Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability

DEFF Research Database (Denmark)

Trego, Kelly S.; Groesser, Torsten; Davalos, Albert R.

2016-01-01

XPG is a structure-specific endonuclease required for nucleotide excision repair, and incision-defective XPG mutations cause the skin cancer-prone syndrome xeroderma pigmentosum. Truncating mutations instead cause the neurodevelopmental progeroid disorder Cockayne syndrome, but little is known ab......-phosphorylation and persistent chromatin binding. These unexpected findings establish XPG as an HRR protein with important roles in genome stability and suggest how XPG defects produce severe clinical consequences including cancer and accelerated aging....... about how XPG loss results in this devastating disease. We identify XPG as a partner of BRCA1 and BRCA2 in maintaining genomic stability through homologous recombination (HRR). XPG depletion causes DNA double-strand breaks, chromosomal abnormalities, cell-cycle delays, defective HRR, inability...

Editorial: 3Rs tightly intertwined to maintain genome stability

DEFF Research Database (Denmark)

Lisby, Michael; Mortensen, Uffe H.

2017-01-01

, replication of damaged DNA results in stalled replication forks that await DNA damage repair before replication can be resumed. In turn, the repair of most lesions depends on processes involving DNA synthesis. At the same time, the stalled forks may engage in recombination, either as part of a controlled...... repair process or by accident, just because it can, with the risk of producing genome rearrangements and loss of heterozygosity. The set of reviews presented in this thematic issue (https://academic-oup-com.proxy.findit.dtu.dk/femsyr/pages/replication_recombination_and_repair) of FEMSYR has been selected...

DNA double-strand break response in stem cells: mechanisms to maintain genomic integrity.

Science.gov (United States)

Nagaria, Pratik; Robert, Carine; Rassool, Feyruz V

2013-02-01

Embryonic stem cells (ESCs) represent the point of origin of all cells in a given organism and must protect their genomes from both endogenous and exogenous genotoxic stress. DNA double-strand breaks (DSBs) are one of the most lethal forms of damage, and failure to adequately repair DSBs would not only compromise the ability of SCs to self-renew and differentiate, but will also lead to genomic instability and disease. Herein, we describe the mechanisms by which ESCs respond to DSB-inducing agents such as reactive oxygen species (ROS) and ionizing radiation, compared to somatic cells. We will also discuss whether the DSB response is fully reprogrammed in induced pluripotent stem cells (iPSCs) and the role of the DNA damage response (DDR) in the reprogramming of these cells. ESCs have distinct mechanisms to protect themselves against DSBs and oxidative stress compared to somatic cells. The response to damage and stress is crucial for the maintenance of self-renewal and differentiation capacity in SCs. iPSCs appear to reprogram some of the responses to genotoxic stress. However, it remains to be determined if iPSCs also retain some DDR characteristics of the somatic cells of origin. The mechanisms regulating the genomic integrity in ESCs and iPSCs are critical for its safe use in regenerative medicine and may shed light on the pathways and factors that maintain genomic stability, preventing diseases such as cancer. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice.

Science.gov (United States)

Wanner, Roger M; Güthlein, Carolin; Springer, Burkhard; Böttger, Erik C; Ackermann, Martin

2008-05-28

The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable. We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability. These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.

Stabilization of the genome of the mismatch repair deficient Mycobacterium tuberculosis by context-dependent codon choice

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Ackermann Martin

2008-05-01

Full Text Available Abstract Background The rate at which a stretch of DNA mutates is determined by the cellular systems for DNA replication and repair, and by the nucleotide sequence of the stretch itself. One sequence feature with a particularly strong influence on the mutation rate are nucleotide repeats. Some microbial pathogens use nucleotide repeats in their genome to stochastically vary phenotypic traits and thereby evade host defense. However, such unstable sequences also come at a cost, as mutations are often deleterious. Here, we analyzed how these opposing forces shaped genome stability in the human pathogen Mycobacterium tuberculosis. M. tuberculosis lacks a mismatch repair system, and this renders nucleotide repeats particularly unstable. Results We found that proteins of M. tuberculosis are encoded by using codons in a context-dependent manner that prevents the emergence of nucleotide repeats. This context-dependent codon choice leads to a strong decrease in the estimated frame-shift mutation rate and thus to an increase in genome stability. Conclusion These results indicate that a context-specific codon choice can partially compensate for the lack of a mismatch repair system, and helps to maintain genome integrity in this pathogen.

Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis.

Science.gov (United States)

Pushpavalli, Sreerangam N C V L; Sarkar, Arpita; Ramaiah, M Janaki; Chowdhury, Debabani Roy; Bhadra, Utpal; Pal-Bhadra, Manika

2013-01-24

In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk) is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof¹/+; mnkp⁶/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using Drosophila as model system and carry out the interaction of MOF

Drosophila MOF controls Checkpoint protein2 and regulates genomic stability during early embryogenesis

Directory of Open Access Journals (Sweden)

Pushpavalli Sreerangam NCVL

2013-01-01

Full Text Available Abstract Background In Drosophila embryos, checkpoints maintain genome stability by delaying cell cycle progression that allows time for damage repair or to complete DNA synthesis. Drosophila MOF, a member of MYST histone acetyl transferase is an essential component of male X hyperactivation process. Until recently its involvement in G2/M cell cycle arrest and defects in ionizing radiation induced DNA damage pathways was not well established. Results Drosophila MOF is highly expressed during early embryogenesis. In the present study we show that haplo-insufficiency of maternal MOF leads to spontaneous mitotic defects like mitotic asynchrony, mitotic catastrophe and chromatid bridges in the syncytial embryos. Such abnormal nuclei are eliminated and digested in the yolk tissues by nuclear fall out mechanism. MOF negatively regulates Drosophila checkpoint kinase 2 tumor suppressor homologue. In response to DNA damage the checkpoint gene Chk2 (Drosophila mnk is activated in the mof mutants, there by causing centrosomal inactivation suggesting its role in response to genotoxic stress. A drastic decrease in the fall out nuclei in the syncytial embryos derived from mof1/+; mnkp6/+ females further confirms the role of DNA damage response gene Chk2 to ensure the removal of abnormal nuclei from the embryonic precursor pool and maintain genome stability. The fact that mof mutants undergo DNA damage has been further elucidated by the increased number of single and double stranded DNA breaks. Conclusion mof mutants exhibited genomic instability as evidenced by the occurance of frequent mitotic bridges in anaphase, asynchronous nuclear divisions, disruption of cytoskeleton, inactivation of centrosomes finally leading to DNA damage. Our findings are consistent to what has been reported earlier in mammals that; reduced levels of MOF resulted in increased genomic instability while total loss resulted in lethality. The study can be further extended using

The transcription elongation factor Bur1-Bur2 interacts with replication protein A and maintains genome stability during replication stress

DEFF Research Database (Denmark)

Clausing, Emanuel; Mayer, Andreas; Chanarat, Sittinan

2010-01-01

Multiple DNA-associated processes such as DNA repair, replication, and recombination are crucial for the maintenance of genome integrity. Here, we show a novel interaction between the transcription elongation factor Bur1-Bur2 and replication protein A (RPA), the eukaryotic single-stranded DNA......-binding protein with functions in DNA repair, recombination, and replication. Bur1 interacted via its C-terminal domain with RPA, and bur1-¿C mutants showed a deregulated DNA damage response accompanied by increased sensitivity to DNA damage and replication stress as well as increased levels of persisting Rad52...... foci. Interestingly, the DNA damage sensitivity of an rfa1 mutant was suppressed by bur1 mutation, further underscoring a functional link between these two protein complexes. The transcription elongation factor Bur1-Bur2 interacts with RPA and maintains genome integrity during DNA replication stress....

Mitotic accumulation of dimethylated lysine 79 of histone H3 is important for maintaining genome integrity during mitosis in human cells.

Science.gov (United States)

Guppy, Brent J; McManus, Kirk J

2015-02-01

The loss of genome stability is an early event that drives the development and progression of virtually all tumor types. Recent studies have revealed that certain histone post-translational modifications exhibit dynamic and global increases in abundance that coincide with mitosis and exhibit essential roles in maintaining genomic stability. Histone H2B ubiquitination at lysine 120 (H2Bub1) is regulated by RNF20, an E3 ubiquitin ligase that is altered in many tumor types. Through an evolutionarily conserved trans-histone pathway, H2Bub1 is an essential prerequisite for subsequent downstream dimethylation events at lysines 4 (H3K4me2) and 79 (H3K79me2) of histone H3. Although the role that RNF20 plays in tumorigenesis has garnered much attention, the downstream components of the trans-histone pathway, H3K4me2 and H3K79me2, and their potential contributions to genome stability remain largely overlooked. In this study, we employ single-cell imaging and biochemical approaches to investigate the spatial and temporal patterning of RNF20, H2Bub1, H3K4me2, and H3K79me2 throughout the cell cycle, with a particular focus on mitosis. We show that H2Bub1, H3K4me2, and H3K79me2 exhibit distinct temporal progression patterns throughout the cell cycle. Most notably, we demonstrate that H3K79me2 is a highly dynamic histone post-translational modification that reaches maximal abundance during mitosis in an H2Bub1-independent manner. Using RNAi and chemical genetic approaches, we identify DOT1L as a histone methyltransferase required for the mitotic-associated increases in H3K79me2. We also demonstrate that the loss of mitotic H3K79me2 levels correlates with increases in chromosome numbers and increases in mitotic defects. Collectively, these data suggest that H3K79me2 dynamics during mitosis are normally required to maintain genome stability and further implicate the loss of H3K79me2 during mitosis as a pathogenic event that contributes to the development and progression of tumors

The C-terminal domain of the Bloom syndrome DNA helicase is essential for genomic stability

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Noonan James P

2001-07-01

Full Text Available Abstract Background Bloom syndrome is a rare cancer-prone disorder in which the cells of affected persons have a high frequency of somatic mutation and genomic instability. Bloom syndrome cells have a distinctive high frequency of sister chromatid exchange and quadriradial formation. BLM, the protein altered in BS, is a member of the RecQ DNA helicase family, whose members share an average of 40% identity in the helicase domain and have divergent N-terminal and C-terminal flanking regions of variable lengths. The BLM DNA helicase has been shown to localize to the ND10 (nuclear domain 10 or PML (promyelocytic leukemia nuclear bodies, where it associates with TOPIIIα, and to the nucleolus. Results This report demonstrates that the N-terminal domain of BLM is responsible for localization of the protein to the nuclear bodies, while the C-terminal domain directs the protein to the nucleolus. Deletions of the N-terminal domain of BLM have little effect on sister chromatid exchange frequency and chromosome stability as compared to helicase and C-terminal mutations which can increase SCE frequency and chromosome abnormalities. Conclusion The helicase activity and the C-terminal domain of BLM are critical for maintaining genomic stability as measured by the sister chromatid exchange assay. The localization of BLM into the nucleolus by the C-terminal domain appears to be more important to genomic stability than localization in the nuclear bodies.

Aspects of ribonucleotide reductase regulation and genome stability

DEFF Research Database (Denmark)

Nielsen, Helena Berner Nedergaard

yeast, and Sml1, Hug1, and Dif1 in budding yeast. An elevated, as well as a reduced dNTP pool is shown to lead to an increase in spontaneous mutation rates, hence regulation of RNR is very important in order to maintain genomic stability. No human inhibitory proteins have yet been identified to regulate....... RNR consists of two subunits: R1 and R2, both of which are essential. The activity of RNR is strictly regulated to control the dNTP pool, both by allosteric feedback control and transcriptional and translational controls. Four inhibitory proteins of RNR have been identified in yeast: Spd1 in fission...... the human RNR enzyme. In this study regulation of human RNR was investigated using a fission yeast strain that depended solely on the human genes of R1 and R2 for dNTP synthesis. Even though this strain could grow like wild-type fission yeast it was hypersensitive to hydroxyurea (HU) and depended...

The Aging Clock and Circadian Control of Metabolism and Genome Stability

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Victoria P. Belancio

2015-01-01

Full Text Available It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.

Maintaining replication origins in the face of genomic change.

Science.gov (United States)

Di Rienzi, Sara C; Lindstrom, Kimberly C; Mann, Tobias; Noble, William S; Raghuraman, M K; Brewer, Bonita J

2012-10-01

Origins of replication present a paradox to evolutionary biologists. As a collection, they are absolutely essential genomic features, but individually are highly redundant and nonessential. It is therefore difficult to predict to what extent and in what regard origins are conserved over evolutionary time. Here, through a comparative genomic analysis of replication origins and chromosomal replication patterns in the budding yeasts Saccharomyces cerevisiae and Lachancea waltii, we assess to what extent replication origins survived genomic change produced from 150 million years of evolution. We find that L. waltii origins exhibit a core consensus sequence and nucleosome occupancy pattern highly similar to those of S. cerevisiae origins. We further observe that the overall progression of chromosomal replication is similar between L. waltii and S. cerevisiae. Nevertheless, few origins show evidence of being conserved in location between the two species. Among the conserved origins are those surrounding centromeres and adjacent to histone genes, suggesting that proximity to an origin may be important for their regulation. We conclude that, over evolutionary time, origins maintain sequence, structure, and regulation, but are continually being created and destroyed, with the result that their locations are generally not conserved.

Ten years of maintaining and expanding a microbial genome and metagenome analysis system.

Science.gov (United States)

Markowitz, Victor M; Chen, I-Min A; Chu, Ken; Pati, Amrita; Ivanova, Natalia N; Kyrpides, Nikos C

2015-11-01

Launched in March 2005, the Integrated Microbial Genomes (IMG) system is a comprehensive data management system that supports multidimensional comparative analysis of genomic data. At the core of the IMG system is a data warehouse that contains genome and metagenome datasets sequenced at the Joint Genome Institute or provided by scientific users, as well as public genome datasets available at the National Center for Biotechnology Information Genbank sequence data archive. Genomes and metagenome datasets are processed using IMG's microbial genome and metagenome sequence data processing pipelines and are integrated into the data warehouse using IMG's data integration toolkits. Microbial genome and metagenome application specific data marts and user interfaces provide access to different subsets of IMG's data and analysis toolkits. This review article revisits IMG's original aims, highlights key milestones reached by the system during the past 10 years, and discusses the main challenges faced by a rapidly expanding system, in particular the complexity of maintaining such a system in an academic setting with limited budgets and computing and data management infrastructure. Copyright © 2015 Elsevier Ltd. All rights reserved.

Karyotype Stability and Unbiased Fractionation in the Paleo-Allotetraploid Cucurbita Genomes.

Science.gov (United States)

Sun, Honghe; Wu, Shan; Zhang, Guoyu; Jiao, Chen; Guo, Shaogui; Ren, Yi; Zhang, Jie; Zhang, Haiying; Gong, Guoyi; Jia, Zhangcai; Zhang, Fan; Tian, Jiaxing; Lucas, William J; Doyle, Jeff J; Li, Haizhen; Fei, Zhangjun; Xu, Yong

2017-10-09

The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Here, we report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber, and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), respectively, and the allotetraploidization happened at some point between 26 Mya and 3 Mya, the estimated date when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization has not been commonly observed in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima × C. moschata interspecific F 1 hybrid and their two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into polyploid genome evolution and valuable resources for genetic improvement of cucurbit crops. Copyright © 2017 The Author. Published by Elsevier Inc. All rights reserved.

[Genetic system for maintaining the mitochondrial human genome in yeast Yarrowia lipolytica].

Science.gov (United States)

Isakova, E P; Deryabina, Yu I; Velyakova, A V; Biryukova, J K; Teplova, V V; Shevelev, A B

2016-01-01

For the first time, the possibility of maintaining an intact human mitochondrial genome in a heterologous system in the mitochondria of yeast Yarrowia lipolytica is shown. A method for introducing directional changes into the structure of the mitochondrial human genome replicating in Y. lipolytica by an artificially induced ability of yeast mitochondria for homologous recombination is proposed. A method of introducing and using phenotypic selection markers for the presence or absence of defects in genes tRNA-Lys and tRNA-Leu of the mitochondrial genome is developed. The proposed system can be used to correct harmful mutations of the human mitochondrial genome associated with mitochondrial diseases and for preparative amplification of intact mitochondrial DNA with an adjusted sequence in yeast cells. The applicability of the new system for the correction of mutations in the genes of Lys- and Leu-specific tRNAs of the human mitochondrial genome associated with serious and widespread human mitochondrial diseases such as myoclonic epilepsy with lactic acidosis (MELAS) and myoclonic epilepsy with ragged-red fibers (MERRF) is shown.

Cooperativity of the SUMO and Ubiquitin Pathways in Genome Stability

Directory of Open Access Journals (Sweden)

Minghua Nie

2016-02-01

Full Text Available Covalent attachment of ubiquitin (Ub or SUMO to DNA repair proteins plays critical roles in maintaining genome stability. These structurally related polypeptides can be viewed as distinct road signs, with each being read by specific protein interaction motifs. Therefore, via their interactions with selective readers in the proteome, ubiquitin and SUMO can elicit distinct cellular responses, such as directing DNA lesions into different repair pathways. On the other hand, through the action of the SUMO-targeted ubiquitin ligase (STUbL family proteins, ubiquitin and SUMO can cooperate in the form of a hybrid signal. These mixed SUMO-ubiquitin chains recruit “effector” proteins such as the AAA+ ATPase Cdc48/p97-Ufd1-Npl4 complex that contain both ubiquitin and SUMO interaction motifs. This review will summarize recent key findings on collaborative and distinct roles that ubiquitin and SUMO play in orchestrating DNA damage responses.

DNA damage checkpoint kinase ATM regulates germination and maintains genome stability in seeds.

Science.gov (United States)

Waterworth, Wanda M; Footitt, Steven; Bray, Clifford M; Finch-Savage, William E; West, Christopher E

2016-08-23

Genome integrity is crucial for cellular survival and the faithful transmission of genetic information. The eukaryotic cellular response to DNA damage is orchestrated by the DNA damage checkpoint kinases ATAXIA TELANGIECTASIA MUTATED (ATM) and ATM AND RAD3-RELATED (ATR). Here we identify important physiological roles for these sensor kinases in control of seed germination. We demonstrate that double-strand breaks (DSBs) are rate-limiting for germination. We identify that desiccation tolerant seeds exhibit a striking transcriptional DSB damage response during germination, indicative of high levels of genotoxic stress, which is induced following maturation drying and quiescence. Mutant atr and atm seeds are highly resistant to aging, establishing ATM and ATR as determinants of seed viability. In response to aging, ATM delays germination, whereas atm mutant seeds germinate with extensive chromosomal abnormalities. This identifies ATM as a major factor that controls germination in aged seeds, integrating progression through germination with surveillance of genome integrity. Mechanistically, ATM functions through control of DNA replication in imbibing seeds. ATM signaling is mediated by transcriptional control of the cell cycle inhibitor SIAMESE-RELATED 5, an essential factor required for the aging-induced delay to germination. In the soil seed bank, seeds exhibit increased transcript levels of ATM and ATR, with changes in dormancy and germination potential modulated by environmental signals, including temperature and soil moisture. Collectively, our findings reveal physiological functions for these sensor kinases in linking genome integrity to germination, thereby influencing seed quality, crucial for plant survival in the natural environment and sustainable crop production.

Genome Stability Maintenance in Naked Mole-Rat.

Science.gov (United States)

Petruseva, I O; Evdokimov, A N; Lavrik, O I

2017-01-01

The naked mole-rat ( Heterocephalus glaber ) is one of the most promising models used to study genome maintenance systems, including the effective repair of damage to DNA. The naked mole-rat is the longest lived rodent species, which is extraordinarily resistant to cancer and has a number of other unique phenotypic traits. For at least 80% of its lifespan, this animal shows no signs of aging or any increased likelihood of death and retains the ability to reproduce. The naked mole-rat draws the heightened attention of researchers who study the molecular basis of lengthy lifespan and cancer resistance. Despite the fact that the naked mole-rat lives under genotoxic stress conditions (oxidative, etc.), the main characteristics of its genome and proteome are a high stability and effective functioning. Replicative senescence in the somatic cells of naked mole-rats is missing, while an additional p53/pRb-dependent mechanism of early contact inhibition has been revealed in its fibroblasts, which controls cell proliferation and its mechanism of arf- dependent aging. The unique traits of phenotypic and molecular adaptations found in the naked mole-rat speak to a high stability and effective functioning of the molecular machinery that counteract damage accumulation in its genome. This review analyzes existing results in the study of the molecular basis of longevity and high cancer resistance in naked mole-rats.

Organelles genome stability of wheat plantlets produced by anther ...

African Journals Online (AJOL)

Yomi

2012-03-15

Mar 15, 2012 ... 1Department of Biotechnology, Faculty of Agricultural Technology, Al-Balqa' Applied University, ... genetic stability of wheat organelles genomes for plantlets produced by anther culture using restriction ..... of transgenic plants.

Method for rudder roll stabilization control by maintaining ship speed

Directory of Open Access Journals (Sweden)

LIU Zhiquan

2017-01-01

Full Text Available A ship navigating on the surface of the water may experience greater resistance, adversely affect-ing its speed and leading to energy loss. The added resistance of surface ships in both still water and waves are investigated, and the computation method of total speed loss is presented. An autopilot system is intro-duced to constrain the speed loss, and course keeping and rudder roll stabilization sliding mode control laws are proposed according to a compact control strategy. The two working conditions of "heading" and "heading plus anti-roll" are discussed, including roll stabilization, heading error, speed maintenance and rudder abrasion. The results show that the speed can be effectively maintained using this method, and from a commercial point of view, the fin-rudder roll stabilization control is not recommended for vessels equipped with both fins and rudders.

Replication protein A, the laxative that keeps DNA regular: The importance of RPA phosphorylation in maintaining genome stability.

Science.gov (United States)

Byrne, Brendan M; Oakley, Gregory G

2018-04-20

The eukaryotic ssDNA-binding protein, Replication protein A (RPA), was first discovered almost three decades ago. Since then, much progress has been made to elucidate the critical roles for RPA in DNA metabolic pathways that help promote genomic stability. The canonical RPA heterotrimer (RPA1-3) is an essential coordinator of DNA metabolism that interacts with ssDNA and numerous protein partners to coordinate its roles in DNA replication, repair, recombination and telomere maintenance. An alternative form of RPA, termed aRPA, is formed by a complex of RPA4 with RPA1 and RPA3. aRPA is expressed differentially in cells compared to canonical RPA and has been shown to inhibit canonical RPA function while allowing for regular maintenance of cell viability. Interestingly, while aRPA is defective in DNA replication and cell cycle progression, it was shown to play a supporting role in nucleotide excision repair and recombination. The binding domains of canonical RPA interact with a growing number of partners involved in numerous genome maintenance processes. The protein interactions of the RPA-ssDNA complex are not only governed by competition between the binding proteins but also by post-translation modifications such as phosphorylation. Phosphorylation of RPA2 is an important post-translational modification of the RPA complex, and is essential for directing context-specific functions of the RPA complex in the DNA damage response. Due to the importance of RPA in cellular metabolism, it was identified as an appealing target for chemotherapeutic drug development that could be used in future cancer treatment regimens. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinically Applicable Inhibitors Impacting Genome Stability.

Science.gov (United States)

Prakash, Anu; Garcia-Moreno, Juan F; Brown, James A L; Bourke, Emer

2018-05-13

Advances in technology have facilitated the molecular profiling (genomic and transcriptomic) of tumours, and has led to improved stratification of patients and the individualisation of treatment regimes. To fully realize the potential of truly personalised treatment options, we need targeted therapies that precisely disrupt the compensatory pathways identified by profiling which allow tumours to survive or gain resistance to treatments. Here, we discuss recent advances in novel therapies that impact the genome (chromosomes and chromatin), pathways targeted and the stage of the pathways targeted. The current state of research will be discussed, with a focus on compounds that have advanced into trials (clinical and pre-clinical). We will discuss inhibitors of specific DNA damage responses and other genome stability pathways, including those in development, which are likely to synergistically combine with current therapeutic options. Tumour profiling data, combined with the knowledge of new treatments that affect the regulation of essential tumour signalling pathways, is revealing fundamental insights into cancer progression and resistance mechanisms. This is the forefront of the next evolution of advanced oncology medicine that will ultimately lead to improved survival and may, one day, result in many cancers becoming chronic conditions, rather than fatal diseases.

The KRAB Zinc Finger Protein Roma/Zfp157 Is a Critical Regulator of Cell-Cycle Progression and Genomic Stability

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Teresa L.F. Ho

2016-04-01

Full Text Available Regulation of DNA replication and cell division is essential for tissue growth and maintenance of genomic integrity and is particularly important in tissues that undergo continuous regeneration such as mammary glands. We have previously shown that disruption of the KRAB-domain zinc finger protein Roma/Zfp157 results in hyperproliferation of mammary epithelial cells (MECs during pregnancy. Here, we delineate the mechanism by which Roma engenders this phenotype. Ablation of Roma in MECs leads to unscheduled proliferation, replication stress, DNA damage, and genomic instability. Furthermore, mouse embryonic fibroblasts (MEFs depleted for Roma exhibit downregulation of p21Cip1 and geminin and have accelerated replication fork velocities, which is accompanied by a high rate of mitotic errors and polyploidy. In contrast, overexpression of Roma in MECs halts cell-cycle progression, whereas siRNA-mediated p21Cip1 knockdown ameliorates, in part, this phenotype. Thus, Roma is an essential regulator of the cell cycle and is required to maintain genomic stability.

Telomeres and viruses: common themes of genome maintenance

Science.gov (United States)

Deng, Zhong; Wang, Zhuo; Lieberman, Paul M.

2012-01-01

Genome maintenance mechanisms actively suppress genetic instability associated with cancer and aging. Some viruses provoke genetic instability by subverting the host’s control of genome maintenance. Viruses have their own specialized strategies for genome maintenance, which can mimic and modify host cell processes. Here, we review some of the common features of genome maintenance utilized by viruses and host chromosomes, with a particular focus on terminal repeat (TR) elements. The TRs of cellular chromosomes, better known as telomeres, have well-established roles in cellular chromosome stability. Cellular telomeres are themselves maintained by viral-like mechanisms, including self-propagation by reverse transcription, recombination, and retrotransposition. Viral TR elements, like cellular telomeres, are essential for viral genome stability and propagation. We review the structure and function of viral repeat elements and discuss how they may share telomere-like structures and genome protection functions. We consider how viral infections modulate telomere regulatory factors for viral repurposing and can alter normal host telomere structure and chromosome stability. Understanding the common strategies of viral and cellular genome maintenance may provide new insights into viral–host interactions and the mechanisms driving genetic instability in cancer. PMID:23293769

Seeds as emerging hotspot for maintenance of genome stability

Czech Academy of Sciences Publication Activity Database

Diaz, Mariana; Pečinka, Aleš

2017-01-01

Roč. 82, č. 5 (2017), s. 467-470 ISSN 0011-4545 Institutional support: RVO:61389030 Keywords : Chromatin * Chromosome * DNA damage repair * Genome stability * Seed * Structural maintenance of chromosome Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 0.913, year: 2016

Cryo-electron Microscopy Reconstruction and Stability Studies of the Wild Type and the R432A Variant of Adeno-associated Virus Type 2 Reveal that Capsid Structural Stability Is a Major Factor in Genome Packaging.

Science.gov (United States)

Drouin, Lauren M; Lins, Bridget; Janssen, Maria; Bennett, Antonette; Chipman, Paul; McKenna, Robert; Chen, Weijun; Muzyczka, Nicholas; Cardone, Giovanni; Baker, Timothy S; Agbandje-McKenna, Mavis

2016-10-01

The adeno-associated viruses (AAV) are promising therapeutic gene delivery vectors and better understanding of their capsid assembly and genome packaging mechanism is needed for improved vector production. Empty AAV capsids assemble in the nucleus prior to genome packaging by virally encoded Rep proteins. To elucidate the capsid determinants of this process, structural differences between wild-type (wt) AAV2 and a packaging deficient variant, AAV2-R432A, were examined using cryo-electron microscopy and three-dimensional image reconstruction both at an ∼5.0-Å resolution (medium) and also at 3.8- and 3.7-Å resolutions (high), respectively. The high resolution structures showed that removal of the arginine side chain in AAV2-R432A eliminated hydrogen bonding interactions, resulting in altered intramolecular and intermolecular interactions propagated from under the 3-fold axis toward the 5-fold channel. Consistent with these observations, differential scanning calorimetry showed an ∼10°C decrease in thermal stability for AAV2-R432A compared to wt-AAV2. In addition, the medium resolution structures revealed differences in the juxtaposition of the less ordered, N-terminal region of their capsid proteins, VP1/2/3. A structural rearrangement in AAV2-R432A repositioned the βA strand region under the icosahedral 2-fold axis rather than antiparallel to the βB strand, eliminating many intramolecular interactions. Thus, a single amino acid substitution can significantly alter the AAV capsid integrity to the extent of reducing its stability and possibly rendering it unable to tolerate the stress of genome packaging. Furthermore, the data show that the 2-, 3-, and 5-fold regions of the capsid contributed to producing the packaging defect and highlight a tight connection between the entire capsid in maintaining packaging efficiency. The mechanism of AAV genome packaging is still poorly understood, particularly with respect to the capsid determinants of the required capsid

Stability of foot-and-mouth disease virus, its genome and proteins at 37 grad C

International Nuclear Information System (INIS)

Razdan, R.; Sen, A.K.; Rao, B.V.; Suryanarayana, V.V.S.

1996-01-01

Infectivity titers of foot-and-mouth disease virus (FMDV) types Asia 1 and 0 were reduced by 4 and 2 log units, respectively, after incubation at 37 grad C for 12 hours. The stability of the FMDV RNA genome at 37 grad C was studied using 32 P-labelled virus. The RNA of FMDV type 0 was found to be more stable than that of type Asia 1. Oligo(dT)-cellulose chromatography showed that 21 % and 31 % of the labelled RNA were bound to the column in the case of types Asia 1 and 0, respectively. Possible correlation between the poly(A) tail length, accessibility of the genome to nucleases and thermo-stability of the infective virus is discussed. A possible correlation between the thermo-stability of the genome and general distribution of a particular virus type seems to exist. A stable genome associated with poor virus immunogenicity may be responsible for the prevalence of FMDV type 0 in the nature. The isoelectric focussing of structural proteins isolated from the virus samples incubated at 37 grad C revealed charge differences in the major immuno-gen between the two FMDV types. A rapid proteolytic degradation of the viral immuno-gen and stability of the genome may be responsible for frequent outbreaks of FMDV, at least, in the endemic countries. (author)

Maintaining the stability of nonlinear differential equations by the enhancement of HPM

International Nuclear Information System (INIS)

Hosein Nia, S.H.; Ranjbar, A.N.; Ganji, D.D.; Soltani, H.; Ghasemi, J.

2008-01-01

Homotopy perturbation method is an effective method to find a solution of a nonlinear differential equation. In this method, a nonlinear complex differential equation is transformed to a series of linear and nonlinear parts, almost simpler differential equations. These sets of equations are then solved iteratively. Finally, a linear series of the solutions completes the answer if the convergence is maintained. In this Letter, the need for stability verification is shown through some examples. Consequently, HPM is enhanced by a preliminary assumption. The idea is to keep the inherent stability of nonlinear dynamic, even the selected linear part is not

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues

International Nuclear Information System (INIS)

Cifola, Ingrid; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A

2011-01-01

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

RecQL5 promotes genome stabilization through two parallel mechanisms--interacting with RNA polymerase II and acting as a helicase.

Science.gov (United States)

Islam, M Nurul; Fox, David; Guo, Rong; Enomoto, Takemi; Wang, Weidong

2010-05-01

The RecQL5 helicase is essential for maintaining genome stability and reducing cancer risk. To elucidate its mechanism of action, we purified a RecQL5-associated complex and identified its major component as RNA polymerase II (Pol II). Bioinformatics and structural modeling-guided mutagenesis revealed two conserved regions in RecQL5 as KIX and SRI domains, already known in transcriptional regulators for Pol II. The RecQL5-KIX domain binds both initiation (Pol IIa) and elongation (Pol IIo) forms of the polymerase, whereas the RecQL5-SRI domain interacts only with the elongation form. Fully functional RecQL5 requires both helicase activity and associations with the initiation polymerase, because mutants lacking either activity are partially defective in the suppression of sister chromatid exchange and resistance to camptothecin-induced DNA damage, and mutants lacking both activities are completely defective. We propose that RecQL5 promotes genome stabilization through two parallel mechanisms: by participation in homologous recombination-dependent DNA repair as a RecQ helicase and by regulating the initiation of Pol II to reduce transcription-associated replication impairment and recombination.

Strategies for maintaining emotional stability: The case of nurses in private health care industry

Directory of Open Access Journals (Sweden)

Pushpika Subhashinie Mullakanda

2015-12-01

Full Text Available This study examines the emotional intelligence (EI of nurses by differentiating inter-personal and intra-personal dimensions, and explores the measures taken by them to maintain emotional stability. Further, it investigates the relationship of demographic factors (age, gender and year of experience of nurses with their emotional stability. The case organization is a well performing private hospital located closer to the metropolitan city. Study collects data through both quantitative (survey and qualitative means (discussion, observation, and interviews using a sample of 40 nurses selected conveniently from different ranks. The study finds that the level of EI of nurses in case hospital is slightly high, and their inter-personal skills are higher than intra-personal skills. They maintain emotional stability by means of emotion gaps, emotional shifts and sharing. Findings suggest that both inter-personal and intra-personal dimensions of EI will not be equally important for nurses in dealing with patients, and the level of EI required in the job is not equal among different ranks of nurses.

Response of normal stem cells to ionizing radiation: A balance between homeostasis and genomic stability

International Nuclear Information System (INIS)

Harfouche, G.; Martin, M.T.

2010-01-01

Stem cells have been described in most adult tissues, where they play a key role in maintaining tissue homeostasis. As they self-renew throughout life, accumulating genetic anomalies can compromise their genomic integrity and potentially give rise to cancer. Stem cells (SCs) may thus be a major target of radiation carcinogenesis. In addition, unrepaired genotoxic damage may cause cell death and stem cell pool depletion, impairing lineage functionality and accelerating aging. Developments in SC biology enabled the characterization of the responses of stem cells to genotoxic stress and their role in tissue damage. We here examine how these cells react to ionizing radiation (IR), and more specifically their radiosensitivity, stress signaling and DNA repair. We first review embryonic SCs, as a paradigm of primitive pluri-potent cells, then three adult tissues, bone marrow, skin and intestine, capable of long-term regeneration and at high risk for acute radiation syndromes and long-term carcinogenesis. We discuss IR disruption of the fine balance between maintenance of tissue homeostasis and genomic stability. We show that stem cell radiosensitivity does not follow a unique model, but differs notably according to the turnover rates of the tissues. (authors)

Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics

Science.gov (United States)

Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng

2015-12-01

Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains.

Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

Science.gov (United States)

Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

2011-06-13

Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: genome stability and adaptive radiation

Science.gov (United States)

2013-01-01

Background Lyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex. To reconstruct the evolution of B. burgdorferi s.l. and identify the genomic basis of its human virulence, we compared the genomes of 23 B. burgdorferi s.l. isolates from Europe and the United States, including B. burgdorferi sensu stricto (B. burgdorferi s.s., 14 isolates), B. afzelii (2), B. garinii (2), B. “bavariensis” (1), B. spielmanii (1), B. valaisiana (1), B. bissettii (1), and B. “finlandensis” (1). Results Robust B. burgdorferi s.s. and B. burgdorferi s.l. phylogenies were obtained using genome-wide single-nucleotide polymorphisms, despite recombination. Phylogeny-based pan-genome analysis showed that the rate of gene acquisition was higher between species than within species, suggesting adaptive speciation. Strong positive natural selection drives the sequence evolution of lipoproteins, including chromosomally-encoded genes 0102 and 0404, cp26-encoded ospC and b08, and lp54-encoded dbpA, a07, a22, a33, a53, a65. Computer simulations predicted rapid adaptive radiation of genomic groups as population size increases. Conclusions Intra- and inter-specific pan-genome sizes of B. burgdorferi s.l. expand linearly with phylogenetic diversity. Yet gene-acquisition rates in B. burgdorferi s.l. are among the lowest in bacterial pathogens, resulting in high genome stability and few lineage-specific genes. Genome adaptation of B. burgdorferi s.l. is driven predominantly by copy-number and sequence variations of lipoprotein genes. New genomic groups are likely to emerge if the current trend of B. burgdorferi s.l. population expansion continues. PMID:24112474

The expanding universe of cohesin functions: a new genome stability caretaker involved in human disease and cancer.

Science.gov (United States)

Mannini, Linda; Menga, Stefania; Musio, Antonio

2010-06-01

Cohesin is responsible for sister chromatid cohesion, ensuring the correct chromosome segregation. Beyond this role, cohesin and regulatory cohesin genes seem to play a role in preserving genome stability and gene transcription regulation. DNA damage is thought to be a major culprit for many human diseases, including cancer. Our present knowledge of the molecular basis underlying genome instability is extremely limited. Mutations in cohesin genes cause human diseases such as Cornelia de Lange syndrome and Roberts syndrome/SC phocomelia, and all the cell lines derived from affected patients show genome instability. Cohesin mutations have also been identified in colorectal cancer. Here, we will discuss the human disorders caused by alterations of cohesin function, with emphasis on the emerging role of cohesin as a genome stability caretaker.

Genome-Wide Analysis of Grain Yield Stability and Environmental Interactions in a Multiparental Soybean Population

Directory of Open Access Journals (Sweden)

Alencar Xavier

2018-02-01

Full Text Available Genetic improvement toward optimized and stable agronomic performance of soybean genotypes is desirable for food security. Understanding how genotypes perform in different environmental conditions helps breeders develop sustainable cultivars adapted to target regions. Complex traits of importance are known to be controlled by a large number of genomic regions with small effects whose magnitude and direction are modulated by environmental factors. Knowledge of the constraints and undesirable effects resulting from genotype by environmental interactions is a key objective in improving selection procedures in soybean breeding programs. In this study, the genetic basis of soybean grain yield responsiveness to environmental factors was examined in a large soybean nested association population. For this, a genome-wide association to performance stability estimates generated from a Finlay-Wilkinson analysis and the inclusion of the interaction between marker genotypes and environmental factors was implemented. Genomic footprints were investigated by analysis and meta-analysis using a recently published multiparent model. Results indicated that specific soybean genomic regions were associated with stability, and that multiplicative interactions were present between environments and genetic background. Seven genomic regions in six chromosomes were identified as being associated with genotype-by-environment interactions. This study provides insight into genomic assisted breeding aimed at achieving a more stable agronomic performance of soybean, and documented opportunities to exploit genomic regions that were specifically associated with interactions involving environments and subpopulations.

Mitochondria as determinant of nucleotide pools and chromosomal stability

DEFF Research Database (Denmark)

Madsen, Claus Desler; Munch-Petersen, Birgitte; Stevnsner, Tinna

2007-01-01

Mitochondrial function plays an important role in multiple human diseases and mutations in the mitochondrial genome have been detected in nearly every type of cancer investigated to date. However, the mechanism underlying the interrelation is unknown. We used human cell lines depleted of mitochon...... mitochondrial activity. Our results suggest that mitochondria are central players in maintaining genomic stability and in controlling essential nuclear processes such as upholding a balanced supply of nucleotides....

Persistence drives gene clustering in bacterial genomes

Directory of Open Access Journals (Sweden)

Rocha Eduardo PC

2008-01-01

Full Text Available Abstract Background Gene clustering plays an important role in the organization of the bacterial chromosome and several mechanisms have been proposed to explain its extent. However, the controversies raised about the validity of each of these mechanisms remind us that the cause of this gene organization remains an open question. Models proposed to explain clustering did not take into account the function of the gene products nor the likely presence or absence of a given gene in a genome. However, genomes harbor two very different categories of genes: those genes present in a majority of organisms – persistent genes – and those present in very few organisms – rare genes. Results We show that two classes of genes are significantly clustered in bacterial genomes: the highly persistent and the rare genes. The clustering of rare genes is readily explained by the selfish operon theory. Yet, genes persistently present in bacterial genomes are also clustered and we try to understand why. We propose a model accounting specifically for such clustering, and show that indispensability in a genome with frequent gene deletion and insertion leads to the transient clustering of these genes. The model describes how clusters are created via the gene flux that continuously introduces new genes while deleting others. We then test if known selective processes, such as co-transcription, physical interaction or functional neighborhood, account for the stabilization of these clusters. Conclusion We show that the strong selective pressure acting on the function of persistent genes, in a permanent state of flux of genes in bacterial genomes, maintaining their size fairly constant, that drives persistent genes clustering. A further selective stabilization process might contribute to maintaining the clustering.

Bioecological principles of maintaining stability in mountain forest ecosystems of the Ukrainian Carpathians

Directory of Open Access Journals (Sweden)

T. V. Parpan

2016-09-01

Full Text Available The forest cover of the Carpathians has been deeply transformed by productive activities over the past centuries. The forest cover, age and species structure of its ecosystems have been changed. Beech and fir forests were replaced by spruce monocultures. Consequently, nitrogen and mineral elements cycles changed, the genetic and population structures altered and the eco-stabilizing function of forests decreased. These negative trends make it desirable to process the bioecological principles of maintenance the stability of mountain forest ecosystems. The proposed bioecological principles of support and recovery of stability of forest ecosystems are part of the paradigm of mountain dendrology and silviculture. The strategy is based on maintaining bio-ecological and population-genetical features of the main forest forming species, evolutionary typological classification of the forests, landscape and environmental specifics of the mountain part of the Ukrainian Carpathians, features of virgin, old growth and anthropogenically disturbed forest structures, as well as performing the functional role of forest ecosystems. Support for landscape ecosystem stability involves the conservation, selective, health and gradual cutting, formation of forest stands which are close to natural conditions and focusing on natural regeneration (a basis for stable mountain forest ecosystems.

Studies on the effects of persistent RNA priming on DNA replication and genomic stability

OpenAIRE

Stuckey, Ruth

2014-01-01

[EN]: DNA replication and transcription take place on the same DNA template, and the correct interplay between these processes ensures faithful genome duplication. DNA replication must be highly coordinated with other cell cycle events, such as segregation of fully replicated DNA in order to maintain genomic integrity. Transcription generates RNA:DNA hybrids, transient intermediate structures that are degraded by the ribonuclease H (RNaseH) class of enzymes. RNA:DNA hybrids can form R-loops, ...

The influence of micronutrients in cell culture: a reflection on viability and genomic stability.

Science.gov (United States)

Arigony, Ana Lúcia Vargas; de Oliveira, Iuri Marques; Machado, Miriana; Bordin, Diana Lilian; Bergter, Lothar; Prá, Daniel; Henriques, João Antonio Pêgas

2013-01-01

Micronutrients, including minerals and vitamins, are indispensable to DNA metabolic pathways and thus are as important for life as macronutrients. Without the proper nutrients, genomic instability compromises homeostasis, leading to chronic diseases and certain types of cancer. Cell-culture media try to mimic the in vivo environment, providing in vitro models used to infer cells' responses to different stimuli. This review summarizes and discusses studies of cell-culture supplementation with micronutrients that can increase cell viability and genomic stability, with a particular focus on previous in vitro experiments. In these studies, the cell-culture media include certain vitamins and minerals at concentrations not equal to the physiological levels. In many common culture media, the sole source of micronutrients is fetal bovine serum (FBS), which contributes to only 5-10% of the media composition. Minimal attention has been dedicated to FBS composition, micronutrients in cell cultures as a whole, or the influence of micronutrients on the viability and genetics of cultured cells. Further studies better evaluating micronutrients' roles at a molecular level and influence on the genomic stability of cells are still needed.

The RNAPII-CTD Maintains Genome Integrity through Inhibition of Retrotransposon Gene Expression and Transposition.

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Maria J Aristizabal

2015-10-01

Full Text Available RNA polymerase II (RNAPII contains a unique C-terminal domain that is composed of heptapeptide repeats and which plays important regulatory roles during gene expression. RNAPII is responsible for the transcription of most protein-coding genes, a subset of non-coding genes, and retrotransposons. Retrotransposon transcription is the first step in their multiplication cycle, given that the RNA intermediate is required for the synthesis of cDNA, the material that is ultimately incorporated into a new genomic location. Retrotransposition can have grave consequences to genome integrity, as integration events can change the gene expression landscape or lead to alteration or loss of genetic information. Given that RNAPII transcribes retrotransposons, we sought to investigate if the RNAPII-CTD played a role in the regulation of retrotransposon gene expression. Importantly, we found that the RNAPII-CTD functioned to maintaining genome integrity through inhibition of retrotransposon gene expression, as reducing CTD length significantly increased expression and transposition rates of Ty1 elements. Mechanistically, the increased Ty1 mRNA levels in the rpb1-CTD11 mutant were partly due to Cdk8-dependent alterations to the RNAPII-CTD phosphorylation status. In addition, Cdk8 alone contributed to Ty1 gene expression regulation by altering the occupancy of the gene-specific transcription factor Ste12. Loss of STE12 and TEC1 suppressed growth phenotypes of the RNAPII-CTD truncation mutant. Collectively, our results implicate Ste12 and Tec1 as general and important contributors to the Cdk8, RNAPII-CTD regulatory circuitry as it relates to the maintenance of genome integrity.

Critical threshold levels of DNA methyltransferase 1 are required to maintain DNA methylation across the genome in human cancer cells.

Science.gov (United States)

Cai, Yi; Tsai, Hsing-Chen; Yen, Ray-Whay Chiu; Zhang, Yang W; Kong, Xiangqian; Wang, Wei; Xia, Limin; Baylin, Stephen B

2017-04-01

Reversing DNA methylation abnormalities and associated gene silencing, through inhibiting DNA methyltransferases (DNMTs) is an important potential cancer therapy paradigm. Maximizing this potential requires defining precisely how these enzymes maintain genome-wide, cancer-specific DNA methylation. To date, there is incomplete understanding of precisely how the three DNMTs, 1, 3A, and 3B, interact for maintaining DNA methylation abnormalities in cancer. By combining genetic and shRNA depletion strategies, we define not only a dominant role for DNA methyltransferase 1 (DNMT1) but also distinct roles of 3A and 3B in genome-wide DNA methylation maintenance. Lowering DNMT1 below a threshold level is required for maximal loss of DNA methylation at all genomic regions, including gene body and enhancer regions, and for maximally reversing abnormal promoter DNA hypermethylation and associated gene silencing to reexpress key genes. It is difficult to reach this threshold with patient-tolerable doses of current DNMT inhibitors (DNMTIs). We show that new approaches, like decreasing the DNMT targeting protein, UHRF1, can augment the DNA demethylation capacities of existing DNA methylation inhibitors for fully realizing their therapeutic potential. © 2017 Cai et al.; Published by Cold Spring Harbor Laboratory Press.

Mutations in Cytosine-5 tRNA Methyltransferases Impact Mobile Element Expression and Genome Stability at Specific DNA Repeats

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Bianca Genenncher

2018-02-01

Full Text Available The maintenance of eukaryotic genome stability is ensured by the interplay of transcriptional as well as post-transcriptional mechanisms that control recombination of repeat regions and the expression and mobility of transposable elements. We report here that mutations in two (cytosine-5 RNA methyltransferases, Dnmt2 and NSun2, impact the accumulation of mobile element-derived sequences and DNA repeat integrity in Drosophila. Loss of Dnmt2 function caused moderate effects under standard conditions, while heat shock exacerbated these effects. In contrast, NSun2 function affected mobile element expression and genome integrity in a heat shock-independent fashion. Reduced tRNA stability in both RCMT mutants indicated that tRNA-dependent processes affected mobile element expression and DNA repeat stability. Importantly, further experiments indicated that complex formation with RNA could also contribute to the impact of RCMT function on gene expression control. These results thus uncover a link between tRNA modification enzymes, the expression of repeat DNA, and genomic integrity.

Maintaining stability of standalone Micro-Grid by employing electrical and mechanical fault ride through techniques upon fixed speed wind generation systems

International Nuclear Information System (INIS)

Kamel, Rashad M.

2013-01-01

Highlights: • This paper presented two fault ride through techniques for fixed speed wind systems. • The first technique is implemented by inserting a series resistance with the terminals of wind generator. • Second technique is performed by adapting the gear ratio to spill some mechanical power. - Abstract: This study presents two different Fault Ride Through (FRT) techniques to keep and restore stability of Fixed Speed Wind Generation system (FSWGs) installed in standalone Micro-Grid (MG). The first technique is an electrical FRT and is implemented by inserting a series resistance with the terminals of FSWGs during fault to maintain reasonable value of terminal voltage and consequently help stability restoration. The second controller is a mechanical FRT controller and is performed by change the gear ratio of wind generation systems to spill part of extracted mechanical power and consequently improving stability issue. Obtained results proved that each controller able to maintain the stability of FSWGs under the most severe disturbance conditions (400 ms three phase fault at FSWGs terminals). The first controller is faster than the second controller in restoring FSWGs stability. Superior results and performances are obtained when the two FRT techniques are employed simultaneously. Without employing any one of the two FRT techniques, FSWGs is not able to maintain or restore its stability after fault clearing. Consequently, MG will lose one of its micro-sources and cannot keep its stability during the standalone mode, unless load shedding strategy is activated. The two proposed controllers are simple, effective, and economical attractive

Genome-wide comparative transcriptome analysis of CMS-D2 and its maintainer and restorer lines in upland cotton.

Science.gov (United States)

Wu, Jianyong; Zhang, Meng; Zhang, Bingbing; Zhang, Xuexian; Guo, Liping; Qi, Tingxiang; Wang, Hailin; Zhang, Jinfa; Xing, Chaozhu

2017-06-08

Cytoplasmic male sterility (CMS) conferred by the cytoplasm from Gossypium harknessii (D2) is an important system for hybrid seed production in Upland cotton (G. hirsutum). The male sterility of CMS-D2 (i.e., A line) can be restored to fertility by a restorer (i.e., R line) carrying the restorer gene Rf1 transferred from the D2 nuclear genome. However, the molecular mechanisms of CMS-D2 and its restoration are poorly understood. In this study, a genome-wide comparative transcriptome analysis was performed to identify differentially expressed genes (DEGs) in flower buds among the isogenic fertile R line and sterile A line derived from a backcross population (BC 8 F 1 ) and the recurrent parent, i.e., the maintainer (B line). A total of 1464 DEGs were identified among the three isogenic lines, and the Rf1-carrying Chr_D05 and its homeologous Chr_A05 had more DEGs than other chromosomes. The results of GO and KEGG enrichment analysis showed differences in circadian rhythm between the fertile and sterile lines. Eleven DEGs were selected for validation using qRT-PCR, confirming the accuracy of the RNA-seq results. Through genome-wide comparative transcriptome analysis, the differential expression profiles of CMS-D2 and its maintainer and restorer lines in Upland cotton were identified. Our results provide an important foundation for further studies into the molecular mechanisms of the interactions between the restorer gene Rf1 and the CMS-D2 cytoplasm.

Local chromatin structure of heterochromatin regulates repeated DNA stability, nucleolus structure, and genome integrity

Energy Technology Data Exchange (ETDEWEB)

Peng, Jamy C. [Univ. of California, Berkeley, CA (United States)

2007-01-01

Heterochromatin constitutes a significant portion of the genome in higher eukaryotes; approximately 30% in Drosophila and human. Heterochromatin contains a high repeat DNA content and a low density of protein-encoding genes. In contrast, euchromatin is composed mostly of unique sequences and contains the majority of single-copy genes. Genetic and cytological studies demonstrated that heterochromatin exhibits regulatory roles in chromosome organization, centromere function and telomere protection. As an epigenetically regulated structure, heterochromatin formation is not defined by any DNA sequence consensus. Heterochromatin is characterized by its association with nucleosomes containing methylated-lysine 9 of histone H3 (H3K9me), heterochromatin protein 1 (HP1) that binds H3K9me, and Su(var)3-9, which methylates H3K9 and binds HP1. Heterochromatin formation and functions are influenced by HP1, Su(var)3-9, and the RNA interference (RNAi) pathway. My thesis project investigates how heterochromatin formation and function impact nuclear architecture, repeated DNA organization, and genome stability in Drosophila melanogaster. H3K9me-based chromatin reduces extrachromosomal DNA formation; most likely by restricting the access of repair machineries to repeated DNAs. Reducing extrachromosomal ribosomal DNA stabilizes rDNA repeats and the nucleolus structure. H3K9me-based chromatin also inhibits DNA damage in heterochromatin. Cells with compromised heterochromatin structure, due to Su(var)3-9 or dcr-2 (a component of the RNAi pathway) mutations, display severe DNA damage in heterochromatin compared to wild type. In these mutant cells, accumulated DNA damage leads to chromosomal defects such as translocations, defective DNA repair response, and activation of the G2-M DNA repair and mitotic checkpoints that ensure cellular and animal viability. My thesis research suggests that DNA replication, repair, and recombination mechanisms in heterochromatin differ from those in

Comparative analysis of mitochondrial genomes between the hau cytoplasmic male sterility (CMS) line and its iso-nuclear maintainer line in Brassica juncea to reveal the origin of the CMS-associated gene orf288.

Science.gov (United States)

Heng, Shuangping; Wei, Chao; Jing, Bing; Wan, Zhengjie; Wen, Jing; Yi, Bin; Ma, Chaozhi; Tu, Jinxing; Fu, Tingdong; Shen, Jinxiong

2014-04-30

Cytoplasmic male sterility (CMS) is not only important for exploiting heterosis in crop plants, but also as a model for investigating nuclear-cytoplasmic interaction. CMS may be caused by mutations, rearrangement or recombination in the mitochondrial genome. Understanding the mitochondrial genome is often the first and key step in unraveling the molecular and genetic basis of CMS in plants. Comparative analysis of the mitochondrial genome of the hau CMS line and its maintainer line in B. juneca (Brassica juncea) may help show the origin of the CMS-associated gene orf288. Through next-generation sequencing, the B. juncea hau CMS mitochondrial genome was assembled into a single, circular-mapping molecule that is 247,903 bp in size and 45.08% in GC content. In addition to the CMS associated gene orf288, the genome contains 35 protein-encoding genes, 3 rRNAs, 25 tRNA genes and 29 ORFs of unknown function. The mitochondrial genome sizes of the maintainer line and another normal type line "J163-4" are both 219,863 bp and with GC content at 45.23%. The maintainer line has 36 genes with protein products, 3 rRNAs, 22 tRNA genes and 31 unidentified ORFs. Comparative analysis the mitochondrial genomes of the hau CMS line and its maintainer line allowed us to develop specific markers to separate the two lines at the seedling stage. We also confirmed that different mitotypes coexist substoichiometrically in hau CMS lines and its maintainer lines in B. juncea. The number of repeats larger than 100 bp in the hau CMS line (16 repeats) are nearly twice of those found in the maintainer line (9 repeats). Phylogenetic analysis of the CMS-associated gene orf288 and four other homologous sequences in Brassicaceae show that orf288 was clearly different from orf263 in Brassica tournefortii despite of strong similarity. The hau CMS mitochondrial genome was highly rearranged when compared with its iso-nuclear maintainer line mitochondrial genome. This study may be useful for studying the

Multifunctional Role of ATM/Tel1 Kinase in Genome Stability: From the DNA Damage Response to Telomere Maintenance

Science.gov (United States)

2014-01-01

The mammalian protein kinase ataxia telangiectasia mutated (ATM) is a key regulator of the DNA double-strand-break response and belongs to the evolutionary conserved phosphatidylinositol-3-kinase-related protein kinases. ATM deficiency causes ataxia telangiectasia (AT), a genetic disorder that is characterized by premature aging, cerebellar neuropathy, immunodeficiency, and predisposition to cancer. AT cells show defects in the DNA damage-response pathway, cell-cycle control, and telomere maintenance and length regulation. Likewise, in Saccharomyces cerevisiae, haploid strains defective in the TEL1 gene, the ATM ortholog, show chromosomal aberrations and short telomeres. In this review, we outline the complex role of ATM/Tel1 in maintaining genomic stability through its control of numerous aspects of cellular survival. In particular, we describe how ATM/Tel1 participates in the signal transduction pathways elicited by DNA damage and in telomere homeostasis and its importance as a barrier to cancer development. PMID:25247188

Plants from Chernobyl zone could shed light on genome stability in radioactive environment

Science.gov (United States)

Shevchenko, Galina; Talalaiev, Oleksandr; Doonan, John

2016-07-01

For nearly 30 years, despite of chronic radiation, flora in Chernobyl zone continue to flourish, evidencing the adaptation of plants to such an environment. Keeping in mind interplanetary missions, this phenomenon is a challenge for plant space research since it highlights the possible mechanisms of genome protection and stabilization in harmful environment. Plants are sessile organisms and, contrary to animals, could not escape the external impact. Therefore, plants should evolve the robust system allowing DNA-protection against damage, which is of special interest. Our investigations show that Arabidopsis thaliana from Chernobyl zone tolerate radiomimetics and heavy metals better than control plants from non-polluted areas. Besides, its genome is less affected by such mutagens. qPCR investigations have revealed up-regulation of some genes involved in DNA damage response. In particular, expression of ATR is increased slightly and downstream expression of CycB1:1 gene is increased significantly after bleomycin treatment suggesting role of ATR-dependent pathway in genome stabilization. Several DNA repair pathways are known to exist in plants. We continue investigations on gene expression from different DNA repair pathways as well as cell cycle regulation and investigation of PCD hallmarks in order to reveal the mechanism of plant tolerance to radiation environment. Our investigations provide unique information for space researchers working on biotechnology of radiation tolerant plants.

U.S. Security Strategy in the Asia-Pacific: Partnering With Asean to Maintain Stability Within the Region

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Association of Southeast Asian Nations (ASEAN) can serve as a mechanism to strengthen U.S. partnerships in the region while sustaining stability and maintaining the economic growth of the region.... economically in the last few decades. The U.S. has developed key partnerships and alliances in the region and has an obligation to assist its partners in...ensuring that any threats to the social and environmental stability are managed in accordance with the rules of law. The U.S. relies on the region for

WIFE’S STRATEGY IN MAINTAINING THE STABILITY OF RELATIONSHIP WITH HUSBAND THROUGH COMMUNICATION PRIVACY MANAGEMENT THEORY

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Norvitasari Y.

2017-11-01

Full Text Available The discussion on interpersonal communication between husband and wife has become a widely interesting issue. Communication between husband and wife in everyday life is important to maintain the stability of the relationship. By that, this study aims to find the wife’s strategy in managing its private information and to find the act which violates and does not violate the privacy of the husband to maintain the stability of the relationship. This research uses the interpretive approach with phenomenology method. The subjects of this research are wives from the conventional type of couple located in Malang. The findings indicate that wife as the owner of private information limits the private information so that the access of the husband to such information is not similar in every subject, thereby reducing the potential of conflict and the relationship becomes more stable. The preventive action taken by the wife when violating the privacy of the husband is to confirm the information in order to eliminate potential conflicts that will occur.

Flexibility and symmetry of prokaryotic genome rearrangement reveal lineage-associated core-gene-defined genome organizational frameworks.

Science.gov (United States)

Kang, Yu; Gu, Chaohao; Yuan, Lina; Wang, Yue; Zhu, Yanmin; Li, Xinna; Luo, Qibin; Xiao, Jingfa; Jiang, Daquan; Qian, Minping; Ahmed Khan, Aftab; Chen, Fei; Zhang, Zhang; Yu, Jun

2014-11-25

The prokaryotic pangenome partitions genes into core and dispensable genes. The order of core genes, albeit assumed to be stable under selection in general, is frequently interrupted by horizontal gene transfer and rearrangement, but how a core-gene-defined genome maintains its stability or flexibility remains to be investigated. Based on data from 30 species, including 425 genomes from six phyla, we grouped core genes into syntenic blocks in the context of a pangenome according to their stability across multiple isolates. A subset of the core genes, often species specific and lineage associated, formed a core-gene-defined genome organizational framework (cGOF). Such cGOFs are either single segmental (one-third of the species analyzed) or multisegmental (the rest). Multisegment cGOFs were further classified into symmetric or asymmetric according to segment orientations toward the origin-terminus axis. The cGOFs in Gram-positive species are exclusively symmetric and often reversible in orientation, as opposed to those of the Gram-negative bacteria, which are all asymmetric and irreversible. Meanwhile, all species showing strong strand-biased gene distribution contain symmetric cGOFs and often specific DnaE (α subunit of DNA polymerase III) isoforms. Furthermore, functional evaluations revealed that cGOF genes are hub associated with regard to cellular activities, and the stability of cGOF provides efficient indexes for scaffold orientation as demonstrated by assembling virtual and empirical genome drafts. cGOFs show species specificity, and the symmetry of multisegmental cGOFs is conserved among taxa and constrained by DNA polymerase-centric strand-biased gene distribution. The definition of species-specific cGOFs provides powerful guidance for genome assembly and other structure-based analysis. Prokaryotic genomes are frequently interrupted by horizontal gene transfer (HGT) and rearrangement. To know whether there is a set of genes not only conserved in position

A Wheat SIMILAR TO RCD-ONE Gene Enhances Seedling Growth and Abiotic Stress Resistance by Modulating Redox Homeostasis and Maintaining Genomic Integrity[C][W

Science.gov (United States)

Liu, Shuantao; Liu, Shuwei; Wang, Mei; Wei, Tiandi; Meng, Chen; Wang, Meng; Xia, Guangmin

2014-01-01

Plant growth inhibition is a common response to salinity. Under saline conditions, Shanrong No. 3 (SR3), a bread wheat (Triticum aestivum) introgression line, performs better than its parent wheat variety Jinan 177 (JN177) with respect to both seedling growth and abiotic stress tolerance. Furthermore, the endogenous reactive oxygen species (ROS) was also elevated in SR3 relative to JN177. The SR3 allele of sro1, a gene encoding a poly(ADP ribose) polymerase (PARP) domain protein, was identified to be crucial for both aspects of its superior performance. Unlike RADICAL-INDUCED CELL DEATH1 and other Arabidopsis thaliana SIMILAR TO RCD-ONE (SRO) proteins, sro1 has PARP activity. Both the overexpression of Ta-sro1 in wheat and its heterologous expression in Arabidopsis promote the accumulation of ROS, mainly by enhancing the activity of NADPH oxidase and the expression of NAD(P)H dehydrogenase, in conjunction with the suppression of alternative oxidase expression. Moreover, it promotes the activity of ascorbate-GSH cycle enzymes and GSH peroxidase cycle enzymes, which regulate ROS content and cellular redox homeostasis. sro1 is also found to be involved in the maintenance of genomic integrity. We show here that the wheat SRO has PARP activity; such activity could be manipulated to improve the growth of seedlings exposed to salinity stress by modulating redox homeostasis and maintaining genomic stability. PMID:24443520

MIPS plant genome information resources.

Science.gov (United States)

Spannagl, Manuel; Haberer, Georg; Ernst, Rebecca; Schoof, Heiko; Mayer, Klaus F X

2007-01-01

The Munich Institute for Protein Sequences (MIPS) has been involved in maintaining plant genome databases since the Arabidopsis thaliana genome project. Genome databases and analysis resources have focused on individual genomes and aim to provide flexible and maintainable data sets for model plant genomes as a backbone against which experimental data, for example from high-throughput functional genomics, can be organized and evaluated. In addition, model genomes also form a scaffold for comparative genomics, and much can be learned from genome-wide evolutionary studies.

The Drosophila homolog of the mammalian imprint regulator, CTCF, maintains the maternal genomic imprint in Drosophila melanogaster

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Rasheva Vanya

2010-07-01

Full Text Available Abstract Background CTCF is a versatile zinc finger DNA-binding protein that functions as a highly conserved epigenetic transcriptional regulator. CTCF is known to act as a chromosomal insulator, bind promoter regions, and facilitate long-range chromatin interactions. In mammals, CTCF is active in the regulatory regions of some genes that exhibit genomic imprinting, acting as insulator on only one parental allele to facilitate parent-specific expression. In Drosophila, CTCF acts as a chromatin insulator and is thought to be actively involved in the global organization of the genome. Results To determine whether CTCF regulates imprinting in Drosophila, we generated CTCF mutant alleles and assayed gene expression from the imprinted Dp(1;fLJ9 mini-X chromosome in the presence of reduced CTCF expression. We observed disruption of the maternal imprint when CTCF levels were reduced, but no effect was observed on the paternal imprint. The effect was restricted to maintenance of the imprint and was specific for the Dp(1;fLJ9 mini-X chromosome. Conclusions CTCF in Drosophila functions in maintaining parent-specific expression from an imprinted domain as it does in mammals. We propose that Drosophila CTCF maintains an insulator boundary on the maternal X chromosome, shielding genes from the imprint-induced silencing that occurs on the paternally inherited X chromosome. See commentary: http://www.biomedcentral.com/1741-7007/8/104

Epigenetic regulation of ageing: linking environmental inputs to genomic stability

Science.gov (United States)

Benayoun, Bérénice A.; Pollina, Elizabeth A.; Brunet, Anne

2016-01-01

Preface Ageing is affected by both genetic and non-genetic factors. Here, we review the chromatin-based epigenetic changes that occur during ageing, the role of chromatin modifiers in modulating lifespan and the importance of epigenetic signatures as biomarkers of ageing. We also discuss how epigenome remodeling by environmental stimuli impacts several aspects of transcription and genomic stability, with important consequences on longevity, and outline epigenetic differences between the ‘mortal soma’ and the ‘immortal germline’. Finally, we discuss the inheritance of ageing characteristics and potential chromatin-based strategies to delay or reverse hallmarks of ageing or age-related diseases. PMID:26373265

Photobiomodulation effects on mRNA levels from genomic and chromosome stabilization genes in injured muscle.

Science.gov (United States)

da Silva Neto Trajano, Larissa Alexsandra; Trajano, Eduardo Tavares Lima; da Silva Sergio, Luiz Philippe; Teixeira, Adilson Fonseca; Mencalha, Andre Luiz; Stumbo, Ana Carolina; de Souza da Fonseca, Adenilson

2018-04-26

Muscle injuries are the most prevalent type of injury in sports. A great number of athletes have relapsed in muscle injuries not being treated properly. Photobiomodulation therapy is an inexpensive and safe technique with many benefits in muscle injury treatment. However, little has been explored about the infrared laser effects on DNA and telomeres in muscle injuries. Thus, the aim of this study was to evaluate photobiomodulation effects on mRNA relative levels from genes related to telomere and genomic stabilization in injured muscle. Wistar male rats were randomly divided into six groups: control, laser 25 mW, laser 75 mW, injury, injury laser 25 mW, and injury laser 75 mW. Photobiomodulation was performed with 904 nm, 3 J/cm 2 at 25 or 75 mW. Cryoinjury was induced by two applications of a metal probe cooled in liquid nitrogen directly on the tibialis anterior muscle. After euthanasia, skeletal muscle samples were withdrawn and total RNA extracted for evaluation of mRNA levels from genomic (ATM and p53) and chromosome stabilization (TRF1 and TRF2) genes by real-time quantitative polymerization chain reaction. Data show that photobiomodulation reduces the mRNA levels from ATM and p53, as well reduces mRNA levels from TRF1 and TRF2 at 25 and 75 mW in injured skeletal muscle. In conclusion, photobiomodulation alters mRNA relative levels from genes related to genomic and telomere stabilization in injured skeletal muscle.

CDI Systems Are Stably Maintained by a Cell-Contact Mediated Surveillance Mechanism.

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Zachary C Ruhe

2016-06-01

Full Text Available Contact-dependent growth inhibition (CDI systems are widespread amongst Gram-negative bacteria where they play important roles in inter-cellular competition and biofilm formation. CDI+ bacteria use cell-surface CdiA proteins to bind neighboring bacteria and deliver C-terminal toxin domains. CDI+ cells also express CdiI immunity proteins that specifically neutralize toxins delivered from adjacent siblings. Genomic analyses indicate that cdi loci are commonly found on plasmids and genomic islands, suggesting that these Type 5 secretion systems are spread through horizontal gene transfer. Here, we examine whether CDI toxin and immunity activities serve to stabilize mobile genetic elements using a minimal F plasmid that fails to partition properly during cell division. This F plasmid is lost from Escherichia coli populations within 50 cell generations, but is maintained in ~60% of the cells after 100 generations when the plasmid carries the cdi gene cluster from E. coli strain EC93. By contrast, the ccdAB "plasmid addiction" module normally found on F exerts only a modest stabilizing effect. cdi-dependent plasmid stabilization requires the BamA receptor for CdiA, suggesting that plasmid-free daughter cells are inhibited by siblings that retain the CDI+ plasmid. In support of this model, the CDI+ F plasmid is lost rapidly from cells that carry an additional cdiI immunity gene on a separate plasmid. These results indicate that plasmid stabilization occurs through elimination of non-immune cells arising in the population via plasmid loss. Thus, genetic stabilization reflects a strong selection for immunity to CDI. After long-term passage for more than 300 generations, CDI+ plasmids acquire mutations that increase copy number and result in 100% carriage in the population. Together, these results show that CDI stabilizes genetic elements through a toxin-mediated surveillance mechanism in which cells that lose the CDI system are detected and eliminated by

From "Cellular" RNA to "Smart" RNA: Multiple Roles of RNA in Genome Stability and Beyond.

Science.gov (United States)

Michelini, Flavia; Jalihal, Ameya P; Francia, Sofia; Meers, Chance; Neeb, Zachary T; Rossiello, Francesca; Gioia, Ubaldo; Aguado, Julio; Jones-Weinert, Corey; Luke, Brian; Biamonti, Giuseppe; Nowacki, Mariusz; Storici, Francesca; Carninci, Piero; Walter, Nils G; Fagagna, Fabrizio d'Adda di

2018-03-30

Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA biology and genome stability. We start with an account of the emergence of noncoding RNA, and then we discuss the involvement of RNA in DNA damage signaling and repair, telomere maintenance, and genomic rearrangements. We continue with the depiction of single-molecule RNA detection techniques, and we conclude by illustrating the possibilities of RNA modulation in hopes of creating or improving new therapies. The widespread biological functions of RNA have made this molecule a reoccurring theme in basic and translational research, warranting it the transcendence from classically studied "cellular" RNA to "smart" RNA.

Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

Science.gov (United States)

Terasawa, Masahiro; Shinohara, Akira; Shinohara, Miki

2014-12-01

Double-strand breaks (DSBs) are one of the severest types of DNA damage. Unrepaired DSBs easily induce cell death and chromosome aberrations. To maintain genomic stability, cells have checkpoint and DSB repair systems to respond to DNA damage throughout most of the cell cycle. The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation. Therefore, DSB repair is essential for maintenance of genomic stability. During mitosis, however, cells seem to suppress the DNA damage response and proceed to the next G1 phase, even if there are unrepaired DSBs. The biological significance of this suppression is not known. In this review, we summarize recent studies of mitotic DSB repair and discuss the mechanisms of suppression of DSB repair during mitosis. DSB repair, which maintains genomic integrity in other phases of the cell cycle, is rather toxic to cells during mitosis, often resulting in chromosome missegregation and aberration. Cells have multiple safeguards to prevent genomic instability during mitosis: inhibition of 53BP1 or BRCA1 localization to DSB sites, which is important to promote non-homologous end joining or homologous recombination, respectively, and also modulation of the non-homologous end joining core complex to inhibit DSB repair. We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Beclin 1 and UVRAG confer protection from radiation-induced DNA damage and maintain centrosome stability in colorectal cancer cells.

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Jae Myung Park

Full Text Available Beclin 1 interacts with UV-irradiation-resistance-associated gene (UVRAG to form core complexes that induce autophagy. While cells with defective autophagy are prone to genomic instability that contributes to tumorigenesis, it is unknown whether Beclin1 or UVRAG can regulate the DNA damage/repair response to cancer treatment in established tumor cells. We found that siRNA knockdown of Beclin 1 or UVRAG can increase radiation-induced DNA double strand breaks (DSBs, shown by pATM and γH2Ax, and promote colorectal cancer cell death. Furthermore, knockdown of Beclin 1, UVRAG or ATG5 increased the percentage of irradiated cells with nuclear foci expressing 53BP1, a marker of nonhomologous end joining but not RAD51 (homologous recombination, compared to control siRNA. Beclin 1 siRNA was shown to attenuate UVRAG expression. Cells with a UVRAG deletion mutant defective in Beclin 1 binding showed increased radiation-induced DSBs and cell death compared to cells with ectopic wild-type UVRAG. Knockdown of Beclin 1 or UVRAG, but not ATG5, resulted in a significant increase in centrosome number (γ-tubulin staining in irradiated cells compared to control siRNA. Taken together, these data indicate that Beclin 1 and UVRAG confer protection against radiation-induced DNA DSBs and may maintain centrosome stability in established tumor cells.

Replicative Stress and the FHIT Gene: Roles in Tumor Suppression, Genome Stability and Prevention of Carcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Karras, Jenna R.; Paisie, Carolyn A.; Huebner, Kay, E-mail: kay.huebner@osumc.edu [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210 (United States)

2014-06-04

The fragile FHIT gene, encompassing the chromosomal fragile site FRA3B, is an early target of DNA damage in precancerous cells. While vulnerable to DNA damage itself, FHIT protein expression is essential to protect from DNA damage-induced cancer initiation and progression by modulating genome stability, oxidative stress and levels of accumulating DNA damage. Thus, FHIT, whose expression is lost or reduced in many human cancers, is a tumor suppressor and genome caretaker whose loss initiates genome instability in preneoplastic lesions. Ongoing studies are seeking more detailed understanding of the role of FHIT in the cellular response to oxidative damage. This review discusses the relationship between FHIT, reactive oxygen species production, and DNA damage in the context of cancer initiation and progression.

Genomic stability of adipogenic human adenovirus 36.

Science.gov (United States)

Nam, J-H; Na, H-N; Atkinson, R L; Dhurandhar, N V

2014-02-01

Human adenovirus Ad36 increases adiposity in several animal models, including rodents and non-human primates. Importantly, Ad36 is associated with human obesity, which has prompted research to understand its epidemiology and to develop a vaccine to prevent a subgroup of obesity. For this purpose, understanding the genomic stability of Ad36 in vivo and in vitro infections is critical. Here, we examined whether in vitro cell passaging over a 14-year period introduced any genetic variation in Ad36. We sequenced the whole genome of Ad36-which was plaque purified in 1998 from the original strain obtained from American Type Culture Collection, and passaged approximately 12 times over the past 14 years (Ad36-2012). This DNA sequence was compared with a previously published sequence of Ad36 likely obtained from the same source (Ad36-1988). Compared with Ad36-1988, only two nucleotides were altered in Ad36-2012: a T insertion at nucleotide 1862, which may induce early termination of the E1B viral protein, and a T➝C transition at nucleotide 26 136. Virus with the T insertion (designated Ad36-2012-T6) was mixed with wild-type virus lacking the T insertion (designated Ad36-2012-T5) in the viral stock. The transition at nucleotide 26 136 does not change the encoded amino acid (aspartic acid) in the pVIII viral protein. The rate of genetic variation in Ad36 is ∼2.37 × 10(-6) mutations/nucleotide/passage. Of particular importance, there were no mutations in the E4orf1 gene, the critical gene for producing obesity. This very-low-variation rate should reduce concerns about genetic variability when developing Ad36 vaccines or developing assays for detecting Ad36 infection in populations.

The human RecQ helicases BLM and RECQL4 cooperate to preserve genome stability

Czech Academy of Sciences Publication Activity Database

Singh, D.K.; Popuri, V.; Kulikowicz, T.; Shevelev, Igor; Ghosh, A.K.; Ramamoorthy, M.; Rossi, M.L.; Janščák, Pavel; Croteau, D.L.; Bohr, V.A.

2012-01-01

Roč. 40, č. 14 (2012), s. 6632-6648 ISSN 0305-1048 R&D Projects: GA ČR GAP305/10/0281 Grant - others:NIH(US) Z01-AG000726-17 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : RecQ helicase * genome stability * BLM * RECQL4 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.278, year: 2012

Initial processes of radiation effects on genomic stability

International Nuclear Information System (INIS)

Herve du Penhoat, Marie-Anne; Touati, Alain; Sage, Evelyne; Houee-Levin, Chantal; Lacombe, Sandrine; Politis, Marie-Françoise; Gaigeot, Marie-Pierre; Spezia, Riccardo; Vuilleumier, Rodolphe; Wien, Frank; Fujii, Kentaro; Yokoya, Akinari; Shikazono, Naoya

2014-01-01

We describe the progresses and current status of the REIMEI study on 'Initial processes of radiation effects on genomic stability', which is a new collaborative project between France and Japan. The theoretical study on the fragmentation pattern of doubly ionized deoxyribose has reached a new stage focusing on the effect of water molecules surrounding the deoxyribose molecule. In order to substantiate the theoretical predictions, new devices have been installed in a SPring-8 beamline. To explore the origin of signal transduction of DNA repair processes, a preliminary CD measurement in the far UV region was performed to study histone conformation changes. Based on these results, we will propose a new experimental subject in SOLEIL synchrotron to investigate the conformational changes of phosphorylated histone. Preliminary experiments using mammalian cell free extract have also been performed focusing on the role of DNA polymerases on the mutagenic potential of clustered DNA lesions. (author)

Regulation of rDNA stability by sumoylation

DEFF Research Database (Denmark)

Eckert-Boulet, Nadine; Lisby, Michael

2009-01-01

Repair of DNA lesions by homologous recombination relies on the copying of genetic information from an intact homologous sequence. However, many eukaryotic genomes contain repetitive sequences such as the ribosomal gene locus (rDNA), which poses a risk for illegitimate recombination. Therefore, t......6 complex and sumoylation of Rad52, which directs DNA double-strand breaks in the rDNA to relocalize from within the nucleolus to the nucleoplasm before association with the recombination machinery. The relocalization before repair is important for maintaining rDNA stability. The focus...

Bacterial Genome Editing Strategy for Control of Transcription and Protein Stability

DEFF Research Database (Denmark)

Lauritsen, Ida; Martinez, Virginia; Ronda, Carlotta

2018-01-01

In molecular biology and cell factory engineering, tools that enable control of protein production and stability are highly important. Here, we describe protocols for tagging genes in Escherichia coli allowing for inducible degradation and transcriptional control of any soluble protein of interest....... The underlying molecular biology is based on the two cross-kingdom tools CRISPRi and the N-end rule for protein degradation. Genome editing is performed with the CRMAGE technology and randomization of the translational initiation region minimizes the polar effects of tag insertion. The approach has previously...... been applied for targeting proteins originating from essential operon-located genes and has potential to serve as a universal synthetic biology tool....

Comparative analysis of mitochondrial genomes between a wheat K-type cytoplasmic male sterility (CMS) line and its maintainer line.

Science.gov (United States)

Liu, Huitao; Cui, Peng; Zhan, Kehui; Lin, Qiang; Zhuo, Guoyin; Guo, Xiaoli; Ding, Feng; Yang, Wenlong; Liu, Dongcheng; Hu, Songnian; Yu, Jun; Zhang, Aimin

2011-03-29

Plant mitochondria, semiautonomous organelles that function as manufacturers of cellular ATP, have their own genome that has a slow rate of evolution and rapid rearrangement. Cytoplasmic male sterility (CMS), a common phenotype in higher plants, is closely associated with rearrangements in mitochondrial DNA (mtDNA), and is widely used to produce F1 hybrid seeds in a variety of valuable crop species. Novel chimeric genes deduced from mtDNA rearrangements causing CMS have been identified in several plants, such as rice, sunflower, pepper, and rapeseed, but there are very few reports about mtDNA rearrangements in wheat. In the present work, we describe the mitochondrial genome of a wheat K-type CMS line and compare it with its maintainer line. The complete mtDNA sequence of a wheat K-type (with cytoplasm of Aegilops kotschyi) CMS line, Ks3, was assembled into a master circle (MC) molecule of 647,559 bp and found to harbor 34 known protein-coding genes, three rRNAs (18 S, 26 S, and 5 S rRNAs), and 16 different tRNAs. Compared to our previously published sequence of a K-type maintainer line, Km3, we detected Ks3-specific mtDNA (> 100 bp, 11.38%) and repeats (> 100 bp, 29 units) as well as genes that are unique to each line: rpl5 was missing in Ks3 and trnH was absent from Km3. We also defined 32 single nucleotide polymorphisms (SNPs) in 13 protein-coding, albeit functionally irrelevant, genes, and predicted 22 unique ORFs in Ks3, representing potential candidates for K-type CMS. All these sequence variations are candidates for involvement in CMS. A comparative analysis of the mtDNA of several angiosperms, including those from Ks3, Km3, rice, maize, Arabidopsis thaliana, and rapeseed, showed that non-coding sequences of higher plants had mostly divergent multiple reorganizations during the mtDNA evolution of higher plants. The complete mitochondrial genome of the wheat K-type CMS line Ks3 is very different from that of its maintainer line Km3, especially in non

Comparative analysis of mitochondrial genomes between a wheat K-type cytoplasmic male sterility (CMS line and its maintainer line

Directory of Open Access Journals (Sweden)

Liu Dongcheng

2011-03-01

Full Text Available Abstract Background Plant mitochondria, semiautonomous organelles that function as manufacturers of cellular ATP, have their own genome that has a slow rate of evolution and rapid rearrangement. Cytoplasmic male sterility (CMS, a common phenotype in higher plants, is closely associated with rearrangements in mitochondrial DNA (mtDNA, and is widely used to produce F1 hybrid seeds in a variety of valuable crop species. Novel chimeric genes deduced from mtDNA rearrangements causing CMS have been identified in several plants, such as rice, sunflower, pepper, and rapeseed, but there are very few reports about mtDNA rearrangements in wheat. In the present work, we describe the mitochondrial genome of a wheat K-type CMS line and compare it with its maintainer line. Results The complete mtDNA sequence of a wheat K-type (with cytoplasm of Aegilops kotschyi CMS line, Ks3, was assembled into a master circle (MC molecule of 647,559 bp and found to harbor 34 known protein-coding genes, three rRNAs (18 S, 26 S, and 5 S rRNAs, and 16 different tRNAs. Compared to our previously published sequence of a K-type maintainer line, Km3, we detected Ks3-specific mtDNA (> 100 bp, 11.38% and repeats (> 100 bp, 29 units as well as genes that are unique to each line: rpl5 was missing in Ks3 and trnH was absent from Km3. We also defined 32 single nucleotide polymorphisms (SNPs in 13 protein-coding, albeit functionally irrelevant, genes, and predicted 22 unique ORFs in Ks3, representing potential candidates for K-type CMS. All these sequence variations are candidates for involvement in CMS. A comparative analysis of the mtDNA of several angiosperms, including those from Ks3, Km3, rice, maize, Arabidopsis thaliana, and rapeseed, showed that non-coding sequences of higher plants had mostly divergent multiple reorganizations during the mtDNA evolution of higher plants. Conclusion The complete mitochondrial genome of the wheat K-type CMS line Ks3 is very different from that of

Maintaining Genome Stability in Defiance of Mitotic DNA Damage

Science.gov (United States)

Ferrari, Stefano; Gentili, Christian

2016-01-01

The implementation of decisions affecting cell viability and proliferation is based on prompt detection of the issue to be addressed, formulation and transmission of a correct set of instructions and fidelity in the execution of orders. While the first and the last are purely mechanical processes relying on the faithful functioning of single proteins or macromolecular complexes (sensors and effectors), information is the real cue, with signal amplitude, duration, and frequency ultimately determining the type of response. The cellular response to DNA damage is no exception to the rule. In this review article we focus on DNA damage responses in G2 and Mitosis. First, we set the stage describing mitosis and the machineries in charge of assembling the apparatus responsible for chromosome alignment and segregation as well as the inputs that control its function (checkpoints). Next, we examine the type of issues that a cell approaching mitosis might face, presenting the impact of post-translational modifications (PTMs) on the correct and timely functioning of pathways correcting errors or damage before chromosome segregation. We conclude this essay with a perspective on the current status of mitotic signaling pathway inhibitors and their potential use in cancer therapy. PMID:27493659

The Csr system regulates genome-wide mRNA stability and transcription and thus gene expression in Escherichia coli.

Science.gov (United States)

Esquerré, Thomas; Bouvier, Marie; Turlan, Catherine; Carpousis, Agamemnon J; Girbal, Laurence; Cocaign-Bousquet, Muriel

2016-04-26

Bacterial adaptation requires large-scale regulation of gene expression. We have performed a genome-wide analysis of the Csr system, which regulates many important cellular functions. The Csr system is involved in post-transcriptional regulation, but a role in transcriptional regulation has also been suggested. Two proteins, an RNA-binding protein CsrA and an atypical signaling protein CsrD, participate in the Csr system. Genome-wide transcript stabilities and levels were compared in wildtype E. coli (MG1655) and isogenic mutant strains deficient in CsrA or CsrD activity demonstrating for the first time that CsrA and CsrD are global negative and positive regulators of transcription, respectively. The role of CsrA in transcription regulation may be indirect due to the 4.6-fold increase in csrD mRNA concentration in the CsrA deficient strain. Transcriptional action of CsrA and CsrD on a few genes was validated by transcriptional fusions. In addition to an effect on transcription, CsrA stabilizes thousands of mRNAs. This is the first demonstration that CsrA is a global positive regulator of mRNA stability. For one hundred genes, we predict that direct control of mRNA stability by CsrA might contribute to metabolic adaptation by regulating expression of genes involved in carbon metabolism and transport independently of transcriptional regulation.

Pre-genomic, genomic and post-genomic study of microbial communities involved in bioenergy.

Science.gov (United States)

Rittmann, Bruce E; Krajmalnik-Brown, Rosa; Halden, Rolf U

2008-08-01

Microorganisms can produce renewable energy in large quantities and without damaging the environment or disrupting food supply. The microbial communities must be robust and self-stabilizing, and their essential syntrophies must be managed. Pre-genomic, genomic and post-genomic tools can provide crucial information about the structure and function of these microbial communities. Applying these tools will help accelerate the rate at which microbial bioenergy processes move from intriguing science to real-world practice.

维稳的转型及转型安排%Transformation of Maintaining Stability and its Arrangement

Institute of Scientific and Technical Information of China (English)

杨伟东

2015-01-01

经历十年纠纷矛盾多发期，我们开始探索新的处理矛盾机制。由政治维稳向法治维稳转型，是当前重要的政策选择。法治维稳在允许纠纷矛盾存在的前提下，致力于用规则预防和化解纠纷矛盾，做到维权与维稳并重。不过，要顺利实现转型，既要在实质上建立事先的预防纠纷发生的机制和事后的有效处理机制，也要做好转型期的安排，为管理者设置合理的评价标准、恰当引导当事人的行为和建立救助制度。%After the conflict-prone decade, new conflict solving mechanism needs to be explored. Transformation of the maintaining stability base from politics to rule of law is thesignificant policy choice in current situation. Under the premise of allowing the existence of conflicts, the maintaining stability based on rule of law is committed to using the rules to prevent and to resolve conflicts in order to gain both right guarantee and stability maintenance. However, to achieve successful transformation needs not only the establishment of beforehand conflict prevention and afterwards effective conflict-solving mechanisms in essence, but also related arrangement during the transformation period, including a reasonable evaluation criteria for officials, appropriate guide of the parties’ behaviors, and building of the relief system.

On the conformational stability of the smallest RNA kissing complexes maintained through two G·C base pairs

International Nuclear Information System (INIS)

Chu, Wally; Weerasekera, Akila; Kim, Chul-Hyun

2017-01-01

Two identical 5′GACG3′ tetra-loop motifs with different stem sequences (called H2 and H3) are found in the 5′ end region of Moloney Murine Leukemia Virus (MMLV) genomic RNA. They play important roles in RNA dimerization and encapsidation through two identical tetra-loops (5′GACG3′) forming a loop-to-loop kissing complex, the smallest RNA kissing complex ever found in nature. We examined the effects of a loop-closing base pair as well as a stem sequence on the conformational stability of the kissing complex. UV melting analysis and gel electrophoresis were performed on eight RNA sequences mimicking the H2 and H3 hairpin tetra-loops with variation in loop-closing base pairs. Our results show that changing the loop-closing base pair from the wildtype (5′A·U3′ for H3, 5′U·A3′ for H2) to 5′G·C3’/5′C·G3′ has significant effect on the stability of the kissing complexes: the substitution to 5′C·G3′ significantly decreases both thermal and mechanical stability, while switching to the 5′G·C3′ significantly increases the mechanical stability only. The kissing complexes with the wildtype loop-closing base pairs (5′A·U3′ for H3 and 5′U·A3′ for H2) show different stability when attached to a different stem sequence (H2 stem vs. H3 stem). This suggests that not only the loop-closing base pair itself, but also the stem sequence, affects the conformational stability of the RNA kissing complex. - Highlights: • Thermodynamic parameters of the smallest RNA kissing interactions were measured. • The effects of loop-closing base pairs on the RNA kissing complex was investigated. • Changing the base pair to 5′CG3′ decreases the stability of the kissing complex. • Changing it to 5′GC3′ increases the mechanical resilience of the kissing complex. • Difference in its stem sequence also affects the stability of the kissing complex.

Impact of nuclear organization and chromatin structure on DNA repair and genome stability

International Nuclear Information System (INIS)

Batte, Amandine

2016-01-01

The non-random organization of the eukaryotic cell nucleus and the folding of genome in chromatin more or less condensed can influence many functions related to DNA metabolism, including genome stability. Double-strand breaks (DSBs) are the most deleterious DNA damages for the cells. To preserve genome integrity, eukaryotic cells thus developed DSB repair mechanisms conserved from yeast to human, among which homologous recombination (HR) that uses an intact homologous sequence to repair a broken chromosome. HR can be separated in two sub-pathways: Gene Conversion (GC) transfers genetic information from one molecule to its homologous and Break Induced Replication (BIR) establishes a replication fork than can proceed until the chromosome end. My doctorate work was focused on the contribution of the chromatin context and 3D genome organization on DSB repair. In S. cerevisiae, nuclear organization and heterochromatin spreading at sub-telomeres can be modified through the overexpression of the Sir3 or sir3A2Q mutant proteins. We demonstrated that reducing the physical distance between homologous sequences increased GC rates, reinforcing the notion that homology search is a limiting step for recombination. We also showed that hetero-chromatinization of DSB site fine-tunes DSB resection, limiting the loss of the DSB ends required to perform homology search and complete HR. Finally, we noticed that the presence of heterochromatin at the donor locus decreased both GC and BIR efficiencies, probably by affecting strand invasion. This work highlights new regulatory pathways of DNA repair. (author) [fr

Genetic stability of pestivirus genomes cloned into BACs

DEFF Research Database (Denmark)

Rasmussen, Thomas Bruun; Reimann, Ilona; Uttenthal, Åse

pestivirus genomes to demonstrate the suitability of the BAC vector for harbouring pestivirus genomes. Two BAC clones, comprising the complete genomes of BDV Gifhorn (pBeloGif3) and CSFV Paderborn (pBeloPader10) were passaged 15 times in E.coli representing at least 360 bacteria generations. From 15th...

Genomic stability during cellular reprogramming: Mission impossible?

Energy Technology Data Exchange (ETDEWEB)

Joest, Mathieu von; Búa Aguín, Sabela; Li, Han, E-mail: han.li@pasteur.fr

2016-06-15

The generation of induced pluripotent stem cells (iPSCs) from adult somatic cells is one of the most exciting discoveries in recent biomedical research. It holds tremendous potential in drug discovery and regenerative medicine. However, a series of reports highlighting genomic instability in iPSCs raises concerns about their clinical application. Although the mechanisms cause genomic instability during cellular reprogramming are largely unknown, several potential sources have been suggested. This review summarizes current knowledge on this active research field and discusses the latest efforts to alleviate the genomic insults during cellular reprogramming to generate iPSCs with enhanced quality and safety.

Low income Russian families adopt effective behavioral strategies to maintain dietary stability in times of economic crisis.

Science.gov (United States)

Dore, Anna R; Adair, Linda S; Popkin, Barry M

2003-11-01

The social, political and economic reforms of 1992 in Russia led to a decade of rising income inequality, unemployment and economic crises, the most severe of which occurred in 1998. This study assesses dietary trends for children in low and high income households during this politically and economically unstable period from 1994 to 2000. Several possible food-related behaviors were also assessed to evaluate coping strategies adopted in the face of decreasing economic stability. Low income children maintained a steady energy intake per kilogram weight throughout the study period (251.0-259.4 kJ/kg), whereas intake for high income children increased significantly to a per capital average of 297.1 kJ/kg by 2000. At the food group level, the trend in per capita intake for all food groups was maintained for low income children except for a 22% decrease in meat and poultry consumption (P economic crisis.

Akt: A Double-Edged Sword in Cell Proliferation and Genome Stability

Directory of Open Access Journals (Sweden)

Naihan Xu

2012-01-01

Full Text Available The Akt family of serine/threonine protein kinases are key regulators of multiple aspects of cell behaviour, including proliferation, survival, metabolism, and tumorigenesis. Growth-factor-activated Akt signalling promotes progression through normal, unperturbed cell cycles by acting on diverse downstream factors involved in controlling the G1/S and G2/M transitions. Remarkably, several recent studies have also implicated Akt in modulating DNA damage responses and genome stability. High Akt activity can suppress ATR/Chk1 signalling and homologous recombination repair (HRR via direct phosphorylation of Chk1 or TopBP1 or, indirectly, by inhibiting recruitment of double-strand break (DSB resection factors, such as RPA, Brca1, and Rad51, to sites of damage. Loss of checkpoint and/or HRR proficiency is therefore a potential cause of genomic instability in tumor cells with high Akt. Conversely, Akt is activated by DNA double-strand breaks (DSBs in a DNA-PK- or ATM/ATR-dependent manner and in some circumstances can contribute to radioresistance by stimulating DNA repair by nonhomologous end joining (NHEJ. Akt therefore modifies both the response to and repair of genotoxic damage in complex ways that are likely to have important consequences for the therapy of tumors with deregulation of the PI3K-Akt-PTEN pathway.

PGSB/MIPS Plant Genome Information Resources and Concepts for the Analysis of Complex Grass Genomes.

Science.gov (United States)

Spannagl, Manuel; Bader, Kai; Pfeifer, Matthias; Nussbaumer, Thomas; Mayer, Klaus F X

2016-01-01

PGSB (Plant Genome and Systems Biology; formerly MIPS-Munich Institute for Protein Sequences) has been involved in developing, implementing and maintaining plant genome databases for more than a decade. Genome databases and analysis resources have focused on individual genomes and aim to provide flexible and maintainable datasets for model plant genomes as a backbone against which experimental data, e.g., from high-throughput functional genomics, can be organized and analyzed. In addition, genomes from both model and crop plants form a scaffold for comparative genomics, assisted by specialized tools such as the CrowsNest viewer to explore conserved gene order (synteny) between related species on macro- and micro-levels.The genomes of many economically important Triticeae plants such as wheat, barley, and rye present a great challenge for sequence assembly and bioinformatic analysis due to their enormous complexity and large genome size. Novel concepts and strategies have been developed to deal with these difficulties and have been applied to the genomes of wheat, barley, rye, and other cereals. This includes the GenomeZipper concept, reference-guided exome assembly, and "chromosome genomics" based on flow cytometry sorted chromosomes.

A Network of Multi-Tasking Proteins at the DNA Replication Fork Preserves Genome Stability.

Directory of Open Access Journals (Sweden)

2005-12-01

Full Text Available To elucidate the network that maintains high fidelity genome replication, we have introduced two conditional mutant alleles of DNA2, an essential DNA replication gene, into each of the approximately 4,700 viable yeast deletion mutants and determined the fitness of the double mutants. Fifty-six DNA2-interacting genes were identified. Clustering analysis of genomic synthetic lethality profiles of each of 43 of the DNA2-interacting genes defines a network (consisting of 322 genes and 876 interactions whose topology provides clues as to how replication proteins coordinate regulation and repair to protect genome integrity. The results also shed new light on the functions of the query gene DNA2, which, despite many years of study, remain controversial, especially its proposed role in Okazaki fragment processing and the nature of its in vivo substrates. Because of the multifunctional nature of virtually all proteins at the replication fork, the meaning of any single genetic interaction is inherently ambiguous. The multiplexing nature of the current studies, however, combined with follow-up supporting experiments, reveals most if not all of the unique pathways requiring Dna2p. These include not only Okazaki fragment processing and DNA repair but also chromatin dynamics.

Tolerance of Whole-Genome Doubling Propagates Chromosomal Instability and Accelerates Cancer Genome Evolution

DEFF Research Database (Denmark)

Dewhurst, Sally M.; McGranahan, Nicholas; Burrell, Rebecca A.

2014-01-01

The contribution of whole-genome doubling to chromosomal instability (CIN) and tumor evolution is unclear. We use long-term culture of isogenic tetraploid cells from a stable diploid colon cancer progenitor to investigate how a genome-doubling event affects genome stability over time. Rare cells...

Local neutral networks help maintain inaccurately replicating ribozymes.

Science.gov (United States)

Szilágyi, András; Kun, Ádám; Szathmáry, Eörs

2014-01-01

The error threshold of replication limits the selectively maintainable genome size against recurrent deleterious mutations for most fitness landscapes. In the context of RNA replication a distinction between the genotypic and the phenotypic error threshold has been made; where the latter concerns the maintenance of secondary structure rather than sequence. RNA secondary structure is treated as a proxy for function. The phenotypic error threshold allows higher per digit mutation rates than its genotypic counterpart, and is known to increase with the frequency of neutral mutations in sequence space. Here we show that the degree of neutrality, i.e. the frequency of nearest-neighbour (one-step) neutral mutants is a remarkably accurate proxy for the overall frequency of such mutants in an experimentally verifiable formula for the phenotypic error threshold; this we achieve by the full numerical solution for the concentration of all sequences in mutation-selection balance up to length 16. We reinforce our previous result that currently known ribozymes could be selectively maintained by the accuracy known from the best available polymerase ribozymes. Furthermore, we show that in silico stabilizing selection can increase the mutational robustness of ribozymes due to the fact that they were produced by artificial directional selection in the first place. Our finding offers a better understanding of the error threshold and provides further insight into the plausibility of an ancient RNA world.

Supplementary Material for: Whole genome sequencing reveals genomic heterogeneity and antibiotic purification in Mycobacterium tuberculosis isolates

KAUST Repository

Black, PA; Vos, M. de; Louw, GE; Merwe, RG van der; Dippenaar, A.; Streicher, EM; Abdallah, AM; Sampson, SL; Victor, TC; Dolby, T.; Simpson, JA; Helden, PD van; Warren, RM; Pain, Arnab

2015-01-01

Abstract Background Whole genome sequencing has revolutionised the interrogation of mycobacterial genomes. Recent studies have reported conflicting findings on the genomic stability of Mycobacterium tuberculosis during the evolution of drug

Sequencing the CHO DXB11 genome reveals regional variations in genomic stability and haploidy

DEFF Research Database (Denmark)

Kaas, Christian Schrøder; Kristensen, Claus; Betenbaugh, Michael J.

2015-01-01

Background: The DHFR negative CHO DXB11 cell line (also known as DUX-B11 and DUKX) was historically the first CHO cell line to be used for large scale production of heterologous proteins and is still used for production of a number of complex proteins.  Results: Here we present the genomic sequence...... of the CHO DXB11 genome sequenced to a depth of 33x. Overall a significant genomic drift was seen favoring GC -> AT point mutations in line with the chemical mutagenesis strategy used for generation of the cell line. The sequencing depth for each gene in the genome revealed distinct peaks at sequencing...... in eight additional analyzed CHO genomes (15-20% haploidy) but not in the genome of the Chinese hamster. The dhfr gene is confirmed to be haploid in CHO DXB11; transcriptionally active and the remaining allele contains a G410C point mutation causing a Thr137Arg missense mutation. We find similar to 2...

Balancing selection maintains cryptic colour morphs.

Science.gov (United States)

Wellenreuther, Maren

2017-11-01

Animals display incredibly diverse colour patterns, a testament to evolution's endless innovation in shaping life. In many species, the interplay between males and females in the pursuit of mates has driven the evolution of a myriad of colour forms, from the flashy peacock tail feathers to the tiniest colour markings in damselflies. In others, colour provides crypsis by allowing to blend into the background and to escape the eyes of predators. While the obvious benefits of this dazzling diversity for reproduction and survival seem straightforward, its maintenance is not. Theory predicts that genetic drift and various forms of selection reduce variation over time, making the persistence of colour variants over generations a puzzle. In this issue of Molecular Ecology, Lindtke et al. () study the cryptic colour morphs of Timema cristinae walking sticks to shed light on the genetic architecture and mechanisms that allow colour polymorphism maintenance over long timescales. By combining genome-wide data with phenotyping information from natural populations, they were able to map the green and melanistic colour to one genomic region with highly reduced effective recombination rate between two main chromosomal variants, consistent with an inversion polymorphism. These two main chromosomal variants showed geographically widespread heterozygote excess, and genomic signatures consistent with long-term balancing selection. A younger chromosomal variant was detected for the third morph, the green-striped colour morphs, in the same genomic regions as the melanistic and the green-unstriped morphs. Together, these results suggest that the genetic architecture of cryptic T. cristinae morphs is caused by nonrecombining genomic blocks that have been maintained over extended time periods by balancing selection making this study one of the few available empirical examples documenting that balancing selection of various forms may play an important role in maintaining adaptive genetic

DOT1L and H3K79 Methylation in Transcription and Genomic Stability.

Science.gov (United States)

Wood, Katherine; Tellier, Michael; Murphy, Shona

2018-02-27

The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79). H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL)-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability.

DOT1L and H3K79 Methylation in Transcription and Genomic Stability

Directory of Open Access Journals (Sweden)

Katherine Wood

2018-02-01

Full Text Available The organization of eukaryotic genomes into chromatin provides challenges for the cell to accomplish basic cellular functions, such as transcription, DNA replication and repair of DNA damage. Accordingly, a range of proteins modify and/or read chromatin states to regulate access to chromosomal DNA. Yeast Dot1 and the mammalian homologue DOT1L are methyltransferases that can add up to three methyl groups to histone H3 lysine 79 (H3K79. H3K79 methylation is implicated in several processes, including transcription elongation by RNA polymerase II, the DNA damage response and cell cycle checkpoint activation. DOT1L is also an important drug target for treatment of mixed lineage leukemia (MLL-rearranged leukemia where aberrant transcriptional activation is promoted by DOT1L mislocalisation. This review summarizes what is currently known about the role of Dot1/DOT1L and H3K79 methylation in transcription and genomic stability.

Genome-health nutrigenomics and nutrigenetics: nutritional requirements or 'nutriomes' for chromosomal stability and telomere maintenance at the individual level.

Science.gov (United States)

Bull, Caroline; Fenech, Michael

2008-05-01

It is becoming increasingly evident that (a) risk for developmental and degenerative disease increases with more DNA damage, which in turn is dependent on nutritional status, and (b) the optimal concentration of micronutrients for prevention of genome damage is also dependent on genetic polymorphisms that alter the function of genes involved directly or indirectly in the uptake and metabolism of micronutrients required for DNA repair and DNA replication. The development of dietary patterns, functional foods and supplements that are designed to improve genome-health maintenance in individuals with specific genetic backgrounds may provide an important contribution to an optimum health strategy based on the diagnosis and individualised nutritional prevention of genome damage, i.e. genome health clinics. The present review summarises some of the recent knowledge relating to micronutrients that are associated with chromosomal stability and provides some initial insights into the likely nutritional factors that may be expected to have an impact on the maintenance of telomeres. It is evident that developing effective strategies for defining nutrient doses and combinations or 'nutriomes' for genome-health maintenance at the individual level is essential for further progress in this research field.

Comparative genomics reveals diversified CRISPR-Cas systems of globally distributed Microcystis aeruginosa, a freshwater bloom-forming cyanobacterium

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Chen eYang

2015-05-01

Full Text Available Microcystis aeruginosa is one of the most common and dominant bloom-forming cyanobacteria in freshwater lakes around the world. Microcystis cells can produce toxic secondary metabolites, such as microcystins, which are harmful to human health. Two M. aeruginosa strains were isolated from two highly eutrophic lakes in China and their genomes were sequenced. Comparative genomic analysis was performed with the 12 other available M. aeruginosa genomes and closely related unicellular cyanobacterium. Each genome of M. aeruginosa containing at least one clustered regularly interspaced short palindromic repeat (CRISPR locus and total 71 loci were identified, suggesting it is ubiquitous in M. aeruginosa genomes. In addition to the previously reported subtype I-D cas gene sets, three CAS subtypes I-A, III-A and III-B were identified and characterized in this study. Seven types of CRISPR direct repeat have close association with CAS subtype, confirming that different and specific secondary structures of CRISPR repeats are important for the recognition, binding and process of corresponding cas gene sets. Homology search of the CRISPR spacer sequences provides a history of not only resistance to bacteriophages and plasmids known to be associated with M. aeruginosa, but also the ability to target much more exogenous genetic material in the natural environment. These adaptive and heritable defense mechanisms play a vital role in keeping genomic stability and self-maintenance by restriction of horizontal gene transfer. Maintaining genomic stability and modulating genomic plasticity are both important evolutionary strategies for M. aeruginosa in adaptation and survival in various habitats.

Thermodynamic stability of biomolecules and evolution.

Science.gov (United States)

Chakravarty, Ashim K

2017-08-01

The thermodynamic stability of biomolecules in the perspective of evolution is a complex issue and needs discussion. Intra molecular bonds maintain the structure and the state of internal energy (E) of a biomolecule at "local minima". In this communication, possibility of loss in internal energy level of a biomolecule through the changes in the bonds has been discussed, that might earn more thermodynamic stability for the molecule. In the process variations in structure and functions of the molecule could occur. Thus, E of a biomolecule is likely to have energy stature for minimization. Such change in energy status is an intrinsic factor for evolving biomolecules buying more stability and generating variations in the structure and function of DNA molecules undergoing natural selection. Thus, the variations might very well contribute towards the process of evolution. A brief discussion on conserved sequence in the light of proposition in this communication has been made at the end. Extension of the idea may resolve certain standing problems in evolution, such as maintenance of conserved sequences in genome of diverse species, pre- versus post adaptive mutations, 'orthogenesis', etc. Copyright © 2017 Elsevier Ltd. All rights reserved.

Potential mechanisms of carbon monoxide and high oxygen packaging in maintaining color stability of different bovine muscles.

Science.gov (United States)

Liu, Chenglong; Zhang, Yimin; Yang, Xiaoyin; Liang, Rongrong; Mao, Yanwei; Hou, Xu; Lu, Xiao; Luo, Xin

2014-06-01

The objectives were to compare the effects of packaging methods on color stability, metmyoglobin-reducing-activity (MRA), total-reducing-activity and NADH concentration of different bovine muscles and to explore potential mechanisms in the enhanced color stability by carbon monoxide modified atmosphere packaging (CO-MAP, 0.4% CO/30% CO2/69.6% N2). Steaks from longissimus lumborum (LL), psoas major (PM) and longissimus thoracis (LT) packaged in CO-MAP, high-oxygen modified atmosphere packaging (HiOx-MAP, 80% O2/20% CO2) or vacuum packaging were stored for 0day, 4days, 9days, and 14days or stored for 9days then displayed in air for 0day, 1day, or 3days. The CO-MAP significantly increased red color stability of all muscles, and especially for PM. The PM and LT were more red than LL in CO-MAP, whereas PM had lowest redness in HiOx-MAP. The content of MetMb in CO-MAP was lower than in HiOx-MAP. Steaks in CO-MAP maintained a higher MRA compared with those in HiOx-MAP during storage. After opening packages, the red color of steaks in CO-MAP deteriorated more slowly compared with that of steaks in HiOx-MAP. Copyright © 2014 Elsevier Ltd. All rights reserved.

Annotating the genome by DNA methylation.

Science.gov (United States)

Cedar, Howard; Razin, Aharon

2017-01-01

DNA methylation plays a prominent role in setting up and stabilizing the molecular design of gene regulation and by understanding this process one gains profound insight into the underlying biology of mammals. In this article, we trace the discoveries that provided the foundations of this field, starting with the mapping of methyl groups in the genome and the experiments that helped clarify how methylation patterns are maintained through cell division. We then address the basic relationship between methyl groups and gene repression, as well as the molecular rules involved in controlling this process during development in vivo. Finally, we describe ongoing work aimed at defining the role of this modification in disease and deciphering how it may serve as a mechanism for sensing the environment.

Deoxyribonucleic Acid Damage and Repair: Capitalizing on Our Understanding of the Mechanisms of Maintaining Genomic Integrity for Therapeutic Purposes

Directory of Open Access Journals (Sweden)

Jolene Michelle Helena

2018-04-01

Full Text Available Deoxyribonucleic acid (DNA is the self-replicating hereditary material that provides a blueprint which, in collaboration with environmental influences, produces a structural and functional phenotype. As DNA coordinates and directs differentiation, growth, survival, and reproduction, it is responsible for life and the continuation of our species. Genome integrity requires the maintenance of DNA stability for the correct preservation of genetic information. This is facilitated by accurate DNA replication and precise DNA repair. DNA damage may arise from a wide range of both endogenous and exogenous sources but may be repaired through highly specific mechanisms. The most common mechanisms include mismatch, base excision, nucleotide excision, and double-strand DNA (dsDNA break repair. Concurrent with regulation of the cell cycle, these mechanisms are precisely executed to ensure full restoration of damaged DNA. Failure or inaccuracy in DNA repair contributes to genome instability and loss of genetic information which may lead to mutations resulting in disease or loss of life. A detailed understanding of the mechanisms of DNA damage and its repair provides insight into disease pathogeneses and may facilitate diagnosis and the development of targeted therapies.

Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line

International Nuclear Information System (INIS)

Araújo, E.S.S. de; Vasques, L.R.; Stabellini, R.; Krepischi, A.C.V.; Pereira, L.V.

2014-01-01

DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A

Stability of XIST repression in relation to genomic imprinting following global genome demethylation in a human cell line

Energy Technology Data Exchange (ETDEWEB)

Araújo, E.S.S. de [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Vasques, L.R. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Stabellini, R.; Krepischi, A.C.V. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil); Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, São Paulo, SP (Brazil); Pereira, L.V. [Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP (Brazil)

2014-10-17

DNA methylation is essential in X chromosome inactivation and genomic imprinting, maintaining repression of XIST in the active X chromosome and monoallelic repression of imprinted genes. Disruption of the DNA methyltransferase genes DNMT1 and DNMT3B in the HCT116 cell line (DKO cells) leads to global DNA hypomethylation and biallelic expression of the imprinted gene IGF2 but does not lead to reactivation of XIST expression, suggesting that XIST repression is due to a more stable epigenetic mark than imprinting. To test this hypothesis, we induced acute hypomethylation in HCT116 cells by 5-aza-2′-deoxycytidine (5-aza-CdR) treatment (HCT116-5-aza-CdR) and compared that to DKO cells, evaluating DNA methylation by microarray and monitoring the expression of XIST and imprinted genes IGF2, H19, and PEG10. Whereas imprinted genes showed biallelic expression in HCT116-5-aza-CdR and DKO cells, the XIST locus was hypomethylated and weakly expressed only under acute hypomethylation conditions, indicating the importance of XIST repression in the active X to cell survival. Given that DNMT3A is the only active DNMT in DKO cells, it may be responsible for ensuring the repression of XIST in those cells. Taken together, our data suggest that XIST repression is more tightly controlled than genomic imprinting and, at least in part, is due to DNMT3A.

Chromosome-level genome map provides insights into diverse defense mechanisms in the medicinal fungus Ganoderma sinense

Science.gov (United States)

Zhu, Yingjie; Xu, Jiang; Sun, Chao; Zhou, Shiguo; Xu, Haibin; Nelson, David R.; Qian, Jun; Song, Jingyuan; Luo, Hongmei; Xiang, Li; Li, Ying; Xu, Zhichao; Ji, Aijia; Wang, Lizhi; Lu, Shanfa; Hayward, Alice; Sun, Wei; Li, Xiwen; Schwartz, David C.; Wang, Yitao; Chen, Shilin

2015-01-01

Fungi have evolved powerful genomic and chemical defense systems to protect themselves against genetic destabilization and other organisms. However, the precise molecular basis involved in fungal defense remain largely unknown in Basidiomycetes. Here the complete genome sequence, as well as DNA methylation patterns and small RNA transcriptomes, was analyzed to provide a holistic overview of secondary metabolism and defense processes in the model medicinal fungus, Ganoderma sinense. We reported the 48.96 Mb genome sequence of G. sinense, consisting of 12 chromosomes and encoding 15,688 genes. More than thirty gene clusters involved in the biosynthesis of secondary metabolites, as well as a large array of genes responsible for their transport and regulation were highlighted. In addition, components of genome defense mechanisms, namely repeat-induced point mutation (RIP), DNA methylation and small RNA-mediated gene silencing, were revealed in G. sinense. Systematic bioinformatic investigation of the genome and methylome suggested that RIP and DNA methylation combinatorially maintain G. sinense genome stability by inactivating invasive genetic material and transposable elements. The elucidation of the G. sinense genome and epigenome provides an unparalleled opportunity to advance our understanding of secondary metabolism and fungal defense mechanisms. PMID:26046933

Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome.

Directory of Open Access Journals (Sweden)

Damien F Hudson

2016-12-01

Full Text Available Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we report the identification of a second gene, RMI2, that is deleted in affected siblings with Bloom-like features. Cells from homozygous individuals exhibit elevated rates of sister chromatid exchange, anaphase DNA bridges and micronuclei. Similar genome and chromosome instability phenotypes are observed in independently derived RMI2 knockout cells. In both patient and knockout cell lines reduced localisation of BLM to ultra fine DNA bridges and FANCD2 at foci linking bridges are observed. Overall, loss of RMI2 produces a partially active BLM complex with mild features of Bloom syndrome.

i-Genome: A database to summarize oligonucleotide data in genomes

Directory of Open Access Journals (Sweden)

Chang Yu-Chung

2004-10-01

Full Text Available Abstract Background Information on the occurrence of sequence features in genomes is crucial to comparative genomics, evolutionary analysis, the analyses of regulatory sequences and the quantitative evaluation of sequences. Computing the frequencies and the occurrences of a pattern in complete genomes is time-consuming. Results The proposed database provides information about sequence features generated by exhaustively computing the sequences of the complete genome. The repetitive elements in the eukaryotic genomes, such as LINEs, SINEs, Alu and LTR, are obtained from Repbase. The database supports various complete genomes including human, yeast, worm, and 128 microbial genomes. Conclusions This investigation presents and implements an efficiently computational approach to accumulate the occurrences of the oligonucleotides or patterns in complete genomes. A database is established to maintain the information of the sequence features, including the distributions of oligonucleotide, the gene distribution, the distribution of repetitive elements in genomes and the occurrences of the oligonucleotides. The database can provide more effective and efficient way to access the repetitive features in genomes.

Packaging of a unit-length viral genome: the role of nucleotides and the gpD decoration protein in stable nucleocapsid assembly in bacteriophage lambda.

Science.gov (United States)

Yang, Qin; Maluf, Nasib Karl; Catalano, Carlos Enrique

2008-11-28

The developmental pathways for a variety of eukaryotic and prokaryotic double-stranded DNA viruses include packaging of viral DNA into a preformed procapsid structure, catalyzed by terminase enzymes and fueled by ATP hydrolysis. In most instances, a capsid expansion process accompanies DNA packaging, which significantly increases the volume of the capsid to accommodate the full-length viral genome. "Decoration" proteins add to the surface of the expanded capsid lattice, and the terminase motors tightly package DNA, generating up to approximately 20 atm of internal capsid pressure. Herein we describe biochemical studies on genome packaging using bacteriophage lambda as a model system. Kinetic analysis suggests that the packaging motor possesses at least four ATPase catalytic sites that act cooperatively to effect DNA translocation, and that the motor is highly processive. While not required for DNA translocation into the capsid, the phage lambda capsid decoration protein gpD is essential for the packaging of the penultimate 8-10 kb (15-20%) of the viral genome; virtually no DNA is packaged in the absence of gpD when large DNA substrates are used, most likely due to a loss of capsid structural integrity. Finally, we show that ATP hydrolysis is required to retain the genome in a packaged state subsequent to condensation within the capsid. Presumably, the packaging motor continues to "idle" at the genome end and to maintain a positive pressure towards the packaged state. Surprisingly, ADP, guanosine triphosphate, and the nonhydrolyzable ATP analog 5'-adenylyl-beta,gamma-imidodiphosphate (AMP-PNP) similarly stabilize the packaged viral genome despite the fact that they fail to support genome packaging. In contrast, the poorly hydrolyzed ATP analog ATP-gammaS only partially stabilizes the nucleocapsid, and a DNA is released in "quantized" steps. We interpret the ensemble of data to indicate that (i) the viral procapsid possesses a degree of plasticity that is required to

The Arabidopsis thaliana homolog of the helicase RTEL1 plays multiple roles in preserving genome stability.

Science.gov (United States)

Recker, Julia; Knoll, Alexander; Puchta, Holger

2014-12-01

In humans, mutations in the DNA helicase Regulator of Telomere Elongation Helicase1 (RTEL1) lead to Hoyeraal-Hreidarsson syndrome, a severe, multisystem disorder. Here, we demonstrate that the RTEL1 homolog in Arabidopsis thaliana plays multiple roles in preserving genome stability. RTEL1 suppresses homologous recombination in a pathway parallel to that of the DNA translocase FANCM. Cytological analyses of root meristems indicate that RTEL1 is involved in processing DNA replication intermediates independently from FANCM and the nuclease MUS81. Moreover, RTEL1 is involved in interstrand and intrastrand DNA cross-link repair independently from FANCM and (in intrastrand cross-link repair) parallel to MUS81. RTEL1 contributes to telomere homeostasis; the concurrent loss of RTEL1 and the telomerase TERT leads to rapid, severe telomere shortening, which occurs much more rapidly than it does in the single-mutant line tert, resulting in developmental arrest after four generations. The double mutant rtel1-1 recq4A-4 exhibits massive growth defects, indicating that this RecQ family helicase, which is also involved in the suppression of homologous recombination and the repair of DNA lesions, can partially replace RTEL1 in the processing of DNA intermediates. The requirement for RTEL1 in multiple pathways to preserve genome stability in plants can be explained by its putative role in the destabilization of DNA loop structures, such as D-loops and T-loops. © 2014 American Society of Plant Biologists. All rights reserved.

The complete chloroplast genome of Gracilariopsis lemaneiformis (Rhodophyta) gives new insight into the evolution of family Gracilariaceae.

Science.gov (United States)

Du, Qingwei; Bi, Guiqi; Mao, Yunxiang; Sui, Zhenghong

2016-06-01

The complete chloroplast genome of Gracilariopsis lemaneiformis was recovered from a Next Generation Sequencing data set. Without quadripartite structure, this chloroplast genome (183,013 bp, 27.40% GC content) contains 202 protein-coding genes, 34 tRNA genes, 3 rRNA genes, and 1 tmRNA gene. Synteny analysis showed plasmid incorporation regions in chloroplast genomes of three species of family Gracilariaceae and in Grateloupia taiwanensis of family Halymeniaceae. Combined with reported red algal plasmid sequences in nuclear and mitochondrial genomes, we postulated that red algal plasmids may have played an important role in ancient horizontal gene transfer among nuclear, chloroplast, and mitochondrial genomes. Substitution rate analysis showed that purifying selective forces maintaining stability of protein-coding genes of nine red algal chloroplast genomes over long periods must be strong and that the forces acting on gene groups and single genes of nine red algal chloroplast genomes were similar and consistent. The divergence of Gp. lemaneiformis occurred ~447.98 million years ago (Mya), close to the divergence time of genus Pyropia and Porphyra (443.62 Mya). © 2016 Phycological Society of America.

Choline and/or folic acid deficiency is associated with genomic damage and cell death in human lymphocytes in vitro.

Science.gov (United States)

Lu, Lin; Ni, Juan; Zhou, Tao; Xu, Weijiang; Fenech, Michael; Wang, Xu

2012-04-01

Choline and folate are interrelated methyl donors. Previous studies showed that folate prevents genomic damage in human lymphocytes in vitro; however, the association between choline and human genomic stability is uncertain. To explore the genotoxicity, cytotoxicity, and cytostatic effects and possible interactions of choline and/or folate deficiency on the human genome, lymphocytes from 6 volunteers were cultured in 18 combinations of choline (CC) and folic acid (FA) media for 9 days. The genotoxicity was evaluated by micronuclei, nucleoplasmic bridges, and nuclear buds in the binucleated cell; the cytotoxicity indices included apoptosis and necrosis, and the cytostatic effects were indicated by nuclear division index (NDI). Across all choline concentrations, the frequencies of all biomarkers except NDI were diminished when FA concentration was more than or equal to 120 nmol/L. The frequencies of micronuclei, buds, and necrosis were significantly higher at lower levels of CC (0-6 μmol/L) compared with higher concentrations of CC (12-21.5 μmol/L) while maintaining the same FA concentration. We concluded that both choline and folate significantly impact genomic stability and cell death, although effects of folate were 2.5- to 6.2-fold greater, depending on the biomarker and dose. A combination of 12 μmol/L CC and 120 nmol/L FA appears to be optimal for genomic integrity in vitro.

Genome engineering in Vibrio cholerae

DEFF Research Database (Denmark)

Val, Marie-Eve; Skovgaard, Ole; Ducos-Galand, Magaly

2012-01-01

Although bacteria with multipartite genomes are prevalent, our knowledge of the mechanisms maintaining their genome is very limited, and much remains to be learned about the structural and functional interrelationships of multiple chromosomes. Owing to its bi-chromosomal genome architecture and its....... This difficulty was surmounted using a unique and powerful strategy based on massive rearrangement of prokaryotic genomes. We developed a site-specific recombination-based engineering tool, which allows targeted, oriented, and reciprocal DNA exchanges. Using this genetic tool, we obtained a panel of V. cholerae...

Roles of Type 1A Topoisomerases in Genome Maintenance in Escherichia coli

Science.gov (United States)

Usongo, Valentine; Drolet, Marc

2014-01-01

In eukaryotes, type 1A topoisomerases (topos) act with RecQ-like helicases to maintain the stability of the genome. Despite having been the first type 1A enzymes to be discovered, much less is known about the involvement of the E. coli topo I (topA) and III (topB) enzymes in genome maintenance. These enzymes are thought to have distinct cellular functions: topo I regulates supercoiling and R-loop formation, and topo III is involved in chromosome segregation. To better characterize their roles in genome maintenance, we have used genetic approaches including suppressor screens, combined with microscopy for the examination of cell morphology and nucleoid shape. We show that topA mutants can suffer from growth-inhibitory and supercoiling-dependent chromosome segregation defects. These problems are corrected by deleting recA or recQ but not by deleting recJ or recO, indicating that the RecF pathway is not involved. Rather, our data suggest that RecQ acts with a type 1A topo on RecA-generated recombination intermediates because: 1-topo III overproduction corrects the defects and 2-recQ deletion and topo IIII overproduction are epistatic to recA deletion. The segregation defects are also linked to over-replication, as they are significantly alleviated by an oriC::aph suppressor mutation which is oriC-competent in topA null but not in isogenic topA+ cells. When both topo I and topo III are missing, excess supercoiling triggers growth inhibition that correlates with the formation of extremely long filaments fully packed with unsegregated and diffuse DNA. These phenotypes are likely related to replication from R-loops as they are corrected by overproducing RNase HI or by genetic suppressors of double topA rnhA mutants affecting constitutive stable DNA replication, dnaT::aph and rne::aph, which initiates from R-loops. Thus, bacterial type 1A topos maintain the stability of the genome (i) by preventing over-replication originating from oriC (topo I alone) and R-loops and (ii

Quantitative analysis of DNA methylation at all human imprinted regions reveals preservation of epigenetic stability in adult somatic tissue

Directory of Open Access Journals (Sweden)

Woodfine Kathryn

2011-01-01

Full Text Available Abstract Background Genes subject to genomic imprinting are mono-allelically expressed in a parent-of-origin dependent manner. Each imprinted locus has at least one differentially methylated region (DMR which has allele specific DNA methylation and contributes to imprinted gene expression. Once DMRs are established, they are potentially able to withstand normal genome reprogramming events that occur during cell differentiation and germ-line DMRs are stably maintained throughout development. These DMRs, in addition to being either maternally or paternally methylated, have differences in whether methylation was acquired in the germ-line or post fertilization and are present in a variety of genomic locations with different Cytosine-phosphate guanine (CpG densities and CTCF binding capacities. We therefore examined the stability of maintenance of DNA methylation imprints and determined the normal baseline DNA methylation levels in several adult tissues for all imprinted genes. In order to do this, we first developed and validated 50 highly specific, quantitative DNA methylation pyrosequencing assays for the known DMRs associated with human imprinted genes. Results Remarkable stability of the DNA methylation imprint was observed in all germ-line DMRs and paternally methylated somatic DMRs (which maintained average methylation levels of between 35% - 65% in all somatic tissues, independent of gene expression. Maternally methylated somatic DMRs were found to have more variation with tissue specific methylation patterns. Most DMRs, however, showed some intra-individual variability for DNA methylation levels in peripheral blood, suggesting that more than one DMR needs to be examined in order to get an overall impression of the epigenetic stability in a tissue. The plasticity of DNA methylation at imprinted genes was examined in a panel of normal and cancer cell lines. All cell lines showed changes in DNA methylation, especially at the paternal germ

DNA Precursor Metabolism and Mitochondrial Genome Stability

National Research Council Canada - National Science Library

Mathews, Christopher K

2003-01-01

...) metabolism and mutagenesis in the mitochondrial genome. Specific contributions include: (1) We found that conditions altering the normal balance among the four dNTP pools within the mitochondrion stimulate both point and deletion mutagenesis...

The genome portal of the Department of Energy Joint Genome Institute: 2014 updates

Energy Technology Data Exchange (ETDEWEB)

Nordberg, Henrik [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Cantor, Michael [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Dusheyko, Serge [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Hua, Susan [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Poliakov, Alexander [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Shabalov, Igor [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Smirnova, Tatyana [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Grigoriev, Igor V. [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States); Dubchak, Inna [USDOE Joint Genome Institute (JGI), Walnut Creek, CA (United States)

2013-11-12

The U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a national user facility, serves the diverse scientific community by providing integrated high-throughput sequencing and computational analysis to enable system-based scientific approaches in support of DOE missions related to clean energy generation and environmental characterization. The JGI Genome Portal (http://genome.jgi.doe.gov) provides unified access to all JGI genomic databases and analytical tools. The JGI maintains extensive data management systems and specialized analytical capabilities to manage and interpret complex genomic data. A user can search, download and explore multiple data sets available for all DOE JGI sequencing projects including their status, assemblies and annotations of sequenced genomes. In this paper, we describe major updates of the Genome Portal in the past 2 years with a specific emphasis on efficient handling of the rapidly growing amount of diverse genomic data accumulated in JGI.

The life cycle of a genome project: perspectives and guidelines inspired by insect genome projects.

Science.gov (United States)

Papanicolaou, Alexie

2016-01-01

Many research programs on non-model species biology have been empowered by genomics. In turn, genomics is underpinned by a reference sequence and ancillary information created by so-called "genome projects". The most reliable genome projects are the ones created as part of an active research program and designed to address specific questions but their life extends past publication. In this opinion paper I outline four key insights that have facilitated maintaining genomic communities: the key role of computational capability, the iterative process of building genomic resources, the value of community participation and the importance of manual curation. Taken together, these ideas can and do ensure the longevity of genome projects and the growing non-model species community can use them to focus a discussion with regards to its future genomic infrastructure.

Stabilization of pH in solid-matrix hydroponic systems

Science.gov (United States)

Frick, J.; Mitchell, C. A.

1993-01-01

2-[N-morpholino]ethanesulfonic acid (MES) buffer or Amberlite DP-1 (cation-exchange resin beads) were used to stabilize substrate pH of passive-wicking, solid-matrix hydroponic systems in which small canopies of Brassica napus L. (CrGC 5-2, genome : ACaacc) were grown to maturity. Two concentrations of MES (5 or 10 mM) were included in Hoagland 1 nutrient solution. Alternatively, resin beads were incorporated into the 2 vermiculite : 1 perlite (v/v) growth medium at 6% or 12% of total substrate volume. Both strategies stabilized pH without toxic side effects on plants. Average seed yield rates for all four pH stabilization treatments (13.3 to 16.9 g m-2 day-1) were about double that of the control (8.2 g m-2 day-1), for which there was no attempt to buffer substrate pH. Both the highest canopy seed yield rate (16.9 g m-2 day-1) and the highest shoot harvest index (19.5%) occurred with the 6% resin bead treatment, even though the 10 mM MES and 12% bead treatments maintained pH within the narrowest limits. The pH stabilization methods tested did not significantly affect seed oil and protein contents.

dAdd1 and dXNP prevent genome instability by maintaining HP1a localization at Drosophila telomeres.

Science.gov (United States)

Chavez, Joselyn; Murillo-Maldonado, Juan Manuel; Bahena, Vanessa; Cruz, Ana Karina; Castañeda-Sortibrán, América; Rodriguez-Arnaiz, Rosario; Zurita, Mario; Valadez-Graham, Viviana

2017-12-01

Telomeres are important contributors to genome stability, as they prevent linear chromosome end degradation and contribute to the avoidance of telomeric fusions. An important component of the telomeres is the heterochromatin protein 1a (HP1a). Mutations in Su(var)205, the gene encoding HP1a in Drosophila, result in telomeric fusions, retrotransposon regulation loss and larger telomeres, leading to chromosome instability. Previously, it was found that several proteins physically interact with HP1a, including dXNP and dAdd1 (orthologues to the mammalian ATRX gene). In this study, we found that mutations in the genes encoding the dXNP and dAdd1 proteins affect chromosome stability, causing chromosomal aberrations, including telomeric defects, similar to those observed in Su(var)205 mutants. In somatic cells, we observed that dXNP and dAdd1 participate in the silencing of the telomeric HTT array of retrotransposons, preventing anomalous retrotransposon transcription and integration. Furthermore, the lack of dAdd1 results in the loss of HP1a from the telomeric regions without affecting other chromosomal HP1a binding sites; mutations in dxnp also affected HP1a localization but not at all telomeres, suggesting a specialized role for dAdd1 and dXNP proteins in locating HP1a at the tips of the chromosomes. These results place dAdd1 as an essential regulator of HP1a localization and function in the telomere heterochromatic domain.

Effect of Urea on G-Quadruplex Stability.

Science.gov (United States)

Aslanyan, Lusine; Ko, Jordan; Kim, Byul G; Vardanyan, Ishkhan; Dalyan, Yeva B; Chalikian, Tigran V

2017-07-13

G-quadruplexes represent a class of noncanonical nucleic acid structures implicated in transcriptional regulation, cellular function, and disease. An understanding of the forces involved in stabilization and destabilization of the G-quadruplex conformation relative to the duplex or single-stranded conformation is a key to elucidating the biological role of G-quadruplex-based genomic switches and the quest for therapeutic means for controlled induction or suppression of a G-quadruplex at selected genomic loci. Solute-solvent interactions provide a ubiquitous and, in many cases, the determining thermodynamic force in maintaining and modulating the stability of nucleic acids. These interactions involve water as well as water-soluble cosolvents that may be present in the solution or in the crowded environment in the cell. We present here the first quantitative investigation of the effect of urea, a destabilizing cosolvent, on the conformational preferences of a G-quadruplex formed by the telomeric d[A(G 3 T 2 A) 3 G 3 ] sequence (Tel22). At 20 mM NaCl and room temperature, Tel22 undergoes a two-state urea-induced unfolding transition. An increase in salt mitigates the deleterious effect of urea on Tel22. The urea m-value of Tel22 normalized per change in solvent-accessible surface area, ΔS A , is similar to those for other DNA and RNA structures while being several-fold larger than that of proteins. Our results suggest that urea can be employed as an analytical tool in thermodynamic characterizations of G-quadruplexes in a manner similar to the use of urea in protein studies. We emphasize the need for further studies involving a larger selection of G-quadruplexes varying in sequence, topology (parallel, antiparallel, hybrid), and molecularity (monomolecular, bimolecular, tetramolecular) to outline the advantages and the limits of the use of urea in G-quadruplex studies. A deeper understanding of the effect of solvent and cosolvents on the differential stability of the

The Arabidopsis thaliana Homolog of the Helicase RTEL1 Plays Multiple Roles in Preserving Genome Stability[C][W

Science.gov (United States)

Recker, Julia; Knoll, Alexander; Puchta, Holger

2014-01-01

In humans, mutations in the DNA helicase Regulator of Telomere Elongation Helicase1 (RTEL1) lead to Hoyeraal-Hreidarsson syndrome, a severe, multisystem disorder. Here, we demonstrate that the RTEL1 homolog in Arabidopsis thaliana plays multiple roles in preserving genome stability. RTEL1 suppresses homologous recombination in a pathway parallel to that of the DNA translocase FANCM. Cytological analyses of root meristems indicate that RTEL1 is involved in processing DNA replication intermediates independently from FANCM and the nuclease MUS81. Moreover, RTEL1 is involved in interstrand and intrastrand DNA cross-link repair independently from FANCM and (in intrastrand cross-link repair) parallel to MUS81. RTEL1 contributes to telomere homeostasis; the concurrent loss of RTEL1 and the telomerase TERT leads to rapid, severe telomere shortening, which occurs much more rapidly than it does in the single-mutant line tert, resulting in developmental arrest after four generations. The double mutant rtel1-1 recq4A-4 exhibits massive growth defects, indicating that this RecQ family helicase, which is also involved in the suppression of homologous recombination and the repair of DNA lesions, can partially replace RTEL1 in the processing of DNA intermediates. The requirement for RTEL1 in multiple pathways to preserve genome stability in plants can be explained by its putative role in the destabilization of DNA loop structures, such as D-loops and T-loops. PMID:25516598

DNA replication factor C1 mediates genomic stability and transcriptional gene silencing in Arabidopsis

KAUST Repository

Liu, Qian; Wang, Junguo; Miki, Daisuke; Xia, Ran; Yu, Wenxiang; He, Junna; Zheng, Zhimin; Zhu, Jian-Kang; Gonga, Zhizhong

2010-01-01

Genetic screening identified a suppressor of ros1-1, a mutant of REPRESSOR OF SILENCING1 (ROS1; encoding a DNA demethylation protein). The suppressor is a mutation in the gene encoding the largest subunit of replication factor C (RFC1). This mutation of RFC1 reactivates the unlinked 35S-NPTII transgene, which is silenced in ros1 and also increases expression of the pericentromeric Athila retrotransposons named transcriptional silent information in a DNA methylationindependent manner. rfc1 is more sensitive than the wild type to the DNA-damaging agent methylmethane sulphonate and to the DNA inter- and intra- cross-linking agent cisplatin. The rfc1 mutant constitutively expresses the G2/M-specific cyclin CycB1;1 and other DNA repair-related genes. Treatment with DNA-damaging agents mimics the rfc1 mutation in releasing the silenced 35S-NPTII, suggesting that spontaneously induced genomic instability caused by the rfc1 mutation might partially contribute to the released transcriptional gene silencing (TGS). The frequency of somatic homologous recombination is significantly increased in the rfc1 mutant. Interestingly, ros1 mutants show increased telomere length, but rfc1 mutants show decreased telomere length and reduced expression of telomerase. Our results suggest that RFC1 helps mediate genomic stability and TGS in Arabidopsis thaliana. © 2010 American Society of Plant Biologists.

DNA replication factor C1 mediates genomic stability and transcriptional gene silencing in Arabidopsis

KAUST Repository

Liu, Qian

2010-07-01

Genetic screening identified a suppressor of ros1-1, a mutant of REPRESSOR OF SILENCING1 (ROS1; encoding a DNA demethylation protein). The suppressor is a mutation in the gene encoding the largest subunit of replication factor C (RFC1). This mutation of RFC1 reactivates the unlinked 35S-NPTII transgene, which is silenced in ros1 and also increases expression of the pericentromeric Athila retrotransposons named transcriptional silent information in a DNA methylationindependent manner. rfc1 is more sensitive than the wild type to the DNA-damaging agent methylmethane sulphonate and to the DNA inter- and intra- cross-linking agent cisplatin. The rfc1 mutant constitutively expresses the G2/M-specific cyclin CycB1;1 and other DNA repair-related genes. Treatment with DNA-damaging agents mimics the rfc1 mutation in releasing the silenced 35S-NPTII, suggesting that spontaneously induced genomic instability caused by the rfc1 mutation might partially contribute to the released transcriptional gene silencing (TGS). The frequency of somatic homologous recombination is significantly increased in the rfc1 mutant. Interestingly, ros1 mutants show increased telomere length, but rfc1 mutants show decreased telomere length and reduced expression of telomerase. Our results suggest that RFC1 helps mediate genomic stability and TGS in Arabidopsis thaliana. © 2010 American Society of Plant Biologists.

Maintaining ancient organelles: mitochondrial biogenesis and maturation.

Science.gov (United States)

Vega, Rick B; Horton, Julie L; Kelly, Daniel P

2015-05-22

The ultrastructure of the cardiac myocyte is remarkable for the high density of mitochondria tightly packed between sarcomeres. This structural organization is designed to provide energy in the form of ATP to fuel normal pump function of the heart. A complex system comprised of regulatory factors and energy metabolic machinery, encoded by both mitochondrial and nuclear genomes, is required for the coordinate control of cardiac mitochondrial biogenesis, maturation, and high-capacity function. This process involves the action of a transcriptional regulatory network that builds and maintains the mitochondrial genome and drives the expression of the energy transduction machinery. This finely tuned system is responsive to developmental and physiological cues, as well as changes in fuel substrate availability. Deficiency of components critical for mitochondrial energy production frequently manifests as a cardiomyopathic phenotype, underscoring the requirement to maintain high respiration rates in the heart. Although a precise causative role is not clear, there is increasing evidence that perturbations in this regulatory system occur in the hypertrophied and failing heart. This review summarizes current knowledge and highlights recent advances in our understanding of the transcriptional regulatory factors and signaling networks that serve to regulate mitochondrial biogenesis and function in the mammalian heart. © 2015 American Heart Association, Inc.

Nucleotide excision repair : a multi-step mechanism required to maintain genome integrity

NARCIS (Netherlands)

Moser, Jill

2010-01-01

DNA is continuously exposed to exogenous and genotoxic insults including ionizing and ultraviolet radiation as well as chemical agents. DNA damage can compromise the integrity of the genome and have potentially deleterious effects. Ultraviolet light (UV) can induce the formation of helix distorting

Molecular Mechanisms Underlying Genomic Instability in Brca-Deficient Cells

Science.gov (United States)

2014-11-01

increased by hydroxyurea, ATR inhibition, deregulated c-Myc expression and by PARPi treatment of BRCA1 deficient cells. This work was recently published...Genome Stability." 6: May 27, 2013-Collaborative Research Center 655 from Cells to Tissues seminar series at the Max-Planck-Institute in Dresden, Germany ...Eisenach, Germany -“Genome Stability during DNA Replication” 8: May 3, 2013- Chemical and Systems Biology Department Seminar Series at Stanford

ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells

Directory of Open Access Journals (Sweden)

Tompkins Kathleen

2010-10-01

Full Text Available Abstract Background Unrepaired DNA double-stranded breaks (DSBs cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability. NHEJ defects lead to severe combined immunodeficiency (SCID and lymphoid cancer predisposition in both mice and humans. While NHEJ has been thoroughly investigated in lymphocytes, the importance of NHEJ in other cell types, especially with regard to tumor suppression, is less well documented. We previously reported evidence that the NHEJ pathway functions to suppress a range of nonlymphoid tumor types, including various classes of sarcomas, by unknown mechanisms. Results Here we investigate roles for the NHEJ factor ARTEMIS in multipotent mesenchymal stem/progenitor cells (MSCs, as putative sarcomagenic cells of origin. We demonstrate a key role for ARTEMIS in sarcoma suppression in a sensitized mouse tumor model. In this context, we found that ARTEMIS deficiency led to chromosomal damage but, paradoxically, enhanced resistance and proliferative potential in primary MSCs subjected to various stresses. Gene expression analysis revealed abnormally regulated stress response, cell proliferation, and signal transduction pathways in ARTEMIS-defective MSCs. Finally, we identified candidate regulatory genes that may, in part, mediate a stress-resistant, hyperproliferative phenotype in preneoplastic ARTEMIS-deficient MSCs. Conclusions Our discoveries suggest that Art prevents genome damage and restrains proliferation in MSCs exposed to various stress stimuli. We propose that deficiency leads to a preneoplastic state in primary MSCs and is associated with aberrant proliferative control and cellular stress

Genome Stability of Lyme Disease Spirochetes: Comparative Genomics of Borrelia burgdorferi Plasmids

Energy Technology Data Exchange (ETDEWEB)

Casjens S. R.; Dunn J.; Mongodin, E. F.; Qiu, W.-G.; Luft, B. J.; Schutzer, S. E.; Gilcrease, E. B.; Huang, W. M.; Vujadinovic, M.; Aron, J. K.; Vargas, L. C.; Freeman, S.; Radune, D.; Weidman, J. F.; Dimitrov, G. I.; Khouri, H. M.; Sosa, J. E.; Halpin, R. A.; Fraser, C. M.

2012-03-14

Lyme disease is the most common tick-borne human illness in North America. In order to understand the molecular pathogenesis, natural diversity, population structure and epizootic spread of the North American Lyme agent, Borrelia burgdorferi sensu stricto, a much better understanding of the natural diversity of its genome will be required. Towards this end we present a comparative analysis of the nucleotide sequences of the numerous plasmids of B. burgdorferi isolates B31, N40, JD1 and 297. These strains were chosen because they include the three most commonly studied laboratory strains, and because they represent different major genetic lineages and so are informative regarding the genetic diversity and evolution of this organism. A unique feature of Borrelia genomes is that they carry a large number of linear and circular plasmids, and this work shows that strains N40, JD1, 297 and B31 carry related but non-identical sets of 16, 20, 19 and 21 plasmids, respectively, that comprise 33-40% of their genomes. We deduce that there are at least 28 plasmid compatibility types among the four strains. The B. burgdorferi {approx}900 Kbp linear chromosomes are evolutionarily exceptionally stable, except for a short {le}20 Kbp plasmid-like section at the right end. A few of the plasmids, including the linear lp54 and circular cp26, are also very stable. We show here that the other plasmids, especially the linear ones, are considerably more variable. Nearly all of the linear plasmids have undergone one or more substantial inter-plasmid rearrangements since their last common ancestor. In spite of these rearrangements and differences in plasmid contents, the overall gene complement of the different isolates has remained relatively constant.

Crystal Structures of DNA-Whirly Complexes and Their Role in Arabidopsis Organelle Genome Repair

Energy Technology Data Exchange (ETDEWEB)

Cappadocia, Laurent; Maréchal, Alexandre; Parent, Jean-Sébastien; Lepage, Étienne; Sygusch, Jurgen; Brisson, Normand (Montreal)

2010-09-07

DNA double-strand breaks are highly detrimental to all organisms and need to be quickly and accurately repaired. Although several proteins are known to maintain plastid and mitochondrial genome stability in plants, little is known about the mechanisms of DNA repair in these organelles and the roles of specific proteins. Here, using ciprofloxacin as a DNA damaging agent specific to the organelles, we show that plastids and mitochondria can repair DNA double-strand breaks through an error-prone pathway similar to the microhomology-mediated break-induced replication observed in humans, yeast, and bacteria. This pathway is negatively regulated by the single-stranded DNA (ssDNA) binding proteins from the Whirly family, thus indicating that these proteins could contribute to the accurate repair of plant organelle genomes. To understand the role of Whirly proteins in this process, we solved the crystal structures of several Whirly-DNA complexes. These reveal a nonsequence-specific ssDNA binding mechanism in which DNA is stabilized between domains of adjacent subunits and rendered unavailable for duplex formation and/or protein interactions. Our results suggest a model in which the binding of Whirly proteins to ssDNA would favor accurate repair of DNA double-strand breaks over an error-prone microhomology-mediated break-induced replication repair pathway.

Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein

Science.gov (United States)

Marsh, Elizabeth K.; Delury, Craig P.; Davies, Nicholas J.; Weston, Christopher J.; Miah, Mohammed A.L.; Banks, Lawrence; Parish, Joanna L.

2017-01-01

The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome. The loss of the E6 PBM was associated with a significant increase in the frequency of mitotic spindle defects associated with anaphase and telophase. Furthermore, cells carrying this mutant genome had increased chromosome segregation defects and they also exhibited greater levels of genomic instability, as shown by an elevated level of centromere-positive micronuclei. In wild type HPV18 genome-containing organotypic cultures, the majority of mitotic cells reside in the suprabasal layers, in keeping with the hyperplastic morphology of the structures. However, in mutant genome-containing structures a greater proportion of mitotic cells were retained in the basal layer, which were often of undefined polarity, thus correlating with their reduced thickness. We conclude that the ability of E6 to target cellular PDZ proteins plays a critical role in maintaining mitotic stability of HPV infected cells, ensuring stable episome persistence and vegetative amplification. PMID:28061478

Mitotic control of human papillomavirus genome-containing cells is regulated by the function of the PDZ-binding motif of the E6 oncoprotein.

Science.gov (United States)

Marsh, Elizabeth K; Delury, Craig P; Davies, Nicholas J; Weston, Christopher J; Miah, Mohammed A L; Banks, Lawrence; Parish, Joanna L; Higgs, Martin R; Roberts, Sally

2017-03-21

The function of a conserved PDS95/DLG1/ZO1 (PDZ) binding motif (E6 PBM) at the C-termini of E6 oncoproteins of high-risk human papillomavirus (HPV) types contributes to the development of HPV-associated malignancies. Here, using a primary human keratinocyte-based model of the high-risk HPV18 life cycle, we identify a novel link between the E6 PBM and mitotic stability. In cultures containing a mutant genome in which the E6 PBM was deleted there was an increase in the frequency of abnormal mitoses, including multinucleation, compared to cells harboring the wild type HPV18 genome. The loss of the E6 PBM was associated with a significant increase in the frequency of mitotic spindle defects associated with anaphase and telophase. Furthermore, cells carrying this mutant genome had increased chromosome segregation defects and they also exhibited greater levels of genomic instability, as shown by an elevated level of centromere-positive micronuclei. In wild type HPV18 genome-containing organotypic cultures, the majority of mitotic cells reside in the suprabasal layers, in keeping with the hyperplastic morphology of the structures. However, in mutant genome-containing structures a greater proportion of mitotic cells were retained in the basal layer, which were often of undefined polarity, thus correlating with their reduced thickness. We conclude that the ability of E6 to target cellular PDZ proteins plays a critical role in maintaining mitotic stability of HPV infected cells, ensuring stable episome persistence and vegetative amplification.

Considerations in the identification of functional RNA structural elements in genomic alignments

Directory of Open Access Journals (Sweden)

Blencowe Benjamin J

2007-01-01

Full Text Available Abstract Background Accurate identification of novel, functional noncoding (nc RNA features in genome sequence has proven more difficult than for exons. Current algorithms identify and score potential RNA secondary structures on the basis of thermodynamic stability, conservation, and/or covariance in sequence alignments. Neither the algorithms nor the information gained from the individual inputs have been independently assessed. Furthermore, due to issues in modelling background signal, it has been difficult to gauge the precision of these algorithms on a genomic scale, in which even a seemingly small false-positive rate can result in a vast excess of false discoveries. Results We developed a shuffling algorithm, shuffle-pair.pl, that simultaneously preserves dinucleotide frequency, gaps, and local conservation in pairwise sequence alignments. We used shuffle-pair.pl to assess precision and recall of six ncRNA search tools (MSARI, QRNA, ddbRNA, RNAz, Evofold, and several variants of simple thermodynamic stability on a test set of 3046 alignments of known ncRNAs. Relative to mononucleotide shuffling, preservation of dinucleotide content in shuffling the alignments resulted in a drastic increase in estimated false-positive detection rates for ncRNA elements, precluding evaluation of higher order alignments, which cannot not be adequately shuffled maintaining both dinucleotides and alignment structure. On pairwise alignments, none of the covariance-based tools performed markedly better than thermodynamic scoring alone. Although the high false-positive rates call into question the veracity of any individual predicted secondary structural element in our analysis, we nevertheless identified intriguing global trends in human genome alignments. The distribution of ncRNA prediction scores in 75-base windows overlapping UTRs, introns, and intergenic regions analyzed using both thermodynamic stability and EvoFold (which has no thermodynamic component was

Xenopus egg extract: A powerful tool to study genome maintenance mechanisms.

Science.gov (United States)

Hoogenboom, Wouter S; Klein Douwel, Daisy; Knipscheer, Puck

2017-08-15

DNA repair pathways are crucial to maintain the integrity of our genome and prevent genetic diseases such as cancer. There are many different types of DNA damage and specific DNA repair mechanisms have evolved to deal with these lesions. In addition to these repair pathways there is an extensive signaling network that regulates processes important for repair, such as cell cycle control and transcription. Despite extensive research, DNA damage repair and signaling are not fully understood. In vitro systems such as the Xenopus egg extract system, have played, and still play, an important role in deciphering the molecular details of these processes. Xenopus laevis egg extracts contain all factors required to efficiently perform DNA repair outside a cell, using mechanisms conserved in humans. These extracts have been used to study several genome maintenance pathways, including mismatch repair, non-homologous end joining, ICL repair, DNA damage checkpoint activation, and replication fork stability. Here we describe how the Xenopus egg extract system, in combination with specifically designed DNA templates, contributed to our detailed understanding of these pathways. Copyright © 2017. Published by Elsevier Inc.

The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes.

Science.gov (United States)

Treangen, Todd J; Ondov, Brian D; Koren, Sergey; Phillippy, Adam M

2014-01-01

Whole-genome sequences are now available for many microbial species and clades, however existing whole-genome alignment methods are limited in their ability to perform sequence comparisons of multiple sequences simultaneously. Here we present the Harvest suite of core-genome alignment and visualization tools for the rapid and simultaneous analysis of thousands of intraspecific microbial strains. Harvest includes Parsnp, a fast core-genome multi-aligner, and Gingr, a dynamic visual platform. Together they provide interactive core-genome alignments, variant calls, recombination detection, and phylogenetic trees. Using simulated and real data we demonstrate that our approach exhibits unrivaled speed while maintaining the accuracy of existing methods. The Harvest suite is open-source and freely available from: http://github.com/marbl/harvest.

Streamlining genomes: toward the generation of simplified and stabilized microbial systems

NARCIS (Netherlands)

Leprince, A.; Passel, van M.W.J.; Martins Dos Santos, V.A.P.

2012-01-01

At the junction between systems and synthetic biology, genome streamlining provides a solid foundation both for increased understanding of cellular circuitry, and for the tailoring of microbial chassis towards innovative biotechnological applications. Iterative genomic deletions (targeted and

Tetraploid Embryonic Stem Cells Maintain Pluripotency and Differentiation Potency into Three Germ Layers.

Directory of Open Access Journals (Sweden)

Hiroyuki Imai

Full Text Available Polyploid amphibians and fishes occur naturally in nature, while polyploid mammals do not. For example, tetraploid mouse embryos normally develop into blastocysts, but exhibit abnormalities and die soon after implantation. Thus, polyploidization is thought to be harmful during early mammalian development. However, the mechanisms through which polyploidization disrupts development are still poorly understood. In this study, we aimed to elucidate how genome duplication affects early mammalian development. To this end, we established tetraploid embryonic stem cells (TESCs produced from the inner cell masses of tetraploid blastocysts using electrofusion of two-cell embryos in mice and studied the developmental potential of TESCs. We demonstrated that TESCs possessed essential pluripotency and differentiation potency to form teratomas, which differentiated into the three germ layers, including diploid embryonic stem cells. TESCs also contributed to the inner cell masses in aggregated chimeric blastocysts, despite the observation that tetraploid embryos fail in normal development soon after implantation in mice. In TESCs, stability after several passages, colony morphology, and alkaline phosphatase activity were similar to those of diploid ESCs. TESCs also exhibited sufficient expression and localization of pluripotent markers and retained the normal epigenetic status of relevant reprogramming factors. TESCs proliferated at a slower rate than ESCs, indicating that the difference in genomic dosage was responsible for the different growth rates. Thus, our findings suggested that mouse ESCs maintained intrinsic pluripotency and differentiation potential despite tetraploidization, providing insights into our understanding of developmental elimination in polyploid mammals.

Tetraploid Embryonic Stem Cells Maintain Pluripotency and Differentiation Potency into Three Germ Layers.

Science.gov (United States)

Imai, Hiroyuki; Kano, Kiyoshi; Fujii, Wataru; Takasawa, Ken; Wakitani, Shoichi; Hiyama, Masato; Nishino, Koichiro; Kusakabe, Ken Takeshi; Kiso, Yasuo

2015-01-01

Polyploid amphibians and fishes occur naturally in nature, while polyploid mammals do not. For example, tetraploid mouse embryos normally develop into blastocysts, but exhibit abnormalities and die soon after implantation. Thus, polyploidization is thought to be harmful during early mammalian development. However, the mechanisms through which polyploidization disrupts development are still poorly understood. In this study, we aimed to elucidate how genome duplication affects early mammalian development. To this end, we established tetraploid embryonic stem cells (TESCs) produced from the inner cell masses of tetraploid blastocysts using electrofusion of two-cell embryos in mice and studied the developmental potential of TESCs. We demonstrated that TESCs possessed essential pluripotency and differentiation potency to form teratomas, which differentiated into the three germ layers, including diploid embryonic stem cells. TESCs also contributed to the inner cell masses in aggregated chimeric blastocysts, despite the observation that tetraploid embryos fail in normal development soon after implantation in mice. In TESCs, stability after several passages, colony morphology, and alkaline phosphatase activity were similar to those of diploid ESCs. TESCs also exhibited sufficient expression and localization of pluripotent markers and retained the normal epigenetic status of relevant reprogramming factors. TESCs proliferated at a slower rate than ESCs, indicating that the difference in genomic dosage was responsible for the different growth rates. Thus, our findings suggested that mouse ESCs maintained intrinsic pluripotency and differentiation potential despite tetraploidization, providing insights into our understanding of developmental elimination in polyploid mammals.

Telomere maintenance through recruitment of internal genomic regions.

Science.gov (United States)

Seo, Beomseok; Kim, Chuna; Hills, Mark; Sung, Sanghyun; Kim, Hyesook; Kim, Eunkyeong; Lim, Daisy S; Oh, Hyun-Seok; Choi, Rachael Mi Jung; Chun, Jongsik; Shim, Jaegal; Lee, Junho

2015-09-18

Cells surviving crisis are often tumorigenic and their telomeres are commonly maintained through the reactivation of telomerase. However, surviving cells occasionally activate a recombination-based mechanism called alternative lengthening of telomeres (ALT). Here we establish stably maintained survivors in telomerase-deleted Caenorhabditis elegans that escape from sterility by activating ALT. ALT survivors trans-duplicate an internal genomic region, which is already cis-duplicated to chromosome ends, across the telomeres of all chromosomes. These 'Template for ALT' (TALT) regions consist of a block of genomic DNA flanked by telomere-like sequences, and are different between two genetic background. We establish a model that an ancestral duplication of a donor TALT region to a proximal telomere region forms a genomic reservoir ready to be incorporated into telomeres on ALT activation.

Recent Insights into the Control of Human Papillomavirus (HPV Genome Stability, Loss, and Degradation

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Chris Fisher

2015-01-01

Full Text Available Most human papillomavirus (HPV antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their hosts. They must replicate and hide from the DNA damage response (DDR and innate immune systems, which serve to protect cells from foreign or "non-self" DNA, and yet they draft these same systems to support their life cycles. DNA binding antiviral agents promoting massive viral DNA instability and elimination are reviewed. Mechanistic studies of these agents have identified genetic antiviral enhancers and repressors, antiviral sensitizers, and host cell elements that protect and stabilize HPV genomes. Viral DNA degradation appears to be an important means of controlling HPV DNA levels in some cases, but the underlying mechanisms remain poorly understood. These findings may prove useful not only for understanding viral DNA persistence but also in devising future antiviral strategies.

Recent Insights into the Control of Human Papillomavirus (HPV) Genome Stability, Loss, and Degradation.

Science.gov (United States)

Fisher, Chris

2015-01-01

Most human papillomavirus (HPV) antiviral strategies have focused upon inhibiting viral DNA replication, but it is increasingly apparent that viral DNA levels can be chemically controlled by approaches that promote its instability. HPVs and other DNA viruses have a tenuous relationship with their hosts. They must replicate and hide from the DNA damage response (DDR) and innate immune systems, which serve to protect cells from foreign or "non-self" DNA, and yet they draft these same systems to support their life cycles. DNA binding antiviral agents promoting massive viral DNA instability and elimination are reviewed. Mechanistic studies of these agents have identified genetic antiviral enhancers and repressors, antiviral sensitizers, and host cell elements that protect and stabilize HPV genomes. Viral DNA degradation appears to be an important means of controlling HPV DNA levels in some cases, but the underlying mechanisms remain poorly understood. These findings may prove useful not only for understanding viral DNA persistence but also in devising future antiviral strategies.

The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

Science.gov (United States)

The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G2/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 depositi...

Genomic instability following irradiation

International Nuclear Information System (INIS)

Hacker-Klom, U.B.; Goehde, W.

2001-01-01

Ionising irradiation may induce genomic instability. The broad spectrum of stress reactions in eukaryontic cells to irradiation complicates the discovery of cellular targets and pathways inducing genomic instability. Irradiation may initiate genomic instability by deletion of genes controlling stability, by induction of genes stimulating instability and/or by activating endogeneous cellular viruses. Alternatively or additionally it is discussed that the initiation of genomic instability may be a consequence of radiation or other agents independently of DNA damage implying non nuclear targets, e.g. signal cascades. As a further mechanism possibly involved our own results may suggest radiation-induced changes in chromatin structure. Once initiated the process of genomic instability probably is perpetuated by endogeneous processes necessary for proliferation. Genomic instability may be a cause or a consequence of the neoplastic phenotype. As a conclusion from the data available up to now a new interpretation of low level radiation effects for radiation protection and in radiotherapy appears useful. The detection of the molecular mechanisms of genomic instability will be important in this context and may contribute to a better understanding of phenomenons occurring at low doses <10 cSv which are not well understood up to now. (orig.)

A universal genomic coordinate translator for comparative genomics.

Science.gov (United States)

Zamani, Neda; Sundström, Görel; Meadows, Jennifer R S; Höppner, Marc P; Dainat, Jacques; Lantz, Henrik; Haas, Brian J; Grabherr, Manfred G

2014-06-30

Genomic duplications constitute major events in the evolution of species, allowing paralogous copies of genes to take on fine-tuned biological roles. Unambiguously identifying the orthology relationship between copies across multiple genomes can be resolved by synteny, i.e. the conserved order of genomic sequences. However, a comprehensive analysis of duplication events and their contributions to evolution would require all-to-all genome alignments, which increases at N2 with the number of available genomes, N. Here, we introduce Kraken, software that omits the all-to-all requirement by recursively traversing a graph of pairwise alignments and dynamically re-computing orthology. Kraken scales linearly with the number of targeted genomes, N, which allows for including large numbers of genomes in analyses. We first evaluated the method on the set of 12 Drosophila genomes, finding that orthologous correspondence computed indirectly through a graph of multiple synteny maps comes at minimal cost in terms of sensitivity, but reduces overall computational runtime by an order of magnitude. We then used the method on three well-annotated mammalian genomes, human, mouse, and rat, and show that up to 93% of protein coding transcripts have unambiguous pairwise orthologous relationships across the genomes. On a nucleotide level, 70 to 83% of exons match exactly at both splice junctions, and up to 97% on at least one junction. We last applied Kraken to an RNA-sequencing dataset from multiple vertebrates and diverse tissues, where we confirmed that brain-specific gene family members, i.e. one-to-many or many-to-many homologs, are more highly correlated across species than single-copy (i.e. one-to-one homologous) genes. Not limited to protein coding genes, Kraken also identifies thousands of newly identified transcribed loci, likely non-coding RNAs that are consistently transcribed in human, chimpanzee and gorilla, and maintain significant correlation of expression levels across

Targets of balancing selection in the human genome

DEFF Research Database (Denmark)

Andrés, Aida M; Hubisz, Melissa J; Indap, Amit

2009-01-01

Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant...... to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism data set......, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows enrichment...

Stability of Hyperthermophilic Proteins

DEFF Research Database (Denmark)

Stiefler-Jensen, Daniel

stability by randomly generate mutants and lengthy screening processes to identify the best new mutants. However, with the increase in available genomic sequences of thermophilic or hyperthermophilic organisms a world of enzymes with intrinsic high stability are now available. As these organisms are adapted...... to life at high temperatures so are their enzymes, as a result the high stability is accompanied by low activity at moderate temperatures. Thus, much effort had been put into decoding the mechanisms behind the high stability of the thermophilic enzymes. The hope is to enable scientist to design enzymes...... in the high stability of hyperthermophilic enzymes. The thesis starts with an introduction to the field of protein and enzyme stability with special focus on the thermophilic and hyperthermophilic enzymes and proteins. After the introduction three original research manuscripts present the experimental data...

Genome sequence analysis of the model grass Brachypodium distachyon: insights into grass genome evolution

Energy Technology Data Exchange (ETDEWEB)

Schulman, Al

2009-08-09

Three subfamilies of grasses, the Erhardtoideae (rice), the Panicoideae (maize, sorghum, sugar cane and millet), and the Pooideae (wheat, barley and cool season forage grasses) provide the basis of human nutrition and are poised to become major sources of renewable energy. Here we describe the complete genome sequence of the wild grass Brachypodium distachyon (Brachypodium), the first member of the Pooideae subfamily to be completely sequenced. Comparison of the Brachypodium, rice and sorghum genomes reveals a precise sequence- based history of genome evolution across a broad diversity of the grass family and identifies nested insertions of whole chromosomes into centromeric regions as a predominant mechanism driving chromosome evolution in the grasses. The relatively compact genome of Brachypodium is maintained by a balance of retroelement replication and loss. The complete genome sequence of Brachypodium, coupled to its exceptional promise as a model system for grass research, will support the development of new energy and food crops

Roles of POLD4, smallest subunit of DNA polymerase {delta}, in nuclear structures and genomic stability of human cells

Energy Technology Data Exchange (ETDEWEB)

Huang, Qin Miao [Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan); Akashi, Tomohiro [Division of Molecular Mycology and Medicine, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan); Masuda, Yuji; Kamiya, Kenji [Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan); Takahashi, Takashi [Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan); Suzuki, Motoshi, E-mail: msuzuki@med.nagoya-u.ac.jp [Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya (Japan)

2010-01-01

Mammalian DNA polymerase {delta} (pol {delta}) is essential for DNA replication, though the functions of this smallest subunit of POLD4 have been elusive. We investigated pol {delta} activities in vitro and found that it was less active in the absence of POLD4, irrespective of the presence of the accessory protein PCNA. shRNA-mediated reduction of POLD4 resulted in a marked decrease in colony formation activity by Calu6, ACC-LC-319, and PC-10 cells. We also found that POLD4 reduction was associated with an increased population of karyomere-like cells, which may be an indication of DNA replication stress and/or DNA damage. The karyomere-like cells retained an ability to progress through the cell cycle, suggesting that POLD4 reduction induces modest genomic instability, while allowing cells to grow until DNA damage reaches an intolerant level. Our results indicate that POLD4 is required for the in vitro pol {delta} activity, and that it functions in cell proliferation and maintenance of genomic stability of human cells.

Roles of POLD4, smallest subunit of DNA polymerase δ, in nuclear structures and genomic stability of human cells

International Nuclear Information System (INIS)

Huang, Qin Miao; Akashi, Tomohiro; Masuda, Yuji; Kamiya, Kenji; Takahashi, Takashi; Suzuki, Motoshi

2010-01-01

Mammalian DNA polymerase δ (pol δ) is essential for DNA replication, though the functions of this smallest subunit of POLD4 have been elusive. We investigated pol δ activities in vitro and found that it was less active in the absence of POLD4, irrespective of the presence of the accessory protein PCNA. shRNA-mediated reduction of POLD4 resulted in a marked decrease in colony formation activity by Calu6, ACC-LC-319, and PC-10 cells. We also found that POLD4 reduction was associated with an increased population of karyomere-like cells, which may be an indication of DNA replication stress and/or DNA damage. The karyomere-like cells retained an ability to progress through the cell cycle, suggesting that POLD4 reduction induces modest genomic instability, while allowing cells to grow until DNA damage reaches an intolerant level. Our results indicate that POLD4 is required for the in vitro pol δ activity, and that it functions in cell proliferation and maintenance of genomic stability of human cells.

Efficient replication, and evolution of Sindbis virus genomes with non-canonical 3'A/U-rich elements (NC3ARE) in neonatal mice.

Science.gov (United States)

James, Frederick D; Hietala, Katie A; Eldar, Dganit; Guess, Tiffany E; Cone, Cecil; Mundell, Nathan A; Mundall, Nathan; Barnett, Joey V; Raju, Ramaswamy

2007-12-01

Sindbis virus (SIN) is a mosquito-transmitted animal RNA virus. We previously reported that SIN genomes lacking a canonical 19 nt 3'CSE undergo novel repair processes in BHK cells to generate a library of stable atypical SIN genomes with non-canonical 3'A/U-rich elements (NC3AREs) adjacent to the 3' poly(A) tail [1]. To determine the stability and evolutionary pressures on the SIN genomes with NC3AREs to regain a 3'CSE, five representative SIN isolates and a wild type SIN were tested in newborn mice. The key findings of this study are: (a) all six SIN isolates, including those that have extensive NC3AREs in the 3'NTRs, replicate well and produce high titer viremia in newborn mice; (b) 7-9 successive passages of these isolates in newborn mice produced comparable levels of viremia; (c) while all isolates produced only small-sized plaques during primary infection in animals, both small- and large-sized plaques were generated in all other passages; (d) polymerase stuttering occurs on select 3' oligo(U) motifs to add more U residues within the NC3AREs; (e) the S3-8 isolate with an internal UAUUU motif in the 3'poly(A) tail maintains this element even after 9 passages in animals; (f) despite differences in 3'NTRs and variable tissue distribution, all SIN isolates appear to produce similar tissue pathology in infected animals. Competition experiments with wt SIN and atypical SIN isolates in BHK cells show dominance of wt SIN. As shown for BHK cells in culture, the 3'CSE of the SIN genome is not required for virus replication and genome stability in live animals. Since the NC3AREs of atypical SIN genomes are not specific to SIN replicases, alternate RNA motifs of alphavirus genome must confer specificity in template selection. These studies fulfill the need to confirm the long-term viability of atypical SIN genomes in newborn mice and offer a basis for exploring the use of atypical SIN genomes in biotechnology.

Multiscale modeling of three-dimensional genome

Science.gov (United States)

Zhang, Bin; Wolynes, Peter

The genome, the blueprint of life, contains nearly all the information needed to build and maintain an entire organism. A comprehensive understanding of the genome is of paramount interest to human health and will advance progress in many areas, including life sciences, medicine, and biotechnology. The overarching goal of my research is to understand the structure-dynamics-function relationships of the human genome. In this talk, I will be presenting our efforts in moving towards that goal, with a particular emphasis on studying the three-dimensional organization, the structure of the genome with multi-scale approaches. Specifically, I will discuss the reconstruction of genome structures at both interphase and metaphase by making use of data from chromosome conformation capture experiments. Computationally modeling of chromatin fiber at atomistic level from first principles will also be presented as our effort for studying the genome structure from bottom up.

Analysis of cis-elements that facilitate extrachromosomal persistence of human papillomavirus genomes

International Nuclear Information System (INIS)

Pittayakhajonwut, Daraporn; Angeletti, Peter C.

2008-01-01

Human papillomaviruses (HPVs) are maintained latently in dividing epithelial cells as nuclear plasmids. Two virally encoded proteins, E1, a helicase, and E2, a transcription factor, are important players in replication and stable plasmid maintenance in host cells. Recent experiments in yeast have demonstrated that viral genomes retain replication and maintenance function independently of E1 and E2 [Angeletti, P.C., Kim, K., Fernandes, F.J., and Lambert, P.F. (2002). Stable replication of papillomavirus genomes in Saccharomyces cerevisiae. J. Virol. 76(7), 3350-8; Kim, K., Angeletti, P.C., Hassebroek, E.C., and Lambert, P.F. (2005). Identification of cis-acting elements that mediate the replication and maintenance of human papillomavirus type 16 genomes in Saccharomyces cerevisiae. J. Virol. 79(10), 5933-42]. Flow cytometry studies of EGFP-reporter vectors containing subgenomic HPV fragments with or without a human ARS (hARS), revealed that six fragments located in E6-E7, E1-E2, L1, and L2 regions showed a capacity for plasmid stabilization in the absence of E1 and E2 proteins. Interestingly, four fragments within E7, the 3' end of L2, and the 5' end of L1 exhibited stability in plasmids that lacked an hARS, indicating that they possess both replication and maintenance functions. Two fragments lying in E1-E2 and the 3' region of L1 were stable only in the presence of hARS, that they contained only maintenance function. Mutational analyses of HPV16-GFP reporter constructs provided evidence that genomes lacking E1 and E2 could replicate to an extent similar to wild type HPV16. Together these results support the concept that cellular factors influence HPV replication and maintenance, independently, and perhaps in conjunction with E1 and E2, suggesting a role in the persistent phase of the viral lifecycle

Phase noise cancellation in polarisation-maintaining fibre links

Science.gov (United States)

Rauf, B.; Vélez López, M. C.; Thoumany, P.; Pizzocaro, M.; Calonico, D.

2018-03-01

The distribution of ultra-narrow linewidth laser radiation is an integral part of many challenging metrological applications. Changes in the optical pathlength induced by environmental disturbances compromise the stability and accuracy of optical fibre networks distributing the laser light and call for active phase noise cancellation. Here we present a laboratory scale optical (at 578 nm) fibre network featuring all polarisation maintaining fibres in a setup with low optical powers available and tracking voltage-controlled oscillators implemented. The stability and accuracy of this system reach performance levels below 1 × 10-19 after 10 000 s of averaging.

Proximity of signallers can maintain sexual signal variation under stabilizing selection

NARCIS (Netherlands)

van Wijk, M.; Heath, J.; Lievers, R.; Schal, C.; Groot, A.T.

2017-01-01

How sexual communication systems can evolve under stabilizing selection is still a paradox in evolutionary biology. In moths, females emit a species-specific sex pheromone, consisting of a blend of biochemically related components, to which males are attracted. Although males appear to exert strong

Genome landscape and evolutionary plasticity of chromosomes in malaria mosquitoes.

Directory of Open Access Journals (Sweden)

Ai Xia

2010-05-01

Full Text Available Nonrandom distribution of rearrangements is a common feature of eukaryotic chromosomes that is not well understood in terms of genome organization and evolution. In the major African malaria vector Anopheles gambiae, polymorphic inversions are highly nonuniformly distributed among five chromosomal arms and are associated with epidemiologically important adaptations. However, it is not clear whether the genomic content of the chromosomal arms is associated with inversion polymorphism and fixation rates.To better understand the evolutionary dynamics of chromosomal inversions, we created a physical map for an Asian malaria mosquito, Anopheles stephensi, and compared it with the genome of An. gambiae. We also developed and deployed novel Bayesian statistical models to analyze genome landscapes in individual chromosomal arms An. gambiae. Here, we demonstrate that, despite the paucity of inversion polymorphisms on the X chromosome, this chromosome has the fastest rate of inversion fixation and the highest density of transposable elements, simple DNA repeats, and GC content. The highly polymorphic and rapidly evolving autosomal 2R arm had overrepresentation of genes involved in cellular response to stress supporting the role of natural selection in maintaining adaptive polymorphic inversions. In addition, the 2R arm had the highest density of regions involved in segmental duplications that clustered in the breakpoint-rich zone of the arm. In contrast, the slower evolving 2L, 3R, and 3L, arms were enriched with matrix-attachment regions that potentially contribute to chromosome stability in the cell nucleus.These results highlight fundamental differences in evolutionary dynamics of the sex chromosome and autosomes and revealed the strong association between characteristics of the genome landscape and rates of chromosomal evolution. We conclude that a unique combination of various classes of genes and repetitive DNA in each arm, rather than a single type

Recombination-Driven Genome Evolution and Stability of Bacterial Species.

Science.gov (United States)

Dixit, Purushottam D; Pang, Tin Yau; Maslov, Sergei

2017-09-01

While bacteria divide clonally, horizontal gene transfer followed by homologous recombination is now recognized as an important contributor to their evolution. However, the details of how the competition between clonality and recombination shapes genome diversity remains poorly understood. Using a computational model, we find two principal regimes in bacterial evolution and identify two composite parameters that dictate the evolutionary fate of bacterial species. In the divergent regime, characterized by either a low recombination frequency or strict barriers to recombination, cohesion due to recombination is not sufficient to overcome the mutational drift. As a consequence, the divergence between pairs of genomes in the population steadily increases in the course of their evolution. The species lacks genetic coherence with sexually isolated clonal subpopulations continuously formed and dissolved. In contrast, in the metastable regime, characterized by a high recombination frequency combined with low barriers to recombination, genomes continuously recombine with the rest of the population. The population remains genetically cohesive and temporally stable. Notably, the transition between these two regimes can be affected by relatively small changes in evolutionary parameters. Using the Multi Locus Sequence Typing (MLST) data, we classify a number of bacterial species to be either the divergent or the metastable type. Generalizations of our framework to include selection, ecologically structured populations, and horizontal gene transfer of nonhomologous regions are discussed as well. Copyright © 2017 by the Genetics Society of America.

Super DNAging-New insights into DNA integrity, genome stability and telomeres in the oldest old.

Science.gov (United States)

Franzke, Bernhard; Neubauer, Oliver; Wagner, Karl-Heinz

2015-01-01

Reductions in DNA integrity, genome stability, and telomere length are strongly associated with the aging process, age-related diseases as well as the age-related loss of muscle mass. However, in people reaching an age far beyond their statistical life expectancy the prevalence of diseases, such as cancer, cardiovascular disease, diabetes or dementia, is much lower compared to "averagely" aged humans. These inverse observations in nonagenarians (90-99 years), centenarians (100-109 years) and super-centenarians (110 years and older) require a closer look into dynamics underlying DNA damage within the oldest old of our society. Available data indicate improved DNA repair and antioxidant defense mechanisms in "super old" humans, which are comparable with much younger cohorts. Partly as a result of these enhanced endogenous repair and protective mechanisms, the oldest old humans appear to cope better with risk factors for DNA damage over their lifetime compared to subjects whose lifespan coincides with the statistical life expectancy. This model is supported by study results demonstrating superior chromosomal stability, telomere dynamics and DNA integrity in "successful agers". There is also compelling evidence suggesting that life-style related factors including regular physical activity, a well-balanced diet and minimized psycho-social stress can reduce DNA damage and improve chromosomal stability. The most conclusive picture that emerges from reviewing the literature is that reaching "super old" age appears to be primarily determined by hereditary/genetic factors, while a healthy lifestyle additionally contributes to achieving the individual maximum lifespan in humans. More research is required in this rapidly growing population of super old people. In particular, there is need for more comprehensive investigations including short- and long-term lifestyle interventions as well as investigations focusing on the mechanisms causing DNA damage, mutations, and telomere

Radiotaxons and reliability of a genome

International Nuclear Information System (INIS)

Korogodin, V.I.

1982-01-01

Radiosensitivity of cells (D 0 ) is considered with regard to the structural organization of the genome. The following terms are introduced: ''karyotaxon'', organisms with identical structural organization of the genome, and ''specific genome stability'' K=D 0 C, where C is the quantity of DNA in the cell nucleus; K is the amount of energy (eV) the sorption of which in DNA is necessary and sufficient for one elementary damage to occur. It was shown that Ksub(i)=const. within every karyotaxon ''i''. K 1 =100 eV for viruses, and K 4 =61000 eV for the highest level of genome organization (diploid eukaryotes including man). Potential mechanisms of increasing Ksub(i) with increasing level of genome organization and the role of this factor in evolution are discussed [ru

A Trichosporonales genome tree based on 27 haploid and three evolutionarily conserved 'natural' hybrid genomes.

Science.gov (United States)

Takashima, Masako; Sriswasdi, Sira; Manabe, Ri-Ichiroh; Ohkuma, Moriya; Sugita, Takashi; Iwasaki, Wataru

2018-01-01

To construct a backbone tree consisting of basidiomycetous yeasts, draft genome sequences from 25 species of Trichosporonales (Tremellomycetes, Basidiomycota) were generated. In addition to the hybrid genomes of Trichosporon coremiiforme and Trichosporon ovoides that we described previously, we identified an interspecies hybrid genome in Cutaneotrichosporon mucoides (formerly Trichosporon mucoides). This hybrid genome had a gene retention rate of ~55%, and its closest haploid relative was Cutaneotrichosporon dermatis. After constructing the C. mucoides subgenomes, we generated a phylogenetic tree using genome data from the 27 haploid species and the subgenome data from the three hybrid genome species. It was a high-quality tree with 100% bootstrap support for all of the branches. The genome-based tree provided superior resolution compared with previous multi-gene analyses. Although our backbone tree does not include all Trichosporonales genera (e.g. Cryptotrichosporon), it will be valuable for future analyses of genome data. Interest in interspecies hybrid fungal genomes has recently increased because they may provide a basis for new technologies. The three Trichosporonales hybrid genomes described in this study are different from well-characterized hybrid genomes (e.g. those of Saccharomyces pastorianus and Saccharomyces bayanus) because these hybridization events probably occurred in the distant evolutionary past. Hence, they will be useful for studying genome stability following hybridization and speciation events. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Actomyosin drives cancer cell nuclear dysmorphia and threatens genome stability.

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Takaki, Tohru; Montagner, Marco; Serres, Murielle P; Le Berre, Maël; Russell, Matt; Collinson, Lucy; Szuhai, Karoly; Howell, Michael; Boulton, Simon J; Sahai, Erik; Petronczki, Mark

2017-07-24

Altered nuclear shape is a defining feature of cancer cells. The mechanisms underlying nuclear dysmorphia in cancer remain poorly understood. Here we identify PPP1R12A and PPP1CB, two subunits of the myosin phosphatase complex that antagonizes actomyosin contractility, as proteins safeguarding nuclear integrity. Loss of PPP1R12A or PPP1CB causes nuclear fragmentation, nuclear envelope rupture, nuclear compartment breakdown and genome instability. Pharmacological or genetic inhibition of actomyosin contractility restores nuclear architecture and genome integrity in cells lacking PPP1R12A or PPP1CB. We detect actin filaments at nuclear envelope rupture sites and define the Rho-ROCK pathway as the driver of nuclear damage. Lamin A protects nuclei from the impact of actomyosin activity. Blocking contractility increases nuclear circularity in cultured cancer cells and suppresses deformations of xenograft nuclei in vivo. We conclude that actomyosin contractility is a major determinant of nuclear shape and that unrestrained contractility causes nuclear dysmorphia, nuclear envelope rupture and genome instability.

The international Genome sample resource (IGSR): A worldwide collection of genome variation incorporating the 1000 Genomes Project data.

Science.gov (United States)

Clarke, Laura; Fairley, Susan; Zheng-Bradley, Xiangqun; Streeter, Ian; Perry, Emily; Lowy, Ernesto; Tassé, Anne-Marie; Flicek, Paul

2017-01-04

The International Genome Sample Resource (IGSR; http://www.internationalgenome.org) expands in data type and population diversity the resources from the 1000 Genomes Project. IGSR represents the largest open collection of human variation data and provides easy access to these resources. IGSR was established in 2015 to maintain and extend the 1000 Genomes Project data, which has been widely used as a reference set of human variation and by researchers developing analysis methods. IGSR has mapped all of the 1000 Genomes sequence to the newest human reference (GRCh38), and will release updated variant calls to ensure maximal usefulness of the existing data. IGSR is collecting new structural variation data on the 1000 Genomes samples from long read sequencing and other technologies, and will collect relevant functional data into a single comprehensive resource. IGSR is extending coverage with new populations sequenced by collaborating groups. Here, we present the new data and analysis that IGSR has made available. We have also introduced a new data portal that increases discoverability of our data-previously only browseable through our FTP site-by focusing on particular samples, populations or data sets of interest. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genome Sequence of Torulaspora delbrueckii NRRL Y-50541, Isolated from Mezcal Fermentation.

Science.gov (United States)

Gomez-Angulo, Jorge; Vega-Alvarado, Leticia; Escalante-García, Zazil; Grande, Ricardo; Gschaedler-Mathis, Anne; Amaya-Delgado, Lorena; Arrizon, Javier; Sanchez-Flores, Alejandro

2015-07-23

Torulaspora delbrueckii presents metabolic features interesting for biotechnological applications (in the dairy and wine industries). Recently, the T. delbrueckii CBS 1146 genome, which has been maintained under laboratory conditions since 1970, was published. Thus, a genome of a new mezcal yeast was sequenced and characterized and showed genetic differences and a higher genome assembly quality, offering a better reference genome. Copyright © 2015 Gomez-Angulo et al.

Karyotype stability and unbiased fractionation in the paleo-allotetraploid Cucurbita genomes

OpenAIRE

Sun, Honghe; Wu, Shan; Zhang, Guoyu; Jiao, Chen; Guo, Shaogui; Ren, Yi; Zhang, Jie; Zhang, Haiying; Gong, Guoyi; Jia, Zhangcai; Zhang, Fan; Tian, Jiaxing; Lucas, William; Doyle, Jeff; Li, Haizhen

2017-01-01

The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Interspecific hybrids between C. maxima and C. moschata are widely used as rootstocks for other cucurbit crops. We report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber and watermelon in...

A Phase I Clinical Trial of AZD1775 in Combination With Neoadjuvant Weekly Docetaxel and Cisplatin Before Definitive Therapy in Head and Neck Squamous Cell Carcinoma. | Office of Cancer Genomics

Science.gov (United States)

Purpose: The WEE1 tyrosine kinase regulates G2/M transition and maintains genomic stability, particularly in p53-deficient tumors which require DNA repair after genotoxic therapy. There is a need to exploit the role of WEE1 inhibition in head and neck squamous cell carcinoma (HNSCC) mostly driven by tumor-suppressor loss. This completed phase I clinical trial represents the first published clinical experience using the WEE1 inhibitor, AZD1775, with cisplatin and docetaxel.

Designing Inter-Organisational Collectivities for Dynamic Fit: Stability, maneuvrability and Application in Disaster Relief Endeavours

Science.gov (United States)

2011-01-01

changed consumer preferences . Hence, static stability limits initial performance deviation (e.g., maintaining desired airplane altitude, maintaining...by changed consumer preferences . Hence, dynamic stability limits the duration of performance deviation (e.g., maintaining desired airplane altitude...altitude from wind gust. Initial resistance to deviation in profit level from change in consumer preferences . Dynamic stability Quickness of a

Long-Term Stability of Human Genomic and Human Papillomavirus DNA Stored in BD SurePath and Hologic PreservCyt Liquid-Based Cytology Media

Science.gov (United States)

Agreda, Patricia M.; Beitman, Gerard H.; Gutierrez, Erin C.; Harris, James M.; Koch, Kristopher R.; LaViers, William D.; Leitch, Sharon V.; Maus, Courtney E.; McMillian, Ray A.; Nussbaumer, William A.; Palmer, Marcus L. R.; Porter, Michael J.; Richart, Gregory A.; Schwab, Ryan J.

2013-01-01

We evaluated the effect of storage at 2 to 8°C on the stability of human genomic and human papillomavirus (HPV) DNA stored in BD SurePath and Hologic PreservCyt liquid-based cytology media. DNA retained the ability to be extracted and PCR amplified for more than 2.5 years in both medium types. Prior inability to detect DNA in archived specimens may have been due to failure of the extraction method to isolate DNA from fixed cells. PMID:23678069

OPTIMAL CONTROL FOR ELECTRIC VEHICLE STABILIZATION

Directory of Open Access Journals (Sweden)

MARIAN GAICEANU

2016-01-01

Full Text Available This main objective of the paper is to stabilize an electric vehicle in optimal manner to a step lane change maneuver. To define the mathematical model of the vehicle, the rigid body moving on a plane is taken into account. An optimal lane keeping controller delivers the adequate angles in order to stabilize the vehicle’s trajectory in an optimal way. Two degree of freedom linear bicycle model is adopted as vehicle model, consisting of lateral and yaw motion equations. The proposed control maintains the lateral stability by taking the feedback information from the vehicle transducers. In this way only the lateral vehicle’s dynamics are enough to considerate. Based on the obtained linear mathematical model the quadratic optimal control is designed in order to maintain the lateral stability of the electric vehicle. The numerical simulation results demonstrate the feasibility of the proposed solution.

The characterization of twenty sequenced human genomes.

Directory of Open Access Journals (Sweden)

Kimberly Pelak

2010-09-01

Full Text Available We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten "case" genomes from individuals with severe hemophilia A and ten "control" genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways.

Variable presence of the inverted repeat and plastome stability in Erodium.

Science.gov (United States)

Blazier, John C; Jansen, Robert K; Mower, Jeffrey P; Govindu, Madhu; Zhang, Jin; Weng, Mao-Lun; Ruhlman, Tracey A

2016-06-01

Several unrelated lineages such as plastids, viruses and plasmids, have converged on quadripartite genomes of similar size with large and small single copy regions and a large inverted repeat (IR). Except for Erodium (Geraniaceae), saguaro cactus and some legumes, the plastomes of all photosynthetic angiosperms display this structure. The functional significance of the IR is not understood and Erodium provides a system to examine the role of the IR in the long-term stability of these genomes. We compared the degree of genomic rearrangement in plastomes of Erodium that differ in the presence and absence of the IR. We sequenced 17 new Erodium plastomes. Using 454, Illumina, PacBio and Sanger sequences, 16 genomes were assembled and categorized along with one incomplete and two previously published Erodium plastomes. We conducted phylogenetic analyses among these species using a dataset of 19 protein-coding genes and determined if significantly higher evolutionary rates had caused the long branch seen previously in phylogenetic reconstructions within the genus. Bioinformatic comparisons were also performed to evaluate plastome evolution across the genus. Erodium plastomes fell into four types (Type 1-4) that differ in their substitution rates, short dispersed repeat content and degree of genomic rearrangement, gene and intron content and GC content. Type 4 plastomes had significantly higher rates of synonymous substitutions (dS) for all genes and for 14 of the 19 genes non-synonymous substitutions (dN) were significantly accelerated. We evaluated the evidence for a single IR loss in Erodium and in doing so discovered that Type 4 plastomes contain a novel IR. The presence or absence of the IR does not affect plastome stability in Erodium. Rather, the overall repeat content shows a negative correlation with genome stability, a pattern in agreement with other angiosperm groups and recent findings on genome stability in bacterial endosymbionts. © The Author 2016

MBGD update 2015: microbial genome database for flexible ortholog analysis utilizing a diverse set of genomic data.

Science.gov (United States)

Uchiyama, Ikuo; Mihara, Motohiro; Nishide, Hiroyo; Chiba, Hirokazu

2015-01-01

The microbial genome database for comparative analysis (MBGD) (available at http://mbgd.genome.ad.jp/) is a comprehensive ortholog database for flexible comparative analysis of microbial genomes, where the users are allowed to create an ortholog table among any specified set of organisms. Because of the rapid increase in microbial genome data owing to the next-generation sequencing technology, it becomes increasingly challenging to maintain high-quality orthology relationships while allowing the users to incorporate the latest genomic data available into an analysis. Because many of the recently accumulating genomic data are draft genome sequences for which some complete genome sequences of the same or closely related species are available, MBGD now stores draft genome data and allows the users to incorporate them into a user-specific ortholog database using the MyMBGD functionality. In this function, draft genome data are incorporated into an existing ortholog table created only from the complete genome data in an incremental manner to prevent low-quality draft data from affecting clustering results. In addition, to provide high-quality orthology relationships, the standard ortholog table containing all the representative genomes, which is first created by the rapid classification program DomClust, is now refined using DomRefine, a recently developed program for improving domain-level clustering using multiple sequence alignment information. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Genomic stability and physiological assessments of live offspring sired by a bull clone, Starbuck II.

Science.gov (United States)

Ortegon, H; Betts, D H; Lin, L; Coppola, G; Perrault, S D; Blondin, P; King, W A

2007-01-01

It appears that overt phenotypic abnormalities observed in some domestic animal clones are not transmitted to their progeny. The current study monitored Holstein heifers sired by a bull clone, Starbuck II, from weaning to puberty. Genomic stability was assessed by telomere length status and chromosomal analysis. Growth parameters, blood profiles, physical exams and reproductive parameters were assessed for 12 months (and compared to age-matched control heifers). Progeny sired by the clone bull did not differ (P>0.05) in weight, length and height compared to controls. However, progeny had lower heart rates (HR) (P=0.009), respiratory rates (RR) (P=0.007) and body temperature (P=0.03). Hematological profiles were within normal ranges and did not differ (P>0.05) between both groups. External and internal genitalia were normal and both groups reached puberty at expected ages. Progeny had two or three ovarian follicular waves per estrous cycle and serum progesterone concentrations were similar (P=0.99) to controls. Telomere lengths of sperm and blood cells from Starbuck II were not different (P>0.05) than those of non-cloned cattle; telomere lengths of progeny were not different (P>0.05) from age-matched controls. In addition, progeny had normal karyotypes in peripheral blood leukocytes compared to controls (89.1% versus 86.3% diploid, respectively). In summary, heifers sired by a bull clone had normal chromosomal stability, growth, physical, hematological and reproductive parameters, compared to normal heifers. Furthermore, they had moderate stress responses to routine handling and restraint.

Slope stabilization guide for Minnesota local government engineers.

Science.gov (United States)

2017-06-01

This user guide provides simple, costeffective methods for stabilizing locally maintained slopes along roadways in Minnesota. Eight slope stabilization techniques are presented that local government engineers can undertake using locally available ...

Optical Materials with a Genome: Nanophotonics with DNA-Stabilized Silver Clusters

Science.gov (United States)

Copp, Stacy M.

Fluorescent silver clusters with unique rod-like geometries are stabilized by DNA. The sizes and colors of these clusters, or AgN-DNA, are selected by DNA base sequence, which can tune peak emission from blue-green into the near-infrared. Combined with DNA nanostructures, AgN-DNA promise exciting applications in nanophotonics and sensing. Until recently, however, a lack of understanding of the mechanisms controlling AgN-DNA fluorescence has challenged such applications. This dissertation discusses progress toward understanding the role of DNA as a "genome" for silver clusters and toward using DNA to achieve atomic-scale precision of silver cluster size and nanometer-scale precision of silver cluster position on a DNA breadboard. We also investigate sensitivity of AgN-DNA to local solvent environment, with an eye toward applications in chemical and biochemical sensing. Using robotic techniques to generate large data sets, we show that fluorescent silver clusters are templated by certain DNA base motifs that select "magic-sized" cluster cores of enhanced stabilities. The linear arrangement of bases on the phosphate backbone imposes a unique rod-like geometry on the clusters. Harnessing machine learning and bioinformatics techniques, we also demonstrate that sequences of DNA templates can be selected to stabilize silver clusters with desired optical properties, including high fluorescence intensity and specific fluorescence wavelengths, with much higher rates of success as compared to current strategies. The discovered base motifs can be also used to design modular DNA host strands that enable individual silver clusters with atomically precise sizes to bind at specific programmed locations on a DNA nanostructure. We show that DNA-mediated nanoscale arrangement enables near-field coupling of distinct clusters, demonstrated by dual-color cluster assemblies exhibiting resonant energy transfer. These results demonstrate a new degree of control over the optical properties

Polyploidy: adaptation to the genomic environment.

Science.gov (United States)

Hollister, Jesse D

2015-02-01

Genomic evidence of ancestral whole genome duplication (WGD) and polyploidy is widespread among eukaryotic species, and especially among plants. WGD is thought to provide the raw material for adaptation in the form of duplicated genes, and polyploids are thought to benefit from both physiological and genetic buffering. Comparatively little attention has focused on the genomic challenge of polyploidy, however, although much evidence exists that polyploidy severely perturbs important cellular functions. Here, I review recent progress in the study of the re-establishment of stable meiosis in recently evolved polyploids, focusing on four plant species. This work has yielded an insight into the mechanisms underlying stabilization of genome transmission in polyploids, and is revealing remarkable parallels among diverse taxa. Importantly, these studies also provide a road map for investigating how polyploids respond to the challenge of WGD.

Molecular characterization of genome segments 1 and 3 encoding two capsid proteins of Antheraea mylitta cytoplasmic polyhedrosis virus

Directory of Open Access Journals (Sweden)

Chakrabarti Mrinmay

2010-08-01

Full Text Available Abstract Background Antheraea mylitta cytoplasmic polyhedrosis virus (AmCPV, a cypovirus of Reoviridae family, infects Indian non-mulberry silkworm, Antheraea mylitta, and contains 11 segmented double stranded RNA (S1-S11 in its genome. Some of its genome segments (S2 and S6-S11 have been previously characterized but genome segments encoding viral capsid have not been characterized. Results In this study genome segments 1 (S1 and 3 (S3 of AmCPV were converted to cDNA, cloned and sequenced. S1 consisted of 3852 nucleotides, with one long ORF of 3735 nucleotides and could encode a protein of 1245 amino acids with molecular mass of ~141 kDa. Similarly, S3 consisted of 3784 nucleotides having a long ORF of 3630 nucleotides and could encode a protein of 1210 amino acids with molecular mass of ~137 kDa. BLAST analysis showed 20-22% homology of S1 and S3 sequence with spike and capsid proteins, respectively, of other closely related cypoviruses like Bombyx mori CPV (BmCPV, Lymantria dispar CPV (LdCPV, and Dendrolimus punctatus CPV (DpCPV. The ORFs of S1 and S3 were expressed as 141 kDa and 137 kDa insoluble His-tagged fusion proteins, respectively, in Escherichia coli M15 cells via pQE-30 vector, purified through Ni-NTA chromatography and polyclonal antibodies were raised. Immunoblot analysis of purified polyhedra, virion particles and virus infected mid-gut cells with the raised anti-p137 and anti-p141 antibodies showed specific immunoreactive bands and suggest that S1 and S3 may code for viral structural proteins. Expression of S1 and S3 ORFs in insect cells via baculovirus recombinants showed to produce viral like particles (VLPs by transmission electron microscopy. Immunogold staining showed that S3 encoded proteins self assembled to form viral outer capsid and VLPs maintained their stability at different pH in presence of S1 encoded protein. Conclusion Our results of cloning, sequencing and functional analysis of AmCPV S1 and S3 indicate that S3

The role of the Fanconi anemia pathway in DNA repair and maintenance of genome stability

Directory of Open Access Journals (Sweden)

Aleksandra M. Koczorowska

2014-05-01

Full Text Available The Fanconi anemia (FA pathway is one of the DNA repair systems involved in removal of DNA crosslinks. Proteins which belong to this pathway are crucial to the protection of genetic information, whereas disturbances in their function have serious implications for the whole organism. Biallelic mutations in FA genes are the cause of Fanconi anemia – a genetic disease which manifests itself through numerous congenital abnormalities, chromosomal instability and increased predisposition to cancer. The FA pathway is composed of fifteen proteins. Eight of them, in the presence of DNA interstrand crosslinks (ICLs, form a nuclear core complex responsible for monoubiquitination of FANCD2 and FANCI, which is a key step of ICL repair. FA proteins which are not involved in the monoubiquitination step participate in repair of DNA double strand breaks via homologous recombination. Some of the FA proteins, besides having a direct role in the repair of DNA damage, are engaged in replication, cell cycle control and mitosis. The unperturbed course of those processes determines the maintenance of genome stability.

Characterizing genomic alterations in cancer by complementary functional associations.

Science.gov (United States)

Kim, Jong Wook; Botvinnik, Olga B; Abudayyeh, Omar; Birger, Chet; Rosenbluh, Joseph; Shrestha, Yashaswi; Abazeed, Mohamed E; Hammerman, Peter S; DiCara, Daniel; Konieczkowski, David J; Johannessen, Cory M; Liberzon, Arthur; Alizad-Rahvar, Amir Reza; Alexe, Gabriela; Aguirre, Andrew; Ghandi, Mahmoud; Greulich, Heidi; Vazquez, Francisca; Weir, Barbara A; Van Allen, Eliezer M; Tsherniak, Aviad; Shao, Diane D; Zack, Travis I; Noble, Michael; Getz, Gad; Beroukhim, Rameen; Garraway, Levi A; Ardakani, Masoud; Romualdi, Chiara; Sales, Gabriele; Barbie, David A; Boehm, Jesse S; Hahn, William C; Mesirov, Jill P; Tamayo, Pablo

2016-05-01

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes.

Assessment of the mechanical stability of underground excavations

International Nuclear Information System (INIS)

Kuroki, Shigemori; Taniguchi, Wataru

1999-01-01

Each tunnel in the underground high level radioactive waste repository must be mechanically stable to maintain safety throughout the construction, emplacement operations and closure phase. The mechanical stability of underground excavations were assessed using a theoretical analysis and a finite element method taking a wide range of geological environment in Japan into consideration to establish confidence in the construction of disposal facilities. The results show that it is possible to maintain the mechanical stability with adequate tunnel spacing and disposal pit pitch and proper mechanical support. The procedure used for the analysis of the mechanical stability in the H12 report and the results are described in this report. (author)

Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

Science.gov (United States)

Leung, Wilson; Shaffer, Christopher D.; Reed, Laura K.; Smith, Sheryl T.; Barshop, William; Dirkes, William; Dothager, Matthew; Lee, Paul; Wong, Jeannette; Xiong, David; Yuan, Han; Bedard, James E. J.; Machone, Joshua F.; Patterson, Seantay D.; Price, Amber L.; Turner, Bryce A.; Robic, Srebrenka; Luippold, Erin K.; McCartha, Shannon R.; Walji, Tezin A.; Walker, Chelsea A.; Saville, Kenneth; Abrams, Marita K.; Armstrong, Andrew R.; Armstrong, William; Bailey, Robert J.; Barberi, Chelsea R.; Beck, Lauren R.; Blaker, Amanda L.; Blunden, Christopher E.; Brand, Jordan P.; Brock, Ethan J.; Brooks, Dana W.; Brown, Marie; Butzler, Sarah C.; Clark, Eric M.; Clark, Nicole B.; Collins, Ashley A.; Cotteleer, Rebecca J.; Cullimore, Peterson R.; Dawson, Seth G.; Docking, Carter T.; Dorsett, Sasha L.; Dougherty, Grace A.; Downey, Kaitlyn A.; Drake, Andrew P.; Earl, Erica K.; Floyd, Trevor G.; Forsyth, Joshua D.; Foust, Jonathan D.; Franchi, Spencer L.; Geary, James F.; Hanson, Cynthia K.; Harding, Taylor S.; Harris, Cameron B.; Heckman, Jonathan M.; Holderness, Heather L.; Howey, Nicole A.; Jacobs, Dontae A.; Jewell, Elizabeth S.; Kaisler, Maria; Karaska, Elizabeth A.; Kehoe, James L.; Koaches, Hannah C.; Koehler, Jessica; Koenig, Dana; Kujawski, Alexander J.; Kus, Jordan E.; Lammers, Jennifer A.; Leads, Rachel R.; Leatherman, Emily C.; Lippert, Rachel N.; Messenger, Gregory S.; Morrow, Adam T.; Newcomb, Victoria; Plasman, Haley J.; Potocny, Stephanie J.; Powers, Michelle K.; Reem, Rachel M.; Rennhack, Jonathan P.; Reynolds, Katherine R.; Reynolds, Lyndsey A.; Rhee, Dong K.; Rivard, Allyson B.; Ronk, Adam J.; Rooney, Meghan B.; Rubin, Lainey S.; Salbert, Luke R.; Saluja, Rasleen K.; Schauder, Taylor; Schneiter, Allison R.; Schulz, Robert W.; Smith, Karl E.; Spencer, Sarah; Swanson, Bryant R.; Tache, Melissa A.; Tewilliager, Ashley A.; Tilot, Amanda K.; VanEck, Eve; Villerot, Matthew M.; Vylonis, Megan B.; Watson, David T.; Wurzler, Juliana A.; Wysocki, Lauren M.; Yalamanchili, Monica; Zaborowicz, Matthew A.; Emerson, Julia A.; Ortiz, Carlos; Deuschle, Frederic J.; DiLorenzo, Lauren A.; Goeller, Katie L.; Macchi, Christopher R.; Muller, Sarah E.; Pasierb, Brittany D.; Sable, Joseph E.; Tucci, Jessica M.; Tynon, Marykathryn; Dunbar, David A.; Beken, Levent H.; Conturso, Alaina C.; Danner, Benjamin L.; DeMichele, Gabriella A.; Gonzales, Justin A.; Hammond, Maureen S.; Kelley, Colleen V.; Kelly, Elisabeth A.; Kulich, Danielle; Mageeney, Catherine M.; McCabe, Nikie L.; Newman, Alyssa M.; Spaeder, Lindsay A.; Tumminello, Richard A.; Revie, Dennis; Benson, Jonathon M.; Cristostomo, Michael C.; DaSilva, Paolo A.; Harker, Katherine S.; Jarrell, Jenifer N.; Jimenez, Luis A.; Katz, Brandon M.; Kennedy, William R.; Kolibas, Kimberly S.; LeBlanc, Mark T.; Nguyen, Trung T.; Nicolas, Daniel S.; Patao, Melissa D.; Patao, Shane M.; Rupley, Bryan J.; Sessions, Bridget J.; Weaver, Jennifer A.; Goodman, Anya L.; Alvendia, Erica L.; Baldassari, Shana M.; Brown, Ashley S.; Chase, Ian O.; Chen, Maida; Chiang, Scott; Cromwell, Avery B.; Custer, Ashley F.; DiTommaso, Tia M.; El-Adaimi, Jad; Goscinski, Nora C.; Grove, Ryan A.; Gutierrez, Nestor; Harnoto, Raechel S.; Hedeen, Heather; Hong, Emily L.; Hopkins, Barbara L.; Huerta, Vilma F.; Khoshabian, Colin; LaForge, Kristin M.; Lee, Cassidy T.; Lewis, Benjamin M.; Lydon, Anniken M.; Maniaci, Brian J.; Mitchell, Ryan D.; Morlock, Elaine V.; Morris, William M.; Naik, Priyanka; Olson, Nicole C.; Osterloh, Jeannette M.; Perez, Marcos A.; Presley, Jonathan D.; Randazzo, Matt J.; Regan, Melanie K.; Rossi, Franca G.; Smith, Melanie A.; Soliterman, Eugenia A.; Sparks, Ciani J.; Tran, Danny L.; Wan, Tiffany; Welker, Anne A.; Wong, Jeremy N.; Sreenivasan, Aparna; Youngblom, Jim; Adams, Andrew; Alldredge, Justin; Bryant, Ashley; Carranza, David; Cifelli, Alyssa; Coulson, Kevin; Debow, Calise; Delacruz, Noelle; Emerson, Charlene; Farrar, Cassandra; Foret, Don; Garibay, Edgar; Gooch, John; Heslop, Michelle; Kaur, Sukhjit; Khan, Ambreen; Kim, Van; Lamb, Travis; Lindbeck, Peter; Lucas, Gabi; Macias, Elizabeth; Martiniuc, Daniela; Mayorga, Lissett; Medina, Joseph; Membreno, Nelson; Messiah, Shady; Neufeld, Lacey; Nguyen, San Francisco; Nichols, Zachary; Odisho, George; Peterson, Daymon; Rodela, Laura; Rodriguez, Priscilla; Rodriguez, Vanessa; Ruiz, Jorge; Sherrill, Will; Silva, Valeria; Sparks, Jeri; Statton, Geeta; Townsend, Ashley; Valdez, Isabel; Waters, Mary; Westphal, Kyle; Winkler, Stacey; Zumkehr, Joannee; DeJong, Randall J.; Hoogewerf, Arlene J.; Ackerman, Cheri M.; Armistead, Isaac O.; Baatenburg, Lara; Borr, Matthew J.; Brouwer, Lindsay K.; Burkhart, Brandon J.; Bushhouse, Kelsey T.; Cesko, Lejla; Choi, Tiffany Y. Y.; Cohen, Heather; Damsteegt, Amanda M.; Darusz, Jess M.; Dauphin, Cory M.; Davis, Yelena P.; Diekema, Emily J.; Drewry, Melissa; Eisen, Michelle E. 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Johnson, Christen; Jones, Melissa; Kabaso, Rita; Lemmon, Eric; Vieira, Carolina Marques dos Santos; McFarland, Darryl; McLaughlin, Christopher; Morgan, Abbie; Musokotwane, Sepo; Neutzling, William; Nietmann, Jana; Paluskievicz, Christina; Penn, Jessica; Peoples, Emily; Pozmanter, Caitlin; Reed, Emily; Rigby, Nichole; Schmidt, Lasse; Shelton, Micah; Shuford, Rebecca; Tirasawasdichai, Tiara; Undem, Blair; Urick, Damian; Vondy, Kayla; Yarrington, Bryan; Eckdahl, Todd T.; Poet, Jeffrey L.; Allen, Alica B.; Anderson, John E.; Barnett, Jason M.; Baumgardner, Jordan S.; Brown, Adam D.; Carney, Jordan E.; Chavez, Ramiro A.; Christgen, Shelbi L.; Christie, Jordan S.; Clary, Andrea N.; Conn, Michel A.; Cooper, Kristen M.; Crowley, Matt J.; Crowley, Samuel T.; Doty, Jennifer S.; Dow, Brian A.; Edwards, Curtis R.; Elder, Darcie D.; Fanning, John P.; Janssen, Bridget M.; Lambright, Anthony K.; Lane, Curtiss E.; Limle, Austin B.; Mazur, Tammy; McCracken, Marly R.; McDonough, Alexa M.; Melton, Amy D.; Minnick, Phillip J.; Musick, Adam E.; Newhart, William H.; Noynaert, Joseph W.; Ogden, Bradley J.; Sandusky, Michael W.; Schmuecker, Samantha M.; Shipman, Anna L.; Smith, Anna L.; Thomsen, Kristen M.; Unzicker, Matthew R.; Vernon, William B.; Winn, Wesley W.; Woyski, Dustin S.; Zhu, Xiao; Du, Chunguang; Ament, Caitlin; Aso, Soham; Bisogno, Laura Simone; Caronna, Jason; Fefelova, Nadezhda; Lopez, Lenin; Malkowitz, Lorraine; Marra, Jonathan; Menillo, Daniella; Obiorah, Ifeanyi; Onsarigo, Eric Nyabeta; Primus, Shekerah; Soos, Mahdi; Tare, Archana; Zidan, Ameer; Jones, Christopher J.; Aronhalt, Todd; Bellush, James M.; Burke, Christa; DeFazio, Steve; Does, Benjamin R.; Johnson, Todd D.; Keysock, Nicholas; Knudsen, Nelson H.; Messler, James; Myirski, Kevin; Rekai, Jade Lea; Rempe, Ryan Michael; Salgado, Michael S.; Stagaard, Erica; Starcher, Justin R.; Waggoner, Andrew W.; Yemelyanova, Anastasia K.; Hark, Amy T.; Bertolet, Anne; Kuschner, Cyrus E.; Parry, Kesley; Quach, Michael; Shantzer, Lindsey; Shaw, Mary E.; Smith, Mary A.; Glenn, Omolara; Mason, Portia; Williams, Charlotte; Key, S. Catherine Silver; Henry, Tyneshia C. P.; Johnson, Ashlee G.; White, Jackie X.; Haberman, Adam; Asinof, Sam; Drumm, Kelly; Freeburg, Trip; Safa, Nadia; Schultz, Darrin; Shevin, Yakov; Svoronos, Petros; Vuong, Tam; Wellinghoff, Jules; Hoopes, Laura L. M.; Chau, Kim M.; Ward, Alyssa; Regisford, E. 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Devin; Stemler, Kristina M.; Throm, Allison A.; Van Camp, Matt; Weihbrecht, Katie; Wiles, T. Aaron; Williams, Mallory A.; Williams, Matthew; Zoll, Kyle; Bailey, Cheryl; Zhou, Leming; Balthaser, Darla M.; Bashiri, Azita; Bower, Mindy E.; Florian, Kayla A.; Ghavam, Nazanin; Greiner-Sosanko, Elizabeth S.; Karim, Helmet; Mullen, Victor W.; Pelchen, Carly E.; Yenerall, Paul M.; Zhang, Jiayu; Rubin, Michael R.; Arias-Mejias, Suzette M.; Bermudez-Capo, Armando G.; Bernal-Vega, Gabriela V.; Colon-Vazquez, Mariela; Flores-Vazquez, Arelys; Gines-Rosario, Mariela; Llavona-Cartagena, Ivan G.; Martinez-Rodriguez, Javier O.; Ortiz-Fuentes, Lionel; Perez-Colomba, Eliezer O.; Perez-Otero, Joseph; Rivera, Elisandra; Rodriguez-Giron, Luke J.; Santiago-Sanabria, Arnaldo J.; Senquiz-Gonzalez, Andrea M.; delValle, Frank R. 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2015-01-01

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu. PMID:25740935

Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

Science.gov (United States)

Leung, Wilson; Shaffer, Christopher D; Reed, Laura K; Smith, Sheryl T; Barshop, William; Dirkes, William; Dothager, Matthew; Lee, Paul; Wong, Jeannette; Xiong, David; Yuan, Han; Bedard, James E J; Machone, Joshua F; Patterson, Seantay D; Price, Amber L; Turner, Bryce A; Robic, Srebrenka; Luippold, Erin K; McCartha, Shannon R; Walji, Tezin A; Walker, Chelsea A; Saville, Kenneth; Abrams, Marita K; Armstrong, Andrew R; Armstrong, William; Bailey, Robert J; Barberi, Chelsea R; Beck, Lauren R; Blaker, Amanda L; Blunden, Christopher E; Brand, Jordan P; Brock, Ethan J; Brooks, Dana W; Brown, Marie; Butzler, Sarah C; Clark, Eric M; Clark, Nicole B; Collins, Ashley A; Cotteleer, Rebecca J; Cullimore, Peterson R; Dawson, Seth G; Docking, Carter T; Dorsett, Sasha L; Dougherty, Grace A; Downey, Kaitlyn A; Drake, Andrew P; Earl, Erica K; Floyd, Trevor G; Forsyth, Joshua D; Foust, Jonathan D; Franchi, Spencer L; Geary, James F; Hanson, Cynthia K; Harding, Taylor S; Harris, Cameron B; Heckman, Jonathan M; Holderness, Heather L; Howey, Nicole A; Jacobs, Dontae A; Jewell, Elizabeth S; Kaisler, Maria; Karaska, Elizabeth A; Kehoe, James L; Koaches, Hannah C; Koehler, Jessica; Koenig, Dana; Kujawski, Alexander J; Kus, Jordan E; Lammers, Jennifer A; Leads, Rachel R; Leatherman, Emily C; Lippert, Rachel N; Messenger, Gregory S; Morrow, Adam T; Newcomb, Victoria; Plasman, Haley J; Potocny, Stephanie J; Powers, Michelle K; Reem, Rachel M; Rennhack, Jonathan P; Reynolds, Katherine R; Reynolds, Lyndsey A; Rhee, Dong K; Rivard, Allyson B; Ronk, Adam J; Rooney, Meghan B; Rubin, Lainey S; Salbert, Luke R; Saluja, Rasleen K; Schauder, Taylor; Schneiter, Allison R; Schulz, Robert W; Smith, Karl E; Spencer, Sarah; Swanson, Bryant R; Tache, Melissa A; Tewilliager, Ashley A; Tilot, Amanda K; VanEck, Eve; Villerot, Matthew M; Vylonis, Megan B; Watson, David T; Wurzler, Juliana A; Wysocki, Lauren M; Yalamanchili, Monica; Zaborowicz, Matthew A; Emerson, Julia A; Ortiz, Carlos; Deuschle, Frederic J; DiLorenzo, Lauren A; Goeller, Katie L; Macchi, Christopher R; Muller, Sarah E; Pasierb, Brittany D; Sable, Joseph E; Tucci, Jessica M; Tynon, Marykathryn; Dunbar, David A; Beken, Levent H; Conturso, Alaina C; Danner, Benjamin L; DeMichele, Gabriella A; Gonzales, Justin A; Hammond, Maureen S; Kelley, Colleen V; Kelly, Elisabeth A; Kulich, Danielle; Mageeney, Catherine M; McCabe, Nikie L; Newman, Alyssa M; Spaeder, Lindsay A; Tumminello, Richard A; Revie, Dennis; Benson, Jonathon M; Cristostomo, Michael C; DaSilva, Paolo A; Harker, Katherine S; Jarrell, Jenifer N; Jimenez, Luis A; Katz, Brandon M; Kennedy, William R; Kolibas, Kimberly S; LeBlanc, Mark T; Nguyen, Trung T; Nicolas, Daniel S; Patao, Melissa D; Patao, Shane M; Rupley, Bryan J; Sessions, Bridget J; Weaver, Jennifer A; Goodman, Anya L; Alvendia, Erica L; Baldassari, Shana M; Brown, Ashley S; Chase, Ian O; Chen, Maida; Chiang, Scott; Cromwell, Avery B; Custer, Ashley F; DiTommaso, Tia M; El-Adaimi, Jad; Goscinski, Nora C; Grove, Ryan A; Gutierrez, Nestor; Harnoto, Raechel S; Hedeen, Heather; Hong, Emily L; Hopkins, Barbara L; Huerta, Vilma F; Khoshabian, Colin; LaForge, Kristin M; Lee, Cassidy T; Lewis, Benjamin M; Lydon, Anniken M; Maniaci, Brian J; Mitchell, Ryan D; Morlock, Elaine V; Morris, William M; Naik, Priyanka; Olson, Nicole C; Osterloh, Jeannette M; Perez, Marcos A; Presley, Jonathan D; Randazzo, Matt J; Regan, Melanie K; Rossi, Franca G; Smith, Melanie A; Soliterman, Eugenia A; Sparks, Ciani J; Tran, Danny L; Wan, Tiffany; Welker, Anne A; Wong, Jeremy N; Sreenivasan, Aparna; Youngblom, Jim; Adams, Andrew; Alldredge, Justin; Bryant, Ashley; Carranza, David; Cifelli, Alyssa; Coulson, Kevin; Debow, Calise; Delacruz, Noelle; Emerson, Charlene; Farrar, Cassandra; Foret, Don; Garibay, Edgar; Gooch, John; Heslop, Michelle; Kaur, Sukhjit; Khan, Ambreen; Kim, Van; Lamb, Travis; Lindbeck, Peter; Lucas, Gabi; Macias, Elizabeth; Martiniuc, Daniela; Mayorga, Lissett; Medina, Joseph; Membreno, Nelson; Messiah, Shady; Neufeld, Lacey; Nguyen, San Francisco; 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Eckdahl, Todd T; Poet, Jeffrey L; Allen, Alica B; Anderson, John E; Barnett, Jason M; Baumgardner, Jordan S; Brown, Adam D; Carney, Jordan E; Chavez, Ramiro A; Christgen, Shelbi L; Christie, Jordan S; Clary, Andrea N; Conn, Michel A; Cooper, Kristen M; Crowley, Matt J; Crowley, Samuel T; Doty, Jennifer S; Dow, Brian A; Edwards, Curtis R; Elder, Darcie D; Fanning, John P; Janssen, Bridget M; Lambright, Anthony K; Lane, Curtiss E; Limle, Austin B; Mazur, Tammy; McCracken, Marly R; McDonough, Alexa M; Melton, Amy D; Minnick, Phillip J; Musick, Adam E; Newhart, William H; Noynaert, Joseph W; Ogden, Bradley J; Sandusky, Michael W; Schmuecker, Samantha M; Shipman, Anna L; Smith, Anna L; Thomsen, Kristen M; Unzicker, Matthew R; Vernon, William B; Winn, Wesley W; Woyski, Dustin S; Zhu, Xiao; Du, Chunguang; Ament, Caitlin; Aso, Soham; Bisogno, Laura Simone; Caronna, Jason; Fefelova, Nadezhda; Lopez, Lenin; Malkowitz, Lorraine; Marra, Jonathan; Menillo, Daniella; Obiorah, Ifeanyi; Onsarigo, Eric Nyabeta; Primus, Shekerah; Soos, Mahdi; Tare, Archana; Zidan, Ameer; Jones, Christopher J; Aronhalt, Todd; Bellush, James M; Burke, Christa; DeFazio, Steve; Does, Benjamin R; Johnson, Todd D; Keysock, Nicholas; Knudsen, Nelson H; Messler, James; Myirski, Kevin; Rekai, Jade Lea; Rempe, Ryan Michael; Salgado, Michael S; Stagaard, Erica; Starcher, Justin R; Waggoner, Andrew W; Yemelyanova, Anastasia K; Hark, Amy T; Bertolet, Anne; Kuschner, Cyrus E; Parry, Kesley; Quach, Michael; Shantzer, Lindsey; Shaw, Mary E; Smith, Mary A; Glenn, Omolara; Mason, Portia; Williams, Charlotte; Key, S Catherine Silver; Henry, Tyneshia C P; Johnson, Ashlee G; White, Jackie X; Haberman, Adam; Asinof, Sam; Drumm, Kelly; Freeburg, Trip; Safa, Nadia; Schultz, Darrin; Shevin, Yakov; Svoronos, Petros; Vuong, Tam; Wellinghoff, Jules; Hoopes, Laura L M; Chau, Kim M; Ward, Alyssa; Regisford, E Gloria C; Augustine, LaJerald; Davis-Reyes, Brionna; Echendu, Vivienne; Hales, Jasmine; Ibarra, Sharon; Johnson, Lauriaun; Ovu, Steven; Braverman, John M; Bahr, Thomas J; Caesar, Nicole M; Campana, Christopher; Cassidy, Daniel W; Cognetti, Peter A; English, Johnathan D; Fadus, Matthew C; Fick, Cameron N; Freda, Philip J; Hennessy, Bryan M; Hockenberger, Kelsey; Jones, Jennifer K; King, Jessica E; Knob, Christopher R; Kraftmann, Karen J; Li, Linghui; Lupey, Lena N; Minniti, Carl J; Minton, Thomas F; Moran, Joseph V; Mudumbi, Krishna; Nordman, Elizabeth C; Puetz, William J; Robinson, Lauren M; Rose, Thomas J; Sweeney, Edward P; Timko, Ashley S; Paetkau, Don W; Eisler, Heather L; Aldrup, Megan E; Bodenberg, Jessica M; Cole, Mara G; Deranek, Kelly M; DeShetler, Megan; Dowd, Rose M; Eckardt, Alexandra K; Ehret, Sharon C; Fese, Jessica; Garrett, Amanda D; Kammrath, Anna; Kappes, Michelle L; Light, Morgan R; Meier, Anne C; O'Rouke, Allison; Perella, Mallory; Ramsey, Kimberley; Ramthun, Jennifer R; Reilly, Mary T; Robinett, Deirdre; Rossi, Nadine L; Schueler, Mary Grace; Shoemaker, Emma; Starkey, Kristin M; Vetor, Ashley; Vrable, Abby; Chandrasekaran, Vidya; Beck, Christopher; Hatfield, Kristen R; Herrick, Douglas A; Khoury, Christopher B; Lea, Charlotte; Louie, Christopher A; Lowell, Shannon M; Reynolds, Thomas J; Schibler, Jeanine; Scoma, Alexandra H; Smith-Gee, Maxwell T; Tuberty, Sarah; Smith, Christopher D; Lopilato, Jane E; Hauke, Jeanette; Roecklein-Canfield, Jennifer A; Corrielus, Maureen; Gilman, Hannah; Intriago, Stephanie; Maffa, Amanda; Rauf, Sabya A; Thistle, Katrina; Trieu, Melissa; Winters, Jenifer; Yang, Bib; Hauser, Charles R; Abusheikh, Tariq; Ashrawi, Yara; Benitez, Pedro; Boudreaux, Lauren R; Bourland, Megan; Chavez, Miranda; Cruz, Samantha; Elliott, GiNell; Farek, Jesse R; Flohr, Sarah; Flores, Amanda H; Friedrichs, Chelsey; Fusco, Zach; Goodwin, Zane; Helmreich, Eric; Kiley, John; Knepper, John Mark; Langner, Christine; Martinez, Megan; Mendoza, Carlos; Naik, Monal; Ochoa, Andrea; Ragland, Nicolas; Raimey, England; Rathore, Sunil; Reza, Evangelina; Sadovsky, Griffin; Seydoux, Marie-Isabelle B; Smith, Jonathan E; 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Sunjed, Ray; Stamm, Joyce; Anderson, Morgan C; Bonifield, Bethany Grace; Coomes, Daniel; Dillman, Adam; Durchholz, Elaine J; Fafara-Thompson, Antoinette E; Gross, Meleah J; Gygi, Amber M; Jackson, Lesley E; Johnson, Amy; Kocsisova, Zuzana; Manghelli, Joshua L; McNeil, Kylie; Murillo, Michael; Naylor, Kierstin L; Neely, Jessica; Ogawa, Emmy E; Rich, Ashley; Rogers, Anna; Spencer, J Devin; Stemler, Kristina M; Throm, Allison A; Van Camp, Matt; Weihbrecht, Katie; Wiles, T Aaron; Williams, Mallory A; Williams, Matthew; Zoll, Kyle; Bailey, Cheryl; Zhou, Leming; Balthaser, Darla M; Bashiri, Azita; Bower, Mindy E; Florian, Kayla A; Ghavam, Nazanin; Greiner-Sosanko, Elizabeth S; Karim, Helmet; Mullen, Victor W; Pelchen, Carly E; Yenerall, Paul M; Zhang, Jiayu; Rubin, Michael R; Arias-Mejias, Suzette M; Bermudez-Capo, Armando G; Bernal-Vega, Gabriela V; Colon-Vazquez, Mariela; Flores-Vazquez, Arelys; Gines-Rosario, Mariela; Llavona-Cartagena, Ivan G; Martinez-Rodriguez, Javier O; Ortiz-Fuentes, Lionel; 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Giddens, Michelle M; McNeil, Gerard P; Adebayo, Adeola; Bagaeva, Kate; Chinwong, Justina; Dol, Chrystel; George, Eunice; Haltaufderhyde, Kirk; Haye, Joanna; Kaur, Manpreet; Semon, Max; Serjanov, Dmitri; Toorie, Anika; Wilson, Christopher; Riddle, Nicole C; Buhler, Jeremy; Mardis, Elaine R; Elgin, Sarah C R

2015-03-04

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu. Copyright © 2015 Leung et al.

A universal trend of reduced mRNA stability near the translation-initiation site in prokaryotes and eukaryotes.

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Wanjun Gu

2010-02-01

Full Text Available Recent studies have suggested that the thermodynamic stability of mRNA secondary structure near the start codon can regulate translation efficiency in Escherichia coli, and that translation is more efficient the less stable the secondary structure. We survey the complete genomes of 340 species for signals of reduced mRNA secondary structure near the start codon. Our analysis includes bacteria, archaea, fungi, plants, insects, fishes, birds, and mammals. We find that nearly all species show evidence for reduced mRNA stability near the start codon. The reduction in stability generally increases with increasing genomic GC content. In prokaryotes, the reduction also increases with decreasing optimal growth temperature. Within genomes, there is variation in the stability among genes, and this variation correlates with gene GC content, codon bias, and gene expression level. For birds and mammals, however, we do not find a genome-wide trend of reduced mRNA stability near the start codon. Yet the most GC rich genes in these organisms do show such a signal. We conclude that reduced stability of the mRNA secondary structure near the start codon is a universal feature of all cellular life. We suggest that the origin of this reduction is selection for efficient recognition of the start codon by initiator-tRNA.

Genome instability: Linking ageing and brain degeneration.

Science.gov (United States)

Barzilai, Ari; Schumacher, Björn; Shiloh, Yosef

2017-01-01

Ageing is a multifactorial process affected by cumulative physiological changes resulting from stochastic processes combined with genetic factors, which together alter metabolic homeostasis. Genetic variation in maintenance of genome stability is emerging as an important determinant of ageing pace. Genome instability is also closely associated with a broad spectrum of conditions involving brain degeneration. Similarities and differences can be found between ageing-associated decline of brain functionality and the detrimental effect of genome instability on brain functionality and development. This review discusses these similarities and differences and highlights cell classes whose role in these processes might have been underestimated-glia and microglia. Copyright © 2016. Published by Elsevier B.V.

hSSB1 associates with and promotes stability of the BLM helicase

OpenAIRE

O'BYRNE, KEN

2017-01-01

Background Maintenance of genome stability is critical in human cells. Mutations in or loss of genome stability pathways can lead to a number of pathologies including cancer. hSSB1 is a critical DNA repair protein functioning in the repair and signalling of stalled DNA replication forks, double strand DNA breaks and oxidised DNA lesions. The BLM helicase is central to the repair of both collapsed DNA replication forks and double strand DNA breaks by homologous recombination. Results In this s...

MIPS: analysis and annotation of proteins from whole genomes in 2005.

Science.gov (United States)

Mewes, H W; Frishman, D; Mayer, K F X; Münsterkötter, M; Noubibou, O; Pagel, P; Rattei, T; Oesterheld, M; Ruepp, A; Stümpflen, V

2006-01-01

The Munich Information Center for Protein Sequences (MIPS at the GSF), Neuherberg, Germany, provides resources related to genome information. Manually curated databases for several reference organisms are maintained. Several of these databases are described elsewhere in this and other recent NAR database issues. In a complementary effort, a comprehensive set of >400 genomes automatically annotated with the PEDANT system are maintained. The main goal of our current work on creating and maintaining genome databases is to extend gene centered information to information on interactions within a generic comprehensive framework. We have concentrated our efforts along three lines (i) the development of suitable comprehensive data structures and database technology, communication and query tools to include a wide range of different types of information enabling the representation of complex information such as functional modules or networks Genome Research Environment System, (ii) the development of databases covering computable information such as the basic evolutionary relations among all genes, namely SIMAP, the sequence similarity matrix and the CABiNet network analysis framework and (iii) the compilation and manual annotation of information related to interactions such as protein-protein interactions or other types of relations (e.g. MPCDB, MPPI, CYGD). All databases described and the detailed descriptions of our projects can be accessed through the MIPS WWW server (http://mips.gsf.de).

Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication

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Antonio Postigo

2017-05-01

Full Text Available In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Consistent with this, pharmacological and RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. RPA and the sliding clamp PCNA interact with the viral polymerase E9 and are required for DNA replication. Moreover, the ATR activator TOPBP1 promotes genome replication and associates with the viral replisome component H5. Our study suggests that, in contrast to long-held beliefs, vaccinia recruits conserved components of the eukaryote DNA replication and repair machinery to amplify its genome in the host cytoplasm.

The raccoon polyomavirus genome and tumor antigen transcription are stable and abundant in neuroglial tumors.

Science.gov (United States)

Brostoff, Terza; Dela Cruz, Florante N; Church, Molly E; Woolard, Kevin D; Pesavento, Patricia A

2014-11-01

Raccoon polyomavirus (RacPyV) is associated with 100% of neuroglial tumors in free-ranging raccoons. Other tumor-associated polyomaviruses (PyVs), including simian virus 40 (SV40), murine PyV, and Merkel cell PyV, are found integrated in the host genome in neoplastic cells, where they constitutively express splice variants of the tumor antigen (TAg) gene. We have previously reported that RacPyV exists only as an episome (nonintegrated) in neuroglial tumors. Here, we have investigated TAg transcription in primary tumor tissue by transcriptome analysis, and we identified the alternatively spliced TAg transcripts for RacPyV. We also determined that TAg was highly transcribed relative to host cellular genes. We further colocalized TAg DNA and mRNA by in situ hybridization and found that the majority of tumor cells showed positive staining. Lastly, we examined the stability of the viral genome and TAg transcription by quantitative reverse transcriptase PCR in cultured tumor cells in vitro and in a mouse xenograft model. When tumor cells were cultured in vitro, TAg transcription increased nearly 2 log-fold over that of parental tumor tissue by passage 17. Both episomal viral genome and TAg transcription were faithfully maintained in culture and in tumors arising from xenotransplantation of cultured cells in mice. This study represents a minimal criterion for RacPyV's association with neuroglial tumors and a novel mechanism of stability for a polyomavirus in cancer. The natural cycle of polyomaviruses in mammals is to persist in the host without causing disease, but they can cause cancer in humans or in other animals. Because this is an unpredictable and rare event, the oncogenic potential of polyomavirus is primarily evaluated in laboratory animal models. Recently, raccoon polyomavirus (RacPyV) was identified in neuroglial tumors of free-ranging raccoons. Viral copy number was consistently high in these tumors but was low or undetectable in nontumor tissue or in

Promotion of Homologous Recombination and Genomic Stability byRAD51AP1 via RAD51 Recombinase Enhancement

Energy Technology Data Exchange (ETDEWEB)

Wiese, Claudia; Dray, Eloise; Groesser, Torsten; San Filippo,Joseph; Shi, Idina; Collins, David W.; Tsai, Miaw-Sheue; Williams,Gareth; Rydberg, Bjorn; Sung, Patrick; Schild, David

2007-04-11

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand pairing step in HR. RAD51AP1 (RAD51 Associated Protein 1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA damaging treatment. Purified RAD51AP1 binds dsDNA and RAD51, and it greatly stimulates the RAD51-mediated D-loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide the first evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

Directory of Open Access Journals (Sweden)

David H. Dreyfus

2017-01-01

Full Text Available Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame termed BART (BamHI A right transcripts are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBα that regulate host NF-κB. BALF-2 (BamHI A left frame transcript, a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1, may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.

Investigation of Oxidation stability of Pongamia Biodiesel and its blends

Directory of Open Access Journals (Sweden)

Gaurav Dwivedi

2016-03-01

Full Text Available Biodiesel from Pongamia oil is one of the promising non edible sources in India. But the main problem of using Pongamia biodiesel as fuel is its poor stability characteristics. Poor stability leads to gum formation which further leads to a storage problem of these fuels for a longer period of time. This paper investigates the methodology of improving the stability characteristics of Pongamia biodiesel by blending with diesel and use of the antioxidant Pyrogallol. The experimental investigation shows that blending with diesel and using of antioxidant Pyrogallol improves the stability characteristics of Pongamia biodiesel significantly. Results of the study show that the optimum amount of antioxidant (PY for pure PB20 is 300 ppm to maintain the oxidation stability specification and blending of diesel with Pongamia shows that PB10 requires no additive to maintain its stability characteristics.

Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism.

Science.gov (United States)

Reynolds, John J; Bicknell, Louise S; Carroll, Paula; Higgs, Martin R; Shaheen, Ranad; Murray, Jennie E; Papadopoulos, Dimitrios K; Leitch, Andrea; Murina, Olga; Tarnauskaitė, Žygimantė; Wessel, Sarah R; Zlatanou, Anastasia; Vernet, Audrey; von Kriegsheim, Alex; Mottram, Rachel M A; Logan, Clare V; Bye, Hannah; Li, Yun; Brean, Alexander; Maddirevula, Sateesh; Challis, Rachel C; Skouloudaki, Kassiani; Almoisheer, Agaadir; Alsaif, Hessa S; Amar, Ariella; Prescott, Natalie J; Bober, Michael B; Duker, Angela; Faqeih, Eissa; Seidahmed, Mohammed Zain; Al Tala, Saeed; Alswaid, Abdulrahman; Ahmed, Saleem; Al-Aama, Jumana Yousuf; Altmüller, Janine; Al Balwi, Mohammed; Brady, Angela F; Chessa, Luciana; Cox, Helen; Fischetto, Rita; Heller, Raoul; Henderson, Bertram D; Hobson, Emma; Nürnberg, Peter; Percin, E Ferda; Peron, Angela; Spaccini, Luigina; Quigley, Alan J; Thakur, Seema; Wise, Carol A; Yoon, Grace; Alnemer, Maha; Tomancak, Pavel; Yigit, Gökhan; Taylor, A Malcolm R; Reijns, Martin A M; Simpson, Michael A; Cortez, David; Alkuraya, Fowzan S; Mathew, Christopher G; Jackson, Andrew P; Stewart, Grant S

2017-04-01

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability.

Visualization of Genome Diversity in German Shepherd Dogs

OpenAIRE

Sally-Anne Mortlock; Rachel Booth; Hamutal Mazrier; Mehar S. Khatkar; Peter Williamson

2016-01-01

A loss of genetic diversity may lead to increased disease risks in subpopulations of dogs. The canine breed structure has contributed to relatively small effective population size in many breeds and can limit the options for selective breeding strategies to maintain diversity. With the completion of the canine genome sequencing project, and the subsequent reduction in the cost of genotyping on a genomic scale, evaluating diversity in dogs has become much more accurate and accessible. This pro...

14 CFR 25.173 - Static longitudinal stability.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Static longitudinal stability. 25.173... AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Flight Stability § 25.173 Static... forces (including friction) must be as follows: (a) A pull must be required to obtain and maintain speeds...

CMS-G from Beta vulgaris ssp. maritima is maintained in natural populations despite containing an atypical cytochrome c oxidase.

Science.gov (United States)

Meyer, Etienne H; Lehmann, Caroline; Boivin, Stéphane; Brings, Lea; De Cauwer, Isabelle; Bock, Ralph; Kühn, Kristina; Touzet, Pascal

2018-02-23

While mitochondrial mutants of the respiratory machinery are rare and often lethal, cytoplasmic male sterility (CMS), a mitochondrially inherited trait that results in pollen abortion, is frequently encountered in wild populations. It generates a breeding system called gynodioecy. In Beta vulgaris ssp. maritima , a gynodioecious species, we found CMS-G to be widespread across the distribution range of the species. Despite the sequencing of the mitochondrial genome of CMS-G, the mitochondrial sterilizing factor causing CMS-G is still unknown. By characterizing biochemically CMS-G, we found that the expression of several mitochondrial proteins is altered in CMS-G plants. In particular, Cox1, a core subunit of the cytochrome c oxidase (complex IV), is larger but can still assemble into complex IV. However, the CMS-G-specific complex IV was only detected as a stabilized dimer. We did not observe any alteration of the affinity of complex IV for cytochrome c ; however, in CMS-G, complex IV capacity is reduced. Our results show that CMS-G is maintained in many natural populations despite being associated with an atypical complex IV. We suggest that the modified complex IV could incur the associated cost predicted by theoretical models to maintain gynodioecy in wild populations. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Biobanking and translation of human genetics and genomics for infectious diseases

Directory of Open Access Journals (Sweden)

Ivan Branković

2014-06-01

Full Text Available Biobanks are invaluable resources in genomic research of both the infectious diseases and their hosts. This article examines the role of biobanks in basic research of infectious disease genomics, as well as the relevance and applicability of biobanks in the translation of impending knowledge and the clinical uptake of knowledge of infectious diseases. Our research identifies potential fields of interaction between infectious disease genomics and biobanks, in line with global trends in the integration of genome-based knowledge into clinical practice. It also examines various networks and biobanks that specialize in infectious diseases (including HIV, HPV and Chlamydia trachomatis, and provides examples of successful research and clinical uptake stemming from these biobanks. Finally, it outlines key issues with respect to data privacy in infectious disease genomics, as well as the utility of adequately designed and maintained electronic health records. We maintain that the public should be able to easily access a clear and detailed outline of regulations and procedures for sample and data utilization by academic or commercial investigators, and also should be able to understand the precise roles of relevant governing bodies. This would ultimately facilitate uptake by researchers and clinics. As a result of the efforts and resources invested by several networks and consortia, there is an increasing awareness of the prospective uses of biobanks in advancing infectious disease genomic research, diagnostics and their clinical management.

Biobanking and translation of human genetics and genomics for infectious diseases.

Science.gov (United States)

Branković, Ivan; Malogajski, Jelena; Morré, Servaas A

2014-06-01

Biobanks are invaluable resources in genomic research of both the infectious diseases and their hosts. This article examines the role of biobanks in basic research of infectious disease genomics, as well as the relevance and applicability of biobanks in the translation of impending knowledge and the clinical uptake of knowledge of infectious diseases. Our research identifies potential fields of interaction between infectious disease genomics and biobanks, in line with global trends in the integration of genome-based knowledge into clinical practice. It also examines various networks and biobanks that specialize in infectious diseases (including HIV, HPV and Chlamydia trachomatis), and provides examples of successful research and clinical uptake stemming from these biobanks. Finally, it outlines key issues with respect to data privacy in infectious disease genomics, as well as the utility of adequately designed and maintained electronic health records. We maintain that the public should be able to easily access a clear and detailed outline of regulations and procedures for sample and data utilization by academic or commercial investigators, and also should be able to understand the precise roles of relevant governing bodies. This would ultimately facilitate uptake by researchers and clinics. As a result of the efforts and resources invested by several networks and consortia, there is an increasing awareness of the prospective uses of biobanks in advancing infectious disease genomic research, diagnostics and their clinical management.

Mechanisms of Low Dose Radio-Suppression of Genomic Instability

Energy Technology Data Exchange (ETDEWEB)

Engelward, Bevin P. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

2009-09-16

The major goal of this project is to contribute toward the elucidation of the impact of long term low dose radiation on genomic stability. We have created and characterized novel technologies for delivering long term low dose radiation to animals, and we have studied genomic stability by applying cutting edge molecular analysis technologies. Remarkably, we have found that a dose rate that is 300X higher than background radiation does not lead to any detectable genomic damage, nor is there any significant change in gene expression for genes pertinent to the DNA damage response. These results point to the critical importance of dose rate, rather than just total dose, when evaluating public health risks and when creating regulatory guidelines. In addition to these studies, we have also further developed a mouse model for quantifying cells that have undergone a large scale DNA sequence rearrangement via homologous recombination, and we have applied these mice in studies of both low dose radiation and space radiation. In addition to more traditional approaches for assessing genomic stability, we have also explored radiation and possible beneficial effects (adaptive response), long term effects (persistent effects) and effects on communication among cells (bystander effects), both in vitro and in vivo. In terms of the adaptive response, we have not observed any significant induction of an adaptive response following long term low dose radiation in vivo, delivered at 300X background. In terms of persistent and bystander effects, we have revealed evidence of a bystander effect in vivo and with researchers at and demonstrated for the first time the molecular mechanism by which cells “remember” radiation exposure. Understanding the underlying molecular mechanisms by which radiation can induce genomic instability is fundamental to our ability to assess the biological impact of low dose radiation. Finally, in a parallel set of studies we have explored the effects of heavy

The Past, Present, and Future of Human Centromere Genomics

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Megan E. Aldrup-MacDonald

2014-01-01

Full Text Available The centromere is the chromosomal locus essential for chromosome inheritance and genome stability. Human centromeres are located at repetitive alpha satellite DNA arrays that compose approximately 5% of the genome. Contiguous alpha satellite DNA sequence is absent from the assembled reference genome, limiting current understanding of centromere organization and function. Here, we review the progress in centromere genomics spanning the discovery of the sequence to its molecular characterization and the work done during the Human Genome Project era to elucidate alpha satellite structure and sequence variation. We discuss exciting recent advances in alpha satellite sequence assembly that have provided important insight into the abundance and complex organization of this sequence on human chromosomes. In light of these new findings, we offer perspectives for future studies of human centromere assembly and function.

Brassica ASTRA: an integrated database for Brassica genomic research.

Science.gov (United States)

Love, Christopher G; Robinson, Andrew J; Lim, Geraldine A C; Hopkins, Clare J; Batley, Jacqueline; Barker, Gary; Spangenberg, German C; Edwards, David

2005-01-01

Brassica ASTRA is a public database for genomic information on Brassica species. The database incorporates expressed sequences with Swiss-Prot and GenBank comparative sequence annotation as well as secondary Gene Ontology (GO) annotation derived from the comparison with Arabidopsis TAIR GO annotations. Simple sequence repeat molecular markers are identified within resident sequences and mapped onto the closely related Arabidopsis genome sequence. Bacterial artificial chromosome (BAC) end sequences derived from the Multinational Brassica Genome Project are also mapped onto the Arabidopsis genome sequence enabling users to identify candidate Brassica BACs corresponding to syntenic regions of Arabidopsis. This information is maintained in a MySQL database with a web interface providing the primary means of interrogation. The database is accessible at http://hornbill.cspp.latrobe.edu.au.

Cell size, genome size and the dominance of Angiosperms

Science.gov (United States)

Simonin, K. A.; Roddy, A. B.

2016-12-01

Angiosperms are capable of maintaining the highest rates of photosynthetic gas exchange of all land plants. High rates of photosynthesis depends mechanistically both on efficiently transporting water to the sites of evaporation in the leaf and on regulating the loss of that water to the atmosphere as CO2 diffuses into the leaf. Angiosperm leaves are unique in their ability to sustain high fluxes of liquid and vapor phase water transport due to high vein densities and numerous, small stomata. Despite the ubiquity of studies characterizing the anatomical and physiological adaptations that enable angiosperms to maintain high rates of photosynthesis, the underlying mechanism explaining why they have been able to develop such high leaf vein densities, and such small and abundant stomata, is still incomplete. Here we ask whether the scaling of genome size and cell size places a fundamental constraint on the photosynthetic metabolism of land plants, and whether genome downsizing among the angiosperms directly contributed to their greater potential and realized primary productivity relative to the other major groups of terrestrial plants. Using previously published data we show that a single relationship can predict guard cell size from genome size across the major groups of terrestrial land plants (e.g. angiosperms, conifers, cycads and ferns). Similarly, a strong positive correlation exists between genome size and both stomatal density and vein density that together ultimately constrains maximum potential (gs, max) and operational stomatal conductance (gs, op). Further the difference in the slopes describing the covariation between genome size and both gs, max and gs, op suggests that genome downsizing brings gs, op closer to gs, max. Taken together the data presented here suggests that the smaller genomes of angiosperms allow their final cell sizes to vary more widely and respond more directly to environmental conditions and in doing so bring operational photosynthetic

PTEN C-Terminal Deletion Causes Genomic Instability and Tumor Development

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Zhuo Sun

2014-03-01

Full Text Available Tumor suppressor PTEN controls genomic stability and inhibits tumorigenesis. The N-terminal phosphatase domain of PTEN antagonizes the PI3K/AKT pathway, but its C-terminal function is less defined. Here, we describe a knockin mouse model of a nonsense mutation that results in the deletion of the entire Pten C-terminal region, referred to as PtenΔC. Mice heterozygous for PtenΔC develop multiple spontaneous tumors, including cancers and B cell lymphoma. Heterozygous deletion of the Pten C-terminal domain also causes genomic instability and common fragile site rearrangement. We found that Pten C-terminal disruption induces p53 and its downstream targets. Simultaneous depletion of p53 promotes metastasis without influencing the initiation of tumors, suggesting that p53 mainly suppresses tumor progression. Our data highlight the essential role of the PTEN C terminus in the maintenance of genomic stability and suppression of tumorigenesis.

30 CFR 56.3130 - Wall, bank, and slope stability.

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Wall, bank, and slope stability. 56.3130... Mining Methods § 56.3130 Wall, bank, and slope stability. Mining methods shall be used that will maintain wall, bank, and slope stability in places where persons work or travel in performing their assigned...

SINEs as driving forces in genome evolution.

Science.gov (United States)

Schmitz, J

2012-01-01

SINEs are short interspersed elements derived from cellular RNAs that repetitively retropose via RNA intermediates and integrate more or less randomly back into the genome. SINEs propagate almost entirely vertically within their host cells and, once established in the germline, are passed on from generation to generation. As non-autonomous elements, their reverse transcription (from RNA to cDNA) and genomic integration depends on the activity of the enzymatic machinery of autonomous retrotransposons, such as long interspersed elements (LINEs). SINEs are widely distributed in eukaryotes, but are especially effectively propagated in mammalian species. For example, more than a million Alu-SINE copies populate the human genome (approximately 13% of genomic space), and few master copies of them are still active. In the organisms where they occur, SINEs are a challenge to genomic integrity, but in the long term also can serve as beneficial building blocks for evolution, contributing to phenotypic heterogeneity and modifying gene regulatory networks. They substantially expand the genomic space and introduce structural variation to the genome. SINEs have the potential to mutate genes, to alter gene expression, and to generate new parts of genes. A balanced distribution and controlled activity of such properties is crucial to maintaining the organism's dynamic and thriving evolution. Copyright © 2012 S. Karger AG, Basel.

Dengue Virus Genome Uncoating Requires Ubiquitination

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Laura A. Byk

2016-06-01

Full Text Available The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process.

Functional and comparative genome analysis of novel virulent actinophages belonging to Streptomyces flavovirens

Czech Academy of Sciences Publication Activity Database

Sharaf, Abdoallah; Mercati, F.; Elmaghraby, I.; Elbaz, R. M.; Marei, E. M.

2017-01-01

Roč. 17, 3 March (2017), č. článku 51. ISSN 1471-2180 Institutional support: RVO:60077344 Keywords : bacteriophage * biological stability * whole genome sequence * ngs * comparative genomics Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 2.644, year: 2016

THE FINANCIAL STABILITY ANALYSIS THROUGH THE WORKING CAPITAL

Directory of Open Access Journals (Sweden)

LĂPĂDUŞI MIHAELA LOREDANA

2012-12-01

Full Text Available The main goal of any business is to maintain the financial stability not only on the short term but also on medium and long term, in other words to maintain a harmony between financial sources and financial needs, respectively the equality between the assets and liabilities from the balance sheet. On short term, maintaining the financial stability involves correlating the temporary resources with the temporary uses by using the necessary working capital, and on the long-term, the financial stability involves comparing the permanent resources with the permanent uses by working capital indicator. The determination of the financial state of the company at a certain moment represents the key moment in establishing and adopting the economic and financial decisions in the management of the company. Maintaining the financial stability of the company represents one of the main objectives of the financial analysis and management and it also provides the optimum development of the entire economic and financial activity of the company. The analysis of the working capital size is based on the financial statement data and information, and based on this analysis is considered the financial situation of the company, the financial equilibrium state at a certain moment. The purpose of this article is to highlight the fact that the maintenance of the financial stability on medium and long term is subordinated to the “working capital” indicator, its content and interpretation evolving in time and varying differently from one company to another. The results of this research may have broad applicability in the field of the companies’ activity and it materializes in the complex approach of the working capital regarded as a classic indicator, frequently used in the financial analysis and with profound significance in establishing the financial state in general and the equilibrium state in particular.

Inter-genomic DNA Exchanges and Homeologous Gene Silencing Shaped the Nascent Allopolyploid Coffee Genome (Coffea arabica L.

Directory of Open Access Journals (Sweden)

Philippe Lashermes

2016-09-01

Full Text Available Allopolyploidization is a biological process that has played a major role in plant speciation and evolution. Genomic changes are common consequences of polyploidization, but their dynamics over time are still poorly understood. Coffea arabica, a recently formed allotetraploid, was chosen to study genetic changes that accompany allopolyploid formation. Both RNA-seq and DNA-seq data were generated from two genetically distant C. arabica accessions. Genomic structural variation was investigated using C. canephora, one of its diploid progenitors, as reference genome. The fate of 9047 duplicate homeologous genes was inferred and compared between the accessions. The pattern of SNP density along the reference genome was consistent with the allopolyploid structure. Large genomic duplications or deletions were not detected. Two homeologous copies were retained and expressed in 96% of the genes analyzed. Nevertheless, duplicated genes were found to be affected by various genomic changes leading to homeolog loss or silencing. Genetic and epigenetic changes were evidenced that could have played a major role in the stabilization of the unique ancestral allotetraploid and its subsequent diversification. While the early evolution of C. arabica mainly involved homeologous crossover exchanges, the later stage appears to have relied on more gradual evolution involving gene conversion and homeolog silencing.

Gene calling and bacterial genome annotation with BG7.

Science.gov (United States)

Tobes, Raquel; Pareja-Tobes, Pablo; Manrique, Marina; Pareja-Tobes, Eduardo; Kovach, Evdokim; Alekhin, Alexey; Pareja, Eduardo

2015-01-01

New massive sequencing technologies are providing many bacterial genome sequences from diverse taxa but a refined annotation of these genomes is crucial for obtaining scientific findings and new knowledge. Thus, bacterial genome annotation has emerged as a key point to investigate in bacteria. Any efficient tool designed specifically to annotate bacterial genomes sequenced with massively parallel technologies has to consider the specific features of bacterial genomes (absence of introns and scarcity of nonprotein-coding sequence) and of next-generation sequencing (NGS) technologies (presence of errors and not perfectly assembled genomes). These features make it convenient to focus on coding regions and, hence, on protein sequences that are the elements directly related with biological functions. In this chapter we describe how to annotate bacterial genomes with BG7, an open-source tool based on a protein-centered gene calling/annotation paradigm. BG7 is specifically designed for the annotation of bacterial genomes sequenced with NGS. This tool is sequence error tolerant maintaining their capabilities for the annotation of highly fragmented genomes or for annotating mixed sequences coming from several genomes (as those obtained through metagenomics samples). BG7 has been designed with scalability as a requirement, with a computing infrastructure completely based on cloud computing (Amazon Web Services).

Reprogramming suppresses premature senescence phenotypes of Werner syndrome cells and maintains chromosomal stability over long-term culture.

Science.gov (United States)

Shimamoto, Akira; Kagawa, Harunobu; Zensho, Kazumasa; Sera, Yukihiro; Kazuki, Yasuhiro; Osaki, Mitsuhiko; Oshimura, Mitsuo; Ishigaki, Yasuhito; Hamasaki, Kanya; Kodama, Yoshiaki; Yuasa, Shinsuke; Fukuda, Keiichi; Hirashima, Kyotaro; Seimiya, Hiroyuki; Koyama, Hirofumi; Shimizu, Takahiko; Takemoto, Minoru; Yokote, Koutaro; Goto, Makoto; Tahara, Hidetoshi

2014-01-01

Werner syndrome (WS) is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs). In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. WS iPSCs also showed recapitulation of the phenotypes during differentiation. Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of the descendant clones had chromosomal profiles that were similar to those of parental cells. These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming, which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells. These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term. WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS.

Reprogramming suppresses premature senescence phenotypes of Werner syndrome cells and maintains chromosomal stability over long-term culture.

Directory of Open Access Journals (Sweden)

Akira Shimamoto

Full Text Available Werner syndrome (WS is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease and cause telomere dysfunction, resulting in accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem cells (iPSCs. In the present study, we describe the effects of long-term culture on WS iPSCs, which acquired and maintained infinite proliferative potential for self-renewal over 2 years. After long-term cultures, WS iPSCs exhibited stable undifferentiated states and differentiation capacity, and premature upregulation of senescence-associated genes in WS cells was completely suppressed in WS iPSCs despite WRN deficiency. WS iPSCs also showed recapitulation of the phenotypes during differentiation. Furthermore, karyotype analysis indicated that WS iPSCs were stable, and half of the descendant clones had chromosomal profiles that were similar to those of parental cells. These unexpected properties might be achieved by induced expression of endogenous telomerase gene during reprogramming, which trigger telomerase reactivation leading to suppression of both replicative senescence and telomere dysfunction in WS cells. These findings demonstrated that reprogramming suppressed premature senescence phenotypes in WS cells and WS iPSCs could lead to chromosomal stability over the long term. WS iPSCs will provide opportunities to identify affected lineages in WS and to develop a new strategy for the treatment of WS.

MIPS: a database for genomes and protein sequences.

Science.gov (United States)

Mewes, H W; Frishman, D; Güldener, U; Mannhaupt, G; Mayer, K; Mokrejs, M; Morgenstern, B; Münsterkötter, M; Rudd, S; Weil, B

2002-01-01

The Munich Information Center for Protein Sequences (MIPS-GSF, Neuherberg, Germany) continues to provide genome-related information in a systematic way. MIPS supports both national and European sequencing and functional analysis projects, develops and maintains automatically generated and manually annotated genome-specific databases, develops systematic classification schemes for the functional annotation of protein sequences, and provides tools for the comprehensive analysis of protein sequences. This report updates the information on the yeast genome (CYGD), the Neurospora crassa genome (MNCDB), the databases for the comprehensive set of genomes (PEDANT genomes), the database of annotated human EST clusters (HIB), the database of complete cDNAs from the DHGP (German Human Genome Project), as well as the project specific databases for the GABI (Genome Analysis in Plants) and HNB (Helmholtz-Netzwerk Bioinformatik) networks. The Arabidospsis thaliana database (MATDB), the database of mitochondrial proteins (MITOP) and our contribution to the PIR International Protein Sequence Database have been described elsewhere [Schoof et al. (2002) Nucleic Acids Res., 30, 91-93; Scharfe et al. (2000) Nucleic Acids Res., 28, 155-158; Barker et al. (2001) Nucleic Acids Res., 29, 29-32]. All databases described, the protein analysis tools provided and the detailed descriptions of our projects can be accessed through the MIPS World Wide Web server (http://mips.gsf.de).

Mms1 binds to G-rich regions in Saccharomyces cerevisiae and influences replication and genome stability

NARCIS (Netherlands)

Wanzek, Katharina; Schwindt, Eike; Capra, John A.; Paeschke, Katrin

2017-01-01

The regulation of replication is essential to preserve genome integrity. Mms1 is part of the E3 ubiquitin ligase complex that is linked to replication fork progression. By identifying Mms1 binding sites genome-wide in Saccharomyces cerevisiae we connected Mms1 function to genome integrity and

PfClpC Is an Essential Clp Chaperone Required for Plastid Integrity and Clp Protease Stability in Plasmodium falciparum

Directory of Open Access Journals (Sweden)

Anat Florentin

2017-11-01

Full Text Available Summary: The deadly malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid, known as the apicoplast, that functions to produce essential metabolites, and drugs that target the apicoplast are clinically effective. Several prokaryotic caseinolytic protease (Clp genes have been identified in the Plasmodium genome. Using phylogenetic analysis, we focused on the Clp members that may form a regulated proteolytic complex in the apicoplast. We genetically targeted members of this complex and generated conditional mutants of the apicoplast-localized PfClpC chaperone and PfClpP protease. Conditional inhibition of the PfClpC chaperone resulted in growth arrest and apicoplast loss and was rescued by addition of the essential apicoplast-derived metabolite IPP. Using a double-conditional mutant parasite line, we discovered that the chaperone activity is required to stabilize the mature protease, revealing functional interactions. These data demonstrate the essential function of PfClpC in maintaining apicoplast integrity and its role in regulating the proteolytic activity of the Clp complex. : Plasmodium falciparum contains a unique organelle, the apicoplast. Using genetic and phenotypic assays, Florentin et al. characterize the apicoplast Clp chaperone and protease. They find that the chaperone is essential for protease stability and that together they function to maintain organelle integrity and segregation into daughter cells. Keywords: malaria, Plasmodium, apicoplast, IPP, Clp, chaperone, caseinolytic protease

55th Annual Canadian Society for Molecular Biosciences Conference on Epigenetics and Genomic Stability. Whistler, British Columbia, Canada, 14–18 March 2012.

Science.gov (United States)

Nelson, Christopher J; Ausió, Juan

2012-06-01

The 55th Annual Canadian Society for Molecular Biosciences Conference on Epigenetics and Genomic Stability in Whistler, Canada, 14-18 March 2012, brought together 31 speakers from different nationalities. The organizing committee, led by Jim Davie (Chair) at the University of Manitoba (Manitoba, Canada), consisted of several established researchers in the fields of chromatin and epigenetics from across Canada. The meeting was centered on the contribution of epigenetics to gene expression, DNA damage and repair, and the role of environmental factors. A few interesting talks on replication added some insightful information on the controversial issue of histone post-translational modifications as genuine epigenetic marks that are inherited through cell division.

Competition and system stability -- The reward and the penalty

International Nuclear Information System (INIS)

Mansour, Y.

2000-01-01

The business protocols and rules of the competitive electricity market are resulting in fragmentation of the historical vertically integrated structures. Electric services are offered at either cost or market-based prices depending on their type and the level of competition in a particular product. System stabilizing measures are essential for maintaining system security, yet their value is either underestimated or not understood. This paper describes practical methods to quantify the value of some of the stabilizing measures and ways to ensure maintaining the dynamic security of the power systems through business procedures and monetary sanctions

Epigenetic control of mobile DNA as an interface between experience and genome change

Directory of Open Access Journals (Sweden)

James A. Shapiro

2014-04-01

Full Text Available Mobile DNA in the genome is subject to RNA-targeted epigenetic control. This control regulates the activity of transposons, retrotransposons and genomic proviruses. Many different life history experiences alter the activities of mobile DNA and the expression of genetic loci regulated by nearby insertions. The same experiences induce alterations in epigenetic formatting and lead to trans-generational modifications of genome expression and stability. These observations lead to the hypothesis that epigenetic formatting directed by non-coding RNA provides a molecular interface between life history events and genome alteration.

Development of a duplex real-time RT-qPCR assay to monitor genome replication, gene expression and gene insert stability during in vivo replication of a prototype live attenuated canine distemper virus vector encoding SIV gag.

Science.gov (United States)

Coleman, John W; Wright, Kevin J; Wallace, Olivia L; Sharma, Palka; Arendt, Heather; Martinez, Jennifer; DeStefano, Joanne; Zamb, Timothy P; Zhang, Xinsheng; Parks, Christopher L

2015-03-01

Advancement of new vaccines based on live viral vectors requires sensitive assays to analyze in vivo replication, gene expression and genetic stability. In this study, attenuated canine distemper virus (CDV) was used as a vaccine delivery vector and duplex 2-step quantitative real-time RT-PCR (RT-qPCR) assays specific for genomic RNA (gRNA) or mRNA have been developed that concurrently quantify coding sequences for the CDV nucleocapsid protein (N) and a foreign vaccine antigen (SIV Gag). These amplicons, which had detection limits of about 10 copies per PCR reaction, were used to show that abdominal cavity lymphoid tissues were a primary site of CDV vector replication in infected ferrets, and importantly, CDV gRNA or mRNA was undetectable in brain tissue. In addition, the gRNA duplex assay was adapted for monitoring foreign gene insert genetic stability during in vivo replication by analyzing the ratio of CDV N and SIV gag genomic RNA copies over the course of vector infection. This measurement was found to be a sensitive probe for assessing the in vivo genetic stability of the foreign gene insert. Copyright © 2014 Elsevier B.V. All rights reserved.

RTEL1 is a replisome-associated helicase that promotes telomere and genome-wide replication.

Science.gov (United States)

Vannier, Jean-Baptiste; Sandhu, Sumit; Petalcorin, Mark I R; Wu, Xiaoli; Nabi, Zinnatun; Ding, Hao; Boulton, Simon J

2013-10-11

Regulator of telomere length 1 (RTEL1) is an essential DNA helicase that disassembles telomere loops (T loops) and suppresses telomere fragility to maintain the integrity of chromosome ends. We established that RTEL1 also associates with the replisome through binding to proliferating cell nuclear antigen (PCNA). Mouse cells disrupted for the RTEL1-PCNA interaction (PIP mutant) exhibited accelerated senescence, replication fork instability, reduced replication fork extension rates, and increased origin usage. Although T-loop disassembly at telomeres was unaffected in the mutant cells, telomere replication was compromised, leading to fragile sites at telomeres. RTEL1-PIP mutant mice were viable, but loss of the RTEL1-PCNA interaction accelerated the onset of tumorigenesis in p53-deficient mice. We propose that RTEL1 plays a critical role in both telomere and genome-wide replication, which is crucial for genetic stability and tumor avoidance.

Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics.

Science.gov (United States)

Gamwell, Lisa F; Gambaro, Karen; Merziotis, Maria; Crane, Colleen; Arcand, Suzanna L; Bourada, Valerie; Davis, Christopher; Squire, Jeremy A; Huntsman, David G; Tonin, Patricia N; Vanderhyden, Barbara C

2013-02-21

The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. Spectral karyotyping revealed a largely normal diploid karyotype (in greater than 95% of cells) with a visibly shorter chromosome 20 contig. High density SNP array analysis also revealed few genomic anomalies in BIN-67 cells, which included loss of heterozygosity of an estimated 16.7 Mb interval on chromosome 20. SNP array analyses of four SCCOHT samples also indicated a low frequency of genomic anomalies in the majority of cases. Although resistant to platinum chemotherapeutic drugs, BIN-67 cell viability in vitro was reduced by > 75% after infection with oncolytic viruses. These results show that SCCOHT differs from high-grade serous carcinomas by exhibiting few chromosomal anomalies and lacking TP53 mutations. Although BIN-67 cells are

PGSB/MIPS PlantsDB Database Framework for the Integration and Analysis of Plant Genome Data.

Science.gov (United States)

Spannagl, Manuel; Nussbaumer, Thomas; Bader, Kai; Gundlach, Heidrun; Mayer, Klaus F X

2017-01-01

Plant Genome and Systems Biology (PGSB), formerly Munich Institute for Protein Sequences (MIPS) PlantsDB, is a database framework for the integration and analysis of plant genome data, developed and maintained for more than a decade now. Major components of that framework are genome databases and analysis resources focusing on individual (reference) genomes providing flexible and intuitive access to data. Another main focus is the integration of genomes from both model and crop plants to form a scaffold for comparative genomics, assisted by specialized tools such as the CrowsNest viewer to explore conserved gene order (synteny). Data exchange and integrated search functionality with/over many plant genome databases is provided within the transPLANT project.

Stabilization process in Saccharomyces intra and interspecific hybrids in fermentative conditions.

Science.gov (United States)

Pérez-Través, Laura; Lopes, Christian A; Barrio, Eladio; Querol, Amparo

2014-12-01

We evaluated the genetic stabilization of artificial intra- (Saccharomyces cerevisiae) and interspecific (S. cerevisiae × S. kudriavzevii) hybrids under wine fermentative conditions. Large-scale transitions in genome size and genome reorganizations were observed during this process. Interspecific hybrids seem to need fewer generations to reach genetic stability than intraspecific hybrids. The largest number of molecular patterns recovered among the derived clones was observed for intraspecific hybrids, particularly for those obtained by rare-mating. Molecular marker analyses revealed that unstable clones could change during the industrial process to obtain active dry yeast. When no changes in molecular markers and ploidy were observed after this process, no changes in genetic composition were confirmed by comparative genome hybridization, considering the clone as a stable hybrid. According to our results, under these conditions, fermentation steps 3 and 5 (30-50 generations) would suffice to obtain genetically stable interspecific and intraspecific hybrids, respectively. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

Does selection against transcriptional interference shape retroelement-free regions in mammalian genomes?

DEFF Research Database (Denmark)

Mourier, Tobias; Willerslev, Eske

2008-01-01

in generating and maintaining retroelement-free regions in the human genome. METHODOLOGY/PRINCIPAL FINDINGS: Based on the known transcriptional properties of retroelements, we expect long interspersed elements (LINEs) to be able to display a high degree of transcriptional interference. In contrast, we expect......BACKGROUND: Eukaryotic genomes are scattered with retroelements that proliferate through retrotransposition. Although retroelements make up around 40 percent of the human genome, large regions are found to be completely devoid of retroelements. This has been hypothesised to be a result of genomic...... activity of LINEs has been identified previously. CONCLUSIONS/SIGNIFICANCE: Our observations are consistent with the notion that selection against transcriptional interference has contributed to the maintenance and/or generation of retroelement-free regions in the human genome....

Wind Power Plant Voltage Stability Evaluation: Preprint

Energy Technology Data Exchange (ETDEWEB)

Muljadi, E.; Zhang, Y. C.

2014-09-01

Voltage stability refers to the ability of a power system to maintain steady voltages at all buses in the system after being subjected to a disturbance from a given initial operating condition. Voltage stability depends on a power system's ability to maintain and/or restore equilibrium between load demand and supply. Instability that may result occurs in the form of a progressive fall or rise of voltages of some buses. Possible outcomes of voltage instability are the loss of load in an area or tripped transmission lines and other elements by their protective systems, which may lead to cascading outages. The loss of synchronism of some generators may result from these outages or from operating conditions that violate a synchronous generator's field current limit, or in the case of variable speed wind turbine generator, the current limits of power switches. This paper investigates the impact of wind power plants on power system voltage stability by using synchrophasor measurements.

Genome-Wide Mutation Rate Response to pH Change in the Coral Reef Pathogen Vibrio shilonii AK1.

Science.gov (United States)

Strauss, Chloe; Long, Hongan; Patterson, Caitlyn E; Te, Ronald; Lynch, Michael

2017-08-22

Recent application of mutation accumulation techniques combined with whole-genome sequencing (MA/WGS) has greatly promoted studies of spontaneous mutation. However, such explorations have rarely been conducted on marine organisms, and it is unclear how marine habitats have influenced genome stability. This report resolves the mutation rate and spectrum of the coral reef pathogen Vibrio shilonii , which causes coral bleaching and endangers the biodiversity maintained by coral reefs. We found that its mutation rate and spectrum are highly similar to those of other studied bacteria from various habitats, despite the saline environment. The mutational properties of this marine bacterium are thus controlled by other general evolutionary forces such as natural selection and genetic drift. We also found that as pH drops, the mutation rate decreases and the mutation spectrum is biased in the direction of generating G/C nucleotides. This implies that evolutionary features of this organism and perhaps other marine microbes might be altered by the increasingly acidic ocean water caused by excess CO 2 emission. Nonetheless, further exploration is needed as the pH range tested in this study was rather narrow and many other possible mutation determinants, such as carbonate increase, are associated with ocean acidification. IMPORTANCE This study explored the pH dependence of a bacterial genome-wide mutation rate. We discovered that the genome-wide rates of appearance of most mutation types decrease linearly and that the mutation spectrum is biased in generating more G/C nucleotides with pH drop in the coral reef pathogen V. shilonii . Copyright © 2017 Strauss et al.

Cellular Factors Shape 3D Genome Landscape

Science.gov (United States)

Researchers, using novel large-scale imaging technology, have mapped the spatial location of individual genes in the nucleus of human cells and identified 50 cellular factors required for the proper 3D positioning of genes. These spatial locations play important roles in gene expression, DNA repair, genome stability, and other cellular activities.

Deep ancestry of programmed genome rearrangement in lampreys.

Science.gov (United States)

Timoshevskiy, Vladimir A; Lampman, Ralph T; Hess, Jon E; Porter, Laurie L; Smith, Jeramiah J

2017-09-01

In most multicellular organisms, the structure and content of the genome is rigorously maintained over the course of development. However some species have evolved genome biologies that permit, or require, developmentally regulated changes in the physical structure and content of the genome (programmed genome rearrangement: PGR). Relatively few vertebrates are known to undergo PGR, although all agnathans surveyed to date (several hagfish and one lamprey: Petromyzon marinus) show evidence of large scale PGR. To further resolve the ancestry of PGR within vertebrates, we developed probes that allow simultaneous tracking of nearly all sequences eliminated by PGR in P. marinus and a second lamprey species (Entosphenus tridentatus). These comparative analyses reveal conserved subcellular structures (lagging chromatin and micronuclei) associated with PGR and provide the first comparative embryological evidence in support of the idea that PGR represents an ancient and evolutionarily stable strategy for regulating inherent developmental/genetic conflicts between germline and soma. Copyright © 2017 Elsevier Inc. All rights reserved.

Complete Genome Sequence of the Anaerobic Halophilic Alkalithermophile Natranaerobius thermophilus JW/NM-WN-LFT

Energy Technology Data Exchange (ETDEWEB)

Mesbah, Noha [University of Georgia, Athens, GA; Dalin, Eileen [U.S. Department of Energy, Joint Genome Institute; Goodwin, Lynne A. [Los Alamos National Laboratory (LANL); Nolan, Matt [U.S. Department of Energy, Joint Genome Institute; Pitluck, Sam [U.S. Department of Energy, Joint Genome Institute; Chertkov, Olga [Los Alamos National Laboratory (LANL); Han, James [U.S. Department of Energy, Joint Genome Institute; Larimer, Frank W [ORNL; Land, Miriam L [ORNL; Hauser, Loren John [ORNL; Kyrpides, Nikos C [U.S. Department of Energy, Joint Genome Institute; Wiegel, Juergen [University of Georgia, Athens, GA

2011-01-01

The genome of the anaerobic halophilic alkalithermophile Natranaerobius thermophiles consists of one chromosome and two plasmids.The present study is the first to report the completely sequenced genome of polyextremophile and the harboring genes harboring genes associated with roles in regulation of intracellular osmotic pressure, pH homeostasis, and thermophilic stability.

Evaluation of the frequency of polymorphisms in XRCC1 (Arg399Gln) and XPD (Lys751Gln) genes related to the genome stability maintenance in individuals of the resident population from Monte Alegre, PA/Brazil municipality

International Nuclear Information System (INIS)

Duarte, Isabelle Magliano

2010-01-01

The human exposure to ionizing radiation coming from natural sources is an inherent feature of human life on Earth. Ionizing radiation is a known genotoxic agent, which can affect biological molecules, causing DNA damage and genomic instability. The cellular system of DNA repair plays an important role in maintaining genomic stability by repairing DNA damage caused by genotoxic agents. However, genes related to DNA repair may have their role committed when presenting a certain polymorphism. This study intended to analyze the frequency of single nucleotide polymorphisms (SNPs) in genes of DNA repair XRCC1 (Arg39-9Gln) and XPD (Lys751Gln) in a: population of the city of Monte Alegre, that resides in an area of high exposure to natural radioactivity. Samples of saliva were collected from individuals of the population of Monte Alegre, in which 40 samples were of male and 46 female. Through the use of RFLP (length polymorphism restriction fragment) the frequency of homozygous genotypes and / or heterozygous was determined for polymorphic genes. The XRCC1 gene had 65.4% of the presence of the allele 399Gln and XPD gene had 32.9% of the 751Gln allele. These values are similar to those found in previous studies for the XPD gene, whereas XRCC1 showed a frequency much higher than described in the literature. The. influence of these polymorphisms, which are involved in DNA repair and consequent genotoxicity induced by radiation depends on dose and exposure factors such as smoking, statistically a factor in public health surveillance in the region. This study gathered information and molecular epidemiology for risk assessment of cancer in the population of Monte Alegre. (author)

Functional genomics for food microbiology: Molecular mechanisms of weak organic acid preservative adaptation in yeast

NARCIS (Netherlands)

Brul, S.; Kallemeijn, W.; Smits, G.

2008-01-01

The recent era of genomics has offered tremendous possibilities to biology. This concise review describes the possibilities of applying (functional) genomics studies to the field of microbial food stability. In doing so, the studies on weak-organic-acid stress response in yeast are discussed by way

The Information Technology Infrastructure for the Translational Genomics Core and the Partners Biobank at Partners Personalized Medicine

Directory of Open Access Journals (Sweden)

Natalie Boutin

2016-01-01

Full Text Available The Biobank and Translational Genomics core at Partners Personalized Medicine requires robust software and hardware. This Information Technology (IT infrastructure enables the storage and transfer of large amounts of data, drives efficiencies in the laboratory, maintains data integrity from the time of consent to the time that genomic data is distributed for research, and enables the management of complex genetic data. Here, we describe the functional components of the research IT infrastructure at Partners Personalized Medicine and how they integrate with existing clinical and research systems, review some of the ways in which this IT infrastructure maintains data integrity and security, and discuss some of the challenges inherent to building and maintaining such infrastructure.

Whole genome sequencing reveals genomic heterogeneity and antibiotic purification in Mycobacterium tuberculosis isolates

KAUST Repository

Black, PA

2015-10-24

Background Whole genome sequencing has revolutionised the interrogation of mycobacterial genomes. Recent studies have reported conflicting findings on the genomic stability of Mycobacterium tuberculosis during the evolution of drug resistance. In an age where whole genome sequencing is increasingly relied upon for defining the structure of bacterial genomes, it is important to investigate the reliability of next generation sequencing to identify clonal variants present in a minor percentage of the population. This study aimed to define a reliable cut-off for identification of low frequency sequence variants and to subsequently investigate genetic heterogeneity and the evolution of drug resistance in M. tuberculosis. Methods Genomic DNA was isolated from single colonies from 14 rifampicin mono-resistant M. tuberculosis isolates, as well as the primary cultures and follow up MDR cultures from two of these patients. The whole genomes of the M. tuberculosis isolates were sequenced using either the Illumina MiSeq or Illumina HiSeq platforms. Sequences were analysed with an in-house pipeline. Results Using next-generation sequencing in combination with Sanger sequencing and statistical analysis we defined a read frequency cut-off of 30 % to identify low frequency M. tuberculosis variants with high confidence. Using this cut-off we demonstrated a high rate of genetic diversity between single colonies isolated from one population, showing that by using the current sequencing technology, single colonies are not a true reflection of the genetic diversity within a whole population and vice versa. We further showed that numerous heterogeneous variants emerge and then disappear during the evolution of isoniazid resistance within individual patients. Our findings allowed us to formulate a model for the selective bottleneck which occurs during the course of infection, acting as a genomic purification event. Conclusions Our study demonstrated true levels of genetic diversity

GGRaSP: A R-package for selecting representative genomes using Gaussian mixture models.

Science.gov (United States)

Clarke, Thomas H; Brinkac, Lauren M; Sutton, Granger; Fouts, Derrick E

2018-04-14

The vast number of available sequenced bacterial genomes occasionally exceeds the facilities of comparative genomic methods or is dominated by a single outbreak strain, and thus a diverse and representative subset is required. Generation of the reduced subset currently requires a priori supervised clustering and sequence-only selection of medoid genomic sequences, independent of any additional genome metrics or strain attributes. The GGRaSP R-package described below generates a reduced subset of genomes that prioritizes maintaining genomes of interest to the user as well as minimizing the loss of genetic variation. The package also allows for unsupervised clustering by modeling the genomic relationships using a Gaussian Mixture Model to select an appropriate cluster threshold. We demonstrate the capabilities of GGRaSP by generating a reduced list of 315 genomes from a genomic dataset of 4600 Escherichia coli genomes, prioritizing selection by type strain and by genome completeness. GGRaSP is available at https://github.com/JCVenterInstitute/ggrasp/. tclarke@jcvi.org. Supplementary data are available at the GitHub site.

Femtosecond all-polarization-maintaining fiber laser operating at 1028 nm

DEFF Research Database (Denmark)

Olsson, R.K.; Andersen, T.V.; Leick, Lasse

2008-01-01

We present an effective solution for an all-polarization-maintaining modelocked femtosecond fiber laser operating at the central wavelength of 1028 nm. The laser is based on an Yb-doped active fiber. Modelocking is enabled by a semiconductor saturable absorber mirror, and the central wavelength i...... is enforced by a fiber Bragg grating. The laser is self-starting and demonstrates excellent stability gainst Q-switching. Pulse energies reach 13 nJ at 34 MHz repetition rate. External compression leads to near transform-limited pulses of 140 fs.......We present an effective solution for an all-polarization-maintaining modelocked femtosecond fiber laser operating at the central wavelength of 1028 nm. The laser is based on an Yb-doped active fiber. Modelocking is enabled by a semiconductor saturable absorber mirror, and the central wavelength...

Prospects for stability in a nuclear subcontinent

International Nuclear Information System (INIS)

Rajagopal, S; Chari, Sridhar K.

2003-01-01

This book explore the prospects for stability in a nuclear sub-continent. The nonproliferation regimes and nuclear threat reduction, nonproliferation regimes and south asia - is there a meeting point?; maintaining a threshold of strategic autonomy at least cost: continuity in the evolution of India's nuclear policies; role of nuclear doctrines and the state of the armed forces in South Asia; nuclear weapons, deterrence and stability in the international system: South Asian dynamics; assessing China's Asian role and security policies; Kargil war to current threat of war: prospects for stability; discussion; international terrorism and its impact on South Asian stability; a view from Bangladesh etc. are some of the topics covered

gb4gv: a genome browser for geminivirus

Directory of Open Access Journals (Sweden)

Eric S. Ho

2017-04-01

Full Text Available Background Geminiviruses (family Geminiviridae are prevalent plant viruses that imperil agriculture globally, causing serious damage to the livelihood of farmers, particularly in developing countries. The virus evolves rapidly, attributing to its single-stranded genome propensity, resulting in worldwide circulation of diverse and viable genomes. Genomics is a prominent approach taken by researchers in elucidating the infectious mechanism of the virus. Currently, the NCBI Viral Genome website is a popular repository of viral genomes that conveniently provides researchers a centralized data source of genomic information. However, unlike the genome of living organisms, viral genomes most often maintain peculiar characteristics that fit into no single genome architecture. By imposing a unified annotation scheme on the myriad of viral genomes may downplay their hallmark features. For example, the viron of begomoviruses prevailing in America encapsulates two similar-sized circular DNA components and both are required for systemic infection of plants. However, the bipartite components are kept separately in NCBI as individual genomes with no explicit association in linking them. Thus, our goal is to build a comprehensive Geminivirus genomics database, namely gb4gv, that not only preserves genomic characteristics of the virus, but also supplements biologically relevant annotations that help to interrogate this virus, for example, the targeted host, putative iterons, siRNA targets, etc. Methods We have employed manual and automatic methods to curate 508 genomes from four major genera of Geminiviridae, and 161 associated satellites obtained from NCBI RefSeq and PubMed databases. Results These data are available for free access without registration from our website. Besides genomic content, our website provides visualization capability inherited from UCSC Genome Browser. Discussion With the genomic information readily accessible, we hope that our database

Adaptive divergence in the monkey flower Mimulus guttatus is maintained by a chromosomal inversion.

Science.gov (United States)

Twyford, Alex D; Friedman, Jannice

2015-06-01

Organisms exhibit an incredible diversity of life history strategies as adaptive responses to environmental variation. The establishment of novel life history strategies involves multilocus polymorphisms, which will be challenging to establish in the face of gene flow and recombination. Theory predicts that adaptive allelic combinations may be maintained and spread if they occur in genomic regions of reduced recombination, such as chromosomal inversion polymorphisms, yet empirical support for this prediction is lacking. Here, we use genomic data to investigate the evolution of divergent adaptive ecotypes of the yellow monkey flower Mimulus guttatus. We show that a large chromosomal inversion polymorphism is the major region of divergence between geographically widespread annual and perennial ecotypes. In contrast, ∼40,000 single nucleotide polymorphisms in collinear regions of the genome show no signal of life history, revealing genomic patterns of diversity have been shaped by localized homogenizing gene flow and large-scale Pleistocene range expansion. Our results provide evidence for an inversion capturing and protecting loci involved in local adaptation, while also explaining how adaptive divergence can occur with gene flow. © 2015 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Species dispersal rates alter diversity and ecosystem stability in pond metacommunities.

Science.gov (United States)

Howeth, Jennifer G; Leibold, Mathew A

2010-09-01

Metacommunity theory suggests that relationships between diversity and ecosystem stability can be determined by the rate of species dispersal among local communities. The predicted relationships, however, may depend upon the relative strength of local environmental processes and disturbance. Here we evaluate the role of dispersal frequency and local predation perturbations in affecting patterns of diversity and stability in pond plankton metacommunities. Pond metacommunities were composed of three mesocosm communities: one of the three communities maintained constant "press" predation from a selective predator, bluegill sunfish (Lepomis macrochirus); the second community maintained "press" conditions without predation; and the third community experienced recurrent "pulsed" predation from bluegill sunfish. The triads of pond communities were connected at either no, low (0.7%/d), or high (20%/d) planktonic dispersal. Richness and composition of zooplankton and stability of plankton biomass and ecosystem productivity were measured at local and regional spatial scales. Dispersal significantly affected diversity such that local and regional biotas at the low dispersal rate maintained the greatest number of species. The unimodal local dispersal-diversity relationship was predator-dependent, however, as selective press predation excluded species regardless of dispersal. Further, there was no effect of dispersal on beta diversity because predation generated local conditions that selected for distinct community assemblages. Spatial and temporal ecosystem stability responded to dispersal frequency but not predation. Low dispersal destabilized the spatial stability of producer biomass but stabilized temporal ecosystem productivity. The results indicate that selective predation can prevent species augmentation from mass effects but has no apparent influence on stability. Dispersal rates, in contrast, can have significant effects on both species diversity and ecosystem

MendeLIMS: a web-based laboratory information management system for clinical genome sequencing.

Science.gov (United States)

Grimes, Susan M; Ji, Hanlee P

2014-08-27

Large clinical genomics studies using next generation DNA sequencing require the ability to select and track samples from a large population of patients through many experimental steps. With the number of clinical genome sequencing studies increasing, it is critical to maintain adequate laboratory information management systems to manage the thousands of patient samples that are subject to this type of genetic analysis. To meet the needs of clinical population studies using genome sequencing, we developed a web-based laboratory information management system (LIMS) with a flexible configuration that is adaptable to continuously evolving experimental protocols of next generation DNA sequencing technologies. Our system is referred to as MendeLIMS, is easily implemented with open source tools and is also highly configurable and extensible. MendeLIMS has been invaluable in the management of our clinical genome sequencing studies. We maintain a publicly available demonstration version of the application for evaluation purposes at http://mendelims.stanford.edu. MendeLIMS is programmed in Ruby on Rails (RoR) and accesses data stored in SQL-compliant relational databases. Software is freely available for non-commercial use at http://dna-discovery.stanford.edu/software/mendelims/.

Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

Directory of Open Access Journals (Sweden)

Elissa J. Chesler

2016-12-01

Full Text Available Multi-parent populations (MPPs capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility.

Leadership, Literacy, and Translational Expertise in Genomics: Challenges and Opportunities for Social Work.

Science.gov (United States)

Werner-Lin, Allison; McCoyd, Judith L M; Doyle, Maya H; Gehlert, Sarah J

2016-08-01

The transdisciplinary field of genomics is revolutionizing conceptualizations of health, mental health, family formation, and public policy. Many professions must rapidly acquire genomic expertise to maintain state-of-the-art knowledge in their practice. Calls for social workers to build genomic capacity come regularly, yet social work education has not prepared practitioners to join the genomics workforce in providing socially just, ethically informed care to all clients, particularly those from vulnerable and marginalized groups. The authors suggest a set of action steps for bringing social work skills and practice into the 21st century. They propose that good genomic practice entails bringing social work values, skills, and behaviors to genomics. With education and training, social workers may facilitate socially just dissemination of genomic knowledge and services across practice domains. Increased genomic literacy will support the profession's mission to address disparities in health, health care access, and mortality. © 2016 National Association of Social Workers.

Genome editing and assisted reproduction: curing embryos, society or prospective parents?

Science.gov (United States)

Cavaliere, Giulia

2018-06-01

This paper explores the ethics of introducing genome-editing technologies as a new reproductive option. In particular, it focuses on whether genome editing can be considered a morally valuable alternative to preimplantation genetic diagnosis (PGD). Two arguments against the use of genome editing in reproduction are analysed, namely safety concerns and germline modification. These arguments are then contrasted with arguments in favour of genome editing, in particular with the argument of the child's welfare and the argument of parental reproductive autonomy. In addition to these two arguments, genome editing could be considered as a worthy alternative to PGD as it may not be subjected to some of the moral critiques moved against this technology. Even if these arguments offer sound reasons in favour of introducing genome editing as a new reproductive option, I conclude that these benefits should be balanced against other considerations. More specifically, I maintain that concerns regarding the equality of access to assisted reproduction and the allocation of scarce resources should be addressed prior to the adoption of genome editing as a new reproductive option.

Genome stability: recent insights in the topoisomerase reverse gyrase and thermophilic DNA alkyltransferase.

Science.gov (United States)

Vettone, Antonella; Perugino, Giuseppe; Rossi, Mosè; Valenti, Anna; Ciaramella, Maria

2014-09-01

Repair and defence of genome integrity from endogenous and environmental hazard is a primary need for all organisms. Natural selection has driven the evolution of multiple cell pathways to deal with different DNA damaging agents. Failure of such processes can hamper cell functions and induce inheritable mutations, which in humans may cause cancerogenicity or certain genetic syndromes, and ultimately cell death. A special case is that of hyperthermophilic bacteria and archaea, flourishing at temperatures higher than 80 °C, conditions that favor genome instability and thus call for specific, highly efficient or peculiar mechanisms to keep their genome intact and functional. Over the last few years, numerous studies have been performed on the activity, function, regulation, physical and functional interaction of enzymes and proteins from hyperthermophilic microorganisms that are able to bind, repair, bypass damaged DNA, or modify its structure or conformation. The present review is focused on two enzymes that act on DNA catalyzing unique reactions: reverse gyrase and DNA alkyltransferase. Although both enzymes belong to evolutionary highly conserved protein families present in organisms of the three domains (Eucarya, Bacteria and Archaea), recently characterized members from hyperthermophilic archaea show both common and peculiar features.

Maintaining Breast Cancer Specimen Integrity and Individual or Simultaneous Extraction of Quality DNA, RNA, and Proteins from Allprotect-Stabilized and Nonstabilized Tissue Samples

LENUS (Irish Health Repository)

Mee, Blanaid C.

2011-12-29

The Saint James\\'s Hospital Biobank was established in 2008, to develop a high-quality breast tissue BioResource, as a part of the breast cancer clinical care pathway. The aims of this work were: (1) to ascertain the quality of RNA, DNA, and protein in biobanked carcinomas and normal breast tissues, (2) to assess the efficacy of AllPrep® (Qiagen) in isolating RNA, DNA, and protein simultaneously, (3) to compare AllPrep with RNEasy® and QIAamp® (both Qiagen), and (4) to examine the effectiveness of Allprotect® (Qiagen), a new tissue stabilization medium in preserving DNA, RNA, and proteins. One hundred eleven frozen samples of carcinoma and normal breast tissue were analyzed. Tumor and normal tissue morphology were confirmed by frozen sections. Tissue type, tissue treatment (Allprotect vs. no Allprotect), extraction kit, and nucleic acid quantification were analyzed by utilizing a 4 factorial design (SPSS PASW 18 Statistics Software®). QIAamp (DNA isolation), AllPrep (DNA, RNA, and Protein isolation), and RNeasy (RNA isolation) kits were assessed and compared. Mean DNA yield and A260\\/280 values using QIAamp were 33.2 ng\\/μL and 1.86, respectively, and using AllPrep were 23.2 ng\\/μL and 1.94. Mean RNA yield and RNA Integrity Number (RIN) values with RNeasy were 73.4 ng\\/μL and 8.16, respectively, and with AllPrep were 74.8 ng\\/μL and 7.92. Allprotect-treated tissues produced higher RIN values of borderline significance (P=0.055). No discernible loss of RNA stability was detected after 6 h incubation of stabilized or nonstabilized tissues at room temperature or 4°C or in 9 freeze-thaw cycles. Allprotect requires further detailed evaluation, but we consider AllPrep to be an excellent option for the simultaneous extraction of RNA, DNA, and protein from tumor and normal breast tissues. The essential presampling procedures that maintain the diagnostic integrity of pathology specimens do not appear to compromise the quality of molecular isolates.

Mitosis, double strand break repair, and telomeres: a view from the end: how telomeres and the DNA damage response cooperate during mitosis to maintain genome stability.

Science.gov (United States)

Cesare, Anthony J

2014-11-01

Double strand break (DSB) repair is suppressed during mitosis because RNF8 and downstream DNA damage response (DDR) factors, including 53BP1, do not localize to mitotic chromatin. Discovery of the mitotic kinase-dependent mechanism that inhibits DSB repair during cell division was recently reported. It was shown that restoring mitotic DSB repair was detrimental, resulting in repair dependent genome instability and covalent telomere fusions. The telomere DDR that occurs naturally during cellular aging and in cancer is known to be refractory to G2/M checkpoint activation. Such DDR-positive telomeres, and those that occur as part of the telomere-dependent prolonged mitotic arrest checkpoint, normally pass through mitosis without covalent ligation, but result in cell growth arrest in G1 phase. The discovery that suppressing DSB repair during mitosis may function primarily to protect DDR-positive telomeres from fusing during cell division reinforces the unique cooperation between telomeres and the DDR to mediate tumor suppression. © 2014 The Author. Bioessays published by WILEY Periodicals, Inc.

MIPS: analysis and annotation of proteins from whole genomes.

Science.gov (United States)

Mewes, H W; Amid, C; Arnold, R; Frishman, D; Güldener, U; Mannhaupt, G; Münsterkötter, M; Pagel, P; Strack, N; Stümpflen, V; Warfsmann, J; Ruepp, A

2004-01-01

The Munich Information Center for Protein Sequences (MIPS-GSF), Neuherberg, Germany, provides protein sequence-related information based on whole-genome analysis. The main focus of the work is directed toward the systematic organization of sequence-related attributes as gathered by a variety of algorithms, primary information from experimental data together with information compiled from the scientific literature. MIPS maintains automatically generated and manually annotated genome-specific databases, develops systematic classification schemes for the functional annotation of protein sequences and provides tools for the comprehensive analysis of protein sequences. This report updates the information on the yeast genome (CYGD), the Neurospora crassa genome (MNCDB), the database of complete cDNAs (German Human Genome Project, NGFN), the database of mammalian protein-protein interactions (MPPI), the database of FASTA homologies (SIMAP), and the interface for the fast retrieval of protein-associated information (QUIPOS). The Arabidopsis thaliana database, the rice database, the plant EST databases (MATDB, MOsDB, SPUTNIK), as well as the databases for the comprehensive set of genomes (PEDANT genomes) are described elsewhere in the 2003 and 2004 NAR database issues, respectively. All databases described, and the detailed descriptions of our projects can be accessed through the MIPS web server (http://mips.gsf.de).

Stability of Genome Composition and Recombination between Homoeologous Chromosomes in Festulolium (Festuca × Lolium) Cultivars

Czech Academy of Sciences Publication Activity Database

Kopecký, David; Šimoníková, Denisa; Ghesquière, M.; Doležel, Jaroslav

2017-01-01

Roč. 151, č. 2 (2017), s. 106-114 ISSN 1424-8581 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Festulolium * Genome composition * Genomic in situ hybridization * Grass hybrids * Homoeologous recombination * Lolium × Festuca Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 1.354, year: 2016

Evolutionary maintenance of filovirus-like genes in bat genomes

Directory of Open Access Journals (Sweden)

Taylor Derek J

2011-11-01

Full Text Available Abstract Background Little is known of the biological significance and evolutionary maintenance of integrated non-retroviral RNA virus genes in eukaryotic host genomes. Here, we isolated novel filovirus-like genes from bat genomes and tested for evolutionary maintenance. We also estimated the age of filovirus VP35-like gene integrations and tested the phylogenetic hypotheses that there is a eutherian mammal clade and a marsupial/ebolavirus/Marburgvirus dichotomy for filoviruses. Results We detected homologous copies of VP35-like and NP-like gene integrations in both Old World and New World species of Myotis (bats. We also detected previously unknown VP35-like genes in rodents that are positionally homologous. Comprehensive phylogenetic estimates for filovirus NP-like and VP35-like loci support two main clades with a marsupial and a rodent grouping within the ebolavirus/Lloviu virus/Marburgvirus clade. The concordance of VP35-like, NP-like and mitochondrial gene trees with the expected species tree supports the notion that the copies we examined are orthologs that predate the global spread and radiation of the genus Myotis. Parametric simulations were consistent with selective maintenance for the open reading frame (ORF of VP35-like genes in Myotis. The ORF of the filovirus-like VP35 gene has been maintained in bat genomes for an estimated 13. 4 MY. ORFs were disrupted for the NP-like genes in Myotis. Likelihood ratio tests revealed that a model that accommodates positive selection is a significantly better fit to the data than a model that does not allow for positive selection for VP35-like sequences. Moreover, site-by-site analysis of selection using two methods indicated at least 25 sites in the VP35-like alignment are under positive selection in Myotis. Conclusions Our results indicate that filovirus-like elements have significance beyond genomic imprints of prior infection. That is, there appears to be, or have been, functionally maintained

Comparative genomics of Wolbachia and the bacterial species concept.

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Kirsten Maren Ellegaard

2013-04-01

Full Text Available The importance of host-specialization to speciation processes in obligate host-associated bacteria is well known, as is also the ability of recombination to generate cohesion in bacterial populations. However, whether divergent strains of highly recombining intracellular bacteria, such as Wolbachia, can maintain their genetic distinctness when infecting the same host is not known. We first developed a protocol for the genome sequencing of uncultivable endosymbionts. Using this method, we have sequenced the complete genomes of the Wolbachia strains wHa and wNo, which occur as natural double infections in Drosophila simulans populations on the Seychelles and in New Caledonia. Taxonomically, wHa belong to supergroup A and wNo to supergroup B. A comparative genomics study including additional strains supported the supergroup classification scheme and revealed 24 and 33 group-specific genes, putatively involved in host-adaptation processes. Recombination frequencies were high for strains of the same supergroup despite different host-preference patterns, leading to genomic cohesion. The inferred recombination fragments for strains of different supergroups were of short sizes, and the genomes of the co-infecting Wolbachia strains wHa and wNo were not more similar to each other and did not share more genes than other A- and B-group strains that infect different hosts. We conclude that Wolbachia strains of supergroup A and B represent genetically distinct clades, and that strains of different supergroups can co-exist in the same arthropod host without converging into the same species. This suggests that the supergroups are irreversibly separated and that barriers other than host-specialization are able to maintain distinct clades in recombining endosymbiont populations. Acquiring a good knowledge of the barriers to genetic exchange in Wolbachia will advance our understanding of how endosymbiont communities are constructed from vertically and horizontally

308 Building zone I stabilization and confinement

International Nuclear Information System (INIS)

Metcalf, I.L.; Schwartz, K.E.; Rich, J.W.; Benecke, M.W.; Lanham, G.W.

1994-08-01

The 308 Building located on the Hanford Site near Richland, Washington, is currently in transition to shutdown status. After this transition is complete, the facility will be maintained/surveilled and given to the U.S. Department of Energy Office of Facility Transition and Management (EM-60) for utilization, remedial action, or decontamination and decommissioning (D ampersand D). This may require that the facility be maintained in the shutdown status for as long as 30 yrs. To date, all of the special nuclear material (SNM) has been removed, potential fuel supply equipment preserved, surplus materials and equipment excessed, and enclosure cleanup and stabilization completed. A major activity in support of the 308 Building shutdown was the cleanup and stabilization of the enclosures and surface contamination areas. This document discusses the specific designs, processes, and methods used to stabilize and confine the radiological material within the enclosure and exhaust ducts to allow the shutdown of the active support systems. The process and designs employed were effective, yet simple, and maximized the use of current technologies and commercial products

The Glyphosate-Based Herbicide Roundup Does not Elevate Genome-Wide Mutagenesis of Escherichia coli.

Science.gov (United States)

Tincher, Clayton; Long, Hongan; Behringer, Megan; Walker, Noah; Lynch, Michael

2017-10-05

Mutations induced by pollutants may promote pathogen evolution, for example by accelerating mutations conferring antibiotic resistance. Generally, evaluating the genome-wide mutagenic effects of long-term sublethal pollutant exposure at single-nucleotide resolution is extremely difficult. To overcome this technical barrier, we use the mutation accumulation/whole-genome sequencing (MA/WGS) method as a mutagenicity test, to quantitatively evaluate genome-wide mutagenesis of Escherichia coli after long-term exposure to a wide gradient of the glyphosate-based herbicide (GBH) Roundup Concentrate Plus. The genome-wide mutation rate decreases as GBH concentration increases, suggesting that even long-term GBH exposure does not compromise the genome stability of bacteria. Copyright © 2017 Tincher et al.

Synthetic Jets Flow Control on a vertical stabilizer

Science.gov (United States)

Rathay, Nicholas; Boucher, Matthew; Amitay, Michael

2011-11-01

The vertical stabilizer on most commercial transport aircraft is much larger than required for stability and control. The tail is significantly oversized in order to maintain controllability in the event of asymmetric engine failure and meet flying qualities requirements related to dynamic motion. Using aerodynamic flow control techniques, it may be possible to reduce the size of the tail while maintaining similar control authority during inclement flight conditions. Reducing the size of the tail decreases the weight and the drag of the airplane, which results in considerable savings in fuel costs. In this work, it is shown that synthetic jet (zero-net-mass-flux) actuators are capable of reattaching the separated flow on the rudder and augmenting the performance of the stabilizer. Experiments were conducted in an open-return wind tunnel on a 1/25th scale model of a vertical stabilizer and a partial fuselage section. The surface pressure, aerodynamic loads and data acquired with a Stereo PIV system were used to investigate the effectiveness of this technology as well as provide a more detailed analysis of the flowfield and showed that the synthetic jets are capable of augmenting the side-force by up to 20%.

RatMap--rat genome tools and data.

Science.gov (United States)

Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M; Ståhl, Fredrik

2005-01-01

The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB-Genetics at Goteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided.

RatMap—rat genome tools and data

Science.gov (United States)

Petersen, Greta; Johnson, Per; Andersson, Lars; Klinga-Levan, Karin; Gómez-Fabre, Pedro M.; Ståhl, Fredrik

2005-01-01

The rat genome database RatMap (http://ratmap.org or http://ratmap.gen.gu.se) has been one of the main resources for rat genome information since 1994. The database is maintained by CMB–Genetics at Göteborg University in Sweden and provides information on rat genes, polymorphic rat DNA-markers and rat quantitative trait loci (QTLs), all curated at RatMap. The database is under the supervision of the Rat Gene and Nomenclature Committee (RGNC); thus much attention is paid to rat gene nomenclature. RatMap presents information on rat idiograms, karyotypes and provides a unified presentation of the rat genome sequence and integrated rat linkage maps. A set of tools is also available to facilitate the identification and characterization of rat QTLs, as well as the estimation of exon/intron number and sizes in individual rat genes. Furthermore, comparative gene maps of rat in regard to mouse and human are provided. PMID:15608244

lncRNA Panct1 Maintains Mouse Embryonic Stem Cell Identity by Regulating TOBF1 Recruitment to Oct-Sox Sequences in Early G1

DEFF Research Database (Denmark)

Chakraborty, Debojyoti; Paszkowski-Rogacz, Maciej; Berger, Nicolas

2017-01-01

-chromosome-encoded protein A830080D01Rik, hereafter referred to as transient octamer binding factor 1 (TOBF1), to genomic sites resembling the canonical Oct-Sox motif. TOBF1 physically interacts with Panct1 and exhibits a cell-cycle-specific punctate localization in ESCs. At the chromatin level, this correlates with its......-cycle-dependent manner and suggest that lncRNAs might function as barcodes for identifying genomic addresses for maintaining cellular states....

A Rad53 independent function of Rad9 becomes crucial for genome maintenance in the absence of the Recq helicase Sgs1.

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Ida Nielsen

Full Text Available The conserved family of RecQ DNA helicases consists of caretaker tumour suppressors, that defend genome integrity by acting on several pathways of DNA repair that maintain genome stability. In budding yeast, Sgs1 is the sole RecQ helicase and it has been implicated in checkpoint responses, replisome stability and dissolution of double Holliday junctions during homologous recombination. In this study we investigate a possible genetic interaction between SGS1 and RAD9 in the cellular response to methyl methane sulphonate (MMS induced damage and compare this with the genetic interaction between SGS1 and RAD24. The Rad9 protein, an adaptor for effector kinase activation, plays well-characterized roles in the DNA damage checkpoint response, whereas Rad24 is characterized as a sensor protein also in the DNA damage checkpoint response. Here we unveil novel insights into the cellular response to MMS-induced damage. Specifically, we show a strong synergistic functionality between SGS1 and RAD9 for recovery from MMS induced damage and for suppression of gross chromosomal rearrangements, which is not the case for SGS1 and RAD24. Intriguingly, it is a Rad53 independent function of Rad9, which becomes crucial for genome maintenance in the absence of Sgs1. Despite this, our dissection of the MMS checkpoint response reveals parallel, but unequal pathways for Rad53 activation and highlights significant differences between MMS- and hydroxyurea (HU-induced checkpoint responses with relation to the requirement of the Sgs1 interacting partner Topoisomerase III (Top3. Thus, whereas earlier studies have documented a Top3-independent role of Sgs1 for an HU-induced checkpoint response, we show here that upon MMS treatment, Sgs1 and Top3 together define a minor but parallel pathway to that of Rad9.

The genomic landscape at a late stage of stickleback speciation: High genomic divergence interspersed by small localized regions of introgression.

Directory of Open Access Journals (Sweden)

Mark Ravinet

2018-05-01

Full Text Available Speciation is a continuous process and analysis of species pairs at different stages of divergence provides insight into how it unfolds. Previous genomic studies on young species pairs have revealed peaks of divergence and heterogeneous genomic differentiation. Yet less known is how localised peaks of differentiation progress to genome-wide divergence during the later stages of speciation in the presence of persistent gene flow. Spanning the speciation continuum, stickleback species pairs are ideal for investigating how genomic divergence builds up during speciation. However, attention has largely focused on young postglacial species pairs, with little knowledge of the genomic signatures of divergence and introgression in older stickleback systems. The Japanese stickleback species pair, composed of the Pacific Ocean three-spined stickleback (Gasterosteus aculeatus and the Japan Sea stickleback (G. nipponicus, which co-occur in the Japanese islands, is at a late stage of speciation. Divergence likely started well before the end of the last glacial period and crosses between Japan Sea females and Pacific Ocean males result in hybrid male sterility. Here we use coalescent analyses and Approximate Bayesian Computation to show that the two species split approximately 0.68-1 million years ago but that they have continued to exchange genes at a low rate throughout divergence. Population genomic data revealed that, despite gene flow, a high level of genomic differentiation is maintained across the majority of the genome. However, we identified multiple, small regions of introgression, occurring mainly in areas of low recombination rate. Our results demonstrate that a high level of genome-wide divergence can establish in the face of persistent introgression and that gene flow can be localized to small genomic regions at the later stages of speciation with gene flow.

The genomic landscape at a late stage of stickleback speciation: High genomic divergence interspersed by small localized regions of introgression.

Science.gov (United States)

Ravinet, Mark; Yoshida, Kohta; Shigenobu, Shuji; Toyoda, Atsushi; Fujiyama, Asao; Kitano, Jun

2018-05-01

Speciation is a continuous process and analysis of species pairs at different stages of divergence provides insight into how it unfolds. Previous genomic studies on young species pairs have revealed peaks of divergence and heterogeneous genomic differentiation. Yet less known is how localised peaks of differentiation progress to genome-wide divergence during the later stages of speciation in the presence of persistent gene flow. Spanning the speciation continuum, stickleback species pairs are ideal for investigating how genomic divergence builds up during speciation. However, attention has largely focused on young postglacial species pairs, with little knowledge of the genomic signatures of divergence and introgression in older stickleback systems. The Japanese stickleback species pair, composed of the Pacific Ocean three-spined stickleback (Gasterosteus aculeatus) and the Japan Sea stickleback (G. nipponicus), which co-occur in the Japanese islands, is at a late stage of speciation. Divergence likely started well before the end of the last glacial period and crosses between Japan Sea females and Pacific Ocean males result in hybrid male sterility. Here we use coalescent analyses and Approximate Bayesian Computation to show that the two species split approximately 0.68-1 million years ago but that they have continued to exchange genes at a low rate throughout divergence. Population genomic data revealed that, despite gene flow, a high level of genomic differentiation is maintained across the majority of the genome. However, we identified multiple, small regions of introgression, occurring mainly in areas of low recombination rate. Our results demonstrate that a high level of genome-wide divergence can establish in the face of persistent introgression and that gene flow can be localized to small genomic regions at the later stages of speciation with gene flow.

Mitigating Mitochondrial Genome Erosion Without Recombination.

Science.gov (United States)

Radzvilavicius, Arunas L; Kokko, Hanna; Christie, Joshua R

2017-11-01

Mitochondria are ATP-producing organelles of bacterial ancestry that played a key role in the origin and early evolution of complex eukaryotic cells. Most modern eukaryotes transmit mitochondrial genes uniparentally, often without recombination among genetically divergent organelles. While this asymmetric inheritance maintains the efficacy of purifying selection at the level of the cell, the absence of recombination could also make the genome susceptible to Muller's ratchet. How mitochondria escape this irreversible defect accumulation is a fundamental unsolved question. Occasional paternal leakage could in principle promote recombination, but it would also compromise the purifying selection benefits of uniparental inheritance. We assess this tradeoff using a stochastic population-genetic model. In the absence of recombination, uniparental inheritance of freely-segregating genomes mitigates mutational erosion, while paternal leakage exacerbates the ratchet effect. Mitochondrial fusion-fission cycles ensure independent genome segregation, improving purifying selection. Paternal leakage provides opportunity for recombination to slow down the mutation accumulation, but always at a cost of increased steady-state mutation load. Our findings indicate that random segregation of mitochondrial genomes under uniparental inheritance can effectively combat the mutational meltdown, and that homologous recombination under paternal leakage might not be needed. Copyright © 2017 by the Genetics Society of America.

Stability analysis of free piston Stirling engines

Science.gov (United States)

Bégot, Sylvie; Layes, Guillaume; Lanzetta, François; Nika, Philippe

2013-03-01

This paper presents a stability analysis of a free piston Stirling engine. The model and the detailed calculation of pressures losses are exposed. Stability of the machine is studied by the observation of the eigenvalues of the model matrix. Model validation based on the comparison with NASA experimental results is described. The influence of operational and construction parameters on performance and stability issues is exposed. The results show that most parameters that are beneficial for machine power seem to induce irregular mechanical characteristics with load, suggesting that self-sustained oscillations could be difficult to maintain and control.

The Solanum commersonii Genome Sequence Provides Insights into Adaptation to Stress Conditions and Genome Evolution of Wild Potato Relatives

Science.gov (United States)

Aversano, Riccardo; Contaldi, Felice; Ercolano, Maria Raffaella; Grosso, Valentina; Iorizzo, Massimo; Tatino, Filippo; Xumerle, Luciano; Dal Molin, Alessandra; Avanzato, Carla; Ferrarini, Alberto; Delledonne, Massimo; Sanseverino, Walter; Cigliano, Riccardo Aiese; Capella-Gutierrez, Salvador; Gabaldón, Toni; Frusciante, Luigi; Bradeen, James M.; Carputo, Domenico

2015-01-01

Here, we report the draft genome sequence of Solanum commersonii, which consists of ∼830 megabases with an N50 of 44,303 bp anchored to 12 chromosomes, using the potato (Solanum tuberosum) genome sequence as a reference. Compared with potato, S. commersonii shows a striking reduction in heterozygosity (1.5% versus 53 to 59%), and differences in genome sizes were mainly due to variations in intergenic sequence length. Gene annotation by ab initio prediction supported by RNA-seq data produced a catalog of 1703 predicted microRNAs, 18,882 long noncoding RNAs of which 20% are shown to target cold-responsive genes, and 39,290 protein-coding genes with a significant repertoire of nonredundant nucleotide binding site-encoding genes and 126 cold-related genes that are lacking in S. tuberosum. Phylogenetic analyses indicate that domesticated potato and S. commersonii lineages diverged ∼2.3 million years ago. Three duplication periods corresponding to genome enrichment for particular gene families related to response to salt stress, water transport, growth, and defense response were discovered. The draft genome sequence of S. commersonii substantially increases our understanding of the domesticated germplasm, facilitating translation of acquired knowledge into advances in crop stability in light of global climate and environmental changes. PMID:25873387

Methods and devices for maintaining a resonant wavelength of a photonic microresonator

Science.gov (United States)

Jones, Adam; Zortman, William A.

2015-07-14

A photonic microresonator incorporates a localized heater element within a section of an optical bus waveguide that is in proximity to the resonator structure. The application of an adjustable control voltage to the heater element provides a localized change in the refractive index value of the bus waveguide, compensating for temperature-induced wavelength drift and maintaining a stabilized value of the microresonator's resonant wavelength.

Experimental Evolution Reveals Interplay between Sch9 and Polyploid Stability in Yeast.

Directory of Open Access Journals (Sweden)

Yi-Jin Lu

2016-11-01

Full Text Available Polyploidization has crucial impacts on the evolution of different eukaryotic lineages including fungi, plants and animals. Recent genome data suggest that, for many polyploidization events, all duplicated chromosomes are maintained and genome reorganizations occur much later during evolution. However, newly-formed polyploid genomes are intrinsically unstable and often quickly degenerate into aneuploidy or diploidy. The transition between these two states remains enigmatic. In this study, laboratory evolution experiments were conducted to investigate this phenomenon. We show that robust tetraploidy is achieved in evolved yeast cells by increasing the abundance of Sch9-a protein kinase activated by the TORC1 (Target of Rapamycin Complex 1 and other signaling pathways. Overexpressing SCH9, but not TOR1, allows newly-formed tetraploids to exhibit evolved phenotypes and knocking out SCH9 diminishes the evolved phenotypes. Furthermore, when cells were challenged with conditions causing ancestral cells to evolve aneuploidy, tetraploidy was maintained in the evolved lines. Our results reveal a determinant role for Sch9 during the early stage of polyploid evolution.

Genomic analyses of modern dog breeds.

Science.gov (United States)

Parker, Heidi G

2012-02-01

A rose may be a rose by any other name, but when you call a dog a poodle it becomes a very different animal than if you call it a bulldog. Both the poodle and the bulldog are examples of dog breeds of which there are >400 recognized worldwide. Breed creation has played a significant role in shaping the modern dog from the length of his leg to the cadence of his bark. The selection and line-breeding required to maintain a breed has also reshaped the genome of the dog, resulting in a unique genetic pattern for each breed. The breed-based population structure combined with extensive morphologic variation and shared human environments have made the dog a popular model for mapping both simple and complex traits and diseases. In order to obtain the most benefit from the dog as a genetic system, it is necessary to understand the effect structured breeding has had on the genome of the species. That is best achieved by looking at genomic analyses of the breeds, their histories, and their relationships to each other.

Exceptionally high levels of recombination across the honey bee genome.

Science.gov (United States)

Beye, Martin; Gattermeier, Irene; Hasselmann, Martin; Gempe, Tanja; Schioett, Morten; Baines, John F; Schlipalius, David; Mougel, Florence; Emore, Christine; Rueppell, Olav; Sirviö, Anu; Guzmán-Novoa, Ernesto; Hunt, Greg; Solignac, Michel; Page, Robert E

2006-11-01

The first draft of the honey bee genome sequence and improved genetic maps are utilized to analyze a genome displaying 10 times higher levels of recombination (19 cM/Mb) than previously analyzed genomes of higher eukaryotes. The exceptionally high recombination rate is distributed genome-wide, but varies by two orders of magnitude. Analysis of chromosome, sequence, and gene parameters with respect to recombination showed that local recombination rate is associated with distance to the telomere, GC content, and the number of simple repeats as described for low-recombining genomes. Recombination rate does not decrease with chromosome size. On average 5.7 recombination events per chromosome pair per meiosis are found in the honey bee genome. This contrasts with a wide range of taxa that have a uniform recombination frequency of about 1.6 per chromosome pair. The excess of recombination activity does not support a mechanistic role of recombination in stabilizing pairs of homologous chromosome during chromosome pairing. Recombination rate is associated with gene size, suggesting that introns are larger in regions of low recombination and may improve the efficacy of selection in these regions. Very few transposons and no retrotransposons are present in the high-recombining genome. We propose evolutionary explanations for the exceptionally high genome-wide recombination rate.

Involvement of Disperse Repetitive Sequences in Wheat/Rye Genome Adjustment

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Manuela Silva

2012-07-01

Full Text Available The union of different genomes in the same nucleus frequently results in hybrid genotypes with improved genome plasticity related to both genome remodeling events and changes in gene expression. Most modern cereal crops are polyploid species. Triticale, synthesized by the cross between wheat and rye, constitutes an excellent model to study polyploidization functional implications. We intend to attain a deeper knowledge of dispersed repetitive sequence involvement in parental genome reshuffle in triticale and in wheat-rye addition lines that have the entire wheat genome plus each rye chromosome pair. Through Random Amplified Polymorphic DNA (RAPD analysis with OPH20 10-mer primer we unraveled clear alterations corresponding to the loss of specific bands from both parental genomes. Moreover, the sequential nature of those events was revealed by the increased absence of rye-origin bands in wheat-rye addition lines in comparison with triticale. Remodeled band sequencing revealed that both repetitive and coding genome domains are affected in wheat-rye hybrid genotypes. Additionally, the amplification and sequencing of pSc20H internal segments showed that the disappearance of parental bands may result from restricted sequence alterations and unraveled the involvement of wheat/rye related repetitive sequences in genome adjustment needed for hybrid plant stabilization.

Sustained levels of FGF2 maintain undifferentiated stem cell cultures with biweekly feeding.

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Steven Lotz

Full Text Available An essential aspect of stem cell culture is the successful maintenance of the undifferentiated state. Many types of stem cells are FGF2 dependent, and pluripotent stem cells are maintained by replacing FGF2-containing media daily, while tissue-specific stem cells are typically fed every 3rd day. Frequent feeding, however, results in significant variation in growth factor levels due to FGF2 instability, which limits effective maintenance due to spontaneous differentiation. We report that stabilization of FGF2 levels using controlled release PLGA microspheres improves expression of stem cell markers, increases stem cell numbers and decreases spontaneous differentiation. The controlled release FGF2 additive reduces the frequency of media changes needed to maintain stem cell cultures, so that human embryonic stem cells and induced pluripotent stem cells can be maintained successfully with biweekly feedings.

Complete replication-competent adenovirus 11p vectors with E1 or E3 insertions show improved heat stability

Energy Technology Data Exchange (ETDEWEB)

Mei, Ya-Fang, E-mail: ya-fang.mei@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden); Wu, Haidong, E-mail: haidong.wu@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden); Hultenby, Kjell, E-mail: kjell.hultenby@ki.se [Division of Clinical Research Centre, Department of Laboratory Medicine, Karolinska Institute, SE-14186 Stockholm (Sweden); Silver, Jim, E-mail: jim.silver@umu.se [Department of Clinical Microbiology and Virology, Umeå University, SE-901 85 Umeå (Sweden)

2016-10-15

Conventional adenovirus vectors harboring E1 or E3 deletions followed by the insertion of an exogenous gene show considerably reduced virion stability. Here, we report strategies to generate complete replication-competent Ad11p(RCAd11p) vectors that overcome the above disadvantage. A GFP cassette was successfully introduced either upstream of E1A or in the E3A region. The resulting vectors showed high expression levels of the hexon and E1genes and also strongly induced the cytopathic effect in targeted cells. When harboring oversized genomes, the RCAd11pE1 and RCAd11pE3 vectors showed significantly improved heat stability in comparison to Ad11pwt;of the three, RCAd11pE3 was the most tolerant to heat treatment. Electron microscopy showed that RCAd11pE3, RCAd11pE1, Ad11pwt, and Ad11pE1 Delmanifested dominant, moderate, minimum, or no full virus particles after heat treatment at 47 °C for 5 h. Our results demonstrated that both genome size and the insertion site in the viral genome affect virion stability. -- Highlights: •Replicating adenovirus 11p GFP vectors at the E1 or E3 region were generated. •RCAd11pE3 and RCAd11pE1 vectors manifested significantly improved heat stability. •RCAd11pE3 and RCAd11pE1 showed more full viral particles than Ad11pwt after heating. •We demonstrated that both genome size and the insertion site affect virion stability.

Complete replication-competent adenovirus 11p vectors with E1 or E3 insertions show improved heat stability

International Nuclear Information System (INIS)

Mei, Ya-Fang; Wu, Haidong; Hultenby, Kjell; Silver, Jim

2016-01-01

Conventional adenovirus vectors harboring E1 or E3 deletions followed by the insertion of an exogenous gene show considerably reduced virion stability. Here, we report strategies to generate complete replication-competent Ad11p(RCAd11p) vectors that overcome the above disadvantage. A GFP cassette was successfully introduced either upstream of E1A or in the E3A region. The resulting vectors showed high expression levels of the hexon and E1genes and also strongly induced the cytopathic effect in targeted cells. When harboring oversized genomes, the RCAd11pE1 and RCAd11pE3 vectors showed significantly improved heat stability in comparison to Ad11pwt;of the three, RCAd11pE3 was the most tolerant to heat treatment. Electron microscopy showed that RCAd11pE3, RCAd11pE1, Ad11pwt, and Ad11pE1 Delmanifested dominant, moderate, minimum, or no full virus particles after heat treatment at 47 °C for 5 h. Our results demonstrated that both genome size and the insertion site in the viral genome affect virion stability. -- Highlights: •Replicating adenovirus 11p GFP vectors at the E1 or E3 region were generated. •RCAd11pE3 and RCAd11pE1 vectors manifested significantly improved heat stability. •RCAd11pE3 and RCAd11pE1 showed more full viral particles than Ad11pwt after heating. •We demonstrated that both genome size and the insertion site affect virion stability.

Codon usage bias: causative factors, quantification methods and genome-wide patterns: with emphasis on insect genomes.

Science.gov (United States)

Behura, Susanta K; Severson, David W

2013-02-01

Codon usage bias refers to the phenomenon where specific codons are used more often than other synonymous codons during translation of genes, the extent of which varies within and among species. Molecular evolutionary investigations suggest that codon bias is manifested as a result of balance between mutational and translational selection of such genes and that this phenomenon is widespread across species and may contribute to genome evolution in a significant manner. With the advent of whole-genome sequencing of numerous species, both prokaryotes and eukaryotes, genome-wide patterns of codon bias are emerging in different organisms. Various factors such as expression level, GC content, recombination rates, RNA stability, codon position, gene length and others (including environmental stress and population size) can influence codon usage bias within and among species. Moreover, there has been a continuous quest towards developing new concepts and tools to measure the extent of codon usage bias of genes. In this review, we outline the fundamental concepts of evolution of the genetic code, discuss various factors that may influence biased usage of synonymous codons and then outline different principles and methods of measurement of codon usage bias. Finally, we discuss selected studies performed using whole-genome sequences of different insect species to show how codon bias patterns vary within and among genomes. We conclude with generalized remarks on specific emerging aspects of codon bias studies and highlight the recent explosion of genome-sequencing efforts on arthropods (such as twelve Drosophila species, species of ants, honeybee, Nasonia and Anopheles mosquitoes as well as the recent launch of a genome-sequencing project involving 5000 insects and other arthropods) that may help us to understand better the evolution of codon bias and its biological significance. © 2012 The Authors. Biological Reviews © 2012 Cambridge Philosophical Society.

A DNMT3A2-HDAC2 Complex Is Essential for Genomic Imprinting and Genome Integrity in Mouse Oocytes

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Pengpeng Ma

2015-11-01

Full Text Available Maternal genomic imprints are established during oogenesis. Histone deacetylases (HDACs 1 and 2 are required for oocyte development in mouse, but their role in genomic imprinting is unknown. We find that Hdac1:Hdac2−/− double-mutant growing oocytes exhibit global DNA hypomethylation and fail to establish imprinting marks for Igf2r, Peg3, and Srnpn. Global hypomethylation correlates with increased retrotransposon expression and double-strand DNA breaks. Nuclear-associated DNMT3A2 is reduced in double-mutant oocytes, and injecting these oocytes with Hdac2 partially restores DNMT3A2 nuclear staining. DNMT3A2 co-immunoprecipitates with HDAC2 in mouse embryonic stem cells. Partial loss of nuclear DNMT3A2 and HDAC2 occurs in Sin3a−/− oocytes, which exhibit decreased DNA methylation of imprinting control regions for Igf2r and Srnpn, but not Peg3. These results suggest seminal roles of HDAC1/2 in establishing maternal genomic imprints and maintaining genomic integrity in oocytes mediated in part through a SIN3A complex that interacts with DNMT3A2.

Functional stability of cerebral circulatory system

Science.gov (United States)

Moskalenko, Y. Y.

1980-01-01

The functional stability of the cerebral circulation system seems to be based on the active mechanisms and on those stemming from specific of the biophysical structure of the system under study. This latter parameter has some relevant criteria for its quantitative estimation. The data obtained suggest that the essential part of the mechanism for active responses of cerebral vessels which maintains the functional stability of this portion of the vascular system, consists of a neurogenic component involving central nervous structures localized, for instance, in the medulla oblongata.

Evolution of molecular phenotypes under stabilizing selection

International Nuclear Information System (INIS)

Nourmohammad, Armita; Schiffels, Stephan; Lässig, Michael

2013-01-01

Molecular phenotypes are important links between genomic information and organismic functions, fitness, and evolution. Complex phenotypes, which are also called quantitative traits, often depend on multiple genomic loci. Their evolution builds on genome evolution in a complicated way, which involves selection, genetic drift, mutations and recombination. Here we develop a coarse-grained evolutionary statistics for phenotypes, which decouples from details of the underlying genotypes. We derive approximate evolution equations for the distribution of phenotype values within and across populations. This dynamics covers evolutionary processes at high and low recombination rates, that is, it applies to sexual and asexual populations. In a fitness landscape with a single optimal phenotype value, the phenotypic diversity within populations and the divergence between populations reach evolutionary equilibria, which describe stabilizing selection. We compute the equilibrium distributions of both quantities analytically and we show that the ratio of mean divergence and diversity depends on the strength of selection in a universal way: it is largely independent of the phenotype’s genomic encoding and of the recombination rate. This establishes a new method for the inference of selection on molecular phenotypes beyond the genome level. We discuss the implications of our findings for the predictability of evolutionary processes. (paper)

Nanostructured Mineral Coatings Stabilize Proteins for Therapeutic Delivery.

Science.gov (United States)

Yu, Xiaohua; Biedrzycki, Adam H; Khalil, Andrew S; Hess, Dalton; Umhoefer, Jennifer M; Markel, Mark D; Murphy, William L

2017-09-01

Proteins tend to lose their biological activity due to their fragile structural conformation during formulation, storage, and delivery. Thus, the inability to stabilize proteins in controlled-release systems represents a major obstacle in drug delivery. Here, a bone mineral inspired protein stabilization strategy is presented, which uses nanostructured mineral coatings on medical devices. Proteins bound within the nanostructured coatings demonstrate enhanced stability against extreme external stressors, including organic solvents, proteases, and ethylene oxide gas sterilization. The protein stabilization effect is attributed to the maintenance of protein conformational structure, which is closely related to the nanoscale feature sizes of the mineral coatings. Basic fibroblast growth factor (bFGF) released from a nanostructured mineral coating maintains its biological activity for weeks during release, while it maintains activity for less than 7 d during release from commonly used polymeric microspheres. Delivery of the growth factors bFGF and vascular endothelial growth factor using a mineral coated surgical suture significantly improves functional Achilles tendon healing in a rabbit model, resulting in increased vascularization, more mature collagen fiber organization, and a two fold improvement in mechanical properties. The findings of this study demonstrate that biomimetic interactions between proteins and nanostructured minerals provide a new, broadly applicable mechanism to stabilize proteins in the context of drug delivery and regenerative medicine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genome Dynamics of Escherichia coli during Antibiotic Treatment: Transfer, Loss, and Persistence of Genetic Elements In situ of the Infant Gut.

Science.gov (United States)

Porse, Andreas; Gumpert, Heidi; Kubicek-Sutherland, Jessica Z; Karami, Nahid; Adlerberth, Ingegerd; Wold, Agnes E; Andersson, Dan I; Sommer, Morten O A

2017-01-01

Elucidating the adaptive strategies and plasticity of bacterial genomes in situ is crucial for understanding the epidemiology and evolution of pathogens threatening human health. While much is known about the evolution of Escherichia coli in controlled laboratory environments, less effort has been made to elucidate the genome dynamics of E. coli in its native settings. Here, we follow the genome dynamics of co-existing E. coli lineages in situ of the infant gut during the first year of life. One E. coli lineage causes a urinary tract infection (UTI) and experiences several alterations of its genomic content during subsequent antibiotic treatment. Interestingly, all isolates of this uropathogenic E. coli strain carried a highly stable plasmid implicated in virulence of diverse pathogenic strains from all over the world. While virulence elements are certainly beneficial during infection scenarios, their role in gut colonization and pathogen persistence is poorly understood. We performed in vivo competitive fitness experiments to assess the role of this highly disseminated virulence plasmid in gut colonization, but found no evidence for a direct benefit of plasmid carriage. Through plasmid stability assays, we demonstrate that this plasmid is maintained in a parasitic manner, by strong first-line inheritance mechanisms, acting on the single-cell level, rather than providing a direct survival advantage in the gut. Investigating the ecology of endemic accessory genetic elements, in their pathogenic hosts and native environment, is of vital importance if we want to understand the evolution and persistence of highly virulent and drug resistant bacterial isolates.

Stability measures in arid ecosystems

Science.gov (United States)

Nosshi, M. I.; Brunsell, N. A.; Koerner, S.

2015-12-01

Stability, the capacity of ecosystems to persist in the face of change, has proven its relevance as a fundamental component of ecological theory. Here, we would like to explore meaningful and quantifiable metrics to define stability, with a focus on highly variable arid and semi-arid savanna ecosystems. Recognizing the importance of a characteristic timescale to any definition of stability, our metrics will be focused scales from annual to multi-annual, capturing different aspects of stability. Our three measures of stability, in increasing order of temporal scale, are: (1) Ecosystem resistance, quantified as the degree to which the system maintains its mean state in response to a perturbation (drought), based on inter-annual variability in Normalized Difference Vegetation Index (NDVI). (2) An optimization approach, relevant to arid systems with pulse dynamics, that models vegetation structure and function based on a trade off between the ability to respond to resource availability and avoid stress. (3) Community resilience, measured as species turnover rate (β diversity). Understanding the nature of stability in structurally-diverse arid ecosystems, which are highly variable, yields theoretical insight which has practical implications.

RPA Stabilization of Single-Stranded DNA Is Critical for Break-Induced Replication.

Science.gov (United States)

Ruff, Patrick; Donnianni, Roberto A; Glancy, Eleanor; Oh, Julyun; Symington, Lorraine S

2016-12-20

DNA double-strand breaks (DSBs) are cytotoxic lesions that must be accurately repaired to maintain genome stability. Replication protein A (RPA) plays an important role in homology-dependent repair of DSBs by protecting the single-stranded DNA (ssDNA) intermediates formed by end resection and by facilitating Rad51 loading. We found that hypomorphic mutants of RFA1 that support intra-chromosomal homologous recombination are profoundly defective for repair processes involving long tracts of DNA synthesis, in particular break-induced replication (BIR). The BIR defects of the rfa1 mutants could be partially suppressed by eliminating the Sgs1-Dna2 resection pathway, suggesting that Dna2 nuclease attacks the ssDNA formed during end resection when not fully protected by RPA. Overexpression of Rad51 was also found to suppress the rfa1 BIR defects. We suggest that Rad51 binding to the ssDNA formed by excessive end resection and during D-loop migration can partially compensate for dysfunctional RPA. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

The Micronutrient Genomics Project: A community-driven knowledge base for micronutrient research

NARCIS (Netherlands)

Ommen, B. van; El-Sohemy, A.; Hesketh, J.; Kaput, J.; Fenech, M.; Evelo, C.T.; McArdle, H.J.; Bouwman, J.; Lietz, G.; Mathers, J.C.; Fairweather-Tait, S.; Kranen, H. van; Elliott, R.; Wopereis, S.; Ferguson, L.R.; Méplan, C.; Perozzi, G.; Allen, L.; Rivero, D.

2010-01-01

Micronutrients influence multiple metabolic pathways including oxidative and inflammatory processes. Optimum micronutrient supply is important for the maintenance of homeostasis in metabolism and, ultimately, for maintaining good health. With advances in systems biology and genomics technologies, it

21 CFR 211.166 - Stability testing.

Science.gov (United States)

2010-04-01

... record of such data shall be maintained. Accelerated studies, combined with basic stability information on the components, drug products, and container-closure system, may be used to support tentative expiration dates provided full shelf life studies are not available and are being conducted. Where data from...

Characterizing a thermostable Cas9 for bacterial genome editing and silencing

NARCIS (Netherlands)

Mougiakos, Ioannis; Mohanraju, Prarthana; Bosma, Elleke F.; Vrouwe, Valentijn; Finger Bou, Max; Naduthodi, Mihris I.S.; Gussak, Alex; Brinkman, Rudolf B.L.; Kranenburg, Van Richard; Oost, Van Der John

2017-01-01

CRISPR-Cas9-based genome engineering tools have revolutionized fundamental research and biotechnological exploitation of both eukaryotes and prokaryotes. However, the mesophilic nature of the established Cas9 systems does not allow for applications that require enhanced stability, including

Characterizing a thermostable Cas9 for bacterial genome editing and silencing

DEFF Research Database (Denmark)

Mougiakos, Ioannis; Mohanraju, Prarthana; Bosma, Elleke Fenna

2017-01-01

CRISPR-Cas9-based genome engineering tools have revolutionized fundamental research and biotechnological exploitation of both eukaryotes and prokaryotes. However, the mesophilic nature of the established Cas9 systems does not allow for applications that require enhanced stability, including...

The complete chloroplast genome sequence of Abies nephrolepis (Pinaceae: Abietoideae

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Dong-Keun Yi

2016-06-01

Full Text Available The plant chloroplast (cp genome has maintained a relatively conserved structure and gene content throughout evolution. Cp genome sequences have been used widely for resolving evolutionary and phylogenetic issues at various taxonomic levels of plants. Here, we report the complete cp genome of Abies nephrolepis. The A. nephrolepis cp genome is 121,336 base pairs (bp in length including a pair of short inverted repeat regions (IRa and IRb of 139 bp each separated by a small single copy (SSC region of 54,323 bp (SSC and a large single copy region of 66,735 bp (LSC. It contains 114 genes, 68 of which are protein coding genes, 35 tRNA and four rRNA genes, six open reading frames, and one pseudogene. Seventeen repeat units and 64 simple sequence repeats (SSR have been detected in A. nephrolepis cp genome. Large IR sequences locate in 42-kb inversion points (1186 bp. The A. nephrolepis cp genome is identical to Abies koreana’s which is closely related to taxa. Pairwise comparison between two cp genomes revealed 140 polymorphic sites in each. Complete cp genome sequence of A. nephrolepis has a significant potential to provide information on the evolutionary pattern of Abietoideae and valuable data for development of DNA markers for easy identification and classification.

Ubiquitylation and the Fanconi Anemia Pathway

Science.gov (United States)

Garner, Elizabeth; Smogorzewska, Agata

2012-01-01

The Fanconi anemia (FA) pathway maintains genome stability through co-ordination of DNA repair of interstrand crosslinks (ICLs). Disruption of the FA pathway yields hypersensitivity to interstrand crosslinking agents, bone marrow failure and cancer predisposition. Early steps in DNA damage dependent activation of the pathway are governed by monoubiquitylation of FANCD2 and FANCI by the intrinsic FA E3 ubiquitin ligase, FANCL. Downstream FA pathway components and associated factors such as FAN1 and SLX4 exhibit ubiquitin-binding motifs that are important for their DNA repair function, underscoring the importance of ubiquitylation in FA pathway mediated repair. Importantly, ubiquitylation provides the foundations for cross-talk between repair pathways, which in concert with the FA pathway, resolve interstrand crosslink damage and maintain genomic stability. PMID:21605559

Maintainability allocation

International Nuclear Information System (INIS)

Guyot, Christian.

1980-06-01

The author gives the general lines of a method for the allocation and for the evaluation of maintainability of complex systems which is to be developed during the conference. The maintainability objective is supposed to be formulated under the form of a mean time to repair (M.T.T.R.) [fr

Thermally Optimized Polarization-Maintaining Photonic Crystal Fiber and Its FOG Application.

Science.gov (United States)

Zhang, Chunxi; Zhang, Zhihao; Xu, Xiaobin; Cai, Wei

2018-02-13

In this paper, we propose a small-diameter polarization-maintaining solid-core photonic crystal fiber. The coating diameter, cladding diameter and other key parameters relating to the thermal properties were studied. Based on the optimized parameters, a fiber with a Shupe constant 15% lower than commercial photonic crystal fibers (PCFs) was fabricated, and the transmission loss was lower than 2 dB/km. The superior thermal stability of our fiber design was proven through both simulation and measurement. Using the small-diameter fiber, a split high precision fiber optic gyro (FOG) prototype was fabricated. The bias stability of the FOG was 0.0023 °/h, the random walk was 0.0003 °/ h , and the scale factor error was less than 1 ppm. Throughout a temperature variation ranging from -40 to 60 °C, the bias stability was less than 0.02 °/h without temperature compensation which is notably better than FOG with panda fiber. As a result, the PCF FOG is a promising choice for high precision FOG applications.

Current regulator for stabilizing electrostatic generators; Regulateur de courant pour stabilisation de generateur electrostatique

Energy Technology Data Exchange (ETDEWEB)

Gabet, A; Taieb, J

1950-07-01

An instrument consisting of two electronic tubes, a triode and a pentode, connected in series, serves as a stabilizer of the current that charges a working model of a van de Graaff generator. The current is maintained at a level corresponding to an auxiliary variable voltage. The triode maintains that voltage, while the pentode regulates the current. Another application of the circuit, viz., the stabilizing of the generator voltage, will be described elsewhere. (author)

Is floral divergence sufficient to maintain species boundaries upon secondary contact in Mediterranean food-deceptive orchids?

OpenAIRE

Zitari, A; Scopece, G; Helal, A N; Widmer, A; Cozzolino, S

2011-01-01

Analyzing the processes that determine whether species boundaries are maintained on secondary contact may shed light on the early phase of speciation. In Anacamptis morio and Anacamptis longicornu, two Mediterranean orchid sister-species, we used molecular and morphological analyses, together with estimates of pollination success and experimental crosses, to assess whether floral isolation can shelter the species' genomes from genetic admixture on secondary contact. We found substantial genet...

Statistical analyses of conserved features of genomic islands in bacteria.

Science.gov (United States)

Guo, F-B; Xia, Z-K; Wei, W; Zhao, H-L

2014-03-17

We performed statistical analyses of five conserved features of genomic islands of bacteria. Analyses were made based on 104 known genomic islands, which were identified by comparative methods. Four of these features include sequence size, abnormal G+C content, flanking tRNA gene, and embedded mobility gene, which are frequently investigated. One relatively new feature, G+C homogeneity, was also investigated. Among the 104 known genomic islands, 88.5% were found to fall in the typical length of 10-200 kb and 80.8% had G+C deviations with absolute values larger than 2%. For the 88 genomic islands whose hosts have been sequenced and annotated, 52.3% of them were found to have flanking tRNA genes and 64.7% had embedded mobility genes. For the homogeneity feature, 85% had an h homogeneity index less than 0.1, indicating that their G+C content is relatively uniform. Taking all the five features into account, 87.5% of 88 genomic islands had three of them. Only one genomic island had only one conserved feature and none of the genomic islands had zero features. These statistical results should help to understand the general structure of known genomic islands. We found that larger genomic islands tend to have relatively small G+C deviations relative to absolute values. For example, the absolute G+C deviations of 9 genomic islands longer than 100,000 bp were all less than 5%. This is a novel but reasonable result given that larger genomic islands should have greater restrictions in their G+C contents, in order to maintain the stable G+C content of the recipient genome.

The Hydromechanics of Vegetation for Slope Stabilization

Science.gov (United States)

Mulyono, A.; Subardja, A.; Ekasari, I.; Lailati, M.; Sudirja, R.; Ningrum, W.

2018-02-01

Vegetation is one of the alternative technologies in the prevention of shallow landslide prevention that occurs mostly during the rainy season. The application of plant for slope stabilization is known as bioengineering. Knowledge of the vegetative contribution that can be considered in bioengineering was the hydrological and mechanical aspects (hydromechanical). Hydrological effect of the plant on slope stability is to reduce soil water content through transpiration, interception, and evapotranspiration. The mechanical impact of vegetation on slope stability is to stabilize the slope with mechanical reinforcement of soils through roots. Vegetation water consumption varies depending on the age and density, rainfall factors and soil types. Vegetation with high ability to absorb water from the soil and release into the atmosphere through a transpiration process will reduce the pore water stress and increase slope stability, and vegetation with deep root anchoring and strong root binding was potentially more significant to maintain the stability of the slope.

Matrin 3 binds and stabilizes mRNA.

Directory of Open Access Journals (Sweden)

Maayan Salton

Full Text Available Matrin 3 (MATR3 is a highly conserved, inner nuclear matrix protein with two zinc finger domains and two RNA recognition motifs (RRM, whose function is largely unknown. Recently we found MATR3 to be phosphorylated by the protein kinase ATM, which activates the cellular response to double strand breaks in the DNA. Here, we show that MATR3 interacts in an RNA-dependent manner with several proteins with established roles in RNA processing, and maintains its interaction with RNA via its RRM2 domain. Deep sequencing of the bound RNA (RIP-seq identified several small noncoding RNA species. Using microarray analysis to explore MATR3's role in transcription, we identified 77 transcripts whose amounts depended on the presence of MATR3. We validated this finding with nine transcripts which were also bound to the MATR3 complex. Finally, we demonstrated the importance of MATR3 for maintaining the stability of several of these mRNA species and conclude that it has a role in mRNA stabilization. The data suggest that the cellular level of MATR3, known to be highly regulated, modulates the stability of a group of gene transcripts.

78 FR 58612 - Genomic Medicine Program Advisory Committee, Notice of Meeting

Science.gov (United States)

2013-09-24

... make recommendations to the Secretary of Veterans Affairs on using genetic information to optimize... appropriate ethical oversight and protecting the privacy of Veterans. The meeting focus will be on developing infrastructure and guidelines for phenotyping and maintaining privacy and security of genomic information. The...

Genome flux and stasis in a five millennium transect of European prehistory.

Science.gov (United States)

Gamba, Cristina; Jones, Eppie R; Teasdale, Matthew D; McLaughlin, Russell L; Gonzalez-Fortes, Gloria; Mattiangeli, Valeria; Domboróczki, László; Kővári, Ivett; Pap, Ildikó; Anders, Alexandra; Whittle, Alasdair; Dani, János; Raczky, Pál; Higham, Thomas F G; Hofreiter, Michael; Bradley, Daniel G; Pinhasi, Ron

2014-10-21

The Great Hungarian Plain was a crossroads of cultural transformations that have shaped European prehistory. Here we analyse a 5,000-year transect of human genomes, sampled from petrous bones giving consistently excellent endogenous DNA yields, from 13 Hungarian Neolithic, Copper, Bronze and Iron Age burials including two to high (~22 × ) and seven to ~1 × coverage, to investigate the impact of these on Europe's genetic landscape. These data suggest genomic shifts with the advent of the Neolithic, Bronze and Iron Ages, with interleaved periods of genome stability. The earliest Neolithic context genome shows a European hunter-gatherer genetic signature and a restricted ancestral population size, suggesting direct contact between cultures after the arrival of the first farmers into Europe. The latest, Iron Age, sample reveals an eastern genomic influence concordant with introduced Steppe burial rites. We observe transition towards lighter pigmentation and surprisingly, no Neolithic presence of lactase persistence.

CONSIDERATIONS ON THE CONTENT AND OBJECTIVES OF FINANCIAL STABILITY

Directory of Open Access Journals (Sweden)

TENEA ANDREI COSMIN

2017-12-01

Full Text Available This paper is a thorough examination of the concept of financial stability by studying and exposing opinions from the relevant literature regarding the content and objectives of financial stability. I considered that such a study could be useful in an academic perspective, but also from the perspective of performers and those interested in the activities and actions of central banks. Financial stability shows us the capacity of a financial system to maintain its basic functions and adapt to disruptions threatening these functions

The Organelle Genomes of Hassawi Rice (Oryza sativa L.) and Its Hybrid in Saudi Arabia: Genome Variation, Rearrangement, and Origins

Science.gov (United States)

Zhang, Tongwu; Hu, Songnian; Zhang, Guangyu; Pan, Linlin; Zhang, Xiaowei; Al-Mssallem, Ibrahim S.; Yu, Jun

2012-01-01

Hassawi rice (Oryza sativa L.) is a landrace adapted to the climate of Saudi Arabia, characterized by its strong resistance to soil salinity and drought. Using high quality sequencing reads extracted from raw data of a whole genome sequencing project, we assembled both chloroplast (cp) and mitochondrial (mt) genomes of the wild-type Hassawi rice (Hassawi-1) and its dwarf hybrid (Hassawi-2). We discovered 16 InDels (insertions and deletions) but no SNP (single nucleotide polymorphism) is present between the two Hassawi cp genomes. We identified 48 InDels and 26 SNPs in the two Hassawi mt genomes and a new type of sequence variation, termed reverse complementary variation (RCV) in the rice cp genomes. There are two and four RCVs identified in Hassawi-1 when compared to 93–11 (indica) and Nipponbare (japonica), respectively. Microsatellite sequence analysis showed there are more SSRs in the genic regions of both cp and mt genomes in the Hassawi rice than in the other rice varieties. There are also large repeats in the Hassawi mt genomes, with the longest length of 96,168 bp and 96,165 bp in Hassawi-1 and Hassawi-2, respectively. We believe that frequent DNA rearrangement in the Hassawi mt and cp genomes indicate ongoing dynamic processes to reach genetic stability under strong environmental pressures. Based on sequence variation analysis and the breeding history, we suggest that both Hassawi-1 and Hassawi-2 originated from the Indonesian variety Peta since genetic diversity between the two Hassawi cultivars is very low albeit an unknown historic origin of the wild-type Hassawi rice. PMID:22870184

DNMT1 maintains progenitor function in self-renewing somatic tissue.

Science.gov (United States)

Sen, George L; Reuter, Jason A; Webster, Daniel E; Zhu, Lilly; Khavari, Paul A

2010-01-28

Progenitor cells maintain self-renewing tissues throughout life by sustaining their capacity for proliferation while suppressing cell cycle exit and terminal differentiation. DNA methylation provides a potential epigenetic mechanism for the cellular memory needed to preserve the somatic progenitor state through repeated cell divisions. DNA methyltransferase 1 (DNMT1) maintains DNA methylation patterns after cellular replication. Although dispensable for embryonic stem cell maintenance, the role for DNMT1 in maintaining the progenitor state in constantly replenished somatic tissues, such as mammalian epidermis, is unclear. Here we show that DNMT1 is essential for epidermal progenitor cell function. DNMT1 protein was found enriched in undifferentiated cells, where it was required to retain proliferative stamina and suppress differentiation. In tissue, DNMT1 depletion led to exit from the progenitor cell compartment, premature differentiation and eventual tissue loss. Genome-wide analysis showed that a significant portion of epidermal differentiation gene promoters were methylated in self-renewing conditions but were subsequently demethylated during differentiation. Furthermore, UHRF1 (refs 9, 10), a component of the DNA methylation machinery that targets DNMT1 to hemi-methylated DNA, is also necessary to suppress premature differentiation and sustain proliferation. In contrast, Gadd45A and B, which promote active DNA demethylation, are required for full epidermal differentiation gene induction. These data demonstrate that proteins involved in the dynamic regulation of DNA methylation patterns are required for progenitor maintenance and self-renewal in mammalian somatic tissue.

New roles of the human Suv3 helicase in genome maintenance

DEFF Research Database (Denmark)

Venø, Susanne Trillingsgaard

During her PhD studies, Susanne Trillingsgaard Venø carried out research into the role of the human Suv3 protein in stabilising the human genome – DNA. Suv3 is a helicase that separates the two strands of the DNA’s double helix. Throughout our lives, the DNA in our cells is constantly exposed...... maintenance. Based on these new research results, the Suv3 protein could be a valuable model for genome stability as an important factor in our understanding of why we get old....

Supplementary Material for: Whole genome sequencing reveals genomic heterogeneity and antibiotic purification in Mycobacterium tuberculosis isolates

KAUST Repository

Black, PA

2015-01-01

Abstract Background Whole genome sequencing has revolutionised the interrogation of mycobacterial genomes. Recent studies have reported conflicting findings on the genomic stability of Mycobacterium tuberculosis during the evolution of drug resistance. In an age where whole genome sequencing is increasingly relied upon for defining the structure of bacterial genomes, it is important to investigate the reliability of next generation sequencing to identify clonal variants present in a minor percentage of the population. This study aimed to define a reliable cut-off for identification of low frequency sequence variants and to subsequently investigate genetic heterogeneity and the evolution of drug resistance in M. tuberculosis. Methods Genomic DNA was isolated from single colonies from 14 rifampicin mono-resistant M. tuberculosis isolates, as well as the primary cultures and follow up MDR cultures from two of these patients. The whole genomes of the M. tuberculosis isolates were sequenced using either the Illumina MiSeq or Illumina HiSeq platforms. Sequences were analysed with an in-house pipeline. Results Using next-generation sequencing in combination with Sanger sequencing and statistical analysis we defined a read frequency cut-off of 30 % to identify low frequency M. tuberculosis variants with high confidence. Using this cut-off we demonstrated a high rate of genetic diversity between single colonies isolated from one population, showing that by using the current sequencing technology, single colonies are not a true reflection of the genetic diversity within a whole population and vice versa. We further showed that numerous heterogeneous variants emerge and then disappear during the evolution of isoniazid resistance within individual patients. Our findings allowed us to formulate a model for the selective bottleneck which occurs during the course of infection, acting as a genomic purification event. Conclusions Our study demonstrated true levels of genetic

CHOgenome.org 2.0: Genome resources and website updates.

Science.gov (United States)

Kremkow, Benjamin G; Baik, Jong Youn; MacDonald, Madolyn L; Lee, Kelvin H

2015-07-01

Chinese hamster ovary (CHO) cells are a major host cell line for the production of therapeutic proteins, and CHO cell and Chinese hamster (CH) genomes have recently been sequenced using next-generation sequencing methods. CHOgenome.org was launched in 2011 (version 1.0) to serve as a database repository and to provide bioinformatics tools for the CHO community. CHOgenome.org (version 1.0) maintained GenBank CHO-K1 genome data, identified CHO-omics literature, and provided a CHO-specific BLAST service. Recent major updates to CHOgenome.org (version 2.0) include new sequence and annotation databases for both CHO and CH genomes, a more user-friendly website, and new research tools, including a proteome browser and a genome viewer. CHO cell-line specific sequences and annotations facilitate cell line development opportunities, several of which are discussed. Moving forward, CHOgenome.org will host the increasing amount of CHO-omics data and continue to make useful bioinformatics tools available to the CHO community. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

p53, a New Master Regulator of Stem Cell Differentiation | Center for Cancer Research

Science.gov (United States)

When the genome is damaged, a key player in stabilizing and maintaining genomic integrity is a protein called p53.  This protein can activate or shut down gene activity in response to DNA damage.  But how exactly does p53 accomplish its task? This question has yet to be answered completely at the molecular level.   

Insights into three whole-genome duplications gleaned from the Paramecium caudatum genome sequence.

Science.gov (United States)

McGrath, Casey L; Gout, Jean-Francois; Doak, Thomas G; Yanagi, Akira; Lynch, Michael

2014-08-01

Paramecium has long been a model eukaryote. The sequence of the Paramecium tetraurelia genome reveals a history of three successive whole-genome duplications (WGDs), and the sequences of P. biaurelia and P. sexaurelia suggest that these WGDs are shared by all members of the aurelia species complex. Here, we present the genome sequence of P. caudatum, a species closely related to the P. aurelia species group. P. caudatum shares only the most ancient of the three WGDs with the aurelia complex. We found that P. caudatum maintains twice as many paralogs from this early event as the P. aurelia species, suggesting that post-WGD gene retention is influenced by subsequent WGDs and supporting the importance of selection for dosage in gene retention. The availability of P. caudatum as an outgroup allows an expanded analysis of the aurelia intermediate and recent WGD events. Both the Guanine+Cytosine (GC) content and the expression level of preduplication genes are significant predictors of duplicate retention. We find widespread asymmetrical evolution among aurelia paralogs, which is likely caused by gradual pseudogenization rather than by neofunctionalization. Finally, cases of divergent resolution of intermediate WGD duplicates between aurelia species implicate this process acts as an ongoing reinforcement mechanism of reproductive isolation long after a WGD event. Copyright © 2014 by the Genetics Society of America.

Marine Genomics: A clearing-house for genomic and transcriptomic data of marine organisms

Directory of Open Access Journals (Sweden)

Trent Harold F

2005-03-01

Full Text Available Abstract Background The Marine Genomics project is a functional genomics initiative developed to provide a pipeline for the curation of Expressed Sequence Tags (ESTs and gene expression microarray data for marine organisms. It provides a unique clearing-house for marine specific EST and microarray data and is currently available at http://www.marinegenomics.org. Description The Marine Genomics pipeline automates the processing, maintenance, storage and analysis of EST and microarray data for an increasing number of marine species. It currently contains 19 species databases (over 46,000 EST sequences that are maintained by registered users from local and remote locations in Europe and South America in addition to the USA. A collection of analysis tools are implemented. These include a pipeline upload tool for EST FASTA file, sequence trace file and microarray data, an annotative text search, automated sequence trimming, sequence quality control (QA/QC editing, sequence BLAST capabilities and a tool for interactive submission to GenBank. Another feature of this resource is the integration with a scientific computing analysis environment implemented by MATLAB. Conclusion The conglomeration of multiple marine organisms with integrated analysis tools enables users to focus on the comprehensive descriptions of transcriptomic responses to typical marine stresses. This cross species data comparison and integration enables users to contain their research within a marine-oriented data management and analysis environment.

MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR.

Science.gov (United States)

Krause, Claudia J; Popp, Oliver; Thirunarayanan, Nanthakumar; Dittmar, Gunnar; Lipp, Martin; Müller, Gerd

2016-03-01

The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi's sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR-induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability.

The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

Science.gov (United States)

Eppig, Janan T; Blake, Judith A; Bult, Carol J; Kadin, James A; Richardson, Joel E

2015-01-01

The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

MHD stability calculations of high-β quasi-axisymmetric stellarators

International Nuclear Information System (INIS)

Fu, G.Y.; Ku, L.P.; Pomphrey, N.; Redi, M.; Kessel, C.; Monticello, D.; Reiman, A.; Hughes, M.; Cooper, W.A.; Nuehrenberg, C.

2001-01-01

The MHD stability of quasi-axisymmetric compact stellarators is investigated. It is shown that bootstrap current driven external kink modes can be stabilized by a combination of edge magnetic shear and appropriate 3D plasma boundary shaping while maintaining good quasi-axisymmetry. The results demonstrate that there exists a new class of stellarators with quasi-axisymmetry, large bootstrap current, high MHD beta limit, and compact size. (author)

MHD stability calculations of high-β quasi-axisymmetric stellarators

International Nuclear Information System (INIS)

Fu, G.Y.; Ku, L.P.; Pomphrey, N.; Redi, M.H.; Kessel, C.; Monticello, D.A.; Reiman, A.; Hughes, M.; Cooper, W.A.; Nuehrenberg, C.

1999-01-01

The MHD stability of quasi-axisymmetric compact stellarators is investigated. It is shown that bootstrap current driven external kink modes can be stabilized by a combination of edge magnetic shear and appropriate 3D plasma boundary shaping while maintaining good quasi-axisymmetry. The results demonstrate that there exists a new class of stellarators with quasi-axisymmetry, large bootstrap current, high MHD beta limit, and compact size. (author)

MHD Stability Calculations of High-Beta Quasi-Axisymmetric Stellarators

International Nuclear Information System (INIS)

Kessel, C.; Fu, G.Y.; Ku, L.P.; Redi, M.H.; Pomphrey, N.

1999-01-01

The MHD stability of quasi-axisymmetric compact stellarators is investigated. It is shown that bootstrap current driven external kink modes can be stabilized by a combination of edge magnetic shear and appropriate 3D plasma boundary shaping while maintaining good quasi-axisymmetry. The results demonstrate that there exists a new class of stellarators with quasi-axisymmetry, large bootstrap current, high MHD beta limit, and compact size

High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination

Directory of Open Access Journals (Sweden)

Michelle Hawkins

2013-11-01

Full Text Available Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci.

Comparative genomics and evolution of eukaryotic phospholipidbiosynthesis

Energy Technology Data Exchange (ETDEWEB)

Lykidis, Athanasios

2006-12-01

Phospholipid biosynthetic enzymes produce diverse molecular structures and are often present in multiple forms encoded by different genes. This work utilizes comparative genomics and phylogenetics for exploring the distribution, structure and evolution of phospholipid biosynthetic genes and pathways in 26 eukaryotic genomes. Although the basic structure of the pathways was formed early in eukaryotic evolution, the emerging picture indicates that individual enzyme families followed unique evolutionary courses. For example, choline and ethanolamine kinases and cytidylyltransferases emerged in ancestral eukaryotes, whereas, multiple forms of the corresponding phosphatidyltransferases evolved mainly in a lineage specific manner. Furthermore, several unicellular eukaryotes maintain bacterial-type enzymes and reactions for the synthesis of phosphatidylglycerol and cardiolipin. Also, base-exchange phosphatidylserine synthases are widespread and ancestral enzymes. The multiplicity of phospholipid biosynthetic enzymes has been largely generated by gene expansion in a lineage specific manner. Thus, these observations suggest that phospholipid biosynthesis has been an actively evolving system. Finally, comparative genomic analysis indicates the existence of novel phosphatidyltransferases and provides a candidate for the uncharacterized eukaryotic phosphatidylglycerol phosphate phosphatase.

RECQL5 Suppresses Oncogenic JAK2-Induced Replication Stress and Genomic Instability

Directory of Open Access Journals (Sweden)

Edwin Chen

2015-12-01

Full Text Available JAK2V617F is the most common oncogenic lesion in patients with myeloproliferative neoplasms (MPNs. Despite the ability of JAK2V617F to instigate DNA damage in vitro, MPNs are nevertheless characterized by genomic stability. In this study, we address this paradox by identifying the DNA helicase RECQL5 as a suppressor of genomic instability in MPNs. We report increased RECQL5 expression in JAK2V617F-expressing cells and demonstrate that RECQL5 is required to counteract JAK2V617F-induced replication stress. Moreover, RECQL5 depletion sensitizes JAK2V617F mutant cells to hydroxyurea (HU, a pharmacological inducer of replication stress and the most common treatment for MPNs. Using single-fiber chromosome combing, we show that RECQL5 depletion in JAK2V617F mutant cells impairs replication dynamics following HU treatment, resulting in increased double-stranded breaks and apoptosis. Cumulatively, these findings identify RECQL5 as a critical regulator of genome stability in MPNs and demonstrate that replication stress-associated cytotoxicity can be amplified specifically in JAK2V617F mutant cells through RECQL5-targeted synthetic lethality.

Studies on antigenic and genomic properties of Brazilian rabies virus isolates

NARCIS (Netherlands)

Schaefer, R.; Batista, H.B.; Franco, A.C.; Rijsewijk, F.A.M.; Roehe, P.M.

2005-01-01

Despite the recognized stability of rabies virus, differences among isolates from different species have been found. This work was carried out with the aim to identify antigenic and genomic differences in Brazilian rabies virus isolates and to verify whether such alterations would bear any

The formation of the economic mechanism of stabilization of enterprise’s activity

Directory of Open Access Journals (Sweden)

L. A. Zaporozhtseva

2018-01-01

Full Text Available The authors bring the research of regularities of enterprise’s economic development; bring the research of change sequence of life cycle stages in the article. There is established that a stage of maturity not always gives way to decline stage and in the next to crisis stage. Life processes of "ageing" of the enterprise can be successfully resisted. It is proved that the stage of maturity of the enterprise is associated with a "crisis of stability". Getting into the stages of recession, growth or maintaining stability becomes the way out of the crisis. The authors prove that there are such zones of staying on the life cycle’s curve in the practice of commercial organizations functioning when it is necessary to use the mechanism of stabilization (at detection of "crisis of stability", at transfer from the stage of maturity to the stage of recession and at diagnostics of hit to the stage of recession. In this regard the authors elaborate an economic mechanism for stabilization of the enterprise’s activity as a system of measures aimed at maintaining the achieved financial balance of the enterprise in a long period, which includes the following blocks: information support of the assessment of financial condition; assessment of the level of payment, business and capital stability of the enterprise; determination of the stage of the enterprise’s life cycle; characteristics of the applicable strategy; the need to use the tools for adjust the strategy to stabilize the enterprise’s activity and evaluate the results. At the same time, it is important to focus on maintaining achievable growth rates through the using of special management decisions, along with monitoring the life cycle and controlling the financial condition of the enterprise. The introduction of the economic stabilization mechanism in the enterprise’s activity jointly with the existing organizational and economic mechanism will correct the elements of the basic mechanism and

The Quiescent Cellular State is Arf/p53-Dependent and Associated with H2AX Downregulation and Genome Stability

Directory of Open Access Journals (Sweden)

Mitsuko Masutani

2012-05-01

Full Text Available Cancer is a disease associated with genomic instability and mutations. Excluding some tumors with specific chromosomal translocations, most cancers that develop at an advanced age are characterized by either chromosomal or microsatellite instability. However, it is still unclear how genomic instability and mutations are generated during the process of cellular transformation and how the development of genomic instability contributes to cellular transformation. Recent studies of cellular regulation and tetraploidy development have provided insights into the factors triggering cellular transformation and the regulatory mechanisms that protect chromosomes from genomic instability.

Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication

Directory of Open Access Journals (Sweden)

Michael Niepmann

2018-03-01

Full Text Available Hepatitis C virus (HCV preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES in the 5′ untranslated region (5′ UTR, while also downstream elements like the cis-replication element (CRE in the coding region and the 3′ UTR are involved in translation regulation. The cis-elements controlling replication of the viral RNA genome are located mainly in the 5′- and 3′-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA–RNA interactions (LRIs are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis-elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122 binds to two target sites at the 5′ end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3′ UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis-elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis-element in

Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication.

Science.gov (United States)

Niepmann, Michael; Shalamova, Lyudmila A; Gerresheim, Gesche K; Rossbach, Oliver

2018-01-01

Hepatitis C virus (HCV) preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES) in the 5' untranslated region (5' UTR), while also downstream elements like the cis -replication element (CRE) in the coding region and the 3' UTR are involved in translation regulation. The cis -elements controlling replication of the viral RNA genome are located mainly in the 5'- and 3'-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA-RNA interactions (LRIs) are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis -elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122) binds to two target sites at the 5' end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3' UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis -elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis -element in question acts on HCV

Ergonomics Contribution in Maintainability

Science.gov (United States)

Teymourian, Kiumars; Seneviratne, Dammika; Galar, Diego

2017-09-01

The objective of this paper is to describe an ergonomics contribution in maintainability. The economical designs, inputs and training helps to increase the maintainability indicators for industrial devices. This analysis can be helpful, among other cases, to compare systems, to achieve a better design regarding maintainability requirements, to improve this maintainability under specific industrial environment and to foresee maintainability problems due to eventual changes in a device operation conditions. With this purpose, this work first introduces the notion of ergonomics and human factors, maintainability and the implementation of assessment of human postures, including some important postures to perform maintenance activities. A simulation approach is used to identify the critical posture of the maintenance personnel and implements the defined postures with minimal loads on the personnel who use the equipment in a practical scenario. The simulation inputs are given to the designers to improve the workplace/equipment in order to high level of maintainability. Finally, the work concludes summarizing the more significant aspects and suggesting future research.

BFAST: an alignment tool for large scale genome resequencing.

Directory of Open Access Journals (Sweden)

Nils Homer

2009-11-01

Full Text Available The new generation of massively parallel DNA sequencers, combined with the challenge of whole human genome resequencing, result in the need for rapid and accurate alignment of billions of short DNA sequence reads to a large reference genome. Speed is obviously of great importance, but equally important is maintaining alignment accuracy of short reads, in the 25-100 base range, in the presence of errors and true biological variation.We introduce a new algorithm specifically optimized for this task, as well as a freely available implementation, BFAST, which can align data produced by any of current sequencing platforms, allows for user-customizable levels of speed and accuracy, supports paired end data, and provides for efficient parallel and multi-threaded computation on a computer cluster. The new method is based on creating flexible, efficient whole genome indexes to rapidly map reads to candidate alignment locations, with arbitrary multiple independent indexes allowed to achieve robustness against read errors and sequence variants. The final local alignment uses a Smith-Waterman method, with gaps to support the detection of small indels.We compare BFAST to a selection of large-scale alignment tools -- BLAT, MAQ, SHRiMP, and SOAP -- in terms of both speed and accuracy, using simulated and real-world datasets. We show BFAST can achieve substantially greater sensitivity of alignment in the context of errors and true variants, especially insertions and deletions, and minimize false mappings, while maintaining adequate speed compared to other current methods. We show BFAST can align the amount of data needed to fully resequence a human genome, one billion reads, with high sensitivity and accuracy, on a modest computer cluster in less than 24 hours. BFAST is available at (http://bfast.sourceforge.net.

Genomic dairy cattle breeding

DEFF Research Database (Denmark)

Mark, Thomas; Sandøe, Peter

2010-01-01

the thoughts of breeders and other stakeholders on how to best make use of genomic breeding in the future. Intensive breeding has played a major role in securing dramatic increases in milk yield since the Second World War. Until recently, the main focus in dairy cattle breeding was on production traits...... it less accountable to the concern of private farmers for the welfare of their animals. It is argued that there is a need to mobilise a wide range of stakeholders to monitor developments and maintain pressure on breeding companies so that they are aware of the need to take precautionary measures to avoid...

Chemical stabilization of graphite surfaces

Energy Technology Data Exchange (ETDEWEB)

Bistrika, Alexander A.; Lerner, Michael M.

2018-04-03

Embodiments of a device, or a component of a device, including a stabilized graphite surface, methods of stabilizing graphite surfaces, and uses for the devices or components are disclosed. The device or component includes a surface comprising graphite, and a plurality of haloaryl ions and/or haloalkyl ions bound to at least a portion of the graphite. The ions may be perhaloaryl ions and/or perhaloalkyl ions. In certain embodiments, the ions are perfluorobenzenesulfonate anions. Embodiments of the device or component including stabilized graphite surfaces may maintain a steady-state oxidation or reduction surface current density after being exposed to continuous oxidation conditions for a period of at least 1-100 hours. The device or component is prepared by exposing a graphite-containing surface to an acidic aqueous solution of the ions under oxidizing conditions. The device or component can be exposed in situ to the solution.

Features and Mechanisms for Ensuring Social and Political Stability in Contemporary Chinese Society

Directory of Open Access Journals (Sweden)

Максим Алексеевич Сущенко

2017-12-01

Full Text Available This article discusses the features and mechanisms of ensuring and maintaining social and political stability in China. Analyzes the scientific theoretical foundation in the study of this phenomenon, developed by Russian and Chinese scientists. Political stability in contemporary China is understood as a precondition for effective social and economic development. The paper studied the treatment of leadership in China from different generations to tools approval of social and political stability as a way of implementing the modernization program of the political course. It has been found that maintaining the political stability of the society in modern China made possible by the harmonization of public relations, flexible national policy, economic growth, trends in socio-economic development and the use of ideological tools. The author studied the basic mechanisms of the stability of the political system of China at the present stage. It is concluded that a stable political development in contemporary China strengthens the regime and the preservation of the monopoly of the CCP to political power.

Genome Assembly and Computational Analysis Pipelines for Bacterial Pathogens

KAUST Repository

Rangkuti, Farania Gama Ardhina

2011-06-01

Pathogens lie behind the deadliest pandemics in history. To date, AIDS pandemic has resulted in more than 25 million fatal cases, while tuberculosis and malaria annually claim more than 2 million lives. Comparative genomic analyses are needed to gain insights into the molecular mechanisms of pathogens, but the abundance of biological data dictates that such studies cannot be performed without the assistance of computational approaches. This explains the significant need for computational pipelines for genome assembly and analyses. The aim of this research is to develop such pipelines. This work utilizes various bioinformatics approaches to analyze the high-­throughput genomic sequence data that has been obtained from several strains of bacterial pathogens. A pipeline has been compiled for quality control for sequencing and assembly, and several protocols have been developed to detect contaminations. Visualization has been generated of genomic data in various formats, in addition to alignment, homology detection and sequence variant detection. We have also implemented a metaheuristic algorithm that significantly improves bacterial genome assemblies compared to other known methods. Experiments on Mycobacterium tuberculosis H37Rv data showed that our method resulted in improvement of N50 value of up to 9697% while consistently maintaining high accuracy, covering around 98% of the published reference genome. Other improvement efforts were also implemented, consisting of iterative local assemblies and iterative correction of contiguated bases. Our result expedites the genomic analysis of virulent genes up to single base pair resolution. It is also applicable to virtually every pathogenic microorganism, propelling further research in the control of and protection from pathogen-­associated diseases.

Stability of position control system in JIPP T-II

International Nuclear Information System (INIS)

Sakurai, Keiichi; Tanahashi, Shygo

1980-01-01

Computations and experiments on the stability of a feedback control system for maintaining a plasma column in equilibrium are described. The time response of the displacement of the plasma to the desired position is examined by solving the equation of motion of the plasma column. We show that the stability of the feedback control system is improved by using an additional term which represents the shift velocity of the plasma column. (author)

Performance of the PBX-M passive plate stabilization system

International Nuclear Information System (INIS)

Kugel, H.W.; Bell, R.; Bernabei, S.

1994-02-01

The PBX-M passive plate stabilization system provides significant stabilization of long-wavelength external kink modes, the slowing of vertical instability growth rates, and the amelioration of disruption characteristics. The passive plate stabilization system has allowed the use of LHCD and IBW to induce current density and pressure profile modifications, and m = 1 divertor biasing for modifying edge plasma transport. Improvements in the passive plate system insulators and support structures have provided reliable operation. Impurity influxes with the close-fitting passive plates are low. Solid target boronization is applied routinely to reduce conditioning time and maintain clean conditions

A decade of understanding spatio-temporal regulation of DNA repair by the nuclear architecture.

Science.gov (United States)

Saad, Hicham; Cobb, Jennifer A

2016-10-01

The nucleus is a hub for gene expression and is a highly organized entity. The nucleoplasm is heterogeneous, owing to the preferential localization of specific metabolic factors, which lead to the definition of nuclear compartments or bodies. The genome is organized into chromosome territories, as well as heterochromatin and euchromatin domains. Recent observations have indicated that nuclear organization is important for maintaining genomic stability. For example, nuclear organization has been implicated in stabilizing damaged DNA, repair-pathway choice, and in preventing chromosomal rearrangements. Over the past decade, several studies have revealed that dynamic changes in the nuclear architecture are important during double-strand break repair. Stemming from work in yeast, relocation of a damaged site prior to repair appears to be at least partially conserved in multicellular eukaryotes. In this review, we will discuss genome and nucleoplasm architecture, particularly the importance of the nuclear periphery in genome stability. We will also discuss how the site of relocation regulates repair-pathway choice.

Ovarian carcinoma CDK12 mutations misregulate expression of DNA repair genes via deficient formation and function of the Cdk12/CycK complex

Czech Academy of Sciences Publication Activity Database

Ekumi, K.M.; Paculova, H.; Lenasi, T.; Pospíchalová, V.; Boesken, C.A.; Rybaříková, J.; Bryja, Vítězslav; Geyer, M.; Blažek, D.; Barboric, M.

2015-01-01

Roč. 43, č. 5 (2015), s. 2575-2589 ISSN 0305-1048 Institutional support: RVO:68081707 Keywords : RNA-POLYMERASE-II * PRE-MESSENGER-RNA * MAINTAINS GENOMIC STABILITY Subject RIV: BO - Biophysics Impact factor: 9.202, year: 2015

European Chlamydia abortus livestock isolate genomes reveal unusual stability and limited diversity, reflected in geographical signatures.

Science.gov (United States)

Seth-Smith, H M B; Busó, Leonor Sánchez; Livingstone, M; Sait, M; Harris, S R; Aitchison, K D; Vretou, Evangelia; Siarkou, V I; Laroucau, K; Sachse, K; Longbottom, D; Thomson, N R

2017-05-04

Chlamydia abortus (formerly Chlamydophila abortus) is an economically important livestock pathogen, causing ovine enzootic abortion (OEA), and can also cause zoonotic infections in humans affecting pregnancy outcome. Large-scale genomic studies on other chlamydial species are giving insights into the biology of these organisms but have not yet been performed on C. abortus. Our aim was to investigate a broad collection of European isolates of C. abortus, using next generation sequencing methods, looking at diversity, geographic distribution and genome dynamics. Whole genome sequencing was performed on our collection of 57 C. abortus isolates originating primarily from the UK, Germany, France and Greece, but also from Tunisia, Namibia and the USA. Phylogenetic analysis of a total of 64 genomes shows a deep structural division within the C. abortus species with a major clade displaying limited diversity, in addition to a branch carrying two more distantly related Greek isolates, LLG and POS. Within the major clade, seven further phylogenetic groups can be identified, demonstrating geographical associations. The number of variable nucleotide positions across the sampled isolates is significantly lower than those published for C. trachomatis and C. psittaci. No recombination was identified within C. abortus, and no plasmid was found. Analysis of pseudogenes showed lineage specific loss of some functions, notably with several Pmp and TMH/Inc proteins predicted to be inactivated in many of the isolates studied. The diversity within C. abortus appears to be much lower compared to other species within the genus. There are strong geographical signatures within the phylogeny, indicating clonal expansion within areas of limited livestock transport. No recombination has been identified within this species, showing that different species of Chlamydia may demonstrate different evolutionary dynamics, and that the genome of C. abortus is highly stable.

Adapting to Biology: Maintaining Container-Closure System Compatibility with the Therapeutic Biologic Revolution.

Science.gov (United States)

Degrazio, Dominick

Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to the dimension of evolving therapeutic biologics. Important concerns associated with this changeover are becoming forefront, as challenges develop of varying complexity uncommon with the synthesis and production of traditional drugs. Therefore, alternative measures must be established that aim to preserve the efficacy and functionality of a biologic that might not be implemented for small molecules. Conserving protein stability is relative to perpetuating a net equilibrium of both intrinsic and extrinsic factors. Key to sustaining this balance is the ability of container-closure systems to maintain their compatibility with the ever-changing dynamics of therapeutic biologics. Failure to recognize and adjust the material properties of packaging components to support compatibility with therapeutic biologics can compromise patient safety, drug productivity, and biological stability. This review will examine the differences between small-molecule drugs and therapeutic biologics, lay a basic foundation for understanding the stability of therapeutic biologics, and demonstrate potential sources of container-closure systems' incompatibilities with therapeutic biologics at a mechanistic level. Many pharmaceutical companies are transitioning their research and development drug product pipeline from traditional small-molecule injectables to recombinantly derived therapeutic biologics. Concerns associated with this transformation are becoming prominent, as therapeutic biologics are uncharacteristic to small-molecule drugs. Maintaining the stability of a therapeutic biologic is a combination of balancing intrinsic factors and external elements within the biologic's microenvironment. An important aspect of this balance is relegated to the overall compatibility of primary, parenteral container-closure systems with therapeutic biologics

Selection against recombinant hybrids maintains reproductive isolation in hybridizing Populus species despite F1 fertility and recurrent gene flow.

Science.gov (United States)

Christe, Camille; Stölting, Kai N; Bresadola, Luisa; Fussi, Barbara; Heinze, Berthold; Wegmann, Daniel; Lexer, Christian

2016-06-01

Natural hybrid zones have proven to be precious tools for understanding the origin and maintenance of reproductive isolation (RI) and therefore species. Most available genomic studies of hybrid zones using whole- or partial-genome resequencing approaches have focused on comparisons of the parental source populations involved in genome admixture, rather than exploring fine-scale patterns of chromosomal ancestry across the full admixture gradient present between hybridizing species. We have studied three well-known European 'replicate' hybrid zones of Populus alba and P. tremula, two widespread, ecologically divergent forest trees, using up to 432 505 single-nucleotide polymorphisms (SNPs) from restriction site-associated DNA (RAD) sequencing. Estimates of fine-scale chromosomal ancestry, genomic divergence and differentiation across all 19 poplar chromosomes revealed strikingly contrasting results, including an unexpected preponderance of F1 hybrids in the centre of genomic clines on the one hand, and genomically localized, spatially variable shared variants consistent with ancient introgression between the parental species on the other. Genetic ancestry had a significant effect on survivorship of hybrid seedlings in a common garden trial, pointing to selection against early-generation recombinants. Our results indicate a role for selection against recombinant genotypes in maintaining RI in the face of apparent F1 fertility, consistent with the intragenomic 'coadaptation' model of barriers to introgression upon secondary contact. Whole-genome resequencing of hybridizing populations will clarify the roles of specific genetic pathways in RI between these model forest trees and may reveal which loci are affected most strongly by its cyclic breakdown. © 2016 John Wiley & Sons Ltd.

RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity.

Science.gov (United States)

Vannier, Jean-Baptiste; Pavicic-Kaltenbrunner, Visnja; Petalcorin, Mark I R; Ding, Hao; Boulton, Simon J

2012-05-11

T loops and telomeric G-quadruplex (G4) DNA structures pose a potential threat to genome stability and must be dismantled to permit efficient telomere replication. Here we implicate the helicase RTEL1 in the removal of telomeric DNA secondary structures, which is essential for preventing telomere fragility and loss. In the absence of RTEL1, T loops are inappropriately resolved by the SLX4 nuclease complex, resulting in loss of the telomere as a circle. Depleting SLX4 or blocking DNA replication abolished telomere circles (TCs) and rescued telomere loss in RTEL1(-/-) cells but failed to suppress telomere fragility. Conversely, stabilization of telomeric G4-DNA or loss of BLM dramatically enhanced telomere fragility in RTEL1-deficient cells but had no impact on TC formation or telomere loss. We propose that RTEL1 performs two distinct functions at telomeres: it disassembles T loops and also counteracts telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere. Copyright © 2012 Elsevier Inc. All rights reserved.

Dengue Virus Genome Uncoating Requires Ubiquitination.

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Byk, Laura A; Iglesias, Néstor G; De Maio, Federico A; Gebhard, Leopoldo G; Rossi, Mario; Gamarnik, Andrea V

2016-06-28

The process of genome release or uncoating after viral entry is one of the least-studied steps in the flavivirus life cycle. Flaviviruses are mainly arthropod-borne viruses, including emerging and reemerging pathogens such as dengue, Zika, and West Nile viruses. Currently, dengue virus is one of the most significant human viral pathogens transmitted by mosquitoes and is responsible for about 390 million infections every year around the world. Here, we examined for the first time molecular aspects of dengue virus genome uncoating. We followed the fate of the capsid protein and RNA genome early during infection and found that capsid is degraded after viral internalization by the host ubiquitin-proteasome system. However, proteasome activity and capsid degradation were not necessary to free the genome for initial viral translation. Unexpectedly, genome uncoating was blocked by inhibiting ubiquitination. Using different assays to bypass entry and evaluate the first rounds of viral translation, a narrow window of time during infection that requires ubiquitination but not proteasome activity was identified. In this regard, ubiquitin E1-activating enzyme inhibition was sufficient to stabilize the incoming viral genome in the cytoplasm of infected cells, causing its retention in either endosomes or nucleocapsids. Our data support a model in which dengue virus genome uncoating requires a nondegradative ubiquitination step, providing new insights into this crucial but understudied viral process. Dengue is the most significant arthropod-borne viral infection in humans. Although the number of cases increases every year, there are no approved therapeutics available for the treatment of dengue infection, and many basic aspects of the viral biology remain elusive. After entry, the viral membrane must fuse with the endosomal membrane to deliver the viral genome into the cytoplasm for translation and replication. A great deal of information has been obtained in the last decade

Use of an extracapsular stabilization technique to repair cruciate ligament ruptures in two avian species.

Science.gov (United States)

Chinnadurai, Sathya K; Spodnick, Gary; Degernes, Laurel; DeVoe, Ryan S; Marcellin-Little, Denis J

2009-12-01

An extracapsular stabilization technique was used to repair cruciate ligament ruptures in a trumpeter hornbill (Bycanistes bucinator) and an African grey parrot (Psittacus erithacus). The hornbill demonstrated cranial drawer motion and severe rotational instability of the stifle from ruptures of the cranial and caudal cruciate ligaments and stifle joint capsule. The luxation was reduced, and the fibula was cranially transposed, in relation to the tibiotarsus, and anchored with 2 positive profile threaded acrylic pins. A lateral extracapsular stabilization was then performed. The African grey parrot had a traumatic stifle luxation, and an open reduction and a lateral extracapsular stabilization were performed. Both birds regained function of the affected leg by 1 month after surgery. Extracapsular stabilization allows motion of the stifle joint to be maintained during the postoperative recovery period, an advantage over rigid stabilization. Maintaining motion in the stifle joint facilitates physical therapy and can aid in full recovery after avian stifle injuries.

Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

Science.gov (United States)

Pampalona, Judit; Roscioli, Emanuele; Silkworth, William T; Bowden, Brent; Genescà, Anna; Tusell, Laura; Cimini, Daniela

2016-01-01

Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

Complete sequence and analysis of plastid genomes of two economically important red algae: Pyropia haitanensis and Pyropia yezoensis.

Directory of Open Access Journals (Sweden)

Li Wang

Full Text Available Pyropia haitanensis and P. yezoensis are two economically important marine crops that are also considered to be research models to study the physiological ecology of intertidal seaweed communities, evolutionary biology of plastids, and the origins of sexual reproduction. This plastid genome information will facilitate study of breeding, population genetics and phylogenetics.We have fully sequenced using next-generation sequencing the circular plastid genomes of P. hatanensis (195,597 bp and P. yezoensis (191,975 bp, the largest of all the plastid genomes of the red lineage sequenced to date. Organization and gene contents of the two plastids were similar, with 211-213 protein-coding genes (including 29-31 unknown-function ORFs, 37 tRNA genes, and 6 ribosomal RNA genes, suggesting a largest coding capacity in the red lineage. In each genome, 14 protein genes overlapped and no interrupted genes were found, indicating a high degree of genomic condensation. Pyropia maintain an ancient gene content and conserved gene clusters in their plastid genomes, containing nearly complete repertoires of the plastid genes known in photosynthetic eukaryotes. Similarity analysis based on the whole plastid genome sequences showed the distance between P. haitanensis and P. yezoensis (0.146 was much smaller than that of Porphyra purpurea and P. haitanensis (0.250, and P. yezoensis (0.251; this supports re-grouping the two species in a resurrected genus Pyropia while maintaining P. purpurea in genus Porphyra. Phylogenetic analysis supports a sister relationship between Bangiophyceae and Florideophyceae, though precise phylogenetic relationships between multicellular red alage and chromists were not fully resolved.These results indicate that Pyropia have compact plastid genomes. Large coding capacity and long intergenic regions contribute to the size of the largest plastid genomes reported for the red lineage. Possessing the largest coding capacity and ancient gene

Lactococcus lactis Diversity in Undefined Mixed Dairy Starter Cultures as Revealed by Comparative Genome Analyses and Targeted Amplicon Sequencing of epsD.

Science.gov (United States)

Frantzen, Cyril A; Kleppen, Hans Petter; Holo, Helge

2018-02-01

Undefined mesophilic mixed (DL) starter cultures are used in the production of continental cheeses and contain unknown strain mixtures of Lactococcus lactis and leuconostocs. The choice of starter culture affects the taste, aroma, and quality of the final product. To gain insight into the diversity of Lactococcus lactis strains in starter cultures, we whole-genome sequenced 95 isolates from three different starter cultures. Pan-genomic analyses, which included 30 publically available complete genomes, grouped the strains into 21 L. lactis subsp . lactis and 28 L. lactis subsp. cremoris lineages. Only one of the 95 isolates grouped with previously sequenced strains, and the three starter cultures showed no overlap in lineage distributions. The culture diversity was assessed by targeted amplicon sequencing using purR , a core gene, and epsD , present in 93 of the 95 starter culture isolates but absent in most of the reference strains. This enabled an unprecedented discrimination of starter culture Lactococcus lactis and revealed substantial differences between the three starter cultures and compositional shifts during the cultivation of cultures in milk. IMPORTANCE In contemporary cheese production, standardized frozen seed stock starter cultures are used to ensure production stability, reproducibility, and quality control of the product. The dairy industry experiences significant disruptions of cheese production due to phage attacks, and one commonly used countermeasure to phage attack is to employ a starter rotation strategy, in which two or more starters with minimal overlap in phage sensitivity are used alternately. A culture-independent analysis of the lactococcal diversity in complex undefined starter cultures revealed large differences between the three starter cultures and temporal shifts in lactococcal composition during the production of bulk starters. A better understanding of the lactococcal diversity in starter cultures will enable the development of

Stability of glassy hierarchical networks

Science.gov (United States)

Zamani, M.; Camargo-Forero, L.; Vicsek, T.

2018-02-01

The structure of interactions in most animal and human societies can be best represented by complex hierarchical networks. In order to maintain close-to-optimal function both stability and adaptability are necessary. Here we investigate the stability of hierarchical networks that emerge from the simulations of an organization type with an efficiency function reminiscent of the Hamiltonian of spin glasses. Using this quantitative approach we find a number of expected (from everyday observations) and highly non-trivial results for the obtained locally optimal networks, including, for example: (i) stability increases with growing efficiency and level of hierarchy; (ii) the same perturbation results in a larger change for more efficient states; (iii) networks with a lower level of hierarchy become more efficient after perturbation; (iv) due to the huge number of possible optimal states only a small fraction of them exhibit resilience and, finally, (v) ‘attacks’ targeting the nodes selectively (regarding their position in the hierarchy) can result in paradoxical outcomes.

Motor Difficulties in Autism Spectrum Disorder: Linking Symptom Severity and Postural Stability

Science.gov (United States)

Travers, Brittany G.; Powell, Patrick S.; Klinger, Laura G.; Klinger, Mark R.

2013-01-01

Postural stability is a fundamental aspect of motor ability that allows individuals to sustain and maintain the desired physical position of one's body. The present study examined postural stability in average-IQ adolescents and adults with Autism Spectrum Disorder (ASD). Twenty-six individuals with ASD and 26 age-and-IQ-matched individuals…

The Contribution of Tissue Level Organization to Genomic Stability Following Low Dose/Low Dose Rate Gamma and Proton Irradiation

Energy Technology Data Exchange (ETDEWEB)

Cheryl G. Burrell, Ph.D.

2012-05-14

The formation of functional tissue units is necessary in maintaining homeostasis within living systems, with individual cells contributing to these functional units through their three-dimensional organization with integrin and adhesion proteins to form a complex extra-cellular matrix (ECM). This is of particular importance in those tissues susceptible to radiation-induced tumor formation, such as epithelial glands. The assembly of epithelial cells of the thyroid is critical to their normal receipt of, and response to, incoming signals. Traditional tissue culture and live animals present significant challenges to radiation exposure and continuous sampling, however, the production of bioreactor-engineered tissues aims to bridge this gap by improve capabilities in continuous sampling from the same functional tissue, thereby increasing the ability to extrapolate changes induced by radiation to animals and humans in vivo. Our study proposes that the level of tissue organization will affect the induction and persistence of low dose radiation-induced genomic instability. Rat thyroid cells, grown in vitro as 3D tissue analogs in bioreactors and as 2D flask grown cultures were exposed to acute low dose (1, 5, 10 and 200 cGy) gamma rays. To assess immediate (6 hours) and delayed (up to 30 days) responses post-irradiation, various biological endpoints were studied including cytogenetic analyses, apoptosis analysis and cell viability/cytotoxicity analyses. Data assessing caspase 3/7 activity levels show that, this activity varies with time post radiation and that, overall, 3D cultures display more genomic instability (as shown by the lower levels of apoptosis over time) when compared to the 2D cultures. Variation in cell viability levels were only observed at the intermediate and late time points post radiation. Extensive analysis of chromosomal aberrations will give further insight on the whether the level of tissue organization influences genomic instability patterns after

Roles of the creatine kinase system and myoglobin in maintaining energetic state in the working heart

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Beard Daniel A

2009-02-01

Full Text Available Abstract Background The heart is capable of maintaining contractile function despite a transient decrease in blood flow and increase in cardiac ATP demand during systole. This study analyzes a previously developed model of cardiac energetics and oxygen transport to understand the roles of the creatine kinase system and myoglobin in maintaining the ATP hydrolysis potential during beat-to-beat transient changes in blood flow and ATP hydrolysis rate. Results The theoretical investigation demonstrates that elimination of myoglobin only slightly increases the predicted range of oscillation of cardiac oxygenation level during beat-to-beat transients in blood flow and ATP utilization. In silico elimination of myoglobin has almost no impact on the cytoplasmic ATP hydrolysis potential (ΔGATPase. In contrast, disabling the creatine kinase system results in considerable oscillations of cytoplasmic ADP and ATP levels and seriously deteriorates the stability of ΔGATPase in the beating heart. Conclusion The CK system stabilizes ΔGATPase by both buffering ATP and ADP concentrations and enhancing the feedback signal of inorganic phosphate in regulating mitochondrial oxidative phosphorylation.

PATRIMONIAL ANALYSIS OF FINANCIAL STABILITY

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GABRIELA CORINA SLUSARIUC

2011-01-01

Full Text Available Patrimonial analysis of financial stability is realized with the help of some indicator determined on the balance: working capital; required working capital and net treasury. These indicators are determined and presented in evolution at two companies with different situations, and there are given conclusions and suggestions concerning achieving and maintaining the financial equilibrium or initiating corrective measures in time, before the imbalance would take irrecoverable forms.

Ensembl Genomes 2016: more genomes, more complexity.

Science.gov (United States)

Kersey, Paul Julian; Allen, James E; Armean, Irina; Boddu, Sanjay; Bolt, Bruce J; Carvalho-Silva, Denise; Christensen, Mikkel; Davis, Paul; Falin, Lee J; Grabmueller, Christoph; Humphrey, Jay; Kerhornou, Arnaud; Khobova, Julia; Aranganathan, Naveen K; Langridge, Nicholas; Lowy, Ernesto; McDowall, Mark D; Maheswari, Uma; Nuhn, Michael; Ong, Chuang Kee; Overduin, Bert; Paulini, Michael; Pedro, Helder; Perry, Emily; Spudich, Giulietta; Tapanari, Electra; Walts, Brandon; Williams, Gareth; Tello-Ruiz, Marcela; Stein, Joshua; Wei, Sharon; Ware, Doreen; Bolser, Daniel M; Howe, Kevin L; Kulesha, Eugene; Lawson, Daniel; Maslen, Gareth; Staines, Daniel M

2016-01-04

Ensembl Genomes (http://www.ensemblgenomes.org) is an integrating resource for genome-scale data from non-vertebrate species, complementing the resources for vertebrate genomics developed in the context of the Ensembl project (http://www.ensembl.org). Together, the two resources provide a consistent set of programmatic and interactive interfaces to a rich range of data including reference sequence, gene models, transcriptional data, genetic variation and comparative analysis. This paper provides an update to the previous publications about the resource, with a focus on recent developments. These include the development of new analyses and views to represent polyploid genomes (of which bread wheat is the primary exemplar); and the continued up-scaling of the resource, which now includes over 23 000 bacterial genomes, 400 fungal genomes and 100 protist genomes, in addition to 55 genomes from invertebrate metazoa and 39 genomes from plants. This dramatic increase in the number of included genomes is one part of a broader effort to automate the integration of archival data (genome sequence, but also associated RNA sequence data and variant calls) within the context of reference genomes and make it available through the Ensembl user interfaces. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Comprehensive characterization of genomic instability in pluripotent stem cells and their derived neuroprogenitor cell lines

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Nestor Luis Lopez Corrales

2012-12-01

Full Text Available The genomic integrity of two human pluripotent stem cells and their derived neuroprogenitor cell lines was studied, applying a combination of high-resolution genetic methodologies. The usefulness of combining array-comparative genomic hybridization (aCGH and multiplex fluorescence in situ hybridization (M-FISH techniques should be delineated to exclude/detect a maximum of possible genomic structural aberrations. Interestingly, in parts different genomic imbalances at chromosomal and subchromosomal levels were detected in pluripotent stem cells and their derivatives. Some of the copy number variations were inherited from the original cell line, whereas other modifications were presumably acquired during the differentiation and manipulation procedures. These results underline the necessity to study both pluripotent stem cells and their differentiated progeny by as many approaches as possible in order to assess their genomic stability before using them in clinical therapies.

Pushing Boundaries while Maintaining Stability

DEFF Research Database (Denmark)

Lippke, Lena; Wegener, Charlotte

at the same time. The exploration of transforming practices shows how disturbances in relation to the ‘normal’ practices are created and thus makes invisible conventions which are taken for granted visible. Thus, this paper addresses two types of invisibility: the unnoticed boundary-pushing practices...

[Stabilization and long-term effect of chromium contaminated soil].

Science.gov (United States)

Wang, Jing; Luo, Qi-Shi; Zhang, Chang-Bo; Tan, Liang; Li, Xu

2013-10-01

Short-term (3 d and 28 d) and long-term (1 a) stabilization effects of Cr contaminated soil were investigated through nature curing, using four amendments including ferrous sulfide, ferrous sulfate, zero-valent iron and sodium dithionite. The results indicated that ferrous sulfide and zero-valent iron were not helpful for the stabilization of Cr(VI) when directly used because of their poor solubility and immobility. Ferrous sulfate could effectively and rapidly decrease total leaching Cr and Cr(VI) content. The stabilization effect was further promoted by the generation of iron hydroxides after long-term curing. Sodium dithionite also had positive effect on soil stabilization. Appropriate addition ratio of the two chemicals could help maintain the soil pH in range of 6-8.

Crossing the LINE toward genomic instability: LINE-1 retrotransposition in cancer

Science.gov (United States)

Kemp, Jacqueline; Longworth, Michelle

2015-12-01

Retrotransposons are repetitive DNA sequences that are positioned throughout the human genome. Retrotransposons are capable of copying themselves and mobilizing new copies to novel genomic locations in a process called retrotransposition. While most retrotransposon sequences in the human genome are incomplete and incapable of mobilization, the LINE-1 retrotransposon, which comprises approximately 17% of the human genome, remains active. The disruption of cellular mechanisms that suppress retrotransposon activity is linked to the generation of aneuploidy, a potential driver of tumor development. When retrotransposons insert into a novel genomic region, they have the potential to disrupt the coding sequence of endogenous genes and alter gene expression, which can lead to deleterious consequences for the organism. Additionally, increased LINE-1 copy numbers provide more chances for recombination events to occur between retrotransposons, which can lead to chromosomal breaks and rearrangements. LINE-1 activity is increased in various cancer cell lines and in patient tissues resected from primary tumors. LINE-1 activity also correlates with increased cancer metastasis. This review aims to give a brief overview of the connections between LINE-1 retrotransposition and the loss of genome stability. We will also discuss the mechanisms that repress retrotransposition in human cells and their links to cancer.

The structure-specific endonuclease Ercc1-Xpf is required for targeted gene replacement in embryonic stem cells

NARCIS (Netherlands)

L.J. Niedernhofer (Laura); J. Essers (Jeroen); G. Weeda (Geert); H.B. Beverloo (Berna); J. de Wit (Jan); M. Muijtjens (Manja); H. Odijk (Hanny); J.H.J. Hoeijmakers (Jan); R. Kanaar (Roland)

2001-01-01

textabstractThe Ercc1-Xpf heterodimer, a highly conserved structure-specific endonuclease, functions in multiple DNA repair pathways that are pivotal for maintaining genome stability, including nucleotide excision repair, interstrand crosslink repair and homologous recombination. Erccl-Xpf incises

Re-exploration of U's Triangle Brassica Species Based on Chloroplast Genomes and 45S nrDNA Sequences.

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Kim, Chang-Kug; Seol, Young-Joo; Perumal, Sampath; Lee, Jonghoon; Waminal, Nomar Espinosa; Jayakodi, Murukarthick; Lee, Sang-Choon; Jin, Seungwoo; Choi, Beom-Soon; Yu, Yeisoo; Ko, Ho-Cheol; Choi, Ji-Weon; Ryu, Kyoung-Yul; Sohn, Seong-Han; Parkin, Isobel; Yang, Tae-Jin

2018-05-09

The concept of U's triangle, which revealed the importance of polyploidization in plant genome evolution, described natural allopolyploidization events in Brassica using three diploids [B. rapa (A genome), B. nigra (B), and B. oleracea (C)] and derived allotetraploids [B. juncea (AB genome), B. napus (AC), and B. carinata (BC)]. However, comprehensive understanding of Brassica genome evolution has not been fully achieved. Here, we performed low-coverage (2-6×) whole-genome sequencing of 28 accessions of Brassica as well as of Raphanus sativus [R genome] to explore the evolution of six Brassica species based on chloroplast genome and ribosomal DNA variations. Our phylogenomic analyses led to two main conclusions. (1) Intra-species-level chloroplast genome variations are low in the three allotetraploids (2~7 SNPs), but rich and variable in each diploid species (7~193 SNPs). (2) Three allotetraploids maintain two 45SnrDNA types derived from both ancestral species with maternal dominance. Furthermore, this study sheds light on the maternal origin of the AC chloroplast genome. Overall, this study clarifies the genetic relationships of U's triangle species based on a comprehensive genomics approach and provides important genomic resources for correlative and evolutionary studies.

Long term stability of yttria-stabilized zirconia waste forms. Stability for secular change of partitioned TRU waste composition by disintegration

International Nuclear Information System (INIS)

Kuramoto, Ken-ichi; Banba, Tsunetaka; Mitamura, Hisayoshi; Sakai, Etsuro; Uno, Masayoshi; Kinoshita, H.; Yamanaka, Shinsuke

1999-01-01

In this study, the stability of YSZ waste forms for secular change of partitioned TRU waste composition by disintegration, one of important terms in long-term stability, is the special concern. Designed amount of waste and YSZ powder were mixed and sintered. These TRU waste forms were submitted to tests of phase stability, chemical durability, mechanical property and compactness. The results were compared with those of another YSZ waste forms, non-radioactive Ce and/or Nd doped YSZ samples, and glass and Synroc waste forms. Experimental results show following: (1) Phase stability of (Np+Am)-, (Np+U)-, and (Np+U+Bi)-doped YSZ waste forms could be maintained of that of the initial Np+Am-doped YSZ waste form permanently even when the composition of partitioned TRU waste were changed by disintegration. (2) Secular change also accelerated volume increase of YSZ waste forms as well as alpha-decay damage. (3) Hv, E and K IC of (Np+U)- and (Np+U+Bi)-doped YSZ waste forms were independent of the secular change of the partitioned TRU waste composition by disintegration. (4) Mechanical properties of YSZ waste forms were more than those of a glass and Synroc waste forms. (5) Compactness of YSZ waste forms was good as waste forms for the partitioned TRU wastes. (J.P.N.)

phiGENOME: an integrative navigation throughout bacteriophage genomes.

Science.gov (United States)

Stano, Matej; Klucar, Lubos

2011-11-01

phiGENOME is a web-based genome browser generating dynamic and interactive graphical representation of phage genomes stored in the phiSITE, database of gene regulation in bacteriophages. phiGENOME is an integral part of the phiSITE web portal (http://www.phisite.org/phigenome) and it was optimised for visualisation of phage genomes with the emphasis on the gene regulatory elements. phiGENOME consists of three components: (i) genome map viewer built using Adobe Flash technology, providing dynamic and interactive graphical display of phage genomes; (ii) sequence browser based on precisely formatted HTML tags, providing detailed exploration of genome features on the sequence level and (iii) regulation illustrator, based on Scalable Vector Graphics (SVG) and designed for graphical representation of gene regulations. Bringing 542 complete genome sequences accompanied with their rich annotations and references, makes phiGENOME a unique information resource in the field of phage genomics. Copyright © 2011 Elsevier Inc. All rights reserved.

The roles of the Saccharomyces cerevisiae RecQ helicase SGS1 in meiotic genome surveillance.

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Amit Dipak Amin

2010-11-01

Full Text Available The Saccharomyces cerevisiae RecQ helicase Sgs1 is essential for mitotic and meiotic genome stability. The stage at which Sgs1 acts during meiosis is subject to debate. Cytological experiments showed that a deletion of SGS1 leads to an increase in synapsis initiation complexes and axial associations leading to the proposal that it has an early role in unwinding surplus strand invasion events. Physical studies of recombination intermediates implicate it in the dissolution of double Holliday junctions between sister chromatids.In this work, we observed an increase in meiotic recombination between diverged sequences (homeologous recombination and an increase in unequal sister chromatid events when SGS1 is deleted. The first of these observations is most consistent with an early role of Sgs1 in unwinding inappropriate strand invasion events while the second is consistent with unwinding or dissolution of recombination intermediates in an Mlh1- and Top3-dependent manner. We also provide data that suggest that Sgs1 is involved in the rejection of 'second strand capture' when sequence divergence is present. Finally, we have identified a novel class of tetrads where non-sister spores (pairs of spores where each contains a centromere marker from a different parent are inviable. We propose a model for this unusual pattern of viability based on the inability of sgs1 mutants to untangle intertwined chromosomes. Our data suggest that this role of Sgs1 is not dependent on its interaction with Top3. We propose that in the absence of SGS1 chromosomes may sometimes remain entangled at the end of pre-meiotic replication. This, combined with reciprocal crossing over, could lead to physical destruction of the recombined and entangled chromosomes. We hypothesise that Sgs1, acting in concert with the topoisomerase Top2, resolves these structures.This work provides evidence that Sgs1 interacts with various partner proteins to maintain genome stability throughout

The mitochondrial genome of Phallusia mammillata and Phallusia fumigata (Tunicata, Ascidiacea: high genome plasticity at intra-genus level

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Pesole Graziano

2007-08-01

Full Text Available Abstract Background Within Chordata, the subphyla Vertebrata and Cephalochordata (lancelets are characterized by a remarkable stability of the mitochondrial (mt genome, with constancy of gene content and almost invariant gene order, whereas the limited mitochondrial data on the subphylum Tunicata suggest frequent and extensive gene rearrangements, observed also within ascidians of the same genus. Results To confirm this evolutionary trend and to better understand the evolutionary dynamics of the mitochondrial genome in Tunicata Ascidiacea, we have sequenced and characterized the complete mt genome of two congeneric ascidian species, Phallusia mammillata and Phallusia fumigata (Phlebobranchiata, Ascidiidae. The two mtDNAs are surprisingly rearranged, both with respect to one another and relative to those of other tunicates and chordates, with gene rearrangements affecting both protein-coding and tRNA genes. The new data highlight the extraordinary variability of ascidian mt genome in base composition, tRNA secondary structure, tRNA gene content, and non-coding regions (number, size, sequence and location. Indeed, both Phallusia genomes lack the trnD gene, show loss/acquisition of DHU-arm in two tRNAs, and have a G+C content two-fold higher than other ascidians. Moreover, the mt genome of P. fumigata presents two identical copies of trnI, an extra tRNA gene with uncertain amino acid specificity, and four almost identical sequence regions. In addition, a truncated cytochrome b, lacking a C-terminal tail that commonly protrudes into the mt matrix, has been identified as a new mt feature probably shared by all tunicates. Conclusion The frequent occurrence of major gene order rearrangements in ascidians both at high taxonomic level and within the same genus makes this taxon an excellent model to study the mechanisms of gene rearrangement, and renders the mt genome an invaluable phylogenetic marker to investigate molecular biodiversity and speciation

Scaffold expulsion and genome packaging trigger stabilization of herpes simplex virus capsids

Science.gov (United States)

Roos, Wouter H.; Radtke, Kerstin; Kniesmeijer, Edward; Geertsema, Hylkje; Sodeik, Beate; Wuite, Gijs J. L.

2009-01-01

Herpes simplex virus type 1 (HSV1) capsids undergo extensive structural changes during maturation and DNA packaging. As a result, they become more stable and competent for nuclear egress. To further elucidate this stabilization process, we used biochemical and nanoindentation approaches to analyze the structural and mechanical properties of scaffold-containing (B), empty (A), and DNA-containing (C) nuclear capsids. Atomic force microscopy experiments revealed that A and C capsids were mechanically indistinguishable, indicating that the presence of DNA does not account for changes in mechanical properties during capsid maturation. Despite having the same rigidity, the scaffold-containing B capsids broke at significantly lower forces than A and C capsids. An extraction of pentons with guanidine hydrochloride (GuHCl) increased the flexibility of all capsids. Surprisingly, the breaking forces of the modified A and C capsids dropped to similar values as those of the GuHCl-treated B capsids, indicating that mechanical reinforcement occurs at the vertices. Nonetheless, it also showed that HSV1 capsids possess a remarkable structural integrity that was preserved after removal of pentons. We suggest that HSV1 capsids are stabilized after removal of the scaffold proteins, and that this stabilization is triggered by the packaging of DNA, but independent of the actual presence of DNA. PMID:19487681

Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia.

Science.gov (United States)

Mamrak, Nicholas E; Shimamura, Akiko; Howlett, Niall G

2017-05-01

Fanconi anemia (FA) is a rare autosomal and X-linked genetic disease characterized by congenital abnormalities, progressive bone marrow failure (BMF), and increased cancer risk during early adulthood. The median lifespan for FA patients is approximately 33years. The proteins encoded by the FA genes function together in the FA-BRCA pathway to repair DNA damage and to maintain genome stability. Within the past two years, five new FA genes have been identified-RAD51/FANCR, BRCA1/FANCS, UBE2T/FANCT, XRCC2/FANCU, and REV7/FANCV-bringing the total number of disease-causing genes to 21. This review summarizes the discovery of these new FA genes and describes how these proteins integrate into the FA-BRCA pathway to maintain genome stability and critically prevent early-onset BMF and cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-term memory stabilized by noise-induced rehearsal.

Science.gov (United States)

Wei, Yi; Koulakov, Alexei A

2014-11-19

Cortical networks can maintain memories for decades despite the short lifetime of synaptic strengths. Can a neural network store long-lasting memories in unstable synapses? Here, we study the effects of ongoing spike-timing-dependent plasticity (STDP) on the stability of memory patterns stored in synapses of an attractor neural network. We show that certain classes of STDP rules can stabilize all stored memory patterns despite a short lifetime of synapses. In our model, unstructured neural noise, after passing through the recurrent network connections, carries the imprint of all memory patterns in temporal correlations. STDP, combined with these correlations, leads to reinforcement of all stored patterns, even those that are never explicitly visited. Our findings may provide the functional reason for irregular spiking displayed by cortical neurons and justify models of system memory consolidation. Therefore, we propose that irregular neural activity is the feature that helps cortical networks maintain stable connections. Copyright © 2014 the authors 0270-6474/14/3415804-12$15.00/0.

The Relationship Between Postural and Movement Stability.

Science.gov (United States)

Feldman, Anatol G

2016-01-01

Postural stabilization is provided by stretch reflexes, intermuscular reflexes, and intrinsic muscle properties. Taken together, these posture-stabilizing mechanisms resist deflections from the posture at which balance of muscle and external forces is maintained. Empirical findings suggest that for each muscle, these mechanisms become functional at a specific, spatial threshold-the muscle length or respective joint angle at which motor units begin to be recruited. Empirical data suggest that spinal and supraspinal centers can shift the spatial thresholds for a group of muscles that stabilized the initial posture. As a consequence, the same stabilizing mechanisms, instead of resisting motion from the initial posture, drive the body to another stable posture. In other words by shifting spatial thresholds, the nervous system converts movement resisting to movement-producing mechanisms. It is illustrated that, contrary to conventional view, this control strategy allows the system to transfer body balance to produce locomotion and other actions without loosing stability at any point of them. It also helps orient posture and movement with the direction of gravity. It is concluded that postural and movement stability is provided by a common mechanism.

Genome Maps, a new generation genome browser.

Science.gov (United States)

Medina, Ignacio; Salavert, Francisco; Sanchez, Rubén; de Maria, Alejandro; Alonso, Roberto; Escobar, Pablo; Bleda, Marta; Dopazo, Joaquín

2013-07-01

Genome browsers have gained importance as more genomes and related genomic information become available. However, the increase of information brought about by new generation sequencing technologies is, at the same time, causing a subtle but continuous decrease in the efficiency of conventional genome browsers. Here, we present Genome Maps, a genome browser that implements an innovative model of data transfer and management. The program uses highly efficient technologies from the new HTML5 standard, such as scalable vector graphics, that optimize workloads at both server and client sides and ensure future scalability. Thus, data management and representation are entirely carried out by the browser, without the need of any Java Applet, Flash or other plug-in technology installation. Relevant biological data on genes, transcripts, exons, regulatory features, single-nucleotide polymorphisms, karyotype and so forth, are imported from web services and are available as tracks. In addition, several DAS servers are already included in Genome Maps. As a novelty, this web-based genome browser allows the local upload of huge genomic data files (e.g. VCF or BAM) that can be dynamically visualized in real time at the client side, thus facilitating the management of medical data affected by privacy restrictions. Finally, Genome Maps can easily be integrated in any web application by including only a few lines of code. Genome Maps is an open source collaborative initiative available in the GitHub repository (https://github.com/compbio-bigdata-viz/genome-maps). Genome Maps is available at: http://www.genomemaps.org.

Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability

Directory of Open Access Journals (Sweden)

Annika Tuomela

2016-05-01

Full Text Available Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed.

Fanconi anaemia and the repair of Watson and Crick DNA crosslinks.

Science.gov (United States)

Kottemann, Molly C; Smogorzewska, Agata

2013-01-17

The function of Fanconi anaemia proteins is to maintain genomic stability. Their main role is in the repair of DNA interstrand crosslinks, which, by covalently binding the Watson and the Crick strands of DNA, impede replication and transcription. Inappropriate repair of interstrand crosslinks causes genomic instability, leading to cancer; conversely, the toxicity of crosslinking agents makes them a powerful chemotherapeutic. Fanconi anaemia proteins can promote stem-cell function, prevent tumorigenesis, stabilize replication forks and inhibit inaccurate repair. Recent advances have identified endogenous aldehydes as possible culprits of DNA damage that may induce the phenotypes seen in patients with Fanconi anaemia.

Statistical Study on Respiratory Stability Through RPM Signal Analysis according to Patient Position Under Radiation Therapy and Device

International Nuclear Information System (INIS)

Park, Myung Hwan; Seo, Jeong Min; Choi, Byeong Gi; Shin, Eun Hyeok; Song, Gi Won

2011-01-01

This study statistically analyzed the difference of the stability of maintaining a respiratory period shown according to position and use of a device to search the tendency and usefulness of a device. The study obtained respiratory signals which maintained a respiratory period for 20 minutes each supine and prone position for 11 subjects. The study obtained respiratory signals in a state of using a belly board for 7 patients in a bad condition of a respiratory period in a prone position to analyze a change in respiration and the stability before and after the use of a device. The supine part showed 54.5%, better than the prone part of 36.4% in a case that the stability for maintaining a respiratory period was in a good condition as a fixed respiratory period was well maintained according to the position. 6 patients (85%) showed a maintenance pattern of a respiratory period significantly different before the use and 4 patients showed a significantly good change in the stability for maintaining a respiratory period as a result that belly boards were used for 7 patients that the maintenance of a respiratory period was not in a good condition on a prone position. It seemed that this study could contribute to the maintenance of respiratory period and of respiratory stability as the optimal position for maintenance of respiration and the use of a device such as a belly board were decided through statistic analysis of respiratory signals and its application even if patient position and use of device were decided by the beam arrangement a treatment part of a patient, location of a target, and an expected plan.

Late replication domains are evolutionary conserved in the Drosophila genome.

Science.gov (United States)

Andreyenkova, Natalya G; Kolesnikova, Tatyana D; Makunin, Igor V; Pokholkova, Galina V; Boldyreva, Lidiya V; Zykova, Tatyana Yu; Zhimulev, Igor F; Belyaeva, Elena S

2013-01-01

Drosophila chromosomes are organized into distinct domains differing in their predominant chromatin composition, replication timing and evolutionary conservation. We show on a genome-wide level that genes whose order has remained unaltered across 9 Drosophila species display late replication timing and frequently map to the regions of repressive chromatin. This observation is consistent with the existence of extensive domains of repressive chromatin that replicate extremely late and have conserved gene order in the Drosophila genome. We suggest that such repressive chromatin domains correspond to a handful of regions that complete replication at the very end of S phase. We further demonstrate that the order of genes in these regions is rarely altered in evolution. Substantial proportion of such regions significantly coincide with large synteny blocks. This indicates that there are evolutionary mechanisms maintaining the integrity of these late-replicating chromatin domains. The synteny blocks corresponding to the extremely late-replicating regions in the D. melanogaster genome consistently display two-fold lower gene density across different Drosophila species.

ZUFSP Deubiquitylates K63-Linked Polyubiquitin Chains to Promote Genome Stability

DEFF Research Database (Denmark)

Haahr, Peter; Borgermann, Nikoline; Guo, Xiaohu

2018-01-01

Deubiquitylating enzymes (DUBs) enhance the dynamics of the versatile ubiquitin (Ub) code by reversing and regulating cellular ubiquitylation processes at multiple levels. Here we discovered that the uncharacterized human protein ZUFSP (zinc finger with UFM1-specific peptidase domain protein/C6orf......113/ZUP1), which has been annotated as a potentially inactive UFM1 protease, and its fission yeast homolog Mug105 define a previously unrecognized class of evolutionarily conserved cysteine protease DUBs. Human ZUFSP selectively interacts with and cleaves long K63-linked poly-Ub chains by means...... establish ZUFSP as a new type of linkage-selective cysteine peptidase DUB with a role in genome maintenance pathways....

The interaction of iron and the genome: For better and for worse.

Science.gov (United States)

Troadec, Marie-Bérengère; Loréal, Olivier; Brissot, Pierre

2017-10-01

Iron, as an essential nutrient, and the DNA, as the carrier of genetic information which is physically compacted into chromosomes, are both needed for normal life and well-being. Therefore, it is not surprising that close interactions exist between iron and the genome. On the one hand, iron, especially when present in excess, may alter genome stability through oxidative stress, and may favor cell cycle abnormalities and the development of malignant diseases. The genome also receives a feedback signal from the systemic iron status, leading to promotion of expression of genes that regulate iron metabolism. Conversely, on the other hand, DNA mutations may cause genetic iron-related diseases such as hemochromatosis, archetype of iron-overload diseases, or refractory iron deficiency anemia (IRIDA). Copyright © 2017 Elsevier B.V. All rights reserved.

The sunflower genome provides insights into oil metabolism, flowering and Asterid evolution.

Science.gov (United States)

Badouin, Hélène; Gouzy, Jérôme; Grassa, Christopher J; Murat, Florent; Staton, S Evan; Cottret, Ludovic; Lelandais-Brière, Christine; Owens, Gregory L; Carrère, Sébastien; Mayjonade, Baptiste; Legrand, Ludovic; Gill, Navdeep; Kane, Nolan C; Bowers, John E; Hubner, Sariel; Bellec, Arnaud; Bérard, Aurélie; Bergès, Hélène; Blanchet, Nicolas; Boniface, Marie-Claude; Brunel, Dominique; Catrice, Olivier; Chaidir, Nadia; Claudel, Clotilde; Donnadieu, Cécile; Faraut, Thomas; Fievet, Ghislain; Helmstetter, Nicolas; King, Matthew; Knapp, Steven J; Lai, Zhao; Le Paslier, Marie-Christine; Lippi, Yannick; Lorenzon, Lolita; Mandel, Jennifer R; Marage, Gwenola; Marchand, Gwenaëlle; Marquand, Elodie; Bret-Mestries, Emmanuelle; Morien, Evan; Nambeesan, Savithri; Nguyen, Thuy; Pegot-Espagnet, Prune; Pouilly, Nicolas; Raftis, Frances; Sallet, Erika; Schiex, Thomas; Thomas, Justine; Vandecasteele, Céline; Varès, Didier; Vear, Felicity; Vautrin, Sonia; Crespi, Martin; Mangin, Brigitte; Burke, John M; Salse, Jérôme; Muños, Stéphane; Vincourt, Patrick; Rieseberg, Loren H; Langlade, Nicolas B

2017-06-01

The domesticated sunflower, Helianthus annuus L., is a global oil crop that has promise for climate change adaptation, because it can maintain stable yields across a wide variety of environmental conditions, including drought. Even greater resilience is achievable through the mining of resistance alleles from compatible wild sunflower relatives, including numerous extremophile species. Here we report a high-quality reference for the sunflower genome (3.6 gigabases), together with extensive transcriptomic data from vegetative and floral organs. The genome mostly consists of highly similar, related sequences and required single-molecule real-time sequencing technologies for successful assembly. Genome analyses enabled the reconstruction of the evolutionary history of the Asterids, further establishing the existence of a whole-genome triplication at the base of the Asterids II clade and a sunflower-specific whole-genome duplication around 29 million years ago. An integrative approach combining quantitative genetics, expression and diversity data permitted development of comprehensive gene networks for two major breeding traits, flowering time and oil metabolism, and revealed new candidate genes in these networks. We found that the genomic architecture of flowering time has been shaped by the most recent whole-genome duplication, which suggests that ancient paralogues can remain in the same regulatory networks for dozens of millions of years. This genome represents a cornerstone for future research programs aiming to exploit genetic diversity to improve biotic and abiotic stress resistance and oil production, while also considering agricultural constraints and human nutritional needs.

Ectopic Expression of Testis Germ Cell Proteins in Cancer and Its Potential Role in Genomic Instability

Directory of Open Access Journals (Sweden)

Aaraby Yoheswaran Nielsen

2016-06-01

Full Text Available Genomic instability is a hallmark of human cancer and an enabling factor for the genetic alterations that drive cancer development. The processes involved in genomic instability resemble those of meiosis, where genetic material is interchanged between homologous chromosomes. In most types of human cancer, epigenetic changes, including hypomethylation of gene promoters, lead to the ectopic expression of a large number of proteins normally restricted to the germ cells of the testis. Due to the similarities between meiosis and genomic instability, it has been proposed that activation of meiotic programs may drive genomic instability in cancer cells. Some germ cell proteins with ectopic expression in cancer cells indeed seem to promote genomic instability, while others reduce polyploidy and maintain mitotic fidelity. Furthermore, oncogenic germ cell proteins may indirectly contribute to genomic instability through induction of replication stress, similar to classic oncogenes. Thus, current evidence suggests that testis germ cell proteins are implicated in cancer development by regulating genomic instability during tumorigenesis, and these proteins therefore represent promising targets for novel therapeutic strategies.

An Upper Limit on the Functional Fraction of the Human Genome.

Science.gov (United States)

Graur, Dan

2017-07-01

For the human population to maintain a constant size from generation to generation, an increase in fertility must compensate for the reduction in the mean fitness of the population caused, among others, by deleterious mutations. The required increase in fertility due to this mutational load depends on the number of sites in the genome that are functional, the mutation rate, and the fraction of deleterious mutations among all mutations in functional regions. These dependencies and the fact that there exists a maximum tolerable replacement level fertility can be used to put an upper limit on the fraction of the human genome that can be functional. Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 25%, and is probably considerably lower. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

The impact of genome triplication on tandem gene evolution in Brassica rapa

Directory of Open Access Journals (Sweden)

Lu eFang

2012-11-01

Full Text Available Whole genome duplication (WGD and tandem duplication (TD are both important modes of gene expansion. However, how whole genome duplication influences tandemly duplicated genes is not well studied. We used Brassica rapa, which has undergone an additional genome triplication (WGT and shares a common ancestor with Arabidopsis thaliana, Arabidopsis lyrata and Thellungiella parvula, to investigate the impact of genome triplication on tandem gene evolution. We identified 2,137, 1,569, 1,751 and 1,135 tandem gene arrays in B. rapa, A. thaliana, A. lyrata and T. parvula respectively. Among them, 414 conserved tandem arrays are shared by the 3 species without WGT, which were also considered as existing in the diploid ancestor of B. rapa. Thus, after genome triplication, B. rapa should have 1,242 tandem arrays according to the 414 conserved tandems. Here, we found 400 out of the 414 tandems had at least one syntenic ortholog in the genome of B. rapa. Furthermore, 294 out of the 400 shared syntenic orthologs maintain tandem arrays (more than one gene for each syntenic hit in B. rapa. For the 294 tandem arrays, we obtained 426 copies of syntenic paralogous tandems in the triplicated genome of B. rapa. In this study, we demonstrated that tandem arrays in B. rapa were dramatically fractionated after WGT when compared either to non-tandem genes in the B. rapa genome or to the tandem arrays in closely related species that have not experienced a recent whole-genome polyploidization event.

Genomics using the Assembly of the Mink Genome

DEFF Research Database (Denmark)

Guldbrandtsen, Bernt; Cai, Zexi; Sahana, Goutam

2018-01-01

The American Mink’s (Neovison vison) genome has recently been sequenced. This opens numerous avenues of research both for studying the basic genetics and physiology of the mink as well as genetic improvement in mink. Using genotyping-by-sequencing (GBS) generated marker data for 2,352 Danish farm...... mink runs of homozygosity (ROH) were detect in mink genomes. Detectable ROH made up on average 1.7% of the genome indicating the presence of at most a moderate level of genomic inbreeding. The fraction of genome regions found in ROH varied. Ten percent of the included regions were never found in ROH....... The ability to detect ROH in the mink genome also demonstrates the general reliability of the new mink genome assembly. Keywords: american mink, run of homozygosity, genome, selection, genomic inbreeding...

tRNA's wobble decoding of the genome: 40 years of modification.

Science.gov (United States)

Agris, Paul F; Vendeix, Franck A P; Graham, William D

2007-02-09

The genetic code is degenerate, in that 20 amino acids are encoded by 61 triplet codes. In 1966, Francis Crick hypothesized that the cell's limited number of tRNAs decoded the genome by recognizing more than one codon. The ambiguity of that recognition resided in the third base-pair, giving rise to the Wobble Hypothesis. Post-transcriptional modifications at tRNA's wobble position 34, especially modifications of uridine 34, enable wobble to occur. The Modified Wobble Hypothesis proposed in 1991 that specific modifications of a tRNA wobble nucleoside shape the anticodon architecture in such a manner that interactions were restricted to the complementary base plus a single wobble pairing for amino acids with twofold degenerate codons. However, chemically different modifications at position 34 would expand the ability of a tRNA to read three or even four of the fourfold degenerate codons. One foundation of Crick's Wobble Hypothesis was that a near-constant geometry of canonical base-pairing be maintained in forming all three base-pairs between the tRNA anticodon and mRNA codon on the ribosome. In accepting an aminoacyl-tRNA, the ribosome requires maintenance of a specific geometry for the anticodon-codon base-pairing. However, it is the post-transcriptional modifications at tRNA wobble position 34 and purine 37, 3'-adjacent to the anticodon, that pre-structure the anticodon domain to ensure the correct codon binding. The modifications create both the architecture and the stability needed for decoding through restraints on anticodon stereochemistry and conformational space, and through selective hydrogen bonding. A physicochemical understanding of modified nucleoside contributions to the tRNA anticodon domain architecture and its decoding of the genome has advanced RNA world evolutionary theory, the principles of RNA chemistry, and the application of this knowledge to the introduction of new amino acids to proteins.

Visualization for genomics: the Microbial Genome Viewer.

NARCIS (Netherlands)

Kerkhoven, R.; Enckevort, F.H.J. van; Boekhorst, J.; Molenaar, D; Siezen, R.J.

2004-01-01

SUMMARY: A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a

The stability of the High-Density Z-Pinch

International Nuclear Information System (INIS)

Glasser, A.H.; Nebel, R.A.

1989-01-01

Fiber-initiated High Density Z-Pinches at Los Alamos, NRL, and Karlsruhe have shown anomalously good stability. Kink modes are never seen, and sausage modes are at least delayed until late in the discharge. The success of these devices in reaching fusion conditions may depend on maintaining and understanding this anomalous stability. We have developed two numerical methods to study the stability in the regime where fluid theory is valid. While our methods are applicable to all modes, we will describe them only for the m = 0 sausage mode. The appearance of sausage modes late in the discharge and the total absence of kink modes suggest that an understanding of sausage modes is more urgent, and it is also simpler. 14 refs., 8 figs

The stability of the high-density z-pinch

International Nuclear Information System (INIS)

Glasser, A.H.; Nebel, R.A.

1989-01-01

Fiber-initiated High Density Z-Pinches at Los Alamos, NRL, and Karlsruhe have shown anomalously good stability. Kink modes are never seen, and sausage modes are at least delayed until late in the discharge. The success of these devices in reaching fusion conditions may depend on maintaining and understanding this anomalous stability. We have developed two numerical methods to study the stability in the regime where fluid theory is valid. While our methods are applicable to all modes, we will describe them only for the m=0 sausage mode. The appearance of sausage modes late in the discharge and the total absence of kink modes suggest that an understanding of sausage modes is more urgent, and it is also simpler

Mouse Genome Informatics (MGI) Resource: Genetic, Genomic, and Biological Knowledgebase for the Laboratory Mouse.

Science.gov (United States)

Eppig, Janan T

2017-07-01

The Mouse Genome Informatics (MGI) Resource supports basic, translational, and computational research by providing high-quality, integrated data on the genetics, genomics, and biology of the laboratory mouse. MGI serves a strategic role for the scientific community in facilitating biomedical, experimental, and computational studies investigating the genetics and processes of diseases and enabling the development and testing of new disease models and therapeutic interventions. This review describes the nexus of the body of growing genetic and biological data and the advances in computer technology in the late 1980s, including the World Wide Web, that together launched the beginnings of MGI. MGI develops and maintains a gold-standard resource that reflects the current state of knowledge, provides semantic and contextual data integration that fosters hypothesis testing, continually develops new and improved tools for searching and analysis, and partners with the scientific community to assure research data needs are met. Here we describe one slice of MGI relating to the development of community-wide large-scale mutagenesis and phenotyping projects and introduce ways to access and use these MGI data. References and links to additional MGI aspects are provided. © The Author 2017. Published by Oxford University Press.

Vibrational stability of graphene

Directory of Open Access Journals (Sweden)

Yangfan Hu

2013-05-01

Full Text Available The mechanical stability of graphene as temperature rises is analyzed based on three different self-consistent phonon (SCP models. Compared with three-dimensional (3-D materials, the critical temperature Ti at which instability occurs for graphene is much closer to its melting temperature Tm obtained from Monte Carlo simulation (Ti ≃ 2Tm, K. V. Zakharchenko, A. Fasolino, J. H. Los, and M. I. Katsnelson, J. Phys. Condens. Matter 23, 202202. This suggests that thermal vibration plays a significant role in melting of graphene while melting for 3-D materials is often dominated by topologic defects. This peculiar property of graphene derives from its high structural anisotropy, which is characterized by the vibrational anisotropic coefficient (VAC, defined upon its Lindermann ratios in different directions. For any carbon based material with a graphene-like structure, the VAC value must be smaller than 5.4 to maintain its stability. It is also found that the high VAC value of graphene is responsible for its negative thermal expansion coefficient at low temperature range. We believe that the VAC can be regarded as a new criterion concerning the vibrational stability of any low-dimensional (low-D materials.

Study of the 50 mg Propylthiouracil tablets stability

International Nuclear Information System (INIS)

Valdes Bendoyro, Maria Olga; Garcia Penna, Caridad Margarita; Lugones Fernandez, Juan

2010-01-01

Authors developed a stability study of 50 mg Propylthiouracil tablets and determination of its expiry date. This study was conducted by fixed life methods and of accelerated stability by high-performance liquid chromatography, validated in Drugs Research and Development Center. Fixed life study was conducted during 24 months at room temperature; whereas the accelerated stability study was conducted exposing the product to light influence, humidity and temperature; during 3 months a analysis was performed for the two first ones and over 6 months in the case of temperature study. Propylthiouracil formula (50 mg tablets) fulfilled the quality specifications described in Pharmacopeia. Results of stability study by fixed life after 24 months showed that thr product maintain the parameter determining its quality during this period, and in the accelerated studies there was not a significant degradation of product. Two years was the expity date established in above mentioned conditions

Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network

OpenAIRE

Mart?n-Jim?nez, Cynthia A.; Salazar-Barreto, Diego; Barreto, George E.; Gonz?lez, Janneth

2017-01-01

Astrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current experimental approaches given the high number of reactions and metabolites present. Thus, genome-scale metabolic networks derived from transcriptomic data can be used as a framework t...

G-Quadruplexes Involving Both Strands of Genomic DNA Are Highly Abundant and Colocalize with Functional Sites in the Human Genome.

Directory of Open Access Journals (Sweden)

Andrzej S Kudlicki

Full Text Available The G-quadruplex is a non-canonical DNA structure biologically significant in DNA replication, transcription and telomere stability. To date, only G4s with all guanines originating from the same strand of DNA have been considered in the context of the human nuclear genome. Here, I discuss interstrand topological configurations of G-quadruplex DNA, consisting of guanines from both strands of genomic DNA; an algorithm is presented for predicting such structures. I have identified over 550,000 non-overlapping interstrand G-quadruplex forming sequences in the human genome--significantly more than intrastrand configurations. Functional analysis of interstrand G-quadruplex sites shows strong association with transcription initiation, the results are consistent with the XPB and XPD transcriptional helicases binding only to G-quadruplex DNA with interstrand topology. Interstrand quadruplexes are also enriched in origin of replication sites. Several topology classes of interstrand quadruplex-forming sequences are possible, and different topologies are enriched in different types of structural elements. The list of interstrand quadruplex forming sequences, and the computer program used for their prediction are available at the web address http://moment.utmb.edu/allquads.

Pseudomonas putida CSV86: a candidate genome for genetic bioaugmentation.

Directory of Open Access Journals (Sweden)

Vasundhara Paliwal

Full Text Available Pseudomonas putida CSV86, a plasmid-free strain possessing capability to transfer the naphthalene degradation property, has been explored for its metabolic diversity through genome sequencing. The analysis of draft genome sequence of CSV86 (6.4 Mb revealed the presence of genes involved in the degradation of naphthalene, salicylate, benzoate, benzylalcohol, p-hydroxybenzoate, phenylacetate and p-hydroxyphenylacetate on the chromosome thus ensuring the stability of the catabolic potential. Moreover, genes involved in the metabolism of phenylpropanoid and homogentisate, as well as heavy metal resistance, were additionally identified. Ability to grow on vanillin, veratraldehyde and ferulic acid, detection of inducible homogentisate dioxygenase and growth on aromatic compounds in the presence of heavy metals like copper, cadmium, cobalt and arsenic confirm in silico observations reflecting the metabolic versatility. In silico analysis revealed the arrangement of genes in the order: tRNA(Gly, integrase followed by nah operon, supporting earlier hypothesis of existence of a genomic island (GI for naphthalene degradation. Deciphering the genomic architecture of CSV86 for aromatic degradation pathways and identification of elements responsible for horizontal gene transfer (HGT suggests that genetic bioaugmentation strategies could be planned using CSV86 for effective bioremediation.

Project Management Plan to Maintain Safe and Compliant Conditions at the Plutonium Finishing Plant

International Nuclear Information System (INIS)

COX, G.J.

1999-01-01

This Project Management Plan presents the overall plan, description, mission, and workscope for the Plutonium Finishing Plant (PFP) maintain safe and compliant conditions project at PFP. This plan presents the overall description, mission, work scope, and planning for the Plutonium Finishing Plant (PFP) Maintain Safe and Compliant Conditions Project at PFP. This project includes all tasks required to maintain the safety boundary for the PFP Complex, except for the 2736-2 Vault Complex and the 234-52 vaults and vault-type rooms. The intent of this plan is to describe how this project will be managed and integrated with the stabilization, and deactivation activities. This plan supplements the overall integrated plan presented in the Plutonium Finishing Plant Integrated Project Management Plan (IPMP), HNF-3617, Rev. 0. This is the top-level definitive project management document that specifies the technical (work scope), schedule, and cost baselines that will manage the execution of this project. It describes the organizational approach and roles/responsibilities implemented to execute the project. This plan is under configuration management and any deviations must be authorized by appropriate change control action

Histone hypoacetylation is required to maintain late replication timing of constitutive heterochromatin.

Science.gov (United States)

Casas-Delucchi, Corella S; van Bemmel, Joke G; Haase, Sebastian; Herce, Henry D; Nowak, Danny; Meilinger, Daniela; Stear, Jeffrey H; Leonhardt, Heinrich; Cardoso, M Cristina

2012-01-01

The replication of the genome is a spatio-temporally highly organized process. Yet, its flexibility throughout development suggests that this process is not genetically regulated. However, the mechanisms and chromatin modifications controlling replication timing are still unclear. We made use of the prominent structure and defined heterochromatic landscape of pericentric regions as an example of late replicating constitutive heterochromatin. We manipulated the major chromatin markers of these regions, namely histone acetylation, DNA and histone methylation, as well as chromatin condensation and determined the effects of these altered chromatin states on replication timing. Here, we show that manipulation of DNA and histone methylation as well as acetylation levels caused large-scale heterochromatin decondensation. Histone demethylation and the concomitant decondensation, however, did not affect replication timing. In contrast, immuno-FISH and time-lapse analyses showed that lowering DNA methylation, as well as increasing histone acetylation, advanced the onset of heterochromatin replication. While dnmt1(-)(/)(-) cells showed increased histone acetylation at chromocenters, histone hyperacetylation did not induce DNA demethylation. Hence, we propose that histone hypoacetylation is required to maintain normal heterochromatin duplication dynamics. We speculate that a high histone acetylation level might increase the firing efficiency of origins and, concomitantly, advances the replication timing of distinct genomic regions.

Forced evolution of a regulatory RNA helix in the HIV-1 genome

NARCIS (Netherlands)

Berkhout, B.; Klaver, B.; Das, A. T.

1997-01-01

The 5'and 3'end of the HIV-1 RNA genome forms a repeat (R) element that encodes a double stem-loop structure (the TAR and polyA hairpins). Phylogenetic analysis of the polyA hairpin in different human and simian immunodeficiency viruses suggests that the thermodynamic stability of the helix is

The perennial ryegrass GenomeZipper: targeted use of genome resources for comparative grass genomics.

Science.gov (United States)

Pfeifer, Matthias; Martis, Mihaela; Asp, Torben; Mayer, Klaus F X; Lübberstedt, Thomas; Byrne, Stephen; Frei, Ursula; Studer, Bruno

2013-02-01

Whole-genome sequences established for model and major crop species constitute a key resource for advanced genomic research. For outbreeding forage and turf grass species like ryegrasses (Lolium spp.), such resources have yet to be developed. Here, we present a model of the perennial ryegrass (Lolium perenne) genome on the basis of conserved synteny to barley (Hordeum vulgare) and the model grass genome Brachypodium (Brachypodium distachyon) as well as rice (Oryza sativa) and sorghum (Sorghum bicolor). A transcriptome-based genetic linkage map of perennial ryegrass served as a scaffold to establish the chromosomal arrangement of syntenic genes from model grass species. This scaffold revealed a high degree of synteny and macrocollinearity and was then utilized to anchor a collection of perennial ryegrass genes in silico to their predicted genome positions. This resulted in the unambiguous assignment of 3,315 out of 8,876 previously unmapped genes to the respective chromosomes. In total, the GenomeZipper incorporates 4,035 conserved grass gene loci, which were used for the first genome-wide sequence divergence analysis between perennial ryegrass, barley, Brachypodium, rice, and sorghum. The perennial ryegrass GenomeZipper is an ordered, information-rich genome scaffold, facilitating map-based cloning and genome assembly in perennial ryegrass and closely related Poaceae species. It also represents a milestone in describing synteny between perennial ryegrass and fully sequenced model grass genomes, thereby increasing our understanding of genome organization and evolution in the most important temperate forage and turf grass species.

A PTIP-PA1 subcomplex promotes transcription for IgH class switching independently from the associated MLL3/MLL4 methyltransferase complex

DEFF Research Database (Denmark)

Starnes, Linda M; Su, Dan; Pikkupeura, Laura M

2016-01-01

Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transacti...

Family genome browser: visualizing genomes with pedigree information.

Science.gov (United States)

Juan, Liran; Liu, Yongzhuang; Wang, Yongtian; Teng, Mingxiang; Zang, Tianyi; Wang, Yadong

2015-07-15

Families with inherited diseases are widely used in Mendelian/complex disease studies. Owing to the advances in high-throughput sequencing technologies, family genome sequencing becomes more and more prevalent. Visualizing family genomes can greatly facilitate human genetics studies and personalized medicine. However, due to the complex genetic relationships and high similarities among genomes of consanguineous family members, family genomes are difficult to be visualized in traditional genome visualization framework. How to visualize the family genome variants and their functions with integrated pedigree information remains a critical challenge. We developed the Family Genome Browser (FGB) to provide comprehensive analysis and visualization for family genomes. The FGB can visualize family genomes in both individual level and variant level effectively, through integrating genome data with pedigree information. Family genome analysis, including determination of parental origin of the variants, detection of de novo mutations, identification of potential recombination events and identical-by-decent segments, etc., can be performed flexibly. Diverse annotations for the family genome variants, such as dbSNP memberships, linkage disequilibriums, genes, variant effects, potential phenotypes, etc., are illustrated as well. Moreover, the FGB can automatically search de novo mutations and compound heterozygous variants for a selected individual, and guide investigators to find high-risk genes with flexible navigation options. These features enable users to investigate and understand family genomes intuitively and systematically. The FGB is available at http://mlg.hit.edu.cn/FGB/. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Parallel altitudinal clines reveal trends in adaptive evolution of genome size in Zea mays

Science.gov (United States)

Berg, Jeremy J.; Birchler, James A.; Grote, Mark N.; Lorant, Anne; Quezada, Juvenal

2018-01-01

While the vast majority of genome size variation in plants is due to differences in repetitive sequence, we know little about how selection acts on repeat content in natural populations. Here we investigate parallel changes in intraspecific genome size and repeat content of domesticated maize (Zea mays) landraces and their wild relative teosinte across altitudinal gradients in Mesoamerica and South America. We combine genotyping, low coverage whole-genome sequence data, and flow cytometry to test for evidence of selection on genome size and individual repeat abundance. We find that population structure alone cannot explain the observed variation, implying that clinal patterns of genome size are maintained by natural selection. Our modeling additionally provides evidence of selection on individual heterochromatic knob repeats, likely due to their large individual contribution to genome size. To better understand the phenotypes driving selection on genome size, we conducted a growth chamber experiment using a population of highland teosinte exhibiting extensive variation in genome size. We find weak support for a positive correlation between genome size and cell size, but stronger support for a negative correlation between genome size and the rate of cell production. Reanalyzing published data of cell counts in maize shoot apical meristems, we then identify a negative correlation between cell production rate and flowering time. Together, our data suggest a model in which variation in genome size is driven by natural selection on flowering time across altitudinal clines, connecting intraspecific variation in repetitive sequence to important differences in adaptive phenotypes. PMID:29746459

Stability of ‘mangaba’ pulp powder obtained by freeze drying

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Juliana Conegero

Full Text Available ABSTRACT This work examined the stability of lyophilized ‘mangaba’ pulp powder, rolled and packaged in plastic containers, with and without vacuum during 90 days of storage under room temperature, with evaluation of the parameters every 15 days. Analyses of ascorbic acid concentration, pH, color and water activity were carried out. It was found that ascorbic acid remained in accordance with the standards specified for daily consumption according to the Brazilian legislation in all analyzed packages, with preservation of stability in the laminated package with vacuum, which was also effective in maintaining water activity, which contributes to better stability of the product.

Exploratory re-encoding of Yellow Fever Virus genome: new insights for the design of live-attenuated viruses

OpenAIRE

Klitting, Raphaelle; Riziki, Toilhata; Moureau, Gregory; De Lamballerie, Xavier; Piorkowski, Geraldine

2018-01-01

Virus attenuation by genome re-encoding is a pioneering approach for generating live-attenuated vaccine candidates. Its core principle is to introduce a large number of slightly deleterious synonymous mutations into the viral genome to produce a stable attenuation of the targeted virus. The large number of mutations introduced is supposed to guarantee the stability of the attenuated phenotype by lowering the risks of reversion and recombination for re-encoded sequences. In this prospect, iden...

Constraints on genes shape long-term conservation of macro-synteny in metazoan genomes

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Putnam Nicholas H

2011-10-01

Full Text Available Abstract Background Many metazoan genomes conserve chromosome-scale gene linkage relationships (“macro-synteny” from the common ancestor of multicellular animal life 1234, but the biological explanation for this conservation is still unknown. Double cut and join (DCJ is a simple, well-studied model of neutral genome evolution amenable to both simulation and mathematical analysis 5, but as we show here, it is not sufficent to explain long-term macro-synteny conservation. Results We examine a family of simple (one-parameter extensions of DCJ to identify models and choices of parameters consistent with the levels of macro- and micro-synteny conservation observed among animal genomes. Our software implements a flexible strategy for incorporating genomic context into the DCJ model to incorporate various types of genomic context (“DCJ-[C]”, and is available as open source software from http://github.com/putnamlab/dcj-c. Conclusions A simple model of genome evolution, in which DCJ moves are allowed only if they maintain chromosomal linkage among a set of constrained genes, can simultaneously account for the level of macro-synteny conservation and for correlated conservation among multiple pairs of species. Simulations under this model indicate that a constraint on approximately 7% of metazoan genes is sufficient to constrain genome rearrangement to an average rate of 25 inversions and 1.7 translocations per million years.

Genomes of the Mouse Collaborative Cross.

Science.gov (United States)

Srivastava, Anuj; Morgan, Andrew P; Najarian, Maya L; Sarsani, Vishal Kumar; Sigmon, J Sebastian; Shorter, John R; Kashfeen, Anwica; McMullan, Rachel C; Williams, Lucy H; Giusti-Rodríguez, Paola; Ferris, Martin T; Sullivan, Patrick; Hock, Pablo; Miller, Darla R; Bell, Timothy A; McMillan, Leonard; Churchill, Gary A; de Villena, Fernando Pardo-Manuel

2017-06-01

The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 30× coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of

eGenomics: Cataloguing Our Complete Genome Collection III

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Dawn Field

2007-01-01

Full Text Available This meeting report summarizes the proceedings of the “eGenomics: Cataloguing our Complete Genome Collection III” workshop held September 11–13, 2006, at the National Institute for Environmental eScience (NIEeS, Cambridge, United Kingdom. This 3rd workshop of the Genomic Standards Consortium was divided into two parts. The first half of the three-day workshop was dedicated to reviewing the genomic diversity of our current and future genome and metagenome collection, and exploring linkages to a series of existing projects through formal presentations. The second half was dedicated to strategic discussions. Outcomes of the workshop include a revised “Minimum Information about a Genome Sequence” (MIGS specification (v1.1, consensus on a variety of features to be added to the Genome Catalogue (GCat, agreement by several researchers to adopt MIGS for imminent genome publications, and an agreement by the EBI and NCBI to input their genome collections into GCat for the purpose of quantifying the amount of optional data already available (e.g., for geographic location coordinates and working towards a single, global list of all public genomes and metagenomes.

Genomics-assisted breeding for boosting crop improvement in pigeonpea (Cajanus cajan

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Lekha ePazhamala

2015-02-01

Full Text Available Pigeonpea is an important pulse crop grown predominantly in the tropical and sub-tropical regions of the world. Although pigeonpea growing area has considerably increased, yield has remained stagnant for the last six decades mainly due to the exposure of the crop to various biotic and abiotic constraints. In addition, low level of genetic variability and limited genomic resources have been serious impediments to pigeonpea crop improvement through modern breeding approaches. In recent years, however, due to the availability of next generation sequencing and high-throughput genotyping technologies, the scenario has changed tremendously. The reduced sequencing costs resulting in the decoding of the pigeonpea genome has led to the development of various genomic resources including molecular markers, transcript sequences and comprehensive genetic maps. Mapping of some important traits including resistance to Fusarium wilt and sterility mosaic disease, fertility restoration, determinacy with other agronomically important traits have paved the way for applying genomics-assisted breeding (GAB through marker assisted selection as well as genomic selection. This would lead to accelerate the development and improvement of both varieties and hybrids in pigeonpea. Particularly for hybrid breeding programme, mitochondrial genomes of cytoplasmic male sterile lines, maintainers and hybrids have also been sequenced to identify genes responsible for cytoplasmic male sterility. Furthermore, several diagnostic molecular markers have been developed to assess the purity of commercial hybrids. In summary, pigeonpea has become a genomic resources-rich crop and efforts have already been initiated to integrate these resources in pigeonpea breeding.

PROBING GENOME MAINTENANCE FUNCTIONS OF HUMAN RECQ1

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Furqan Sami

2013-03-01

Full Text Available The RecQ helicases are a highly conserved family of DNA-unwinding enzymes that play key roles in protecting the genome stability in all kingdoms of life.'Human RecQ homologs include RECQ1, BLM, WRN, RECQ4, and RECQ5β.'Although the individual RecQ-related diseases are characterized by a variety of clinical features encompassing growth defects (Bloom Syndrome and Rothmund Thomson Syndrome to premature aging (Werner Syndrome, all these patients have a high risk of cancer predisposition.'Here, we present an overview of recent progress towards elucidating functions of RECQ1 helicase, the most abundant but poorly characterized RecQ homolog in humans.'Consistent with a conserved role in genome stability maintenance, deficiency of RECQ1 results in elevated frequency of spontaneous sister chromatid exchanges, chromosomal instability, increased DNA damage and greater sensitivity to certain genotoxic stress.'Delineating what aspects of RECQ1 catalytic functions contribute to the observed cellular phenotypes, and how this is regulated is critical to establish its biological functions in DNA metabolism.'Recent studies have identified functional specialization of RECQ1 in DNA repair; however, identification of fundamental similarities will be just as critical in developing a unifying theme for RecQ actions, allowing the functions revealed from studying one homolog to be extrapolated and generalized to other RecQ homologs.

Genomic V exons from whole genome shotgun data in reptiles.

Science.gov (United States)

Olivieri, D N; von Haeften, B; Sánchez-Espinel, C; Faro, J; Gambón-Deza, F

2014-08-01

Reptiles and mammals diverged over 300 million years ago, creating two parallel evolutionary lineages amongst terrestrial vertebrates. In reptiles, two main evolutionary lines emerged: one gave rise to Squamata, while the other gave rise to Testudines, Crocodylia, and Aves. In this study, we determined the genomic variable (V) exons from whole genome shotgun sequencing (WGS) data in reptiles corresponding to the three main immunoglobulin (IG) loci and the four main T cell receptor (TR) loci. We show that Squamata lack the TRG and TRD genes, and snakes lack the IGKV genes. In representative species of Testudines and Crocodylia, the seven major IG and TR loci are maintained. As in mammals, genes of the IG loci can be grouped into well-defined IMGT clans through a multi-species phylogenetic analysis. We show that the reptilian IGHV and IGLV genes are distributed amongst the established mammalian clans, while their IGKV genes are found within a single clan, nearly exclusive from the mammalian sequences. The reptilian and mammalian TRAV genes cluster into six common evolutionary clades (since IMGT clans have not been defined for TR). In contrast, the reptilian TRBV genes cluster into three clades, which have few mammalian members. In this locus, the V exon sequences from mammals appear to have undergone different evolutionary diversification processes that occurred outside these shared reptilian clans. These sequences can be obtained in a freely available public repository (http://vgenerepertoire.org).

A novel Snf2 protein maintains trans-generational regulatory states established by paramutation in maize.

Directory of Open Access Journals (Sweden)

Christopher J Hale

2007-10-01

Full Text Available Paramutations represent heritable epigenetic alterations that cause departures from Mendelian inheritance. While the mechanism responsible is largely unknown, recent results in both mouse and maize suggest paramutations are correlated with RNA molecules capable of affecting changes in gene expression patterns. In maize, multiple required to maintain repression (rmr loci stabilize these paramutant states. Here we show rmr1 encodes a novel Snf2 protein that affects both small RNA accumulation and cytosine methylation of a proximal transposon fragment at the Pl1-Rhoades allele. However, these cytosine methylation differences do not define the various epigenetic states associated with paramutations. Pedigree analyses also show RMR1 does not mediate the allelic interactions that typically establish paramutations. Strikingly, our mutant analyses show that Pl1-Rhoades RNA transcript levels are altered independently of transcription rates, implicating a post-transcriptional level of RMR1 action. These results suggest the RNA component of maize paramutation maintains small heterochromatic-like domains that can affect, via the activity of a Snf2 protein, the stability of nascent transcripts from adjacent genes by way of a cotranscriptional repression process. These findings highlight a mechanism by which alleles of endogenous loci can acquire novel expression patterns that are meiotically transmissible.

dbEM: A database of epigenetic modifiers curated from cancerous and normal genomes

Science.gov (United States)

Singh Nanda, Jagpreet; Kumar, Rahul; Raghava, Gajendra P. S.

2016-01-01

We have developed a database called dbEM (database of Epigenetic Modifiers) to maintain the genomic information of about 167 epigenetic modifiers/proteins, which are considered as potential cancer targets. In dbEM, modifiers are classified on functional basis and comprise of 48 histone methyl transferases, 33 chromatin remodelers and 31 histone demethylases. dbEM maintains the genomic information like mutations, copy number variation and gene expression in thousands of tumor samples, cancer cell lines and healthy samples. This information is obtained from public resources viz. COSMIC, CCLE and 1000-genome project. Gene essentiality data retrieved from COLT database further highlights the importance of various epigenetic proteins for cancer survival. We have also reported the sequence profiles, tertiary structures and post-translational modifications of these epigenetic proteins in cancer. It also contains information of 54 drug molecules against different epigenetic proteins. A wide range of tools have been integrated in dbEM e.g. Search, BLAST, Alignment and Profile based prediction. In our analysis, we found that epigenetic proteins DNMT3A, HDAC2, KDM6A, and TET2 are highly mutated in variety of cancers. We are confident that dbEM will be very useful in cancer research particularly in the field of epigenetic proteins based cancer therapeutics. This database is available for public at URL: http://crdd.osdd.net/raghava/dbem.

Reconsideration of the m=0 Z-pinch stability

International Nuclear Information System (INIS)

Scheffel, J.; Coppins, M.

1993-01-01

Possible paths for obtaining linear stability against the m=0 mode in the Z-pinch are studied. Using a generalized energy principle, the necessary and sufficient Chew-Goldberger-Low (CGL) m=0 stability criterion is derived. This criterion is less restrictive than that of ideal MHD, although it also requires the boundary plasma pressure to be finite. It is shown that the edge pressure cannot be stably upheld by a surface current. By instead assuming a finite pressure external gas, it is found that an edge pressure to on-axis pressure ratio of 0.5 is required for stability of a constant current density profile. A parabolic current density profile lowers the limit to the value 0.17. The growth rates are shown to be monotonically decreasing as a function of the external gas pressure. Detailed derivations of the boundary conditions are also given. The results aid in clarifying the experimental stability of four major Z-pinch experiments. Finite Larmor radius stabilization is hence required to maintain stability in future fibre pinch experiments in vacuum, implying line densities less than 10 19 m -1 . (author). 28 refs, 10 figs

Genomic Prediction from Whole Genome Sequence in Livestock: The 1000 Bull Genomes Project

DEFF Research Database (Denmark)

Hayes, Benjamin J; MacLeod, Iona M; Daetwyler, Hans D

Advantages of using whole genome sequence data to predict genomic estimated breeding values (GEBV) include better persistence of accuracy of GEBV across generations and more accurate GEBV across breeds. The 1000 Bull Genomes Project provides a database of whole genome sequenced key ancestor bulls....... In a dairy data set, predictions using BayesRC and imputed sequence data from 1000 Bull Genomes were 2% more accurate than with 800k data. We could demonstrate the method identified causal mutations in some cases. Further improvements will come from more accurate imputation of sequence variant genotypes...

Genome-wide variation in recombination rate in Eucalyptus.

Science.gov (United States)

Gion, Jean-Marc; Hudson, Corey J; Lesur, Isabelle; Vaillancourt, René E; Potts, Brad M; Freeman, Jules S

2016-08-09

chromosomes in recombination rates appear stable across Eucalyptus species. Together with the strong correlations between recombination rate and features of the Eucalyptus reference genome, we maintain these findings provide further evidence for a broad conservation of genome architecture across the globally significant lineages of Eucalyptus.

Whole-genome sequencing of spermatocytic tumors provides insights into the mutational processes operating in the male germline

DEFF Research Database (Denmark)

Giannoulatou, Eleni; Maher, Geoffrey J; Ding, Zhihao

2017-01-01

Adult male germline stem cells (spermatogonia) proliferate by mitosis and, after puberty, generate spermatocytes that undertake meiosis to produce haploid spermatozoa. Germ cells are under evolutionary constraint to curtail mutations and maintain genome integrity. Despite constant turnover...

Scaffold expulsion and genome packaging trigger stabilization of herpes simplex virus capsids

NARCIS (Netherlands)

Roos, W.H.; Radtke, K.; Kniesmeijer, E.G.R.; Geertsema, H.J.; Sodeik, B.; Wuite, G.J.L.

2009-01-01

Herpes simplex virus type 1 (HSV1) capsids undergo extensive structural changes during maturation and DNA packaging. As a result, they become more stable and competent for nuclear egress. To further elucidate this stabilization process, we used biochemical and nanoindentation approaches to analyze

Scaffold expulsion and genome packaging trigger stabilization of Herpes Simplex Virus capsids

NARCIS (Netherlands)

Roos, W.H.; Radtke, K.; Kniesmeijer, E.; Geertsema, H.J.; Sodeik, B.; Wuite, G.J.L.

2009-01-01

Herpes simplex virus type 1 (HSV1) capsids undergo extensive structural changes during maturation and DNA packaging. As a result, they become more stable and competent for nuclear egress. To further elucidate this stabilization process, we used biochemical and nanoindentation approaches to analyze

PML-RARα stabilized by zinc in human acute promyelocytic leukemia NB4 cells.

Science.gov (United States)

Zhu, Bo; Wang, Jia-Yu; Zhou, Jun-Jie; Zhou, Feng; Cheng, Wei; Liu, Ying-Ting; Wang, Jie; Chen, Xiao; Chen, Dian-Hua; Luo, Lan; Hua, Zi-Chun

2017-10-01

Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway. In contrast, autophagy protected TPEN-mediated PML-RARα degradation in NB4 APL cells. We further demonstrated that crosstalk between zinc homeostasis and nitric oxide pathway played a key role in maintaining PML-RARα stability in NB4 APL cells. These results demonstrate that zinc homeostasis is vital for maintaining PML-RARα stability, and zinc depletion by TPEN may be useful as a potential strategy to trigger PML-RARα degradation in APL cells. We also found that TPEN triggered apoptosis of NB4 APL cells in a time-dependent manner. The relationship between PML-RARα degradation and apoptosis triggered by TPEN deserves further study. Copyright © 2017 Elsevier Inc. All rights reserved.

Active stabilization of a diode laser injection lock.

Science.gov (United States)

Saxberg, Brendan; Plotkin-Swing, Benjamin; Gupta, Subhadeep

2016-06-01

We report on a device to electronically stabilize the optical injection lock of a semiconductor diode laser. Our technique uses as discriminator the peak height of the laser's transmission signal on a scanning Fabry-Perot cavity and feeds back to the diode current, thereby maintaining maximum optical power in the injected mode. A two-component feedback algorithm provides constant optimization of the injection lock, keeping it robust to slow thermal drifts and allowing fast recovery from sudden failures such as temporary occlusion of the injection beam. We demonstrate the successful performance of our stabilization method in a diode laser setup at 399 nm used for laser cooling of Yb atoms. The device eases the requirements on passive stabilization and can benefit any diode laser injection lock application, particularly those where several such locks are employed.

PairWise Neighbours database: overlaps and spacers among prokaryote genomes

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Garcia-Vallvé Santiago

2009-06-01

Full Text Available Abstract Background Although prokaryotes live in a variety of habitats and possess different metabolic and genomic complexity, they have several genomic architectural features in common. The overlapping genes are a common feature of the prokaryote genomes. The overlapping lengths tend to be short because as the overlaps become longer they have more risk of deleterious mutations. The spacers between genes tend to be short too because of the tendency to reduce the non coding DNA among prokaryotes. However they must be long enough to maintain essential regulatory signals such as the Shine-Dalgarno (SD sequence, which is responsible of an efficient translation. Description PairWise Neighbours is an interactive and intuitive database used for retrieving information about the spacers and overlapping genes among bacterial and archaeal genomes. It contains 1,956,294 gene pairs from 678 fully sequenced prokaryote genomes and is freely available at the URL http://genomes.urv.cat/pwneigh. This database provides information about the overlaps and their conservation across species. Furthermore, it allows the wide analysis of the intergenic regions providing useful information such as the location and strength of the SD sequence. Conclusion There are experiments and bioinformatic analysis that rely on correct annotations of the initiation site. Therefore, a database that studies the overlaps and spacers among prokaryotes appears to be desirable. PairWise Neighbours database permits the reliability analysis of the overlapping structures and the study of the SD presence and location among the adjacent genes, which may help to check the annotation of the initiation sites.

Studies on storage stability of radurised Indian Mackerel (Rastrelliger Kanagurta)

International Nuclear Information System (INIS)

Ghadi, S.V.; Alur, M.D.; Venugopal, V.; Doke, S.N.; Ghosh, S.K.; Lewis, N.F.; Nadkarni, G.B.

1977-01-01

The present report describes the storage stability of mackerel maintained at various temperatures (0deg-20degC). The investigations include radiation-induced shifts in microflora of mackerel during storage, and time-temperature-tolerance (TTT) studies with the unirradiated and radurized mackerel. (author)

Looking at the stability of life-support microorganisms in space : the MELGEN activity highlights the cyanobacterium Arthrospira sp. PCC8005

Science.gov (United States)

Morin, Nicolas

The MELGEN activity (MELiSSA Genetic Stability Study) mainly covers the molecular aspects of the regenerative life-support system MELiSSA (Micro-Ecological Life Support System Alternative) of the European Space Agency (ESA). The general objective of MELGEN is to establish and validate methods and the related hardware in order to detect genetic instability and microbial contaminants in the MELISSA compartments. This includes (1) a genetic description of the MELISSA strains, (2) studies of microbial behavior and genetic stability in bioreactors and (3) the detection of chemical, genetical and biological contamination and their effect on microbial metabolism. Selected as oxygen producer and complementary food source, the cyanobacterium Arthrospira sp. PCC8005 plays a major role within the MELiSSA loop. As the genomic information on this organism was insufficient, sequencing of its genome was proposed at the French National Sequencing Center, Genoscope, as a joint effort between ESA and different laboratories. So far, a preliminary assembly of 16 contigs representing circa 6.3 million basepairs was obtained. Even though the finishing of the genome is on its way, automatic annotation of the contigs has already been performed on the MaGe annotation platform, and curation of the sequence is currently being carried out, with a special focus on biosynthesis pathways, photosynthesis, and maintenance processes of the cell. According to the index of repetitiveness described by Haubold and Wiehe (2006), we discovered that the genome of Arthrospira sp. is among the 50 most repeated bacterial genomes sequenced to date. Thanks to the sequencing project, we have identified and catalogued mobile genetics elements (MGEs) dispersed throughout the unique chromosome of this cyanobacterium. They represent a quite large proportion of the genome, as genes identified as putative transposases are indeed found in circa 5 Results : We currently have a first draft of the complete genome of

Bread wheat progenitors: Aegilops tauschii (DD genome) and Triticum dicoccoides (AABB genome) reveal differential antioxidative response under water stress.

Science.gov (United States)

Suneja, Yadhu; Gupta, Anil Kumar; Bains, Navtej Singh

2017-01-01

Antioxidant enzymes are known to play a significant role in scavenging reactive oxygen species and maintaining cellular homeostasis. Activity of four antioxidant enzymes viz., superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR) was examined in the flag leaves of nine Aegilops tauschii and three Triticum dicoccoides accessions along with two bread wheat cultivars under irrigated and rain-fed conditions. These accessions were shortlisted from a larger set on the basis of field performance for a set of morpho-physiological traits. At anthesis, significant differences were observed in enzyme activities in two environments. A 45% elevation in average GR activity was observed under rain-fed conditions. Genotypic variation was evident within each environment as well as in terms of response to stress environment. Aegilops tauschii accession 3769 (86% increase in SOD, 41% in CAT, 72% in APX, 48% in GR activity) and acc. 14096 (37% increase in SOD, 32% CAT, 25% APX, 42% GR) showed up-regulation in the activity of all the four studied antioxidant enzymes. Aegilops tauschii accessions-9809, 14189 and 14113 also seemed to have strong induction mechanism as elevated activity of at least three enzymes was observed in them under rain-fed conditions. T. dicoccoides , on the other hand, maintained active antioxidative machinery under irrigated condition with relatively lower induction under stress. A significant positive correlation (r = 0.760) was identified between change in the activity of CAT and GR under stress. Changes in plant height, spike length and grain weight were recorded under stress and non-stress conditions on the basis of which a cumulative tolerance index was deduced and accessions were ranked for drought tolerance. Overall, Ae. tauschii accession 3769, 14096, 14113 (DD-genome) and T. dicoccoides accession 7054 (AABB-genome) may be used as donors to combine beneficial stress adaptive traits of all the three sub-genomes

Thermohydraulic stability coupled to the neutronic in a BWR

International Nuclear Information System (INIS)

Calleros M, G.; Zapata Y, M.; Gomez H, R.A.; Mendez M, A.; Castlllo D, R.

2006-01-01

In a BWR type reactor the phenomenon of the nuclear fission is presented, in which are liberated in stochastic form neutrons, originating that the population of the same ones varies in statistic form around a mean value. This variation will cause that when the neutron flow impacts on the neutron detectors, its are had as a result neutron flow signals with fluctuations around an average value. In this article it is shown that it conforms it lapses the time, this variations in the neutron flow (and therefore, in the flow signal due only to the fission), they presented oscillations inside a stable range, which won't be divergent. Considering that the BWR is characterized because boiling phenomena are presented, which affect the moderation of the neutrons, additional variations will be had in the signal coming from the neutron detectors, with relationship to the fission itself, which will be influenced by the feedback of the moderator's reactivity and of the temperature of the fuel pellet. Also, as the BWR it has coupled control systems to maintain the coolant level one and of the thermal power of the reactor, for each control action it was affected the neutron population. This means that the reactor could end up straying of a stable state condition. By it previously described, the study of the thermohydraulic stability coupled to the neutronic is complex. In this work it is shown the phenomenology, the mathematical models and the theoretical behavior associated to the stability of the BWR type reactor; the variables that affect it are identified, the models that reproduce the behavior of the thermohydraulic stability coupled to the neutronic, the way to maintain stable the reactor and the instrumentation that can settle to detect and to suppress uncertainties is described. In particular, is make reference to the evolution of the methods to maintain the stability of the reactor and the detection system and suppression of uncertainties implemented in the Laguna Verde

Evolutionary Fates and Dynamic Functionalization of Young Duplicate Genes in Arabidopsis Genomes.

Science.gov (United States)

Wang, Jun; Tao, Feng; Marowsky, Nicholas C; Fan, Chuanzhu

2016-09-01

Gene duplication is a primary means to generate genomic novelties, playing an essential role in speciation and adaptation. Particularly in plants, a high abundance of duplicate genes has been maintained for significantly long periods of evolutionary time. To address the manner in which young duplicate genes were derived primarily from small-scale gene duplication and preserved in plant genomes and to determine the underlying driving mechanisms, we generated transcriptomes to produce the expression profiles of five tissues in Arabidopsis thaliana and the closely related species Arabidopsis lyrata and Capsella rubella Based on the quantitative analysis metrics, we investigated the evolutionary processes of young duplicate genes in Arabidopsis. We determined that conservation, neofunctionalization, and specialization are three main evolutionary processes for Arabidopsis young duplicate genes. We explicitly demonstrated the dynamic functionalization of duplicate genes along the evolutionary time scale. Upon origination, duplicates tend to maintain their ancestral functions; but as they survive longer, they might be likely to develop distinct and novel functions. The temporal evolutionary processes and functionalization of plant duplicate genes are associated with their ancestral functions, dynamic DNA methylation levels, and histone modification abundances. Furthermore, duplicate genes tend to be initially expressed in pollen and then to gain more interaction partners over time. Altogether, our study provides novel insights into the dynamic retention processes of young duplicate genes in plant genomes. © 2016 American Society of Plant Biologists. All rights reserved.

Genomic Prediction of Barley Hybrid Performance

Directory of Open Access Journals (Sweden)

Norman Philipp

2016-07-01

Full Text Available Hybrid breeding in barley ( L. offers great opportunities to accelerate the rate of genetic improvement and to boost yield stability. A crucial requirement consists of the efficient selection of superior hybrid combinations. We used comprehensive phenotypic and genomic data from a commercial breeding program with the goal of examining the potential to predict the hybrid performances. The phenotypic data were comprised of replicated grain yield trials for 385 two-way and 408 three-way hybrids evaluated in up to 47 environments. The parental lines were genotyped using a 3k single nucleotide polymorphism (SNP array based on an Illumina Infinium assay. We implemented ridge regression best linear unbiased prediction modeling for additive and dominance effects and evaluated the prediction ability using five-fold cross validations. The prediction ability of hybrid performances based on general combining ability (GCA effects was moderate, amounting to 0.56 and 0.48 for two- and three-way hybrids, respectively. The potential of GCA-based hybrid prediction requires that both parental components have been evaluated in a hybrid background. This is not necessary for genomic prediction for which we also observed moderate cross-validated prediction abilities of 0.51 and 0.58 for two- and three-way hybrids, respectively. This exemplifies the potential of genomic prediction in hybrid barley. Interestingly, prediction ability using the two-way hybrids as training population and the three-way hybrids as test population or vice versa was low, presumably, because of the different genetic makeup of the parental source populations. Consequently, further research is needed to optimize genomic prediction approaches combining different source populations in barley.

Grp/DChk1 is required for G(2)-M checkpoint activation in Drosophila S2 cells, whereas Dmnk/DChk2 is dispensable

NARCIS (Netherlands)

de Vries, HI; Uyetake, L; Lemstra, W; Brunsting, JF; Su, TT; Kampinga, HH; Sibon, OCM

2005-01-01

Cell-cycle checkpoints are signal-transduction pathways required to maintain genomic stability in dividing cells. Previously, it was reported that two kinases essential for checkpoint signalling, Chk1 and Chk2 are structurally conserved. In contrast to yeast, Xenopus and mammals, the Chk1- and

Massively parallel whole genome amplification for single-cell sequencing using droplet microfluidics.

Science.gov (United States)

Hosokawa, Masahito; Nishikawa, Yohei; Kogawa, Masato; Takeyama, Haruko

2017-07-12

Massively parallel single-cell genome sequencing is required to further understand genetic diversities in complex biological systems. Whole genome amplification (WGA) is the first step for single-cell sequencing, but its throughput and accuracy are insufficient in conventional reaction platforms. Here, we introduce single droplet multiple displacement amplification (sd-MDA), a method that enables massively parallel amplification of single cell genomes while maintaining sequence accuracy and specificity. Tens of thousands of single cells are compartmentalized in millions of picoliter droplets and then subjected to lysis and WGA by passive droplet fusion in microfluidic channels. Because single cells are isolated in compartments, their genomes are amplified to saturation without contamination. This enables the high-throughput acquisition of contamination-free and cell specific sequence reads from single cells (21,000 single-cells/h), resulting in enhancement of the sequence data quality compared to conventional methods. This method allowed WGA of both single bacterial cells and human cancer cells. The obtained sequencing coverage rivals those of conventional techniques with superior sequence quality. In addition, we also demonstrate de novo assembly of uncultured soil bacteria and obtain draft genomes from single cell sequencing. This sd-MDA is promising for flexible and scalable use in single-cell sequencing.

Genome U-Plot: a whole genome visualization.

Science.gov (United States)

Gaitatzes, Athanasios; Johnson, Sarah H; Smadbeck, James B; Vasmatzis, George

2018-05-15

The ability to produce and analyze whole genome sequencing (WGS) data from samples with structural variations (SV) generated the need to visualize such abnormalities in simplified plots. Conventional two-dimensional representations of WGS data frequently use either circular or linear layouts. There are several diverse advantages regarding both these representations, but their major disadvantage is that they do not use the two-dimensional space very efficiently. We propose a layout, termed the Genome U-Plot, which spreads the chromosomes on a two-dimensional surface and essentially quadruples the spatial resolution. We present the Genome U-Plot for producing clear and intuitive graphs that allows researchers to generate novel insights and hypotheses by visualizing SVs such as deletions, amplifications, and chromoanagenesis events. The main features of the Genome U-Plot are its layered layout, its high spatial resolution and its improved aesthetic qualities. We compare conventional visualization schemas with the Genome U-Plot using visualization metrics such as number of line crossings and crossing angle resolution measures. Based on our metrics, we improve the readability of the resulting graph by at least 2-fold, making apparent important features and making it easy to identify important genomic changes. A whole genome visualization tool with high spatial resolution and improved aesthetic qualities. An implementation and documentation of the Genome U-Plot is publicly available at https://github.com/gaitat/GenomeUPlot. vasmatzis.george@mayo.edu. Supplementary data are available at Bioinformatics online.

Comparative Genomic Analysis of Lactobacillus plantarum GB-LP1 Isolated from Traditional Korean Fermented Food.

Science.gov (United States)

Yu, Jihyun; Ahn, Sojin; Kim, Kwondo; Caetano-Anolles, Kelsey; Lee, Chanho; Kang, Jungsun; Cho, Kyungjin; Yoon, Sook Hee; Kang, Dae-Kyung; Kim, Heebal

2017-08-28

As probiotics play an important role in maintaining a healthy gut flora environment through antitoxin activity and inhibition of pathogen colonization, they have been of interest to the medical research community for quite some time now. Probiotic bacteria such as Lactobacillus plantarum , which can be found in fermented food, are of particular interest given their easy accessibility. We performed whole-genome sequencing and genomic analysis on a GB-LP1 strain of L. plantarum isolated from Korean traditional fermented food; this strain is well known for its functions in immune response, suppression of pathogen growth, and antitoxin effects. The complete genome sequence of GB-LP1 is a single chromosome of 3,040,388 bp with 2,899 predicted open reading frames. Genomic analysis of GB-LP1 revealed two CRISPR regions and genes showing accelerated evolution, which may have antibiotic and antitoxin functions. The aim of the present study was to predict strain specific-genomic characteristics and assess the potential of this new strain as lactic acid bacteria at the genomic level using in silico analysis. These results provide insight into the L. plantarum species as well as confirm the possibility of its utility as a candidate probiotic.

A Thousand Fly Genomes: An Expanded Drosophila Genome Nexus.

Science.gov (United States)

Lack, Justin B; Lange, Jeremy D; Tang, Alison D; Corbett-Detig, Russell B; Pool, John E

2016-12-01

The Drosophila Genome Nexus is a population genomic resource that provides D. melanogaster genomes from multiple sources. To facilitate comparisons across data sets, genomes are aligned using a common reference alignment pipeline which involves two rounds of mapping. Regions of residual heterozygosity, identity-by-descent, and recent population admixture are annotated to enable data filtering based on the user's needs. Here, we present a significant expansion of the Drosophila Genome Nexus, which brings the current data object to a total of 1,121 wild-derived genomes. New additions include 305 previously unpublished genomes from inbred lines representing six population samples in Egypt, Ethiopia, France, and South Africa, along with another 193 genomes added from recently-published data sets. We also provide an aligned D. simulans genome to facilitate divergence comparisons. This improved resource will broaden the range of population genomic questions that can addressed from multi-population allele frequencies and haplotypes in this model species. The larger set of genomes will also enhance the discovery of functionally relevant natural variation that exists within and between populations. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Visualization for genomics: the Microbial Genome Viewer.

Science.gov (United States)

Kerkhoven, Robert; van Enckevort, Frank H J; Boekhorst, Jos; Molenaar, Douwe; Siezen, Roland J

2004-07-22

A Web-based visualization tool, the Microbial Genome Viewer, is presented that allows the user to combine complex genomic data in a highly interactive way. This Web tool enables the interactive generation of chromosome wheels and linear genome maps from genome annotation data stored in a MySQL database. The generated images are in scalable vector graphics (SVG) format, which is suitable for creating high-quality scalable images and dynamic Web representations. Gene-related data such as transcriptome and time-course microarray experiments can be superimposed on the maps for visual inspection. The Microbial Genome Viewer 1.0 is freely available at http://www.cmbi.kun.nl/MGV

[Spectrophotometric and HPLC evaluation of ceftazidime stability].

Science.gov (United States)

Palade, B; Cioroiu, B; Lazăr, Doina; Corciovă, Andreia; Lazăr, M I

2010-01-01

In this paper we followed up the stability of ceftazidime, raw material used in drug industry. Matherials and methods: We used three spectrophotometric methods based on ceftazidime property to form complexes with p-chloranilic acid (ac. p-CA), 3-methylbenzothiazolin-2-on hydrazone (MBTH) and N-(1-naphtil) etilendiamine (NEDA) and a chromatographic method (HPLC). Our results revealed that the substances analyzed maintained minimum content allowable.

Power stabilized CO2 gas transport laser

International Nuclear Information System (INIS)

Foster, J.D.; Kirk, R.F.; Moreno, F.E.; Ahmed, S.A.

1975-01-01

The output power of a high power (1 kW or more) CO 2 gas transport laser is stabilized by flowing the gas mixture over copper plated baffles in the gas channel during operation of the laser. Several other metals may be used instead of copper, for example, nickel, manganese, palladium, platinum, silver and gold. The presence of copper in the laser gas circuit stabilizes output power by what is believed to be a compensation of the chemical changes in the gas due to the cracking action of the electrical discharge which has the effect of diminishing the capactiy of the carbon dioxide gas mixture to maintain the rated power output of the laser. (U.S.)

DNA secondary structures: stability and function of G-quadruplex structures

Science.gov (United States)

Bochman, Matthew L.; Paeschke, Katrin; Zakian, Virginia A.

2013-01-01

In addition to the canonical double helix, DNA can fold into various other inter- and intramolecular secondary structures. Although many such structures were long thought to be in vitro artefacts, bioinformatics demonstrates that DNA sequences capable of forming these structures are conserved throughout evolution, suggesting the existence of non-B-form DNA in vivo. In addition, genes whose products promote formation or resolution of these structures are found in diverse organisms, and a growing body of work suggests that the resolution of DNA secondary structures is critical for genome integrity. This Review focuses on emerging evidence relating to the characteristics of G-quadruplex structures and the possible influence of such structures on genomic stability and cellular processes, such as transcription. PMID:23032257

Chromatinization of the KSHV Genome During the KSHV Life Cycle

Energy Technology Data Exchange (ETDEWEB)

Uppal, Timsy [Department of Microbiology and Immunology, School of Medicine, University of Nevada, 1664 N Virginia Street, MS 320, Reno, NV 89557 (United States); Jha, Hem C. [Department of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States); Verma, Subhash C. [Department of Microbiology and Immunology, School of Medicine, University of Nevada, 1664 N Virginia Street, MS 320, Reno, NV 89557 (United States); Robertson, Erle S., E-mail: erle@mail.med.upenn.edu [Department of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States)

2015-01-14

Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family and is the causative agent of various lymphoproliferative diseases in humans. KSHV, like other herpesviruses, establishes life-long latent infection with the expression of a limited number of viral genes. Expression of these genes is tightly regulated by both the viral and cellular factors. Recent advancements in identifying the expression profiles of viral transcripts, using tilling arrays and next generation sequencing have identified additional coding and non-coding transcripts in the KSHV genome. Determining the functions of these transcripts will provide a better understanding of the mechanisms utilized by KSHV in altering cellular pathways involved in promoting cell growth and tumorigenesis. Replication of the viral genome is critical in maintaining the existing copies of the viral episomes during both latent and lytic phases of the viral life cycle. The replication of the viral episome is facilitated by viral components responsible for recruiting chromatin modifying enzymes and replication factors for altering the chromatin complexity and replication initiation functions, respectively. Importantly, chromatin modification of the viral genome plays a crucial role in determining whether the viral genome will persist as latent episome or undergo lytic reactivation. Additionally, chromatinization of the incoming virion DNA, which lacks chromatin structure, in the target cells during primary infection, helps in establishing latent infection. Here, we discuss the recent advancements on our understating of KSHV genome chromatinization and the consequences of chromatin modifications on viral life cycle.

Chromatinization of the KSHV Genome During the KSHV Life Cycle

International Nuclear Information System (INIS)

Uppal, Timsy; Jha, Hem C.; Verma, Subhash C.; Robertson, Erle S.

2015-01-01

Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family and is the causative agent of various lymphoproliferative diseases in humans. KSHV, like other herpesviruses, establishes life-long latent infection with the expression of a limited number of viral genes. Expression of these genes is tightly regulated by both the viral and cellular factors. Recent advancements in identifying the expression profiles of viral transcripts, using tilling arrays and next generation sequencing have identified additional coding and non-coding transcripts in the KSHV genome. Determining the functions of these transcripts will provide a better understanding of the mechanisms utilized by KSHV in altering cellular pathways involved in promoting cell growth and tumorigenesis. Replication of the viral genome is critical in maintaining the existing copies of the viral episomes during both latent and lytic phases of the viral life cycle. The replication of the viral episome is facilitated by viral components responsible for recruiting chromatin modifying enzymes and replication factors for altering the chromatin complexity and replication initiation functions, respectively. Importantly, chromatin modification of the viral genome plays a crucial role in determining whether the viral genome will persist as latent episome or undergo lytic reactivation. Additionally, chromatinization of the incoming virion DNA, which lacks chromatin structure, in the target cells during primary infection, helps in establishing latent infection. Here, we discuss the recent advancements on our understating of KSHV genome chromatinization and the consequences of chromatin modifications on viral life cycle

Trajectory Generation and Stability Analysis for Reconfigurable Klann Mechanism Based Walking Robot

Directory of Open Access Journals (Sweden)

Jaichandar Kulandaidaasan Sheba

2016-06-01

Full Text Available Reconfigurable legged robots based on one degree of freedom are highly desired because they are effective on rough and irregular terrains and they provide mobility in such terrain with simple control schemes. It is necessary that reconfigurable legged robots should maintain stability during rest and motion, with a minimum number of legs while maintaining their full range of walking patterns resulting from different gait configuration. In this paper we present a method to generate input trajectory for reconfigurable quadruped robots based on Klann mechanism to properly synchronize movement. Six useful gait cycles based on this reconfigurable Klann mechanism for quadruped robots has been clearly shown here. The platform stability for these six useful gait cycles are validated through simulated results which clearly shows the capabilities of reconfigurable design.

Mapping Second Chromosome Mutations to Defined Genomic Regions in Drosophila melanogaster.

Science.gov (United States)

Kahsai, Lily; Cook, Kevin R

2018-01-04

Hundreds of Drosophila melanogaster stocks are currently maintained at the Bloomington Drosophila Stock Center with mutations that have not been associated with sequence-defined genes. They have been preserved because they have interesting loss-of-function phenotypes. The experimental value of these mutations would be increased by tying them to specific genomic intervals so that geneticists can more easily associate them with annotated genes. Here, we report the mapping of 85 second chromosome complementation groups in the Bloomington collection to specific, small clusters of contiguous genes or individual genes in the sequenced genome. This information should prove valuable to Drosophila geneticists interested in processes associated with particular phenotypes and those searching for mutations affecting specific sequence-defined genes. Copyright © 2018 Kahsai,Cook.

Mapping Second Chromosome Mutations to Defined Genomic Regions in Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Lily Kahsai

2018-01-01

Full Text Available Hundreds of Drosophila melanogaster stocks are currently maintained at the Bloomington Drosophila Stock Center with mutations that have not been associated with sequence-defined genes. They have been preserved because they have interesting loss-of-function phenotypes. The experimental value of these mutations would be increased by tying them to specific genomic intervals so that geneticists can more easily associate them with annotated genes. Here, we report the mapping of 85 second chromosome complementation groups in the Bloomington collection to specific, small clusters of contiguous genes or individual genes in the sequenced genome. This information should prove valuable to Drosophila geneticists interested in processes associated with particular phenotypes and those searching for mutations affecting specific sequence-defined genes.

Dynamic trunk stabilization: a conceptual back injury prevention program for volleyball athletes.

Science.gov (United States)

Smith, Chad E; Nyland, John; Caudill, Paul; Brosky, Joseph; Caborn, David N M

2008-11-01

The sport of volleyball creates considerable dynamic trunk stability demands. Back injury occurs all too frequently in volleyball, particularly among female athletes. The purpose of this clinical commentary is to review functional anatomy, muscle coactivation strategies, assessment of trunk muscle performance, and the characteristics of effective exercises for the trunk or core. From this information, a conceptual progressive 3-phase volleyball-specific training program is presented to improve dynamic trunk stability and to potentially reduce the incidence of back injury among volleyball athletes. Phase 1 addresses low-velocity motor control, kinesthetic awareness, and endurance, with the clinician providing cues to teach achievement of biomechanically neutral spine alignment. Phase 2 focuses on progressively higher velocity dynamic multiplanar endurance, coordination, and strength-power challenges integrating upper and lower extremity movements, while maintaining neutral spine alignment. Phase 3 integrates volleyball-specific skill simulations by breaking down composite movement patterns into their component parts, with differing dynamic trunk stability requirements, while maintaining neutral spine alignment. Prospective research is needed to validate the efficacy of this program.

Morphogenetic and chemical stability of long-term maintained Agrobacterium-mediated transgenic Catharanthus roseus plants.

Science.gov (United States)

Verma, Priyanka; Sharma, Abhishek; Khan, Shamshad Ahmad; Mathur, Ajay Kumar; Shanker, Karuna

2015-01-01

Transgenic Catharanthus roseus plants (transgenic Dhawal [DT] and transgenic Nirmal [NT]) obtained from the Agrobacterium tumefaciens and Agrobacterium rhizognenes-mediated transformations, respectively, have been maintained in vitro for 5 years. Plants were studied at regular intervals for various parameters such as plant height, leaf size, multiplication rate, alkaloid profile and presence of marker genes. DT plant gradually lost the GUS gene expression and it was not detected in the fifth year while NT plant demonstrated the presence of genes rolA, rolB and rolC even in the fifth year, indicating the more stable nature of Ri transgene. Vindoline content in the DT was two times more than in non-transformed control plants. Alkaloid and tryptophan profiles were almost constant during the 5 years. The cluster analysis revealed that the DT plant is more close to the control Nirmal plant followed by NT plant.

Relaxation of selective constraints causes independent selenoprotein extinction in insect genomes.

Directory of Open Access Journals (Sweden)

Charles E Chapple

Full Text Available BACKGROUND: Selenoproteins are a diverse family of proteins notable for the presence of the 21st amino acid, selenocysteine. Until very recently, all metazoan genomes investigated encoded selenoproteins, and these proteins had therefore been believed to be essential for animal life. Challenging this assumption, recent comparative analyses of insect genomes have revealed that some insect genomes appear to have lost selenoprotein genes. METHODOLOGY/PRINCIPAL FINDINGS: In this paper we investigate in detail the fate of selenoproteins, and that of selenoprotein factors, in all available arthropod genomes. We use a variety of in silico comparative genomics approaches to look for known selenoprotein genes and factors involved in selenoprotein biosynthesis. We have found that five insect species have completely lost the ability to encode selenoproteins and that selenoprotein loss in these species, although so far confined to the Endopterygota infraclass, cannot be attributed to a single evolutionary event, but rather to multiple, independent events. Loss of selenoproteins and selenoprotein factors is usually coupled to the deletion of the entire no-longer functional genomic region, rather than to sequence degradation and consequent pseudogenisation. Such dynamics of gene extinction are consistent with the high rate of genome rearrangements observed in Drosophila. We have also found that, while many selenoprotein factors are concomitantly lost with the selenoproteins, others are present and conserved in all investigated genomes, irrespective of whether they code for selenoproteins or not, suggesting that they are involved in additional, non-selenoprotein related functions. CONCLUSIONS/SIGNIFICANCE: Selenoproteins have been independently lost in several insect species, possibly as a consequence of the relaxation in insects of the selective constraints acting across metazoans to maintain selenoproteins. The dispensability of selenoproteins in insects may

Closed chamber globe stabilization and needle capsulorhexis using irrigation hand piece of bimanual irrigation and aspiration system

Directory of Open Access Journals (Sweden)

Rai Harminder K

2005-08-01

Full Text Available Abstract Background The prerequisites for a good capsulorhexis include a deep, well maintained anterior chamber, globe stabilization and globe manipulation. This helps to achieve a capsulorhexis of optimal size, shape and obtain the best possible position for a red glow under retroillumination. We report the use of irrigation handpiece of bimanual irrigation aspiration system to stabilize the globe, maintain a deep anterior chamber and manipulate the globe to a position of optimal red reflex during needle capsulorhexis in phacoemulsification. Methods Two side ports are made with 20 G MVR 'V' lance knife (Alcon, USA. The irrigation handpiece with irrigation on is introduced into the anterior chamber through one side port and the 26-G cystitome (made from 26-G needle is introduced through the other. The capsolurhexis is completed with the needle. Results Needle capsulorhexis with this technique was used in 30 cases of uncomplicated immature senile cataracts. 10 cases were done under peribulbar anaesthesia and 20 under topical anaesthesia. A complete capsulorhexis was achieved in all cases. Conclusion The irrigating handpiece maintains deep anterior chamber, stabilizes the globe, facilitates pupillary dilatation, and helps in maintaining the eye in the position with optimal red reflex during needle capsulorhexis. This technique is a safe and effective way to perform needle capsulorhexis.

A reversible histone H3 acetylation cooperates with mismatch repair and replicative polymerases in maintaining genome stability.

Directory of Open Access Journals (Sweden)

Lyudmila Y Kadyrova

2013-10-01

Full Text Available Mutations are a major driving force of evolution and genetic disease. In eukaryotes, mutations are produced in the chromatin environment, but the impact of chromatin on mutagenesis is poorly understood. Previous studies have determined that in yeast Saccharomyces cerevisiae, Rtt109-dependent acetylation of histone H3 on K56 is an abundant modification that is introduced in chromatin in S phase and removed by Hst3 and Hst4 in G2/M. We show here that the chromatin deacetylation on histone H3 K56 by Hst3 and Hst4 is required for the suppression of spontaneous gross chromosomal rearrangements, base substitutions, 1-bp insertions/deletions, and complex mutations. The rate of base substitutions in hst3Δ hst4Δ is similar to that in isogenic mismatch repair-deficient msh2Δ mutant. We also provide evidence that H3 K56 acetylation by Rtt109 is important for safeguarding DNA from small insertions/deletions and complex mutations. Furthermore, we reveal that both the deacetylation and acetylation on histone H3 K56 are involved in mutation avoidance mechanisms that cooperate with mismatch repair and the proofreading activities of replicative DNA polymerases in suppressing spontaneous mutagenesis. Our results suggest that cyclic acetylation and deacetylation of chromatin contribute to replication fidelity and play important roles in the protection of nuclear DNA from diverse spontaneous mutations.

Evolutionary Fates and Dynamic Functionalization of Young Duplicate Genes in Arabidopsis Genomes1[OPEN

Science.gov (United States)

Wang, Jun; Tao, Feng; Marowsky, Nicholas C.; Fan, Chuanzhu

2016-01-01

Gene duplication is a primary means to generate genomic novelties, playing an essential role in speciation and adaptation. Particularly in plants, a high abundance of duplicate genes has been maintained for significantly long periods of evolutionary time. To address the manner in which young duplicate genes were derived primarily from small-scale gene duplication and preserved in plant genomes and to determine the underlying driving mechanisms, we generated transcriptomes to produce the expression profiles of five tissues in Arabidopsis thaliana and the closely related species Arabidopsis lyrata and Capsella rubella. Based on the quantitative analysis metrics, we investigated the evolutionary processes of young duplicate genes in Arabidopsis. We determined that conservation, neofunctionalization, and specialization are three main evolutionary processes for Arabidopsis young duplicate genes. We explicitly demonstrated the dynamic functionalization of duplicate genes along the evolutionary time scale. Upon origination, duplicates tend to maintain their ancestral functions; but as they survive longer, they might be likely to develop distinct and novel functions. The temporal evolutionary processes and functionalization of plant duplicate genes are associated with their ancestral functions, dynamic DNA methylation levels, and histone modification abundances. Furthermore, duplicate genes tend to be initially expressed in pollen and then to gain more interaction partners over time. Altogether, our study provides novel insights into the dynamic retention processes of young duplicate genes in plant genomes. PMID:27485883

Genomic variation landscape of the human gut microbiome

DEFF Research Database (Denmark)

Schloissnig, Siegfried; Arumugam, Manimozhiyan; Sunagawa, Shinichi

2013-01-01

Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal...... polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates...

Diversity and stability of plasmids from glycopeptide resistant Enterococcus faecium isolated from pigs in Denmark

DEFF Research Database (Denmark)

Hasman, H.; Villadsen, A. G.; Aarestrup, Frank Møller

2005-01-01

was seen at the end of the 7-year period, coinciding with the ban in 1998 of the macrolide tylosin as growth promoter for pig production. The stability of the plasmid in its original host was compared with stability of the same plasmid in BM4105RF, when both strains were maintained in liquid cultures...

Active stabilization of a diode laser injection lock

Energy Technology Data Exchange (ETDEWEB)

Saxberg, Brendan; Plotkin-Swing, Benjamin; Gupta, Subhadeep [Department of Physics, University of Washington, P.O. Box 351560, Seattle, Washington 98195-1560 (United States)

2016-06-15

We report on a device to electronically stabilize the optical injection lock of a semiconductor diode laser. Our technique uses as discriminator the peak height of the laser’s transmission signal on a scanning Fabry-Perot cavity and feeds back to the diode current, thereby maintaining maximum optical power in the injected mode. A two-component feedback algorithm provides constant optimization of the injection lock, keeping it robust to slow thermal drifts and allowing fast recovery from sudden failures such as temporary occlusion of the injection beam. We demonstrate the successful performance of our stabilization method in a diode laser setup at 399 nm used for laser cooling of Yb atoms. The device eases the requirements on passive stabilization and can benefit any diode laser injection lock application, particularly those where several such locks are employed.

Active stabilization of a diode laser injection lock

International Nuclear Information System (INIS)

Saxberg, Brendan; Plotkin-Swing, Benjamin; Gupta, Subhadeep

2016-01-01

We report on a device to electronically stabilize the optical injection lock of a semiconductor diode laser. Our technique uses as discriminator the peak height of the laser’s transmission signal on a scanning Fabry-Perot cavity and feeds back to the diode current, thereby maintaining maximum optical power in the injected mode. A two-component feedback algorithm provides constant optimization of the injection lock, keeping it robust to slow thermal drifts and allowing fast recovery from sudden failures such as temporary occlusion of the injection beam. We demonstrate the successful performance of our stabilization method in a diode laser setup at 399 nm used for laser cooling of Yb atoms. The device eases the requirements on passive stabilization and can benefit any diode laser injection lock application, particularly those where several such locks are employed.

The Sequenced Angiosperm Genomes and Genome Databases.

Science.gov (United States)

Chen, Fei; Dong, Wei; Zhang, Jiawei; Guo, Xinyue; Chen, Junhao; Wang, Zhengjia; Lin, Zhenguo; Tang, Haibao; Zhang, Liangsheng

2018-01-01

Angiosperms, the flowering plants, provide the essential resources for human life, such as food, energy, oxygen, and materials. They also promoted the evolution of human, animals, and the planet earth. Despite the numerous advances in genome reports or sequencing technologies, no review covers all the released angiosperm genomes and the genome databases for data sharing. Based on the rapid advances and innovations in the database reconstruction in the last few years, here we provide a comprehensive review for three major types of angiosperm genome databases, including databases for a single species, for a specific angiosperm clade, and for multiple angiosperm species. The scope, tools, and data of each type of databases and their features are concisely discussed. The genome databases for a single species or a clade of species are especially popular for specific group of researchers, while a timely-updated comprehensive database is more powerful for address of major scientific mysteries at the genome scale. Considering the low coverage of flowering plants in any available database, we propose construction of a comprehensive database to facilitate large-scale comparative studies of angiosperm genomes and to promote the collaborative studies of important questions in plant biology.

Rotation stability of high speed neutron time-of-flight mechanical chopper

International Nuclear Information System (INIS)

Habib, N.; Adib, M.

1998-01-01

A modified rotation stabilization system has been designed to maintain the stability of a neutron time-of-flight (TOF) mechanical chopper rates from 460 rpm to 16000 rpm. The main principle of the system is based on comparing the chopper's rotation period with the preselected one from a quartz timer. The result of comparison is used to control the current driver of the chopper's motor. A 600 Hz three phase generator controlled by a magnetic amplifier was used as a current driver. The stability of the chopper's rotation rate at 16000 rpm was 0.02%. An improved method precise time scale calibration of the TOF spectrometer is applied

DNA Repair and Genome Maintenance in Bacillus subtilis

Science.gov (United States)

Lenhart, Justin S.; Schroeder, Jeremy W.; Walsh, Brian W.

2012-01-01

Summary: From microbes to multicellular eukaryotic organisms, all cells contain pathways responsible for genome maintenance. DNA replication allows for the faithful duplication of the genome, whereas DNA repair pathways preserve DNA integrity in response to damage originating from endogenous and exogenous sources. The basic pathways important for DNA replication and repair are often conserved throughout biology. In bacteria, high-fidelity repair is balanced with low-fidelity repair and mutagenesis. Such a balance is important for maintaining viability while providing an opportunity for the advantageous selection of mutations when faced with a changing environment. Over the last decade, studies of DNA repair pathways in bacteria have demonstrated considerable differences between Gram-positive and Gram-negative organisms. Here we review and discuss the DNA repair, genome maintenance, and DNA damage checkpoint pathways of the Gram-positive bacterium Bacillus subtilis. We present their molecular mechanisms and compare the functions and regulation of several pathways with known information on other organisms. We also discuss DNA repair during different growth phases and the developmental program of sporulation. In summary, we present a review of the function, regulation, and molecular mechanisms of DNA repair and mutagenesis in Gram-positive bacteria, with a strong emphasis on B. subtilis. PMID:22933559