene. The most common movements were distalization and intrusion of teeth. More than a third of the cases involved complex movements in more than one plane of space. The success rate of skeletal anchorage system miniplates is high and predictable for a wide range of complex orthodontic movements.

  4. A Portrait of Ribosomal DNA Contacts with Hi-C Reveals 5S and 45S rDNA Anchoring Points in the Folded Human Genome.

    Science.gov (United States)

    Yu, Shoukai; Lemos, Bernardo

    2016-12-31

    Ribosomal RNAs (rRNAs) account for >60% of all RNAs in eukaryotic cells and are encoded in the ribosomal DNA (rDNA) arrays. The rRNAs are produced from two sets of loci: the 5S rDNA array resides exclusively on human chromosome 1, whereas the 45S rDNA array resides on the short arm of five human acrocentric chromosomes. The 45S rDNA gives origin to the nucleolus, the nuclear organelle that is the site of ribosome biogenesis. Intriguingly, 5S and 45S rDNA arrays exhibit correlated copy number variation in lymphoblastoid cells (LCLs). Here we examined the genomic architecture and repeat content of the 5S and 45S rDNA arrays in multiple human genome assemblies (including PacBio MHAP assembly) and ascertained contacts between the rDNA arrays and the rest of the genome using Hi-C datasets from two human cell lines (erythroleukemia K562 and lymphoblastoid cells). Our analyses revealed that 5S and 45S arrays each have thousands of contacts in the folded genome, with rDNA-associated regions and genes dispersed across all chromosomes. The rDNA contact map displayed conserved and disparate features between two cell lines, and pointed to specific chromosomes, genomic regions, and genes with evidence of spatial proximity to the rDNA arrays; the data also showed a lack of direct physical interaction between the 5S and 45S rDNA arrays. Finally, the analysis identified an intriguing organization in the 5S array with Alu and 5S elements adjacent to one another and organized in opposite orientation along the array. Portraits of genome folding centered on the ribosomal DNA array could help understand the emergence of concerted variation, the control of 5S and 45S expression, as well as provide insights into an organelle that contributes to the spatial localization of human chromosomes during interphase. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  5. Orthodontic space closure after first molar extraction without skeletal anchorage.

    Science.gov (United States)

    Jacobs, Collin; Jacobs-Müller, Claudia; Luley, Carolin; Erbe, Christina; Wehrbein, Heiner

    2011-03-01

    The aim of the study was an analysis of effects and side-effects during mesialization of second molars after extraction of the first permanent molars using the anterior dentition/premolars (PM) as an anchorage unit. A total of 35 patients were examined retrospectively who had undergone unilateral or bilateral first permanent molar extraction in the upper or lower arch due to carious lesions. Space closure was carried out in all cases through mesialization of the second molar using an elastic chain fixed to an edgewise stainless steel archwire and tying the anterior dentition/PM together with a continuous laceback ligature. Tooth movement was assessed from lateral cephalograms, orthopantomograms (OPGs) and images of the patient's study casts taken before and after the end of therapy. Space closure after first molar extractions by mesialization of the second molars without skeletal anchorage was largely achieved by bodily forward movement of the teeth, including a small tipping component or tooth-uprighting component when molars were already mesially inclined. Unilateral and bilateral mesialization of the second molars led to retrusion in the maxilla and mandible [(∆incl.=-3.6° (max., bil.), ∆incl.=-4.2° (mand., bil.)] and to translational retraction [(∆s=-2.3 mm (max., bil.), ∆s=-1.6 mm (mand., bil.)] of the incisors. Examination of the soft tissues revealed an increased posterior displacement of the upper and lower lips to the esthetic line [(∆s=-2.8 mm (max. bil.), ∆s=-2.2 mm (mand., bil.)]. In cases of unilateral mesialization less than 50% of the patients had a slight midline deviation in the mandible towards the extraction side. Side effects during mesialization of the second molars without skeletal anchorage in the anterior dentition/PM were observed primarily affecting the incisors integrated into the anterior anchorage unit. These side-effects resulted in posterior displacement of the soft tissues, including a change in profile. This must be

  6. [Comparison between J-hook and micro-implant anchorage in the treatment of patients with bimaxillary protrusion].

    Science.gov (United States)

    Chen, Wen-Jing; Li, Qing-Yi; Gong, Ai-Xiu; Hu, Fang; Gu, Yong-Jia

    2008-02-01

    To compare the difference between J-hook and micro-implant anchorage in the treatment of patient with bimaxillary protrusion. Thirty patients with bimaxillary protrusion were divided into two groups (J-hook and micro-implant groups) and treated with MBT appliance. Four first premolars were extracted in all patients. Cephalometric analyses were carried out before and after treatment. In J-hook group and micro-implant group,computerized cephalometric analysis revealed that before treatment U6C-PP was (12.4 +/- 0.2) mm and (12.5 +/- 0.1) mm, respectively,and after treatment U6C-PP was (12.6 +/- 0.1) mm and (12.8 +/- 0.1) mm,respectively. The difference between J-hook group and microimplant group was significant (P micro-implant group was not significant. Both J-hook and micro-implant could provide adequate anchorage in the treatment of patients with bimaxillary protrusion.

  7. Fatigue of cable anchorage of large cable stayed bridge; Daikibo shachokyo cable teichaku kozo no hiro

    Energy Technology Data Exchange (ETDEWEB)

    Endo, T.; Matsumoto, T. [Honshu-Shikoku Bridge Authority, Tokyo (Japan); Tsukahara, H. [Yokogawa Bridge Corp., Tokyo (Japan); Miki, C. [Tokyo Institute of Technology, Tokyo (Japan)

    1995-10-21

    Design considerations such as design schemes, the assemblage and welding of steel plates, and safety for fatigue of welded connections have to be taken for the cable anchorages of the steel cable stayed bridges. In this study, two full scale models, which have different shape of box anchorages welded to the web of the main girder, were made to investigate fatigue characteristics as well as assemblage of plate and gelding details. Finite element analyses for both test models and actual bridges here carried out to compare stress distribution. It was confirmed that the assemblage and welding of both types of box anchorage were attainable kith required quality and accuracy. According to the fatigue test, fatigue cracks originated from the weldings of the bearing plate to which the load from cable socket applied directly were caused by out-of-plane bending of the bearing plate. It was proved that the slight modifications of the details around the bearing plate resulted in sufficient fatigue strength in both types of anchorage. 1 ref., 23 figs., 2 tabs.

  8. The benefit of differential moment concept in managing posterior anchorage and avoiding bite deepening

    Directory of Open Access Journals (Sweden)

    Harryanto Wijaya

    2012-09-01

    Full Text Available Background: Anchorage is one of the major concerns in orthodontic space closure. Various methods have been proposed to enhance posterior anchorage in space closure such as headgear, Nance holding appliance, and micro implant as temporary anchorage devices. However, several issues such as patient's compliance, appliance effectiveness, and cost of the device become many clinicians concern. The differential moment concept in segmented arch is a technique that requires no patient compliance but can effectively manage posterior anchorage and avoid bite deepening by careful application of forces and moments. Purpose: The purpose of this case report is to show the use of differential moment concept in segmented arch technique to manage posterior anchorage and to avoid bite deepening. Case: A 21 years old female patient with protrusive teeth as her chief complaint was treated using fixed orthodontic appliance. Case management: The treatment included four first bicuspid extraction and space closure utilizing differential moment concept in segmented arch. Conclusion: It can be concluded that application of differential moment concept in segmented arch technique is a non invasive, compliance independent, effective, and cost efficient method to manage posterior anchorage and to avoid bite deepening.latar belakang: Penjangkaran merupakan salah satu aspek yang sering kali menjadi masalah dalam penutupan ruang pada perawatan ortodonti. Berbagai metode disarankan untuk memperkuat penjangkaran posterior dalam penutupan ruang seperti headgear, piranti penahan Nance, dan implan mikro sebagai alat penjangkar sementara. Namun demikian, beberapa hal seperti kerjasama pasien, efektivitas piranti, dan biaya dari alat-alat tersebut sering menjadi perhatian/pertimbangan bagi klinisi. Konsep momen diferensial pada segmented arch adalah suatu cara yang efektif untuk memperkuat penjangkaran dan menghindari pendalaman gigitan tanpa memerlukan kerjasama pasien. tujuan

  9. Anchorage of equipment - requirements and verification methods with emphasis on equipment of existing and constructed VVER-type nuclear power plants

    International Nuclear Information System (INIS)

    Masopust, R.

    1999-01-01

    Criteria and verification methods which are recommended for use in the capacity evaluation of anchorage of safety-related equipment at WWER-type nuclear power plants are presented. Developed in compliance with the relevant basic standards documents specifically for anchorage of WWER-type equipment components, the criteria and methods cover different types of anchor bolts and other anchorage elements which are typical of existing, constructed, or reconstructed WWER-type nuclear power plants

  10. Herbst appliance with skeletal anchorage versus dental anchorage in adolescents with Class II malocclusion: study protocol for a randomised controlled trial.

    Science.gov (United States)

    Batista, Klaus Barretto Dos Santos Lopes; Lima, Tatiana; Palomares, Nathália; Carvalho, Felipe de Assis; Quintão, Cátia; Miguel, José Augusto Mendes; Lin, Yin-Ling; Su, Ting-Li; O'Brien, Kevin

    2017-11-25

    The Herbst appliance is an orthodontic appliance that is used for the correction of class II malocclusion with skeletal discrepancies. Research has shown that this is effective. However, a potential harm is excessive protrusion of the lower front teeth. This is associated with gingival recession, loss of tooth support, and root resorption. This trial evaluates a method of reducing this problem. The study is a single-center, randomised, assessor-blinded, superiority clinical trial with parallel 1:1 allocation. Male and female young people (10-14 years old) with prominent front teeth (class II, division 1) will be treated in one orthodontic clinic. Group 1 will be treated with the conventional Herbst appliance with dental anchorage and group 2 with the Herbst appliance with indirect skeletal anchorage for 12 months. The primary objective will be to compare the proclination of the lower incisors between the Herbst appliance with dental anchorage and skeletal anchorage. Secondary objectives will be to evaluate the changes occurring between the groups in the mandible, maxilla, lower and upper molars, and in gingival recession and root resorption at the end of the treatment. Additionally, the young patient's experience using the appliances will be assessed. The primary outcome measure will be the amount of lower incisor proclination at the end of treatment. This will be assessed by cone-beam computed tomography (CBCT) superimposition. Secondary outcome measures will be the changes in the mandible, maxilla, lower and upper molars at the end of treatment assessed by tomography superimposition and the young patient's experience using the appliances assessed by self-reported questionnaires and semi-structured interviews. The randomisation method will be blocked randomisation, using software to generate a randomised list. The allocation concealment will be done in opaque envelopes numbered from 1 to 40 containing the treatment modality. The randomisation will be

  11. Molecular and functional analysis of anchorage independent, treatment-evasive neuroblastoma tumorspheres with enhanced malignant properties: A possible explanation for radio-therapy resistance.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Nazarian, Javad; Ghanem, Anthony; Vukmanovic, Stanislav; Sandler, Anthony D

    2018-01-01

    Despite significant advances in cancer treatment and management, more than 60% of patients with neuroblastoma present with very poor prognosis in the form of metastatic and aggressive disease. Solid tumors including neuroblastoma are thought to be heterogeneous with a sub-population of stem-like cells that are treatment-evasive with highly malignant characteristics. We previously identified a phenomenon of reversible adaptive plasticity (RAP) between anchorage dependent (AD) cells and anchorage independent (AI) tumorspheres in neuroblastoma cell cultures. To expand our molecular characterization of the AI tumorspheres, we sought to define the comprehensive proteomic profile of murine AD and AI neuroblastoma cells. The proteomic profiles of the two phenotypic cell populations were compared to each other to determine the differential protein expression and molecular pathways of interest. We report exclusive or significant up-regulation of tumorigenic pathways expressed by the AI tumorspheres compared to the AD cancer cells. These pathways govern metastatic potential, enhanced malignancy and epithelial to mesenchymal transition. Furthermore, radio-therapy induced significant up-regulation of specific tumorigenic and proliferative proteins, namely survivin, CDC2 and the enzyme Poly [ADP-ribose] polymerase 1. Bio-functional characteristics of the AI tumorspheres were resistant to sutent inhibition of receptor tyrosine kinases (RTKs) as well as to 2.5 Gy radio-therapy as assessed by cell survival, proliferation, apoptosis and migration. Interestingly, PDGF-BB stimulation of the PDGFRβ led to transactivation of EGFR and VEGFR in AI tumorspheres more potently than in AD cells. Sutent inhibition of PDGFRβ abrogated this transactivation in both cell types. In addition, 48 h sutent treatment significantly down-regulated the protein expression of PDGFRβ, MYCN, SOX2 and Survivin in the AI tumorspheres and inhibited tumorsphere self-renewal. Radio-sensitivity in AI

  12. The properties of genome conformation and spatial gene interaction and regulation networks of normal and malignant human cell types.

    Directory of Open Access Journals (Sweden)

    Zheng Wang

    Full Text Available The spatial conformation of a genome plays an important role in the long-range regulation of genome-wide gene expression and methylation, but has not been extensively studied due to lack of genome conformation data. The recently developed chromosome conformation capturing techniques such as the Hi-C method empowered by next generation sequencing can generate unbiased, large-scale, high-resolution chromosomal interaction (contact data, providing an unprecedented opportunity to investigate the spatial structure of a genome and its applications in gene regulation, genomics, epigenetics, and cell biology. In this work, we conducted a comprehensive, large-scale computational analysis of this new stream of genome conformation data generated for three different human leukemia cells or cell lines by the Hi-C technique. We developed and applied a set of bioinformatics methods to reliably generate spatial chromosomal contacts from high-throughput sequencing data and to effectively use them to study the properties of the genome structures in one-dimension (1D and two-dimension (2D. Our analysis demonstrates that Hi-C data can be effectively applied to study tissue-specific genome conformation, chromosome-chromosome interaction, chromosomal translocations, and spatial gene-gene interaction and regulation in a three-dimensional genome of primary tumor cells. Particularly, for the first time, we constructed genome-scale spatial gene-gene interaction network, transcription factor binding site (TFBS - TFBS interaction network, and TFBS-gene interaction network from chromosomal contact information. Remarkably, all these networks possess the properties of scale-free modular networks.

  13. I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

    International Nuclear Information System (INIS)

    Kusano, Shuichi; Yoshimitsu, Makoto; Hachiman, Miho; Ikeda, Masanori

    2015-01-01

    The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.

  14. I-mfa domain proteins specifically interact with HTLV-1 Tax and repress its transactivating functions

    Energy Technology Data Exchange (ETDEWEB)

    Kusano, Shuichi, E-mail: skusano@m2.kufm.kagoshima-u.ac.jp [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Yoshimitsu, Makoto; Hachiman, Miho [Division of Hematology and Immunology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan); Ikeda, Masanori [Division of Persistent and Oncogenic Viruses, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544 (Japan)

    2015-12-15

    The I-mfa domain proteins HIC (also known as MDFIC) and I-mfa (also known as MDFI) are candidate tumor suppressor genes that are involved in cellular and viral transcriptional regulation. Here, we show that HIC and I-mfa directly interact with human T-cell leukemia virus type-1 (HTLV-1) Tax protein in vitro. In addition, HIC and I-mfa repress Tax-dependent transactivation of an HTLV-1 long terminal repeat (LTR) reporter construct in COS-1, Jurkat and high-Tax-producing HTLV-1-infected T cells. HIC also interacts with Tax through its I-mfa domain in vivo and represses Tax-dependent transactivation of HTLV-1 LTR and NF-κB reporter constructs in an interaction-dependent manner. Furthermore, we show that HIC decreases the nuclear distribution and stimulates the proteasomal degradation of Tax. These data reveal that HIC specifically interacts with HTLV-1 Tax and negatively regulates Tax transactivational activity by altering its subcellular distribution and stability. - Highlights: • I-mfa domain proteins, HIC and I-mfa, specifically interact with HTLV-1 Tax. • HIC and I-mfa repress the Tax-dependent transactivation of HTLV-1 LTR. • HIC represses the Tax-dependent transactivation of NF-κΒ. • HIC decreases the nuclear distribution of Tax. • HIC stimulates the proteasomal degradation of Tax.

  15. Distinct spinning patterns gain differentiated loading tolerance of silk thread anchorages in spiders with different ecology.

    Science.gov (United States)

    Wolff, Jonas O; van der Meijden, Arie; Herberstein, Marie E

    2017-07-26

    Building behaviour in animals extends biological functions beyond bodies. Many studies have emphasized the role of behavioural programmes, physiology and extrinsic factors for the structure and function of buildings. Structure attachments associated with animal constructions offer yet unrealized research opportunities. Spiders build a variety of one- to three-dimensional structures from silk fibres. The evolution of economic web shapes as a key for ecological success in spiders has been related to the emergence of high performance silks and thread coating glues. However, the role of thread anchorages has been widely neglected in those models. Here, we show that orb-web (Araneidae) and hunting spiders (Sparassidae) use different silk application patterns that determine the structure and robustness of the joint in silk thread anchorages. Silk anchorages of orb-web spiders show a greater robustness against different loading situations, whereas the silk anchorages of hunting spiders have their highest pull-off resistance when loaded parallel to the substrate along the direction of dragline spinning. This suggests that the behavioural 'printing' of silk into attachment discs along with spinneret morphology was a prerequisite for the evolution of extended silk use in a three-dimensional space. This highlights the ecological role of attachments in the evolution of animal architectures. © 2017 The Author(s).

  16. Customized lingual bracket system and skeletal anchorage system for open bite correction

    Directory of Open Access Journals (Sweden)

    Toru Inami

    2016-01-01

    Full Text Available We treated a female patient with open bite and high-angle Class II Division 2 malocclusion using fully customized lingual appliances, orthodontic anchor screws (OAS, and a skeletal anchorage system (SAS. By carefully controlling torque, anchorage, and vertical skeletal and dental factors, we were able to obtain proper anterior coupling. Even after the retention phase of treatment, the occlusion was maintained, indicating that we provided proper treatment according to the properly designed treatment plan. This also indicates that cases with an extremely high level of difficulty, as in the present case with high-angle retrognathic mandible and open bite, can be treated by combining the Incognito appliance (a fully customized lingual bracket appliance with a SAS and OAS.

  17. Sortilin regulates progranulin action in castration-resistant prostate cancer cells.

    Science.gov (United States)

    Tanimoto, Ryuta; Morcavallo, Alaide; Terracciano, Mario; Xu, Shi-Qiong; Stefanello, Manuela; Buraschi, Simone; Lu, Kuojung G; Bagley, Demetrius H; Gomella, Leonard G; Scotlandi, Katia; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

    2015-01-01

    The growth factor progranulin is as an important regulator of transformation in several cellular systems. We have previously demonstrated that progranulin acts as an autocrine growth factor and stimulates motility, proliferation, and anchorage-independent growth of castration-resistant prostate cancer cells, supporting the hypothesis that progranulin may play a critical role in prostate cancer progression. However, the mechanisms regulating progranulin action in castration-resistant prostate cancer cells have not been characterized. Sortilin, a single-pass type I transmembrane protein of the vacuolar protein sorting 10 family, binds progranulin in neurons and negatively regulates progranulin signaling by mediating progranulin targeting for lysosomal degradation. However, whether sortilin is expressed in prostate cancer cells and plays any role in regulating progranulin action has not been established. Here, we show that sortilin is expressed at very low levels in castration-resistant PC3 and DU145 cells. Significantly, enhancing sortilin expression in PC3 and DU145 cells severely diminishes progranulin levels and inhibits motility, invasion, proliferation, and anchorage-independent growth. In addition, sortilin overexpression negatively modulates Akt (protein kinase B, PKB) stability. These results are recapitulated by depleting endogenous progranulin in PC3 and DU145 cells. On the contrary, targeting sortilin by short hairpin RNA approaches enhances progranulin levels and promotes motility, invasion, and anchorage-independent growth. We dissected the mechanisms of sortilin action and demonstrated that sortilin promotes progranulin endocytosis through a clathrin-dependent pathway, sorting into early endosomes and subsequent lysosomal degradation. Collectively, these results point out a critical role for sortilin in regulating progranulin action in castration-resistant prostate cancer cells, suggesting that sortilin loss may contribute to prostate cancer progression.

  18. Maxillary distraction osteogenesis in cleft lip and palate patients with skeletal anchorage.

    Science.gov (United States)

    Minami, Katsuhiro; Mori, Yoshihide; Tae-Geon, Kwon; Shimizu, Hidetaka; Ohtani, Miyuki; Yura, Yoshiaki

    2007-03-01

    Maxillary distraction osteogenesis with the rigid external distraction (RED) system has been used to treat cleft lip and palate (CLP) patients with severe maxillary hypoplasia. We introduce maxillary distraction osteogenesis for CLP patients with skeletal anchorage adapted on a stereolithographic model. Six maxillary deficiency CLP patients treated according to our CLP treatment protocol had undergone maxillary distraction osteogenesis. In all patients, computed tomography (CT) images were recorded preoperatively, and the data were transferred to a workstation. Three-dimensional skeletal structures were reconstructed with CT data sets, and a stereolithographic model was produced. On the stereolithographic model, miniplates were adapted to the surface of maxilla beside aperture piriforms. The operation performed involved a high Le Fort I osteotomy with pterygomaxillary disjunction. Miniplates were fixed to the maxillary segment with three or four screws and used for anchorage of the RED system. Retraction of the maxillary segment was initiated after 1 week. The accuracy of the stereolithographic models was enough to adapt the miniplates so that there was no need to readjust the plates during surgery. Postoperative cephalometric analysis showed that the direction of the retraction was almost parallel to the palatal plane, and dental compensation did not occur. We performed maxillary distraction osteogenesis with skeletal anchorage adapted on the stereolithographic models. Excellent esthetic outcome and skeletal advancement were achieved without dentoalveolar compensations.

  19. 7 CFR 301.89-5 - Movement of regulated articles from regulated areas.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Movement of regulated articles from regulated areas. 301.89-5 Section 301.89-5 Agriculture Regulations of the Department of Agriculture (Continued) ANIMAL... § 301.89-5 Movement of regulated articles from regulated areas. (a) Any regulated article may be moved...

  20. Anchorage strategies in geriatric hip fracture management

    Directory of Open Access Journals (Sweden)

    Knobe Matthias

    2016-12-01

    Full Text Available There is an enormous humanitarian and socioeconomic need to improve the quality and effectiveness of care for patients with hip fracture. To reduce mechanical complications in the osteosynthesis of proximal femoral fractures, improved fixation techniques have been developed including blade or screw-anchor devices, locked minimally invasive or cement augmentation strategies. However, despite numerous innovations and advances regarding implant design and surgical techniques, systemic and mechanical complication rates remain high. Treatment success depends on secure implant fixation in often-osteoporotic bone as well as on patient-specific factors (fracture stability, bone quality, comorbidity, and gender and surgeon-related factors (experience, correct reduction, and optimal screw placement in the head/neck fragment. For fracture fixation, the anchorage of the lag screw within the femoral head plays a crucial role depending on the implant’s design. Meta-analyses and randomized controlled studies demonstrate that there is a strong trend towards arthroplasty treating geriatric femoral neck fractures. However, for young adults as well as older patients with less compromised bone quality, or in undisplaced fractures, head-preserving therapy is preferred as it is less invasive and associated with good functional results. This review summarizes the evidence for the internal fixation of femoral neck fractures and trochanteric femoral fractures in elderly patients. In addition, biomechanical considerations regarding implant anchorage in the femoral head including rotation, migration, and femoral neck shortening are made. Finally, cement augmentation strategies for hip fracture implants are evaluated critically.

  1. CYB5D2 requires heme-binding to regulate HeLa cell growth and confer survival from chemotherapeutic agents.

    Directory of Open Access Journals (Sweden)

    Anthony Bruce

    Full Text Available The cytochrome b5 domain containing 2 (CYB5D2; Neuferricin protein has been reported to bind heme, however, the critical residues responsible for heme-binding are undefined. Furthermore, the relationship between heme-binding and CYB5D2-mediated intracellular functions remains unknown. Previous studies examining heme-binding in two cytochrome b5 heme-binding domain-containing proteins, damage-associated protein 1 (Dap1; Saccharomyces cerevisiae and human progesterone receptor membrane component 1 (PGRMC1, have revealed that conserved tyrosine (Y 73, Y79, aspartic acid (D 86, and Y127 residues present in human CYB5D2 may be involved in heme-binding. CYB5D2 binds to type b heme, however, only the substitution of glycine (G at D86 (D86G within its cytochrome b5 heme-binding (cyt-b5 domain abolished its heme-binding ability. Both CYB5D2 and CYB5D2(D86G localize to the endoplasmic reticulum. Ectopic CYB5D2 expression inhibited cell proliferation and anchorage-independent colony growth of HeLa cells. Conversely, CYB5D2 knockdown and ectopic CYB5D2(D86G expression increased cell proliferation and colony growth. As PGRMC1 has been reported to regulate the expression and activities of cytochrome P450 proteins (CYPs, we examined the role of CYB5D2 in regulating the activities of CYPs involved in sterol synthesis (CYP51A1 and drug metabolism (CYP3A4. CYB5D2 co-localizes with cytochrome P450 reductase (CYPOR, while CYB5D2 knockdown reduced lanosterol demethylase (CYP51A1 levels and rendered HeLa cells sensitive to mevalonate. Additionally, knockdown of CYB5D2 reduced CYP3A4 activity. Lastly, CYB5D2 expression conferred HeLa cell survival from chemotherapeutic agents (paclitaxel, cisplatin and doxorubicin, with its ability to promote survival being dependent on its heme-binding ability. Taken together, this study provides evidence that heme-binding is critical for CYB5D2 in regulating HeLa cell growth and survival, with endogenous CYB5D2 being required to

  2. Revisiting the stability of mini-implants used for orthodontic anchorage

    Directory of Open Access Journals (Sweden)

    Chung-Chen Jane Yao

    2015-11-01

    Conclusion: This study revealed that once the dental surgeon becomes familiar with the procedure, the stability of orthodontic mini-implants depends on the type of mini-implant, age of the patient, implantation site, and the healing time of the mini-implant. Miniplates are a more feasible anchorage system when miniscrews fail repeatedly.

  3. Clinical application of micro-implant anchorage in initial orthodontic retraction.

    Science.gov (United States)

    Wahabuddin, Shaji; Mascarenhas, Rohan; Iqbal, Mahamad; Husain, Akhter

    2015-02-01

    Micro-implant is a device that is temporarily fixed to bone for the purpose of enhancing orthodontic anchorage either by supporting the teeth of the reactive unit or by obviating the need for the reactive unit altogether, and which is subsequently removed after use. The purpose of this study was to evaluate the clinical efficiency of micro-implants in reinforcing anchorage during the initial retraction of anterior teeth, check the rate of initial retraction for 8 weeks, and assess the stability of micro-implants during this period. Eighteen micro-implants were placed (10 in the maxilla and 8 in the mandible) and immediately loaded with 200-250 g of force using 9-mm closed coil Nitinol springs. The amount of space closure was measured every 2 weeks until the eighth week. Cephalometric measurements were made at the end of the study to evaluate anchor loss, if any. Micro-implant stability was also assessed. The rate of initial retraction in the maxilla at the end of 8 weeks was 1.65 mm/quadrant and 1.51 mm/quadrant in the mandible. The amount of retraction on the left side of the arches was 1.66 mm/quadrant and 1.49 mm/quadrant on the right side. The average initial retraction for both arches per month was 0.78 mm. An anchor loss of 0.1 mm (0.06%) was observed in the maxilla while no mandibular anchor loss was recorded. The rate of initial retraction observed in the maxilla was more than that achieved in the mandible. Initial retraction was also more on the left side of the arches. There was no anchor loss in the mandible. The micro-implant-reinforced anchorage was helpful in minimizing anchor loss and accepted heavy traction forces but did not bring about a faster rate of retraction.

  4. A novel anchorage technique for transnasal traction in rigid external maxillary distraction.

    Science.gov (United States)

    Varol, A; Basa, S

    2013-12-01

    We describe an effective technique for anchorage of transnasal traction in the management of maxillary rotation during external distraction. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  5. Effect of non-metallic inclusions on hydrogen-induced cracking of API5L X100 steel

    Energy Technology Data Exchange (ETDEWEB)

    Jin, T.Y.; Liu, Z.Y.; Cheng, Y.F. [Department of Mechanical and Manufacturing Engineering, University of Calgary, Calgary, Alberta (Canada)

    2010-08-15

    In this work, the type, composition and distribution of inclusions contained in an API5L X100 steel were characterized by scanning electron microscopy and energy-dispersive x-ray analysis. A hydrogen-charging at various current densities was used to introduce hydrogen into the steel, and the correlation between HIC and the inclusions was established. The microstructure of the steel consists of a leather-like bainitic ferrite matrix, with martensite/austenite as the second phase particles. At least four types of inclusions are contained in API5L X100 steel, elongated MnS inclusions and spherical Al-, Si- and Ca-Al-O-S-enriched inclusions. In particular, the majority of inclusions in the steel are Al-enriched. Upon hydrogen-charging, hydrogen blisters and HIC could be caused in the steel in the absence of external stress. The cracks are primarily associated with the Al- and Si-enriched inclusions, rather than the elongated MnS inclusion. The critical amount of hydrogen resulting in HIC of the tested API5L X100 steel is determined to be 3.24 ppm under condition in this work. (author)

  6. Elevated p21-Activated Kinase 2 Activity Results in Anchorage-Independent Growth and Resistance to Anticancer Drug–Induced Cell Death

    Directory of Open Access Journals (Sweden)

    Jerry W. Marlin

    2009-03-01

    Full Text Available p21-Activated kinase 2 (PAK-2 seems to be a regulatory switch between cell survival and cell death signaling. We have shown previously that activation of full-length PAK-2 by Rac or Cdc42 stimulates cell survival, whereas caspase activation of PAK-2 to the proapoptotic PAK-2p34 fragment is involved in the cell death response. In this study, we present a role of elevated activity of full-length PAK-2 in anchorage-independent growth and resistance to anticancer drug–induced apoptosis of cancer cells. Hs578T human breast cancer cells that have low levels of PAK-2 activity were more sensitive to anticancer drug–induced apoptosis and showed higher levels of caspase activation of PAK-2 than MDA-MB435 and MCF-7 human breast cancer cells that have high levels of PAK-2 activity. To examine the role of elevated PAK-2 activity in breast cancer, we have introduced a conditionally active PAK-2 into Hs578T human breast cells. Conditional activation of PAK-2 causes loss of contact inhibition and anchorage-independent growth of Hs578T cells. Furthermore, conditional activation of PAK-2 suppresses activation of caspase 3, caspase activation of PAK-2, and apoptosis of Hs578T cells in response to the anticancer drug cisplatin. Our data suggest a novel mechanism by which full-length PAK-2 activity controls the apoptotic response by regulating levels of activated caspase 3 and thereby its own cleavage to the proapoptotic PAK-2p34 fragment. As a result, elevated PAK-2 activity interrupts the apoptotic response and thereby causes anchorage-independent survival and growth and resistance to anticancer drug–induced apoptosis.

  7. Three-dimensional printing spiders: back-and-forth glue application yields silk anchorages with high pull-off resistance under varying loading situations.

    Science.gov (United States)

    Wolff, Jonas O; Herberstein, Marie E

    2017-02-01

    The anchorage of structures is a crucial element of construction, both for humans and animals. Spiders use adhesive plaques to attach silk threads to substrates. Both biological and artificial adhesive structures usually have an optimal loading angle, and are prone to varying loading situations. Silk anchorages, however, must cope with loading in highly variable directions. Here we show that the detachment forces of thread anchorages of orb-web spiders are highly robust against pulling in different directions. This is gained by a two-step back-and-forth spinning pattern during the rapid production of the adhesive plaque, which shifts the thread insertion point towards the plaque centre and forms a flexible tree root-like network of branching fibres around the loading point. Using a morphometric approach and a tape-and-thread model we show that neither area, nor width of the plaque, but the shift of the loading point towards the plaque centre has the highest effect on pull-off resistance. This is explained by a circular propagation of the delamination crack with a low peeling angle. We further show that silken attachment discs are highly directional and adjusted to provide maximal performance in the upstream dragline. These results show that the way the glue is applied, crucially enhances the toughness of the anchorage without the need of additional material intake. This work is a starting point to study the evolution of tough and universal thread anchorages among spiders, and to develop bioinspired 'instant' anchorages of thread- and cable-like structures to a broad bandwidth of substrates. © 2017 The Author(s).

  8. Remains of the ancient ports and anchorage points at Miyani and Visawada, on the west coast of India: A study based on underwater investigations

    Digital Repository Service at National Institute of Oceanography (India)

    Gaur, A.S.; Sundaresh; Tripati, S.

    as an excellent natural harbour. The important antiquities include varieties of stone anchors, which are very similar to those reported from Dwarka and Bet Dwarka. The identification of ancient anchorage points between water depth of 5 and 15 m is another...

  9. Randomized clinical trial comparing control of maxillary anchorage with 2 retraction techniques.

    Science.gov (United States)

    Xu, Tian-Min; Zhang, Xiaoyun; Oh, Hee Soo; Boyd, Robert L; Korn, Edward L; Baumrind, Sheldon

    2010-11-01

    The objective of this pilot randomized clinical trial was to investigate the relative effectiveness of anchorage conservation of en-masse and 2-step retraction techniques during maximum anchorage treatment in patients with Angle Class I and Class II malocclusions. Sixty-four growing subjects (25 boys, 39 girls; 10.2-15.9 years old) who required maximum anchorage were randomized to 2 treatment techniques: en-masse retraction (n = 32) and 2-step retraction (n = 32); the groups were stratified by sex and starting age. Each patient was treated by a full-time clinic instructor experienced in the use of both retraction techniques at the orthodontic clinic of Peking University School of Stomatology in China. All patients used headgear, and most had transpalatal appliances. Lateral cephalograms taken before treatment and at the end of treatment were used to evaluate treatment-associated changes. Differences in maxillary molar mesial displacement and maxillary incisor retraction were measured with the before and after treatment tracings superimposed on the anatomic best fit of the palatal structures. Differences in mesial displacement of the maxillary first molar were compared between the 2 treatment techniques, between sexes, and between different starting-age groups. Average mesial displacement of the maxillary first molar was slightly less in the en-masse group than in the 2-step group (mean, -0.36 mm; 95% CI, -1.42 to 0.71 mm). The average mesial displacement of the maxillary first molar for both treatment groups pooled (n = 63, because 1 patient was lost to follow-up) was 4.3 ± 2.1 mm (mean ± standard deviation). Boys had significantly more mesial displacement than girls (mean difference, 1.3 mm; P <0.03). Younger adolescents had significantly more mesial displacement than older adolescents (mean difference, 1.3 mm; P <0.02). Average mesial displacement of the maxillary first molar with 2-step retraction was slightly greater than that for en-masse retraction, but the

  10. A review on the technical basis for ACI 349 code revision to anchorage criteria

    International Nuclear Information System (INIS)

    Lee, N. H.; You, S. H.

    1999-01-01

    Anchors are widely used to attach structural and nonstructural elements to concrete in nuclear power plant construction. Anchorage to concrete in nuclear-related structure plant has been designed per ACI 349-90 Appendix B. However, a new criteria for anchorage based on the concrete capacity design(CCD) approach is ready for publication under the normal publication procedures by ACI 349 Code Committee. Both design procedures(ACI 349-90 and ACI 349-New) show rather different concrete capacities. Earlier comparable studies show that the CCD method is a more reliable predictor of concrete breakout than the 45-degree cone method(ACI 349-90), hence the CCD method adopted by ACI 349-New Code has been recommended. The philosophy of the current code is to design ductile fastenings, which requires a limit to guard against brittle concrete failure. On the other hand, the new code requires calculations for the concrete breakout strength, pullout strength, side-face blowout strength of fastener in tension, and concrete breakout strength, pryout strength of fastener in shear. Therefore, the new code can accurately predict the concrete failure capacity for different behavior of the anchorage system. In this review, the provisions of ACI 349-90 and ACI 349-New are compared to show the major differences with emphasis on the concrete breakout capacity

  11. Biofilm formation on surface characterized micro-implants for skeletal anchorage in orthodontics

    NARCIS (Netherlands)

    Chin, Yeen; Sandham, John; de Vries, Jacob; van der Mei, Henderina; Busscher, Hendrik

    Micro-implants are increasingly popular in clinical orthodontics to effect skeletal anchorage. However, biofilm formation on their surfaces and subsequent infection of peri-implant tissues can result in either exfoliation or surgical removal of these devices. The present study aimed to assess

  12. Impedance-Based Cable Force Monitoring in Tendon-Anchorage Using Portable PZT-Interface Technique

    Directory of Open Access Journals (Sweden)

    Thanh-Canh Huynh

    2014-01-01

    Full Text Available In this paper, a portable PZT interface for tension force monitoring in the cable-anchorage subsystem is developed. Firstly, the theoretical background of the impedance-based method is presented. A few damage evaluation approaches are outlined to quantify the variation of impedance signatures. Secondly, a portable PZT interface is designed to monitor impedance signatures from the cable-anchorage subsystem. One degree-of-freedom analytical model of the PZT interface is established to explain how to represent the loss of cable force from the change in the electromechanical impedance of the PZT interface as well as reducing the sensitive frequency band by implementing the interface device. Finally, the applicability of the proposed PZT-interface technique is experimentally evaluated for cable force-loss monitoring in a lab-scaled test structure.

  13. Testing of large prestressing tendon end anchorage regions

    International Nuclear Information System (INIS)

    Johnson, T.E.

    1976-01-01

    Tests were performed on concrete end anchorage regions for prestressing tendons with ultimate strengths of approximately 8,900 kN. One test structure simulated a full scale concrete containment buttress and the other two test specimens were concrete blocks. The behavior of the test structure and specimens, when subjected to loading, was monitored by strain gages and dial gages. The testing illustrated that all of the amounts of reinforcing tested should be acceptable for the end anchor zones of large tendons presently used in prestressed concrete containment structures. (author)

  14. Indian Board of Orthodontics case report: Orthodontic management of vertical excess using skeletal anchorage

    Directory of Open Access Journals (Sweden)

    Ajit J Kalia

    2016-01-01

    Full Text Available B.B., a 21-year-old girl, presented with the chief complaint of forwardly placed upper front teeth and gummy smile. Diagnosis revealed prognathic maxilla and average mandible, Class II skeletal base with vertical growth pattern, end-on molars and Class II canine relationship bilaterally, convex profile, potentially incompetent lips, gummy smile, and protrusive lower lip. The patient′s treatment plan was extraction of all first bicuspids and retraction using temporary anchorage devices. Anchorage was reinforced using microimplants in the maxillary arch and second molar banding in the mandibular arch. The implants were placed high up in the vestibule to have more of an intrusive component and to reduce gummy smile at the end of the treatment.

  15. Numerical implementation of multiple peeling theory and its application to spider web anchorages.

    Science.gov (United States)

    Brely, Lucas; Bosia, Federico; Pugno, Nicola M

    2015-02-06

    Adhesion of spider web anchorages has been studied in recent years, including the specific functionalities achieved through different architectures. To better understand the delamination mechanisms of these and other biological or artificial fibrillar adhesives, and how their adhesion can be optimized, we develop a novel numerical model to simulate the multiple peeling of structures with arbitrary branching and adhesion angles, including complex architectures. The numerical model is based on a recently developed multiple peeling theory, which extends the energy-based single peeling theory of Kendall, and can be applied to arbitrarily complex structures. In particular, we numerically show that a multiple peeling problem can be treated as the superposition of single peeling configurations even for complex structures. Finally, we apply the developed numerical approach to study spider web anchorages, showing how their function is achieved through optimal geometrical configurations.

  16. Advances in cell culture: anchorage dependence

    Science.gov (United States)

    Merten, Otto-Wilhelm

    2015-01-01

    Anchorage-dependent cells are of great interest for various biotechnological applications. (i) They represent a formidable production means of viruses for vaccination purposes at very large scales (in 1000–6000 l reactors) using microcarriers, and in the last decade many more novel viral vaccines have been developed using this production technology. (ii) With the advent of stem cells and their use/potential use in clinics for cell therapy and regenerative medicine purposes, the development of novel culture devices and technologies for adherent cells has accelerated greatly with a view to the large-scale expansion of these cells. Presently, the really scalable systems—microcarrier/microcarrier-clump cultures using stirred-tank reactors—for the expansion of stem cells are still in their infancy. Only laboratory scale reactors of maximally 2.5 l working volume have been evaluated because thorough knowledge and basic understanding of critical issues with respect to cell expansion while retaining pluripotency and differentiation potential, and the impact of the culture environment on stem cell fate, etc., are still lacking and require further studies. This article gives an overview on critical issues common to all cell culture systems for adherent cells as well as specifics for different types of stem cells in view of small- and large-scale cell expansion and production processes. PMID:25533097

  17. 27 CFR 5.2 - Related regulations.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Related regulations. 5.2 Section 5.2 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF DISTILLED SPIRITS Scope § 5.2 Related regulations...

  18. 27 CFR 4.5 - Related regulations.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Related regulations. 4.5 Section 4.5 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS LABELING AND ADVERTISING OF WINE Scope § 4.5 Related regulations. The following...

  19. Anchorage onto deciduous teeth: effectiveness of early rapid maxillary expansion in increasing dental arch dimension and improving anterior crowding

    OpenAIRE

    Mutinelli, Sabrina; Manfredi, Mario; Guiducci, Antonio; Denotti, Gloria; Cozzani, Mauro

    2015-01-01

    Background Anchorage onto permanent dentition is a common procedure in rapid maxillary expansion. However, replacing first permanent molars with the second deciduous molars seems to be an option to reduce some negative side effects during orthodontic treatment. The purpose of this study was to evaluate the dental effect of rapid maxillary expansion with anchorage exclusively onto deciduous teeth performed in the first period of transition. Methods Twenty patients with a lateral cross-bite tre...

  20. 33 CFR 110.85 - Niagara River, Youngstown, N.Y.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Niagara River, Youngstown, N.Y... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.85 Niagara River, Youngstown, N.Y. (a) Area 1... of the Niagara River at latitude 43°14′33″ N, longitude 79°03′7.5″ W; thence westerly to a point at...

  1. Internal structure of mandible around mandibular molar using computed tomography. Anatomical consideration of molar anchorage in orthodontic treatment

    International Nuclear Information System (INIS)

    Enomoto, Yutaka; Yamashita, Daisuke; Saito, Katsuhiko; Kasai, Kazutaka

    2008-01-01

    For establishment of fine occlusion, facial profile and oral function in orthodontic treatment, molar anchorage in teeth movement is important manner in extracted cases. The aims of this study were to investigate the relationship between facial morphology and internal structure of mandibular body in molar region by computer tomography, and to discuss about molar anchorage in orthodontic treatment. The data for this study were obtained from 35 modern male Japanese skulls (mean age; 27 year-old, ranged from 18 year-old to 47 year-old). Measurement variables were FMA, SN to mandibular plane angle, gonial angle, alveolar breadth, cortical bone thickness of buccal and lingual sides, and the distance between dental root and cortical bone. As a result, alveolar breadth and the distance between dental root and cortical bone were narrow in long facial type, on the contrary, these variables were wide in short facial type. The result suggested that these variables were considered important factors as molar anchorage in extracted cases. (author)

  2. 45 CFR 4.5 - Effect of regulations.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Effect of regulations. 4.5 Section 4.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION SERVICE OF PROCESS § 4.5 Effect of regulations. The regulations in this part are intended solely to identify Department officials who are...

  3. [Treatment of adult bimaxillary arch protrusion with micro-implant anchorage].

    Science.gov (United States)

    Chen, Cheng; Zhang, Xiao-Rong

    2015-02-01

    In this study, micro-implants were used in 15 adult patients with mild and moderate bimaxillary arch protrusion or crowding. Cephalometric analysis was used to analyze hard and soft-tissues change before and after treatment, with the aim to investigate the effects of treatment on adult bimaxillary arch protrusion with micro-implant anchorage. Fifteen adult patients with mild and moderate bimaxillary arch protrusion were selected in this study. Micro-implants were inserted into the zygomaticoalveolar ridge of maxilla and the external oblique line of mandible. A NiTi coil spring was attached to the micro-implant to drag the whole upper and lower dentition for distal movement. Cephalometrics were taken before and after treatment, and the changes of soft and hard-tissue profile were studied. SPSS13.0 software package was used to analyze the data. (1)Sixty micro-implants remained stable.(2)SNA, SNB had no significant changes (P>0.05), and the relationship between the maxilla and the mandible did not change significantly. U1/NA, U1-NA, L1/NB, L1-NB and U1/L1 changes in hard tissue had significant difference in cephalometric measurement (PMicro-implant can provide not only excellent skeletal anchorage but also a novel way to distalize the whole dentition efficiently.

  4. Explaining the democratic anchorage of governance networks

    DEFF Research Database (Denmark)

    Skelcher, Chris; Klijn, Erik-Hans; Kübler, Daniel

    2011-01-01

    Advances in understanding the democratic anchorage of governance networks require carefully designed and contextually grounded empirical analysis that take into account contextual factors. The article uses a conjectural framework to study the impact of the national democratic milieu...... on the relationship between network governance and representative institutions in four European countries: the United Kingdom, Switzerland, the Netherlands, and Denmark. The article shows that the distinction between majoritarian and consensus democracy as well as the varying strength of voluntary associations...... are important contextual factors that help explain cross-national differences in the relationship between governance networks and representative institutions. We conclude that a context of weak associationalism in majoritarian democracies facilitates the instrumentalization of networks by government actors...

  5. Comparative Hi-C Reveals that CTCF Underlies Evolution of Chromosomal Domain Architecture

    Directory of Open Access Journals (Sweden)

    Matteo Vietri Rudan

    2015-03-01

    Full Text Available Topological domains are key architectural building blocks of chromosomes, but their functional importance and evolutionary dynamics are not well defined. We performed comparative high-throughput chromosome conformation capture (Hi-C in four mammals and characterized the conservation and divergence of chromosomal contact insulation and the resulting domain architectures within distantly related genomes. We show that the modular organization of chromosomes is robustly conserved in syntenic regions and that this is compatible with conservation of the binding landscape of the insulator protein CTCF. Specifically, conserved CTCF sites are co-localized with cohesin, are enriched at strong topological domain borders, and bind to DNA motifs with orientations that define the directionality of CTCF’s long-range interactions. Conversely, divergent CTCF binding between species is correlated with divergence of internal domain structure, likely driven by local CTCF binding sequence changes, demonstrating how genome evolution can be linked to a continuous flux of local conformation changes. We also show that large-scale domains are reorganized during genome evolution as intact modules.

  6. 34 CFR 303.5 - Applicable regulations.

    Science.gov (United States)

    2010-07-01

    ... this part; (2) Special education, related services, free appropriate public education, free public... 34 Education 2 2010-07-01 2010-07-01 false Applicable regulations. 303.5 Section 303.5 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND...

  7. Mini-placa como ancoragem ortodôntica: relato de caso Mini screw as orthodontic anchorage: case report

    Directory of Open Access Journals (Sweden)

    André Luiz Zétola

    2005-08-01

    ígida pode ser utilizada com bastante propriedade no tratamento ortodôntico qunado for requerida uma ancoragem máxima.It is needless to say that anchorage control is necessary to a successful orthodontic treatment. Without it, it would be impossible to obtain an ideal occlusion through orthodontic mechanics in the majority of cases. The utilization of rigid devices, originated from face traumatology and implant dentistry principles, to obtain rigid anchorage in orthodontics revolutionized the way of treating cases with an unsatisfactory prognosis. Specially in cases where a lot of anchorage is needed and it is difficult or impossible to get it. The objective of this article was to revise the literature related to the use of mini-screw implant systems, to report a case where it was utilized and to discuss some aspects related to the usage of rigid anchorage orthodontics. The rigid anchorage was used in a 39 year old female patient, who had the upper left molars with a relevant extrusion due to the absence of the lower left molars. Fixed appliances were placed on the upper arch with a TPA connecting the second bicuspids. The TPA was used to anchor the intrusion of the upper left molars. A quad-helix appliance was used to correct the upper right third molar crossbite. Since the orthodontic intrusion with only dental anchorage did not have a satisfactory result, an "L" shaped titanium plate was placed on the maxilla, at the apical region of the upper first and second left molars, with the purpose of obtaining a rigid orthodontic anchorage to intrude them. Elastics were used during five months with intrusive force,the obtained intrusion was 6 millimeters. After the removal of the appliance, upper and lower dental bleaching was made and final prosthesis were placed over the implants. Through the literature reviewed and the case reported, it can be concluded that rigid anchorage can be indicated in orthodontic treatments where there is lack of anchorage or the need of an absolute

  8. Comparison of rate of En masse retraction and anchorage loss in conventional labial appliance with labial and lingual force: A clinical study

    Directory of Open Access Journals (Sweden)

    Dilshad Quraishi

    2018-01-01

    Full Text Available Aims: The rate of en masse retraction and anchorage loss were compared between labial appliance with lingual force and conventional labial appliance. Subjects and Methods: The sample consists of 14 patients and they were divided into two groups. In Group 1 – labial appliance with lingual force, elastomeric chain was placed from the palatal surface of the canines to the palatal surface of the molars. In Group 2 – labial appliance with labial force, elastomeric chain was placed from the crimpable hook distal to lateral incisor to the molar tube hooks. The rate of en masse retraction and anchorage loss was calculated for both the groups during retraction in dental casts (R0, initial; R1, 4 weeks; R2, 8 weeks; and R3, 12 weeks. Statistical Analysis Used: Student's paired t-test. Results: The rate of retraction was faster and anchorage loss was lower with labial appliance with lingual force, i.e., Group 1. The difference of anchorage loss in Group 1 and Group 2 shows t = 4.824 and P value= 0.000, which is statistically highly significant. The difference of rate of retraction in Group 1 and Group 2 shows t = 3.573 and P value = 0.004, which is statistically signifcant. Conclusions: The rate of retraction was faster and anchorage loss was lower with labial appliance with lingual force, thus indicating that this new technique of space closure utilizes biomechanical advantage of lingual force in conventional labial appliance.

  9. De novo assembly of the Aedes aegypti genome using Hi-C yields chromosome-length scaffolds.

    Science.gov (United States)

    Dudchenko, Olga; Batra, Sanjit S; Omer, Arina D; Nyquist, Sarah K; Hoeger, Marie; Durand, Neva C; Shamim, Muhammad S; Machol, Ido; Lander, Eric S; Aiden, Aviva Presser; Aiden, Erez Lieberman

    2017-04-07

    The Zika outbreak, spread by the Aedes aegypti mosquito, highlights the need to create high-quality assemblies of large genomes in a rapid and cost-effective way. Here we combine Hi-C data with existing draft assemblies to generate chromosome-length scaffolds. We validate this method by assembling a human genome, de novo, from short reads alone (67× coverage). We then combine our method with draft sequences to create genome assemblies of the mosquito disease vectors Ae aegypti and Culex quinquefasciatus , each consisting of three scaffolds corresponding to the three chromosomes in each species. These assemblies indicate that almost all genomic rearrangements among these species occur within, rather than between, chromosome arms. The genome assembly procedure we describe is fast, inexpensive, and accurate, and can be applied to many species. Copyright © 2017, American Association for the Advancement of Science.

  10. Disimpaction of maxillary canines using temporary bone anchorage and cantilever springs.

    Science.gov (United States)

    Thebault, Benoit; Dutertre, Eric

    2015-03-01

    Impacted canines, particularly in the maxilla, are frequently encountered in orthodontic practice. Unfortunately, depending on their position, correction can often be difficult and sometimes unsuccessful. Thorough diagnosis along with orthodontic treatment combining bone-supported anchorage and cantilever springs appears, in our view, to offer the best solution to this tricky orthodontic challenge while limiting, as far as possible, the risk of failure. Copyright © 2015. Published by Elsevier Masson SAS.

  11. Strontium ranelate improved tooth anchorage and reduced root resorption in orthodontic treatment of rats.

    Science.gov (United States)

    Kirschneck, Christian; Wolf, Michael; Reicheneder, Claudia; Wahlmann, Ulrich; Proff, Peter; Roemer, Piero

    2014-12-05

    The anchorage mechanisms currently used in orthodontic treatment have various disadvantages. The objective of this study was to determine the applicability of the osteoporosis medication strontium ranelate in pharmacologically induced orthodontic tooth anchorage. In 48 male Wistar rats, a constant orthodontic force of 0.25 N was reciprocally applied to the upper first molar and the incisors by means of a Sentalloy(®) closed coil spring for two to four weeks. 50% of the animals received strontium ranelate at a daily oral dosage of 900 mg per kilogramme of body weight. Bioavailability was determined by blood analyses. The extent of tooth movement was measured both optometrically and cephalometrically (CBCT). Relative alveolar gene expression of osteoclastic markers and OPG-RANKL was assessed by qRT-PCR and root resorption area and osteoclastic activity were determined in TRAP-stained histologic sections of the alveolar process. Compared to controls, the animals treated with strontium ranelate showed up to 40% less tooth movement after four weeks of orthodontic treatment. Gene expression and histologic analyses showed significantly less osteoclastic activity and a significantly smaller root resorption area. Blood analyses confirmed sufficient bioavailability of strontium ranelate. Because of its pharmacologic effects on bone metabolism, strontium ranelate significantly reduced tooth movement and root resorption in orthodontic treatment of rats. Strontium ranelate may be a viable agent for inducing tooth anchorage and reducing undesired root resorption in orthodontic treatment. Patients under medication of strontium ranelate have to expect prolonged orthodontic treatment times. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Early bone anchorage to micro- and nano-topographically complex implant surfaces in hyperglycemia.

    Science.gov (United States)

    Ajami, Elnaz; Bell, Spencer; Liddell, Robert S; Davies, John E

    2016-07-15

    The aim of this work was to investigate the effect of implant surface design on early bone anchorage in the presence of hyperglycemia. 108 Wistar rats were separated into euglycemic (EG) controls and STZ-treated hyperglycemic (HG) groups, and received bilateral femoral custom rectangular implants of two surface topographies: grit blasted (GB) and grit-blast with a superimposed calcium phosphate nanotopography (GB-DCD). The peri-implant bone was subjected to a tensile disruption test 5, 7, and 9days post-operatively (n=28/time point); the force was measured; and the residual peri-implant bone was observed by scanning electron microscopy (SEM). Disruption forces at 5days were not significantly different from zero for the GB implants (p=0.24) in either metabolic group; but were for GB+DCD implants in both metabolic groups (pmicro-surfaced implants showed significantly different disruption forces at all time points (e.g. >15N and implants, as all values were very low (implant bone showed compromised intra-fibrillar collagen mineralization in hyperglycemia, while inter-fibrillar and cement line mineralization remained unaffected. Enhanced bone anchorage to the implant surfaces was observed on the nanotopographically complex surface independent of metabolic group. The compromised intra-fibrillar mineralization observed provides a mechanism by which early bone mineralization is affected in hyperglycemia. It is generally accepted that the hyperglycemia associated with diabetes mellitus compromises bone quality, although the mechanism by which this occurs is unknown. Uncontrolled hyperglycemia is therefore a contra-indication for bone implant placement. It is also known that nano-topographically complex implant surfaces accelerate early peri-implant healing. In this report we show that, in our experimental model, nano-topographically complex surfaces can mitigate the compromised bone healing seen in hyperglycemia. Importantly, we also provide a mechanistic explanation for

  13. Root perforation associated with the use of a miniscrew implant used for orthodontic anchorage: a case report.

    Science.gov (United States)

    McCabe, P; Kavanagh, C

    2012-07-01

    To highlight one of the possible complications associated with the inter-radicular placement of orthodontic miniscrews. This case report describes the endodontic treatment and surgical repair of an iatrogenic root perforation involving a maxillary first molar tooth following the placement of an orthodontic miniscrew placed for anchorage purposes in the treatment of an adult patient. The orthodontic treatment plan was completed. The long-term follow-up shows a successful treatment outcome. Inter-radicular placement of orthodontic miniscrews is a valuable source of anchorage in the treatment of orthodontic patients. Root perforation is a possible complication from inter-radicular placement of orthodontic miniscrews. Root perforation can be successfully treated, but may involve apical surgery. © 2012 International Endodontic Journal.

  14. [Comparing the anchorage effects of micro-implant and J hook on treating patients with maxillary protrusion].

    Science.gov (United States)

    Wu, Xin; Liu, Guo-yuan; Jiang, Yong-lian

    2015-10-01

    To investigate the differences in anchorage effects between micro-implants and J hook in treating patients with Class II division 1 maxillary protrusion. Thirty-one cases of adult patients with Class II division 1 maxillary protrusion were treated. They were divided into 2 groups depending on their selection. The first group included 17 patients for micro-implant anchorage, who adopted micro-implant and sliding mechanism to close maxillary extraction space and depress the mandibular molar. The second group encompassed 14 cases for J hook, who adopted sliding mechanism, J hooks in high traction and Class II intermaxillary traction to close extraction space. X-ray lateral cephalometric radiographs were measured before and after treatment, and SPSS16.0 software package was employed to compare the differences in soft and hard tissue changes before and after treatment between 2 groups. There were statistically significant differences in SNB, ANB, MP-FH, U1-Y, U6-Y, L6-MP, NLA, and UL-Y between the 2 groups before and after treatment, while there was no significant difference in SNA, U1-SN, U1-X, and U6-X between the 2 groups. In treating patients with Class II division 1 maxillary protrusion, micro-implant has stronger anchorage effects than J hook, while at the same time depressing the mandibular molars, and making it more favorable to improve Class II faces.

  15. Skeletal anchorage in orthodontics : A review of various systems in animal and human studies

    NARCIS (Netherlands)

    Janssen, Krista I.; Raghoebar, Gerry M.; Vissink, Arjan; Sandham, John

    2008-01-01

    Purpose: The aim of the present investigation was to review and evaluate the current literature on skeletal bone anchorage in orthodontics with regard to success rates of the various systems. Materials and Methods: MEDLINE, PubMed, and Cochrane searches (period January 1966 to January 2006, English

  16. 5 CFR 179.301 - Scope of regulations.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Scope of regulations. 179.301 Section 179.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS CLAIMS COLLECTION STANDARDS Administrative Offset § 179.301 Scope of regulations. These regulations apply to the...

  17. 77 FR 8252 - Adequacy Status of the Anchorage, Alaska, Carbon Monoxide Maintenance Plan for Transportation...

    Science.gov (United States)

    2012-02-14

    ... a SIP means that transportation activities will not produce new air quality violations, worsen... Anchorage, Alaska, Carbon Monoxide Maintenance Plan for Transportation Conformity Purposes AGENCY... Transportation & Public Facilities, and the U.S. Department of Transportation will be required to use [[Page 8253...

  18. Transverse maxillary distraction in patients with periodontal pathology or insufficient tooth anchorage using custom-made devices.

    Science.gov (United States)

    Fernández-Sanromán, Jacinto; Donascimento, Montserrat González; López, Alberto Costas; Ferro, Martín Fernández; Berrondo, Ibon Almandoz

    2010-07-01

    We present our experience using modified Hyrax devices for treating transverse deficiencies of the maxilla in adult patients with periodontal pathology or insufficient tooth anchorage. The surgical technique, clinical indications, and results are discussed. Eight adult patients (6 females, 2 males) requiring maxillary expansion were studied prospectively between July 2002 and July 2007. All the patients had periodontal pathology or insufficient tooth anchorage preventing the use of conventional Hyrax devices. Patients underwent surgically assisted rapid maxillary expansion with the use of custom-made modified Hyrax devices (bone-borne or tooth-bone-borne devices). Patients received preoperatively (T1), at the end of distraction (T2), at removal of the expansion device (T3), and 12 months after surgery (T4) lateral and posterior anterior cephalograms and study models to measure the width of the anterior and posterior dental arches with a digital sliding calliper. Mean age was 28.5 years (range, 18-45 years). A significant widening of the anterior (6.3 +/- 1.6 mm) and posterior (7.1 +/- 1.2 mm) dental arches was demonstrated. No significant differences were found when comparing T3 with T4 measures. No significant complications were found. The results indicated that maxillary expansion with custom-made devices in adults was an easy, affordable, predictable and stable technique without significant complications in patients who suffer periodontal pathology or patients without enough dental support. Copyright 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  19. Anchorage failure of young trees in sandy soils is prevented by a rigid central part of the root system with various designs

    Science.gov (United States)

    Danquechin Dorval, Antoine; Meredieu, Céline; Danjon, Frédéric

    2016-01-01

    Background and Aims Storms can cause huge damage to European forests. Even pole-stage trees with 80-cm rooting depth can topple. Therefore, good anchorage is needed for trees to survive and grow up from an early age. We hypothesized that root architecture is a predominant factor determining anchorage failure caused by strong winds. Methods We sampled 48 seeded or planted Pinus pinaster trees of similar aerial size from four stands damaged by a major storm 3 years before. The trees were gathered into three classes: undamaged, leaning and heavily toppled. After uprooting and 3D digitizing of their full root architectures, we computed the mechanical characteristics of the main components of the root system from our morphological measurements. Key Results Variability in root architecture was quite large. A large main taproot, either short and thick or long and thin, and guyed by a large volume of deep roots, was the major component that prevented stem leaning. Greater shallow root flexural stiffness mainly at the end of the zone of rapid taper on the windward side also prevented leaning. Toppling in less than 90-cm-deep soil was avoided in trees with a stocky taproots or with a very big leeward shallow root. Toppled trees also had a lower relative root biomass – stump excluded – than straight trees. Conclusions It was mainly the flexural stiffness of the central part of the root system that secured anchorage, preventing a weak displacement of the stump. The distal part of the longest taproot and attached deep roots may be the only parts of the root system contributing to anchorage through their maximum tensile load. Several designs provided good anchorage, depending partly on available soil depth. Pole-stage trees are in-between the juvenile phase when they fail by toppling and the mature phase when they fail by uprooting. PMID:27456136

  20. Silver oxide-containing hydroxyapatite coating supports osteoblast function and enhances implant anchorage strength in rat femur.

    Science.gov (United States)

    Eto, Shuichi; Miyamoto, Hiroshi; Shobuike, Takeo; Noda, Iwao; Akiyama, Takayuki; Tsukamoto, Masatsugu; Ueno, Masaya; Someya, Shinsuke; Kawano, Shunsuke; Sonohata, Motoki; Mawatari, Masaaki

    2015-09-01

    Antibacterial silver with hydroxyapatite (Ag-HA) is a promising coating material for imparting antibacterial properties to implants. We previously reported that 3% (w/w) silver with HA (3% Ag-HA) has both antibacterial activity and osteoconductivity. In this study, we investigated the effects of Ag-HA on the in vitro osteoblast function and the in vivo anchorage strength and osteoconductivity of implants. Production of the osteoblast marker alkaline phosphatase, but not cytotoxicity, was observed in cells of the osteoblast cell line MC3T3-E1 cultured on the 3% Ag-HA-coated surface. These results were similar to those observed with silver-free HA coating. In contrast, a significant high level of cytotoxicity was observed when the cells were cultured on a 50% Ag-HA-coated surface. The anchorage strength of implants inserted into the femur of Sprague-Dawley (SD) rats was enhanced by coating the implants with 3% Ag-HA. On the 3% Ag-HA-coated surface, both metaphyseal and diaphyseal areas were largely covered with new bone and had adequate osteoconductivity. These results suggest that 3% Ag-HA, like conventional HA, promotes osteogenesis by supporting osteoblast viability and function and thereby contributes to sufficient anchorage strength of implants. Application of 3% Ag-HA, which combines the osteoconductivity of HA and the antibacterial activity of silver, to prosthetic joints will help prevent postoperative infections. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Ground-water quality beneath solid-waste disposal sites at anchorage, Alaska

    Science.gov (United States)

    Zenone, Chester; Donaldson, D.E.; Grunwaldt, J.J.

    1975-01-01

    Studies at three solid-waste disposal sites in the Anchorage area suggest that differences in local geohydrologic conditions influence ground-water quality. A leachate was detected in ground water within and beneath two sites where the water table is very near land surface and refuse is deposited either at or below the water table in some parts of the filled areas. No leachate was detected in ground water beneath a third site where waste disposal is well above the local water table.

  2. Epigenetic mediated transcriptional activation of WNT5A participates in arsenical-associated malignant transformation

    International Nuclear Information System (INIS)

    Jensen, Taylor J.; Wozniak, Ryan J.; Eblin, Kylee E.; Wnek, Sean M.; Gandolfi, A. Jay; Futscher, Bernard W.

    2009-01-01

    Arsenic is a human carcinogen with exposure associated with cancer of the lung, skin, and bladder. Many potential mechanisms have been implicated as playing a role in the process of arsenical-induced malignancy including the perturbation of signaling pathways and aberrant epigenetic regulation. We initiated studies to examine the role of a member of the non-canonical WNT signaling pathway, WNT5A, in UROtsa cells and arsenite [URO-ASSC] and monomethylarsonous acid [URO-MSC] malignantly transformed variants. We present data herein that suggest that WNT5A is transcriptionally activated during arsenical-induced malignant transformation. This WNT5A transcriptional activation is correlated with the enrichment of permissive histone modifications and the reduction of repressive modifications in the WNT5A promoter region. The epigenetic activation of WNT5A expression and acetylation of its promoter remain after the removal of the arsenical, consistent with the maintenance of an anchorage independent growth phenotype in these cells. Additionally, treatment with epigenetic modifying drugs supports a functional role for these epigenetic marks in controlling gene expression. Reduction of WNT5A using lentiviral shRNA greatly attenuated the ability of these cells to grow in an anchorage independent fashion. Extension of our model into human bladder cancer cell lines indicates that each of the cell lines examined also express WNT5A. Taken together, these data suggest that the epigenetic remodeling of the WNT5A promoter is correlated with its transcriptional activation and this upregulation likely participates in arsenical-induced malignant transformation

  3. The tumor suppressor gene hypermethylated in cancer 1 is transcriptionally regulated by E2F1

    DEFF Research Database (Denmark)

    Jenal, Mathias; Trinh, Emmanuelle; Britschgi, Christian

    2009-01-01

    to the HIC1 promoter was shown by chromatin immunoprecipitation assays in human TIG3 fibroblasts expressing tamoxifen-activated E2F1. In agreement, activation of E2F1 in TIG3-E2F1 cells markedly increased HIC1 expression. Interestingly, expression of E2F1 in the p53(-/-) hepatocellular carcinoma cell line...

  4. Success rates and factors associated with failure of temporary anchorage devices: A prospective clinical trial.

    Science.gov (United States)

    Aly, Shehab A; Alyan, Doha; Fayed, Mona S; Alhammadi, Maged S; Mostafa, Yehya A

    2018-03-06

    The objective of the present study was to investigate success rates and associated factors affecting temporary anchorage device (TAD) failure in different biomechanical applications. A total of 180 TADs were used as a part of 82 patients' treatment plan (24 males and 58 females); their mean age was 21.41 years. Three types of TADs were used: 50 (3M ESPE, Neuss, Germany), 56 (Bone screw; Jeil Medical, Seoul, Korea), and 74 (Morelli, Sorocaba, Brazil). Eight maxillary and four mandibular sites were selected for insertion. Three different lengths (6, 8, and 10 mm) and three different diameters (1.5, 1.6, and 1.8 mm) were used. The force levels were set at 50, 100, 150, 200, and 250 g. Patient-, implant-, and operator-dependent factors were evaluated throughout the 266 days of function. Qualitative variables were described by proportions and percentages and analyzed using χ 2 test. The overall success rate was 82.2%. The higher age group showed a significantly higher success rate. Oral hygiene showed a statistically-significant (P ˂ .05) difference between both success and failure groups. All other patient-related factors showed no significant differences. Regarding force levels used, the highest success rate was in 250 g and the lowest was in 100 g. There were no significant differences between both groups regarding other implant- and operator-related factors. Temporary anchorage devices have a good success rate and are beneficial to be integrated in orthodontic treatment planning. Patient age, oral hygiene, and force level are the most significant factors affecting TAD success. © 2018 John Wiley & Sons Australia, Ltd.

  5. Management of post midface distraction occlusal discrepancy using temporary anchorage devices in a cleft patient

    Science.gov (United States)

    Koteswara Prasad, N. K.; Hussain, Syed Altaf; Chitharanjan, Arun B.; Murthy, Jyotsna

    2015-01-01

    Open bite deformity following a successful midface advancement by distraction osteogenesis is a common complication. Temporary anchorage devices can be deployed during the distraction and post-distraction settling phases for restoring the occlusion even in severe cases. The following report describes the management of severe anterior open bite following maxillary distraction. PMID:25991895

  6. A Manual for the Anchorage School District Bilingual Education Program Revised Scope and Sequence, K-3.

    Science.gov (United States)

    Heinrich, Maria Nieves Bumanlag Lilagan

    The manual offers a systematic set of procedures and relevant information to facilitate effective use of the Anchorage school district (ASD) bilingual education program (BEP). The historical background of the program's development is presented, available manuals for teaching English to limited English proficiency (LEP) students and related…

  7. Management of post midface distraction occlusal discrepancy using temporary anchorage devices in a cleft patient

    Directory of Open Access Journals (Sweden)

    N K Koteswara Prasad

    2015-01-01

    Full Text Available Open bite deformity following a successful midface advancement by distraction osteogenesis is a common complication. Temporary anchorage devices can be deployed during the distraction and post-distraction settling phases for restoring the occlusion even in severe cases. The following report describes the management of severe anterior open bite following maxillary distraction.

  8. 5 CFR 831.602 - Relation to other regulations.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Relation to other regulations. 831.602 Section 831.602 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) RETIREMENT Survivor Annuities Organization and Structure of Regulations on Survivor...

  9. Mini-screw implant or transpalatal arch-mediated anchorage reinforcement during canine retraction: a randomized clinical trial.

    Science.gov (United States)

    Sharma, Mohit; Sharma, Vineet; Khanna, Bharat

    2012-06-01

    To compare mesial movement of upper first molars during maxillary canine retraction using a pre-adjusted edgewise appliance provided by anchorage reinforcement and a transpalatal arch or mini-screw implant. Randomized clinical trial. Department of Orthodontics and Dentofacial Orthopedics, Armed Forces Medical College, Pune, India. From a cohort of subjects requiring the extraction of both upper first premolars and pre-adjusted edgewise appliances to correct their malocclusion, a total of 30 were randomly allocated to receive two different forms of anchorage reinforcement: group A--receiving mini-screw implant and group B--receiving a transpalatal arch Group A subjects received titanium mini-screw implants placed at the start of treatment between the maxillary second premolar and maxillary first molar. Maxillary second premolars were secured to the mini-screw implants using of 0.010-inch stainless steel ligature wire. Group B subjects received a custom-made transpalatal arch which was soldered to maxillary first molar bands. Active canine retraction was initiated in both groups on placement of a 0.019×0.025-inch stainless steel archwire using nickel titanium closed coil springs. Mesial movement of the upper first molars as measured on pre- (T1) and post-treatment (T2) lateral skull radiographs. The results showed that in group A the mean mesial movement of the first molars between T1 and T2 was 0.0 mm (SD 0.02; P = 0.90), whereas in Group B there was a mean forward movement of the first maolars of 2.48 mm (SD 0.71; Pimplants placed prior to levelling and aligning were able to provide absolute anchorage during maxillary canine retraction, in contrast to a transpalatal arch.

  10. A comparitive clinical study between self tapping and drill free screws as a source of rigid orthodontic anchorage.

    Science.gov (United States)

    Gupta, Nishant; Kotrashetti, S M; Naik, Vijay

    2012-03-01

    Self-tapping miniscrews are commonly being used as a temporary anchorage device for orthodontic purpose. A prerequisite for the insertion of these screws is the preparation of a pilot hole, which is time consuming and may result in damage to nerves, tooth root, drill bit breakage and thermal necrosis of bone. On the other hand the design of drill-free screws enables them to be inserted without drilling. The aim of this prospective study was to compare the stability and clinical response of the soft tissue around the self tapping and drill free screws when used for orthodontic anchorage for en mass retraction of maxillary anterior teeth. The study sample consisted of 20 patients requiring retraction of maxillary anterior teeth. The screws were placed in the alveolar bone between maxillary 2nd premolar and 1st molar bilaterally at the junction of attached gingiva and moveable mucosa. Pilot hole was drilled on the side which was selected for insertion of the self tapping screw under copious irrigation, after which it was inserted. Drill free screw was inserted on the contralateral side without predrilling. All screws were immediately loaded with 150-200 gm of retraction force. Patients were recalled for regular follow up for a period of 6 months. If the screws became mobile or showed any signs of inflammation during the course of the study, they were considered to be a failure. After a period of 6 months an overall success rate of 77.5% was noted. Four self tapping and five drill-free screws failed during the study. There was no statistically significant difference between the two types of screws with respect to success/failure. Mobility was found to be the major cause for the failure. Both self-tapping and the drill-free screws are effective anchorage units. But the latter have an edge over the conventional self-tapping screws because of decrease in operative time, little bone debris, less thermal damage, lower morbidity, and minimal patient discomfort as

  11. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern

    OpenAIRE

    Farret,Marcel Marchiori

    2016-01-01

    ABSTRACT This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end...

  12. Dental Extrusion with Orthodontic Miniscrew Anchorage: A Case Report Describing a Modified Method

    OpenAIRE

    Horliana, Ricardo Fidos; Horliana, Anna Carolina Ratto Tempestini; Wuo, Alexandre do Vale; Perez, Fl?vio Eduardo Guillin; Abr?o, Jorge

    2015-01-01

    In recent years, the skeletal anchorage through miniscrews has expanded the treatment options in orthodontics (Yamaguchi et al., 2012). We hereby present a modified method for tooth extrusion for cases where crown-lengthening surgery is contraindicated for aesthetic reasons. This modified method uses three orthodontic appliances: a mini-implant, an orthodontic wire, and a bracket. The aim of this case report was to increase the length of the clinical crown of a fractured tooth (tooth 23) by m...

  13. 77 FR 35104 - Notice of Request To Release Airport Property at Merrill Field Airport, Anchorage, AK

    Science.gov (United States)

    2012-06-12

    ... delivered to: Michelle Colby, Real Estate Services Manager, DOWL HKM, 4041 B Street, Anchorage, AK 99503...- 271-3665, email [email protected] or Michelle Colby, Real Estate Services Manager, DOWL HKM, 4041... Section 6.13 of the State of Alaska Right of Way Manual. This purchase offer was predicated on DOT&PF's...

  14. Transfer and anchorage bond behaviour in self-compacting concrete

    Directory of Open Access Journals (Sweden)

    Rigueira-Víctor, J. W.

    2006-12-01

    Full Text Available Self-compacting concretes (SCC provide solutions to the problems facing precast concrete construction, enhancing competitiveness, reducing turnaround times and improving final product quality. SCC is fast becoming a key product for the future development of the precast pre-stressed concrete industry.The present paper compares the bond performance of SCC and traditional concrete (TC. The bond performance results confirm the viability of SCC in precast pre-stressed concrete manufacture, despite a slightly higher loss of pre-stressing force and slightly greater anchorage lengths in SCC with a low water/cement ratio. No differences in transfer or anchorage length were detected,however, when high strength TC and SCC were compared. The ECADA test method proved to be well suited to detecting the differences between the concretes analyzed.El desarrollo de los hormigones autocompactantes (SCCofrece muchas posibilidades a las construcciones con hormigón prefabricado, aumentando su competitividad, reduciéndolos plazos de fabricación y ofreciendo mejoras en la calidad del producto final. El SCC se está convirtiendo en un producto clave para el futuro desarrollo de la industria de prefabricados de hormigón pretensado.En este estudio se compara el comportamiento adherente de los SCC con el de los hormigones tradicionales (TC actuales. Los resultados obtenidos confirman la viabilidad del uso de los SCC para la fabricación de elementos prefabricados con hormigón pretensado, en lo relativo a su comportamiento adherente, aunque con la necesidad de considerar unas pérdidas de pretensado ligeramente mayores. Asimismo,debe esperarse un ligero aumento de las longitudes de anclaje cuando se trabaje con SCC de baja relación agua/cemento. Sin embargo, no se han detectado diferencias de comportamiento entre ambos tipos de hormigón cuando la resistencia a compresión es alta en lo relativo a las longitudes de transmisión y anclaje. El método de ensayo ECADA

  15. Digital lingual orthodontics and temporary anchorage devices for efficient biomechanics

    Directory of Open Access Journals (Sweden)

    Pravin Shetty

    2016-01-01

    Full Text Available Adult patients seeking orthodontic treatment at all times present with an esthetic demand even during treatment. The lingual orthodontics, apart from its esthetic values, also presents several other advantages. Currently, it has become a complete system in itself, starting from an accurate diagnosis, treatment protocol, and laboratory procedure to placement of the appliance in the patient′s mouth. With the advent of computer-aided design/computer-aided manufacturing system, the lingual orthodontics is more evolved and made ease operators in respect to more efficient mechanics and reduced archwire adjustments. The present article presents two cases to show the efficiency of lingual orthodontics with temporary anchorage devices and anterior retraction hook.

  16. Enzymatic Degradation of Poly(ethylene 2,5-furanoate Powders and Amorphous Films

    Directory of Open Access Journals (Sweden)

    Simone Weinberger

    2017-10-01

    Full Text Available Poly(ethylene 2,5-furanoate (PEF is arousing great interest as a biobased alternative to plastics like poly(ethylene terephthalate (PET due to its wide range of potential applications, such as food and beverage packaging, clothing, and in the car industry. In the present study, the hydrolysis of PEF powders of different molecular masses (Mn = 55, Mw = 104 kg/mol and Mn = 18, Mw = 29 kg/mol and various particle sizes (180 < d and 180 < d < 425 µm using cutinase 1 from Thermobifida cellulosilytica (Thc_cut1 was studied. Thereby, the effects of molecular mass, particle size and crystallinity on enzymatic hydrolysis were investigated. The results show that particles with lower molecular mass are hydrolyzed faster than those with higher masses, and that the higher the molecular mass, the lower the influence of the particle size on the hydrolysis. Furthermore, cutinases from Humicola insolens (HiC and Thc_cut1 were compared with regard to their hydrolytic activity on amorphous PEF films (measured as release of 2,5-furandicarboxylic acid (FDCA and weight loss in different reaction media (1 M KPO pH 8, 0.1 M Tris-HCl pH 7 and at different temperatures (50 °C and 65 °C. A 100% hydrolysis of the PEF films was achieved after only 72 h of incubation with a HiC in 1 M KPO pH 8 at 65 °C. Moreover, the hydrolysis reaction was monitored by LC/TOF-MS analysis of the released reaction products and by Scanning Electron Microscopy (SEM examination of the polymer surfaces. Enzymatic hydrolysis of PEF with Thc_cut1 and HiC has potential for use in surface functionalization and recycling purposes.

  17. Study on reinforced concrete high-rise building using prefabricated beam-column joints. Part 3. ; Basic anchorage behaviors of longitudinal bars of beams. Hahsirater dot hari setsugobu PC ka koho (PG connection koho) wo mochiita RC koso tatemono no kaihatsu. 3. ; Hari shukin no kisoteki teichaku seijo

    Energy Technology Data Exchange (ETDEWEB)

    SEkine, M.; Yoshioka, K.; Eto, H. (Obayashi Corp., Tokyo (Japan))

    1991-08-10

    Pull-out tests were carried out to examine basic anchorage behaviors of through holes for beam re-bars by using a PG connection method, in which columns and beam-column joints with through holes for beam re-bars in the reinforced concrete framed construction are precast simultaneously. Specimens made by the PG connection method showed better anchorage behaviors than specimens made by the conventional anchorage method. In case of anchorage width of 80cm and concrete strength of about 350kgf/cm{sup 2}, it was recognized that large slipping of re-bars did not occur under allowable bond stress when the interval between re-bars was not less than 15cm and covering depth to the core of re-bars was not less than 8cm. Concerning a specimen which did not show splitting bond failure because of lateral compressive stress, bond stress of re-bars when large slipping occurred was 1.5 times or more in comparison with the allowable bond stress. Since this specimen held high slipping rigidity even after increase of slipping, its anchoring stress increased by 32-57% compared with a specimen without lateral compressive stress. 4 refs., 7 figs., 3 tabs.

  18. 78 FR 21861 - Tribal Consultation on the Draft Regulations Governing the Tribal Transportation Program

    Science.gov (United States)

    2013-04-12

    ... Welcome and Introductions. 9:15 a.m.-9:30 a.m Brief history of 25 CFR part 170 and process for updating... following dates, at the following locations: Meeting date Location Time May 14, 2013 Anchorage, AK 9 a.m.-4... result of the enactment of SAFETEA-LU but the regulation was not revised at that time. MAP-21 effectively...

  19. Verification of the local structural response of building structures in the anchorage areas of heavy components

    International Nuclear Information System (INIS)

    Krutzik, N.J.; Tropp, R.

    1989-01-01

    In conventional dynamic structural analyses for determining dynamic system response for various locations at which components are installed inside the structures it is common practice (in order to simplify analytical effort) to assume that the anchorage (anchor plate, anchor bolts or throughbolts, concrete and reinforcement in the area of bound) has rigid body characteristics and that the building structure itself does not display any local response of its own. The influence of the stiffness of the anchor plate as well anchor bolts and its stress level on the dynamic response is also neglected. For a large number of anchoring systems, especially for all those components and systems having only a small mass, this assumption is certainly appropriate. At some locations, particularly at points where heavy components are anchored or when loading input has been increased, this can lead to local loading of the anchor system as well as of the building structure well into the nonlinear range. Often, verification of capability to accommodate these loads is not possible without changing the wall thicknesses or increasing the percentage of reinforcement. Since the presence of linear or nonlinear effects can be expected to result in energy dissipation (increase in damping capacity and also a change in the stiffness of the coupled system) it must be assumed that the dynamic response between the theoretical coupling point A and the real connection point B of the component on the anchor plate can be considerably altered. Some changes of the dynamic response in the connection point B have to be expected generally even in cases of linear-elastic loading of the anchorage. Using typical anchoring systems as an example, the influence of consideration of nonlinear effects in the anchorage area of a typical anchor plate on the dynamic response as well as the conservatism of conventional analytical approaches are investigated

  20. RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism

    International Nuclear Information System (INIS)

    Yamaki, Nao; Negishi, Manabu; Katoh, Hironori

    2007-01-01

    In normal epithelial cells, cell-matrix interaction is required for cell survival and proliferation, whereas disruption of this interaction causes epithelial cells to undergo apoptosis called anoikis. Here we show that the small GTPase RhoG plays an important role in the regulation of anoikis. HeLa cells are capable of anchorage-independent cell growth and acquire resistance to anoikis. We found that RNA interference-mediated knockdown of RhoG promoted anoikis in HeLa cells. Previous studies have shown that RhoG activates Rac1 and induces several cellular functions including promotion of cell migration through its effector ELMO and the ELMO-binding protein Dock180 that function as a Rac-specific guanine nucleotide exchange factor. However, RhoG-induced suppression of anoikis was independent of the ELMO- and Dock180-mediated activation of Rac1. On the other hand, the regulation of anoikis by RhoG required phosphatidylinositol 3-kinase (PI3K) activity, and constitutively active RhoG bound to the PI3K regulatory subunit p85α and induced the PI3K-dependent phosphorylation of Akt. Taken together, these results suggest that RhoG protects cells from apoptosis caused by the loss of anchorage through a PI3K-dependent mechanism, independent of its activation of Rac1

  1. 78 FR 11745 - Anchorages; Lower Mississippi River, Above Head of Passes, Convent, LA and Point Pleasant, LA

    Science.gov (United States)

    2013-02-20

    ... able to maneuver in, around, and through the anchorage. Operators who choose to maneuver their vessels... respects the First Amendment rights of protesters. Protesters are asked to contact the person listed in the FOR FURTHER INTFORMATION CONTACT section to coordinate protest activities so that your message can be...

  2. Bioreactor design for successive culture of anchorage-dependent cells operated in an automated manner.

    Science.gov (United States)

    Kino-Oka, Masahiro; Ogawa, Natsuki; Umegaki, Ryota; Taya, Masahito

    2005-01-01

    A novel bioreactor system was designed to perform a series of batchwise cultures of anchorage-dependent cells by means of automated operations of medium change and passage for cell transfer. The experimental data on contamination frequency ensured the biological cleanliness in the bioreactor system, which facilitated the operations in a closed environment, as compared with that in flask culture system with manual handlings. In addition, the tools for growth prediction (based on growth kinetics) and real-time growth monitoring by measurement of medium components (based on small-volume analyzing machinery) were installed into the bioreactor system to schedule the operations of medium change and passage and to confirm that culture proceeds as scheduled, respectively. The successive culture of anchorage-dependent cells was conducted with the bioreactor running in an automated way. The automated bioreactor gave a successful culture performance with fair accordance to preset scheduling based on the information in the latest subculture, realizing 79- fold cell expansion for 169 h. In addition, the correlation factor between experimental data and scheduled values through the bioreactor performance was 0.998. It was concluded that the proposed bioreactor with the integration of the prediction and monitoring tools could offer a feasible system for the manufacturing process of cultured tissue products.

  3. Cellular Dichotomy Between Anchorage-Independent Growth Responses to bFGF and TA Reflects Molecular Switch in Commitment to Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Waters, Katrina M.; Tan, Ruimin; Opresko, Lee K.; Quesenberry, Ryan D.; Bandyopadhyay, Somnath; Chrisler, William B.; Weber, Thomas J.

    2009-11-01

    We have investigated gene expression patterns underlying reversible and irreversible anchorage-independent growth (AIG) phenotypes to identify more sensitive markers of cell transformation for studies directed at interrogating carcinogenesis responses. In JB6 mouse epidermal cells, basic fibroblast growth factor (bFGF) induces an unusually efficient and reversible AIG response, relative to 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced AIG which is irreversible. The reversible and irreversible AIG phenotypes are characterized by largely non-overlapping global gene expression profiles. However, a subset of differentially expressed genes were identified as common to reversible and irreversible AIG phenotypes, including genes regulated in a reciprocal fashion. Hepatic leukemia factor (HLF) and D-site albumin promoter-binding protein (DBP) were increased in both bFGF and TPA soft agar colonies and selected for functional validation. Ectopic expression of human HLF and DBP in JB6 cells resulted in a marked increase in TPA- and bFGF-regulated AIG responses. HLF and DBP expression were increased in soft agar colonies arising from JB6 cells exposed to gamma radiation and in a human basal cell carcinoma tumor tissue, relative to paired non-tumor tissue. Subsequent biological network analysis suggests that many of the differentially expressed genes that are common to bFGF- and TPA-dependent AIG are regulated by c-Myc, SP-1 and HNF-4 transcription factors. Collectively, we have identified a potential molecular switch that mediates the transition from reversible to irreversible AIG.

  4. The Provisional Staff Regulations of the Agency. Amendment to Regulation 5.04(a)

    International Nuclear Information System (INIS)

    1973-01-01

    On 20 February 1973 the Board of Governors approved the substitution of the figure '1500' for '1000' in the second sentence of Provisional Staff Regulation 5.04(a) as set forth in document INFCIRC/6/Rev.2/Mod.1, thus amending that Regulation to read

  5. Mechanical anchorage of FRP tendons – A literature review

    DEFF Research Database (Denmark)

    Schmidt, Jacob W.; Bennitz, Anders; Täljsten, Björn

    2012-01-01

    High tensile strength, good resistance to degradation and creep, low weight and, to some extent, the ability to change the modulus of elasticity are some of the advantages of using prestressed, unidirectional FRP (Fibre Reinforced Polymer) tendon systems. Bonded and non-bonded versions of these s......High tensile strength, good resistance to degradation and creep, low weight and, to some extent, the ability to change the modulus of elasticity are some of the advantages of using prestressed, unidirectional FRP (Fibre Reinforced Polymer) tendon systems. Bonded and non-bonded versions...... with such systems. This is especially important in external post-tensioned tendon systems, where the anchorage points are exposed to the full load throughout the life span of the structure. Consequently, there are large requirements related to the long-term capacity and fatigue resistance of such systems. Several...

  6. A novel role for drebrin in regulating progranulin bioactivity in bladder cancer.

    Science.gov (United States)

    Xu, Shi-Qiong; Buraschi, Simone; Morcavallo, Alaide; Genua, Marco; Shirao, Tomoaki; Peiper, Stephen C; Gomella, Leonard G; Birbe, Ruth; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

    2015-05-10

    We recently established a critical role for the growth factor progranulin in bladder cancer insofar as progranulin promotes urothelial cancer cell motility and contributes, as an autocrine growth factor, to the transformed phenotype by modulating invasion and anchorage-independent growth. In addition, progranulin expression is upregulated in invasive bladder cancer tissues compared to normal controls. However, the molecular mechanisms of progranulin action in bladder cancer have not been fully elucidated. In this study, we searched for novel progranulin-interacting proteins using pull-down assays with recombinant progranulin and proteomics. We discovered that drebrin, an F-actin binding protein, bound progranulin in urothelial cancer cells. We characterized drebrin function in urothelial cancer cell lines and showed that drebrin is critical for progranulin-dependent activation of the Akt and MAPK pathways and modulates motility, invasion and anchorage-independent growth. In addition, drebrin regulates tumor formation in vivo and its expression is upregulated in bladder cancer tissues compared to normal tissue controls. Our data are translationally relevant as indicate that drebrin exerts an essential functional role in the regulation of progranulin action and may constitute a novel target for therapeutic intervention in bladder tumors. In addition, drebrin may serve as novel biomarker for bladder cancer.

  7. Asymmetrical distalization of maxillary molars with zygomatic anchorage, improved superelastic nickel-titanium alloy wires, and open-coil springs.

    Science.gov (United States)

    Ishida, Takayoshi; Yoon, Hyung Sik; Ono, Takashi

    2013-10-01

    In nongrowing patients with skeletal Class II malocclusion, premolar extraction or maxillary distalization can be used as camouflage treatment. Zygomatic anchorage enables distalization in uncooperative or noncompliant patients. We describe 1 such procedure in a 24-year-old woman. We used novel improved superelastic nickel-titanium archwires combined with nickel-titanium open-coil springs to provide a constant and continuous low force to the dentition. We were able to successfully eliminate the protrusive profile and correct the Class II molar relationship using this system of zygomatic anchorage. The posterior occlusal relationships were improved to achieve Class I canine and molar relationships on both sides, and ideal overbite and overjet relationships were established. Facial esthetics was improved with decreased protrusion of the upper and lower lips. The method used here is a promising alternative to traditional distalization techniques and might offer an effective and simple means of distalizing maxillary molars in uncooperative patients. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  8. 46 CFR 386.5 - Conformity with signs and posted regulations.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Conformity with signs and posted regulations. 386.5 Section 386.5 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION MISCELLANEOUS REGULATIONS GOVERNING PUBLIC BUILDINGS AND GROUNDS AT THE UNITED STATES MERCHANT MARINE ACADEMY § 386.5 Conformity with...

  9. Glucose Regulates the Expression of the Apolipoprotein A5 Gene

    Energy Technology Data Exchange (ETDEWEB)

    Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2008-04-07

    The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

  10. Dental extrusion with orthodontic miniscrew anchorage: a case report describing a modified method.

    Science.gov (United States)

    Horliana, Ricardo Fidos; Horliana, Anna Carolina Ratto Tempestini; Wuo, Alexandre do Vale; Perez, Flávio Eduardo Guillin; Abrão, Jorge

    2015-01-01

    In recent years, the skeletal anchorage through miniscrews has expanded the treatment options in orthodontics (Yamaguchi et al., 2012). We hereby present a modified method for tooth extrusion for cases where crown-lengthening surgery is contraindicated for aesthetic reasons. This modified method uses three orthodontic appliances: a mini-implant, an orthodontic wire, and a bracket. The aim of this case report was to increase the length of the clinical crown of a fractured tooth (tooth 23) by means of an orthodontic extrusion with the modified method of Roth and Diedrich.

  11. 33 CFR 110.238 - Apra Harbor, Guam.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Apra Harbor, Guam. 110.238 Section 110.238 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.238 Apra Harbor, Guam. (a) The anchorage grounds (Datum: WGS...

  12. 33 CFR 110.208 - Buffalo Harbor, N.Y.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Buffalo Harbor, N.Y. 110.208 Section 110.208 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.208 Buffalo Harbor, N.Y. (a) The anchorage grounds—(1...

  13. 41 CFR 102-2.5 - What is the Federal Management Regulation (FMR)?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What is the Federal Management Regulation (FMR)? 102-2.5 Section 102-2.5 Public Contracts and Property Management Federal... MANAGEMENT REGULATION SYSTEM Regulation System General § 102-2.5 What is the Federal Management Regulation...

  14. Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Jesus Adrian [Laboratorio de Terapia Genica, Departamento de Genetica y Biologia Molecular, CINVESTAV, Av. IPN 2508, Mexico 07360 D.F. (Mexico); Alvarez-Salas, Luis Marat, E-mail: lalvarez@cinvestav.mx [Laboratorio de Terapia Genica, Departamento de Genetica y Biologia Molecular, CINVESTAV, Av. IPN 2508, Mexico 07360 D.F. (Mexico)

    2011-06-10

    Highlights: {yields} In this study we examine miR-34c-3p and miR-34c-5p functions in SiHa cells. {yields} We study miRNA effect on cell proliferation, anchorage independent growth, apoptosis, cell motility and invasion. {yields} We find that miR-34c-3p and miR-34c-5p inhibition of proliferation and anchorage independent growth are exclusive to SiHa cells. {yields} miR-34c-3p induces apoptosis and inhibits cell motility and invasion in SiHa cells. {yields} In this study we conclude that miR-34c-3p functions as a tumor suppressor differ from miR-34c-5p. -- Abstract: MicroRNAs (miRNA) regulate expression of several genes associated with human cancer. Here, we analyzed the function of miR-34c, an effector of p53, in cervical carcinoma cells. Expression of either miR-34c-3p or miR-34c-5p mimics caused inhibition of cell proliferation in the HPV-containing SiHa cells but not in other cervical cells irrespective of tumorigenicity and HPV content. These results suggest that SiHa cells may lack of regulatory mechanisms for miR-34c. Monolayer proliferation results showed that miR-34c-3p produced a more pronounced inhibitory effect although both miRNAs caused inhibition of anchorage independent growth at similar extent. However, ectopic expression of pre-miR-34c-3p, but not pre-miR-34c-5p, caused S-phase arrest in SiHa cells triggering a strong dose-dependent apoptosis. A significant inhibition was observed only for miR-34c-3p on SiHa cells migration and invasion, therefore implying alternative regulatory pathways and targets. These results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights in the understanding of miRNA biology.

  15. Differential effects of miR-34c-3p and miR-34c-5p on SiHa cells proliferation apoptosis, migration and invasion

    International Nuclear Information System (INIS)

    Lopez, Jesus Adrian; Alvarez-Salas, Luis Marat

    2011-01-01

    Highlights: → In this study we examine miR-34c-3p and miR-34c-5p functions in SiHa cells. → We study miRNA effect on cell proliferation, anchorage independent growth, apoptosis, cell motility and invasion. → We find that miR-34c-3p and miR-34c-5p inhibition of proliferation and anchorage independent growth are exclusive to SiHa cells. → miR-34c-3p induces apoptosis and inhibits cell motility and invasion in SiHa cells. → In this study we conclude that miR-34c-3p functions as a tumor suppressor differ from miR-34c-5p. -- Abstract: MicroRNAs (miRNA) regulate expression of several genes associated with human cancer. Here, we analyzed the function of miR-34c, an effector of p53, in cervical carcinoma cells. Expression of either miR-34c-3p or miR-34c-5p mimics caused inhibition of cell proliferation in the HPV-containing SiHa cells but not in other cervical cells irrespective of tumorigenicity and HPV content. These results suggest that SiHa cells may lack of regulatory mechanisms for miR-34c. Monolayer proliferation results showed that miR-34c-3p produced a more pronounced inhibitory effect although both miRNAs caused inhibition of anchorage independent growth at similar extent. However, ectopic expression of pre-miR-34c-3p, but not pre-miR-34c-5p, caused S-phase arrest in SiHa cells triggering a strong dose-dependent apoptosis. A significant inhibition was observed only for miR-34c-3p on SiHa cells migration and invasion, therefore implying alternative regulatory pathways and targets. These results suggest differential tumor suppressor roles for miR-34c-3p and miR-34c-5p and provide new insights in the understanding of miRNA biology.

  16. Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5)·extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1.

    Science.gov (United States)

    Mazalouskas, Matthew D; Godoy-Ruiz, Raquel; Weber, David J; Zimmer, Danna B; Honkanen, Richard E; Wadzinski, Brian E

    2014-02-14

    Serine/threonine protein phosphatase 5 (PP5, PPP5C) is known to interact with the chaperonin heat shock protein 90 (HSP90) and is involved in the regulation of multiple cellular signaling cascades that control diverse cellular processes, such as cell growth, differentiation, proliferation, motility, and apoptosis. Here, we identify PP5 in stable complexes with extracellular signal-regulated kinases (ERKs). Studies using mutant proteins reveal that the formation of PP5·ERK1 and PP5·ERK2 complexes partially depends on HSP90 binding to PP5 but does not require PP5 or ERK1/2 activity. However, PP5 and ERK activity regulates the phosphorylation state of Raf1 kinase, an upstream activator of ERK signaling. Whereas expression of constitutively active Rac1 promotes the assembly of PP5·ERK1/2 complexes, acute activation of ERK1/2 fails to influence the phosphatase-kinase interaction. Introduction of oncogenic HRas (HRas(V12)) has no effect on PP5-ERK1 binding but selectively decreases the interaction of PP5 with ERK2, in a manner that is independent of PP5 and MAPK/ERK kinase (MEK) activity, yet paradoxically requires ERK2 activity. Additional studies conducted with oncogenic variants of KRas4B reveal that KRas(L61), but not KRas(V12), also decreases the PP5-ERK2 interaction. The expression of wild type HRas or KRas proteins fails to reduce PP5-ERK2 binding, indicating that the effect is specific to HRas(V12) and KRas(L61) gain-of-function mutations. These findings reveal a novel, differential responsiveness of PP5-ERK1 and PP5-ERK2 interactions to select oncogenic Ras variants and also support a role for PP5·ERK complexes in regulating the feedback phosphorylation of PP5-associated Raf1.

  17. SIRT5 regulation of ammonia-induced autophagy and mitophagy

    Science.gov (United States)

    Polletta, Lucia; Vernucci, Enza; Carnevale, Ilaria; Arcangeli, Tania; Rotili, Dante; Palmerio, Silvia; Steegborn, Clemens; Nowak, Theresa; Schutkowski, Mike; Pellegrini, Laura; Sansone, Luigi; Villanova, Lidia; Runci, Alessandra; Pucci, Bruna; Morgante, Emanuela; Fini, Massimo; Mai, Antonello; Russo, Matteo A; Tafani, Marco

    2015-01-01

    In liver the mitochondrial sirtuin, SIRT5, controls ammonia detoxification by regulating CPS1, the first enzyme of the urea cycle. However, while SIRT5 is ubiquitously expressed, urea cycle and CPS1 are only present in the liver and, to a minor extent, in the kidney. To address the possibility that SIRT5 is involved in ammonia production also in nonliver cells, clones of human breast cancer cell lines MDA-MB-231 and mouse myoblast C2C12, overexpressing or silenced for SIRT5 were produced. Our results show that ammonia production increased in SIRT5-silenced and decreased in SIRT5-overexpressing cells. We also obtained the same ammonia increase when using a new specific inhibitor of SIRT5 called MC3482. SIRT5 regulates ammonia production by controlling glutamine metabolism. In fact, in the mitochondria, glutamine is transformed in glutamate by the enzyme glutaminase, a reaction producing ammonia. We found that SIRT5 and glutaminase coimmunoprecipitated and that SIRT5 inhibition resulted in an increased succinylation of glutaminase. We next determined that autophagy and mitophagy were increased by ammonia by measuring autophagic proteolysis of long-lived proteins, increase of autophagy markers MAP1LC3B, GABARAP, and GABARAPL2, mitophagy markers BNIP3 and the PINK1-PARK2 system as well as mitochondrial morphology and dynamics. We observed that autophagy and mitophagy increased in SIRT5-silenced cells and in WT cells treated with MC3482 and decreased in SIRT5-overexpressing cells. Moreover, glutaminase inhibition or glutamine withdrawal completely prevented autophagy. In conclusion we propose that the role of SIRT5 in nonliver cells is to regulate ammonia production and ammonia-induced autophagy by regulating glutamine metabolism. PMID:25700560

  18. 33 CFR 110.156 - Randall Bay, Freeport, Long Island, N.Y.

    Science.gov (United States)

    2010-07-01

    ... Island, N.Y. 110.156 Section 110.156 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.156 Randall Bay, Freeport, Long Island, N.Y. (a) The anchorage grounds. Southward of a line 312 feet south of and parallel to the south side...

  19. Carbonic anhydrase 5 regulates acid-base homeostasis in zebrafish.

    Directory of Open Access Journals (Sweden)

    Ruben Postel

    Full Text Available The regulation of the acid-base balance in cells is essential for proper cellular homeostasis. Disturbed acid-base balance directly affects cellular physiology, which often results in various pathological conditions. In every living organism, the protein family of carbonic anhydrases regulate a broad variety of homeostatic processes. Here we describe the identification, mapping and cloning of a zebrafish carbonic anhydrase 5 (ca5 mutation, collapse of fins (cof, which causes initially a collapse of the medial fins followed by necrosis and rapid degeneration of the embryo. These phenotypical characteristics can be mimicked in wild-type embryos by acetazolamide treatment, suggesting that CA5 activity in zebrafish is essential for a proper development. In addition we show that CA5 regulates acid-base balance during embryonic development, since lowering the pH can compensate for the loss of CA5 activity. Identification of selective modulators of CA5 activity could have a major impact on the development of new therapeutics involved in the treatment of a variety of disorders.

  20. Automation of the Design of the Anchorage System Taking into Account the Geomechanical State of the Massif and Mining Development Schemes

    Directory of Open Access Journals (Sweden)

    Demin Vladimir

    2018-01-01

    Full Text Available The article presents the system for the automation of the design of the anchorage, which regulates the calculation of the required parameters of the fasteners for the fastening of the fastening system. The main factors affecting the operation of the anchor support are grouped in the following way: mining and geological conditions, technical characteristics of the anchor support, geomechanical conditions for conducting and operating the mine workings. Mining and geological conditions for carrying out excavations include: physical and mechanical properties of rocks, the category of roof stability, fracturing, etc. Technical characteristics of the anchor support: material of the rod, filler, filling completeness, etc. Conditions (geomechanical of carrying out and exploitation of the mine workings: the depth of the conduct, the location relative to the zone of influence of the cleaning works, the location relative to the waste zone, etc. As a result of calculations the program gives out the basic parameters of the anchor support, which coincide with the parameters adopted by the passport.

  1. Identification of a novel interspecific hybrid yeast from a metagenomic spontaneously inoculated beer sample using Hi-C.

    Science.gov (United States)

    Smukowski Heil, Caiti; Burton, Joshua N; Liachko, Ivan; Friedrich, Anne; Hanson, Noah A; Morris, Cody L; Schacherer, Joseph; Shendure, Jay; Thomas, James H; Dunham, Maitreya J

    2018-01-01

    Interspecific hybridization is a common mechanism enabling genetic diversification and adaptation; however, the detection of hybrid species has been quite difficult. The identification of microbial hybrids is made even more complicated, as most environmental microbes are resistant to culturing and must be studied in their native mixed communities. We have previously adapted the chromosome conformation capture method Hi-C to the assembly of genomes from mixed populations. Here, we show the method's application in assembling genomes directly from an uncultured, mixed population from a spontaneously inoculated beer sample. Our assembly method has enabled us to de-convolute four bacterial and four yeast genomes from this sample, including a putative yeast hybrid. Downstream isolation and analysis of this hybrid confirmed its genome to consist of Pichia membranifaciens and that of another related, but undescribed, yeast. Our work shows that Hi-C-based metagenomic methods can overcome the limitation of traditional sequencing methods in studying complex mixtures of genomes. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  2. Bio-cultural anchorage of the prickly pear cactus in Tlalnepantla (Morelos, Mexico

    Directory of Open Access Journals (Sweden)

    Torres-Salcido, Gerardo

    2016-06-01

    Full Text Available The prickly pear cactus is a source of food with strong bio-cultural anchorage in Mexico. This is due to at least three factors: 1 the nature and heritage of cacti; 2 cultural heritage; and 3 the socio-cultural relationships with historical and symbolic roots that have facilitated knowledge of how to cultivate it and how to use it. The aim of this article is to put factors of territorial anchorage and its historical transformation in context by examining the case of the municipality of Tlalnepantla in the state of Morelos, Mexico. This community has experienced accelerated change due to the exchange of traditional crops for the prickly pear cactus and the integration of farming, commercialization and agro-transformation. Our hypothesis is that the market, internal conflicts and a lack of socio-institutional coordination have put social organization into crisis, favoring the territorial spread of the prickly pear cactus and making the Local Agro-Food Systems (LAFS of Tlalnepantla less competitive. The conclusions highlight important economic and social advances whose roots lie in the strengthening and anchorage of the territory-product. However, circumstances both internal and external to the community persist, such as intra-community conflicts, the international market and cultural paradigm shifts that affect the producers and put consolidation of the LAFS at risk.El nopal es un alimento con un fuerte anclaje bio-cultural en México, propiciado por al menos tres factores: 1 la naturaleza y el patrimonio de cactáceas; 2 el patrimonio cultural; y, 3 las relaciones socio-culturales que han permitido un “saber hacer” y un “saber utilizar” con raíces históricas y simbólicas. El objetivo es situar los factores de anclaje territorial y su transformación histórica tomando como caso el municipio de Tlalnepantla, en el estado de Morelos, México. Esta comunidad ha experimentado un acelerado cambio por la reconversión de los cultivos

  3. Subcellular distribution of cyclin-dependent kinase-like 5 (CDKL5) is regulated through phosphorylation by dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A)

    International Nuclear Information System (INIS)

    Oi, Ami; Katayama, Syouichi; Hatano, Naoya; Sugiyama, Yasunori; Kameshita, Isamu; Sueyoshi, Noriyuki

    2017-01-01

    Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase primarily expressed in the central nervous system and is known to cause X-linked neurodevelopmental disorders such as Rett syndrome. However, the mechanisms regulating CDKL5 have not yet been fully clarified. Therefore, in this study, we investigated the protein kinase that directly phosphorylates CDKL5, identifying it as dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), an enzyme binding to and phosphorylating CDKL5. We showed that subcellular distribution of CDKL5 was regulated by its phosphorylation by DYRK1A. In mouse neuroblastoma Neuro2a cells, CDKL5 was localized in both the cytosol and nucleus, whereas DYRK1A showed a typical nuclear localization. When CDKL5 and DYRK1A were co-expressed, the cytosolic localization of CDKL5 was significantly increased. Results of site-directed mutagenesis revealed that the phosphorylation site was Ser-308, in the vicinity of the nuclear localization signal. A mutation mimicking the phosphorylated serine residue by aspartate substitution (S308D) changed CDKL5 localization to the cytosol, whereas the corresponding alanine-substituted analog, CDKL5(S308A), was primarily localized to the nucleus. Taken together, these results strongly suggested that DYRK1A bound to CDKL5 and phosphorylated it on Ser-308, thus interfering with its nuclear localization. - Highlights: • We investigated the mechanism regulating subcellular localization of CDKL5. • DYRK1A was identified as an enzyme that bound to and phosphorylated CDKL5. • The phosphorylation site of CDKL5 was Ser-308, in the vicinity of the NLS. • When DYRK1A was co-expressed, the cytosolic CDKL5 was significantly increased. • In conclusion, DYRK1A regulates CDKL5 localization via phosphorylation on Ser-308.

  4. Prestressed CFRP Strips with Gradient Anchorage for Structural Concrete Retrofitting: Experiments and Numerical Modeling

    Directory of Open Access Journals (Sweden)

    Julien Michels

    2014-01-01

    Full Text Available This paper presents a study on the load carrying capacity of reinforced concrete (RC beams strengthened with externally bonded (EB carbon fiber reinforced polymer (CFRP strips prestressed up to 0.6% in strain. At the strip ends, the innovative gradient anchorage is used instead of conventional mechanical fasteners. This method, based on the epoxy resin’s ability to rapidly cure under high temperatures, foresees a sector-wise heating followed by a gradual decrease of the initial prestress force towards the strip ends. The experimental investigation shows a promising structural behavior, resulting in high strip tensile strains, eventually almost reaching tensile failure of the composite strip. Additionally, ductility when considering deflection at steel yielding and at ultimate load is satisfying, too. From a practical point of view, it is demonstrated that premature strip grinding in the anchorage zone is not beneficial. In addition, a non-commercial 1D finite element code has been enlarged to an EB reinforcement with prestressed composite strips. A bilinear bond stress-slip relation obtained in earlier investigations is introduced as an additional failure criterion to the code. The numerical code is able to almost perfectly predict the overall structural behavior. Furthermore, the calculations are used for comparison purposes between an initially unstressed and a prestressed externally bonded composite reinforcement. The increase in cracking and yielding load, as well as differences in structural stiffness are apparent.

  5. 33 CFR 110.233 - Prince William Sound, Alaska.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Prince William Sound, Alaska. 110... ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.233 Prince William Sound, Alaska. (a) The anchorage grounds. In Prince William Sound, Alaska, beginning at a point at latitude 60°40′00″ N., longitude 146°40...

  6. Verification of the local structural response of building structures in the anchorage areas of heavy components

    International Nuclear Information System (INIS)

    Krutzik, N.J.; Tropp, R.

    1993-01-01

    In both nuclear and non-nuclear areas of power plants, sections of structures, parts of systems and components are attached to walls and floors by means of anchor plates with bolts, anchor sleeves and bolts and through bolts arranged either in groups or individually. In order to simplify the determination of the transfered vibrations induced by external events (e.g. earthquake, aircraft crash), it is normally assumed that the nodal point between component and concrete possesses rigid body characteristics and the building structure (walls, floors) is also inflexible in the anchorage area. In the course of the parametric studies performed, the nonlinear effects on the anchorage area of a component (in this case an anchor plate and concrete slab) were calculated and the effect of these on the actual vibration behavior and the local structural responses of the building structure at the place of installation of heavy components were investigated. The investigations performed reveal that by taking into account the local behaviour in the anchoring point, it is possible to reduce the dynamic response considerably. More detailed examination of the influence of additional parameters (especially of the geometry of the anchor plates and anchor bolts and their material characteristics) will require further investigations aimed at establishing the characteristics of typical anchor plates. (orig.)

  7. Phospho-Caveolin-1 Mediates Integrin-Regulated Membrane Domain Internalisation

    Science.gov (United States)

    del Pozo, Miguel A.; Alderson, Nazilla B.; Grande-García, Araceli; Balasubramanian, Nagaraj; Schwartz, Martin A.; Kiosses, William B.; Anderson, Richard G.W.

    2005-01-01

    Growth of normal cells is anchorage-dependent because signalling through multiple pathways including Erk, PI 3-kinase and Rac requires integrin-mediated cell adhesion 1. Components of these pathways localize to low density, cholesterol-rich domains in the plasma membrane named “lipid rafts” 2,3 or “cholesterol enriched membrane microdomains” (CEMM) 4. We previously reported that integrin-mediated adhesion regulates CEMM trafficking such that cell detachment from the extracellular matrix (ECM) triggers CEMM internalisation and clearance from the plasma membrane 5. We now report that this internalisation is mediated by dynamin-2 and caveolin-1. Internalisation requires phosphorylation of caveolin-1 on tyrosine 14. A shift in localisation of phospho-caveolin-1 from focal adhesions to caveolae induces CEMM internalisation upon cell detachment, which mediates inhibition of Erk, PI 3-kinase and Rac. These data define a novel molecular mechanism for growth and tumour suppression by caveolin-1. PMID:16113676

  8. Infrastructure for genomic interactions: Bioconductor classes for Hi-C, ChIA-PET and related experiments [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Aaron T. L. Lun

    2016-05-01

    Full Text Available The study of genomic interactions has been greatly facilitated by techniques such as chromatin conformation capture with high-throughput sequencing (Hi-C. These genome-wide experiments generate large amounts of data that require careful analysis to obtain useful biological conclusions. However, development of the appropriate software tools is hindered by the lack of basic infrastructure to represent and manipulate genomic interaction data. Here, we present the InteractionSet package that provides classes to represent genomic interactions and store their associated experimental data, along with the methods required for low-level manipulation and processing of those classes. The InteractionSet package exploits existing infrastructure in the open-source Bioconductor project, while in turn being used by Bioconductor packages designed for higher-level analyses. For new packages, use of the functionality in InteractionSet will simplify development, allow access to more features and improve interoperability between packages.

  9. Infrastructure for genomic interactions: Bioconductor classes for Hi-C, ChIA-PET and related experiments [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Aaron T. L. Lun

    2016-06-01

    Full Text Available The study of genomic interactions has been greatly facilitated by techniques such as chromatin conformation capture with high-throughput sequencing (Hi-C. These genome-wide experiments generate large amounts of data that require careful analysis to obtain useful biological conclusions. However, development of the appropriate software tools is hindered by the lack of basic infrastructure to represent and manipulate genomic interaction data. Here, we present the InteractionSet package that provides classes to represent genomic interactions and store their associated experimental data, along with the methods required for low-level manipulation and processing of those classes. The InteractionSet package exploits existing infrastructure in the open-source Bioconductor project, while in turn being used by Bioconductor packages designed for higher-level analyses. For new packages, use of the functionality in InteractionSet will simplify development, allow access to more features and improve interoperability between packages.

  10. Reconstructing spatial organizations of chromosomes through manifold learning.

    Science.gov (United States)

    Zhu, Guangxiang; Deng, Wenxuan; Hu, Hailin; Ma, Rui; Zhang, Sai; Yang, Jinglin; Peng, Jian; Kaplan, Tommy; Zeng, Jianyang

    2018-02-02

    Decoding the spatial organizations of chromosomes has crucial implications for studying eukaryotic gene regulation. Recently, chromosomal conformation capture based technologies, such as Hi-C, have been widely used to uncover the interaction frequencies of genomic loci in a high-throughput and genome-wide manner and provide new insights into the folding of three-dimensional (3D) genome structure. In this paper, we develop a novel manifold learning based framework, called GEM (Genomic organization reconstructor based on conformational Energy and Manifold learning), to reconstruct the three-dimensional organizations of chromosomes by integrating Hi-C data with biophysical feasibility. Unlike previous methods, which explicitly assume specific relationships between Hi-C interaction frequencies and spatial distances, our model directly embeds the neighboring affinities from Hi-C space into 3D Euclidean space. Extensive validations demonstrated that GEM not only greatly outperformed other state-of-art modeling methods but also provided a physically and physiologically valid 3D representations of the organizations of chromosomes. Furthermore, we for the first time apply the modeled chromatin structures to recover long-range genomic interactions missing from original Hi-C data. © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Design of steel-liners and their anchorage with regard to non-linear behaviour of liner-material and anchorage

    International Nuclear Information System (INIS)

    Oberpichler, R.

    1979-01-01

    The thin steel liner attached by studs or rib-type anchors to the interior wall of a Prestressed Concrete Reactor Pressure Vessel (PCRV) or a Concrete Containment Vessel (PCCV) has to provide the leak-tightness of the vessel. The liner also may serve as internal shuttering for placing concrete as well as a support for the cooling system or thermal isolation. Mainly strained by self-limited loads imposed on the liner by deformations of the vessel-wall or by heatup inside the vessel the liner predominantly will function in a compressive biaxially strained state like a membrane. The vessel-wall is assumed to be a rigid boundary without reactions caused by the liner-anchor-restraints. Furthermore it is assumed that the liner supported in a close-spaced pattern to the concrete with respect to self-limited loads and all effects of non-linear behaviour of liner-material and non-linear anchor-characteristics will not fail by instability, especially not by an effect of snapthrough. Only one essential mode of failure, the shear connector failure is assumed to be basis for all liner investigations. Design of the liner and its anchorage therefore is based on the analysis of large deformations with regard to elastic-plastic behaviour of liner-material and non-linear anchor characteristics. By this method both economical and safe sizing and spacing of the anchors can be calculated. (orig.)

  12. Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity

    Directory of Open Access Journals (Sweden)

    Coccia Raffaella

    2009-01-01

    Full Text Available Abstract Background Melanin synthesis, the elective trait of melanocytes, is regulated by tyrosinase activity. In tyrosinase-positive amelanotic melanomas this rate limiting enzyme is inactive because of acidic endo-melanosomal pH. The E5 oncogene of the Human Papillomavirus Type 16 is a small transmembrane protein with a weak transforming activity and a role during the early steps of viral infections. E5 has been shown to interact with 16 kDa subunit C of the trans-membrane Vacuolar ATPase proton pump ultimately resulting in its functional suppressions. However, the cellular effects of such an interaction are still under debate. With this work we intended to explore whether the HPV16 E5 oncoprotein does indeed interact with the vacuolar ATPase proton pump once expressed in intact human cells and whether this interaction has functional consequences on cell metabolism and phenotype. Methods The expression of the HPV16-E5 oncoproteins was induced in two Tyrosinase-positive amelanotic melanomas (the cell lines FRM and M14 by a retroviral expression construct. Modulation of the intracellular pH was measured with Acridine orange and fluorescence microscopy. Expression of tyrosinase and its activity was followed by RT-PCR, Western Blot and enzyme assay. The anchorage-independence growth and the metabolic activity of E5 expressing cells were also monitored. Results We provide evidence that in the E5 expressing cells interaction between E5 and V-ATPase determines an increase of endo-cellular pH. The cellular alkalinisation in turn leads to the post-translational activation of tyrosinase, melanin synthesis and phenotype modulation. These effects are associated with an increased activation of tyrosine analogue anti-blastic drugs. Conclusion Once expressed within intact human cells the HPV16-E5 oncoprotein does actually interact with the vacuolar V-ATPase proton pump and this interaction induces a number of functional effects. In amelanotic melanomas these

  13. The Nesprin family member ANC-1 regulates synapse formation and axon termination by functioning in a pathway with RPM-1 and β-Catenin.

    Science.gov (United States)

    Tulgren, Erik D; Turgeon, Shane M; Opperman, Karla J; Grill, Brock

    2014-07-01

    Mutations in Nesprin-1 and 2 (also called Syne-1 and 2) are associated with numerous diseases including autism, cerebellar ataxia, cancer, and Emery-Dreifuss muscular dystrophy. Nesprin-1 and 2 have conserved orthologs in flies and worms called MSP-300 and abnormal nuclear Anchorage 1 (ANC-1), respectively. The Nesprin protein family mediates nuclear and organelle anchorage and positioning. In the nervous system, the only known function of Nesprin-1 and 2 is in regulation of neurogenesis and neural migration. It remains unclear if Nesprin-1 and 2 regulate other functions in neurons. Using a proteomic approach in C. elegans, we have found that ANC-1 binds to the Regulator of Presynaptic Morphology 1 (RPM-1). RPM-1 is part of a conserved family of signaling molecules called Pam/Highwire/RPM-1 (PHR) proteins that are important regulators of neuronal development. We have found that ANC-1, like RPM-1, regulates axon termination and synapse formation. Our genetic analysis indicates that ANC-1 functions via the β-catenin BAR-1, and the ANC-1/BAR-1 pathway functions cell autonomously, downstream of RPM-1 to regulate neuronal development. Further, ANC-1 binding to the nucleus is required for its function in axon termination and synapse formation. We identify variable roles for four different Wnts (LIN-44, EGL-20, CWN-1 and CWN-2) that function through BAR-1 to regulate axon termination. Our study highlights an emerging, broad role for ANC-1 in neuronal development, and unveils a new and unexpected mechanism by which RPM-1 functions.

  14. Pedicle screw anchorage of carbon fiber-reinforced PEEK screws under cyclic loading.

    Science.gov (United States)

    Lindtner, Richard A; Schmid, Rene; Nydegger, Thomas; Konschake, Marko; Schmoelz, Werner

    2018-03-01

    Pedicle screw loosening is a common and significant complication after posterior spinal instrumentation, particularly in osteoporosis. Radiolucent carbon fiber-reinforced polyetheretherketone (CF/PEEK) pedicle screws have been developed recently to overcome drawbacks of conventional metallic screws, such as metal-induced imaging artifacts and interference with postoperative radiotherapy. Beyond radiolucency, CF/PEEK may also be advantageous over standard titanium in terms of pedicle screw loosening due to its unique material properties. However, screw anchorage and loosening of CF/PEEK pedicle screws have not been evaluated yet. The aim of this biomechanical study therefore was to evaluate whether the use of this alternative nonmetallic pedicle screw material affects screw loosening. The hypotheses tested were that (1) nonmetallic CF/PEEK pedicle screws resist an equal or higher number of load cycles until loosening than standard titanium screws and that (2) PMMA cement augmentation further increases the number of load cycles until loosening of CF/PEEK screws. In the first part of the study, left and right pedicles of ten cadaveric lumbar vertebrae (BMD 70.8 mg/cm 3  ± 14.5) were randomly instrumented with either CF/PEEK or standard titanium pedicle screws. In the second part, left and right pedicles of ten vertebrae (BMD 56.3 mg/cm 3  ± 15.8) were randomly instrumented with either PMMA-augmented or nonaugmented CF/PEEK pedicle screws. Each pedicle screw was subjected to cyclic cranio-caudal loading (initial load ranging from - 50 N to + 50 N) with stepwise increasing compressive loads (5 N every 100 cycles) until loosening or a maximum of 10,000 cycles. Angular screw motion ("screw toggling") within the vertebra was measured with a 3D motion analysis system every 100 cycles and by stress fluoroscopy every 500 cycles. The nonmetallic CF/PEEK pedicle screws resisted a similar number of load cycles until loosening as the contralateral standard

  15. Morphologic and hemodynamic analysis of dental pulp in dogs after molar intrusion with the skeletal anchorage system.

    Science.gov (United States)

    Konno, Yuichi; Daimaruya, Takayoshi; Iikubo, Masahiro; Kanzaki, Reiko; Takahashi, Ichiro; Sugawara, Junji; Sasano, Takashi

    2007-08-01

    We have successfully treated skeletal open bite by intruding posterior teeth with the skeletal anchorage system. Our aim in this study was to morphologically and hemodynamically evaluate the changes in pulp tissues when molars are radically intruded. The mandibular fourth premolars of 9 adult beagle dogs were divided into 3 groups: a sham operated group (n = 6, 3 dogs), 4-month intrusion group (n = 6, 3 dogs), and a further 4-month retention group (n = 6, 3 dogs). We evaluated the morphological changes of the pulp and dentin-the amount of vacuolar degeneration in the odontoblast layer, the predentin width and nervous continuity in the pulp tissue, and the pulpal blood-flow response evoked by electrical stimulation in the dental pulp. Extreme molar intrusion with the skeletal anchorage system caused slight degenerative changes in the pulp tissue, followed by recovery after the orthodontic force was released. Circulatory system and nervous functions were basically maintained during the intrusion, although a certain level of downregulation was observed. These morphologic and functional regressive changes in the pulp tissue after molar intrusion improved during the retention period. Histologic changes and changes in pulpal blood flow and function are reversible, even during radical intrusion of molars.

  16. Crystallographic texture control helps improve pipeline steel resistance to hydrogen-induced cracking

    Energy Technology Data Exchange (ETDEWEB)

    Caleyo, F; Hallen, J M; Herrera, O; Venegas, V [ESIQIE, Instituto Politecnico Nacional, Mexico, (Mexico); Baudin, T [Universite de Paris Sud, Orsay, (France)

    2010-07-01

    The resistance to HIC of sour service pipeline steels has been improved through several strategies but none have proven to be totally efficient in the preservation of HIC in difficult operating conditions. The crystallographic texture plays a significant role in determining the behavior of HIC in pipeline steels. The present study tried to prove that crystallographic texture control, through warm rolling schedules, helps improve pipeline steel resistance to HIC. Several samples of an API 5L X52 grade pipeline steel were produced using different thermomechanical processes (austenization, controlled rolling and recrystallization). These samples were subjected to cathodic charging. Scanning electron microscopy and automated FEG/EBSD were used to perform metallographic inspections and to collect microstructure data. The results showed that the strong y fiber texture significantly reduces or even prevents the HIC damage. It is possible to improve the HIC resistance of pipeline steels using crystallography texture control and grain boundary engineering.

  17. Hydrogen-induced crack interaction and coalescence: the role of local crystallographic texture

    Energy Technology Data Exchange (ETDEWEB)

    Caleyo, F.; Hallen, J. M.; Venegas, V. [ESIQIE, Instituto Politecnico Nacional, Mexico, (Mexico); Baudin, T. [Universite de Paris Sud, Orsay, (France)

    2010-07-01

    Hydrogen induced cracking (HIC) is a big concern in pipeline industry specialized in sour service. The strategies to improve HIC resistance of pipeline steel have not been completely efficient. This study investigated the role of grain orientation in the interaction and coalescence of non-coplanar HIC cracks through experimental analysis. HIC samples of pipeline steels (API 5L X46 and ASME-A106) were studied using automated electron backscatter diffraction (EBSD) and orientation imaging microscopy (OIM). The results showed that the microtexture can play a significant role in the coalescence of closely spaced non-coplanar HIC cracks. It was also found that the presence of cleavage planes and slip systems correctly oriented to the mixed-mode stresses can activate low-resistance transgranular paths along in which cracks can merge. It is demonstrated that crystallographic texture must be considered in developing predictive models for the study of the stepwise propagation of HIC cracking in pipeline steels.

  18. Tartrate-resistant acid phosphatase (TRAP/ACP5) promotes metastasis-related properties via TGFβ2/TβR and CD44 in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Reithmeier, Anja; Panizza, Elena; Krumpel, Michael; Orre, Lukas M; Branca, Rui M M; Lehtiö, Janne; Ek-Rylander, Barbro; Andersson, Göran

    2017-09-15

    Tartrate-resistant acid phosphatase (TRAP/ACP5), a metalloenzyme that is characteristic for its expression in activated osteoclasts and in macrophages, has recently gained considerable focus as a driver of metastasis and was associated with clinically relevant parameters of cancer progression and cancer aggressiveness. MDA-MB-231 breast cancer cells with different TRAP expression levels (overexpression and knockdown) were generated and characterized for protein expression and activity levels. Functional cell experiments, such as proliferation, migration and invasion assays were performed as well as global phosphoproteomic and proteomic analysis was conducted to connect molecular perturbations to the phenotypic changes. We identified an association between metastasis-related properties of TRAP-overexpressing MDA-MB-231 breast cancer cells and a TRAP-dependent regulation of Transforming growth factor (TGFβ) pathway proteins and Cluster of differentiation 44 (CD44). Overexpression of TRAP increased anchorage-independent and anchorage-dependent cell growth and proliferation, induced a more elongated cellular morphology and promoted cell migration and invasion. Migration was increased in the presence of the extracellular matrix (ECM) proteins osteopontin and fibronectin and the basement membrane proteins collagen IV and laminin I. TRAP-induced properties were reverted upon shRNA-mediated knockdown of TRAP or treatment with the small molecule TRAP inhibitor 5-PNA. Global phosphoproteomics and proteomics analyses identified possible substrates of TRAP phosphatase activity or signaling intermediates and outlined a TRAP-dependent regulation of proteins involved in cell adhesion and ECM organization. Upregulation of TGFβ isoform 2 (TGFβ2), TGFβ receptor type 1 (TβR1) and Mothers against decapentaplegic homolog 2 (SMAD2), as well as increased intracellular phosphorylation of CD44 were identified upon TRAP perturbation. Functional antibody-mediated blocking and chemical

  19. 5 CFR 470.313 - Project implementation regulations.

    Science.gov (United States)

    2010-01-01

    ... project must be approved by OPM and shall have full force and authority pursuant to Title VI of the Civil... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Project implementation regulations. 470... PERSONNEL MANAGEMENT RESEARCH PROGRAMS AND DEMONSTRATIONS PROJECTS Regulatory Requirements Pertaining to...

  20. Regulator of G protein signaling 5 (RGS5) inhibits sonic hedgehog function in mouse cortical neurons.

    Science.gov (United States)

    Liu, Chuanliang; Hu, Qiongqiong; Jing, Jia; Zhang, Yun; Jin, Jing; Zhang, Liulei; Mu, Lili; Liu, Yumei; Sun, Bo; Zhang, Tongshuai; Kong, Qingfei; Wang, Guangyou; Wang, Dandan; Zhang, Yao; Liu, Xijun; Zhao, Wei; Wang, Jinghua; Feng, Tao; Li, Hulun

    2017-09-01

    Regulator of G protein signaling 5 (RGS5) acts as a GTPase-activating protein (GAP) for the Gαi subunit and negatively regulates G protein-coupled receptor signaling. However, its presence and function in postmitotic differentiated primary neurons remains largely uncharacterized. During neural development, sonic hedgehog (Shh) signaling is involved in cell signaling pathways via Gαi activity. In particular, Shh signaling is essential for embryonic neural tube patterning, which has been implicated in neuronal polarization involving neurite outgrowth. Here, we examined whether RGS5 regulates Shh signaling in neurons. RGS5 transcripts were found to be expressed in cortical neurons and their expression gradually declined in a time-dependent manner in culture system. When an adenovirus expressing RGS5 was introduced into an in vitro cell culture model of cortical neurons, RGS5 overexpression significantly reduced neurite outgrowth and FM4-64 uptake, while cAMP-PKA signaling was also affected. These findings suggest that RGS5 inhibits Shh function during neurite outgrowth and the presynaptic terminals of primary cortical neurons mature via modulation of cAMP. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Maxine; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Rommens, Corinne; Martin, Genevieve; Duran-Sandoval, Daniel; Staels, Bart; Rubin, Edward M.; Pennacchio, Len A.; Taskinen, Marja-Riitta; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-02-15

    The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment with insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.

  2. 33 CFR 110.25 - Salem Sound, Mass.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Salem Sound, Mass. 110.25 Section 110.25 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.25 Salem Sound, Mass. (a) Beverly Harbor, north of Salem...

  3. 33 CFR 110.170 - Lockwoods Folly Inlet, N.C.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lockwoods Folly Inlet, N.C. 110.170 Section 110.170 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.170 Lockwoods Folly Inlet, N.C. (a) Explosives...

  4. 33 CFR 110.250 - St. Thomas Harbor, Charlotte Amalie, V.I.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false St. Thomas Harbor, Charlotte... SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.250 St. Thomas Harbor, Charlotte Amalie.... Thomas, V.I. of the United States and approaches thereto, including all waters under its jurisdiction, as...

  5. 5 CFR 5.1 - Civil Service regulations.

    Science.gov (United States)

    2010-01-01

    ... if such a variation is within the spirit of the regulations, and the efficiency of the Government and... hardship involved, (b) what is permitted in place of what is required by regulations, (c) the circumstances...

  6. 33 CFR 110.27 - Lynn Harbor in Broad Sound, Mass.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lynn Harbor in Broad Sound, Mass. 110.27 Section 110.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.27 Lynn Harbor in Broad Sound, Mass. North of...

  7. 33 CFR 110.31 - Hull Bay and Allerton Harbor at Hull, Mass.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Hull Bay and Allerton Harbor at Hull, Mass. 110.31 Section 110.31 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.31 Hull Bay and Allerton Harbor at...

  8. 33 CFR 110.128b - Island of Hawaii, Hawaii.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Island of Hawaii, Hawaii. 110.128b Section 110.128b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.128b Island of Hawaii, Hawaii. (a) Hilo Bay...

  9. 33 CFR 110.179 - Skidaway River, Isle of Hope, Ga.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Skidaway River, Isle of Hope, Ga. 110.179 Section 110.179 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.179 Skidaway River, Isle of Hope, Ga. (a) The...

  10. Multiple upstream modules regulate zebrafish myf5 expression

    Directory of Open Access Journals (Sweden)

    Weng Chih-Wei

    2007-01-01

    Full Text Available Abstract Background Myf5 is one member of the basic helix-loop-helix family of transcription factors, and it functions as a myogenic factor that is important for the specification and differentiation of muscle cells. The expression of myf5 is somite- and stage-dependent during embryogenesis through a delicate regulation. However, this complex regulatory mechanism of myf5 is not clearly understood. Results We isolated a 156-kb bacterial artificial chromosome clone that includes an upstream 80-kb region and a downstream 70-kb region of zebrafish myf5 and generated a transgenic line carrying this 156-kb segment fused to a green fluorescent protein (GFP reporter gene. We find strong GFP expression in the most rostral somite and in the presomitic mesoderm during segmentation stages, similar to endogenous myf5 expression. Later, the GFP signals persist in caudal somites near the tail bud but are down-regulated in the older, rostral somites. During the pharyngula period, we detect GFP signals in pectoral fin buds, dorsal rostral myotomes, hypaxial myotomes, and inferior oblique and superior oblique muscles, a pattern that also corresponds well with endogenous myf5 transcripts. To characterize the specific upstream cis-elements that regulate this complex and dynamic expression pattern, we also generated several transgenic lines that harbor various lengths within the upstream 80-kb segment. We find that (1 the -80 kb/-9977 segment contains a fin and cranial muscle element and a notochord repressor; (2 the -9977/-6213 segment contains a strong repressive element that does not include the notochord-specific repressor; (3 the -6212/-2938 segment contains tissue-specific elements for bone and spinal cord; (4 the -2937/-291 segment contains an eye enhancer, and the -2937/-2457 segment is required for notochord and myocyte expression; and (5 the -290/-1 segment is responsible for basal transcription in somites and the presomitic mesoderm. Conclusion We suggest

  11. Bst1 is required for Candida albicans infecting host via facilitating cell wall anchorage of Glycosylphosphatidyl inositol anchored proteins

    Science.gov (United States)

    Liu, Wei; Zou, Zui; Huang, Xin; Shen, Hui; He, Li Juan; Chen, Si Min; Li, Li Ping; Yan, Lan; Zhang, Shi Qun; Zhang, Jun Dong; Xu, Zheng; Xu, Guo Tong; An, Mao Mao; Jiang, Yuan Ying

    2016-01-01

    Glycosylphosphatidyl inositol anchored proteins (GPI-APs) on fungal cell wall are essential for invasive infections. While the function of inositol deacylation of GPI-APs in mammalian cells has been previously characterized the impact of inositol deacylation in fungi and implications to host infection remains largely unexplored. Herein we describe our identification of BST1, an inositol deacylase of GPI-Aps in Candida albicans, was critical for GPI-APs cell wall attachment and host infection. BST1-deficient C. albicans (bst1Δ/Δ) was associated with severely impaired cell wall anchorage of GPI-APs and subsequen unmasked β-(1,3)-glucan. Consistent with the aberrant cell wall structures, bst1Δ/Δ strain did not display an invasive ability and could be recognized more efficiently by host immune systems. Moreover, BST1 null mutants or those expressing Bst1 variants did not display inositol deacylation activity and exhibited severely attenuated virulence and reduced organic colonization in a murine systemic candidiasis model. Thus, Bst1 can facilitate cell wall anchorage of GPI-APs in C. albicans by inositol deacylation, and is critical for host invasion and immune escape. PMID:27708385

  12. Nuclear receptor 5A (NR5A) family regulates 5-aminolevulinic acid synthase 1 (ALAS1) gene expression in steroidogenic cells.

    Science.gov (United States)

    Ju, Yunfeng; Mizutani, Tetsuya; Imamichi, Yoshitaka; Yazawa, Takashi; Matsumura, Takehiro; Kawabe, Shinya; Kanno, Masafumi; Umezawa, Akihiro; Kangawa, Kenji; Miyamoto, Kaoru

    2012-11-01

    5-Aminolevulinic acid synthase 1 (ALAS1) is a rate-limiting enzyme for heme biosynthesis in mammals. Heme is essential for the catalytic activities of P450 enzymes including steroid metabolic enzymes. Nuclear receptor 5A (NR5A) family proteins, steroidogenic factor-1 (SF-1), and liver receptor homolog-1 (LRH-1) play pivotal roles in regulation of steroidogenic enzymes. Recently, we showed that expression of SF-1/LRH-1 induces differentiation of mesenchymal stem cells into steroidogenic cells. In this study, genome-wide analysis revealed that ALAS1 was a novel SF-1-target gene in differentiated mesenchymal stem cells. Chromatin immunoprecipitation and reporter assays revealed that SF-1/LRH-1 up-regulated ALAS1 gene transcription in steroidogenic cells via binding to a 3.5-kb upstream region of ALAS1. The ALAS1 gene was up-regulated by overexpression of SF-1/LRH-1 in steroidogenic cells and down-regulated by knockdown of SF-1 in these cells. Peroxisome proliferator-activated receptor-γ coactivator-1α, a coactivator of nuclear receptors, also strongly coactivated expression of NR5A-target genes. Reporter analysis revealed that peroxisome proliferator-activated receptor-γ coactivator-1α strongly augmented ALAS1 gene transcription caused by SF-1 binding to the 3.5-kb upstream region. Finally knockdown of ALAS1 resulted in reduced progesterone production by steroidogenic cells. These results indicate that ALAS1 is a novel NR5A-target gene and participates in steroid hormone production.

  13. Health insurance coverage with or without a nurse-led task shifting strategy for hypertension control: A pragmatic cluster randomized trial in Ghana.

    Directory of Open Access Journals (Sweden)

    Gbenga Ogedegbe

    2018-05-01

    Full Text Available Poor access to care and physician shortage are major barriers to hypertension control in sub-Saharan Africa. Implementation of evidence-based systems-level strategies targeted at these barriers are lacking. We conducted a study to evaluate the comparative effectiveness of provision of health insurance coverage (HIC alone versus a nurse-led task shifting strategy for hypertension control (TASSH plus HIC on systolic blood pressure (SBP reduction among patients with uncontrolled hypertension in Ghana.Using a pragmatic cluster randomized trial, 32 community health centers within Ghana's public healthcare system were randomly assigned to either HIC alone or TASSH + HIC. A total of 757 patients with uncontrolled hypertension were recruited between November 28, 2012, and June 11, 2014, and followed up to October 7, 2016. Both intervention groups received health insurance coverage plus scheduled nurse visits, while TASSH + HIC comprised cardiovascular risk assessment, lifestyle counseling, and initiation/titration of antihypertensive medications for 12 months, delivered by trained nurses within the healthcare system. The primary outcome was change in SBP from baseline to 12 months. Secondary outcomes included lifestyle behaviors and blood pressure control at 12 months and sustainability of SBP reduction at 24 months. Of the 757 patients (389 in the HIC group and 368 in the TASSH + HIC group, 85% had 12-month data available (60% women, mean BP 155.9/89.6 mm Hg. In intention-to-treat analyses adjusted for clustering, the TASSH + HIC group had a greater SBP reduction (-20.4 mm Hg; 95% CI -25.2 to -15.6 than the HIC group (-16.8 mm Hg; 95% CI -19.2 to -15.6, with a statistically significant between-group difference of -3.6 mm Hg (95% CI -6.1 to -0.5; p = 0.021. Blood pressure control improved significantly in both groups (55.2%, 95% CI 50.0% to 60.3%, for the TASSH + HIC group versus 49.9%, 95% CI 44.9% to 54.9%, for the HIC group, with a non

  14. 33 CFR 110.129a - Apra Harbor, Guam. (Datum: WGS 84)

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Apra Harbor, Guam. (Datum: WGS 84) 110.129a Section 110.129a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.129a Apra Harbor, Guam. (Datum: WGS 84) (a...

  15. 33 CFR 110.60 - Captain of the Port, New York.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Captain of the Port, New York... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.60 Captain of the Port, New York. (a) Western... point of origin. (d) New York Harbor. (1) Newark Bay, Southeast. All waters bound by the following...

  16. 33 CFR 110.128c - Island of Kauai, Hawaii.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Island of Kauai, Hawaii. 110.128c Section 110.128c Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.128c Island of Kauai, Hawaii. (a) Nawiliwili Bay. The...

  17. 33 CFR 110.70a - Northeast River, North East, Md.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

  18. A comparison of lower canine retraction and loss of anchorage between conventional and self-ligating brackets: a single-center randomized split-mouth controlled trial.

    Science.gov (United States)

    da Costa Monini, André; Júnior, Luiz Gonzaga Gandini; Vianna, Alexandre Protásio; Martins, Renato Parsekian

    2017-05-01

    To evaluate the rate of lower canine retraction, anchorage loss, and changes on lower canines and first molars axial inclination using self-ligating and conventional brackets. Twenty-five adult patients with a treatment plan involving extractions of four first premolars were selected for this split-mouth trial and had either conventional or self-ligating brackets bonded to lower canines in a block randomization. Retraction was accomplished using 100-g nickel titanium closed-coil springs, which were reactivated each 4 weeks. Oblique radiographs were taken before and after total canine retraction and the cephalograms were superimposed on stable structures of the mandible. Cephalometric points were digitized twice by a single-blinded operator for error control and the average of the points were used to determine the following variables: canine cusp horizontal changes, molar cusp horizontal changes, and angulation changes in canines and molars. Paired t tests were used to analyze the blinded data for group differences. All patients reached final phase without bracket debonds. No differences were found between the two groups for all variables tested. No serious harm was observed. Both brackets showed the same rate of canine retraction and loss of anteroposterior anchorage of the molars. No changes were found between brackets regarding the inclination of canines and first molars. Using self-ligating brackets to retract lower canines will not increase the velocity of tooth movement, does not increase anchorage, and does not decrease tipping.

  19. Skin-specific regulation of SREBP processing and lipid biosynthesis by glycerol kinase 5

    OpenAIRE

    Zhang, Duanwu; Tomisato, Wataru; Su, Lijing; Sun, Lei; Choi, Jin Huk; Zhang, Zhao; Wang, Kuan-wen; Zhan, Xiaoming; Choi, Mihwa; Li, Xiaohong; Tang, Miao; Castro-Perez, Jose M.; Hildebrand, Sara; Murray, Anne R.; Moresco, Eva Marie Y.

    2017-01-01

    We discovered a previously unrecognized regulator of cholesterol biosynthesis, glycerol kinase 5 (GK5), which functions exclusively in the skin independently of cholesterol regulation in other tissues. GK5 negatively regulates the processing and nuclear localization of sterol regulatory element binding proteins, transcription factors that control expression of virtually all cholesterol synthesis enzymes. Excessive amounts of cholesterol, triglycerides, and ceramides were found in the skin of ...

  20. MTA3 regulates CGB5 and Snail genes in trophoblast

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States); Miyazaki, Jun [Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Fujita Health University, Toyoake (Japan); Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake (Japan); Nishizawa, Haruki [Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Fujita Health University, Toyoake (Japan); Kurahashi, Hiroki [Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake (Japan); Leach, Richard, E-mail: Richard.Leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group, Grand Rapids, MI 49503 (United States); Wang, Kai, E-mail: Kai.Wang@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States)

    2013-04-19

    Highlights: •Impaired MTA3, raised CGB5 and Snail expression are associated with preeclampsia. •Knock-down of MTA3 causes up-regulation of CGB5 and Snail genes in BeWo cells. •MTA3 occupies CGB5 and Snail gene promoters in BeWo cells. -- Abstract: Secreted by the placental trophoblast, human chorionic gonadotropin (hCG) is an important hormone during pregnancy and is required for the maintenance of pregnancy. Previous studies have shown that dys-regulation of hCG expression is associated with preeclampsia. However, the exact relationship between altered hCG levels and development of preeclampsia is unknown. Metastasis associated protein 3 (MTA3), a chromatin remodeling protein, is abundantly expressed in the placental trophoblasts, but its function is unknown. In breast cancer, MTA3 has been shown to repress the expression of Snail and cell migration. However, whether MTA3 acts similarly in the trophoblast has not been investigated. In the present study, we examined the role of MTA3 in regulating the hCG β-subunit gene (gene name: CGB5) and Snail expression in the trophoblast cell line, BeWo, as well as its relevance to the high hCG expression levels seen in preeclampsia. First, we investigated MTA3 expression in preeclamptic placenta as compared to normal control placenta via gene expression microarray and qRT-PCR and found that MTA3 was significantly down-regulated, whereas both CGB5 and Snail were up-regulated in preeclamptic placenta. Secondly, we knocked down MTA3 gene in trophoblast cell line BeWo and found Snail and hCG were both up-regulated, suggesting that MTA3 represses Snail and hCG gene expression in trophoblasts. Next, we cloned the CGB5 and Snail promoters into the pGL3-basic vector individually and found that silencing of MTA3 by siRNA resulted in an increase of both CGB5 and Snail promoter activities. To confirm that this MTA3 inhibition is a direct effect, we performed a chromatin immune-precipitation (ChIP) assay and found that MTA3

  1. MTA3 regulates CGB5 and Snail genes in trophoblast

    International Nuclear Information System (INIS)

    Chen, Ying; Miyazaki, Jun; Nishizawa, Haruki; Kurahashi, Hiroki; Leach, Richard; Wang, Kai

    2013-01-01

    Highlights: •Impaired MTA3, raised CGB5 and Snail expression are associated with preeclampsia. •Knock-down of MTA3 causes up-regulation of CGB5 and Snail genes in BeWo cells. •MTA3 occupies CGB5 and Snail gene promoters in BeWo cells. -- Abstract: Secreted by the placental trophoblast, human chorionic gonadotropin (hCG) is an important hormone during pregnancy and is required for the maintenance of pregnancy. Previous studies have shown that dys-regulation of hCG expression is associated with preeclampsia. However, the exact relationship between altered hCG levels and development of preeclampsia is unknown. Metastasis associated protein 3 (MTA3), a chromatin remodeling protein, is abundantly expressed in the placental trophoblasts, but its function is unknown. In breast cancer, MTA3 has been shown to repress the expression of Snail and cell migration. However, whether MTA3 acts similarly in the trophoblast has not been investigated. In the present study, we examined the role of MTA3 in regulating the hCG β-subunit gene (gene name: CGB5) and Snail expression in the trophoblast cell line, BeWo, as well as its relevance to the high hCG expression levels seen in preeclampsia. First, we investigated MTA3 expression in preeclamptic placenta as compared to normal control placenta via gene expression microarray and qRT-PCR and found that MTA3 was significantly down-regulated, whereas both CGB5 and Snail were up-regulated in preeclamptic placenta. Secondly, we knocked down MTA3 gene in trophoblast cell line BeWo and found Snail and hCG were both up-regulated, suggesting that MTA3 represses Snail and hCG gene expression in trophoblasts. Next, we cloned the CGB5 and Snail promoters into the pGL3-basic vector individually and found that silencing of MTA3 by siRNA resulted in an increase of both CGB5 and Snail promoter activities. To confirm that this MTA3 inhibition is a direct effect, we performed a chromatin immune-precipitation (ChIP) assay and found that MTA3

  2. British Orthodontic Society national audit of temporary anchorage devices (TADs): report of the first thousand TADs placed.

    Science.gov (United States)

    Bearn, David R; Alharbi, Fahad

    2015-09-01

    To provide data from the British Orthodontic Society (BOS) national clinical audit on temporary anchorage device (TAD) use following the recommendations of the National Institute for Health and Clinical Excellence (NIHCE) Design and setting: The Audit commenced on 1 January 2008 and is still ongoing. This article reports the data for TADs placed from 1 January 2008 to 1 November 2013. Audit data was collected from participants using a system of both on-line data entry and hard copy forms. The criteria and standards for the audit were set following the NIHCE report in conjunction with the Development and Standards Committee of the BOS. Virtually all participants used the on-line data entry available on the BOS website. The data submitted was checked and entered manually into an Excel spreadsheet, and transferred to SPSS for analysis. Written information and documented discussion of risks were provided in over 90% of TADs placed, but 17.4% were placed without a specific signed consent form. Temporary anchorage device failure rate was 24.2% overall. Among failed TADs, 93.1% were lost or removed due to excess mobility. Infection or inflammation resulting in loss or removal was reported in 6% of TADs. The only audit standard that was met was failures due to infection of inflammation. The rest of the audit standards were not met. Recommendations are made to address these issues.

  3. Spheroid Culture of Head and Neck Cancer Cells Reveals an Important Role of EGFR Signalling in Anchorage Independent Survival.

    Science.gov (United States)

    Braunholz, Diana; Saki, Mohammad; Niehr, Franziska; Öztürk, Merve; Borràs Puértolas, Berta; Konschak, Robert; Budach, Volker; Tinhofer, Ingeborg

    2016-01-01

    In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix. The HNSCC cell lines FaDu, SCC-9 and UT-SCC-9 (UT-SCC-9P) as well as its cetuximab (CTX)-resistant sub-clone (UT-SCC-9R) were forced to grow in an anchorage-independent manner by coating culture dishes with the anti-adhesive polymer poly-2-hydroxyethylmethacrylate (poly-HEMA). The extent of apoptosis, clonogenic survival and EGFR signalling under such culture conditions was evaluated. The potential of spheroid formation in suspension culture was found to be positively correlated with the proliferation rate of HNSCC cell lines as well as their basal EGFR expression levels. CTX and gefitinib blocked, whereas the addition of EGFR ligands promoted anchorage-independent cell survival and spheroid formation. Increased spheroid formation and growth were associated with persistent activation of EGFR and its downstream signalling component (MAPK/ERK). Importantly, HNSCC cells derived from spheroid cultures retained their clonogenic potential in the absence of cell-matrix contact. Addition of CTX under these conditions strongly inhibited colony formation in CTX-sensitive cell lines but not their resistant subclones. Altogether, EGFR activation was identified as crucial factor for anchorage-independent survival of HNSCC cells. Targeting EGFR in CTC cluster formation might represent an attractive anti

  4. The regulation of CD5 expression in murine T cells

    Directory of Open Access Journals (Sweden)

    Herzenberg Leonard A

    2001-05-01

    Full Text Available Abstract Background CD5 is a pan-T cell surface marker that is also present on a subset of B cells, B-1a cells.Functional and developmental subsets of T cells express characteristic CD5 levels that vary over roughly a 30-fold range. Previous investigators have cloned a 1.7 Kb fragment containing the CD5 promoter and showed that it can confer similar lymphocyte-specific expression pattern as observed for endogenous CD5 expression. Results We further characterize the CD5 promoter and identify minimal and regulatory regions on the CD5 promoter. Using a luciferase reporter system, we show that a 43 bp region on the CD5 promoter regulates CD5 expression in resting mouse thymoma EL4 T cells and that an Ets binding site within the 43 bp region mediates the CD5 expression. In addition, we show that Ets-1, a member of the Ets family of transcription factors, recognizes the Ets binding site in the electrophoretic mobility shift assay (EMSA. This Ets binding site is directly responsible for the increase in reporter activity when co-transfected with increasing amounts of Ets-1 expression plasmid. We also identify two additional evolutionarily-conserved regions in the CD5 promoter (CD5X and CD5Y and demonstrate the respective roles of the each region in the regulation of CD5 transcription. Conclusion Our studies define a minimal and regulatory promoter for CD5 and show that the CD5 expression level in T cells is at least partially dependent on the level of Ets-1 protein. Based on the findings in this report, we propose a model of CD5 transcriptional regulation in T cells.

  5. 5 CFR 2636.302 - Relationship to other laws and regulations.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Relationship to other laws and... Employees § 2636.302 Relationship to other laws and regulations. The limitations and restrictions contained... applicable standards of conduct or by reason of any statute or regulation relating to conflicts of interest...

  6. 33 CFR 110.155 - Port of New York.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Port of New York. 110.155 Section... ANCHORAGE REGULATIONS Anchorage Grounds § 110.155 Port of New York. (a) Long Island Sound—(1) Anchorage No... northwest corner of the crib icebreaker north of the New York Central Railroad Company drawbridge across...

  7. 33 CFR 110.74c - Bahia de San Juan, PR.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Bahia de San Juan, PR. 110.74c Section 110.74c Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.74c Bahia de San Juan, PR. The waters of San Antonio...

  8. Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro

    International Nuclear Information System (INIS)

    Sun, Yihua; Fang, Rong; Li, Chenguang; Li, Li; Li, Fei; Ye, Xiaolei; Chen, Haiquan

    2010-01-01

    Lung cancer is one of the most devastating diseases worldwide. RGS17 is previously shown to be over-expressed in human lung adenocarcinomas and plays an important role in lung tumor growth. Here we have identified a miRNA, has-mir-182, involved in the regulation of RGS17 expression through two conserved sites located in its 3' UTR region. Consistently, endogenous RGS17 expression level is regulated by hsa-mir-182 in human lung cancer cell lines. Similar to the knockdown of RGS17, ectopic expression of hsa-mir-182 significantly inhibits lung cancer cell proliferation and anchorage-independent cell growth, which can be rescued by re-expression of RGS17. Taken together, these data have provided the first evidence of miRNA regulation of RGS17 expression in lung cancer.

  9. Subcellular distribution of cyclin-dependent kinase-like 5 (CDKL5) is regulated through phosphorylation by dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A).

    Science.gov (United States)

    Oi, Ami; Katayama, Syouichi; Hatano, Naoya; Sugiyama, Yasunori; Kameshita, Isamu; Sueyoshi, Noriyuki

    2017-01-08

    Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase primarily expressed in the central nervous system and is known to cause X-linked neurodevelopmental disorders such as Rett syndrome. However, the mechanisms regulating CDKL5 have not yet been fully clarified. Therefore, in this study, we investigated the protein kinase that directly phosphorylates CDKL5, identifying it as dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), an enzyme binding to and phosphorylating CDKL5. We showed that subcellular distribution of CDKL5 was regulated by its phosphorylation by DYRK1A. In mouse neuroblastoma Neuro2a cells, CDKL5 was localized in both the cytosol and nucleus, whereas DYRK1A showed a typical nuclear localization. When CDKL5 and DYRK1A were co-expressed, the cytosolic localization of CDKL5 was significantly increased. Results of site-directed mutagenesis revealed that the phosphorylation site was Ser-308, in the vicinity of the nuclear localization signal. A mutation mimicking the phosphorylated serine residue by aspartate substitution (S308D) changed CDKL5 localization to the cytosol, whereas the corresponding alanine-substituted analog, CDKL5(S308A), was primarily localized to the nucleus. Taken together, these results strongly suggested that DYRK1A bound to CDKL5 and phosphorylated it on Ser-308, thus interfering with its nuclear localization. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. 33 CFR 110.8 - Lake Champlain, N.Y. and Vt.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Lake Champlain, N.Y. and Vt. 110... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.8 Lake Champlain, N.Y. and Vt. (a) Ticonderoga, N.Y. An area shoreward of a line bearing 312° from Ticonderoga Light to the southeast corner of the...

  11. 33 CFR 110.120 - San Luis Obispo Bay, Calif.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false San Luis Obispo Bay, Calif. 110... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.120 San Luis Obispo Bay, Calif. (a) Area A-1. Area A-1 is the water area bounded by the San Luis Obispo County wharf, the shoreline, a line drawn...

  12. Syk Tyrosine Kinase Acts as a Pancreatic Adenocarcinoma Tumor Suppressor by Regulating Cellular Growth and Invasion

    OpenAIRE

    Layton, Tracy; Stalens, Cristel; Gunderson, Felizza; Goodison, Steve; Silletti, Steve

    2009-01-01

    We have identified the nonreceptor tyrosine kinase syk as a marker of differentiation/tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). Syk expression is lost in poorly differentiated PDAC cells in vitro and in situ, and stable reexpression of syk in endogenously syk-negative Panc1 (Panc1/syk) cells retarded their growth in vitro and in vivo and reduced anchorage-independent growth in vitro. Panc1/syk cells exhibited a more differentiated morphology and down-regulated cyclin D1, ak...

  13. Resveratrol inhibits Cdk5 activity through regulation of p35 expression

    Directory of Open Access Journals (Sweden)

    Kulkarni Ashok B

    2011-07-01

    Full Text Available Abstract Background We have previously reported that cyclin-dependent kinase 5 (Cdk5 participates in the regulation of nociceptive signaling. Through activation of the ERK1/2 pathway, Tumor Necrosis Factor-α (TNF-α induces expression of Egr-1. This results in the sustained and robust expression of p35, a coactivator of Cdk5, in PC12 cells, thereby increasing Cdk5 kinase activity. The aim of our present study was to test whether resveratrol, a polyphenolic compound with known analgesic activity, can regulate Cdk5/p35 activity. Results Here we used a cell-based assay in which a p35 promoter-luciferase construct was stably transfected in PC12 cells. Our studies demonstrate that resveratrol inhibits p35 promoter activity and also blocks the TNF-α mediated increase in Cdk5 activity in PC12 cells. Resveratrol also inhibits p35 expression and blocks the TNF-α mediated increase in Cdk5 activity in DRG neurons. In the presence of resveratrol, the MEK inhibitor decreased p35 promoter activity, whereas the inhibitors of p38 MAPK, JNK and NF-κB increased p35 promoter activity, indicating that these pathways regulate p35 expression differently. The TNF-α-mediated increase in Egr-1 expression was decreased by resveratrol treatment with a concomitant reduction in p35 expression and protein levels, resulting in reduced Cdk5 kinase activity. Conclusions We demonstrate here that resveratrol regulates p35 promoter activity in PC12 cells and DRG neurons. Most importantly, resveratrol blocks the TNF-α-mediated increase in p35 promoter activity, thereby reducing p35 expression and subsequent Cdk5 kinase activity. This new molecular mechanism adds to the known analgesic effects of resveratrol and confirms the need for identifying new analgesics based on their ability to inhibit Cdk5 activity for effective treatment of pain.

  14. 7 CFR 301.48-5 - Inspection and disposal of regulated articles and pests.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Inspection and disposal of regulated articles and pests. 301.48-5 Section 301.48-5 Agriculture Regulations of the Department of Agriculture (Continued... pests. Any properly identified inspector is authorized to stop and inspect, and to seize, destroy, or...

  15. XIAP BIR domain suppresses miR-200a expression and subsequently promotes EGFR protein translation and anchorage-independent growth of bladder cancer cell

    Directory of Open Access Journals (Sweden)

    Chao Huang

    2017-01-01

    Full Text Available Abstract Background The X-linked inhibitor of apoptosis protein (XIAP is a well-known potent apoptosis suppressor and also participates in cancer cell biological behaviors, therefore attracting great attentions as a potential antineoplastic therapeutic target for past years. Anti-IAP therapy is reported to be closely related to epidermal growth factor receptor (EGFR expression level. However, whether and how XIAP modulates EGFR expression remains largely unknown. Methods Human XIAP was knockdown with short-hairpin RNA in two different bladder cancer cell lines, T24T and UMUC3. Two XIAP mutants, XIAP ∆BIR (deletion of N-terminal three BIR domains and XIAP ∆RING (deletion of C-terminal RING domain and keeping the function of BIR domains, were generated to determine which domain is involved in regulating EGFR. Results We found here that lacking of XIAP expression resulted in a remarkable suppression of EGFR expression, consequently leading to the deficiency of anchorage-independent cell growth. Further study demonstrated that BIR domain of XIAP was crucial for regulating the EGFR translation by suppressing the transcription and expression of miR-200a. Mechanistic studies indicated that BIR domain activated the protein phosphatase 2 (PP2A activity by decreasing the phosphorylation of PP2A at Tyr307 in its catalytic subunit, PP2A-C. Such activated PP2A prevented the deviant phosphorylation and activation of MAPK kinases/MAPKs, their downstream effector c-Jun, and in turn inhibiting transcription of c-Jun-regulated the miR-200a. Conclusions Our study uncovered a novel function of BIR domain of XIAP in regulating the EGFR translation, providing significant insight into the understanding of the XIAP overexpression in the cancer development and progression, further offering a new theoretical support for using XIAP BIR domain and EGFR as targets for cancer therapy.

  16. p-Glycoprotein ABCB5 and YB-1 expression plays a role in increased heterogeneity of breast cancer cells: correlations with cell fusion and doxorubicin resistance

    International Nuclear Information System (INIS)

    Yang, Ji Yeon; Ha, Seon-Ah; Yang, Yun-Sik; Kim, Jin Woo

    2010-01-01

    Cancer cells recurrently develop into acquired resistance to the administered drugs. The iatrogenic mechanisms of induced chemotherapy-resistance remain elusive and the degree of drug resistance did not exclusively correlate with reductions of drug accumulation, suggesting that drug resistance may involve additional mechanisms. Our aim is to define the potential targets, that makes drug-sensitive MCF-7 breast cancer cells turn to drug-resistant, for the anti-cancer drug development against drug resistant breast cancer cells. Doxorubicin resistant human breast MCF-7 clones were generated. The doxorubicin-induced cell fusion events were examined. Heterokaryons were identified and sorted by FACS. In the development of doxorubicin resistance, cell-fusion associated genes, from the previous results of microarray, were verified using dot blot array and quantitative RT-PCR. The doxorubicin-induced expression patterns of pro-survival and pro-apoptotic genes were validated. YB-1 and ABCB5 were up regulated in the doxorubicin treated MCF-7 cells that resulted in certain degree of genomic instability that accompanied by the drug resistance phenotype. Cell fusion increased diversity within the cell population and doxorubicin resistant MCF-7 cells emerged probably through clonal selection. Most of the drug resistant hybrid cells were anchorage independent. But some of the anchorage dependent MCF-7 cells exhibited several unique morphological appearances suggesting minor population of the fused cells maybe de-differentiated and have progenitor cell like characteristics. Our work provides valuable insight into the drug induced cell fusion event and outcome, and suggests YB-1, GST, ABCB5 and ERK3 could be potential targets for the anti-cancer drug development against drug resistant breast cancer cells. Especially, the ERK-3 serine/threonine kinase is specifically up-regulated in the resistant cells and known to be susceptible to synthetic antagonists

  17. In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe.

    Science.gov (United States)

    Shimizu, Yoichi; Temma, Takashi; Hara, Isao; Makino, Akira; Kondo, Naoya; Ozeki, Ei-Ichi; Ono, Masahiro; Saji, Hideo

    2014-08-01

    Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2 that mediates cleavage of extracellular matrix components and plays pivotal roles in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging of MT1-MMP would be useful for tumor diagnosis, we developed a novel near-infrared (NIR) fluorescence probe that can be activated following interaction with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles that encapsulate NIR dyes (IC7-1, λem : 858 nm) at concentrations sufficient to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent. Cellular uptake experiments revealed that in MT1-MMP positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that increased with time as compared to hIC7L, a negative control probe lacking the anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P imaging using probes intravenously administered to tumor-bearing mice showed that MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 ± 0.3 [MT1-hIC7L] vs 3.1 ± 0.2 [hIC7L] 48 h after administration, P fluorescence in MCF-7 tumors. Together, these results show that MT1-hIC7L would be a potential activatable NIR probe for specifically detecting MT1-MMP-expressing tumors. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  18. OTUD5 regulates p53 stability by deubiquitinating p53.

    Directory of Open Access Journals (Sweden)

    Judong Luo

    Full Text Available The p53 tumour suppressor protein is a transcription factor that prevents oncogenic progression by activating the expression of apoptosis and cell-cycle arrest genes in stressed cells. The stability of p53 is tightly regulated by ubiquitin-dependent degradation, driven mainly by its negative regulators ubiquitin ligase MDM2.In this study, we have identified OTUD5 as a DUB that interacts with and deubiquitinates p53. OTUD5 forms a direct complex with p53 and controls level of ubiquitination. The function of OTUD5 is required to allow the rapid activation of p53-dependent transcription and a p53-dependent apoptosis in response to DNA damage stress.As a novel deubiquitinating enzyme for p53, OTUD5 is required for the stabilization and the activation of a p53 response.

  19. INPP5E Preserves Genomic Stability through Regulation of Mitosis.

    Science.gov (United States)

    Sierra Potchanant, Elizabeth A; Cerabona, Donna; Sater, Zahi Abdul; He, Ying; Sun, Zejin; Gehlhausen, Jeff; Nalepa, Grzegorz

    2017-03-15

    The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we report that INPP5E further contributes to cellular homeostasis by regulating cell division. We found that silencing or genetic knockout of INPP5E in human and murine cells impairs the spindle assembly checkpoint, centrosome and spindle function, and maintenance of chromosomal integrity. Consistent with a cell cycle regulatory role, we found that INPP5E expression is cell cycle dependent, peaking at mitotic entry. INPP5E localizes to centrosomes, chromosomes, and kinetochores in early mitosis and shuttles to the midzone spindle at mitotic exit. Our findings identify the previously unknown, essential role of INPP5E in mitosis and prevention of aneuploidy, providing a new perspective on the function of this phosphoinositide phosphatase in health and development. Copyright © 2017 Sierra Potchanant et al.

  20. The transcriptional repressor HIC1 regulates intestinal immune homeostasis

    Czech Academy of Sciences Publication Activity Database

    Burrows, K.; Antignano, F.; Bramhall, M.; Chenery, A.; Scheer, S.; Kořínek, Vladimír; Underhill, T. M.; Zaph, C.

    2017-01-01

    Roč. 10, č. 6 (2017), s. 1518-1528 ISSN 1933-0219 Institutional support: RVO:68378050 Keywords : cd4(+) t-cells * anti-interleukin-17 monoclonal-antibody * cd103(+) dendritic cells * acid receptor-alpha * retinoic acid * t(h)17 cells * target genes * double-blind * tgf-beta * differentiation Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 7.478, year: 2016

  1. Hic-Et-Nunc (Here-and-Now Encoding of a Moving Target for its Saccadic Foveation

    Directory of Open Access Journals (Sweden)

    Laurent Goffart

    2012-10-01

    Full Text Available The neural representation of a moving target undergoes a spatiotemporal “diffusion” while the associated retinal activity propagates toward the motor centers and recruits the appropriate muscles for its interception in the external world. Indeed, the divergent projections within the visual system and the transmissions of signals through multiple relays, with diverse conduction velocities and integration times, lead to activities that are spatially and temporally distributed across several brain regions. In spite of this neural “blurring”, accurate saccadic eye movements can be made to bring the image of a moving target onto the fovea. Such a performance indicates that the brain is able to rapidly estimate the current spatiotemporal coordinates of the target, at least at the time of saccade landing. We tested in the monkey the robustness of this estimate when a change in eye position and a delay are experimentally added before the animal launches a saccade toward a moving target and in the absence of visual feedback. These spatiotemporal perturbations were induced by a brief microstimulation in the deep superior colliculus. The results show that the interceptive saccades can remain accurate and relatively independent of the time taken to react and to foveate the target. We propose that the brain builds an estimate of the expected and current spatiotemporal (hic-et-nunc coordinates of the target and that this signal feeds the same local feedback loop as the mechanism proposed for guiding saccades toward a stationary target (Fleuriet and Goffart, 2012 Journal of Neuroscience 32 452–461.

  2. The Effect of Soil Type and Moisture Content on Head Impacts on Natural Grass Athletic Fields

    Directory of Open Access Journals (Sweden)

    Kyley Dickson

    2018-02-01

    Full Text Available Studies are warranted to evaluate head injury criterion (HIC on athletic fields to determine baseline numbers and compare those findings to current critical thresholds for impact attenuation. A two year (2016 and 2017 study was conducted on University of Tennessee athletic fields (Knoxville, TN, USA to determine the effect of soil type (cohesive soil, United States Golf Association sand specifications and grass species (Poa pratensis and Cynodon dactylon × C. transvaalensis on HIC. Additionally soil moisture conditions monitored were: dry (0.06–0.16 m3/m3, acceptable (0.17–0.29 m3/m3, and wet (0.30–0.40 m3/m3. A linear relationship (r = 0.91 was identified between drop height (0.5–2.9 M and HIC value (35-1423 HIC on granular root zones of both grass types. However, HIC on cohesive soil is a function of soil water content in addition to drop height. These results demonstrate to aid in head injury prevention on cohesive soil athletic fields the HIC can be lowered by managing soil water content.

  3. NLRC5: a key regulator of MHC class I-dependent immune responses.

    Science.gov (United States)

    Kobayashi, Koichi S; van den Elsen, Peter J

    2012-12-01

    The expression of MHC class I molecules is crucial for the initiation and regulation of adaptive immune responses against pathogens. NOD-, LRR- and CARD-containing 5 (NLRC5) was recently identified as a specific transactivator of MHC class I genes (CITA). NLRC5 and the master regulator for MHC class II genes, class II transactivator (CIITA), interact with similar MHC promoter-bound factors. Here, we provide a broad overview of the molecular mechanisms behind MHC class I transcription and the role of the class I transactivator NLRC5 in MHC class I-dependent immune responses.

  4. Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development.

    Science.gov (United States)

    Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

    2013-05-28

    The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5-PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5-PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders.

  5. [The application of Edgewise technique auxillary with extra oral anchorage and class III elastic in the treatment of bimaxillary protrusion.].

    Science.gov (United States)

    Liu, H H; Weng, S E; Chen, R J

    1995-12-01

    In the treatment of growing bimaxillary protrusion patients,Edgewise technique auxillary with extra oral anchorage and class III elastic help to improve the patient's chin shape,recover his beauty of lower facial part and get a good occlusion along with the growing of mandible.The purpose of this study is:analysis the force system in the treatment and evaluate the result of the treatment with some typical cases.

  6. Wnt5a regulates hematopoietic stem cell proliferation and repopulation through the Ryk receptor.

    Science.gov (United States)

    Povinelli, Benjamin J; Nemeth, Michael J

    2014-01-01

    Proper regulation of the balance between hematopoietic stem cell (HSC) proliferation, self-renewal, and differentiation is necessary to maintain hematopoiesis throughout life. The Wnt family of ligands has been implicated as critical regulators of these processes through a network of signaling pathways. Previously, we have demonstrated that the Wnt5a ligand can induce HSC quiescence through a noncanonical Wnt pathway, resulting in an increased ability to reconstitute hematopoiesis. In this study, we tested the hypothesis that the Ryk protein, a Wnt ligand receptor that can bind the Wnt5a ligand, regulated the response of HSCs to Wnt5a. We observed that inhibiting Ryk blocked the ability of Wnt5a to induce HSC quiescence and enhance short-term and long-term hematopoietic repopulation. We found that Wnt5a suppressed production of reactive oxygen species, a known inducer of HSC proliferation. The ability of Wnt5a to inhibit ROS production was also regulated by Ryk. From these data, we propose that Wnt5a regulates HSC quiescence and hematopoietic repopulation through the Ryk receptor and that this process is mediated by suppression of reactive oxygen species. © 2013 AlphaMed Press.

  7. The cancer-promoting gene fatty acid-binding protein 5 (FABP5) is epigenetically regulated during human prostate carcinogenesis.

    Science.gov (United States)

    Kawaguchi, Koichiro; Kinameri, Ayumi; Suzuki, Shunsuke; Senga, Shogo; Ke, Youqiang; Fujii, Hiroshi

    2016-02-15

    FABPs (fatty-acid-binding proteins) are a family of low-molecular-mass intracellular lipid-binding proteins consisting of ten isoforms. FABPs are involved in binding and storing hydrophobic ligands such as long-chain fatty acids, as well as transporting these ligands to the appropriate compartments in the cell. FABP5 is overexpressed in multiple types of tumours. Furthermore, up-regulation of FABP5 is strongly associated with poor survival in triple-negative breast cancer. However, the mechanisms underlying the specific up-regulation of the FABP5 gene in these cancers remain poorly characterized. In the present study, we determined that FABP5 has a typical CpG island around its promoter region. The DNA methylation status of the CpG island in the FABP5 promoter of benign prostate cells (PNT2), prostate cancer cells (PC-3, DU-145, 22Rv1 and LNCaP) and human normal or tumour tissue was assessed by bisulfite sequencing analysis, and then confirmed by COBRA (combined bisulfite restriction analysis) and qAMP (quantitative analysis of DNA methylation using real-time PCR). These results demonstrated that overexpression of FABP5 in prostate cancer cells can be attributed to hypomethylation of the CpG island in its promoter region, along with up-regulation of the direct trans-acting factors Sp1 (specificity protein 1) and c-Myc. Together, these mechanisms result in the transcriptional activation of FABP5 expression during human prostate carcinogenesis. Importantly, silencing of Sp1, c-Myc or FABP5 expression led to a significant decrease in cell proliferation, indicating that up-regulation of FABP5 expression by Sp1 and c-Myc is critical for the proliferation of prostate cancer cells. © 2016 Authors; published by Portland Press Limited.

  8. Critical Endothelial Regulation by LRP5 during Retinal Vascular Development

    Science.gov (United States)

    Huang, Wei; Li, Qing; Amiry-Moghaddam, Mahmood; Hokama, Madoka; Sardi, Sylvia H.; Nagao, Masashi; Warman, Matthew L.; Olsen, Bjorn R.

    2016-01-01

    Vascular abnormalities in the eye are the leading cause of many forms of inherited and acquired human blindness. Loss-of-function mutations in the Wnt-binding co-receptor LRP5 leads to aberrant ocular vascularization and loss of vision in genetic disorders such as osteoporosis-pseudoglioma syndrome. The canonical Wnt-β-catenin pathway is known to regulate retinal vascular development. However, it is unclear what precise role LPR5 plays in this process. Here, we show that loss of LRP5 function in mice causes retinal hypovascularization during development as well as retinal neovascularization in adulthood with disorganized and leaky vessels. Using a highly specific Flk1-CreBreier line for vascular endothelial cells, together with several genetic models, we demonstrate that loss of endothelium-derived LRP5 recapitulates the retinal vascular defects in Lrp5-/- mice. In addition, restoring LRP5 function only in endothelial cells in Lrp5-/- mice rescues their retinal vascular abnormalities. Furthermore, we show that retinal vascularization is regulated by LRP5 in a dosage dependent manner and does not depend on LRP6. Our study provides the first direct evidence that endothelium-derived LRP5 is both necessary and sufficient to mediate its critical role in the development and maintenance of retinal vasculature. PMID:27031698

  9. A High Integrity Can Design for Degraded Nuclear Fuel

    International Nuclear Information System (INIS)

    Holmes, P.A.

    1999-01-01

    A high integrity can (HIC), designed to meet the ASME Boiler and Pressure Vessel Code (Section III, Div. 3, static conditions) is proposed for the interim storage and repository disposal of Department of Energy (DOE) spent nuclear fuel. The HIC will be approximately 5 3/8 inches (134.38mm) in outside diameter with 1/4 inch (6.35mm) thick walls, and have a removable lid with a metallic seal that is capable of being welded shut. The opening of the can is approximately 4 3/8 inches (111.13mm). The HIC is primarily designed to contain items in the DOE SNF inventory that do not meet acceptance standards for direct disposal in a geologic repository. This includes fuel in the form of particulate dusts, sectioned pieces of fuel, core rubble, melted or degraded (non-intact) fuel elements, unclad uranium alloys, metallurgical specimens, and chemically reactive fuel components. The HIC is intended to act as a substitute cladding for the spent nuclear fuel, further isolate problematic materials, provide a long-term corrosion barrier, and add an extra internal pressure barrier to the waste package. The HIC will also delay potential fission product release and maintain geometry control for extended periods of time. For the entire disposal package to be licensed by the Nuclear Regulatory Commission, a HIC must effectively eliminate the disposal problems associated with problem SNF including the release of radioactive and/or reactive material and over pressurization of the HIC due to chemical reactions within the can. Two HICs were analyzed to envelop a range of can lengths between 42 and 101 inches. Using Abacus software, the HIC's were analyzed for end, side, and corner drops. Hastelloy C-22 was chosen based upon structural integrity, corrosion resistance, and neutron adsorption properties

  10. Cyclin-dependent kinase 5 regulates degranulation in human eosinophils.

    Science.gov (United States)

    Odemuyiwa, Solomon O; Ilarraza, Ramses; Davoine, Francis; Logan, Michael R; Shayeganpour, Anooshirvan; Wu, Yingqi; Majaesic, Carina; Adamko, Darryl J; Moqbel, Redwan; Lacy, Paige

    2015-04-01

    Degranulation from eosinophils in response to secretagogue stimulation is a regulated process that involves exocytosis of granule proteins through specific signalling pathways. One potential pathway is dependent on cyclin-dependent kinase 5 (Cdk5) and its effector molecules, p35 and p39, which play a central role in neuronal cell exocytosis by phosphorylating Munc18, a regulator of SNARE binding. Emerging evidence suggests a role for Cdk5 in exocytosis in immune cells, although its role in eosinophils is not known. We sought to examine the expression of Cdk5 and its activators in human eosinophils, and to assess the role of Cdk5 in eosinophil degranulation. We used freshly isolated human eosinophils and analysed the expression of Cdk5, p35, p39 and Munc18c by Western blot, RT-PCR, flow cytometry and immunoprecipitation. Cdk5 kinase activity was determined following eosinophil activation. Cdk5 inhibitors were used (roscovitine, AT7519 and small interfering RNA) to determine its role in eosinophil peroxidase (EPX) secretion. Cdk5 was expressed in association with Munc18c, p35 and p39, and phosphorylated following human eosinophil activation with eotaxin/CCL11, platelet-activating factor, and secretory IgA-Sepharose. Cdk5 inhibitors (roscovitine, AT7519) reduced EPX release when cells were stimulated by PMA or secretory IgA. In assays using small interfering RNA knock-down of Cdk5 expression in human eosinophils, we observed inhibition of EPX release. Our findings suggest that in activated eosinophils, Cdk5 is phosphorylated and binds to Munc18c, resulting in Munc18c release from syntaxin-4, allowing SNARE binding and vesicle fusion, with subsequent eosinophil degranulation. Our work identifies a novel role for Cdk5 in eosinophil mediator release by agonist-induced degranulation. © 2014 John Wiley & Sons Ltd.

  11. The perlecan-interacting growth factor progranulin regulates ubiquitination, sorting, and lysosomal degradation of sortilin.

    Science.gov (United States)

    Tanimoto, Ryuta; Palladino, Chiara; Xu, Shi-Qiong; Buraschi, Simone; Neill, Thomas; Gomella, Leonard G; Peiper, Stephen C; Belfiore, Antonino; Iozzo, Renato V; Morrione, Andrea

    2017-12-01

    Despite extensive clinical and experimental studies over the past decades, the pathogenesis and progression to the castration-resistant stage of prostate cancer remains largely unknown. Progranulin, a secreted growth factor, strongly binds the heparin-sulfate proteoglycan perlecan, and counteracts its biological activity. We established that progranulin acts as an autocrine growth factor and promotes prostate cancer cell motility, invasion, and anchorage-independent growth. Progranulin was overexpressed in prostate cancer tissues vis-à-vis non-neoplastic tissues supporting the hypothesis that progranulin may play a key role in prostate cancer progression. However, progranulin's mode of action is not well understood and proteins regulating progranulin signaling have not been identified. Sortilin, a single-pass type I transmembrane protein of the Vps10 family, binds progranulin in neurons and targets progranulin for lysosomal degradation. Significantly, in DU145 and PC3 cells, we detected very low levels of sortilin associated with high levels of progranulin production and enhanced motility. Restoring sortilin expression decreased progranulin levels, inhibited motility and anchorage-independent growth and destabilized Akt. These results demonstrated a critical role for sortilin in regulating progranulin and suggest that sortilin loss may contribute to prostate cancer progression. Here, we provide the novel observation that progranulin downregulated sortilin protein levels independent of transcription. Progranulin induced sortilin ubiquitination, internalization via clathrin-dependent endocytosis and sorting into early endosomes for lysosomal degradation. Collectively, these results constitute a regulatory feed-back mechanism whereby sortilin downregulation ensures sustained progranulin-mediated oncogenesis. Copyright © 2017. Published by Elsevier B.V.

  12. 26 CFR 1.852-5 - Earnings and profits of a regulated investment company.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 9 2010-04-01 2010-04-01 false Earnings and profits of a regulated investment company. 1.852-5 Section 1.852-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Regulated Investment Companies and Real Estate Investment...

  13. Recorded earthquake responses from the integrated seismic monitoring network of the Atwood Building, Anchorage, Alaska

    Science.gov (United States)

    Celebi, M.

    2006-01-01

    An integrated seismic monitoring system with a total of 53 channels of accelerometers is now operating in and at the nearby free-field site of the 20-story steel-framed Atwood Building in highly seismic Anchorage, Alaska. The building has a single-story basement and a reinforced concrete foundation without piles. The monitoring system comprises a 32-channel structural array and a 21-channel site array. Accelerometers are deployed on 10 levels of the building to assess translational, torsional, and rocking motions, interstory drift (displacement) between selected pairs of adjacent floors, and average drift between floors. The site array, located approximately a city block from the building, comprises seven triaxial accelerometers, one at the surface and six in boreholes ranging in depths from 15 to 200 feet (???5-60 meters). The arrays have already recorded low-amplitude shaking responses of the building and the site caused by numerous earthquakes at distances ranging from tens to a couple of hundred kilometers. Data from an earthquake that occurred 186 km away traces the propagation of waves from the deepest borehole to the roof of the building in approximately 0.5 seconds. Fundamental structural frequencies [0.58 Hz (NS) and 0.47 Hz (EW)], low damping percentages (2-4%), mode coupling, and beating effects are identified. The fundamental site frequency at approximately 1.5 Hz is close to the second modal frequencies (1.83 Hz NS and 1.43 EW) of the building, which may cause resonance of the building. Additional earthquakes prove repeatability of these characteristics; however, stronger shaking may alter these conclusions. ?? 2006, Earthquake Engineering Research Institute.

  14. PKC and AMPK regulation of Kv1.5 potassium channels

    DEFF Research Database (Denmark)

    Andersen, Martin Nybo; Skibsbye, Lasse; Tang, Chuyi

    2015-01-01

    The voltage-gated Kv1.5 potassium channel, conducting the ultra-rapid rectifier K(+) current (IKur), is regulated through several pathways. Here we investigate if Kv1.5 surface expression is controlled by the 2 kinases PKC and AMPK, using Xenopus oocytes, MDCK cells and atrial derived HL-1 cells....

  15. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

    International Nuclear Information System (INIS)

    Park, Jae Hyeon; Lee, Jeong Eun; Shin, In Chul; Koh, Hyun Chul

    2013-01-01

    Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

  16. Autophagy regulates chlorpyrifos-induced apoptosis in SH-SY5Y cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jae Hyeon [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of); Lee, Jeong Eun [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Shin, In Chul [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Koh, Hyun Chul, E-mail: hckoh@hanyang.ac.kr [Department of Pharmacology, College of Medicine, Hanyang University (Korea, Republic of); Hanyang Biomedical Research Institute, Seoul (Korea, Republic of); Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul (Korea, Republic of)

    2013-04-01

    Recent studies have shown that up-regulation of autophagy may be a tractable therapeutic intervention for clearing disease-causing proteins, including α-synuclein, ubiquitin, and other misfolded or aggregated proteins in pesticide-induced neurodegeneration. In a previous study, we reported that chlorpyrifos (CPF)-induced mitochondria-dependent apoptosis is mediated through reactive oxygen species in SH-SY5Y cells. In this study, we explored a novel pharmacotherapeutic approach to prevent CPF neurotoxicity involving the regulation of autophagy. We investigated the modulation of CPF-induced apoptosis according to autophagy regulation. We found that CPF induced apoptosis in SH-SY5Y cells, as demonstrated by the activation of caspase-3 and nuclear condensation. In addition, we observed that cells treated with CPF underwent autophagic cell death by monitoring the expression of LC3-II and p62. Pretreatment with the autophagy inducer rapamycin significantly enhanced the cell viability of CPF-exposed cells, and the enhancement of cell viability was partially due to alleviation of CPF-induced apoptosis via a decrease in levels of cleaved caspase-3. Specifically, rapamycin pretreatment decreased Bax and increased Bcl-2 expression in mitochondria. In addition, rapamycin significantly decreased cytochrome c release in from mitochondria into the cytosol. However, pretreatment of cells with the autophagy inhibitor, 3-methyladenine (3MA), remarkably increased CPF toxicity in these cells; this with correlated with increased expression of Bax and decreased expression of Bcl-2 in mitochondria. Our results suggest that CPF-induced cytotoxicity is modified by autophagy regulation and that rapamycin protects against CPF-induced apoptosis by enhancing autophagy. Pharmacologic induction of autophagy by rapamycin may be a useful treatment strategy in neurodegenerative disorders. - Highlights: ► Chlorpyrifos (CPF) is cytotoxic to SH-SY5Y cells ► CPF-induced cytotoxicity is mediated by

  17. Wise regulates bone deposition through genetic interactions with Lrp5.

    Science.gov (United States)

    Ellies, Debra L; Economou, Androulla; Viviano, Beth; Rey, Jean-Philippe; Paine-Saunders, Stephenie; Krumlauf, Robb; Saunders, Scott

    2014-01-01

    In this study using genetic approaches in mouse we demonstrate that the secreted protein Wise plays essential roles in regulating early bone formation through its ability to modulate Wnt signaling via interactions with the Lrp5 co-receptor. In Wise-/- mutant mice we find an increase in the rate of osteoblast proliferation and a transient increase in bone mineral density. This change in proliferation is dependent upon Lrp5, as Wise;Lrp5 double mutants have normal bone mass. This suggests that Wise serves as a negative modulator of Wnt signaling in active osteoblasts. Wise and the closely related protein Sclerostin (Sost) are expressed in osteoblast cells during temporally distinct early and late phases in a manner consistent with the temporal onset of their respective increased bone density phenotypes. These data suggest that Wise and Sost may have common roles in regulating bone development through their ability to control the balance of Wnt signaling. We find that Wise is also required to potentiate proliferation in chondrocytes, serving as a potential positive modulator of Wnt activity. Our analyses demonstrate that Wise plays a key role in processes that control the number of osteoblasts and chondrocytes during bone homeostasis and provide important insight into mechanisms regulating the Wnt pathway during skeletal development.

  18. Bilateral en-masse distalization of maxillary posterior teeth with skeletal anchorage: a case report

    Directory of Open Access Journals (Sweden)

    Saeed Noorollahian

    Full Text Available ABSTRACT Objective: The aim of this study was to introduce a new method for bilateral distal movement of the entire maxillary posterior segment. Case report: A 17-year-old girl with Class I skeletal malocclusion (end-to-end molar relationships, deviated midline and space deficiency for left maxillary canine was referred for orthodontic treatment. She did not accept maxillary first premolars extraction. A modified Hyrax appliance (Dentaurum Ispringen, Germany was used for bilateral distalization of maxillary posterior teeth simultaneously. Expansion vector was set anteroposteriorly. Posterior legs of Hyrax were welded to first maxillary molar bands. All posterior teeth on each side consolidated with a segment of 0.017 × 0.025-in stainless steel wire from the buccal side. Anterior legs of Hyrax were bent into eyelet form and attached to the anterior palate with two mini-screws (2 × 10 mm (Jeil Medical Corporation Seoul, South Korea. Hyrax opening rate was 0.8 mm per month. Lateral cephalometric radiographs were used to evaluate the extent of distal movement. 3.5-mm distalization of posterior maxillary teeth was achieved in five months. Results: A nearly bodily distal movement without anchorage loss was obtained. Conclusion: The mini-screw-supported modified Hyrax appliance was found to be helpful for achieving en-masse distal movement of maxillary posterior teeth.

  19. LnqR, a TetR-family transcriptional regulator, positively regulates lacticin Q production in Lactococcus lactis QU 5.

    Science.gov (United States)

    Iwatani, Shun; Ishibashi, Naoki; Flores, Floirendo P; Zendo, Takeshi; Nakayama, Jiro; Sonomoto, Kenji

    2016-09-01

    Lacticin Q is an unmodified leaderless bacteriocin produced by Lactococcus lactis QU 5. It has been revealed that the production and self-immunity of lacticin Q are facilitated by a gene cluster lnqQBCDEF The gene for a putative TetR-family transcriptional regulator, termed lnqR, was found nearby the lnqQBCDEF cluster, but its involvement in lacticin Q biosynthesis remained unknown. In this study, we created an LnqR-overexpressing QU 5 recombinant by using lactococcal constitutive promoter P32 The recombinant QU 5 showed enhanced production of and self-immunity to lacticin Q. RT-PCR analysis has revealed that an overexpression of LnqR increases the amounts of lnqQBCDEF transcripts, and these six genes are transcribed as an operon in a single transcriptional unit. Interestingly, LnqR expression and thus lacticin Q production by L. lactis QU 5 was found temperature dependent, while LnzR, an LnqR-homologue, in L. lactis QU 14 was expressed in a similar but not identical manner to LnqR, resulting in dissimilar bacteriocin productivities by these strains. This report demonstrates LnqR as the first TetR-family transcriptional regulator involved in LAB bacteriocin biosynthesis and that, as an exceptional case of TetR-family regulators, LnqR positively regulates the transcription of these biosynthetic genes. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Anchorage of TiO2-blasted, HA-coated, and machined implants: an experimental study with rabbits

    DEFF Research Database (Denmark)

    Gotfredsen, K; Wennerberg, A; Johansson, C

    1995-01-01

    The purpose of this study was to evaluate the histometrical and biomechanical anchorage of TiO2-blasted implants and TiO2-blasted implants coated with hydroxyapatite. The control implants were machined. Twenty-six rabbits had a total of 156 implants placed in the proximal part of the tibia. Each...... rabbit had a machined, a TiO2-blasted, and a TiO2-blasted, HA-coated implant placed in each tibia. After a healing period of 3 and 12 weeks, respectively, the implants placed in the right tibia were used for removal torque test, and the implants placed in the left tibia were used for histomorphometrical...

  1. 33 CFR 110.150 - Block Island Sound, N.Y.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Block Island Sound, N.Y. 110.150... ANCHORAGE REGULATIONS Anchorage Grounds § 110.150 Block Island Sound, N.Y. (a) The anchorage ground. A 3/4... following coordinates: latitude 41°06′12″ N., longitude 72°00′05″ W., latitude 41°07′40″ N., longitude 72°01...

  2. Regulator of G-protein signaling - 5 (RGS5 is a novel repressor of hedgehog signaling.

    Directory of Open Access Journals (Sweden)

    William M Mahoney

    Full Text Available Hedgehog (Hh signaling plays fundamental roles in morphogenesis, tissue repair, and human disease. Initiation of Hh signaling is controlled by the interaction of two multipass membrane proteins, patched (Ptc and smoothened (Smo. Recent studies identify Smo as a G-protein coupled receptor (GPCR-like protein that signals through large G-protein complexes which contain the Gαi subunit. We hypothesize Regulator of G-Protein Signaling (RGS proteins, and specifically RGS5, are endogenous repressors of Hh signaling via their ability to act as GTPase activating proteins (GAPs for GTP-bound Gαi, downstream of Smo. In support of this hypothesis, we demonstrate that RGS5 over-expression inhibits sonic hedgehog (Shh-mediated signaling and osteogenesis in C3H10T1/2 cells. Conversely, signaling is potentiated by siRNA-mediated knock-down of RGS5 expression, but not RGS4 expression. Furthermore, using immuohistochemical analysis and co-immunoprecipitation (Co-IP, we demonstrate that RGS5 is present with Smo in primary cilia. This organelle is required for canonical Hh signaling in mammalian cells, and RGS5 is found in a physical complex with Smo in these cells. We therefore conclude that RGS5 is an endogenous regulator of Hh-mediated signaling and that RGS proteins are potential targets for novel therapeutics in Hh-mediated diseases.

  3. Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development

    Science.gov (United States)

    Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

    2013-01-01

    The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5–PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5–PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders. PMID:23671101

  4. Association of ultraviolet-induced retrovirus expression with anchorage-independent survival in rat embryo cells

    International Nuclear Information System (INIS)

    Suk, W.A.

    1985-01-01

    The authors have shown in the AI assay that the nontransforming retrovirus increases the differential in enhanced survival response in infected cultures. To more fully understand this aspect of the system, they examined the effect of UV irradiation on infected and uninfected FRE cells. In this communication the authors report that UV irradiation induces AI survival in infected and uninfected cells;in uninfected cells there is a concomitant induction of endogenous retrovirus expression. The AI survival of both cell lines was determined using a previously described procedure. Anchorage-dependent media control and solvent control cells, when suspended in medium above an agar base layer, showed a rapid decline in cell survival;however, cells that had been treated with carcinogen did not undergo the destructive process that took place in control cells, indicating specificity

  5. Transition-Region/Coronal Signatures of Penumbral Microjets: Hi-C, SDO/AIA and Hinode (SOT/FG) Observations

    Science.gov (United States)

    Tiwari, Sanjiv K.; Alpert, Shane E.; Moore, Ronald L.; Winebarger, Amy R.

    2014-01-01

    Penumbral microjets are bright, transient features seen in the chromosphere of sunspot penumbrae. Katsuaka et al. (2007) noted their ubiquity and characterized them using the Ca II H-line filter on Hinode's Solar Optical Telescope (SOT). The jets are 1000{4000 km in length, 300{400 km in width, and last less than one minute. It was proposed that these penumbral microjets could contribute to the transition-region and coronal heating above sunspots. We examine whether these microjets appear in the transition-region (TR) and/or corona or are related{ temporally and spatially{ to similar brightenings in the TR and/or corona. First, we identify penumbral microjets with the SOT's Ca II H-line filter. The chosen sunspot is observed on July 11, 2012 from 18:50:00 UT to 20:00:00 UT at approx. 14 inches, -30 inches. We then examine the sunspot in the same field of view and at the same time in other wavelengths. We use the High Resolution Coronal Imager Telescope (Hi-C) at 193A and the 1600A, 304A, 171A, 193A, and 94A passbands of the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamic Observatory. We include examples of these jets and where they should appear in the other passbands, but find no signifcant association, except for a few jets with longer lifetimes and bigger sizes seen at locations in the penumbra with repeated stronger brightenings. We conclude that the normal microjets are not heated to transition-region/coronal temperatures, but the larger jets are.

  6. FIN5 positively regulates far-red light responses in Arabidopsis thaliana

    International Nuclear Information System (INIS)

    Cho, D.S.; Hong, S.H.; Nam, H.G.; Soh, M.S.

    2003-01-01

    We report the characterization of a semi-dominant mutation fin5-1 (far-red insensitive 5-1) of Arabidopsis, which was isolated from genetic screening of phytochrome A (phyA) signaling components. Plants with the fin5-1 mutation exhibited a long hypocotyl phenotype when grown under far-red (FR) light, but not under red light. Physiological analyses implied that FIN5 might be differentially involved in diverse responses that are regulated by phyA under continuous FR light. Anthocyanin accumulation, gravitropic response of hypocotyl growth, and FR light-preconditioned blocking of greening were also impaired in the fin5-1 mutant, whereas photoperiodic floral induction was not, if at all, significantly affected. Moreover, light-regulated expression of the CHS, PORA and PsbS genes was attenuated in fin5-1 mutant plants, while the light-induced expression of CAB was normal. The mutation exhibited semi-dominance regarding control of hypocotyl growth in FR light. We suggest that FIN5 defines a novel branch in the network of phyA signaling in Arabidopsis. (author)

  7. PRMT5 regulates IRES-dependent translation via methylation of hnRNP A1

    Science.gov (United States)

    Gao, Guozhen; Dhar, Surbhi

    2017-01-01

    Abstract The type II arginine methyltransferase PRMT5 is responsible for the symmetric dimethylation of histone to generate the H3R8me2s and H4R3me2s marks, which correlate with the repression of transcription. However, the protein level of a number of genes (MEP50, CCND1, MYC, HIF1a, MTIF and CDKN1B) are reported to be downregulated by the loss of PRMT5, while their mRNA levels remain unchanged, which is counterintuitive for PRMT5's proposed role as a transcription repressor. We noticed that the majority of the genes regulated by PRMT5, at the posttranscriptional level, express mRNA containing an internal ribosome entry site (IRES). Using an IRES-dependent reporter system, we established that PRMT5 facilitates the translation of a subset of IRES-containing genes. The heterogeneous nuclear ribonucleoprotein, hnRNP A1, is an IRES transacting factor (ITAF) that regulates the IRES-dependent translation of Cyclin D1 and c-Myc. We showed that hnRNP A1 is methylated by PRMT5 on two residues, R218 and R225, and that this methylation facilitates the interaction of hnRNP A1 with IRES RNA to promote IRES-dependent translation. This study defines a new role for PRMT5 regulation of cellular protein levels, which goes beyond the known functions of PRMT5 as a transcription and splicing regulator. PMID:28115626

  8. IGF-IR promotes prostate cancer growth by stabilizing α5β1 integrin protein levels.

    Directory of Open Access Journals (Sweden)

    Aejaz Sayeed

    Full Text Available Dynamic crosstalk between growth factor receptors, cell adhesion molecules and extracellular matrix is essential for cancer cell migration and invasion. Integrins are transmembrane receptors that bind extracellular matrix proteins and enable cell adhesion and cytoskeletal organization. They also mediate signal transduction to regulate cell proliferation and survival. The type 1 insulin-like growth factor receptor (IGF-IR mediates tumor cell growth, adhesion and inhibition of apoptosis in several types of cancer. We have previously demonstrated that β1 integrins regulate anchorage-independent growth of prostate cancer (PrCa cells by regulating IGF-IR expression and androgen receptor-mediated transcriptional functions. Furthermore, we have recently reported that IGF-IR regulates the expression of β1 integrins in PrCa cells. We have dissected the mechanism through which IGF-IR regulates β1 integrin expression in PrCa. Here we report that IGF-IR is crucial for PrCa cell growth and that β1 integrins contribute to the regulation of proliferation by IGF-IR. We demonstrate that β1 integrin regulation by IGF-IR does not occur at the mRNA level. Exogenous expression of a CD4 - β1 integrin cytoplasmic domain chimera does not interfere with such regulation and fails to stabilize β1 integrin expression in the absence of IGF-IR. This appears to be due to the lack of interaction between the β1 cytoplasmic domain and IGF-IR. We demonstrate that IGF-IR stabilizes the β1 subunit by protecting it from proteasomal degradation. The α5 subunit, one of the binding partners of β1, is also downregulated along with β1 upon IGF-IR knockdown while no change is observed in the expression of the α2, α3, α4, α6 and α7 subunits. Our results reveal a crucial mechanistic role for the α5β1 integrin, downstream of IGF-IR, in regulating cancer growth.

  9. Evaluation of hydrogen-Induced cracking resistance of the In625 laser coating system on a C-Mn steel substrate

    Directory of Open Access Journals (Sweden)

    Vicente Braz Trindade

    Full Text Available Abstract The corrosion of C-Mn steels in the presence of hydrogen sulfide (H2S represents a significant challenge to oil production and natural gas treatment facilities. The failure mechanism induced by hydrogen-induced cracking (HIC in a Inconel 625 coating / C-Mn steel has not been extensively investigated in the past. In the present work, an API 5CT steel was coated with In625 alloy using laser cladding and the HIC resistance of different regions, such as the coating surface, the substrate and HAZ, were evaluated. SEM observations illustrated that all HIC cracks were formed at the hard HAZ after 96h of exposure. No HIC cracks were observed in the substrate and the In625 coating after the same exposure duration. Pitting was recorded in the substrate caused by non-metallic inclusion dissolving.

  10. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern.

    Science.gov (United States)

    Farret, Marcel Marchiori

    2016-06-01

    This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) as one of the requirements to become diplomate by the BBO.

  11. Bombyx mori nucleopolyhedrovirus BM5 protein regulates progeny virus production and viral gene expression

    International Nuclear Information System (INIS)

    Kokusho, Ryuhei; Koh, Yoshikazu; Fujimoto, Masaru; Shimada, Toru; Katsuma, Susumu

    2016-01-01

    Bombyx mori nucleopolyhedrovirus (BmNPV) orf5 (Bm5) is a core gene of lepidopteran baculoviruses and encodes the protein with the conserved amino acid residues (DUF3627) in its C-terminus. Here, we found that Bm5 disruption resulted in lower titers of budded viruses and fewer numbers of occlusion bodies (OBs) in B. mori cultured cells and larvae, although viral genome replication was not affected. Bm5 disruption also caused aberrant expression of various viral genes at the very late stage of infection. Immunocytochemical analysis revealed that BM5 localized to the nuclear membrane. We also found that DUF3627 is important for OB production, transcriptional regulation of viral genes, and subcellular localization of BM5. Compared with wild-type BmNPV infection, larval death was delayed when B. mori larvae were infected with Bm5 mutants. These results suggest that BM5 is involved in progeny virus production and regulation of viral gene expression at the very late stage of infection. -- Highlights: •The role of BmNPV BM5 protein was examined in B. mori cultured cells and larvae. •BM5 contributes to efficient production of budded viruses and occlusion bodies. •BM5 regulates viral gene expression at the very late stage of infection. •BM5 dominantly localizes to the nuclear membrane. •Bm5 mutant showed v-cath down-regulation and resulting delay of larval death.

  12. Bombyx mori nucleopolyhedrovirus BM5 protein regulates progeny virus production and viral gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Kokusho, Ryuhei, E-mail: kokusho@ss.ab.a.u-tokyo.ac.jp; Koh, Yoshikazu; Fujimoto, Masaru; Shimada, Toru; Katsuma, Susumu, E-mail: katsuma@ss.ab.a.u-tokyo.ac.jp

    2016-11-15

    Bombyx mori nucleopolyhedrovirus (BmNPV) orf5 (Bm5) is a core gene of lepidopteran baculoviruses and encodes the protein with the conserved amino acid residues (DUF3627) in its C-terminus. Here, we found that Bm5 disruption resulted in lower titers of budded viruses and fewer numbers of occlusion bodies (OBs) in B. mori cultured cells and larvae, although viral genome replication was not affected. Bm5 disruption also caused aberrant expression of various viral genes at the very late stage of infection. Immunocytochemical analysis revealed that BM5 localized to the nuclear membrane. We also found that DUF3627 is important for OB production, transcriptional regulation of viral genes, and subcellular localization of BM5. Compared with wild-type BmNPV infection, larval death was delayed when B. mori larvae were infected with Bm5 mutants. These results suggest that BM5 is involved in progeny virus production and regulation of viral gene expression at the very late stage of infection. -- Highlights: •The role of BmNPV BM5 protein was examined in B. mori cultured cells and larvae. •BM5 contributes to efficient production of budded viruses and occlusion bodies. •BM5 regulates viral gene expression at the very late stage of infection. •BM5 dominantly localizes to the nuclear membrane. •Bm5 mutant showed v-cath down-regulation and resulting delay of larval death.

  13. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    International Nuclear Information System (INIS)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-01-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  14. Transcriptional Regulation of Apolipoprotein A5 Gene Expression by the Nuclear Receptor ROR alpha

    Energy Technology Data Exchange (ETDEWEB)

    Genoux, Annelise; Dehondt, Helene; Helleboid-Chapman, Audrey; Duhem, Christian; Hum, Dean W.; Martin, Genevieve; Pennacchio, Len; Staels, Bart; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-10-01

    Apolipoprotein A5 has recently been identified as a crucial determinant of plasma triglyceride levels. Our results showed that RORa up-regulates human APOA5 but has no effect on mouse apoa5 promoter. These data suggest an additional important physiological role for RORa in the regulation of genes involved in plasma triglyceride homeostasis in human and probably in the development of atherosclerosis

  15. Characterization of the aspects of osteoprogenitor cell interactions with physical tetracalcium phosphate anchorage on titanium implant surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Chia-Ling [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, Feng Chia University, Taichung 40724, Taiwan (China); Dental Medical Devices and Materials Research Center, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, Ya-Yuan; Liou, Cian-Hua [Alliance Global Technology Co., Ltd., Kaohsiung Medical Device Special Zone in Southern Taiwan Science Park, Kaohsiung 82151, Taiwan (China); Chen, Wen-Cheng, E-mail: wencchen@fcu.edu.tw [Advanced Medical Devices and Composites Laboratory, Department of Fiber and Composite Materials, Feng Chia University, Taichung 40724, Taiwan (China)

    2015-04-01

    Well-designed implants are used not only to modify the geometry of the implant but also to change the chemical properties of its surfaces. The present study aims to assess the biofunctional effects of tetracalcium phosphate (TTCP) particles as a physical anchor on the implant surface derived through sandblasting. The characteristics of the surface, cell viability, and alkaline phosphatase (ALP) activity toward osteoprogenitor cells (D1) were obtained. D1 cells were cultured on a plain surface that underwent sandblasting and acid etching (SLA) (control SLA group) and on different SLA surfaces with different anchoring TTCP rates (new test groups, M and H). The mean anchoring rates were 57% (M) and 74% (H), and the anchored thickness was estimated to range from 12.6 μm to 18.3 μm. Compared with the control SLA surface on Ti substrate, the new test groups with different TTCP anchoring rates (M and H) failed to improve cell proliferation significantly but had a well-differentiated D1 cell phenotype that enhanced ALP expression in the early stage of cell cultures, specifically, at day 7. Results suggest that the SLA surface with anchored TTCP can accelerate progenitor bone cell mineralization. This study shows the potential clinical application of the constructed geometry in TTCP anchorage on Ti for dental implant surface modification. - Highlights: • TTCP (tetracalcium phosphate) as a physical anchorage on implant is characterized. • Theoretical values of anchored thickness and capping areas were estimated. • TTCP anchored by sandblasting can accelerate progenitor bone cell mineralization. • TTCP anchored on SLA (sandblasting and acid etching) surface is a promising method.

  16. Characterization of the aspects of osteoprogenitor cell interactions with physical tetracalcium phosphate anchorage on titanium implant surfaces

    International Nuclear Information System (INIS)

    Ko, Chia-Ling; Chang, Ya-Yuan; Liou, Cian-Hua; Chen, Wen-Cheng

    2015-01-01

    Well-designed implants are used not only to modify the geometry of the implant but also to change the chemical properties of its surfaces. The present study aims to assess the biofunctional effects of tetracalcium phosphate (TTCP) particles as a physical anchor on the implant surface derived through sandblasting. The characteristics of the surface, cell viability, and alkaline phosphatase (ALP) activity toward osteoprogenitor cells (D1) were obtained. D1 cells were cultured on a plain surface that underwent sandblasting and acid etching (SLA) (control SLA group) and on different SLA surfaces with different anchoring TTCP rates (new test groups, M and H). The mean anchoring rates were 57% (M) and 74% (H), and the anchored thickness was estimated to range from 12.6 μm to 18.3 μm. Compared with the control SLA surface on Ti substrate, the new test groups with different TTCP anchoring rates (M and H) failed to improve cell proliferation significantly but had a well-differentiated D1 cell phenotype that enhanced ALP expression in the early stage of cell cultures, specifically, at day 7. Results suggest that the SLA surface with anchored TTCP can accelerate progenitor bone cell mineralization. This study shows the potential clinical application of the constructed geometry in TTCP anchorage on Ti for dental implant surface modification. - Highlights: • TTCP (tetracalcium phosphate) as a physical anchorage on implant is characterized. • Theoretical values of anchored thickness and capping areas were estimated. • TTCP anchored by sandblasting can accelerate progenitor bone cell mineralization. • TTCP anchored on SLA (sandblasting and acid etching) surface is a promising method

  17. Assessing the Frequency and Material Consequences of Collisions with Vessels Lying at an Anchorage in Line with IALA iWrap MkII

    Directory of Open Access Journals (Sweden)

    Hans-Christoph Burmeister

    2014-03-01

    Full Text Available This paper proposes a collision model for ships underway and temporary objects as an extension to state-of-the-art maritime risk assessment like IALA iWrap MkII. It gives a brief review of frequency modeling's and consequence calculation theory as well as its applications, before it analogously derives a model to assess the risk of anchorage areas. Subsequently, its benefit is demonstrated by an example scenario.

  18. Isolated scaphotrapeziotrapezoid osteoarthritis treatment using resurfacing arthroplasty with scaphoid anchorage.

    Science.gov (United States)

    Humada Álvarez, G; Simón Pérez, C; García Medrano, B; Faour Martín, O; Marcos Rodríguez, J J; Vega Castrillo, A; Martín Ferrero, M A

    The aim of this study is to show the results of scaphotrapeziotrapezoid (STT) joint osteoarthritis treatment performing resurfacing arthroplasty with scaphoid anchorage. An observational, descriptive and retrospective study was performed. Ten patients with isolated STT joint osteoarthritis were studied between 2013 and 2015. The mean follow-up time was 26months. Clinical results, functional and subjective scores were reviewed. The patients were satisfied, achieving an average of 2.1 (0-3) on the VAS score and 16 (2 to 28) in the DASH questionnaire, and returning to work in the first three months post-surgery. Recovery of range of motion compared to the contralateral wrist was 96% in extension, 95% in flexion, 87% in ulnar deviation and 91% in radial deviation. The average handgrip strength of the wrist was 95% and pinch strength was 95% compared to the contralateral side. There were no intraoperative complications or alterations in postoperative carpal alignment. Resurfacing arthroplasty is proposed as a good and novel alternative in treating isolated SST joint arthritis. Achieving the correct balance between the strength and mobility of the wrist, without causing carpal destabilisation, is important to obtain satisfactory clinical and functional results. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  19. CsMYB5a and CsMYB5e from Camellia sinensis differentially regulate anthocyanin and proanthocyanidin biosynthesis.

    Science.gov (United States)

    Jiang, Xiaolan; Huang, Keyi; Zheng, Guangshun; Hou, Hua; Wang, Peiqiang; Jiang, Han; Zhao, Xuecheng; Li, Mingzhuo; Zhang, Shuxiang; Liu, Yajun; Gao, Liping; Zhao, Lei; Xia, Tao

    2018-05-01

    Tea is one of the most widely consumed nonalcoholic beverages worldwide. Polyphenols are nutritional compounds present in the leaves of tea plants. Although numerous genes are functionally characterized to encode enzymes that catalyze the formation of diverse polyphenolic metabolites, transcriptional regulation of those different pathways such as late steps of the proanthcoyanidin (PA) pathway remains unclear. In this study, using different tea transcriptome databases, we screened at least 140 R2R3-MYB transcription factors (TFs) and grouped them according to the basic function domains of the R2R3 MYB TF superfamily. Among 140 R2R3 TFs, CsMYB5a and CsMYB5e were chosen for analysis because they may be involved in PA biosynthesis regulation. CsMYB5a-overexpressing tobacco plants exhibited downregulated anthocyanin accumulation but a high polymeric PA content in the flowers. Overexpression of CsMYB5e in tobacco plants did not change the anthocyanin content but increased the dimethylaminocinnamaldehyde-stained PA content. RNA-seq and qRT-PCR analyses revealed that genes related to PA and anthocyanin biosynthesis pathways were markedly upregulated in both CsMYB5a- and CsMYB5e-overexpressing flowers. Three UGTs and four GSTs were identified as involved in PA and anthocyanin glycosylation and transportation in transgenic plants. These results provide new insights into the regulation of PA and anthocyanin biosynthesis in Camellia sinensis. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. 7 CFR 915.305 - Florida Avocado Container Regulation 5.

    Science.gov (United States)

    2010-01-01

    ... Regulation 5. (a) No handler shall handle any avocados for the fresh market from the production area to any... handler shall handle any avocados for the fresh market in 20 bushel plastic field bins to destinations inside the production area. (d) Avocados handled for the fresh market in containers other than those...

  1. An ATF4-ATG5 signaling in hypothalamic POMC neurons regulates obesity.

    Science.gov (United States)

    Xiao, Yuzhong; Deng, Yalan; Yuan, Feixiang; Xia, Tingting; Liu, Hao; Li, Zhigang; Chen, Shanghai; Liu, Zhixue; Ying, Hao; Liu, Yi; Zhai, Qiwei; Guo, Feifan

    2017-06-03

    ATF4 (activating transcription factor 4) is an important transcription factor that has many biological functions, while its role in hypothalamic POMC (pro-opiomelanocortin-α) neurons in the regulation of energy homeostasis has not been explored. We recently discovered that mice with an Atf4 deletion specific to POMC neurons (PAKO mice) are lean and have higher energy expenditure. Furthermore, these mice are resistant to high-fat diet (HFD)-induced obesity and obesity-related metabolic disorders. Mechanistically, we found the expression of ATG5 (autophagy-related 5) is upregulated in POMC neurons of PAKO mice, and ATF4 regulates ATG5 expression by binding directly to its promoter. Mice with Atf4 and Atg5 double knockout in POMC neurons have reduced energy expenditure and gain more fat mass compared with PAKO mice under a HFD. Finally, the effect of Atf4 knockout in POMC neurons is possibly mediated by enhanced ATG5-dependent macroautophagy/autophagy and α-melanocyte-stimulating hormone (α-MSH) production in the hypothalamus. Together, this work not only identifies a beneficial role for ATF4 in hypothalamic POMC neurons in the regulation of obesity, but also provides a new potential therapeutic target for obesity and obesity-related metabolic diseases.

  2. Orthodontic retreatment using anchorage with miniplate to camouflage a Class III skeletal pattern

    Directory of Open Access Journals (Sweden)

    Marcel Marchiori Farret

    Full Text Available ABSTRACT This manuscript describes the treatment of a 27-year-old patient who was previously treated with two maxillary first premolar extractions. The patient had skeletal Class III malocclusion, Class III canine relationship, anterior crossbite, and a concave profile. As the patient refused orthognathic surgery, a miniplate was used on the right side of the lower arch as an anchorage unit after the extraction of mandibular first premolars, aiding the retraction of anterior teeth. At the end of treatment, anterior crossbite was corrected, in which first molars and canines were in a Class I relationship, and an excellent intercuspation was reached. Furthermore, patient's profile remarkably improved as a result of mandibular incisor retraction. A 30-month follow-up showed good stability of the results obtained. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO as one of the requirements to become diplomate by the BBO.

  3. 4Cin: A computational pipeline for 3D genome modeling and virtual Hi-C analyses from 4C data.

    Directory of Open Access Journals (Sweden)

    Ibai Irastorza-Azcarate

    2018-03-01

    Full Text Available The use of 3C-based methods has revealed the importance of the 3D organization of the chromatin for key aspects of genome biology. However, the different caveats of the variants of 3C techniques have limited their scope and the range of scientific fields that could benefit from these approaches. To address these limitations, we present 4Cin, a method to generate 3D models and derive virtual Hi-C (vHi-C heat maps of genomic loci based on 4C-seq or any kind of 4C-seq-like data, such as those derived from NG Capture-C. 3D genome organization is determined by integrative consideration of the spatial distances derived from as few as four 4C-seq experiments. The 3D models obtained from 4C-seq data, together with their associated vHi-C maps, allow the inference of all chromosomal contacts within a given genomic region, facilitating the identification of Topological Associating Domains (TAD boundaries. Thus, 4Cin offers a much cheaper, accessible and versatile alternative to other available techniques while providing a comprehensive 3D topological profiling. By studying TAD modifications in genomic structural variants associated to disease phenotypes and performing cross-species evolutionary comparisons of 3D chromatin structures in a quantitative manner, we demonstrate the broad potential and novel range of applications of our method.

  4. 76 FR 52599 - Anchorage Regulations; Wells, ME

    Science.gov (United States)

    2011-08-23

    ... shape in the ``Actions'' column. If you submit your comments by mail or hand delivery, submit them in an... or shapes as per Rule 30 of the Inland Navigation Rules (33 U.S.C. 2030) when at anchor in a special... limited due to depth (less than or equal to 18 feet). Small Entities Under the Regulatory Flexibility Act...

  5. Characterization of mutagen-activated cellular oncogenes that confer anchorage independence to human fibroblasts and tumorigenicity to NIH 3T3 cells: Sequence analysis of an enzymatically amplified mutant HRAS allele

    International Nuclear Information System (INIS)

    Stevens, C.W.; Manoharan, T.H.; Fahl, W.E.

    1988-01-01

    Treatment of diploid human fibroblasts with an alkylating mutagen has been shown to induce stable, anchorage-independent cell populations at frequencies consistent with an activating mutation. After treatment of human foreskin fibroblasts with the mutagen benzo[α]pyrene (±)anti-7,8-dihydrodiol 9,10-epoxide and selection in soft agar, 17 anchorage-independent clones were isolated and expanded, and their cellular DNA was used to cotransfect NIH 3T3 cells along with pSV2neo. DNA from 11 of the 17 clones induced multiple NIH 3T3 cell tumors in recipient nude mice. Southern blot analyses showed the presence of human Alu repetitive sequences in all of the NIH 3T3 tumor cell DNAs. Intact, human HRAS sequences were observed in 2 of the 11 tumor groups, whereas no hybridization was detected when human KRAS or NRAS probes were used. Slow-migrating ras p21 proteins, consistent with codon 12 mutations, were observed in the same two NIH 3T3 tumor cell groups that contained the human HRAS bands. Genomic DNA from one of these two human anchorage-independent cell populations (clone 21A) was used to enzymatically amplify a portion of exon 1 of the HRAS gene. The results demonstrate that exposure of normal human cells to a common environmental mutagen yields HRAS GC → TA codon 12 transversions that have been commonly observed in human tumors

  6. The Wnt-target gene Dlk-1 is regulated by the Prmt5-associated factor Copr5 during adipogenic conversion

    Directory of Open Access Journals (Sweden)

    Conception Paul

    2015-02-01

    Full Text Available Protein arginine methyl transferase 5 (Prmt5 regulates various differentiation processes, including adipogenesis. Here, we investigated adipogenic conversion in cells and mice in which Copr5, a Prmt5- and histone-binding protein, was genetically invalidated. Compared to control littermates, the retroperitoneal white adipose tissue (WAT of Copr5 KO mice was slightly but significantly reduced between 8 and 16 week/old and contained fewer and larger adipocytes. Moreover, the adipogenic conversion of Copr5 KO embryoid bodies (EB and of primary embryo fibroblasts (Mefs was markedly delayed. Differential transcriptomic analysis identified Copr5 as a negative regulator of the Dlk-1 gene, a Wnt target gene involved in the control of adipocyte progenitors cell fate. Dlk-1 expression was upregulated in Copr5 KO Mefs and the Vascular Stromal Fraction (VSF of Copr5 KO WAT. Chromatin immunoprecipitation (ChIP show that the ablation of Copr5 has impaired both the recruitment of Prmt5 and β-catenin at the Dlk-1 promoter. Overall, our data suggest that Copr5 is involved in the transcriptional control exerted by the Wnt pathway on early steps of adipogenesis.

  7. Uridine 5'-Monophosphate Synthase Is Transcriptionally Regulated by Pyrimidine Levels in Nicotiana plumbaginifolia

    Science.gov (United States)

    Santoso; Thornburg

    1998-02-01

    To understand the regulation and expression of pyrimidine biosynthesis in plants, we have examined the effect of the metabolic inhibitor 5-fluoroorotic acid (FOA) on uridine-5'-monophosphate synthase (UMPSase) expression in cell cultures of Nicotiana plumbaginifolia. UMPSase is the rate-limiting step of pyrimidine biosynthesis in plants. Addition of FOA causes an up-regulation of UMPSase enzyme activity in cell cultures after a lag phase of several days. Western-blot analysis demonstrated that the up-regulation in enzyme activity was caused by increased expression of the UMPSase protein. Northern-blot analysis demonstrated a higher level of UMPSase mRNA in the FOA-induced tissues than in control tissues. Run-on transcriptional assays showed that the UMPSase gene was transcriptionally activated after FOA treatment. The mechanism of toxicity of FOA is through thymine starvation. We found that addition of thymine abrogated the FOA-mediated up-regulation of UMPSase. In addition, methotrexate and aminopterin, which affect thymine levels by inhibiting dihydrofolate reductase, also up-regulate UMPSase in N. plumbaginifolia cells.

  8. Regulation of Translational Efficiency by Disparate 5′-UTRs of PPARγ Splice Variants

    Directory of Open Access Journals (Sweden)

    Shawn McClelland

    2009-01-01

    Full Text Available The PPAR-γ gene encodes for at least 7 unique transcripts due to alternative splicing of five exons in the 5′-untranslated region (UTR. The translated region is encoded by exons 1–6, which are identical in all isoforms. This study investigated the role of the 5′-UTR in regulating the efficiency with which the message is translated to protein. A coupled in vitro transcription-translation assay demonstrated that PPAR-γ1, -γ2, and -γ5 are efficiently translated, whereas PPAR-γ4 and -γ7 are poorly translated. An in vivo reporter gene assay using each 5′-UTR upstream of the firefly luciferase gene showed that the 5′-UTRs for PPAR-γ1, -γ2, and -γ4 enhanced translation, whereas the 5′-UTRs for PPAR-γ5 and -γ7 inhibited translation. Models of RNA secondary structure, obtained by the mfold software, were used to explain the mechanism of regulation by each 5′-UTR. In general, it was found that the translational efficiency was inversely correlated with the stability of the mRNA secondary structure, the presence of base-pairing in the consensus Kozak sequence, the number of start codons in the 5′-UTR, and the length of the 5′-UTR. A better understanding of posttranscriptional regulation of translation will allow modulation of protein levels without altering transcription.

  9. Memory Enhancement by Targeting Cdk5 Regulation of NR2B

    Science.gov (United States)

    Plattner, Florian; Hernandéz, Adan; Kistler, Tara M.; Pozo, Karine; Zhong, Ping; Yuen, Eunice Y.; Tan, Chunfeng; Hawasli, Ammar H.; Cooke, Sam F.; Nishi, Akinori; Guo, Ailan; Wiederhold, Thorsten; Yan, Zhen; Bibb, James A.

    2014-01-01

    SUMMARY Many psychiatric and neurological disorders are characterized by learning and memory deficits, for which cognitive enhancement is considered a valid treatment strategy. The N-methyl-D-aspartate receptor (NMDAR) is a prime target for the development of cognitive enhancers due to its fundamental role in learning and memory. In particular, the NMDAR subunit NR2B improves synaptic plasticity and memory when over-expressed in neurons. However, NR2B regulation is not well understood and no therapies potentiating NMDAR function have been developed. Here, we show that serine 1116 of NR2B is phosphorylated by cyclin-dependent kinase 5 (Cdk5). Cdk5-dependent NR2B phosphorylation is regulated by neuronal activity and controls the receptor’s cell surface expression. Disrupting NR2B-Cdk5 interaction using a small interfering peptide (siP) increases NR2B surface levels, facilitates synaptic transmission, and improves memory formation in vivo. Our results reveal a novel regulatory mechanism critical to NR2B function that can be targeted for the development of cognitive enhancers. PMID:24607229

  10. Down-regulation of microRNA-142-5p attenuates oxygen-glucose deprivation and reoxygenation-induced neuron injury through up-regulating Nrf2/ARE signaling pathway.

    Science.gov (United States)

    Wang, Ning; Zhang, Lingmin; Lu, Yang; Zhang, Mingxin; Zhang, Zhenni; Wang, Kui; Lv, Jianrui

    2017-05-01

    MicroRNAs (miRNAs) play vital roles in regulating neuron survival during cerebral ischemia/reperfusion injury. miR-142-5p is reported to be an important regulator of cellular survival. However, little is known about the role of miR-142-5p in regulating neuron survival during cerebral ischemia/reperfusion injury. In this study, we aimed to investigate the precise function and mechanism of miR-142-5p in the regulation of neuron ischemia/reperfusion injury using a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury in hippocampal neurons in vitro. We found that miR-142-5p was induced in hippocampal neurons with OGD/R treatment. The inhibition of miR-142-5p attenuated OGD/R-induced cell injury and oxidative stress, whereas the overexpression of miR-142-5p aggravated them. Nuclear factor erythroid 2-related factor 2 (Nrf2) was identified as a target gene of miR-142-5p. Moreover, miR-142-5p regulated Nrf2 expression and downstream signaling. Knockdown of Nrf2 abolished the protective effects of miR-142-5p suppression. In addition, we showed an inverse correlation relationship between miR-142-5p and Nrf2 in an in vivo model of middle cerebral artery occlusion in rats. Taken together, these results suggest that miR-142-5p contributes to OGD/R-induced cell injury and the down-regulation of miR-142-5p attenuates OGD/R-induced neuron injury through promoting Nrf2 expression. Our study provides a novel insight into understanding the molecular pathogenesis of cerebral ischemia/reperfusion injury and indicates a potential therapeutic target for the treatment of cerebral ischemia/reperfusion injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Maxillary protraction in adult cleft lip and palate by a rigid external distraction device with dentoskeletal anchorage

    Science.gov (United States)

    Akarsu, Bengisu; Taner, Tulin; Tuncbilek, Gokhan; Mavili, M. Emin

    2012-01-01

    Objective: The objective is to evaluate the effects of maxillary distraction osteogenesis (DO) in an adult patient with unilateral cleft lip and palate (UCLP) by using a rigid external distraction (RED) device with dentoskeletal anchorage. Method: 31-year-old male patient with UCLP with severe maxillary hypoplasia, dolichofacial growth pattern, negative overjet and 1.5 mm openbite. After pre-surgical orthodontic treatment, an intra-oral appliance was modified to prevent extrusion of the molars and clockwise rotation of the mandible. Stainless steel plates were soldered bilaterally to the intra oral appliance at the level of canines. During surgery, miniplates were inserted in the maxillary segment and fixed to the plates of the intra oral appliance with screws. Results: The mean distraction length was 12 mm immediately after DO. SNA increased from 73o to 82o after distraction. A significant advancement of the maxilla and correction of the sagittal Class III skeletal relationship was achieved. The vertical position of the mandible and the face was kept stable, and the soft tissue profile became more balanced. Conclusion: This intra oral appliance design achieved desired skeletal changes during maxillary protraction with RED device in dolichofacial CLP patient. Occlusion and facial profile changes was found to be stable in 1-year follow-up. PMID:22509125

  12. Maxillary protraction in adult cleft lip and palate by a rigid external distraction device with dentoskeletal anchorage.

    Science.gov (United States)

    Akarsu, Bengisu; Taner, Tulin; Tuncbilek, Gokhan; Mavili, M Emin

    2012-04-01

    The objective is to evaluate the effects of maxillary distraction osteogenesis (DO) in an adult patient with unilateral cleft lip and palate (UCLP) by using a rigid external distraction (RED) device with dentoskeletal anchorage. 31-year-old male patient with UCLP with severe maxillary hypoplasia, dolichofacial growth pattern, negative overjet and 1.5 mm openbite. After pre-surgical orthodontic treatment, an intra-oral appliance was modified to prevent extrusion of the molars and clockwise rotation of the mandible. Stainless steel plates were soldered bilaterally to the intra oral appliance at the level of canines. During surgery, miniplates were inserted in the maxillary segment and fixed to the plates of the intra oral appliance with screws. The mean distraction length was 12 mm immediately after DO. SNA increased from 73o to 82o after distraction. A significant advancement of the maxilla and correction of the sagittal Class III skeletal relationship was achieved. The vertical position of the mandible and the face was kept stable, and the soft tissue profile became more balanced. This intra oral appliance design achieved desired skeletal changes during maxillary protraction with RED device in dolichofacial CLP patient. Occlusion and facial profile changes was found to be stable in 1-year follow-up.

  13. FXYD5: Na+/ K+-ATPase Regulator in Health and Disease.

    Directory of Open Access Journals (Sweden)

    Irina eLubarski Gotliv

    2016-03-01

    Full Text Available FXYD5 (Dysadherin, RIC is a single span type I membrane protein that plays multiple roles in regulation of cellular functions. It is expressed in a variety of epithelial tissues and acts as an auxiliary subunit of the Na+/ K+-ATPase. During the past decade, a correlation between enhanced expression of FXYD5 and tumor progression has been established for various tumor types. In this review, current knowledge on FXYD5 is discussed, including experimental data on the functional effects of FXYD5 on the Na+/ K+-ATPase. FXYD5 modulates cellular junctions, influences chemokine production, and affects cell adhesion. The accumulated data may provide a basis for understanding the molecular mechanisms underlying FXYD5 mediated phenotypes.

  14. 33 CFR 110.77 - Amistad Reservoir, Tex.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Amistad Reservoir, Tex. 110.77... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.77 Amistad Reservoir, Tex. (a) Diablo East, Tex. That portion of the Amistad Reservoir enclosed by a line connecting the following points, excluding a 300-foot...

  15. Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure.

    Science.gov (United States)

    Dong, Changsheng; Yang, Shanshan; Fan, Ruiwen; Ji, Kaiyuan; Zhang, Junzhen; Liu, Xuexian; Hu, Shuaipeng; Xie, Jianshan; Liu, Yu; Gao, Wenjun; Wang, Haidong; Yao, Jianbo; Smith, George W; Herrid, Muren

    2017-10-23

    The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (MITF) and paired-box 3 (PAX3) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of MITF and PAX3. Cdk5 knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (K10) resulting from Cdk5 knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of Cdk5 in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system.

  16. Role of postreplication repair in transformation of human fibroblasts to anchorage independence

    International Nuclear Information System (INIS)

    Boyer, J.C.; Kaufmann, W.K.; Cordeiro-Stone, M.

    1991-01-01

    Cellular capacity for postreplication repair (PRR) and sensitivity to transformation to anchorage independence (AI) were quantified in normal foreskin and xeroderma pigmentosum (XP) variant fibroblasts after treatment with UV or benzo(a)pyrene-diol-epoxide I (BPDE-I). PRR is defined here as a collection of pathways that facilitate the replication of DNA damaged by genotoxic agents. It is recognized biochemically as the process by which nascent DNA grows longer than the average distance between two lesions in the DNA template. PRR refers more directly to the elimination of gaps in the daughter-strand DNA by mechanisms which remain to be determined for human cells, but which may include translesion replication and recombination. PRR was measured in diploid human fibroblasts by analysis of the dose kinetics for inhibition of DNA strand growth in carcinogen-treated cells. Logarithmically growing foreskin fibroblasts (NHF1) displayed D0 values of 4.3 J/m 2 and 0.14 microM for the inhibition of DNA synthesis in active replicons by UV and BPDE-I, respectively. XP variant cells (CRL1162) exhibited corresponding D0 values of 1.5 J/m 2 and 0.16 microM. The increased sensitivity to inhibition of DNA replication by UV in these XP variant fibroblasts (2.9-fold greater than normal) was mirrored by an enhanced frequency of transformation to AI. XP variant fibroblasts (CRL1162) were 3.2 times more sensitive to transformation to AI by UV than were the normal foreskin fibroblasts. As predicted by the PRR studies, both cell types exhibited similar frequencies of AI colonies induced by BPDE-I. Apparent thresholds were observed for induction of AI by UV (normal fibroblasts, 2.7 J/m 2 ; XP variant fibroblasts, 0.3 J/m 2 ) and BPDE-I (both, 0.05 microM)

  17. Subcellular localization and regulation of type-1C and type-5 phosphodiesterases

    International Nuclear Information System (INIS)

    Dolci, Susanna; Belmonte, Alessia; Santone, Rocco; Giorgi, Mauro; Pellegrini, Manuela; Carosa, Eleonora; Piccione, Emilio; Lenzi, Andrea; Jannini, Emmanuele A.

    2006-01-01

    We investigated the subcellular localization of PDE5 in in vitro human myometrial cells. We demonstrated for First time that PDE5 is localized in discrete cytoplasmic foci and vesicular compartments corresponding to centrosomes. We also found that PDE5 intracellular localization is not cell- or species-specific, as it is conserved in different animal and human cells. PDE5 protein levels are strongly regulated by the mitotic activity of the smooth muscle cells (SMCs), as they were increased in quiescent, contractile myometrial cultures, and conditions in which proliferation was inhibited. In contrast, PDE1C levels decreased in all conditions that inhibited proliferation. This mirrored the enzymatic activity of both PDE5 and PDE1C. Increasing cGMP intracellular levels by dbcGMP or sildenafil treatments did not block proliferation, while dbcAMP inhibited myometrial cell proliferation. Together, these results suggest that PDE5 regulation of cGMP intracellular levels is not involved in the control of SMC cycle progression, but may represent one of the markers of the contractile phenotype

  18. Experimental provocation of 'ice-cream headache' by ice cubes and ice water.

    Science.gov (United States)

    Mages, Stephan; Hensel, Ole; Zierz, Antonia Maria; Kraya, Torsten; Zierz, Stephan

    2017-04-01

    Background There are various studies on experimentally provoked 'ice-cream headache' or 'headache attributed to ingestion or inhalation of a cold stimulus' (HICS) using different provocation protocols. The aim of this study was to compare two provocation protocols. Methods Ice cubes pressed to the palate and fast ingestion of ice water were used to provoke HICS and clinical features were compared. Results The ice-water stimulus provoked HICS significantly more often than the ice-cube stimulus (9/77 vs. 39/77). Ice-water-provoked HICS had a significantly shorter latency (median 15 s, range 4-97 s vs. median 68 s, range 27-96 s). There was no difference in pain localisation. Character after ice-cube stimulation was predominantly described as pressing and after ice-water stimulation as stabbing. A second HICS followed in 10/39 (26%) of the headaches provoked by ice water. Lacrimation occurred significantly more often in volunteers with than in those without HICS. Discussion HICS provoked by ice water was more frequent, had a shorter latency, different pain character and higher pain intensity than HICS provoked by ice cubes. The finding of two subsequent HICS attacks in the same volunteers supports the notion that two types of HICS exist. Lacrimation during HICS indicates involvement of the trigeminal-autonomic reflex.

  19. Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development

    OpenAIRE

    Zhu, Yong-Chuan; Li, Dan; Wang, Lu; Lu, Bin; Zheng, Jing; Zhao, Shi-Lin; Zeng, Rong; Xiong, Zhi-Qi

    2013-01-01

    The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD...

  20. CED-10/Rac1 regulates endocytic recycling through the RAB-5 GAP TBC-2.

    Directory of Open Access Journals (Sweden)

    Lin Sun

    Full Text Available Rac1 is a founding member of the Rho-GTPase family and a key regulator of membrane remodeling. In the context of apoptotic cell corpse engulfment, CED-10/Rac1 acts with its bipartite guanine nucleotide exchange factor, CED-5/Dock180-CED-12/ELMO, in an evolutionarily conserved pathway to promote phagocytosis. Here we show that in the context of the Caenorhabditis elegans intestinal epithelium CED-10/Rac1, CED-5/Dock180, and CED-12/ELMO promote basolateral recycling. Furthermore, we show that CED-10 binds to the RAB-5 GTPase activating protein TBC-2, that CED-10 contributes to recruitment of TBC-2 to endosomes, and that recycling cargo is trapped in recycling endosomes in ced-12, ced-10, and tbc-2 mutants. Expression of GTPase defective RAB-5(Q78L also traps recycling cargo. Our results indicate that down-regulation of early endosome regulator RAB-5/Rab5 by a CED-5, CED-12, CED-10, TBC-2 cascade is an important step in the transport of cargo through the basolateral recycling endosome for delivery to the plasma membrane.

  1. 5 CFR 735.103 - What other regulations pertain to employee conduct?

    Science.gov (United States)

    2010-01-01

    ... employee's violation of those regulations may cause the employee's agency to take disciplinary action, or corrective action as that term is used in 5 CFR part 2635. Such disciplinary action or corrective action may...

  2. 25 CFR 900.5 - Effect of these regulations on Federal program guidelines, manual, or policy directives.

    Science.gov (United States)

    2010-04-01

    ... SELF-DETERMINATION AND EDUCATION ASSISTANCE ACT General Provisions § 900.5 Effect of these regulations... 25 Indians 2 2010-04-01 2010-04-01 false Effect of these regulations on Federal program guidelines, manual, or policy directives. 900.5 Section 900.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE...

  3. The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Yuta; Katayama, Chisako [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Shinohara, Miki; Shinohara, Akira [Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Maekawa, Shohei [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Miyamoto, Masaaki, E-mail: miya@kobe-u.ac.jp [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan)

    2013-11-29

    Highlights: •Multiple functions of Rab5 GTPase in fission yeast were found. •Roles of Rab5 in fission yeast were discussed. •Relation between Rab5 and actin cytoskeleton were discussed. -- Abstract: Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our data strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions.

  4. The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast

    International Nuclear Information System (INIS)

    Tsukamoto, Yuta; Katayama, Chisako; Shinohara, Miki; Shinohara, Akira; Maekawa, Shohei; Miyamoto, Masaaki

    2013-01-01

    Highlights: •Multiple functions of Rab5 GTPase in fission yeast were found. •Roles of Rab5 in fission yeast were discussed. •Relation between Rab5 and actin cytoskeleton were discussed. -- Abstract: Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our data strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions

  5. Flotillins Regulate Focal Adhesions by Interacting with α-Actinin and by Influencing the Activation of Focal Adhesion Kinase

    Directory of Open Access Journals (Sweden)

    Antje Banning

    2018-04-01

    Full Text Available Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.

  6. High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila

    NARCIS (Netherlands)

    Ramírez, Fidel; Lingg, Thomas; Toscano, Sarah; Lam, Kin Chung; Georgiev, Plamen; Chung, Ho-Ryun; Lajoie, Bryan R; de Wit, Elzo; Zhan, Ye; de Laat, Wouter; Dekker, Job; Manke, Thomas; Akhtar, Asifa

    2015-01-01

    Dosage compensation mechanisms provide a paradigm to study the contribution of chromosomal conformation toward targeting and spreading of epigenetic regulators over a specific chromosome. By using Hi-C and 4C analyses, we show that high-affinity sites (HAS), landing platforms of the male-specific

  7. Allosteric regulation by oleamide of the binding properties of 5-hydroxytryptamine7 receptors.

    Science.gov (United States)

    Hedlund, P B; Carson, M J; Sutcliffe, J G; Thomas, E A

    1999-12-01

    Oleamide belongs to a family of amidated lipids with diverse biological activities, including sleep induction and signaling modulation of several 5-hydroxytryptamine (5-HT) receptor subtypes, including 5-HT1A, 5-HT2A/2C, and 5-HT7. The 5-HT7 receptor, predominantly localized in the hypothalamus, hippocampus, and frontal cortex, stimulates cyclic AMP formation and is thought to be involved in the regulation of sleep-wake cycles. Recently, it was proposed that oleamide acts at an allosteric site on the 5-HT7 receptor to regulate cyclic AMP formation. We have further investigated the interaction between oleamide and 5-HT7 receptors by performing radioligand binding assays with HeLa cells transfected with the 5-HT7 receptor. Methiothepin, clozapine, and 5-HT all displaced specific [3H]5-HT (100 nM) binding, with pK(D) values of 7.55, 7.85, and 8.39, respectively. Oleamide also displaced [3H]5-HT binding, but the maximum inhibition was only 40% of the binding. Taking allosteric (see below) cooperativity into account, a K(D) of 2.69 nM was calculated for oleamide. In saturation binding experiments, oleamide caused a 3-fold decrease in the affinity of [3H]5-HT for the 5-HT7 receptor, without affecting the number of binding sites. A Schild analysis showed that the induced shift in affinity of [3H]5-HT reached a plateau, unlike that of a competitive inhibitor, illustrating the allosteric nature of the interaction between oleamide and the 5-HT7 receptor. Oleic acid, the product of oleamide hydrolysis, had a similar effect on [3H]5-HT binding, whereas structural analogs of oleamide, trans-9,10-octadecenamide, cis-8,9-octadecenamide, and erucamide, did not alter [3H]5-HT binding significantly. The findings support the hypothesis that oleamide acts via an allosteric site on the 5-HT7 receptor regulating receptor affinity.

  8. Peptide array-based interaction assay of solid-bound peptides and anchorage-dependant cells and its effectiveness in cell-adhesive peptide design.

    Science.gov (United States)

    Kato, Ryuji; Kaga, Chiaki; Kunimatsu, Mitoshi; Kobayashi, Takeshi; Honda, Hiroyuki

    2006-06-01

    Peptide array, the designable peptide library covalently synthesized on cellulose support, was applied to assay peptide-cell interaction, between solid-bound peptides and anchorage-dependant cells, to study objective peptide design. As a model case, cell-adhesive peptides that could enhance cell growth as tissue engineering scaffold material, was studied. On the peptide array, the relative cell-adhesion ratio of NIH/3T3 cells was 2.5-fold higher on the RGDS (Arg-Gly-Asp-Ser) peptide spot as compared to the spot with no peptide, thus indicating integrin-mediated peptide-cell interaction. Such strong cell adhesion mediated by the RGDS peptide was easily disrupted by single residue substitution on the peptide array, thus indicating that the sequence recognition accuracy of cells was strictly conserved in our optimized scheme. The observed cellular morphological extension with active actin stress-fiber on the RGD motif-containing peptide supported our strategy that peptide array-based interaction assay of solid-bound peptide and anchorage-dependant cells (PIASPAC) could provide quantitative data on biological peptide-cell interaction. The analysis of 180 peptides obtained from fibronectin type III domain (no. 1447-1629) yielded 18 novel cell-adhesive peptides without the RGD motif. Taken together with the novel candidates, representative rules of ineffective amino acid usage were obtained from non-effective candidate sequences for the effective designing of cell-adhesive peptides. On comparing the amino acid usage of the top 20 and last 20 peptides from the 180 peptides, the following four brief design rules were indicated: (i) Arg or Lys of positively charged amino acids (except His) could enhance cell adhesion, (ii) small hydrophilic amino acids are favored in cell-adhesion peptides, (iii) negatively charged amino acids and small amino acids (except Gly) could reduce cell adhesion, and (iv) Cys and Met could be excluded from the sequence combination since they have

  9. Effect of samarium in corrosion and microstructure of Al-5Zn-0.5Cu as low driving voltage sacrificial anode

    Science.gov (United States)

    Pratesa, Yudha; Ferdian, Deni; Ramadhan, Fajar Yusya; Maulana, Bramuda

    2018-05-01

    Sacrificial Anode Low voltage is the latest generation of the sacrificial anode that can prevent the occurrence of Hydrogen Cracking (HIC) due to overprotection. The Al-5n-0.5Cu alloy showed the potential to be developed as the new sacrificial anode. However, the main problem is copper made Al2Cu intermetallic in grain boundary. Samarium is added to modify the shape of the intermetallic to make it finer and make the corrosion uniform. Several characterizations were conducted to analyze the effect of Samarium. Scanning electron microscope (SEM) and Energy dispersive spectroscopy was used to analyzed the microstructure of the alloy. Metallography preparation was prepared for SEM analysis. Corrosion behavior was characterized by cyclic polarization in 3.5% NaCl solution. The results show samarium can change the shape of intermetallic and refine the grains. In addition, samarium makes better pitting resistance and exhibits a tendency for uniform corrosion. It is indicated by the loop reduction (ΔEpit-prot). Current density increased as an effect of samarium addition from 6x10-5 Ampere (Al-5Zn-0.5Cu) to 2.5x10-4 Ampere (Al-5Zn-0.5Cu-0.5Sm). Steel potential protection increased after addition of samarium which is an indication the possibility of Al-Zn-Cu-Sm to be used as low voltage sacrificial anode.

  10. Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes

    Science.gov (United States)

    Hata, Kenji; Takashima, Rikako; Amano, Katsuhiko; Ono, Koichiro; Nakanishi, Masako; Yoshida, Michiko; Wakabayashi, Makoto; Matsuda, Akio; Maeda, Yoshinobu; Suzuki, Yutaka; Sugano, Sumio; Whitson, Robert H.; Nishimura, Riko; Yoneda, Toshiyuki

    2013-11-01

    Histone modification, a critical step for epigenetic regulation, is an important modulator of biological events. Sox9 is a transcription factor critical for endochondral ossification; however, proof of its epigenetic regulation remains elusive. Here we identify AT-rich interactive domain 5b (Arid5b) as a transcriptional co-regulator of Sox9. Arid5b physically associates with Sox9 and synergistically induces chondrogenesis. Growth of Arid5b-/- mice is retarded with delayed endochondral ossification. Sox9-dependent chondrogenesis is attenuated in Arid5b-deficient cells. Arid5b recruits Phf2, a histone lysine demethylase, to the promoter region of Sox9 target genes and stimulates H3K9me2 demethylation of these genes. In the promoters of chondrogenic marker genes, H3K9me2 levels are increased in Arid5b-/- chondrocytes. Finally, we show that Phf2 knockdown inhibits Sox9-induced chondrocyte differentiation. Our findings establish an epigenomic mechanism of skeletal development, whereby Arid5b promotes chondrogenesis by facilitating Phf2-mediated histone demethylation of Sox9-regulated chondrogenic gene promoters.

  11. Change in attachment predicts change in emotion regulation particularly among 5-HTTLPR short-allele homozygotes.

    Science.gov (United States)

    Viddal, Kristine Rensvik; Berg-Nielsen, Turid Suzanne; Belsky, Jay; Wichstrøm, Lars

    2017-07-01

    In view of the theory that the attachment relationship provides a foundation for the development of emotion regulation, here, we evaluated (a) whether change in attachment security from 4 to 6 years predicts change in emotion regulation from 6 to 8 years and (b) whether 5-HTTLPR moderates this relation in a Norwegian community sample (n = 678, 99.7% Caucasian). Attachment was measured with the Manchester Child Attachment Story Task, and teachers completed the Emotion Regulation Checklist. Attachment security was modestly stable, with children becoming more secure over time. Regression analyses revealed that increased attachment security from 4 to 6 forecasted increases in emotion regulation from 6 to 8 and decreased attachment security forecasted decreases in emotion regulation. This effect was strongest among the 5-HTTLPR short-allele homozygotes and, according to competitive model fitting, in a differential-susceptibility manner. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Lysophosphatidic acid acyltransferase beta regulates mTOR signaling.

    Directory of Open Access Journals (Sweden)

    Michelle A Blaskovich

    Full Text Available Lysophosphatidic acid acyltransferase (LPAAT-β is a phosphatidic acid (PA generating enzyme that plays an essential role in triglyceride synthesis. However, LPAAT-β is now being studied as an important regulator of cell growth and differentiation and as a potential therapeutic target in cancer since PA is necessary for the activity of key proteins such as Raf, PKC-ζ and mTOR. In this report we determine the effect of LPAAT-β silencing with siRNA in pancreatic adenocarcinoma cell lines. We show for the first time that LPAAT-β knockdown inhibits proliferation and anchorage-independent growth of pancreatic cancer cells. This is associated with inhibition of signaling by mTOR as determined by levels of mTORC1- and mTORC2-specific phosphorylation sites on 4E-BP1, S6K and Akt. Since PA regulates the activity of mTOR by modulating its binding to FKBP38, we explored the possibility that LPAAT-β might regulate mTOR by affecting its association with FKBP38. Coimmunoprecipitation studies of FKBP38 with mTOR show increased levels of FKBP38 associated with mTOR when LPAAT-β protein levels are knocked down. Furthermore, depletion of LPAAT-β results in increased Lipin 1 nuclear localization which is associated with increased nuclear eccentricity, a nuclear shape change that is dependent on mTOR, further confirming the ability of LPAAT-β to regulate mTOR function. Our results provide support for the hypothesis that PA generated by LPAAT-β regulates mTOR signaling. We discuss the implications of these findings for using LPAAT-β as a therapeutic target.

  13. Analysis for low and intermediate level radioactive waste disposal of AP1000 nuclear power in China

    International Nuclear Information System (INIS)

    Yang Bin; Ren Li; Hua Wei; Ma Xiaoqiang; Ma Ruoxia; Fang Xianghong

    2014-01-01

    AP1000 nuclear power is adopted in Sanmen Nuclear Power Plant, Zhejiang province and Haiyang Nuclear Power Plant, Shandong province. The filter and resin generated by the operation of nuclear power plants are handled by cement cured process and compression technology in Sanmen Nuclear Power Plant, while they are loaded in polyethylene HIC in Haiyang Nuclear Power Plant. At present, there were not engineering practice for dispose polyethylene HIC in China. The document discusses three disposal options of polyethylene HIC: one is that polyethylene HIC placed in over pack, another is that polyethylene HIC mixed with other drum, the third is that polyethylene HIC placed in disposal unit which is divided into small units. (authors)

  14. En-masse retraction with a preformed nickel-titanium and stainless steel archwire assembly and temporary skeletal anchorage devices without posterior bonding.

    Science.gov (United States)

    Jee, Jeong-Hyun; Ahn, Hyo-Won; Seo, Kyung-Won; Kim, Seong-Hun; Kook, Yoon-Ah; Chung, Kyu-Rhim; Nelson, Gerald

    2014-09-01

    To evaluate the therapeutic effects of a preformed assembly of nickel-titanium (NiTi) and stainless steel (SS) archwires (preformed C-wire) combined with temporary skeletal anchorage devices (TSADs) as the sole source of anchorage and to compare these effects with those of a SS version of C-wire (conventional C-wire) for en-masse retraction. Thirty-one adult female patients with skeletal Class I or II dentoalveolar protrusion, mild-to-moderate anterior crowding (3.0-6.0 mm), and stable Class I posterior occlusion were divided into conventional (n = 15) and preformed (n = 16) C-wire groups. All subjects underwent first premolar extractions and en-masse retraction with pre-adjusted edgewise anterior brackets, the assigned C-wire, and maxillary C-tubes or C-implants; bonded mesh-tube appliances were used in the mandibular dentition. Differences in pretreatment and post-retraction measurements of skeletal, dental, and soft-tissue cephalometric variables were statistically analyzed. Both groups showed full retraction of the maxillary anterior teeth by controlled tipping and space closure without altered posterior occlusion. However, the preformed C-wire group had a shorter retraction period (by 3.2 months). Furthermore, the maxillary molars in this group showed no significant mesialization, mesial tipping, or extrusion; some mesialization and mesial tipping occurred in the conventional C-wire group. Preformed C-wires combined with maxillary TSADs enable simultaneous leveling and space closure from the beginning of the treatment without maxillary posterior bonding. This allows for faster treatment of dentoalveolar protrusion without unwanted side effects, when compared with conventional C-wire, evidencing its clinical expediency.

  15. SNF5 is an essential executor of epigenetic regulation during differentiation.

    Science.gov (United States)

    You, Jueng Soo; De Carvalho, Daniel D; Dai, Chao; Liu, Minmin; Pandiyan, Kurinji; Zhou, Xianghong J; Liang, Gangning; Jones, Peter A

    2013-04-01

    Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to epigenetic regulation along with DNA methylation and histone modifications. Some reports have assessed the roles of the BAF complex subunits and stemness in murine embryonic stem cells. However, the details of the relationships between remodelers and transcription factors in altering chromatin configuration, which ultimately affects gene expression during cell differentiation, remain unclear. Here for the first time we demonstrate that SNF5, a core subunit of the BAF complex, negatively regulates OCT4 levels in pluripotent cells and is essential for cell survival during differentiation. SNF5 is responsible for generating nucleosome-depleted regions (NDRs) at the regulatory sites of OCT4 repressed target genes such as PAX6 and NEUROG1, which are crucial for cell fate determination. Concurrently, SNF5 closes the NDRs at the regulatory regions of OCT4-activated target genes such as OCT4 itself and NANOG. Furthermore, using loss- and gain-of-function experiments followed by extensive genome-wide analyses including gene expression microarrays and ChIP-sequencing, we highlight that SNF5 plays dual roles during differentiation by antagonizing the expression of genes that were either activated or repressed by OCT4, respectively. Together, we demonstrate that SNF5 executes the switch between pluripotency and differentiation.

  16. SNF5 is an essential executor of epigenetic regulation during differentiation.

    Directory of Open Access Journals (Sweden)

    Jueng Soo You

    2013-04-01

    Full Text Available Nucleosome occupancy controls the accessibility of the transcription machinery to DNA regulatory regions and serves an instructive role for gene expression. Chromatin remodelers, such as the BAF complexes, are responsible for establishing nucleosome occupancy patterns, which are key to epigenetic regulation along with DNA methylation and histone modifications. Some reports have assessed the roles of the BAF complex subunits and stemness in murine embryonic stem cells. However, the details of the relationships between remodelers and transcription factors in altering chromatin configuration, which ultimately affects gene expression during cell differentiation, remain unclear. Here for the first time we demonstrate that SNF5, a core subunit of the BAF complex, negatively regulates OCT4 levels in pluripotent cells and is essential for cell survival during differentiation. SNF5 is responsible for generating nucleosome-depleted regions (NDRs at the regulatory sites of OCT4 repressed target genes such as PAX6 and NEUROG1, which are crucial for cell fate determination. Concurrently, SNF5 closes the NDRs at the regulatory regions of OCT4-activated target genes such as OCT4 itself and NANOG. Furthermore, using loss- and gain-of-function experiments followed by extensive genome-wide analyses including gene expression microarrays and ChIP-sequencing, we highlight that SNF5 plays dual roles during differentiation by antagonizing the expression of genes that were either activated or repressed by OCT4, respectively. Together, we demonstrate that SNF5 executes the switch between pluripotency and differentiation.

  17. 31 CFR 5.3 - Do these regulations adopt the Federal Claims Collection Standards (FCCS)?

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Do these regulations adopt the... Secretary of the Treasury TREASURY DEBT COLLECTION General Provisions § 5.3 Do these regulations adopt the Federal Claims Collection Standards (FCCS)? This part adopts and incorporates all provisions of the FCCS...

  18. Staff Rules and Regulations – modification No. 5 to the 11th edition

    CERN Multimedia

    HR Department

    2011-01-01

    Please note that, following decisions taken at the December 2010 Council session, the following pages of the Staff Rules and Regulations have been modified as of 1 January 2011: Monthly basic salaries of Staff Members (Annex R A 5): amendment of page 71. Stipends of Fellows (Annex R A 6): amendment of page 72. The electronic version of this modification and also the complete Staff Rules and Regulations are available on the HR Department intranet site: Staff Rules and Regulations Paper copies are available from the HR-DI Secretariat upon request (Tel. 78003). Department Head Office

  19. Anchorage onto deciduous teeth: effectiveness of early rapid maxillary expansion in increasing dental arch dimension and improving anterior crowding.

    Science.gov (United States)

    Mutinelli, Sabrina; Manfredi, Mario; Guiducci, Antonio; Denotti, Gloria; Cozzani, Mauro

    2015-01-01

    Anchorage onto permanent dentition is a common procedure in rapid maxillary expansion. However, replacing first permanent molars with the second deciduous molars seems to be an option to reduce some negative side effects during orthodontic treatment. The purpose of this study was to evaluate the dental effect of rapid maxillary expansion with anchorage exclusively onto deciduous teeth performed in the first period of transition. Twenty patients with a lateral cross-bite treated exclusively by a Haas expander in early mixed dentition were retrospectively analyzed before treatment, at appliance removal, and at 21 months out of retention. The sagittal and transverse dimensions, together with the inter-canine arch and irregularity index, were digitally measured on scanned images of dental casts. The patients were compared with three balanced control groups (in total, 60 individuals) matched for gender. Two control groups had the same canine dental class as the treated group at T1, were in the inter-transitional period, and either had or lacked a lateral cross-bite. The last control group was comprised of adolescents in permanent dentition with a dental class I. The statistical analysis was performed by means of repeated-measures ANOVA for paired data and one-way ANOVA, the Kruskal-Wallis test, and the Mann-Whitney test for independent measures (α-level p dentition), the dental arch dimensions of treated patients were similar to those of adolescents with a dental class I and significantly wider than those of patients with a lateral cross-bite. Also, the anterior irregularity index was lower among patients who had undergone expansion treatments than in all untreated study participants. The Haas expander anchored to the deciduous teeth is effective in increasing the dental arch width in patients with a lateral cross-bite. The dimensions of the dental arch were modified earlier toward the values of the permanent dentition.

  20. Hydrogen Induced Crack and Phase Transformation in Hydrogen Pressured Tensile Test of 316L Stainless Steel

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Un Bong; Nam, Sung Hoon [Korea Research Institute of Standards and Science, Daejeon (Korea, Republic of); Choe, Byung Hak; Shim, Jong Hun [Gangneung-Wonju National University, Gangneung (Korea, Republic of); Kim, Young Uk [Hanyang University, Ansan (Korea, Republic of); Kim, Young Suk; Kim, Sung Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Hong, Keyyong [Korea Research Institute of Ship and Ocean Engineering, Deajeon (Korea, Republic of)

    2015-02-15

    The aim of this investigation is to prove the mechanism of hydrogen induced crack (HIC) of 316L stainless steels in hydrogen pressured tensile test. Microstructures like twin, planar slip, and abnormal phase transformation around the HIC were analyzed by transmission electron microscopy. Deformation twin accompanied by planar slip could be related to the main cause of HIC in the hydrogen pressured tensile condition, because intragranular HICs were mainly observed along the boundaries of twins and planar slip lines. An abnormal forbidden diffraction was also accompanied by HIC in the hydrogen attacked area. Examination of the HIC mechanism in austenitic stainless steel can be applied to the fitness of use for alloys with the possibility of various susceptible cracks in a hydrogen and stress atmosphere.

  1. Amino acid limitation induces down-regulation of WNT5a at transcriptional level

    International Nuclear Information System (INIS)

    Wang Zuguang; Chen Hong

    2009-01-01

    An aberrant WNT signaling contributes to the development and progression of multiple cancers. WNT5a is one of the WNT signaling molecules. This study was designed to test the hypothesis that amino acid deprivation induces changes in the WNT signaling pathway in colon cancer cells. Results showed that targets of the amino acid response pathway, ATF3 and p21, were induced in the human colon cancer cell line SW480 during amino acid limitation. There was a significant decrease in the WNT5a mRNA level following amino acid deprivation. The down-regulation of WNT5a mRNA by amino acid deprivation is not due to mRNA destabilization. There is a reduction of nuclear β-catenin protein level by amino acid limitation. Under amino acid limitation, phosphorylation of ERK1/2 was increased and the blockage of ERK1/2 by the inhibitor U0126 partially restored WNT5a mRNA level. In conclusion, amino acid limitation in colon cancer cells induces phosphorylation of ERK1/2, which then down-regulates WNT5a expression.

  2. CDKL5, a protein associated with rett syndrome, regulates neuronal morphogenesis via Rac1 signaling.

    Science.gov (United States)

    Chen, Qian; Zhu, Yong-Chuan; Yu, Jing; Miao, Sheng; Zheng, Jing; Xu, Li; Zhou, Yang; Li, Dan; Zhang, Chi; Tao, Jiong; Xiong, Zhi-Qi

    2010-09-22

    Mutations in cyclin-dependent kinase-like 5 (CDKL5), also known as serine/threonine kinase 9 (STK9), have been identified in patients with Rett syndrome (RTT) and X-linked infantile spasm. However, the function of CDKL5 in the brain remains unknown. Here, we report that CDKL5 is a critical regulator of neuronal morphogenesis. We identified a neuron-specific splicing variant of CDKL5 whose expression was markedly induced during postnatal development of the rat brain. Downregulating CDKL5 by RNA interference (RNAi) in cultured cortical neurons inhibited neurite growth and dendritic arborization, whereas overexpressing CDKL5 had opposite effects. Furthermore, knocking down CDKL5 in the rat brain by in utero electroporation resulted in delayed neuronal migration, and severely impaired dendritic arborization. In contrast to its proposed function in the nucleus, we found that CDKL5 regulated dendrite development through a cytoplasmic mechanism. In fibroblasts and in neurons, CDKL5 colocalized and formed a protein complex with Rac1, a critical regulator of actin remodeling and neuronal morphogenesis. Overexpression of Rac1 prevented the inhibition of dendrite growth caused by CDKL5 knockdown, and the growth-promoting effect of ectopically expressed CDKL5 on dendrites was abolished by coexpressing a dominant-negative form of Rac1. Moreover, CDKL5 was required for brain-derived neurotrophic factor (BDNF)-induced activation of Rac1. Together, these results demonstrate a critical role of CDKL5 in neuronal morphogenesis and identify a Rho GTPase signaling pathway which may contribute to CDKL5-related disorders.

  3. Development of a metallic high integrity container

    International Nuclear Information System (INIS)

    Haelsig, R.T.

    1986-01-01

    Nuclear Packaging, a Pacific Nuclear Company, developed a metallic high integrity container (HIC) for the burial of low level radioactive waste. This class of container has received the most extensive review of any burial container licensed in the United States. It is also the first container that has been licensed to meet the requirements of Nuclear Regulatory Commission Regulations 10CFR61. The design and subsequent review considered 300 years corrosion at a depth of 55 feet with no degradation of container structural integrity. The design also included a technical requirement that the container possess a positive vent that would exclude moisture. The alloy that was selected, allows for significant flexibility in container size and configuration which is essential to accommodating the various waste forms. This allowed the development of containers in various sizes and with a variety of closures, that accommodate the internal dimensions of various shipping shields and help minimize radiation exposure during packaging operations. The material used in the metallic container is high corrosion resistant which reduces the need for strict chemical controls at the waste generating facility. This acts to ease the operational requirements in the treatment of several waste streams. The design result is a family of metallic High Integrity Containers (HIC)s that meet all the performance criteria imposed by the regulations, as well as provide a disposable waste container with good transportation efficiency and minimum operational constraints

  4. Anticataleptic and antiepileptic activity of ethanolic extract of leaves of Mucuna pruriens: A study on role of dopaminergic system in epilepsy in albino rats.

    Science.gov (United States)

    Champatisingh, D; Sahu, P K; Pal, A; Nanda, G S

    2011-04-01

    To assess the anticataleptic and antiepileptic activity of leaves of Mucuna pruriens in albino rats. Haloperidol-induced catalepsy (HIC), maximum electro-shock (MES) method, pilocarpine-induced Status epilepticus (PISE) and single-dose effect of M. pruriens were employed. M. pruriens (100 mg/kg) had significant anticataleptic and antiepileptic activity in HIC, MES, and PISE. M. pruriens extract has the potential to be an anticataleptic and antiepileptic drug. Dopamine and 5-HT may have a role in such activity.

  5. Regulation of CCL5 expression in smooth muscle cells following arterial injury.

    Directory of Open Access Journals (Sweden)

    Huan Liu

    Full Text Available Chemokines play a crucial role in inflammation and in the pathophysiology of atherosclerosis by recruiting inflammatory immune cells to the endothelium. Chemokine CCL5 has been shown to be involved in atherosclerosis progression. However, little is known about how CCL5 is regulated in vascular smooth muscle cells. In this study we report that CCL5 mRNA expression was induced and peaked in aorta at day 7 and then declined after balloon artery injury, whereas IP-10 and MCP-1 mRNA expression were induced and peaked at day 3 and then rapidly declined.The expression of CCL5 receptors (CCR1, 3 & 5 were also rapidly induced and then declined except CCR5 which expression was still relatively high at day 14 after balloon injury. In rat smooth muscle cells (SMCs, similar as in aorta CCL5 mRNA expression was induced and kept increasing after LPS plus IFN-gamma stimulation, whereas IP-10 mRNA expression was rapidly induced and then declined. Our data further indicate that induction of CCL5 expression in SMCs was mediated by IRF-1 via binding to the IRF-1 response element in CCL5 promoter. Moreover, p38 MAPK was involved in suppression of CCL5 and IP-10 expression in SMCs through common upstream molecule MKK3. The downstream molecule MK2 was required for p38-mediated CCL5 but not IP-10 inhibition. Our findings indicate that CCL5 induction in aorta and SMCs is mediated by IRF-1 while activation of p38 MAPK signaling inhibits CCL5 and IP-10 expression. Methods targeting MK2 expression could be used to selectively regulate CCL5 but not IP-10 expression in SMCs.

  6. Uridine 5′-Monophosphate Synthase Is Transcriptionally Regulated by Pyrimidine Levels in Nicotiana plumbaginifolia1

    Science.gov (United States)

    Santoso, Djoko; Thornburg, Robert

    1998-01-01

    To understand the regulation and expression of pyrimidine biosynthesis in plants, we have examined the effect of the metabolic inhibitor 5-fluoroorotic acid (FOA) on uridine-5′-monophosphate synthase (UMPSase) expression in cell cultures of Nicotiana plumbaginifolia. UMPSase is the rate-limiting step of pyrimidine biosynthesis in plants. Addition of FOA causes an up-regulation of UMPSase enzyme activity in cell cultures after a lag phase of several days. Western-blot analysis demonstrated that the up-regulation in enzyme activity was caused by increased expression of the UMPSase protein. Northern-blot analysis demonstrated a higher level of UMPSase mRNA in the FOA-induced tissues than in control tissues. Run-on transcriptional assays showed that the UMPSase gene was transcriptionally activated after FOA treatment. The mechanism of toxicity of FOA is through thymine starvation. We found that addition of thymine abrogated the FOA-mediated up-regulation of UMPSase. In addition, methotrexate and aminopterin, which affect thymine levels by inhibiting dihydrofolate reductase, also up-regulate UMPSase in N. plumbaginifolia cells. PMID:9490773

  7. The role of the 5-HT1a receptor in central cardiovascular regulation

    NARCIS (Netherlands)

    G.H. Dreteler

    1991-01-01

    textabstractThe aim of the studies describe~ in this thesis is to further clarify the role of the 5- HT1A receptor in central cardiovascular regulation. The hypotensive action of 5-HT1A receptor agonists is mainly due to differential sympatho-inhibition resulting in an increase in total

  8. Protein arginine methyltransferase 5 regulates multiple signaling pathways to promote lung cancer cell proliferation

    International Nuclear Information System (INIS)

    Sheng, Xiumei; Wang, Zhengxin

    2016-01-01

    Protein arginine methyltransferase 5 (PRMT5) catalyzes the formation of symmetrical dimethylation of arginine residues in proteins. WD repeat domain 77 (WDR77), also known as p44, MEP50, or WD45, forms a stoichiometric complex with PRMT5. The PRMT5/p44 complex is required for cellular proliferation of lung and prostate epithelial cells during earlier stages of development and is re-activated during prostate and lung tumorigenesis. The molecular mechanisms by which PRMT5 and p44 promote cellular proliferation are unknown. Expression of PRMT5 and p44 in lung and prostate cancer cells was silenced and their target genes were identified. The regulation of target genes was validated in various cancer cells during lung development and tumorigenesis. Altered expression of target genes was achieved by ectopic cDNA expression and shRNA-mediated silencing. PRMT5 and p44 regulate expression of a specific set of genes encoding growth and anti-growth factors, including receptor tyrosine kinases and antiproliferative proteins. Genes whose expression was suppressed by PRMT5 and p44 encoded anti-growth factors and inhibited cell growth when ectopically expressed. In contrast, genes whose expression was enhanced by PRMT5 and p44 encoded growth factors and increased cell growth when expressed. Altered expression of target genes is associated with re-activation of PRMT5 and p44 during lung tumorigenesis. Our data provide the molecular basis by which PRMT5 and p44 regulate cell growth and lay a foundation for further investigation of their role in lung tumor initiation. The online version of this article (doi:10.1186/s12885-016-2632-3) contains supplementary material, which is available to authorized users

  9. Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3 and KIT driven Leukemogenesis

    Science.gov (United States)

    Chatterjee, Anindya; Ghosh, Joydeep; Ramdas, Baskar; Mali, Raghuveer Singh; Martin, Holly; Kobayashi, Michihiro; Vemula, Sasidhar; Canela, Victor H.; Waskow, Emily R.; Visconte, Valeria; Tiu, Ramon V.; Smith, Catherine C.; Shah, Neil; Bunting, Kevin D.; Boswell, H. Scott; Liu, Yan; Chan, Rebecca J.; Kapur, Reuben

    2015-01-01

    SUMMARY Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN) and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK), whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis. PMID:25456130

  10. Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis

    Directory of Open Access Journals (Sweden)

    Anindya Chatterjee

    2014-11-01

    Full Text Available Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML and myeloproliferative neoplasms (MPNs, and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis.

  11. 75 FR 76275 - Anchorage Regulations; Long Island Sound

    Science.gov (United States)

    2010-12-08

    ... tailored to the safety purpose of that notification requirement. In paragraph (b)(4), for the convenience... standards (e.g., specifications of materials, performance, design, or operation; test methods; sampling...

  12. Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Nilgun Gurbuz

    Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D-mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

  13. Down-regulation of 5-HT1B and 5-HT1D receptors inhibits proliferation, clonogenicity and invasion of human pancreatic cancer cells.

    Directory of Open Access Journals (Sweden)

    Nilgun Gurbuz

    Full Text Available Pancreatic ductal adenocarcinoma is characterized by extensive local tumor invasion, metastasis and early systemic dissemination. The vast majority of pancreatic cancer (PaCa patients already have metastatic complications at the time of diagnosis, and the death rate of this lethal type of cancer has increased over the past decades. Thus, efforts at identifying novel molecularly targeted therapies are priorities. Recent studies have suggested that serotonin (5-HT contributes to the tumor growth in a variety of cancers including prostate, colon, bladder and liver cancer. However, there is lack of evidence about the impact of 5-HT receptors on promoting pancreatic cancer. Having considered the role of 5-HT-1 receptors, especially 5-HT1B and 5-HT1D subtypes in different types of malignancies, the aim of this study was to investigate the role of 5-HT1B and 5-HT1D receptors in PaCa growth and progression and analyze their potential as cytotoxic targets. We found that knockdown of 5-HT1B and 5-HT1D receptors expression, using specific small interfering RNA (siRNA, induced significant inhibition of proliferation and clonogenicity of PaCa cells. Also, it significantly suppressed PaCa cells invasion and reduced the activity of uPAR/MMP-2 signaling and Integrin/Src/Fak-mediated signaling, as integral tumor cell pathways associated with invasion, migration, adhesion, and proliferation. Moreover, targeting 5-HT1B and 5-HT1D receptors down-regulates zinc finger ZEB1 and Snail proteins, the hallmarks transcription factors regulating epithelial-mesenchymal transition (EMT, concomitantly with up-regulating of claudin-1 and E-Cadherin. In conclusion, our data suggests that 5-HT1B- and 5-HT1D- mediated signaling play an important role in the regulation of the proliferative and invasive phenotype of PaCa. It also highlights the therapeutic potential of targeting of 5-HT1B/1D receptors in the treatment of PaCa, and opens a new avenue for biomarkers identification

  14. Allele-specific physical interactions regulate the heterotic traits in hybrids of Arabidopsis thaliana ecotypes

    Directory of Open Access Journals (Sweden)

    Babita Singh

    2017-10-01

    Full Text Available Heterosis is an important phenomenon for the breeding in agricultural crops as it influences yield related traits such as biomass yield, seed number and weight, adaptive and reproductive traits. However, the level of heterosis greatly varies for different traits and different genotypes. The present study focuses on identification of physical interactions between alleles and their role in transcriptional regulation in heterotic plants. Here, we used two Arabidopsis ecotypes; Col-0 and C24 as parent for crosses. We performed crossing between these ecotypes and screened the F1 hybrids on the basis of different SSR markers. Further, we used Hi-C to capture intra- and inter-chromosomal physical interactions between alleles on genome-wide level. Then, we identified allele-specific chromatin interactions and constructed genome-wide allele-specific contact maps at different resolutions for the entire chromosome. We also performed RNA-seq of hybrids and their parents. RNA-seq analysis identified several differentially expressed genes and non-additively expressed genes in hybrids with respect to their parents. Further, to understand the biological significance of these chromatin interactions, we annotated these interactions and correlated with the transcriptome data. Thus, our study provides alleles-specific chromatin interactions in genome-wide fashion which play a crucial role in regulation of different genes that may be important for heterosis.

  15. En-masse retraction with a preformed nickel-titanium and stainless steel archwire assembly and temporary skeletal anchorage devices without posterior bonding

    Science.gov (United States)

    Jee, Jeong-Hyun; Ahn, Hyo-Won; Seo, Kyung-Won; Kook, Yoon-Ah; Chung, Kyu-Rhim; Nelson, Gerald

    2014-01-01

    Objective To evaluate the therapeutic effects of a preformed assembly of nickel-titanium (NiTi) and stainless steel (SS) archwires (preformed C-wire) combined with temporary skeletal anchorage devices (TSADs) as the sole source of anchorage and to compare these effects with those of a SS version of C-wire (conventional C-wire) for en-masse retraction. Methods Thirty-one adult female patients with skeletal Class I or II dentoalveolar protrusion, mild-to-moderate anterior crowding (3.0-6.0 mm), and stable Class I posterior occlusion were divided into conventional (n = 15) and preformed (n = 16) C-wire groups. All subjects underwent first premolar extractions and en-masse retraction with pre-adjusted edgewise anterior brackets, the assigned C-wire, and maxillary C-tubes or C-implants; bonded mesh-tube appliances were used in the mandibular dentition. Differences in pretreatment and post-retraction measurements of skeletal, dental, and soft-tissue cephalometric variables were statistically analyzed. Results Both groups showed full retraction of the maxillary anterior teeth by controlled tipping and space closure without altered posterior occlusion. However, the preformed C-wire group had a shorter retraction period (by 3.2 months). Furthermore, the maxillary molars in this group showed no significant mesialization, mesial tipping, or extrusion; some mesialization and mesial tipping occurred in the conventional C-wire group. Conclusions Preformed C-wires combined with maxillary TSADs enable simultaneous leveling and space closure from the beginning of the treatment without maxillary posterior bonding. This allows for faster treatment of dentoalveolar protrusion without unwanted side effects, when compared with conventional C-wire, evidencing its clinical expediency. PMID:25309863

  16. Policy development and challenges of global mental health: a systematic review of published studies of national-level mental health policies.

    Science.gov (United States)

    Zhou, Wei; Yu, Yu; Yang, Mei; Chen, Lizhang; Xiao, Shuiyuan

    2018-05-18

    Mental health policy can be an essential and powerful tool to improve a population's mental health. However, around one third of countries do not possess a mental health policy, and there are large disparities in population coverage rates between high- and low-income countries. The goal of this study is to identify the transition and implementation challenges of mental health policies in both high-income countries (HICs) as well as middle- and low-income countries (MLICs). PubMed, Cochrane Library and Campbell Library were searched from inception to 31 December 2017, for studies on implemented mental health policies at the national level. Abstracts and the main texts of papers were double screened, and extracted data were analysed through thematic synthesis. A total of 93 papers were included in this study, covering 24 HICs, 28 MLICs and 5 regions. Studies on mental health policies, especially those of MLICs, kept increasing, but MLICs were still underrepresented in terms of publication quantity and study frequency. Based on the included studies, nine policy domains were summarized: service organizing, service provision, service quality, human resources, legislation and human rights, advocacy, administration, surveillance and research, and financing and budgeting. HICs incrementally enriched their policy content in all domains over centuries of development; following HICs' experience, mental health policies in MLICs have boomed since the 1990s and quickly extended to all domains. Implementation problems in HICs were mainly related to service organizing and service provision; for MLICs, more severe implementation problems converged on financing and budgeting, administration and human resources. Mental health policy developments in both HICs and MLICs present a process of diversification and enrichment. In terms of implementation, MLICs are faced with more and greater challenges than HICs, especially in funding, human resources and administration. Therefore, future

  17. The 5th Symposium on Post-Transcriptional Regulation of Plant Gene Expression (PTRoPGE)

    Energy Technology Data Exchange (ETDEWEB)

    Karen S. Browning; Marie Petrocek; Bonnie Bartel

    2006-06-01

    The 5th Symposium on Post-Transcriptional Regulation of Plant Gene Expression (PTRoPGE) will be held June 8-12, 2005 at the University of Texas at Austin. Exciting new and ongoing discoveries show significant regulation of gene expression occurs after transcription. These post-transcriptional control events in plants range from subtle regulation of transcribed genes and phosphorylation, to the processes of gene regulation through small RNAs. This meeting will focus on the regulatory role of RNA, from transcription, through translation and finally degradation. The cross-disciplinary design of this meeting is necessary to encourage interactions between researchers that have a common interest in post-transcriptional gene expression in plants. By bringing together a diverse group of plant molecular biologist and biochemists at all careers stages from across the world, this meeting will bring about more rapid progress in understanding how plant genomes work and how genes are finely regulated by post-transcriptional processes to ultimately regulate cells.

  18. Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis.

    Science.gov (United States)

    Chatterjee, Anindya; Ghosh, Joydeep; Ramdas, Baskar; Mali, Raghuveer Singh; Martin, Holly; Kobayashi, Michihiro; Vemula, Sasidhar; Canela, Victor H; Waskow, Emily R; Visconte, Valeria; Tiu, Ramon V; Smith, Catherine C; Shah, Neil; Bunting, Kevin D; Boswell, H Scott; Liu, Yan; Chan, Rebecca J; Kapur, Reuben

    2014-11-20

    Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs), and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK) whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Automated Hydrophobic Interaction Chromatography Column Selection for Use in Protein Purification

    Science.gov (United States)

    Murphy, Patrick J. M.; Stone, Orrin J.; Anderson, Michelle E.

    2011-01-01

    should be employed for future, more exhaustive optimization experiments and protein purification runs 4. The specific protein being purified here is recombinant green fluorescent protein (GFP); however, the approach may be adapted for purifying other proteins with one or more hydrophobic surface regions. GFP serves as a useful model protein, due to its stability, unique light absorbance peak at 397 nm, and fluorescence when exposed to UV light 5. Bacterial lysate containing wild type GFP was prepared in a high-salt buffer, loaded into a Bio-Rad DuoFlow medium pressure liquid chromatography system, and adsorbed to HiTrap HIC columns containing different HIC media. The protein was eluted from the columns and analyzed by in-line and post-run detection methods. Buffer blending, dynamic sample loop injection, sequential column selection, multi-wavelength analysis, and split fraction eluate collection increased the functionality of the system and reproducibility of the experimental approach. PMID:21968976

  20. Rab5 regulates internalisation of P2X4 receptors and potentiation by ivermectin.

    Science.gov (United States)

    Stokes, Leanne

    2013-03-01

    The P2X4 receptor is an ATP-gated ion channel expressed in neurons, endothelia and immune cells. Plasma membrane expression of P2X4 is regulated by dynamin-dependent endocytosis, and this study identifies a Rab5-dependent pathway of receptor internalisation. Expression of Rab5 constructs altered the distribution of P2X4 in HEK-293 cells, and both constitutive internalisation and agonist-induced desensitisation of P2X4 were increased by co-expression of wild-type Rab5 or constitutively active Rab5 (Q79L). Expression of inactive dynamin K44A and Rab5 S34N constructs abolished agonist-induced desensitisation, suggesting internalisation as the underlying mechanism. Blocking P2X4 internalisation in this way also abolished potentiation of ATP-induced currents by the allosteric modulator ivermectin. This suggests that the dynamin-Rab5 internalisation pathway is essential for the ivermectin potentiation effect. In agreement with this hypothesis, the co-expression of wild-type dynamin, wild-type Rab5 or active Rab5 (Q79L) could increase the potentiation of the ATP-induced P2X4 response by ivermectin. These findings highlight Rab5 GTPase as a key regulator of P2X4 receptor cell surface expression and internalisation.

  1. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells.

    Science.gov (United States)

    Min, Kyoung-Jin; Nam, Ju-Ock; Kwon, Taeg Kyu

    2017-08-02

    Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki) cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose) polymerase (PARP), which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk) inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5) expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

  2. Polo kinase Cdc5 is a central regulator of meiosis I

    Science.gov (United States)

    Attner, Michelle A.; Miller, Matthew P.; Ee, Ly-sha; Elkin, Sheryl K.; Amon, Angelika

    2013-01-01

    During meiosis, two consecutive rounds of chromosome segregation yield four haploid gametes from one diploid cell. The Polo kinase Cdc5 is required for meiotic progression, but how Cdc5 coordinates multiple cell-cycle events during meiosis I is not understood. Here we show that CDC5-dependent phosphorylation of Rec8, a subunit of the cohesin complex that links sister chromatids, is required for efficient cohesin removal from chromosome arms, which is a prerequisite for meiosis I chromosome segregation. CDC5 also establishes conditions for centromeric cohesin removal during meiosis II by promoting the degradation of Spo13, a protein that protects centromeric cohesin during meiosis I. Despite CDC5’s central role in meiosis I, the protein kinase is dispensable during meiosis II and does not even phosphorylate its meiosis I targets during the second meiotic division. We conclude that Cdc5 has evolved into a master regulator of the unique meiosis I chromosome segregation pattern. PMID:23918381

  3. Semi-Automated Hydrophobic Interaction Chromatography Column Scouting Used in the Two-Step Purification of Recombinant Green Fluorescent Protein

    Science.gov (United States)

    Murphy, Patrick J. M.

    2014-01-01

    Background Hydrophobic interaction chromatography (HIC) most commonly requires experimental determination (i.e., scouting) in order to select an optimal chromatographic medium for purifying a given target protein. Neither a two-step purification of untagged green fluorescent protein (GFP) from crude bacterial lysate using sequential HIC and size exclusion chromatography (SEC), nor HIC column scouting elution profiles of GFP, have been previously reported. Methods and Results Bacterial lysate expressing recombinant GFP was sequentially adsorbed to commercially available HIC columns containing butyl, octyl, and phenyl-based HIC ligands coupled to matrices of varying bead size. The lysate was fractionated using a linear ammonium phosphate salt gradient at constant pH. Collected HIC eluate fractions containing retained GFP were then pooled and further purified using high-resolution preparative SEC. Significant differences in presumptive GFP elution profiles were observed using in-line absorption spectrophotometry (A395) and post-run fluorimetry. SDS-PAGE and western blot demonstrated that fluorometric detection was the more accurate indicator of GFP elution in both HIC and SEC purification steps. Comparison of composite HIC column scouting data indicated that a phenyl ligand coupled to a 34 µm matrix produced the highest degree of target protein capture and separation. Conclusions Conducting two-step protein purification using the preferred HIC medium followed by SEC resulted in a final, concentrated product with >98% protein purity. In-line absorbance spectrophotometry was not as precise of an indicator of GFP elution as post-run fluorimetry. These findings demonstrate the importance of utilizing a combination of detection methods when evaluating purification strategies. GFP is a well-characterized model protein, used heavily in educational settings and by researchers with limited protein purification experience, and the data and strategies presented here may aid in

  4. Hunner-Type (Classic Interstitial Cystitis: A Distinct Inflammatory Disorder Characterized by Pancystitis, with Frequent Expansion of Clonal B-Cells and Epithelial Denudation.

    Directory of Open Access Journals (Sweden)

    Daichi Maeda

    Full Text Available Interstitial cystitis (IC is a chronic bladder disease with urinary frequency, bladder discomfort or bladder pain of unknown etiology. Based on cystoscopic findings, patients with IC are classified as either Hunner-type/classic IC (HIC, presenting with a specific Hunner lesion, or non-Hunner-type IC (NHIC, presenting with no Hunner lesion, but post-hydrodistension mucosal bleeding. Inflammatory cell infiltration, composed predominantly of lymphocytes, plasma cells and epithelial denudation, has in the past been documented as a major pathological IC finding. However, the significance of the pathological evaluation of IC, especially with regard to the difference between HIC and NHIC, has been downplayed in recent years. In this study, we performed immunohistochemical quantification of infiltrating T-lymphocytes, B-lymphocytes and plasma cells, and measured the amount of residual epithelium in urinary bladder biopsy specimens taken from patients with HIC and NHIC, and those with no IC, using image analysis software. In addition, in situ hybridization of the light chains was performed to examine clonal B-cell expansion. Lymphoplasmacytic infiltration was significantly more severe in HIC specimens than in NHIC specimens (P <0.0001. Substantial lymphoplasmacytic inflammation (≥200 cells/mm2 was observed in 93% of HIC specimens, whereas only 8% of NHIC specimens were inflamed. Plasmacytic infiltration was more prominent in HIC specimens compared with NHIC and non-IC cystitis specimens (P <0.005. Furthermore, expansion of light-chain-restricted B-cells was observed in 31% of cases of HIC. The amount of residual epithelium was decreased in HIC specimens compared with NHIC specimens and non-IC cystitis specimens (P <0.0001. These results suggest that NHIC and HIC are distinct pathological entities, with the latter characterized by pancystitis, frequent clonal B-cell expansion and epithelial denudation. An abnormality in the B-cell population may be

  5. DIRECT USAGE OF MINISCREW ANCHORAGE TO INTRUDE OVERERUPTED MAXILLARY POSTERIOR TEETH BEFORE PROSTHODONTIC PREPARATION:A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Yasemin Bahar Acar

    2016-01-01

    Full Text Available Overeruption of maxillary molars due loss of opposing teeth creates occlusal and functional interferences. Before reconstruction can be initiated, intrusion of overerupted molars becomes essential. This report illustrates treatment of overerupted maxillary premolar and molar via direct use of miniscrew anchorage. A 24-year old female had lost first and second left mandibular molars due to pulpal necrotizing agents, resulting with a large alveolar bone defect and overerupted maxillary premolar and molar. She had a history of unsuccessful alveolar distraction of mandibular left premolars to increase the alveolar bone height prior to implant placement. Patient was satisfied with her smile and refused comprehensive orthodontic treatment. Maxillary premolar and molar were intruded segmentally for 4mm in 8 months, using a combination of a mini-implant and partialfixed edgewise appliances. Biological responses of teeth and surrounding bony structures to intrusion appeared normal and acceptable in radiographic and clinical examination.

  6. Anti­-parallel Filament Flows and Bright Dots Observed in the EUV with Hi-­C

    Science.gov (United States)

    Alexander, Caroline E.; Regnier, Stephane; Walsh, Robert; Winebarger, Amy

    2013-01-01

    Hi-C obtained the highest spatial and temporal resolution observations ever taken in the solar EUV corona. Hi-C reveals dynamics and structure at the limit of its temporal and spatial resolution. Hi-C observed various fine-scale features that SDO/AIA could not pick out. For the first time in the corona, Hi-C revealed magnetic braiding and component reconnection consistent with coronal heating. Hi-C shows evidence of reconnection and heating in several different regions and magnetic configurations with plasma being heated to 0.3 - 8 x 10(exp 6) K temperatures. Surprisingly, many of the first results highlight plasma at temperatures that are not at the peak of the response functions.

  7. NFAT5-Regulated Macrophage Polarization Supports the Proinflammatory Function of Macrophages and T Lymphocytes.

    Science.gov (United States)

    Tellechea, Mónica; Buxadé, Maria; Tejedor, Sonia; Aramburu, Jose; López-Rodríguez, Cristina

    2018-01-01

    Macrophages are exquisite sensors of tissue homeostasis that can rapidly switch between pro- and anti-inflammatory or regulatory modes to respond to perturbations in their microenvironment. This functional plasticity involves a precise orchestration of gene expression patterns whose transcriptional regulators have not been fully characterized. We had previously identified the transcription factor NFAT5 as an activator of TLR-induced responses, and in this study we explore its contribution to macrophage functions in different polarization settings. We found that both in classically and alternatively polarized macrophages, NFAT5 enhanced functions associated with a proinflammatory profile such as bactericidal capacity and the ability to promote Th1 polarization over Th2 responses. In this regard, NFAT5 upregulated the Th1-stimulatory cytokine IL-12 in classically activated macrophages, whereas in alternatively polarized ones it enhanced the expression of the pro-Th1 mediators Fizz-1 and arginase 1, indicating that it could promote proinflammatory readiness by regulating independent genes in differently polarized macrophages. Finally, adoptive transfer assays in vivo revealed a reduced antitumor capacity in NFAT5-deficient macrophages against syngeneic Lewis lung carcinoma and ID8 ovarian carcinoma cells, a defect that in the ID8 model was associated with a reduced accumulation of effector CD8 T cells at the tumor site. Altogether, detailed analysis of the effect of NFAT5 in pro- and anti-inflammatory macrophages uncovered its ability to regulate distinct genes under both polarization modes and revealed its predominant role in promoting proinflammatory macrophage functions. Copyright © 2017 by The American Association of Immunologists, Inc.

  8. NLRC5 promotes cell proliferation via regulating the AKT/VEGF-A signaling pathway in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    He, Ying-hua; Li, Ming-fang; Zhang, Xing-yan; Meng, Xiao-ming; Huang, Cheng; Li, Jun

    2016-01-01

    NLRC5, a newly found member of the NLR family and the largest member of nucleotide-binding, has been reported to regulate immune responses and is associated with hepatocellular carcinoma (HCC). We investigated the mechanisms and signaling pathways of NLRC5 in HCC progression. Increased expression of NLRC5, vascular endothelial growth factor-A (VEGF-A) were found in human HCC tissue. There was a positive correlation between NLRC5 and VEGF-A expression and cell proliferation were enhanced in NLRC5-overexpressing HepG2 cells, but inhibited in cells with NLRC5 silencing treatment. Interestingly, we found that up-regulation of NLRC5 also coordinated the activation of PI3K/AKT signaling pathway. An AKT inhibitor LY294002 blocked VEGF-A expression and AKT phosphorylation in HepG2 cells and NLRC5-overexpressing HepG2 cells. These results demonstrate that NLRC5 promotes HCC progression via the AKT/VEGF-A signaling pathway.

  9. Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

    Directory of Open Access Journals (Sweden)

    Kyoung-jin Min

    2017-08-01

    Full Text Available Fisetin is a natural compound found in fruits and vegetables such as strawberries, apples, cucumbers, and onions. Since fisetin can elicit anti-cancer effects, including anti-proliferation and anti-migration, we investigated whether fisetin induced apoptosis in human renal carcinoma (Caki cells. Fisetin markedly induced sub-G1 population and cleavage of poly (ADP-ribose polymerase (PARP, which is a marker of apoptosis, and increased caspase activation. We found that pan-caspase inhibitor (z-VAD-fmk inhibited fisetin-induced apoptosis. In addition, fisetin induced death receptor 5 (DR5 expression at the transcriptional level, and down-regulation of DR5 by siRNA blocked fisetin-induced apoptosis. Furthermore, fisetin induced p53 protein expression through up-regulation of protein stability, whereas down-regulation of p53 by siRNA markedly inhibited fisetin-induced DR5 expression. In contrast, fisetin induced up-regulation of CHOP expression and reactive oxygen species production, which had no effect on fisetin-induced apoptosis. Taken together, our study demonstrates that fisetin induced apoptosis through p53 mediated up-regulation of DR5 expression at the transcriptional level.

  10. Arabidopsis CPR5 regulates ethylene signaling via molecular association with the ETR1 receptor.

    Science.gov (United States)

    Wang, Feifei; Wang, Lijuan; Qiao, Longfei; Chen, Jiacai; Pappa, Maria Belen; Pei, Haixia; Zhang, Tao; Chang, Caren; Dong, Chun-Hai

    2017-11-01

    The plant hormone ethylene plays various functions in plant growth, development and response to environmental stress. Ethylene is perceived by membrane-bound ethylene receptors, and among the homologous receptors in Arabidopsis, the ETR1 ethylene receptor plays a major role. The present study provides evidence demonstrating that Arabidopsis CPR5 functions as a novel ETR1 receptor-interacting protein in regulating ethylene response and signaling. Yeast split ubiquitin assays and bi-fluorescence complementation studies in plant cells indicated that CPR5 directly interacts with the ETR1 receptor. Genetic analyses indicated that mutant alleles of cpr5 can suppress ethylene insensitivity in both etr1-1 and etr1-2, but not in other dominant ethylene receptor mutants. Overexpression of Arabidopsis CPR5 either in transgenic Arabidopsis plants, or ectopically in tobacco, significantly enhanced ethylene sensitivity. These findings indicate that CPR5 plays a critical role in regulating ethylene signaling. CPR5 is localized to endomembrane structures and the nucleus, and is involved in various regulatory pathways, including pathogenesis, leaf senescence, and spontaneous cell death. This study provides evidence for a novel regulatory function played by CPR5 in the ethylene receptor signaling pathway in Arabidopsis. © 2017 Institute of Botany, Chinese Academy of Sciences.

  11. c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model.

    Science.gov (United States)

    Song, Honghua; Zheng, Yuqin; Cai, Fuying; Ma, Yanyan; Yang, Jingyue; Wu, Youjia

    2018-04-01

    The EphA5 receptor is well established as an axon guidance molecule during neural system development and plays an important role in dendritic spine formation and synaptogenesis. Our previous study has showed that EphA5 is decreased in the developing brain of congenital hypothyroidism (CH) and the EphA5 promoter methylation modification participates in its decrease. c-Fos, a well-kown transcription factor, has been considered in association with brain development. Bioinformatics analysis showed that the EphA5 promoter region contained five putative c-fos binding sites. The chromatin immunoprecipitation (ChIP) assays were used to assess the direct binding of c-fos to the EphA5 promoter. Furthermore, dual-luciferase assays showed that these three c-fos protein binding sites were positive regulatory elements for EphA5 expression in PC12 cells. Moreover, We verified c-fos positively regulation for EphA5 expression in CH model. Q-PCR and Western blot showed that c-fos overexpression could upregulate EphA5 expression in hippocampal neurons of rats with CH. Our results suggest that c-fos positively regulates EphA5 expression in CH rat model.

  12. CCN5 modulates the antiproliferative effect of heparin and regulates cell motility in vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Castellot John J

    2003-11-01

    Full Text Available Abstract Background Vascular smooth muscle cell (VSMC hyperplasia plays an important role in both chronic and acute vascular pathologies including atherosclerosis and restenosis. Considerable work has focused on the mechanisms regulating VSMC proliferation and motility. Earlier work in our lab revealed a novel growth arrest-specific (gas gene induced in VSMC exposed to the antiproliferative agent heparin. This gene is a member of the CCN family and has been given the name CCN5. The objective of the present study is to elucidate the function of CCN5 protein and to explore its mechanism of action in VSMC. Results Using RNA interference (RNAi, we first demonstrate that CCN5 is required for the antiproliferative effect of heparin in VSMC. We also use this gene knockdown approach to show that CCN5 is an important negative regulator of motility. To explore the mechanism of action of CCN5 on VSMC motility, we use RNAi to demonstrate that knock down of CCN5 up regulates expression of matrix metalloproteinase-2 (MMP-2, an important stimulator of motility in VSMC. In addition, forced expression of CCN5 via adenovirus results in reduced MMP-2 activity, this also corroborates the gene knock down results. Finally, we show that loss of CCN5 expression in VSMC causes changes in VSMC morphology and cytoskeletal organization, including a reduction in the amount and macromolecular assembly of smooth muscle cell α-actin. Conclusions This work provides important new insights into the regulation of smooth muscle cell proliferation and motility by CCN5 and may aid the development of therapies for vascular diseases.

  13. Assembly and Regulation of the Membrane Attack Complex Based on Structures of C5b6 and sC5b9

    Directory of Open Access Journals (Sweden)

    Michael A. Hadders

    2012-03-01

    Full Text Available Activation of the complement system results in formation of membrane attack complexes (MACs, pores that disrupt lipid bilayers and lyse bacteria and other pathogens. Here, we present the crystal structure of the first assembly intermediate, C5b6, together with a cryo-electron microscopy reconstruction of a soluble, regulated form of the pore, sC5b9. Cleavage of C5 to C5b results in marked conformational changes, distinct from those observed in the homologous C3-to-C3b transition. C6 captures this conformation, which is preserved in the larger sC5b9 assembly. Together with antibody labeling, these structures reveal that complement components associate through sideways alignment of the central MAC-perforin (MACPF domains, resulting in a C5b6-C7-C8β-C8α-C9 arc. Soluble regulatory proteins below the arc indicate a potential dual mechanism in protection from pore formation. These results provide a structural framework for understanding MAC pore formation and regulation, processes important for fighting infections and preventing complement-mediated tissue damage.

  14. Preparation of a novel dual-function strong cation exchange/hydrophobic interaction chromatography stationary phase for protein separation.

    Science.gov (United States)

    Zhao, Kailou; Yang, Li; Wang, Xuejiao; Bai, Quan; Yang, Fan; Wang, Fei

    2012-08-30

    We have explored a novel dual-function stationary phase which combines both strong cation exchange (SCX) and hydrophobic interaction chromatography (HIC) characteristics. The novel dual-function stationary phase is based on porous and spherical silica gel functionalized with ligand containing sulfonic and benzyl groups capable of electrostatic and hydrophobic interaction functionalities, which displays HIC character in a high salt concentration, and IEC character in a low salt concentration in mobile phase employed. As a result, it can be employed to separate proteins with SCX and HIC modes, respectively. The resolution and selectivity of the dual-function stationary phase were evaluated under both HIC and SCX modes with standard proteins and can be comparable to that of conventional IEC and HIC columns. More than 96% of mass and bioactivity recoveries of proteins can be achieved in both HIC and SCX modes, respectively. The results indicated that the novel dual-function column could replace two individual SCX and HIC columns for protein separation. Mixed retention mechanism of proteins on this dual-function column based on stoichiometric displacement theory (SDT) in LC was investigated to find the optimal balance of the magnitude of electrostatic and hydrophobic interactions between protein and the ligand on the silica surface in order to obtain high resolution and selectivity for protein separation. In addition, the effects of the hydrophobicity of the ligand of the dual-function packings and pH of the mobile phase used on protein separation were also investigated in detail. The results show that the ligand with suitable hydrophobicity to match the electrostatic interaction is very important to prepare the dual-function stationary phase, and a better resolution and selectivity can be obtained at pH 6.5 in SCX mode. Therefore, the dual-function column can replace two individual SCX and HIC columns for protein separation and be used to set up two-dimensional liquid

  15. MicroRNA-139-5p acts as a tumor suppressor by targeting ELTD1 and regulating cell cycle in glioblastoma multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Shouping [Department of Diagnostic Imaging, Linyi People' s Hospital, Linyi, Shandong 276000 (China); Wang, Xianjun [Department of Neurology, Linyi People' s Hospital, Linyi, Shandong 276000 (China); Li, Xiao [Department of Pathology, First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Cao, Yuandong, E-mail: yuandongcao@sina.com [Department of Radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province (China)

    2015-11-13

    MicroRNA-139-5p was identified to be significantly down-regulated in glioblastoma multiform (GBM) by miRNA array. In this report we aimed to clarify its biological function, molecular mechanisms and direct target gene in GBM. Twelve patients with GBM were analyzed for the expression of miR-139-5p by quantitative RT-PCR. miR-139-5p overexpression was established by transfecting miR-139-5p-mimic into U87MG and T98G cells, and its effects on cell proliferation were studied using MTT assay and colony formation assays. We concluded that ectopic expression of miR-139-5p in GBM cell lines significantly suppressed cell proliferation and inducing apoptosis. Bioinformatics coupled with luciferase and western blot assays also revealed that miR-139-5p suppresses glioma cell proliferation by targeting ELTD1 and regulating cell cycle. - Highlights: • miR-139-5p is downregulated in GBM. • miR-139-5p regulates cell proliferation through inducing apoptosis. • miR-139-5p regulates glioblastoma tumorigenesis by targeting 3′UTR of ELTD1. • miR-139-5p is involved in cell cycle regulation.

  16. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Kai, E-mail: gk161@163.com [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China); Department of Respiration, 161th Hospital, PLA, Wuhan 430015 (China); Jin, Faguang, E-mail: jinfag@fmmu.edu.cn [Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi' an 710038 (China)

    2015-09-25

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

  17. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    International Nuclear Information System (INIS)

    Guo, Kai; Jin, Faguang

    2015-01-01

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells

  18. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development

    Science.gov (United States)

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C.; Hedgepeth, John W.; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E.; Amacher, Sharon L.; Goessling, Wolfram

    2016-01-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic versus pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. PMID:27474396

  19. An index for the “local‿ influence in social networks

    NARCIS (Netherlands)

    Rossi, Wilbert Samuel; Frasca, Paolo

    2016-01-01

    In this paper we define a novel index of node centrality in social networks that extends the recently proposed Harmonic Influence Centrality (HIC) and that we call Local- Harmonic Influence centrality (L-HIC). Indeed, when compared with the HIC, our index shows a local nature that rules out one

  20. FKBP5 moderation of the relationship between childhood trauma and maladaptive emotion regulation strategies in adolescents.

    Science.gov (United States)

    Halldorsdottir, Thorhildur; de Matos, Ana Paula Soares; Awaloff, Yvonne; Arnarson, Eiríkur Örn; Craighead, W Edward; Binder, Elisabeth B

    2017-10-01

    Maladaptive emotion regulation strategies, such as rumination and catastrophizing, are transdiagnostic risk factors for psychopathology. FK506-binding protein 51 (FKBP5) has been found to moderate the relationship between stressful life events and various psychiatric disorders. Given the cross-disorder moderation effect of FKBP5 at the diagnostic level, the aim of the current study was to examine whether the relationship between exposure to childhood trauma and transdiagnostic maladaptive emotion regulation processes would also be moderated by genetic FKBP5 variation in a community sample of adolescents. We hypothesized that adolescent carriers of the FKBP5 CATT haplotype composed of rs9296158, rs3800373, rs1360780, and rs9470080, that has been associated with increased risk for psychiatric disorders in adulthood, would also show higher levels of rumination and catastrophizing. Participants included 1345 genotyped adolescents (M age =13.95, 64.2% female; 100% European Caucasians of Portuguese descent) who completed self-report measures on exposure to childhood trauma and emotion regulation strategies. Genotypes of rs9296158, rs3800373, rs1360780, and rs9470080 were used to estimate the CATT haplotype (carriers versus non-carriers). Consistent with our hypotheses and previous findings, adolescent CATT haplotype carriers with higher levels of childhood trauma endorsed higher levels of both rumination and catastrophizing compared to non-carriers. Given the association of these maladaptive emotion regulation processes and psychiatric disorders, the findings suggest possible psychological mechanisms why FKBP5 haplotype carriers exposed to childhood trauma are more vulnerable to developing a psychiatric disorder later in life. Copyright © 2017. Published by Elsevier Ltd.

  1. RNAi screening of subtracted transcriptomes reveals tumor suppression by taurine-activated GABAA receptors involved in volume regulation

    Science.gov (United States)

    van Nierop, Pim; Vormer, Tinke L.; Foijer, Floris; Verheij, Joanne; Lodder, Johannes C.; Andersen, Jesper B.; Mansvelder, Huibert D.; te Riele, Hein

    2018-01-01

    To identify coding and non-coding suppressor genes of anchorage-independent proliferation by efficient loss-of-function screening, we have developed a method for enzymatic production of low complexity shRNA libraries from subtracted transcriptomes. We produced and screened two LEGO (Low-complexity by Enrichment for Genes shut Off) shRNA libraries that were enriched for shRNA vectors targeting coding and non-coding polyadenylated transcripts that were reduced in transformed Mouse Embryonic Fibroblasts (MEFs). The LEGO shRNA libraries included ~25 shRNA vectors per transcript which limited off-target artifacts. Our method identified 79 coding and non-coding suppressor transcripts. We found that taurine-responsive GABAA receptor subunits, including GABRA5 and GABRB3, were induced during the arrest of non-transformed anchor-deprived MEFs and prevented anchorless proliferation. We show that taurine activates chloride currents through GABAA receptors on MEFs, causing seclusion of cell volume in large membrane protrusions. Volume seclusion from cells by taurine correlated with reduced proliferation and, conversely, suppression of this pathway allowed anchorage-independent proliferation. In human cholangiocarcinomas, we found that several proteins involved in taurine signaling via GABAA receptors were repressed. Low GABRA5 expression typified hyperproliferative tumors, and loss of taurine signaling correlated with reduced patient survival, suggesting this tumor suppressive mechanism operates in vivo. PMID:29787571

  2. Orphan Nuclear Receptor Small Heterodimer Partner Negatively Regulates Growth Hormone-mediated Induction of Hepatic Gluconeogenesis through Inhibition of Signal Transducer and Activator of Transcription 5 (STAT5) Transactivation*

    Science.gov (United States)

    Kim, Yong Deuk; Li, Tiangang; Ahn, Seung-Won; Kim, Don-Kyu; Lee, Ji-Min; Hwang, Seung-Lark; Kim, Yong-Hoon; Lee, Chul-Ho; Lee, In-Kyu; Chiang, John Y. L.; Choi, Hueng-Sik

    2012-01-01

    Growth hormone (GH) is a key metabolic regulator mediating glucose and lipid metabolism. Ataxia telangiectasia mutated (ATM) is a member of the phosphatidylinositol 3-kinase superfamily and regulates cell cycle progression. The orphan nuclear receptor small heterodimer partner (SHP: NR0B2) plays a pivotal role in regulating metabolic processes. Here, we studied the role of ATM on GH-dependent regulation of hepatic gluconeogenesis in the liver. GH induced phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase gene expression in primary hepatocytes. GH treatment and adenovirus-mediated STAT5 overexpression in hepatocytes increased glucose production, which was blocked by a JAK2 inhibitor, AG490, dominant negative STAT5, and STAT5 knockdown. We identified a STAT5 binding site on the PEPCK gene promoter using reporter assays and point mutation analysis. Up-regulation of SHP by metformin-mediated activation of the ATM-AMP-activated protein kinase pathway led to inhibition of GH-mediated induction of hepatic gluconeogenesis, which was abolished by an ATM inhibitor, KU-55933. Immunoprecipitation studies showed that SHP physically interacted with STAT5 and inhibited STAT5 recruitment on the PEPCK gene promoter. GH-induced hepatic gluconeogenesis was decreased by either metformin or Ad-SHP, whereas the inhibition by metformin was abolished by SHP knockdown. Finally, the increase of hepatic gluconeogenesis following GH treatment was significantly higher in the liver of SHP null mice compared with that of wild-type mice. Overall, our results suggest that the ATM-AMP-activated protein kinase-SHP network, as a novel mechanism for regulating hepatic glucose homeostasis via a GH-dependent pathway, may be a potential therapeutic target for insulin resistance. PMID:22977252

  3. Texture, local misorientation, grain boundary and recrystallization fraction in pipeline steels related to hydrogen induced cracking

    Energy Technology Data Exchange (ETDEWEB)

    Mohtadi-Bonab, M.A., E-mail: m.mohtadi@usask.ca; Eskandari, M.; Szpunar, J.A.

    2015-01-03

    In the present study, API X60 and X60SS pipeline steels were cathodically charged by hydrogen for 8 h using 0.2 M sulfuric acid and 3 g/l ammonium thiocyanate. After charging, SEM observations showed that the hydrogen induced cracking (HIC) appeared at the center of cross section in the X60 specimen. However, HIC did not appear in the X60SS steel. Therefore, electron backscatter diffraction (EBSD) technique was used to analyze the center of cross section of as-received X60SS, X60 and HIC tested X60 specimens. The results showed that the HIC crack not only can propagate through 〈100〉||ND oriented grains but also its growth may happen in various orientations. In HIC tested X60 specimen, an accumulation of low angle grain boundaries around the crack path documented that full recrystallization was not achieved during hot rolling. Kernel Average Misorientaion (KAM) histogram illustrated that the deformation is more concentrated in as-received and HIC tested X60 specimens rather than in as-received X60SS specimen. Moreover, the concentration of coincidence site lattice (CSL) boundary in HIC tested X60 specimen was very low compared with other samples. The recrystallization area fraction in X60SS steel was very high. This high amount of recrystallization fraction with no stored energy is one of the main reasons for high HIC resistance of this steel to HIC. The orientation distribution function (ODF) of the recrystallized, substructured and deformed fractions in as-received X60SS and X60 steel showed relative close orientations in both as-received specimens.

  4. BDNF val66met Polymorphism Impairs Hippocampal Long-Term Depression by Down-Regulation of 5-HT3 Receptors

    Directory of Open Access Journals (Sweden)

    Rui Hao

    2017-10-01

    Full Text Available Brain-derived neurotrophic factor (BDNF is a key regulator of neuronal plasticity and cognitive functions. BDNF val66met polymorphism, a human single-nucleotide polymorphism (SNP in the pro-domain of BDNF gene, is associated with deficits in activity-dependent BDNF secretion and hippocampus-dependent memory. However, the underlying mechanism remains unclear. Here we show that in the BDNFMet/Met mouse line mimicking the human SNP, BDNF expression in the hippocampus was decreased. There was a reduction in the total number of cells in hippocampal CA1 region, while hippocampal expression of mRNAs for NR2a, 2b, GluR1, 2 and GABAARβ3 subunits were up-regulated. Although basal glutamatergic neurotransmission was unaltered, hippocampal long-term depression (LTD induced by low-frequency stimulation was impaired, which was partially rescued by exogenous application of BDNF. Interestingly, 5-HT3a receptors were down-regulated in the hippocampus of BDNFMet/Met mice, whereas 5-HT2c receptors were up-regulated. Moreover, impaired LTD in BDNFMet/Met mice was reversed by 5-HT3aR agonist. Thus, these observations indicate that BDNF val66met polymorphism changes hippocampal synaptic plasticity via down-regulation of 5-HT3a receptors, which may underlie cognition dysfunction of Met allele carriers.

  5. PtdIns(3,4,5)P3 is a regulator of myosin-X localization and filopodia formation

    DEFF Research Database (Denmark)

    Plantard, Laure; Arjonen, Antti; Lock, John G

    2010-01-01

    Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] is a key regulator of cell signaling that acts by recruiting proteins to the cell membrane, such as at the leading edge during cell migration. Here, we show that PtdIns (3,4,5)P3 plays a central role in filopodia formation via the bindi...... endosomal vesicles. Given that the localization of Myo10 was dynamically restored to filopodia upon reinstatement of PtdIns(3,4,5)P3-binding, our results indicate that PtdIns(3,4,5)P3 binding to the Myo10-PH2 domain is involved in Myo10 trafficking and regulation of filopodia dynamics....

  6. [Three dimensional finite element analysis of maxillary anterior teeth retraction with micro-implant anchorage and sliding mechanics].

    Science.gov (United States)

    Zhang, Yi; Zhang, Lei; Fan, Yu-bo; Song, Jin-lin; Deng, Feng

    2009-10-01

    To investigate the biomechanical effects of micro-implant anchorage technique with sliding mechanics on maxillary anterior teeth retraction under different implant insertion heights and different retraction hook heights. The three dimensional finite element model of maxillary anterior teeth retraction force system was constructed with CT scanning and MIMICS software and the relationships between brackets, teeth, wire and micro-implant were simulating the clinical factions. Then the initial tooth displacement was calculated when the insertion heights were 4 mm and 8 mm and the retraction hook heights were 1, 4, 7, 10 mm respectively. With retraction hook height added, the anterior teeth movement changed from lingual crown tipping to labial crown tipping and the intrusion movement was more apparent when the micro-implant was inserted in a higher location. The ideal teeth movement control could be achieved by different insertion heights of micro-implant and different retraction hook heights in straight wire retraction force system.

  7. GCN5 Regulates FGF Signaling and Activates Selective MYC Target Genes during Early Embryoid Body Differentiation

    Directory of Open Access Journals (Sweden)

    Li Wang

    2018-01-01

    Full Text Available Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF signaling pathway in early embryoid bodies (EBs. Gcn5−/− EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage. Genomic analyses identified seven genes as putative direct targets of GCN5 during early differentiation, four of which are cMYC targets. These findings established a link between GCN5 and the FGF signaling pathway and highlighted specific GCN5-MYC partnerships in gene regulation during early differentiation.

  8. Examining the Psychometric Properties of the" Emotional Regulation Checklist" in 4- and 5-Year-Old Preschoolers

    Science.gov (United States)

    Danisman, Sahin; Iman, Esra Dereli; Demircan, Zeynep Akin; Yaya, Dilara

    2016-01-01

    Introduction: Emotional Regulation Checklist is frequently used to determine emotional developments of children by teacher and parents of children. The purpose of this study was to examining the Psychometric Properties of "Emotional Regulation Check List" for 4-5 years age in preschool children. Method: The sample of the research was…

  9. Study of the interactions between a proline-rich protein and a flavan-3-ol by NMR: residual structures in the natively unfolded protein provides anchorage points for the ligands.

    Science.gov (United States)

    Pascal, Christine; Paté, Franck; Cheynier, Véronique; Delsuc, Marc-André

    2009-09-01

    Astringency is one of the major organoleptic properties of food and beverages that are made from plants, such as tea, chocolate, beer, or red wine. This sensation is thought to be due to interactions between tannins and salivary proline-rich proteins, which are natively unfolded proteins. A human salivary proline-rich protein, namely IB-5, was produced by the recombinant method. Its interactions with a model tannin, epigallocatechin gallate (EGCG), the major flavan-3-ol in green tea, were studied here. Circular dichroism experiments showed that IB-5 presents residual structures (PPII helices) when the ionic strength is close to that in saliva. In the presence of these residual structures, IB-5 undergoes an increase in structural content upon binding to EGCG. NMR data corroborated the presence of preformed structural elements within the protein prior to binding and a partial assignment was proposed, showing partial structuration. TOCSY experiments showed that amino acids that are involved in PPII helices are more likely to interact with EGCG than those in random coil regions, as if they were anchorage points for the ligand. The signal from IB-5 in the DOSY NMR spectrum revealed an increase in polydispersity upon addition of EGCG while the mean hydrodynamic radius remained unchanged. This strongly suggests the formation of IB-5/EGCG aggregates.

  10. The effect of motorcycle helmet fit on estimating head impact kinematics from residual liner crush.

    Science.gov (United States)

    Bonin, Stephanie J; Gardiner, John C; Onar-Thomas, Arzu; Asfour, Shihab S; Siegmund, Gunter P

    2017-09-01

    Proper helmet fit is important for optimizing head protection during an impact, yet many motorcyclists wear helmets that do not properly fit their heads. The goals of this study are i) to quantify how a mismatch in headform size and motorcycle helmet size affects headform peak acceleration and head injury criteria (HIC), and ii) to determine if peak acceleration, HIC, and impact speed can be estimated from the foam liner's maximum residual crush depth or residual crush volume. Shorty-style helmets (4 sizes of a single model) were tested on instrumented headforms (4 sizes) during linear impacts between 2.0 and 10.5m/s to the forehead region. Helmets were CT scanned to quantify residual crush depth and volume. Separate linear regression models were used to quantify how the response variables (peak acceleration (g), HIC, and impact speed (m/s)) were related to the predictor variables (maximum crush depth (mm), crush volume (cm 3 ), and the difference in circumference between the helmet and headform (cm)). Overall, we found that increasingly oversized helmets reduced peak headform acceleration and HIC for a given impact speed for maximum residual crush depths less than 7.9mm and residual crush volume less than 40cm 3 . Below these levels of residual crush, we found that peak headform acceleration, HIC, and impact speed can be estimated from a helmet's residual crush. Above these crush thresholds, large variations in headform kinematics are present, possibly related to densification of the foam liner during the impact. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. CDKL5 regulates flagellar length and localizes to the base of the flagella in Chlamydomonas

    Science.gov (United States)

    Tam, Lai-Wa; Ranum, Paul T.; Lefebvre, Paul A.

    2013-01-01

    The length of Chlamydomonas flagella is tightly regulated. Mutations in four genes—LF1, LF2, LF3, and LF4—cause cells to assemble flagella up to three times wild-type length. LF2 and LF4 encode protein kinases. Here we describe a new gene, LF5, in which null mutations cause cells to assemble flagella of excess length. The LF5 gene encodes a protein kinase very similar in sequence to the protein kinase CDKL5. In humans, mutations in this kinase cause a severe form of juvenile epilepsy. The LF5 protein localizes to a unique location: the proximal 1 μm of the flagella. The proximal localization of the LF5 protein is lost when genes that make up the proteins in the cytoplasmic length regulatory complex (LRC)—LF1, LF2, and LF3—are mutated. In these mutants LF5p becomes localized either at the distal tip of the flagella or along the flagellar length, indicating that length regulation involves, at least in part, control of LF5p localization by the LRC. PMID:23283985

  12. SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kgamma Activity through Deacetylation of Specific Lysine Residues in Mammals.

    Directory of Open Access Journals (Sweden)

    Sayaka Akieda-Asai

    Full Text Available BACKGROUND: SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5Kgamma was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268 in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kgamma knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kgamma, PI(4,5P(2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. CONCLUSIONS/SIGNIFICANCE: Our findings indicated that the control of TSH release by the SIRT1-PIP5Kgamma pathway is important for regulating the metabolism of the whole body.

  13. Wnt5a regulates midbrain dopaminergic axon growth and guidance.

    Directory of Open Access Journals (Sweden)

    Brette D Blakely

    2011-03-01

    Full Text Available During development, precise temporal and spatial gradients are responsible for guiding axons to their appropriate targets. Within the developing ventral midbrain (VM the cues that guide dopaminergic (DA axons to their forebrain targets remain to be fully elucidated. Wnts are morphogens that have been identified as axon guidance molecules. Several Wnts are expressed in the VM where they regulate the birth of DA neurons. Here, we describe that a precise temporo-spatial expression of Wnt5a accompanies the development of nigrostriatal projections by VM DA neurons. In mice at E11.5, Wnt5a is expressed in the VM where it was found to promote DA neurite and axonal growth in VM primary cultures. By E14.5, when DA axons are approaching their striatal target, Wnt5a causes DA neurite retraction in primary cultures. Co-culture of VM explants with Wnt5a-overexpressing cell aggregates revealed that Wnt5a is capable of repelling DA neurites. Antagonism experiments revealed that the effects of Wnt5a are mediated by the Frizzled receptors and by the small GTPase, Rac1 (a component of the non-canonical Wnt planar cell polarity pathway. Moreover, the effects were specific as they could be blocked by Wnt5a antibody, sFRPs and RYK-Fc. The importance of Wnt5a in DA axon morphogenesis was further verified in Wnt5a-/- mice, where fasciculation of the medial forebrain bundle (MFB as well as the density of DA neurites in the MFB and striatal terminals were disrupted. Thus, our results identify a novel role of Wnt5a in DA axon growth and guidance.

  14. Differential Regulation of Elastic Fiber Formation by Fibulin-4 and -5*

    Science.gov (United States)

    Choudhury, Rawshan; McGovern, Amanda; Ridley, Caroline; Cain, Stuart A.; Baldwin, Andrew; Wang, Ming-Chuan; Guo, Chun; Mironov, Aleksandr; Drymoussi, Zoe; Trump, Dorothy; Shuttleworth, Adrian; Baldock, Clair; Kielty, Cay M.

    2009-01-01

    Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. We have determined how they interact with tropoelastin, lysyl oxidase, and fibrillin-1, thereby revealing how they differentially regulate assembly. Strong binding between fibulin-4 and lysyl oxidase enhanced the interaction of fibulin-4 with tropoelastin, forming ternary complexes that may direct elastin cross-linking. In contrast, fibulin-5 did not bind lysyl oxidase strongly but bound tropoelastin in terminal and central regions and could concurrently bind fibulin-4. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin. Knockdown experiments revealed that fibulin-5 controlled elastin deposition on microfibrils, although fibulin-4 can also bind fibrillin-1. These experiments provide a molecular account of the distinct roles of fibulin-4 and -5 in elastic fiber assembly and how they act in concert to chaperone cross-linked elastin onto microfibrils. PMID:19570982

  15. 5 CFR 1633.1 - Cross-reference to employee ethical conduct standards and financial disclosure regulations.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Cross-reference to employee ethical... ethical conduct standards and financial disclosure regulations. Employees of the Federal Retirement Thrift Investment Board (Board) are subject to the executive branch-wide Standards of Ethical conduct at 5 CFR part...

  16. Genetic interaction of two abscisic acid signaling regulators, HY5 and FIERY1, in mediating lateral root formation

    KAUST Repository

    Chen, Hao

    2011-01-01

    Root architecture is continuously shaped in a manner that helps plants to better adapt to the environment. Gene regulation at the transcriptional or post-transcriptional levels largely controls this environmental response. Recently, RNA silencing has emerged as an important player in gene regulation and is involved in many aspects of plant development, including lateral root formation. In a recent study, we found that FIERY1, a bifunctional abiotic stress and abscisic acid (ABA) signaling regulator and an endogenous RNA silencing suppressor, mediates auxin response during lateral root formation in Arabidopsis. We proposed that FRY1 regulates lateral root development through its activity on adenosine 3,5-bisphosphate (PAP), a strong inhibitor of exoribonucleases (XRNs). Interestingly, some of the phenotypes of fry1, such as enhanced response to light in repressing hypocotyl elongation and hypersensitivity to ABA in lateral root growth, are opposite to those of another light- and ABA-signaling mutant, hy5. Here we analyzed the hy5 fry1 double mutant for root and hypocotyl growth. We found that the hy5 mutation can suppress the enhanced light sensitivity in fry1 hypocotyl elongation and restore the lateral root formation. The genetic interaction between HY5 and FRY1 indicates that HY5 and FRY1 may act in overlapping pathways that mediate light signaling and lateral root development. © 2011 Landes Bioscience.

  17. An RNA-binding protein, Qki5, regulates embryonic neural stem cells through pre-mRNA processing in cell adhesion signaling.

    Science.gov (United States)

    Hayakawa-Yano, Yoshika; Suyama, Satoshi; Nogami, Masahiro; Yugami, Masato; Koya, Ikuko; Furukawa, Takako; Zhou, Li; Abe, Manabu; Sakimura, Kenji; Takebayashi, Hirohide; Nakanishi, Atsushi; Okano, Hideyuki; Yano, Masato

    2017-09-15

    Cell type-specific transcriptomes are enabled by the action of multiple regulators, which are frequently expressed within restricted tissue regions. In the present study, we identify one such regulator, Quaking 5 (Qki5), as an RNA-binding protein (RNABP) that is expressed in early embryonic neural stem cells and subsequently down-regulated during neurogenesis. mRNA sequencing analysis in neural stem cell culture indicates that Qki proteins play supporting roles in the neural stem cell transcriptome and various forms of mRNA processing that may result from regionally restricted expression and subcellular localization. Also, our in utero electroporation gain-of-function study suggests that the nuclear-type Qki isoform Qki5 supports the neural stem cell state. We next performed in vivo transcriptome-wide protein-RNA interaction mapping to search for direct targets of Qki5 and elucidate how Qki5 regulates neural stem cell function. Combined with our transcriptome analysis, this mapping analysis yielded a bona fide map of Qki5-RNA interaction at single-nucleotide resolution, the identification of 892 Qki5 direct target genes, and an accurate Qki5-dependent alternative splicing rule in the developing brain. Last, our target gene list provides the first compelling evidence that Qki5 is associated with specific biological events; namely, cell-cell adhesion. This prediction was confirmed by histological analysis of mice in which Qki proteins were genetically ablated, which revealed disruption of the apical surface of the lateral wall in the developing brain. These data collectively indicate that Qki5 regulates communication between neural stem cells by mediating numerous RNA processing events and suggest new links between splicing regulation and neural stem cell states. © 2017 Hayakawa-Yano et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Enhancement of high density polyethylene high integrity containers at a low level radioactive waste disposal site

    International Nuclear Information System (INIS)

    Sauer, R.E.; Wong, O.P.

    1989-01-01

    High integrity containers (HIC) made of high density polyethylene (HDPE) have been used for disposal in South Carolina since the late seventies. With the recent definitive position taken by the NRC on the suitability of these containers for disposal, alternative means of assuring the structural integrity of the containers for the long term became necessary. The authors' company has developed an utilized reinforced concrete caissons at the Hanford, Washington site as an additional barrier and structural element to assure the long term high integrity function of the current HDPE HIC's also known as Poly HIC's on the market. This paper outlines the background of the HIC's in question, the NRC positions and ruling, and presents technical bases for the applicability of appropriately designed concrete overpacks to augment the structural integrity of HIC's

  19. The Arabidopsis CROWDED NUCLEI genes regulate seed germination by modulating degradation of ABI5 protein.

    Science.gov (United States)

    Zhao, Wenming; Guan, Chunmei; Feng, Jian; Liang, Yan; Zhan, Ni; Zuo, Jianru; Ren, Bo

    2016-07-01

    In Arabidopsis, the phytohormone abscisic acid (ABA) plays a vital role in inhibiting seed germination and in post-germination seedling establishment. In the ABA signaling pathway, ABI5, a basic Leu zipper transcription factor, has important functions in the regulation of seed germination. ABI5 protein localizes in nuclear bodies, along with AFP, COP1, and SIZ1, and was degraded through the 26S proteasome pathway. However, the mechanisms of ABI5 nuclear body formation and ABI5 protein degradation remain obscure. In this study, we found that the Arabidopsis CROWDED NUCLEI (CRWN) proteins, predicted nuclear matrix proteins essential for maintenance of nuclear morphology, also participate in ABA-controlled seed germination by regulating the degradation of ABI5 protein. During seed germination, the crwn mutants are hypersensitive to ABA and have higher levels of ABI5 protein compared to wild type. Genetic analysis suggested that CRWNs act upstream of ABI5. The observation that CRWN3 colocalizes with ABI5 in nuclear bodies indicates that CRWNs might participate in ABI5 protein degradation in nuclear bodies. Moreover, we revealed that the extreme C-terminal of CRWN3 protein is necessary for its function in the response to ABA in germination. Our results suggested important roles of CRWNs in ABI5 nuclear body organization and ABI5 protein degradation during seed germination. © 2015 Institute of Botany, Chinese Academy of Sciences.

  20. MLL5, a trithorax homolog, indirectly regulates H3K4 methylation, represses cyclin A2 expression, and promotes myogenic differentiation

    Science.gov (United States)

    Sebastian, Soji; Sreenivas, Prethish; Sambasivan, Ramkumar; Cheedipudi, Sirisha; Kandalla, Prashanth; Pavlath, Grace K.; Dhawan, Jyotsna

    2009-01-01

    Most cells in adult tissues are nondividing. In skeletal muscle, differentiated myofibers have exited the cell cycle permanently, whereas satellite stem cells withdraw transiently, returning to active proliferation to repair damaged myofibers. We have examined the epigenetic mechanisms operating in conditional quiescence by analyzing the function of a predicted chromatin regulator mixed lineage leukemia 5 (MLL5) in a culture model of reversible arrest. MLL5 is induced in quiescent myoblasts and regulates both the cell cycle and differentiation via a hierarchy of chromatin and transcriptional regulators. Knocking down MLL5 delays entry of quiescent myoblasts into S phase, but hastens S-phase completion. Cyclin A2 (CycA) mRNA is no longer restricted to S phase, but is induced throughout G0/G1, with activation of the cell cycle regulated element (CCRE) in the CycA promoter. Overexpressed MLL5 physically associates with the CCRE and impairs its activity. MLL5 also regulates CycA indirectly: Cux, an activator of CycA promoter and S phase is induced in RNAi cells, and Brm/Brg1, CCRE-binding repressors that promote differentiation are repressed. In knockdown cells, H3K4 methylation at the CCRE is reduced, reflecting quantitative global changes in methylation. MLL5 appears to lack intrinsic histone methyl transferase activity, but regulates expression of histone-modifying enzymes LSD1 and SET7/9, suggesting an indirect mechanism. Finally, expression of muscle regulators Pax7, Myf5, and myogenin is impaired in MLL5 knockdown cells, which are profoundly differentiation defective. Collectively, our results suggest that MLL5 plays an integral role in novel chromatin regulatory mechanisms that suppress inappropriate expression of S-phase-promoting genes and maintain expression of determination genes in quiescent cells. PMID:19264965

  1. Micro-RNA-128 (miRNA-128) down-regulation in glioblastoma targets ARP5 (ANGPTL6), Bmi-1 and E2F-3a, key regulators of brain cell proliferation.

    Science.gov (United States)

    Cui, J G; Zhao, Y; Sethi, P; Li, Y Y; Mahta, A; Culicchia, F; Lukiw, W J

    2010-07-01

    High density micro-RNA (miRNA) arrays, fluorescent-reporter miRNA assay and Northern miRNA dot-blot analysis show that a brain-enriched miRNA-128 is significantly down-regulated in glioblastoma multiforme (GBM) and in GBM cell lines when compared to age-matched controls. The down-regulation of miRNA-128 was found to inversely correlate with WHO tumor grade. Three bioinformatics-verified miRNA-128 targets, angiopoietin-related growth factor protein 5 (ARP5; ANGPTL6), a transcription suppressor that promotes stem cell renewal and inhibits the expression of known tumor suppressor genes involved in senescence and differentiation, Bmi-1, and a transcription factor critical for the control of cell-cycle progression, E2F-3a, were found to be up-regulated. Addition of exogenous miRNA-128 to CRL-1690 and CRL-2610 GBM cell lines (a) restored 'homeostatic' ARP5 (ANGPTL6), Bmi-1 and E2F-3a expression, and (b) significantly decreased the proliferation of CRL-1690 and CRL-2610 cell lines. Our data suggests that down-regulation of miRNA-128 may contribute to glioma and GBM, in part, by coordinately up-regulating ARP5 (ANGPTL6), Bmi-1 and E2F-3a, resulting in the proliferation of undifferentiated GBM cells.

  2. 77 FR 11651 - Hybrid III 10-Year-Old Child Test Dummy

    Science.gov (United States)

    2012-02-27

    ... words, chin-to- chest contact often caused HIC to exceed the injury assessment reference value (HIC 36... bag tests).\\19\\ \\19\\ The computation of HIC applies a higher signal filter class (CFC 1000 vs. CFC 180... Dorel provided a picture of a torn bib assembly, without further discussion, in its response to the Part...

  3. WNT5A-JNK regulation of vascular insulin resistance in human obesity.

    Science.gov (United States)

    Farb, Melissa G; Karki, Shakun; Park, Song-Young; Saggese, Samantha M; Carmine, Brian; Hess, Donald T; Apovian, Caroline; Fetterman, Jessica L; Bretón-Romero, Rosa; Hamburg, Naomi M; Fuster, José J; Zuriaga, María A; Walsh, Kenneth; Gokce, Noyan

    2016-12-01

    Obesity is associated with the development of vascular insulin resistance; however, pathophysiological mechanisms are poorly understood. We sought to investigate the role of WNT5A-JNK in the regulation of insulin-mediated vasodilator responses in human adipose tissue arterioles prone to endothelial dysfunction. In 43 severely obese (BMI 44±11 kg/m 2 ) and five metabolically normal non-obese (BMI 26±2 kg/m 2 ) subjects, we isolated arterioles from subcutaneous and visceral fat during planned surgeries. Using videomicroscopy, we examined insulin-mediated, endothelium-dependent vasodilator responses and characterized adipose tissue gene and protein expression using real-time polymerase chain reaction and Western blot analyses. Immunofluorescence was used to quantify endothelial nitric oxide synthase (eNOS) phosphorylation. Insulin-mediated vasodilation was markedly impaired in visceral compared to subcutaneous vessels from obese subjects (p<0.001), but preserved in non-obese individuals. Visceral adiposity was associated with increased JNK activation and elevated expression of WNT5A and its non-canonical receptors, which correlated negatively with insulin signaling. Pharmacological JNK antagonism with SP600125 markedly improved insulin-mediated vasodilation by sixfold (p<0.001), while endothelial cells exposed to recombinant WNT5A developed insulin resistance and impaired eNOS phosphorylation (p<0.05). We observed profound vascular insulin resistance in the visceral adipose tissue arterioles of obese subjects that was associated with up-regulated WNT5A-JNK signaling and impaired endothelial eNOS activation. Pharmacological JNK antagonism markedly improved vascular endothelial function, and may represent a potential therapeutic target in obesity-related vascular disease. © The Author(s) 2016.

  4. 33 CFR 110.87 - Henderson Harbor, N.Y.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Henderson Harbor, N.Y. 110.87... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.87 Henderson Harbor, N.Y. (a) Area A. The area in the... latitude 43°51′08.8″ N, longitude 76°12′08.9″ W, thence to latitude 43°51′09.0″ N, longitude 76°12′19.0″ W...

  5. Talk about high integrity container

    International Nuclear Information System (INIS)

    Luo Shanggeng

    2009-01-01

    The high integrity container (HIC) has been paid great attention to recently in China. The reason and the comparison of advantages and disadvantages are described in this article. The characteristics and fabrications of some foreign HIC and their test procedures have been introduced. Finally, some opinion and discussion related to develop HIC are put forward, too. (author)

  6. Regulator of G-protein signaling-5 is a marker of hepatic stellate cells and expression mediates response to liver injury.

    Directory of Open Access Journals (Sweden)

    Arya J Bahrami

    Full Text Available Liver fibrosis is mediated by hepatic stellate cells (HSCs, which respond to a variety of cytokine and growth factors to moderate the response to injury and create extracellular matrix at the site of injury. G-protein coupled receptor (GPCR-mediated signaling, via endothelin-1 (ET-1 and angiotensin II (AngII, increases HSC contraction, migration and fibrogenesis. Regulator of G-protein signaling-5 (RGS5, an inhibitor of vasoactive GPCR agonists, functions to control GPCR-mediated contraction and hypertrophy in pericytes and smooth muscle cells (SMCs. Therefore we hypothesized that RGS5 controls GPCR signaling in activated HSCs in the context of liver injury. In this study, we localize RGS5 to the HSCs and demonstrate that Rgs5 expression is regulated during carbon tetrachloride (CCl4-induced acute and chronic liver injury in Rgs5LacZ/LacZ reporter mice. Furthermore, CCl4 treated RGS5-null mice develop increased hepatocyte damage and fibrosis in response to CCl4 and have increased expression of markers of HSC activation. Knockdown of Rgs5 enhances ET-1-mediated signaling in HSCs in vitro. Taken together, we demonstrate that RGS5 is a critical regulator of GPCR signaling in HSCs and regulates HSC activation and fibrogenesis in liver injury.

  7. Movimentação de molares inferiores ancorados em mini-parafusos Mandibular molar uprighting, using mini-screw as anchorage

    Directory of Open Access Journals (Sweden)

    Rosana Canteras Di Matteo

    2005-08-01

    Full Text Available Freqüentemente a movimentação ortodôntica exige recursos adicionais de ancoragem. Os mini-parafusos têm-se apresentado como uma possível solução. O propósito deste trabalho foi estabelecer um método para a verticalização de molares inferiores inclinados para mesial, utilizando ancoragem em mini-parafusos colocados na região de linha oblíqüa externa da mandíbula. Foram selecionados três pacientes entre 40 a 48 anos (dois do gênero feminino, um do gênero masculino, com molares inferiores inclinados para mesial e distalmente posicionados às áreas edêntulas. Os pacientes foram tratados ortodonticamente durante um período de 6 a 12 meses, com técnica ortodôntica MD3. Mini-parafusos de titânio foram colocados bilateralmente com anestesia local. Uma incisão sobre a linha oblíqüa externa da mandíbula, medindo aproximadamente 1 cm foi realizada em cada lado, distalmente aos molares inclinados. Após descolamento muco-periosteal, mini-parafusos foram implantados e foram realizadas suturas deixando suas cabeças exteriorizadas. Uma semana após a remoção das suturas, cargas ortodônticas (entre 150 a 200 gramas/força foram aplicadas através de forças elásticas. Verificamos que alguma inflamação foi observada ao redor dos mini-parafusos, mas foi controlada com procedimentos de higienização. O procedimento cirúrgico é simples, podendo ser realizado pelo ortodontista; as formas dimensionais dos mini-parafusos são adequadas e estes são de fácil remoção após uso. Concluímos que o uso de mini-parafusos representa uma alternativa efetiva de ancoragem ortodôntica na verticalização de molares inferiores.Tooth movement frequently requires additional anchorage resources. Mini-screws have been used as a possible solution to this matter. The purpose of this study was to establish a method of mandibular molar uprighting, using mini-screw as anchorage, positioned on the mandibular external oblique line, behind and

  8. Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC).

    Science.gov (United States)

    Zhang, Tiening; Cai, Xun; Li, Qi; Xue, Peng; Chen, Zhixiao; Dong, Xiao; Xue, Ying

    2016-07-05

    Hsa-miRNA-875-5p (miR-875-5p) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-875-5p on colorectal carcinoma (CRC) is still ambiguous. In this study, we investigated the role of miR-875-5p on the development of CRC. The results indicated that miR-875-5p was significantly down-regulated in primary tumor tissues and very low levels were found in CRC cell lines. Ectopic expression of miR-875-5p in CRC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-875-5p induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-875-5p inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene EGFR was revealed to be a putative target of miR-875-5p, which was inversely correlated with miR-875-5p expression in CRC. Taken together, our results demonstrated that miR-875-5p played a pivotal role on CRC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic EGFR.

  9. 76 FR 29640 - Special Local Regulations for Marine Events; Chester River, Chestertown, MD

    Science.gov (United States)

    2011-05-23

    ... 200 yards to an anchorage location, embarking and disembarking Tea Party actors by dinghy, and then... reference Datum NAD 1983. (b) Definitions: (1) Coast Guard Patrol Commander means a commissioned, warrant...

  10. α5-GABAA receptors negatively regulate MYC-amplified medulloblastoma growth.

    Science.gov (United States)

    Sengupta, Soma; Weeraratne, Shyamal Dilhan; Sun, Hongyu; Phallen, Jillian; Rallapalli, Sundari K; Teider, Natalia; Kosaras, Bela; Amani, Vladimir; Pierre-Francois, Jessica; Tang, Yujie; Nguyen, Brian; Yu, Furong; Schubert, Simone; Balansay, Brianna; Mathios, Dimitris; Lechpammer, Mirna; Archer, Tenley C; Tran, Phuoc; Reimer, Richard J; Cook, James M; Lim, Michael; Jensen, Frances E; Pomeroy, Scott L; Cho, Yoon-Jae

    2014-04-01

    Neural tumors often express neurotransmitter receptors as markers of their developmental lineage. Although these receptors have been well characterized in electrophysiological, developmental and pharmacological settings, their importance in the maintenance and progression of brain tumors and, importantly, the effect of their targeting in brain cancers remains obscure. Here, we demonstrate high levels of GABRA5, which encodes the α5-subunit of the GABAA receptor complex, in aggressive MYC-driven, "Group 3" medulloblastomas. We hypothesized that modulation of α5-GABAA receptors alters medulloblastoma cell survival and monitored biological and electrophysiological responses of GABRA5-expressing medulloblastoma cells upon pharmacological targeting of the GABAA receptor. While antagonists, inverse agonists and non-specific positive allosteric modulators had limited effects on medulloblastoma cells, a highly specific and potent α5-GABAA receptor agonist, QHii066, resulted in marked membrane depolarization and a significant decrease in cell survival. This effect was GABRA5 dependent and mediated through the induction of apoptosis as well as accumulation of cells in S and G2 phases of the cell cycle. Chemical genomic profiling of QHii066-treated medulloblastoma cells confirmed inhibition of MYC-related transcriptional activity and revealed an enrichment of HOXA5 target gene expression. siRNA-mediated knockdown of HOXA5 markedly blunted the response of medulloblastoma cells to QHii066. Furthermore, QHii066 sensitized GABRA5 positive medulloblastoma cells to radiation and chemotherapy consistent with the role of HOXA5 in directly regulating p53 expression and inducing apoptosis. Thus, our results provide novel insights into the synthetic lethal nature of α5-GABAA receptor activation in MYC-driven/Group 3 medulloblastomas and propose its targeting as a novel strategy for the management of this highly aggressive tumor.

  11. Angiotensin II Type 1 Receptor Mechanoactivation Involves RGS5 (Regulator of G Protein Signaling 5) in Skeletal Muscle Arteries: Impaired Trafficking of RGS5 in Hypertension.

    Science.gov (United States)

    Hong, Kwangseok; Li, Min; Nourian, Zahra; Meininger, Gerald A; Hill, Michael A

    2017-12-01

    Studies suggest that arteriolar pressure-induced vasoconstriction can be initiated by GPCRs (G protein-coupled receptors), including the AT 1 R (angiotensin II type 1 receptor). This raises the question, are such mechanisms regulated by negative feedback? The present studies examined whether RGS (regulators of G protein signaling) proteins in vascular smooth muscle cells are colocalized with the AT 1 R when activated by mechanical stress or angiotensin II and whether this modulates AT 1 R-mediated vasoconstriction. To determine whether activation of the AT 1 R recruits RGS5, an in situ proximity ligation assay was performed in primary cultures of cremaster muscle arteriolar vascular smooth muscle cells treated with angiotensin II or hypotonic solution in the absence or presence of candesartan (an AT 1 R blocker). Proximity ligation assay results revealed a concentration-dependent increase in trafficking/translocation of RGS5 toward the activated AT 1 R, which was attenuated by candesartan. In intact arterioles, knockdown of RGS5 enhanced constriction to angiotensin II and augmented myogenic responses to increased intraluminal pressure. Myogenic constriction was attenuated to a higher degree by candesartan in RGS5 siRNA-transfected arterioles, consistent with RGS5 contributing to downregulation of AT 1 R-mediated signaling. Further, translocation of RGS5 was impaired in vascular smooth muscle cells of spontaneously hypertensive rats. This is consistent with dysregulated (RGS5-mediated) AT 1 R signaling that could contribute to excessive vasoconstriction in hypertension. In intact vessels, candesartan reduced myogenic vasoconstriction to a greater extent in spontaneously hypertensive rats compared with controls. Collectively, these findings suggest that AT 1 R activation results in translocation of RGS5 toward the plasma membrane, limiting AT 1 R-mediated vasoconstriction through its role in G q/11 protein-dependent signaling. © 2017 American Heart Association, Inc.

  12. 7 CFR 340.3 - Notification for the introduction of certain regulated articles. 5

    Science.gov (United States)

    2010-01-01

    ... ALTERED OR PRODUCED THROUGH GENETIC ENGINEERING WHICH ARE PLANT PESTS OR WHICH THERE IS REASON TO BELIEVE... plant parts must be contained or devitalized when no longer in use. (4) There must be no viable vector agent associated with the regulated article. (5) The field trial must be conducted such that: (i) The...

  13. Calcium and cargoes as regulators of myosin 5a activity

    International Nuclear Information System (INIS)

    Sellers, James R.; Thirumurugan, Kavitha; Sakamoto, Takeshi; Hammer, John A.; Knight, Peter J.

    2008-01-01

    Myosin 5a is a two-headed actin-dependent motor that transports various cargoes in cells. Its enzymology and mechanochemistry have been extensively studied in vitro. It is a processive motor that takes multiple 36 nm steps on actin. The enzymatic activity of myosin 5 is regulated by an intramolecular folding mechanism whereby its lever arms fold back against the coiled-coil tail such that the motor domains directly bind the globular tail domains. We show that the structure seen in individual folded molecules is consistent with electron density map of two-dimensional crystals of the molecule. In this compact state, the actin-activated MgATPase activity of the molecule is markedly inhibited and the molecule cannot move processively on surface bound actin filaments. The actin-activated MgATPase activity of myosin 5a is activated by increasing the calcium concentration or by binding of a cargo-receptor molecule, melanophilin, in vitro. However, calcium binding to the calmodulin light chains results in dissociation of some of the calmodulin which disrupts the ability of myosin 5a to move on actin filaments in vitro. Thus we propose that the physiologically relevant activation pathway in vivo involves binding of cargo-receptor proteins

  14. The long non-coding RNA GAS5 cooperates with the eukaryotic translation initiation factor 4E to regulate c-Myc translation.

    Directory of Open Access Journals (Sweden)

    Guangzhen Hu

    Full Text Available Long noncoding RNAs (lncRNAs are important regulators of transcription; however, their involvement in protein translation is not well known. Here we explored whether the lncRNA GAS5 is associated with translation initiation machinery and regulates translation. GAS5 was enriched with eukaryotic translation initiation factor-4E (eIF4E in an RNA-immunoprecipitation assay using lymphoma cell lines. We identified two RNA binding motifs within eIF4E protein and the deletion of each motif inhibited the binding of GAS5 with eIF4E. To confirm the role of GAS5 in translation regulation, GAS5 siRNA and in vitro transcribed GAS5 RNA were used to knock down or overexpress GAS5, respectively. GAS5 siRNA had no effect on global protein translation but did specifically increase c-Myc protein level without an effect on c-Myc mRNA. The mechanism of this increase in c-Myc protein was enhanced association of c-Myc mRNA with the polysome without any effect on protein stability. In contrast, overexpression of in vitro transcribed GAS5 RNA suppressed c-Myc protein without affecting c-Myc mRNA. Interestingly, GAS5 was found to be bound with c-Myc mRNA, suggesting that GAS5 regulates c-Myc translation through lncRNA-mRNA interaction. Our findings have uncovered a role of GAS5 lncRNA in translation regulation through its interactions with eIF4E and c-Myc mRNA.

  15. Arabidopsis MADS-Box Transcription Factor AGL21 Acts as Environmental Surveillance of Seed Germination by Regulating ABI5 Expression.

    Science.gov (United States)

    Yu, Lin-Hui; Wu, Jie; Zhang, Zi-Sheng; Miao, Zi-Qing; Zhao, Ping-Xia; Wang, Zhen; Xiang, Cheng-Bin

    2017-06-05

    Seed germination is a crucial checkpoint for plant survival under unfavorable environmental conditions. Abscisic acid (ABA) signaling plays a vital role in integrating environmental information to regulate seed germination. It has been well known that MCM1/AGAMOUS/DEFICIENS/SRF (MADS)-box transcription factors are key regulators of seed and flower development in Arabidopsis. However, little is known about their functions in seed germination. Here we report that MADS-box transcription factor AGL21 is a negative regulator of seed germination and post-germination growth by controlling the expression of ABA-INSENSITIVE 5 (ABI5) in Arabidopsis. The AGL21-overexpressing plants were hypersensitive to ABA, salt, and osmotic stresses during seed germination and early post-germination growth, whereas agl21 mutants were less sensitive. We found that AGL21 positively regulated ABI5 expression in seeds. Consistently, genetic analyses showed that AGL21 is epistatic to ABI5 in controlling seed germination. Chromatin immunoprecipitation assays further demonstrated that AGL21 could directly bind to the ABI5 promoter in plant cells. Moreover, we found that AGL21 responded to multiple environmental stresses and plant hormones during seed germination. Taken together, our results suggest that AGL21 acts as a surveillance integrator that incorporates environmental cues and endogenous hormonal signals into ABA signaling to regulate seed germination and early post-germination growth. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

  16. Identification of candidate biomarker mass (m/z) ranges in serous ovarian adenocarcinoma using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling.

    Science.gov (United States)

    Periyasamy, Amutha; Gopisetty, Gopal; Veluswami, Sridevi; Joyimallaya Subramanium, Malliga; Thangarajan, Rajkumar

    2015-01-01

    To differentiate plasma from ovarian cancer and healthy individuals using MALDI-TOF mass spectroscopy. MALDI-TOF was used to generate profiles of immuno-depleted plasma samples (89 cancers and 199 healthy individuals) that were fractionated using three types of magnetic beads (HIC8, WCX and IMAC-Cu). Differentially expressed mass ranges showing >1.5-2-fold change in expression from HIC8 (30), WCX (12) and IMAC-Cu (6) fractions were identified. Cross validation and recognition capability scores for the models indicated discrimination between the classes. Spectral profiles can differentiate plasma samples of ovarian cancer patients from healthy individuals.

  17. Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Jingjing [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Xu, Chen [Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Department of Orthopedics, Changzheng Hospital Affiliated to Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003 (China); Fang, Ziyu; Li, Yaoming [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Liu, Houqi; Wang, Yue [Research Center of Developmental Biology, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Translational Medicine Center, Second Military Medical University, 800th Xiangyin Road, Shanghai, 200433 (China); Xu, Chuanliang [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China); Sun, Yinghao, E-mail: sunyh@medmail.com.cn [Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433 (China)

    2016-05-20

    Abstracts: MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3′UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. -- Highlights: •miR-182-5p is the mostly up-regulated miRNA in Chinese prostate cancer. •miR-182-5p is regulated by androgen receptor. •miR-182-5p promotes prostate cancer progression. •miR-182-5p regulates ARRDC3/ITGB4 pathway.

  18. Androgen receptor regulated microRNA miR-182-5p promotes prostate cancer progression by targeting the ARRDC3/ITGB4 pathway

    International Nuclear Information System (INIS)

    Yao, Jingjing; Xu, Chen; Fang, Ziyu; Li, Yaoming; Liu, Houqi; Wang, Yue; Xu, Chuanliang; Sun, Yinghao

    2016-01-01

    Abstracts: MicroRNAs (miRNAs) are important endogenous gene regulators that play key roles in prostate cancer development and metastasis. However, specific miRNA expression patterns in prostate cancer tissues from Chinese patients remain largely unknown. In this study, we compared miRNA expression patterns in 65 pairs of prostate cancer and para-cancer tissues by RNA sequencing and found that miR-182-5p was the most up-regulated miRNA in prostate cancer tissues. The result was validated using realtime PCR in 18 pairs of prostate cancer and para-cancer tissues. In in vitro analysis, it was confirmed that miR-182-5p promotes prostate cancer cell proliferation, invasion and migration and inhibit apoptosis. In addition, the androgen receptor directly regulated the transcription of miR-182-5p, which could target to the 3′UTR of ARRDC3 mRNA and affect the expression of ARRDC3 and its downstream gene ITGB4. For the in vivo experiment, miR-182-5p overexpression also promoted the growth and progression of prostate cancer tumors. In this regard, we suggest that miR-182-5p may be a key androgen receptor-regulated factor that contributes to the development and metastasis of Chinese prostate cancers and may be a potential target for the early diagnosis and therapeutic studies of prostate cancer. -- Highlights: •miR-182-5p is the mostly up-regulated miRNA in Chinese prostate cancer. •miR-182-5p is regulated by androgen receptor. •miR-182-5p promotes prostate cancer progression. •miR-182-5p regulates ARRDC3/ITGB4 pathway.

  19. Identification and characterization of a gibberellin-regulated protein, which is ASR5, in the basal region of rice leaf sheaths.

    Science.gov (United States)

    Takasaki, Hironori; Mahmood, Tariq; Matsuoka, Makoto; Matsumoto, Hiroshi; Komatsu, Setsuko

    2008-04-01

    Gibberellins (GAs) regulate growth and development in higher plants. To identify GA-regulated proteins during rice leaf sheath elongation, a proteomic approach was used. Proteins from the basal region of leaf sheath in rice seedling treated with GA(3) were analyzed by fluorescence two-dimensional difference gel electrophoresis. The levels of abscisic acid-stress-ripening-inducible 5 protein (ASR5), elongation factor-1 beta, translationally controlled tumor protein, fructose-bisphosphate aldolase and a novel protein increased; whereas the level of RuBisCO subunit binding-protein decreased by GA(3) treatment. ASR5 out of these six proteins was significantly regulated by GA(3) at the protein level but not at the mRNA level in the basal region of leaf sheaths. Since this protein is regulated not only by abscisic acid but also by GA(3), these results indicate that ASR5 might be involved in plant growth in addition to stress in the basal regions of leaf sheaths.

  20. Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis.

    Directory of Open Access Journals (Sweden)

    David Garciadiego-Cázares

    Full Text Available The Integrin β1 family is the major receptors of the Extracellular matrix (ECM, and the synthesis and degradation balance of ECM is seriously disrupted during Osteoarthritis (OA. In this scenario, integrins modify their pattern expression and regulate chondrocyte differentiation in the articular cartilage. Members of the Transforming growth factor beta (Tgf-β Superfamily, such as Growth differentiation factor 5 (Gdf-5 and Bone morphogenetic protein 7 (Bmp-7, play a key role in joint formation and could regulate the integrin expression during chondrocyte differentiation and osteoarthritis progression in an experimental OA rat model. Decrease of α5 integrin expression in articular cartilage was related with chondrocyte dedifferentiation during OA progression, while increase of α1, α2, and α3 integrin expression was related with fibrous areas in articular cartilage during OA. Hypertrophic chondrocytes expressed αV integrin and was increased in the articular cartilage of rats with OA. Integrin expression during chondrocyte differentiation was also analyzed in a micromass culture system of mouse embryo mesenchymal cells, micromass cultures was treated with Gdf-5 or Bmp-7 for 4 and 6 days, respectively. Gdf-5 induced the expression of the α5 sub-unit, while Bmp-7 induced the expression of the αV sub-unit. This suggests a switch in signaling for prehypertrophic chondrocyte differentiation towards hypertrophy, where Gdf-5 could maintain the articular chondrocyte phenotype and Bmp-7 would induce hypertrophy. Decrease of Ihh expression during late stages of OA in rat model suggest that the ossification in OA rat knees and endochondral ossification could be activated by Bmp-7 and αV integrin in absence of Ihh. Thus, chondrocyte phenotype in articular cartilage is similar to prehypetrophic chondrocyte in growth plate, and is preserved due to the presence of Indian hedgehog (Ihh, Gdf-5 and α5 integrin to maintain articular cartilage and prevent

  1. The Essential Role of Mbd5 in the Regulation of Somatic Growth and Glucose Homeostasis in Mice

    Science.gov (United States)

    Du, Yarui; Liu, Bo; Guo, Fan; Xu, Guifang; Ding, Yuqiang; Liu, Yong; Sun, Xin; Xu, Guoliang

    2012-01-01

    Methyl-CpG binding domain protein 5 (MBD5) belongs to the MBD family proteins, which play central roles in transcriptional regulation and development. The significance of MBD5 function is highlighted by recent studies implicating it as a candidate gene involved in human 2q23.1 microdeletion syndrome. To investigate the physiological role of Mbd5, we generated knockout mice. The Mbd5-deficient mice showed growth retardation, wasting and pre-weaning lethality. The observed growth retardation was associated with the impairment of GH/IGF-1 axis in Mbd5-null pups. Conditional knockout of Mbd5 in the brain resulted in the similar phenotypes as whole body deletion, indicating that Mbd5 functions in the nervous system to regulate postnatal growth. Moreover, the mutant mice also displayed enhanced glucose tolerance and elevated insulin sensitivity as a result of increased insulin signaling, ultimately resulting in disturbed glucose homeostasis and hypoglycemia. These results indicate Mbd5 as an essential factor for mouse postnatal growth and maintenance of glucose homeostasis. PMID:23077600

  2. Vitamin B5 Reduces Bacterial Growth via Regulating Innate Immunity and Adaptive Immunity in Mice Infected with Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Wenting He

    2018-02-01

    Full Text Available The mechanisms by which vitamins regulate immunity and their effect as an adjuvant treatment for tuberculosis have gradually become very important research topics. Studies have found that vitamin B5 (VB5 can promote epithelial cells to express inflammatory cytokines. We aimed to examine the proinflammatory and antibacterial effect of VB5 in macrophages infected with Mycobacterium tuberculosis (MTB strain H37Rv and the therapeutic potential of VB5 in vivo with tuberculosis. We investigated the activation of inflammatory signal molecules (NF-κB, AKT, JNK, ERK, and p38, the expression of two primary inflammatory cytokines (tumor necrosis factor and interleukin-6 and the bacterial burdens in H37Rv-infected macrophages stimulated with VB5 to explore the effect of VB5 on the inflammatory and antibacterial responses of macrophages. We further treated the H37Rv-infected mice with VB5 to explore VB5’s promotion of the clearance of H37Rv in the lungs and the effect of VB5 on regulating the percentage of inflammatory cells. Our data showed that VB5 enhanced the phagocytosis and inflammatory response in macrophages infected with H37Rv. Oral administration of VB5 decreased the number of colony-forming units of H37Rv in lungs of mice at 1, 2, and 4 weeks after infection. In addition, VB5 regulated the percentage of macrophages and promoted CD4+ T cells to express interferon-γ and interleukin-17; however, it had no effect on the percentage of polymorphonuclear neutrophils, CD4+ and CD8+ T cells. In conclusion, VB5 significantly inhibits the growth of MTB by regulating innate immunity and adaptive immunity.

  3. α5-GABAA receptors negatively regulate MYC-amplified medulloblastoma growth

    Science.gov (United States)

    Sengupta, Soma; Weeraratne, Shyamal Dilhan; Sun, Hongyu; Phallen, Jillian; Rallapalli, Sundari K.; Teider, Natalia; Kosaras, Bela; Amani, Vladimir; Pierre-Francois, Jessica; Tang, Yujie; Nguyen, Brian; Yu, Furong; Schubert, Simone; Balansay, Brianna; Mathios, Dimitris; Lechpammer, Mirna; Archer, Tenley C.; Tran, Phuoc; Reimer, Richard J.; Cook, James M.; Lim, Michael; Jensen, Frances E.; Pomeroy, Scott L.; Cho, Yoon-Jae

    2013-01-01

    Neural tumors often express neurotransmitter receptors as markers of their developmental lineage. Although these receptors have been well characterized in electrophysiological, developmental and pharmacological settings, their importance in the maintenance and progression of brain tumors, and importantly, the effect of their targeting in brain cancers remains obscure. Here, we demonstrate high levels of GABR5, which encodes the α-subunit of the GABAA receptor complex, in aggressive MYC-driven, “Group 3” medulloblastomas. We hypothesized that modulation of α-GABAA receptors alters medulloblastoma cell survival and monitored biological and electrophysiological responses of GABR5-expressing medulloblastoma cells upon pharmacological targeting of the GABAA receptor. While antagonists, inverse agonists and non-specific positive allosteric modulators had limited effects on medulloblastoma cells, a highly specific and potent α5-GABAA receptor agonist, QHii066, resulted in marked membrane depolarization and a significant decrease in cell survival. This effect was GABR5 dependent and mediated through the induction of apoptosis as well as accumulation of cells in S and G2 phases of the cell cycle. Chemical genomic profiling of QHii066-treated medulloblastoma cells confirmed inhibition of MYC-related transcriptional activity and revealed an enrichment of HOX5 target gene expression. siRNA-mediated knockdown of HOX5 markedly blunted the response of medulloblastoma cells to QHii066. Furthermore, QHii066 sensitized GABR5 positive medulloblastoma cells to radiation and chemotherapy consistent with the role of HOX5 in directly regulating p53 expression and inducing apoptosis. Thus, our results provide novel insights into the synthetic lethal nature of α5-GABAA receptor activation in MYC-driven/Group 3 medulloblastomas and propose its targeting as a novel strategy for the management of this highly aggressive tumor. PMID:24196163

  4. 76 FR 71321 - North Pacific Fishery Management Council; Public Meetings

    Science.gov (United States)

    2011-11-17

    ... public meetings, December 5-13, 2011 at the Anchorage Hilton Hotel. DATES: The Council will begin its... sessions. ADDRESSES: The meetings will be held at the Hilton Hotel, 500 West Third Avenue, Anchorage, AK...

  5. The COP9 Signalosome regulates seed germination by facilitating protein degradation of RGL2 and ABI5.

    Directory of Open Access Journals (Sweden)

    Dan Jin

    2018-02-01

    Full Text Available The control of seed germination and seed dormancy are critical for the successful propagation of plant species, and are important agricultural traits. Seed germination is tightly controlled by the balance of gibberellin (GA and abscisic acid (ABA, and is influenced by environmental factors. The COP9 Signalosome (CSN is a conserved multi-subunit protein complex that is best known as a regulator of the Cullin-RING family of ubiquitin E3 ligases (CRLs. Multiple viable mutants of the CSN showed poor germination, except for csn5b-1. Detailed analyses showed that csn1-10 has a stronger seed dormancy, while csn5a-1 mutants exhibit retarded seed germination in addition to hyperdormancy. Both csn5a-1 and csn1-10 plants show defects in the timely removal of the germination inhibitors: RGL2, a repressor of GA signaling, and ABI5, an effector of ABA responses. We provide genetic evidence to demonstrate that the germination phenotype of csn1-10 is caused by over-accumulation of RGL2, a substrate of the SCF (CRL1 ubiquitin E3 ligase, while the csn5a-1 phenotype is caused by over-accumulation of RGL2 as well as ABI5. The genetic data are consistent with the hypothesis that CSN5A regulates ABI5 by a mechanism that may not involve CSN1. Transcriptome analyses suggest that CSN1 has a more prominent role than CSN5A during seed maturation, but CSN5A plays a more important role than CSN1 during seed germination, further supporting the functional distinction of these two CSN genes. Our study delineates the molecular targets of the CSN complex in seed germination, and reveals that CSN5 has additional functions in regulating ABI5, thus the ABA signaling pathway.

  6. Experiment list: SRX873865 [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available 8 cells or in CF tests against SV40, RSV or adenoviruses, mycoplasma contamination was detected and elimin...ated in 1972, (PMID: 6081590) 41679100,97.5,11.6,32630 GSM1607526: GR siHic5 rep1;

  7. Wnt-5a/Frizzled9 Receptor Signaling through the Gαo-Gβγ Complex Regulates Dendritic Spine Formation*

    Science.gov (United States)

    Ramírez, Valerie T.; Ramos-Fernández, Eva; Henríquez, Juan Pablo; Lorenzo, Alfredo; Inestrosa, Nibaldo C.

    2016-01-01

    Wnt ligands play crucial roles in the development and regulation of synapse structure and function. Specifically, Wnt-5a acts as a secreted growth factor that regulates dendritic spine formation in rodent hippocampal neurons, resulting in postsynaptic development that promotes the clustering of the PSD-95 (postsynaptic density protein 95). Here, we focused on the early events occurring after the interaction between Wnt-5a and its Frizzled receptor at the neuronal cell surface. Additionally, we studied the role of heterotrimeric G proteins in Wnt-5a-dependent synaptic development. We report that FZD9 (Frizzled9), a Wnt receptor related to Williams syndrome, is localized in the postsynaptic region, where it interacts with Wnt-5a. Functionally, FZD9 is required for the Wnt-5a-mediated increase in dendritic spine density. FZD9 forms a precoupled complex with Gαo under basal conditions that dissociates after Wnt-5a stimulation. Accordingly, we found that G protein inhibition abrogates the Wnt-5a-dependent pathway in hippocampal neurons. In particular, the activation of Gαo appears to be a key factor controlling the Wnt-5a-induced dendritic spine density. In addition, we found that Gβγ is required for the Wnt-5a-mediated increase in cytosolic calcium levels and spinogenesis. Our findings reveal that FZD9 and heterotrimeric G proteins regulate Wnt-5a signaling and dendritic spines in cultured hippocampal neurons. PMID:27402827

  8. Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production

    DEFF Research Database (Denmark)

    Lee, Ying Shiuan; De Vadder, Filipe; Tremaroli, Valentina

    2016-01-01

    expression in the brain was higher in CONV-R versus GF mice. We also observed that colonic Insl5 expression was suppressed by increasing the energy supply in GF mice by colonization or high-fat feeding. We did not observe any differences in food intake, gut transit or oral glucose tolerance between Insl5......-/- and wild-type mice. However, we showed impaired intraperitoneal glucose tolerance in Insl5-/- mice. We also observed improved insulin tolerance and reduced hepatic glucose production in Insl5-/- mice. CONCLUSIONS: We have shown that colonic Insl5 expression is regulated by the gut microbiota and energy...... availability. We propose that INSL5 is a hormone that could play a role in promoting hepatic glucose production during periods of energy deprivation....

  9. Anchorage strength models for end-debonding predictions in RC beams strengthened with FRP composites

    Science.gov (United States)

    Nardini, V.; Guadagnini, M.; Valluzzi, M. R.

    2008-05-01

    The increase in the flexural capacity of RC beams obtained by externally bonding FRP composites to their tension side is often limited by the premature and brittle debonding of the external reinforcement. An in-depth understanding of this complex failure mechanism, however, has not yet been achieved. With specific regard to end-debonding failure modes, extensive experimental observations reported in the literature highlight the important distinction, often neglected in strength models proposed by researchers, between the peel-off and rip-off end-debonding types of failure. The peel-off failure is generally characterized by a failure plane located within the first few millimetres of the concrete cover, whilst the rip-off failure penetrates deeper into the concrete cover and propagates along the tensile steel reinforcement. A new rip-off strength model is described in this paper. The model proposed is based on the Chen and Teng peel-off model and relies upon additional theoretical considerations. The influence of the amount of the internal tensile steel reinforcement and the effective anchorage length of FRP are considered and discussed. The validity of the new model is analyzed further through comparisons with test results, findings of a numerical investigation, and a parametric study. The new rip-off strength model is assessed against a database comprising results from 62 beams tested by various researchers and is shown to yield less conservative results.

  10. NuChart: an R package to study gene spatial neighbourhoods with multi-omics annotations.

    Directory of Open Access Journals (Sweden)

    Ivan Merelli

    Full Text Available Long-range chromosomal associations between genomic regions, and their repositioning in the 3D space of the nucleus, are now considered to be key contributors to the regulation of gene expression and important links have been highlighted with other genomic features involved in DNA rearrangements. Recent Chromosome Conformation Capture (3C measurements performed with high throughput sequencing (Hi-C and molecular dynamics studies show that there is a large correlation between colocalization and coregulation of genes, but these important researches are hampered by the lack of biologists-friendly analysis and visualisation software. Here, we describe NuChart, an R package that allows the user to annotate and statistically analyse a list of input genes with information relying on Hi-C data, integrating knowledge about genomic features that are involved in the chromosome spatial organization. NuChart works directly with sequenced reads to identify the related Hi-C fragments, with the aim of creating gene-centric neighbourhood graphs on which multi-omics features can be mapped. Predictions about CTCF binding sites, isochores and cryptic Recombination Signal Sequences are provided directly with the package for mapping, although other annotation data in bed format can be used (such as methylation profiles and histone patterns. Gene expression data can be automatically retrieved and processed from the Gene Expression Omnibus and ArrayExpress repositories to highlight the expression profile of genes in the identified neighbourhood. Moreover, statistical inferences about the graph structure and correlations between its topology and multi-omics features can be performed using Exponential-family Random Graph Models. The Hi-C fragment visualisation provided by NuChart allows the comparisons of cells in different conditions, thus providing the possibility of novel biomarkers identification. NuChart is compliant with the Bioconductor standard and it is freely

  11. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides.

    Science.gov (United States)

    Chen, W; Kelly, M A; Opitz-Araya, X; Thomas, R E; Low, M J; Cone, R D

    1997-12-12

    The effects of pituitary-derived melanocortin peptides are primarily attributed to ACTH-mediated adrenocortical glucocorticoid production. Identification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediated systemic effects of these peptides. Targeted disruption of the MC5-R produced mice with a severe defect in water repulsion and thermoregulation due to decreased production of sebaceous lipids. High levels of MC5-R was found in multiple exocrine tissues, including Harderian, preputial, lacrimal, and sebaceous glands, and was also shown to be required for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacrimal gland. These data show a requirement for the MC5-R in multiple exocrine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melanocortin peptides.

  12. The Liver X Receptor Ligand T0901317 Down-regulates APOA5 GeneExpression through Activation of SREBP-1c

    Energy Technology Data Exchange (ETDEWEB)

    Jakel, Heidelinde; Nowak, Maxime; Moitrot, Emanuelle; Dehondt, Helene; Hum, Dean W.; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart,Jean-Charles

    2004-07-23

    Alterations in the expression of the recently discovered apolipoprotein A5 gene strongly affect plasma triglyceride levels. In this study, we investigated the contribution of APOA5 to the liver X-receptor (LXR) ligand mediated effect on plasma triglyceride levels.Following treatment with the LXR ligand T0901317, we found that APOA5mRNA levels were decreased in hepatoma cell lines. The observation that no down-regulation of APOA5 promoter activity was obtained by LXR-retinoid X receptor (RXR) co-transfection prompted us to explore the possible involvement of the known LXR target gene SREBP-1c (sterol regulatory element-binding protein 1c). In fact, we found that co-transfection with the active form of SREBP-1c down-regulated APOA5promoter activity in a dose-dependent manner. We then scanned the human APOA5 promoter sequence and identified two putative E-box elements that were able to bind specifically SREBP-1c in gel-shift assays and were shown to be functional by mutation analysis. Subsequent suppression of SREBP-1 mRNA through small interfering RNA interference abolished the decrease of APOA5 mRNA in response to T0901317. Finally, administration of T0901317 to hAPOA5 transgenic mice revealed a significant decrease OF APOA5 mRNA in liver tissue and circulating apolipoprotein AV protein in plasma, confirming that the described down-regulation also occurs in vivo. Taken together, our results demonstrate that APOA5 gene expression is regulated by the LXR ligand T0901317 in a negative manner through SREBP-1c. These findings may provide a new mechanism responsible for the elevation of plasma triglyceride levels by LXR ligands and support the development of selective LXR agonists, not affecting SREBP-1c, as beneficial modulators of lipid metabolism.

  13. Enhanced caveolin-1 expression increases migration, anchorage-independent growth and invasion of endometrial adenocarcinoma cells

    International Nuclear Information System (INIS)

    Diaz-Valdivia, Natalia; Bravo, Denisse; Huerta, Hernán; Henriquez, Soledad; Gabler, Fernando; Vega, Margarita; Romero, Carmen; Calderon, Claudia; Owen, Gareth I.; Leyton, Lisette; Quest, Andrew F. G.

    2015-01-01

    Caveolin-1 (CAV1) has been implicated both in tumor suppression and progression, whereby the specific role appears to be context dependent. Endometrial cancer is one of the most common malignancies of the female genital tract; however, little is known about the role of CAV1 in this disease. Here, we first determined by immunohistochemistry CAV1 protein levels in normal proliferative human endometrium and endometrial tumor samples. Then using two endometrial cancer cell lines (ECC: Ishikawa and Hec-1A) we evaluated mRNA and protein levels of CAV1 by real time qPCR and Western blot analysis, respectively. The role of CAV1 expression in ECC malignancy was further studied by either inducing its expression in endometrial cancer cells with the tumor promotor 12-O-tetradecanoyl-phorbol-13-acetate (4β-TPA) or decreasing expression using short-hairpin RNA constructs, and then evaluating the effects of these changes on ECC proliferation, transmigration, matrigel invasion, and colony formation in soft agar. Immunohistochemical analysis of endometrial epithelia revealed that substantially higher levels of CAV1 were present in endometrial tumors than the normal proliferative epithelium. Also, in Ishikawa and Hec-1A endometrial cancer cells CAV1 expression was readily detectable. Upon treatment with 4β-TPA CAV1 levels increased and coincided with augmented cell transmigration, matrigel invasion, as well as colony formation in soft agar. Reduction of CAV1 expression using short-hairpin RNA constructs ablated these effects in both cell types whether treated or not with 4β-TPA. Alternatively, CAV1 expression appeared not to modulate significantly proliferation of these cells. Our study shows that elevated CAV1, observed in patients with endometrial cancer, is linked to enhanced malignancy of endometrial cancer cells, as evidenced by increased migration, invasion and anchorage-independent growth. The online version of this article (doi:10.1186/s12885-015-1477-5) contains

  14. Comparison of in-vivo failure of single-thread and dual-thread temporary anchorage devices over 18 months: A split-mouth randomized controlled trial.

    Science.gov (United States)

    Durrani, Owais Khalid; Shaheed, Sohrab; Khan, Arsalan; Bashir, Ulfat

    2017-10-01

    The purpose of this study was to compare the in-vivo failure rates of single-thread and dual-thread temporary anchorage device (TAD) designs over 18 months. Thirty patients with skeletal Class II Division 1 malocclusion requiring anchorage from TADs for retraction of maxillary incisors into the extracted premolar space were recruited in this parallel group, split-mouth, randomized controlled trial. A block randomization sequence was generated with Random Allocation Software (version 2.0; Isfahan, Iran) with the allocations concealed in sequentially numbered, opaque, sealed envelopes. A total of 60 TADs (diameter, 2 mm; length, 10 mm) were placed in the maxillary arches of these patients with random allocation of the 2 types to the left and the right sides in a 1:1 ratio. All TADs were placed between the roots of the second premolar and the first molar and were immediately loaded. Patients were followed for a minimum of 12 months and a maximum of 18 months for the failure of the TADs. Data were analyzed blindly on an intention-to-treat basis. Four TADs (13.3%) failed in the single-thread group, and 6 TADs (20%) failed in the dual-thread group. The McNemar test showed an insignificant difference (P = 0.72) between the 2 groups. An odds ratio of 1.6 (95% confidence interval, 0.39-6.97) showed no significant associations among the variables. Most TADs failed in the first month after insertion (50%). The failure rate of dual-thread TADs compared with single-thread TADs is statistically insignificant when placed in the maxilla for retraction of the anterior segment. Registration: The trial was not registered before commencement. The protocol was not published before the trial. Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  15. Coalition for Global Clinical Surgical Education: The Alliance for Global Clinical Training.

    Science.gov (United States)

    Graf, Jahanara; Cook, Mackenzie; Schecter, Samuel; Deveney, Karen; Hofmann, Paul; Grey, Douglas; Akoko, Larry; Mwanga, Ali; Salum, Kitembo; Schecter, William

    Assessment of the effect of the collaborative relationship between the high-income country (HIC) surgical educators of the Alliance for Global Clinical Training (Alliance) and the low-income country surgical educators at the Muhimbili University of Health and Allied Sciences/Muhimbili National Hospital (MUHAS/MNH), Dar Es Salaam, Tanzania, on the clinical global surgery training of the HIC surgical residents participating in the program. A retrospective qualitative analysis of Alliance volunteer HIC faculty and residents' reports, volunteer case lists and the reports of Alliance academic contributions to MUHAS/MNH from 2012 to 2017. In addition, a survey was circulated in late 2016 to all the residents who participated in the program since its inception. Twelve HIC surgical educators provided rotating 1-month teaching coverage at MUHAS/MNH between academic years 2012 and 2017 for a total of 21 months. During the same time period 11 HIC residents accompanied the HIC faculty for 1-month rotations. HIC surgery residents joined the MUHAS/MNH Department of Surgery, made significant teaching contributions, performed a wide spectrum of "open procedures" including hand-sewn intestinal anastomoses. Most had had either no or limited previous exposure to hand-sewn anastomoses. All of the residents commented that this was a maturing and challenging clinical rotation due to the complexity of the cases, the limited resources available and the ethical and emotional challenges of dealing with preventable complications and death in a resource constrained environment. The Alliance provides an effective clinical global surgery rotation at MUHAS/MNH for HIC Surgery Departments wishing to provide such an opportunity for their residents and faculty. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  16. Histone H3 lysine 9 methyltransferase FvDim5 regulates fungal development, pathogenicity and osmotic stress responses in Fusarium verticillioides.

    Science.gov (United States)

    Gu, Qin; Ji, Tiantian; Sun, Xiao; Huang, Hai; Zhang, Hao; Lu, Xi; Wu, Liming; Huo, Rong; Wu, Huijun; Gao, Xuewen

    2017-10-16

    Histone methylation plays important biological roles in eukaryotic cells. Methylation of lysine 9 at histone H3 (H3K9me) is critical for regulating chromatin structure and gene transcription. Dim5 is a lysine histone methyltransferase (KHMTase) enzyme, which is responsible for the methylation of H3K9 in eukaryotes. In the current study, we identified a single ortholog of Neurospora crassa Dim5 in Fusarium verticillioides. In this study, we report that FvDim5 regulates the trimethylation of H3K9 (H3K9me3). The FvDIM5 deletion mutant (ΔFvDim5) showed significant defects in conidiation, perithecium production and fungal virulence. Unexpectedly, we found that deletion of FvDIM5 resulted in increased tolerance to osmotic stresses and upregulated FvHog1 phosphorylation. These results indicate the importance of FvDim5 for the regulation of fungal development, pathogenicity and osmotic stress responses in F. verticillioides. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Role of type II protein arginine methyltransferase 5 in the regulation of Circadian Per1 gene.

    Directory of Open Access Journals (Sweden)

    Jungtae Na

    Full Text Available Circadian clocks are the endogenous oscillators that regulate rhythmic physiological and behavioral changes to correspond to daily light-dark cycles. Molecular dissections have revealed that transcriptional feedback loops of the circadian clock genes drive the molecular oscillation, in which PER/CRY complexes inhibit the transcriptional activity of the CLOCK/BMAL1 heterodimer to constitute a negative feedback loop. In this study, we identified the type II protein arginine methyltransferase 5 (PRMT5 as an interacting molecule of CRY1. Although the Prmt5 gene was constitutively expressed, increased interaction of PRMT5 with CRY1 was observed when the Per1 gene was repressed both in synchronized mouse liver and NIH3T3 cells. Moreover, rhythmic recruitment of PRMT5 and CRY1 to the Per1 gene promoter was found to be associated with an increased level of histone H4R3 dimethylation and Per1 gene repression. Consistently, decreased histone H4R3 dimethylation and altered rhythmic Per1 gene expression were observed in Prmt5-depleted cells. Taken together, these findings provide an insight into the link between histone arginine methylation by PRMT5 and transcriptional regulation of the circadian Per1 gene.

  18. GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis.

    Science.gov (United States)

    Wang, Lingdi; Scott, Iain; Zhu, Lu; Wu, Kaiyuan; Han, Kim; Chen, Yong; Gucek, Marjan; Sack, Michael N

    2017-09-12

    The mitochondrial enriched GCN5-like 1 (GCN5L1) protein has been shown to modulate mitochondrial protein acetylation, mitochondrial content and mitochondrial retrograde signaling. Here we show that hepatic GCN5L1 ablation reduces fasting glucose levels and blunts hepatic gluconeogenesis without affecting systemic glucose tolerance. PEPCK and G6Pase transcript levels are downregulated in hepatocytes from GCN5L1 liver specific knockout mice and their upstream regulator, FoxO1 protein levels are decreased via proteasome-dependent degradation and via reactive oxygen species mediated ERK-1/2 phosphorylation. ERK inhibition restores FoxO1, gluconeogenic enzyme expression and glucose production. Reconstitution of mitochondrial-targeted GCN5L1 blunts mitochondrial ROS, ERK activation and increases FoxO1, gluconeogenic enzyme expression and hepatocyte glucose production. We suggest that mitochondrial GCN5L1 modulates post-translational control of FoxO1, regulates gluconeogenesis and controls metabolic pathways via mitochondrial ROS mediated ERK activation. Exploring mechanisms underpinning GCN5L1 mediated ROS signaling may expand our understanding of the role of mitochondria in gluconeogenesis control.Hepatic gluconeogenesis is tightly regulated at transcriptional level and is essential for survival during prolonged fasting. Here Wang et al. show that the mitochondrial enriched GCN5-like 1 protein controls hepatic glucose production by regulating FoxO1 protein levels via proteasome-dependent degradation and, in turn, gluconeogenic gene expression.

  19. Hic-5’s Regulatory Role in TGFB Signaling in Prostate Stroma

    Science.gov (United States)

    2012-06-01

    the androgen metabolites 3α-Adiol and 3β-Adiol, and their importance is underscored by high expression levels of the aldo keto reductase (AKR1C...known as aldo -keto reductases (AKR1C) [33]. DU145 cells express AKR1C enzymes and are capable of catalyzing redox reactions at the C17 position of...584-95. 37. Bauman, D.R., et al., Development of nonsteroidal anti-inflammatory drug analogs and steroid carboxylates selective for human aldo -keto

  20. ERK5 pathway regulates the phosphorylation of tumour suppressor hDlg during mitosis

    Energy Technology Data Exchange (ETDEWEB)

    Inesta-Vaquera, Francisco A. [Departamento de Inmunologia y Oncologia, Centro Nacional de Biotecnologia-CSIC, Campus de Cantoblanco-UAM, 28049 Madrid (Spain); Campbell, David G.; Arthur, J. Simon C. [MRC Protein Phosphorylation Unit, Sir James Black Building, School of Life Sciences, University of Dundee, Dundee DD1 5EH (United Kingdom); Cuenda, Ana, E-mail: acuenda@cnb.csic.es [Departamento de Inmunologia y Oncologia, Centro Nacional de Biotecnologia-CSIC, Campus de Cantoblanco-UAM, 28049 Madrid (Spain)

    2010-08-13

    Research highlights: {yields} hDlg is phosphorylated during mitosis in multiple residues. {yields} Prospho-hDlg is excluded from the midbody during mitosis. {yields} hDlg is not phosphorylated by p38{gamma} or JNK1/2 during mitosis. {yields} ERK5 pathway mediates hDlg phosphorylation in mitosis. -- Abstract: Human disc-large (hDlg) is a scaffold protein critical for the maintenance of cell polarity and adhesion. hDlg is thought to be a tumour suppressor that regulates the cell cycle and proliferation. However, the mechanism and pathways involved in hDlg regulation during these processes is still unclear. Here we report that hDlg is phosphorylated during mitosis, and we establish the identity of at least three residues phosphorylated in hDlg; some are previously unreported. Phosphorylation affects hDlg localisation excluding it from the contact point between the two daughter cells. Our results reveal a previously unreported pathway for hDlg phosphorylation in mitosis and show that ERK5 pathway mediates hDlg cell cycle dependent phosphorylation. This is likely to have important implications in the correct timely mitotic entry and mitosis progression.