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Sample records for sar-associated genes surprisingly

  1. Comparative analyses of immunoglobulin genes: surprises and portents.

    Science.gov (United States)

    Flajnik, Martin F

    2002-09-01

    The study of immunoglobulin genes in non-mouse and non-human models has shown that different vertebrate groups have evolved distinct methods of generating antibody diversity. By contrast, the development of T cells in the thymus is quite similar in all of the species that have been examined. The three mechanisms by which B cells uniquely modify their immunoglobulin genes -- somatic hypermutation, gene conversion and class switching -- are increasingly believed to share some fundamental mechanisms, which studies in different vertebrate groups have helped (and will continue to help) to resolve. When these mechanisms are better understood, we should be able to look to the constitutive pathways from which they have evolved and perhaps determine whether the rearrangement of variable, diversity and joining antibody gene segments -- V(D)J recombination -- was superimposed on an existing adaptive immune system.

  2. Surprisingly complex T-box gene complement in diploblastic metazoans.

    Science.gov (United States)

    Yamada, Atsuko; Pang, Kevin; Martindale, Mark Q; Tochinai, Shin

    2007-01-01

    Ctenophores and cnidarians are two metazoan groups that evolved at least 600 Ma, predating the Cambrian explosion. Although both groups are commonly categorized as diploblastic animals without derivatives of the mesodermal germ layer, ctenophores possess definitive contractile "muscle" cells. T-box family transcription factors are an evolutionarily ancient gene family, arising in the common ancestor of metazoans, and have been divided into eight groups in five distinct subfamilies, many of which are involved in the specification of mesodermal as well as ectodermally and endodermally derived structures. Here, we report the cloning and expression of five T-box genes from a ctenophore, Mnemiopsis leidyi. Phylogenetic analyses demonstrated that ctenophores possess members of at least three of the five T-box subfamilies, and expression studies suggested distinct roles of each T-box genes during gastrulation and early organogenesis. Moreover, genome searches of the sea anemone, Nematostella vectensis (anthozoan cnidarian), showed at least 13 T-box genes in Nematostella, which are divided into at least six distinct groups in the same three subfamilies found in ctenophores. Our results from two diploblastic animals indicate that the common ancestor of eumetazoans had a complex set of T-box genes and that two distinct subfamilies might have appeared during triploblastic evolution.

  3. A complete sequence and comparative analysis of a SARS-associated virus (Isolate BJ01)

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The genome sequence of the Severe Acute Respiratory Syndrome (SARS)-associated virus provides essential information for the identification of pathogen(s), exploration of etiology and evolution, interpretation of transmission and pathogenesis, development of diagnostics, prevention by future vaccination, and treatment by developing new drugs. We report the complete genome sequence and comparative analysis of an isolate (BJ01) of the coronavirus that has been recognized as a pathogen for SARS. The genome is 29725 nt in size and has 11 ORFs (Open Reading Frames). It is composed of a stable region encoding an RNA-dependent RNA polymerase (composed of 2 ORFs) and a variable region representing 4 CDSs (coding sequences) for viral structural genes (the S, E, M, N proteins) and 5 PUPs (putative uncharacterized proteins). Its gene order is identical to that of other known coronaviruses. The sequence alignment with all known RNA viruses places this virus as a member in the family of Coronaviridae. Thirty putative substitutions have been identified by comparative analysis of the 5 SARS- associated virus genome sequences in GenBank. Fifteen of them lead to possible amino acid changes (non-synonymousmutations) in the proteins. Three amino acid changes, with predicted alteration of physical and chemical features, have been detected in the S protein that is postulated to be involved in the immunoreactions between the virus and its host. Two amino acid changes have been detected in the M protein, which could be related to viral envelope formation. Phylogenetic analysis suggests the possibility of non-human origin of the SARS-associated viruses but provides no evidence that they are man-made. Further efforts should focus on identifying the etiology of the SARS-associated virus and ruling out conclusively the existence of other possible SARS-related pathogen(s).

  4. Ontological Surprises

    DEFF Research Database (Denmark)

    Leahu, Lucian

    2016-01-01

    This paper investigates how we might rethink design as the technological crafting of human-machine relations in the context of a machine learning technique called neural networks. It analyzes Google’s Inceptionism project, which uses neural networks for image recognition. The surprising output of...... a hybrid approach where machine learning algorithms are used to identify objects as well as connections between them; finally, it argues for remaining open to ontological surprises in machine learning as they may enable the crafting of different relations with and through technologies....

  5. Surprise Trips

    DEFF Research Database (Denmark)

    Korn, Matthias; Kawash, Raghid; Andersen, Lisbet Møller

    We report on a platform that augments the natural experience of exploration in diverse indoor and outdoor environments. The system builds on the theme of surprises in terms of user expectations and finding points of interest. It utilizes physical icons as representations of users' interests and a...

  6. Charming surprise

    CERN Multimedia

    Antonella Del Rosso

    2011-01-01

    The CP violation in charm quarks has always been thought to be extremely small. So, looking at particle decays involving matter and antimatter, the LHCb experiment has recently been surprised to observe that things might be different. Theorists are on the case.   The study of the physics of the charm quark was not in the initial plans of the LHCb experiment, whose letter “b” stands for “beauty quark”. However, already one year ago, the Collaboration decided to look into a wider spectrum of processes that involve charm quarks among other things. The LHCb trigger allows a lot of these processes to be selected, and, among them, one has recently shown interesting features. Other experiments at b-factories have already performed the same measurement but this is the first time that it has been possible to achieve such high precision, thanks to the huge amount of data provided by the very high luminosity of the LHC. “We have observed the decay modes of t...

  7. Charming surprise

    CERN Multimedia

    Antonella Del Rosso

    2011-01-01

    The CP violation in charm quarks has always been thought to be extremely small. So, looking at particle decays involving matter and antimatter, the LHCb experiment has recently been surprised to observe that things might be different. Theorists are on the case. The study of the physics of the charm quark was not in the initial plans of the LHCb experiment, whose letter “b” stands for “beauty quark”. However, already one year ago, the Collaboration decided to look into a wider spectrum of processes that involve charm quarks among other things. The LHCb trigger allows a lot of these processes to be selected, and, among them, one has recently shown interesting features. Other experiments at b-factories have already performed the same measurement but this is the first time that it has been possible to achieve such high precision, thanks to the huge amount of data provided by the very high luminosity of the LHC. “We have observed the decay modes of the D0, a pa...

  8. The surprising negative correlation of gene length and optimal codon use--disentangling translational selection from GC-biased gene conversion in yeast.

    Science.gov (United States)

    Stoletzki, Nina

    2011-04-11

    Surprisingly, in several multi-cellular eukaryotes optimal codon use correlates negatively with gene length. This contrasts with the expectation under selection for translational accuracy. While suggested explanations focus on variation in strength and efficiency of translational selection, it has rarely been noticed that the negative correlation is reported only in organisms whose optimal codons are biased towards codons that end with G or C (-GC). This raises the question whether forces that affect base composition--such as GC-biased gene conversion--contribute to the negative correlation between optimal codon use and gene length. Yeast is a good organism to study this as equal numbers of optimal codons end in -GC and -AT and one may hence compare frequencies of optimal GC- with optimal AT-ending codons to disentangle the forces. Results of this study demonstrate in yeast frequencies of GC-ending (optimal AND non-optimal) codons decrease with gene length and increase with recombination. A decrease of GC-ending codons along genes contributes to the negative correlation with gene length. Correlations with recombination and gene expression differentiate between GC-ending and optimal codons, and also substitution patterns support effects of GC-biased gene conversion. While the general effect of GC-biased gene conversion is well known, the negative correlation of optimal codon use with gene length has not been considered in this context before. Initiation of gene conversion events in promoter regions and the presence of a gene conversion gradient most likely explain the observed decrease of GC-ending codons with gene length and gene position.

  9. Coronaviridae and SARS-associated Coronavirus Strain HSR1

    Science.gov (United States)

    Canducci, Filippo; Pinna, Debora; Mancini, Nicasio; Carletti, Silvia; Lazzarin, Adriano; Bordignon, Claudio; Poli, Guido; Clementi, Massimo

    2004-01-01

    During the recent severe acute respiratory (SARS) outbreak, the etiologic agent was identified as a new coronavirus (CoV). We have isolated a SARS-associated CoV (SARS-CoV) strain by injecting Vero cells with a sputum specimen from an Italian patient affected by a severe pneumonia; the patient traveled from Vietnam to Italy in March 2003. Ultrastructural analysis of infected Vero cells showed the virions within cell vesicles and around the cell membrane. The full-length viral genome sequence was similar to those derived from the Hong-Kong Hotel M isolate. By using both real-time reverse transcription–polymerase chain reaction TaqMan assay and an infectivity plaque assay, we determined that approximately 360 viral genomes were required to generate a PFU. In addition, heparin (100 μg/mL) inhibited infection of Vero cells by 50%. Overall, the molecular and biologic characteristics of the strain HSR1 provide evidence that SARS-CoV forms a fourth genetic coronavirus group with distinct genomic and biologic features. PMID:15109406

  10. Anti-SARS virus antibody responses against human SARS-associated coronavirus and animal SARS-associated coronavirus-like virus

    Institute of Scientific and Technical Information of China (English)

    王鸣; 徐慧芳; 莫自耀; 郑伯健; 高阳; 顾菁; 秦鹏哲; 张周斌; 邹晓忠; 梁彩云; 赵宇腾; 高凯

    2004-01-01

    @@ Severe acute respiratory syndrome (SARS) is an infectious disease first recognized in November 2002 in Guangdong province, China. It was spread to many countries all over the world within a few months.1,2 By April 2003, SARS-associated coronavirus (SARS-CoV) was found to be the etiological agent.

  11. Establishment of a fluorescent polymerase chain reaction method for the detection of the SARS-associated coronavirus and its clinical application

    Institute of Scientific and Technical Information of China (English)

    吴新伟; 程钢; 狄飚; 尹爱华; 何蕴韶; 王鸣; 周新宇; 何丽娟; 罗凯; 杜琳

    2003-01-01

    Objective To establish a fluorescent polymerase chain reaction (F-PCR) method for detecting the coronavirus related to severe acute respiratory syndrome (SARS) and to evaluate its value for clinical application. Methods The primers and the fluorescence-labeled probe were designed and synthesized according to the published sequence of the SARS-associated coronavirus genes. A F-PCR diagnosis kit for detecting the coronavirus was developed, and 115 clinical nasopharyngeal gargling liquid samples were tested. Results The sequence of PCR amplified products completely matched the related sequence of the SARS-associated coronavirus genome. Forty-nine out of 67 samples from identified SARS patients and 8 of 18 samples from persons having close contact with SARS patients showed positive results. All 30 samples from healthy controls were negative. Conclusion The F-PCR method established may be a rapid, accurate and efficient way for screening and for the early diagnosis of SARS patients.

  12. More Supernova Surprises

    Science.gov (United States)

    2010-09-24

    SEP 2010 2. REPORT TYPE 3. DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE More Supernova Surprises 5a. CONTRACT NUMBER 5b. GRANT...PERSPECTIVES More Supernova Surprises ASTRONOMY J. Martin Laming Spectroscopic observations of the supernova SN1987A are providing a new window into high...a core-collapse supernova ) have stretched and motivated research that has expanded our knowledge of astrophysics. The brightest such event in

  13. Surprises with Nonrelativistic Naturalness

    CERN Document Server

    Horava, Petr

    2016-01-01

    We explore the landscape of technical naturalness for nonrelativistic systems, finding surprises which challenge and enrich our relativistic intuition already in the simplest case of a single scalar field. While the immediate applications are expected in condensed matter and perhaps in cosmology, the study is motivated by the leading puzzles of fundamental physics involving gravity: The cosmological constant problem and the Higgs mass hierarchy problem.

  14. Surprises in astrophysical gasdynamics

    CERN Document Server

    Balbus, Steven A

    2016-01-01

    Much of astrophysics consists of the study of ionised gas under the influence of gravitational and magnetic fields. Thus, it is not possible to understand the astrophysical universe without a detailed knowledge of the dynamics of magnetised fluids. Fluid dynamics is, however, a notoriously tricky subject, in which it is all too easy for one's a priori intuition to go astray. In this review, we seek to guide the reader through a series of illuminating yet deceptive problems, all with an enlightening twist. We cover a broad range of topics including the instabilities acting in accretion discs, the hydrodynamics governing the convective zone of the Sun, the magnetic shielding of a cooling galaxy cluster, and the behaviour of thermal instabilities and evaporating clouds. The aim of this review is to surprise and intrigue even veteran astrophysical theorists with an idiosynchratic choice of problems and counterintuitive results. At the same time, we endeavour to bring forth the fundamental ideas, to set out import...

  15. Surprises in astrophysical gasdynamics

    Science.gov (United States)

    Balbus, Steven A.; Potter, William J.

    2016-06-01

    Much of astrophysics consists of the study of ionized gas under the influence of gravitational and magnetic fields. Thus, it is not possible to understand the astrophysical universe without a detailed knowledge of the dynamics of magnetized fluids. Fluid dynamics is, however, a notoriously tricky subject, in which it is all too easy for one’s a priori intuition to go astray. In this review, we seek to guide the reader through a series of illuminating yet deceptive problems, all with an enlightening twist. We cover a broad range of topics including the instabilities acting in accretion discs, the hydrodynamics governing the convective zone of the Sun, the magnetic shielding of a cooling galaxy cluster, and the behaviour of thermal instabilities and evaporating clouds. The aim of this review is to surprise and intrigue even veteran astrophysical theorists with an idiosyncratic choice of problems and counterintuitive results. At the same time, we endeavour to bring forth the fundamental ideas, to set out important assumptions, and to describe carefully whatever novel techniques may be appropriate to the problem at hand. By beginning at the beginning, and analysing a wide variety of astrophysical settings, we seek not only to make this review suitable for fluid dynamic veterans, but to engage novice recruits as well with what we hope will be an unusual and instructive introduction to the subject.

  16. Surprises in astrophysical gasdynamics.

    Science.gov (United States)

    Balbus, Steven A; Potter, William J

    2016-06-01

    Much of astrophysics consists of the study of ionized gas under the influence of gravitational and magnetic fields. Thus, it is not possible to understand the astrophysical universe without a detailed knowledge of the dynamics of magnetized fluids. Fluid dynamics is, however, a notoriously tricky subject, in which it is all too easy for one's a priori intuition to go astray. In this review, we seek to guide the reader through a series of illuminating yet deceptive problems, all with an enlightening twist. We cover a broad range of topics including the instabilities acting in accretion discs, the hydrodynamics governing the convective zone of the Sun, the magnetic shielding of a cooling galaxy cluster, and the behaviour of thermal instabilities and evaporating clouds. The aim of this review is to surprise and intrigue even veteran astrophysical theorists with an idiosyncratic choice of problems and counterintuitive results. At the same time, we endeavour to bring forth the fundamental ideas, to set out important assumptions, and to describe carefully whatever novel techniques may be appropriate to the problem at hand. By beginning at the beginning, and analysing a wide variety of astrophysical settings, we seek not only to make this review suitable for fluid dynamic veterans, but to engage novice recruits as well with what we hope will be an unusual and instructive introduction to the subject.

  17. Phylogenomics reveals surprising sets of essential and dispensable clades of MIKC(c)-group MADS-box genes in flowering plants.

    Science.gov (United States)

    Gramzow, Lydia; Theißen, Günter

    2015-06-01

    MIKC(C)-group MADS-box genes are involved in the control of many developmental processes in flowering plants. All of these genes are members of one of 17 clades that had already been established in the most recent common ancestor (MRCA) of extant angiosperms. These clades trace back to 11 seed plant-specific superclades that were present in the MRCA of extant seed plants. Due to their important role in plant development and evolution, the origin of the clades of MIKC(C)-group genes has been studied in great detail. In contrast, whether any of these ancestral clades has ever been lost completely in any species has not been investigated so far. Here, we determined the presence of these clades by BLAST, PSI-BLAST, and Hidden Markov Model searches and by phylogenetic methods in the whole genomes of 27 flowering plants. Our data suggest that there are only three superclades of which all members have been lost in at least one of the investigated flowering plant species, and only few additional losses of angiosperm-specific MIKC(C)-group gene clades could be identified. Remarkably, for one seed plant superclade (TM8-like genes) and one angiosperm clade (FLC-like genes), multiple losses were identified, suggesting that the function of these genes is dispensable or that gene loss might have even been adaptive. The clades of MIKC(C)-group genes that have never been wiped out in any of the investigated species comprises, in addition to the expected floral organ identity genes, also TM3-like (SOC1-like), StMADS11-like (SVP-like), AGL17-like and GGM13-like (Bsister) genes, suggesting that these genes are more important for angiosperm development and evolution than has previously been appreciated.

  18. Surprise... Surprise..., An Empirical Investigation on How Surprise is Connected to Customer Satisfaction

    NARCIS (Netherlands)

    J. Vanhamme (Joëlle)

    2003-01-01

    textabstractThis research investigates the specific influence of the emotion of surprise on customer transaction-specific satisfaction. Four empirical studies-two field studies (a diary study and a cross section survey) and two experiments-were conducted. The results show that surprise positively

  19. Surprise... Surprise..., An Empirical Investigation on How Surprise is Connected to Customer Satisfaction

    NARCIS (Netherlands)

    J. Vanhamme (Joëlle)

    2003-01-01

    textabstractThis research investigates the specific influence of the emotion of surprise on customer transaction-specific satisfaction. Four empirical studies-two field studies (a diary study and a cross section survey) and two experiments-were conducted. The results show that surprise positively [n

  20. Surprise as a design strategy

    NARCIS (Netherlands)

    Ludden, G.D.S.; Schifferstein, H.N.J.; Hekkert, P.P.M.

    2008-01-01

    Imagine yourself queuing for the cashier’s desk in a supermarket. Naturally, you have picked the wrong line, the one that does not seem to move at all. Soon, you get tired of waiting. Now, how would you feel if the cashier suddenly started to sing? Many of us would be surprised and, regardless of

  1. Surprise as a design strategy

    NARCIS (Netherlands)

    Ludden, G.D.S.; Schifferstein, H.N.J.; Hekkert, P.P.M.

    2008-01-01

    Imagine yourself queuing for the cashier’s desk in a supermarket. Naturally, you have picked the wrong line, the one that does not seem to move at all. Soon, you get tired of waiting. Now, how would you feel if the cashier suddenly started to sing? Many of us would be surprised and, regardless of th

  2. Human LINE1 endonuclease domain as a putative target of SARS-associated autoantibodies involved in the pathogenesis of severe acute respiratory syndrome

    Institute of Scientific and Technical Information of China (English)

    HE Wei-ping; SHU Cui-li; LI Bo-an; ZHAO Jun; CHENG Yun

    2008-01-01

    Background Severe acute respiratory syndrome(SARS)is a disease with a mortality of 9.56%.Although SARS is etiologically linked to a new coronavirus(SARS-CoV)and functional cell receptor has been identified,the pathogenesis of the virus infection is largely unclear.Methods The clinical specimens were processed and analyzed using an indirect enzyme-linked immunosorbent assay (ELISA) in-house.Further investigations of target antigen included reviews of phage display technique,rapid amplification of cDNA ends(RACE)technique,protein expression and purification,Western blotting validation,serological and immunohistochemical staining in postmortem tissue.Results A type of medium or low titer anti-lung tissue antibodies were found in the sera of SARS patients at the early stage of the disease.Human long interspersed nuclear element 1(LINE1)gene endonuclease(EN)domain protein was one of the target autoantigens and it was aberrantly expressed in the lung tissue of SARS patients.Anti-EN antibody was positive in the sera of 40.9% of SARS patients.Conclusions Human LINE1 endonuclease domain was identified as a putative target of SARS-associated autoantibodies,which were presented in the serum of SARS patients and may be involved in the pathogenesis of SARS.

  3. Brazilian rescue plan sparks surprise

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    According to Financial Times,when Guido Mantega,Brazil's finance minister,suddenly proposed a “Bric” rescue package for the eurozone this week,he caught not only other world leaders by surprise but also many of his fellow countrymen.Even as officials from other members of the so-called Bric grouping,Russia,India and China,said it was the first they heard of the idea,many ordinary Brazilians expressed shock at the notion of bailing out the world's richest trading bloc.

  4. Some Surprises in Relativistic Gravity

    CERN Document Server

    Santos, N O

    2016-01-01

    General Relativity has had tremendous success both on the theoretical and the experimental fronts for over a century now. However, the contents of the theory are far from exhausted. Only very recently, with the detection of gravitational waves from colliding black holes, we have started probing the behavior of gravity in the strongly non-linear regime. Even today, the studies of black holes keep revealing more and more paradoxes and bizarre results. In this paper, inspired by David Hilbert's startling observation, we show that, contrary to the conventional wisdom, a freely falling test particle feels gravitational repulsion by a black hole as seen by the asymptotic observer. We dig deeper into this surprising behavior of relativistic gravity and offer some explanations.

  5. Spike protein homology between the SARS-associated virus and murine hepatitis virus implies existence of a putative receptor-binding region

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Coronavirus has been determined to be the cause of the recent outbreak of severe acute respiratory syndrome (SARS). Human coronavirus 229E had been studied well and its receptor-binding domain was restricted to aa417-547 of S protein. However, this region has no homology with the newly separated SARS-associated virus (Hong Kong isolate CUHK-W1). Then we analyzed the phylogenesis of S1 subunit of the coronavirus spike protein (SARS-associated virus, Hong Kong isolate CUHK-W1). Interestingly, the highest homology between murine hepatitis virus (MHV) and SARS-associated coronavirus was found. And the important sites (aa62-65 and aa214-216) on the spike protein of MHV with receptor-binding capacity were highly conservative in comparison with the newly separated SARS-asso- ciated virus (the corresponding sites are aa51-54 and aa195-197). These results from bioinformatics analysis might help us to study the receptor-binding sites of SARS-associ- ated virus and the mechanism of the virus entry into the target cell, and design antiviral drugs and potent vaccines.

  6. Some Surprising Introductory Physics Facts and Numbers

    Science.gov (United States)

    Mallmann, A. James

    2016-01-01

    In the entertainment world, people usually like, and find memorable, novels, short stories, and movies with surprise endings. This suggests that classroom teachers might want to present to their students examples of surprising facts associated with principles of physics. Possible benefits of finding surprising facts about principles of physics are…

  7. Young Galaxy's Magnetism Surprises Astronomers

    Science.gov (United States)

    2008-10-01

    Astronomers have made the first direct measurement of the magnetic field in a young, distant galaxy, and the result is a big surprise. Looking at a faraway protogalaxy seen as it was 6.5 billion years ago, the scientists measured a magnetic field at least 10 times stronger than that of our own Milky Way. They had expected just the opposite. The GBT Robert C. Byrd Green Bank Telescope CREDIT: NRAO/AUI/NSF The scientists made the discovery using the National Science Foundation's ultra-sensitive Robert C. Byrd Green Bank Telescope (GBT) in West Virginia. "This new measurement indicates that magnetic fields may play a more important role in the formation and evolution of galaxies than we have realized," said Arthur Wolfe, of the University of California-San Diego (UCSD). At its great distance, the protogalaxy is seen as it was when the Universe was about half its current age. According to the leading theory, cosmic magnetic fields are generated by the dynamos of rotating galaxies -- a process that would produce stronger fields with the passage of time. In this scenario, the magnetic fields should be weaker in the earlier Universe, not stronger. The new, direct magnetic-field measurement comes on the heels of a July report by Swiss and American astronomers who made indirect measurements that also implied strong magnetic fields in the early Universe. "Our results present a challenge to the dynamo model, but they do not rule it out," Wolfe said. There are other possible explanations for the strong magnetic field seen in the one protogalaxy Wolfe's team studied. "We may be seeing the field close to the central region of a massive galaxy, and we know such fields are stronger toward the centers of nearby galaxies. Also, the field we see may have been amplified by a shock wave caused by the collision of two galaxies," he said. The protogalaxy studied with the GBT, called DLA-3C286, consists of gas with little or no star formation occurring in it. The astronomers suspect that

  8. Evaluative Appraisals of Environmental Mystery and Surprise

    Science.gov (United States)

    Nasar, Jack L.; Cubukcu, Ebru

    2011-01-01

    This study used a desktop virtual environment (VE) of 15 large-scale residential streets to test the effects of environmental mystery and surprise on response. In theory, mystery and surprise should increase interest and visual appeal. For each VE, participants walked through an approach street and turned right onto a post-turn street. We designed…

  9. Evaluative Appraisals of Environmental Mystery and Surprise

    Science.gov (United States)

    Nasar, Jack L.; Cubukcu, Ebru

    2011-01-01

    This study used a desktop virtual environment (VE) of 15 large-scale residential streets to test the effects of environmental mystery and surprise on response. In theory, mystery and surprise should increase interest and visual appeal. For each VE, participants walked through an approach street and turned right onto a post-turn street. We designed…

  10. Analyst Information Precision and Small Earnings Surprises

    NARCIS (Netherlands)

    S. Bissessur; D. Veenman

    2014-01-01

    Prior research attributes zero and small positive earnings surprises to managers’ incentives for earnings management. In contrast, this study introduces and empirically tests an explanation for zero and small positive earnings surprises based on predictable variation in analyst forecast errors. We a

  11. Cognitive and Social Perspectives on Surprise

    Science.gov (United States)

    Adhami, Mundler

    2007-01-01

    Meanings of "surprise" are wide and include uplifting and engaging facets like wonder and amazement on the one hand as well as ones that may be of the opposite nature like interruption and disrupt on the other. Pedagogically, educators who use surprise in class activities are focusing on students being "taken aback" by a situation, hopefully…

  12. A toolkit for detecting technical surprise.

    Energy Technology Data Exchange (ETDEWEB)

    Trahan, Michael Wayne; Foehse, Mark C.

    2010-10-01

    The detection of a scientific or technological surprise within a secretive country or institute is very difficult. The ability to detect such surprises would allow analysts to identify the capabilities that could be a military or economic threat to national security. Sandia's current approach utilizing ThreatView has been successful in revealing potential technological surprises. However, as data sets become larger, it becomes critical to use algorithms as filters along with the visualization environments. Our two-year LDRD had two primary goals. First, we developed a tool, a Self-Organizing Map (SOM), to extend ThreatView and improve our understanding of the issues involved in working with textual data sets. Second, we developed a toolkit for detecting indicators of technical surprise in textual data sets. Our toolkit has been successfully used to perform technology assessments for the Science & Technology Intelligence (S&TI) program.

  13. Deciphering network community structure by surprise

    National Research Council Canada - National Science Library

    Aldecoa, Rodrigo; Marín, Ignacio

    2011-01-01

    .... A fundamental, unsolved problem is how to characterize the community structure of a network. Here, using both standard and novel benchmarks, we show that maximization of a simple global parameter, which we call Surprise...

  14. A Surprising Culprit Behind Celiac Disease?

    Science.gov (United States)

    ... news/fullstory_164503.html A Surprising Culprit Behind Celiac Disease? Study suggests harmless viruses may set stage ... typically harmless type of virus might sometimes trigger celiac disease, a new study suggests. Celiac disease is ...

  15. Surprises in numerical expressions of physical constants

    CERN Document Server

    Amir, Ariel; Tokieda, Tadashi

    2016-01-01

    In science, as in life, `surprises' can be adequately appreciated only in the presence of a null model, what we expect a priori. In physics, theories sometimes express the values of dimensionless physical constants as combinations of mathematical constants like pi or e. The inverse problem also arises, whereby the measured value of a physical constant admits a `surprisingly' simple approximation in terms of well-known mathematical constants. Can we estimate the probability for this to be a mere coincidence, rather than an inkling of some theory? We answer the question in the most naive form.

  16. Surprising Connections between Partitions and Divisors

    Science.gov (United States)

    Osler, Thomas J.; Hassen, Abdulkadir; Chandrupatla, Tirupathi R.

    2007-01-01

    The sum of the divisors of a positive integer is one of the most interesting concepts in multiplicative number theory, while the number of ways of expressing a number as a sum is a primary topic in additive number theory. In this article, we describe some of the surprising connections between and similarities of these two concepts.

  17. Surprises from extragalactic propagation of UHECRs

    CERN Document Server

    Boncioli, Denise; Grillo, Aurelio

    2015-01-01

    Ultra-high energy cosmic ray experimental data are now of very good statistical significance even in the region of the expected GZK feature. The identification of their sources requires sophisticate analysis of their propagation in the extragalactic space. When looking at the details of this propagation some unforeseen features emerge. We will discuss some of these "surprises".

  18. Radar Design to Protect Against Surprise

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin W. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-02-01

    Technological and doctrinal surprise is about rendering preparations for conflict as irrelevant or ineffective . For a sensor, this means essentially rendering the sensor as irrelevant or ineffective in its ability to help determine truth. Recovery from this sort of surprise is facilitated by flexibility in our own technology and doctrine. For a sensor, this mean s flexibility in its architecture, design, tactics, and the designing organizations ' processes. - 4 - Acknowledgements This report is the result of a n unfunded research and development activity . Sandia National Laboratories is a multi - program laboratory manage d and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE - AC04 - 94AL85000.

  19. Surprise Leads to Noisier Perceptual Decisions

    Directory of Open Access Journals (Sweden)

    Marta I Garrido

    2011-02-01

    Full Text Available Surprising events in the environment can impair task performance. This might be due to complete distraction, leading to lapses during which performance is reduced to guessing. Alternatively, unpredictability might cause a graded withdrawal of perceptual resources from the task at hand and thereby reduce sensitivity. Here we attempt to distinguish between these two mechanisms. Listeners performed a novel auditory pitch—duration discrimination, where stimulus loudness changed occasionally and incidentally to the task. Responses were slower and less accurate in the surprising condition, where loudness changed unpredictably, than in the predictable condition, where the loudness was held constant. By explicitly modelling both lapses and changes in sensitivity, we found that unpredictable changes diminished sensitivity but did not increase the rate of lapses. These findings suggest that background environmental uncertainty can disrupt goal-directed behaviour. This graded processing strategy might be adaptive in potentially threatening contexts, and reflect a flexible system for automatic allocation of perceptual resources.

  20. Radar Design to Protect Against Surprise.

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin W.

    2015-02-01

    Technological and doctrinal surprise is about rendering preparations for conflict as irrelevant or ineffective . For a sensor, this means essentially rendering the sensor as irrelevant or ineffective in its ability to help determine truth. Recovery from this sort of surprise is facilitated by flexibility in our own technology and doctrine. For a sensor, this mean s flexibility in its architecture, design, tactics, and the designing organizations ' processes. - 4 - Acknowledgements This report is the result of a n unfunded research and development activity . Sandia National Laboratories is a multi - program laboratory manage d and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE - AC04 - 94AL85000.

  1. Surprise-Based Learning for Autonomous Systems

    Science.gov (United States)

    2009-02-28

    for scientific theories containing recursive theoretical terms". British Journal of Philosophy of Science, 44. 641-652, 1993. Piaget J.. "The Origins...paradigm stems from Piaget’s theory of Developmental Psychology [5], Herben Simon’s theory on dual-space search for knowledge and problem solving [6...34, Twenty-First Conference on Uncertainty in Artificial Intelligence, Edinburgh, Scotland, July 2005. [34] Itti L., Baldi P., "A Surprising Theory of

  2. Pupil size tracks perceptual content and surprise.

    Science.gov (United States)

    Kloosterman, Niels A; Meindertsma, Thomas; van Loon, Anouk M; Lamme, Victor A F; Bonneh, Yoram S; Donner, Tobias H

    2015-04-01

    Changes in pupil size at constant light levels reflect the activity of neuromodulatory brainstem centers that control global brain state. These endogenously driven pupil dynamics can be synchronized with cognitive acts. For example, the pupil dilates during the spontaneous switches of perception of a constant sensory input in bistable perceptual illusions. It is unknown whether this pupil dilation only indicates the occurrence of perceptual switches, or also their content. Here, we measured pupil diameter in human subjects reporting the subjective disappearance and re-appearance of a physically constant visual target surrounded by a moving pattern ('motion-induced blindness' illusion). We show that the pupil dilates during the perceptual switches in the illusion and a stimulus-evoked 'replay' of that illusion. Critically, the switch-related pupil dilation encodes perceptual content, with larger amplitude for disappearance than re-appearance. This difference in pupil response amplitude enables prediction of the type of report (disappearance vs. re-appearance) on individual switches (receiver-operating characteristic: 61%). The amplitude difference is independent of the relative durations of target-visible and target-invisible intervals and subjects' overt behavioral report of the perceptual switches. Further, we show that pupil dilation during the replay also scales with the level of surprise about the timing of switches, but there is no evidence for an interaction between the effects of surprise and perceptual content on the pupil response. Taken together, our results suggest that pupil-linked brain systems track both the content of, and surprise about, perceptual events.

  3. Some surprising facts about (the problem of) surprising facts (from the Dusseldorf Conference, February 2011).

    Science.gov (United States)

    Mayo, D

    2014-03-01

    A common intuition about evidence is that if data x have been used to construct a hypothesis H, then x should not be used again in support of H. It is no surprise that x fits H, if H was deliberately constructed to accord with x. The question of when and why we should avoid such "double-counting" continues to be debated in philosophy and statistics. It arises as a prohibition against data mining, hunting for significance, tuning on the signal, and ad hoc hypotheses, and as a preference for predesignated hypotheses and "surprising" predictions. I have argued that it is the severity or probativeness of the test--or lack of it--that should determine whether a double-use of data is admissible. I examine a number of surprising ambiguities and unexpected facts that continue to bedevil this debate.

  4. Stroke Recovery: Surprising Influences and Residual Consequences

    Directory of Open Access Journals (Sweden)

    Argye E. Hillis

    2014-01-01

    Full Text Available There is startling individual variability in the degree to which people recover from stroke and the duration of time over which recovery of some symptoms occurs. There are a variety of mechanisms of recovery from stroke which take place at distinct time points after stroke and are influenced by different variables. We review recent studies from our laboratory that unveil some surprising findings, such as the role of education in chronic recovery. We also report data showing that the consequences that most plague survivors of stroke and their caregivers are loss of high level cortical functions, such as empathy or written language. These results have implications for rehabilitation and management of stroke.

  5. Surprises and mysteries in urban soils

    Science.gov (United States)

    Groffman, P. M.

    2015-12-01

    In the Baltimore Ecosystem Study, one of two urban long-term ecological research (LTER) projects funded by the U.S. National Science Foundation, we are using "the watershed approach" to integrate ecological, physical and social sciences. Urban and suburban watershed input/output budgets for nitrogen have shown surprisingly high retention which has led to detailed analysis of sources and sinks in soils these watersheds. Home lawns, thought to be major sources of reactive nitrogen in suburban watersheds, have more complex coupled carbon and nitrogen dynamics than previously thought, and are likely the site of much nitrogen retention. Riparian zones, thought to be an important sink for reactive nitrogen in many watersheds, have turned out be nitrogen sources in urban watersheds due to hydrologic changes that disconnect streams from their surrounding landscape. Urban effects on atmospheric carbon dioxide levels and nitrogen deposition have strong effects on soil nitrogen cycling processes and soil:atmosphere fluxes of nitrous oxide, carbon dioxide and methane. Efforts to manage urban soils and watersheds through geomorphic stream restoration, creation of stormwater management features and changes in lawn and forest management can have significant effects on watershed carbon and nitrogen dynamics. Urban soils present a basic and applied science frontier that challenges our understanding of biological, physical, chemical and social science processes. The watershed approach provides an effective platform for integrating these disciplines and for articulating critical questions that arise from surprising results. This approach can help us to meet the challenge of urban soils, which is critical to achieving sustainability goals in cities across the world.

  6. The conceptualization model problem—surprise

    Science.gov (United States)

    Bredehoeft, John

    2005-03-01

    The foundation of model analysis is the conceptual model. Surprise is defined as new data that renders the prevailing conceptual model invalid; as defined here it represents a paradigm shift. Limited empirical data indicate that surprises occur in 20-30% of model analyses. These data suggest that groundwater analysts have difficulty selecting the appropriate conceptual model. There is no ready remedy to the conceptual model problem other than (1) to collect as much data as is feasible, using all applicable methods—a complementary data collection methodology can lead to new information that changes the prevailing conceptual model, and (2) for the analyst to remain open to the fact that the conceptual model can change dramatically as more information is collected. In the final analysis, the hydrogeologist makes a subjective decision on the appropriate conceptual model. The conceptualization problem does not render models unusable. The problem introduces an uncertainty that often is not widely recognized. Conceptual model uncertainty is exacerbated in making long-term predictions of system performance. C'est le modèle conceptuel qui se trouve à base d'une analyse sur un modèle. On considère comme une surprise lorsque le modèle est invalidé par des données nouvelles; dans les termes définis ici la surprise est équivalente à un change de paradigme. Des données empiriques limitées indiquent que les surprises apparaissent dans 20 à 30% des analyses effectuées sur les modèles. Ces données suggèrent que l'analyse des eaux souterraines présente des difficultés lorsqu'il s'agit de choisir le modèle conceptuel approprié. Il n'existe pas un autre remède au problème du modèle conceptuel que: (1) rassembler autant des données que possible en utilisant toutes les méthodes applicables—la méthode des données complémentaires peut conduire aux nouvelles informations qui vont changer le modèle conceptuel, et (2) l'analyste doit rester ouvert au fait

  7. Surprising characteristics of visual systems of invertebrates.

    Science.gov (United States)

    González-Martín-Moro, J; Hernández-Verdejo, J L; Jiménez-Gahete, A E

    2017-01-01

    To communicate relevant and striking aspects about the visual system of some close invertebrates. Review of the related literature. The capacity of snails to regenerate a complete eye, the benefit of the oval shape of the compound eye of many flying insects as a way of stabilising the image during flight, the potential advantages related to the extreme refractive error that characterises the ocelli of many insects, as well as the ability to detect polarised light as a navigation system, are some of the surprising capabilities present in the small invertebrate eyes that are described in this work. The invertebrate eyes have capabilities and sensorial modalities that are not present in the human eye. The study of the eyes of these animals can help us to improve our understanding of our visual system, and inspire the development of optical devices. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Surprises from Saturn: Implications for Other Environments

    Science.gov (United States)

    Coates, A. J.

    2014-05-01

    The exploration of Saturn by Cassini has provided many surprises regarding: Saturn's rapidly rotating magnetosphere, interactions with its diverse moons, and interactions with the solar wind. Enceladus, orbiting at 4 Saturn radii (RS), was found to have plumes of water vapour and ice which are the dominant source for the inner magnetosphere. Charged water clusters, charged dust and photoelectrons provide key populations in the 'dusty plasma' observed. Direct pickup is seen near Enceladus and field-aligned currents create a spot in Saturn's aurora. At Titan, orbiting at 20 RS, unexpected heavy negative and positive ions are seen in the ionosphere, which provide the source for Titan's haze. Ionospheric plasma is seen in Titan's tail, enabling ion escape to be estimated at 7 tonnes per day. Saturn's ring ionosphere was seen early in the mission and a return will be made in 2017. In addition, highly accelerated electrons are seen at Saturn's high Mach number (MA˜100) quasi-parallel bow shock. Here we review some of these key new results, and discuss the implications for other solar system objects.

  9. Plasmid and chromosome partitioning: surprises from phylogeny

    DEFF Research Database (Denmark)

    Gerdes, Kenn; Møller-Jensen, Jakob; Bugge Jensen, Rasmus

    2000-01-01

    Plasmids encode partitioning genes (par) that are required for faithful plasmid segregation at cell division. Initially, par loci were identified on plasmids, but more recently they were also found on bacterial chromosomes. We present here a phylogenetic analysis of par loci from plasmids and chr...

  10. Immunohistochemical, in situ hybridization, and ultrastructural localization of SARS-associated coronavirus in lung of a fatal case of severe acute respiratory syndrome in Taiwan.

    Science.gov (United States)

    Shieh, Wun-Ju; Hsiao, Cheng-Hsiang; Paddock, Christopher D; Guarner, Jeannette; Goldsmith, Cynthia S; Tatti, Kathleen; Packard, Michelle; Mueller, Laurie; Wu, Mu-Zong; Rollin, Pierre; Su, Ih-Jen; Zaki, Sherif R

    2005-03-01

    This article describes the pathological studies of fatal severe acute respiratory syndrome (SARS) in a 73-year-old man during an outbreak of SARS in Taiwan, 2003. Eight days before onset of symptoms, he visited a municipal hospital that was later identified as the epicenter of a large outbreak of SARS. On admission to National Taiwan University Hospital in Taipei, the patient experienced chest tightness, progressive dyspnea, and low-grade fever. His condition rapidly deteriorated with increasing respiratory difficulty, and he died 7 days after admission. The most prominent histopathologic finding was diffuse alveolar damage of the lung. Immunohistochemical and in situ hybridization assays demonstrated evidence of SARS-associated coronavirus (SARS-CoV) infection in various respiratory epithelial cells, predominantly type II pneumocytes, and in alveolar macrophages in the lung. Electron microscopic examination also revealed coronavirus particles in the pneumocytes, and their identity was confirmed as SARS-CoV by immunogold labeling electron microscopy. This report is the first to describe the cellular localization of SARS-CoV in human lung tissue by using a combination of immunohistochemistry, double-stain immunohistochemistry, in situ hybridization, electron microscopy, and immunogold labeling electron microscopy. These techniques represent valuable laboratory diagnostic modalities and provide insights into the pathogenesis of this emerging infection.

  11. A Shocking Surprise in Stephan's Quintet

    Science.gov (United States)

    2006-01-01

    This false-color composite image of the Stephan's Quintet galaxy cluster clearly shows one of the largest shock waves ever seen (green arc). The wave was produced by one galaxy falling toward another at speeds of more than one million miles per hour. The image is made up of data from NASA's Spitzer Space Telescope and a ground-based telescope in Spain. Four of the five galaxies in this picture are involved in a violent collision, which has already stripped most of the hydrogen gas from the interiors of the galaxies. The centers of the galaxies appear as bright yellow-pink knots inside a blue haze of stars, and the galaxy producing all the turmoil, NGC7318b, is the left of two small bright regions in the middle right of the image. One galaxy, the large spiral at the bottom left of the image, is a foreground object and is not associated with the cluster. The titanic shock wave, larger than our own Milky Way galaxy, was detected by the ground-based telescope using visible-light wavelengths. It consists of hot hydrogen gas. As NGC7318b collides with gas spread throughout the cluster, atoms of hydrogen are heated in the shock wave, producing the green glow. Spitzer pointed its infrared spectrograph at the peak of this shock wave (middle of green glow) to learn more about its inner workings. This instrument breaks light apart into its basic components. Data from the instrument are referred to as spectra and are displayed as curving lines that indicate the amount of light coming at each specific wavelength. The Spitzer spectrum showed a strong infrared signature for incredibly turbulent gas made up of hydrogen molecules. This gas is caused when atoms of hydrogen rapidly pair-up to form molecules in the wake of the shock wave. Molecular hydrogen, unlike atomic hydrogen, gives off most of its energy through vibrations that emit in the infrared. This highly disturbed gas is the most turbulent molecular hydrogen ever seen. Astronomers were surprised not only by the turbulence

  12. Computational surprisal analysis speeds-up genomic characterization of cancer processes.

    Science.gov (United States)

    Kravchenko-Balasha, Nataly; Simon, Simcha; Levine, R D; Remacle, F; Exman, Iaakov

    2014-01-01

    Surprisal analysis is increasingly being applied for the examination of transcription levels in cellular processes, towards revealing inner network structures and predicting response. But to achieve its full potential, surprisal analysis should be integrated into a wider range computational tool. The purposes of this paper are to combine surprisal analysis with other important computation procedures, such as easy manipulation of the analysis results--e.g. to choose desirable result sub-sets for further inspection--, retrieval and comparison with relevant datasets from public databases, and flexible graphical displays for heuristic thinking. The whole set of computation procedures integrated into a single practical tool is what we call Computational Surprisal Analysis. This combined kind of analysis should facilitate significantly quantitative understanding of different cellular processes for researchers, including applications in proteomics and metabolomics. Beyond that, our vision is that Computational Surprisal Analysis has the potential to reach the status of a routine method of analysis for practitioners. The resolving power of Computational Surprisal Analysis is here demonstrated by its application to a variety of cellular cancer process transcription datasets, ours and from the literature. The results provide a compact biological picture of the thermodynamic significance of the leading gene expression phenotypes in every stage of the disease. For each transcript we characterize both its inherent steady state weight, its correlation with the other transcripts and its variation due to the disease. We present a dedicated website to facilitate the analysis for researchers and practitioners.

  13. Computational surprisal analysis speeds-up genomic characterization of cancer processes.

    Directory of Open Access Journals (Sweden)

    Nataly Kravchenko-Balasha

    Full Text Available Surprisal analysis is increasingly being applied for the examination of transcription levels in cellular processes, towards revealing inner network structures and predicting response. But to achieve its full potential, surprisal analysis should be integrated into a wider range computational tool. The purposes of this paper are to combine surprisal analysis with other important computation procedures, such as easy manipulation of the analysis results--e.g. to choose desirable result sub-sets for further inspection--, retrieval and comparison with relevant datasets from public databases, and flexible graphical displays for heuristic thinking. The whole set of computation procedures integrated into a single practical tool is what we call Computational Surprisal Analysis. This combined kind of analysis should facilitate significantly quantitative understanding of different cellular processes for researchers, including applications in proteomics and metabolomics. Beyond that, our vision is that Computational Surprisal Analysis has the potential to reach the status of a routine method of analysis for practitioners. The resolving power of Computational Surprisal Analysis is here demonstrated by its application to a variety of cellular cancer process transcription datasets, ours and from the literature. The results provide a compact biological picture of the thermodynamic significance of the leading gene expression phenotypes in every stage of the disease. For each transcript we characterize both its inherent steady state weight, its correlation with the other transcripts and its variation due to the disease. We present a dedicated website to facilitate the analysis for researchers and practitioners.

  14. The Influence of Negative Surprise on Hedonic Adaptation

    Directory of Open Access Journals (Sweden)

    Ana Paula Kieling

    2016-01-01

    Full Text Available After some time using a product or service, the consumer tends to feel less pleasure with consumption. This reduction of pleasure is known as hedonic adaptation. One of the emotions that interfere in this process is surprise. Based on two experiments, we suggest that negative surprise – differently to positive – influences with the level of pleasure foreseen and experienced by the consumer. Study 1 analyzes the influence of negative (vs. positive surprise on the consumer’s post-purchase hedonic adaptation expectation. Results showed that negative surprise influences the intensity of adaptation, augmenting its strength. Study 2 verifies the influence of negative (vs positive surprise over hedonic adaptation. The findings suggested that negative surprise makes adaptation happen more intensively and faster as time goes by, which brings consequences to companies and consumers in the post-purchase process, such as satisfaction and loyalty.

  15. Effects of Surprisal and Locality on Danish Sentence Processing

    DEFF Research Database (Denmark)

    Balling, Laura Winther; Kizach, Johannes

    2017-01-01

    An eye-tracking experiment in Danish investigates two dominant accounts of sentence processing: locality-based theories that predict a processing advantage for sentences where the distance between the major syntactic heads is minimized, and the surprisal theory which predicts that processing time...... constructions with two postverbal NP-objects. An eye-tracking experiment showed a clear advantage for local syntactic relations, with only a marginal effect of lexicalised surprisal and no effect of syntactic surprisal. We conclude that surprisal has a relatively marginal effect, which may be clearest for verbs...

  16. Surprise and Sense Making: Undergraduate Placement Experiences in SMEs

    Science.gov (United States)

    Walmsley, Andreas; Thomas, Rhodri; Jameson, Stephanie

    2006-01-01

    Purpose: This paper seeks to explore undergraduate placement experiences in tourism and hospitality SMEs, focusing on the notions of surprise and sense making. It aims to argue that surprises and sense making are important elements not only of the adjustment process when entering new work environments, but also of the learning experience that…

  17. Neural Responses to Rapid Facial Expressions of Fear and Surprise

    Directory of Open Access Journals (Sweden)

    Ke Zhao

    2017-05-01

    Full Text Available Facial expression recognition is mediated by a distributed neural system in humans that involves multiple, bilateral regions. There are six basic facial expressions that may be recognized in humans (fear, sadness, surprise, happiness, anger, and disgust; however, fearful faces and surprised faces are easily confused in rapid presentation. The functional organization of the facial expression recognition system embodies a distinction between these two emotions, which is investigated in the present study. A core system that includes the right parahippocampal gyrus (BA 30, fusiform gyrus, and amygdala mediates the visual recognition of fear and surprise. We found that fearful faces evoked greater activity in the left precuneus, middle temporal gyrus (MTG, middle frontal gyrus, and right lingual gyrus, whereas surprised faces were associated with greater activity in the right postcentral gyrus and left posterior insula. These findings indicate the importance of common and separate mechanisms of the neural activation that underlies the recognition of fearful and surprised faces.

  18. Defense Science Board (DSB) Summer Study Report on Strategic Surprise

    Science.gov (United States)

    2015-07-01

    DSB Summer Study Report on Strategic Surprise July 2015 Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden...SUBTITLE DSB Summer Study Report on Strategic Surprise 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Defense Science Board ( DSB ),The Pentagon ,OUSD(AT&L

  19. Avoiding surprises when implementing a single quality system.

    Science.gov (United States)

    Donawa, Maria

    2009-01-01

    European medical device manufacturers are sometimes surprised to learn that operating ISO 13485 alone is not sufficient to meet United States (US) quality system requirements. This article discusses important considerations for meeting US and European requirements when operating under a single quality system.

  20. Reconsiderations: Donald Murray and the Pedagogy of Surprise

    Science.gov (United States)

    Ballenger, Bruce

    2008-01-01

    Toward the end of his life, Donald Murray felt that his approach to writing instruction was no longer appreciated by journals in his field. Nevertheless, his emphasis on encouraging students to surprise themselves through informal writing still has considerable value. (Contains 1 note.)

  1. Reconsiderations: Donald Murray and the Pedagogy of Surprise

    Science.gov (United States)

    Ballenger, Bruce

    2008-01-01

    Toward the end of his life, Donald Murray felt that his approach to writing instruction was no longer appreciated by journals in his field. Nevertheless, his emphasis on encouraging students to surprise themselves through informal writing still has considerable value. (Contains 1 note.)

  2. Errors and surprise in patients with focal brain lesions

    NARCIS (Netherlands)

    Ullsperger, M.

    2016-01-01

    Recent theories of performance monitoring suggest that not only errors and negative action outcomes but also valence-free expectancy violations can trigger cognitive and behavioral adaptations. EEG and fMRI evidence suggests that monitoring of both errors and surprising but valence-free action

  3. A conceptual review of the psychosocial genomics of expectancy and surprise: neuroscience perspectives about the deep psychobiology of therapeutic hypnosis.

    Science.gov (United States)

    Rossi, Ernest L

    2002-10-01

    This conceptual review explores some speculative associations between the neuroscience of expectancy and surprise during stress and therapeutic hypnosis. Current neuroscience is exploring how novel interactions between the organism and the environment initiate cascades of gene expression, protein synthesis, neurogenesis, and healing that operate via Darwinian principles of natural variation and selection on all levels from the molecular-genomic to the subjective states of consciousness. From a neuroscience perspective, the novel and surprising experiences of consciousness appear to have as important a role as expectancy in memory, learning and behavior change in the psychobiology of therapeutic hypnosis. This paper explores how we may integrate the psychosocial genomics of expectancy and surprise in therapeutic hypnosis as a complex system of creative adaptation on all levels of human experience from mind to gene expression.

  4. Sleeping beauties in theoretical physics 26 surprising insights

    CERN Document Server

    Padmanabhan, Thanu

    2015-01-01

    This book addresses a fascinating set of questions in theoretical physics which will both entertain and enlighten all students, teachers and researchers and other physics aficionados. These range from Newtonian mechanics to quantum field theory and cover several puzzling issues that do not appear in standard textbooks. Some topics cover conceptual conundrums, the solutions to which lead to surprising insights; some correct popular misconceptions in the textbook discussion of certain topics; others illustrate deep connections between apparently unconnected domains of theoretical physics; and a few provide remarkably simple derivations of results which are not often appreciated. The connoisseur of theoretical physics will enjoy a feast of pleasant surprises skilfully prepared by an internationally acclaimed theoretical physicist. Each topic is introduced with proper background discussion and special effort is taken to make the discussion self-contained, clear and comprehensible to anyone with an undergraduate e...

  5. Association of SARS susceptibility with single nucleic acid polymorphisms of OASI and MxA genes: A case-control study

    NARCIS (Netherlands)

    J. He (Jing); D. Feng (Dan); S.J. de Vlas (Sake); H. Wang (Hongwei); A. Fontanet (Arnaud); F. Zhang (Fang); S. Plancoulaine (Sabine); F. Tang (Fang); L. Zhan (Lin); H. Yang (Honghui); T. Wang (Teng); J.H. Richardus (Jan Hendrik); J.D.F. Habbema (Dik); W.-C. Cao (Wuchun)

    2006-01-01

    textabstractBackground: Host genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV) infection. The study was carried out to investigate the association between the genetic polymorphisms of 2′,5′-oligoadenylate synthetase I (OASI) gene as well as my

  6. Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes : a case-control study

    NARCIS (Netherlands)

    He, Jing; Feng, Dan; de Vlas, Sake J.; Wang, Hongwei; Fontanet, Arnaud; Zhang, Panhe; Plancoulaine, Sabine; Tang, Fang; Zhan, Lin; Yang, Hong; Wang, Tianbao; Richardus, Jan H.; Habbema, J. Dik F.; Cao, Wuchun

    2006-01-01

    Background: Host genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV) infection. The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1) gene as well as myxovirus resi

  7. The June surprises: balls, strikes, and the fog of war.

    Science.gov (United States)

    Fried, Charles

    2013-04-01

    At first, few constitutional experts took seriously the argument that the Patient Protection and Affordable Care Act exceeded Congress's power under the commerce clause. The highly political opinions of two federal district judges - carefully chosen by challenging plaintiffs - of no particular distinction did not shake that confidence that the act was constitutional. This disdain for the challengers' arguments was only confirmed when the act was upheld by two highly respected conservative court of appeals judges in two separate circuits. But after the hostile, even mocking questioning of the government's advocate in the Supreme Court by the five Republican-appointed justices, the expectation was that the act would indeed be struck down on that ground. So it came as no surprise when the five opined the act did indeed exceed Congress's commerce clause power. But it came as a great surprise when Chief Justice John Roberts, joined by the four Democrat-appointed justices, ruled that the act could be sustained as an exercise of Congress's taxing power - a ground urged by the government almost as an afterthought. It was further surprising, even shocking, that Justices Antonin Scalia, Anthony Kennedy, Clarence Thomas, and Samuel Alito not only wrote a joint opinion on the commerce clause virtually identical to that of their chief, but that in writing it they did not refer to or even acknowledge his opinion. Finally surprising was the fact that Justices Ruth Bader Ginsburg and Stephen Breyer joined the chief in holding that aspects of the act's Medicaid expansion were unconstitutional. This essay ponders and tries to unravel some of these puzzles.

  8. Estimations of expectedness and potential surprise in possibility theory

    Science.gov (United States)

    Prade, Henri; Yager, Ronald R.

    1992-01-01

    This note investigates how various ideas of 'expectedness' can be captured in the framework of possibility theory. Particularly, we are interested in trying to introduce estimates of the kind of lack of surprise expressed by people when saying 'I would not be surprised that...' before an event takes place, or by saying 'I knew it' after its realization. In possibility theory, a possibility distribution is supposed to model the relative levels of mutually exclusive alternatives in a set, or equivalently, the alternatives are assumed to be rank-ordered according to their level of possibility to take place. Four basic set-functions associated with a possibility distribution, including standard possibility and necessity measures, are discussed from the point of view of what they estimate when applied to potential events. Extensions of these estimates based on the notions of Q-projection or OWA operators are proposed when only significant parts of the possibility distribution are retained in the evaluation. The case of partially-known possibility distributions is also considered. Some potential applications are outlined.

  9. 10 years of surprises at Saturn: CAPS and INMS highlights

    Science.gov (United States)

    Coates, A. J.; Waite, J. H.

    2014-04-01

    The Cassini mission at Saturn has provided many surprises on Saturn's rapidly rotating magnetosphere and its interaction with the diverse moons, as well as its interaction with the solar wind. One of the early discoveries was the water-rich composition of the magnetosphere. Its structure and dynamics indicate remarkable injections, periodicities and interchange events. Enceladus, orbiting at 4 RS, was found to have plumes of water vapour and ice which are the dominant source for the inner magnetosphere. Charged water clusters, charged dust and photoelectrons provide key populations in the 'dusty plasma' seen here, as well as chemical complexity in the plume material. Direct pickup is seen near Enceladus and field aligned currents create a spot in Saturn's aurora. At Titan, orbiting at 20 RS, heavy negative and positive ions are seen in the ionosphere, as well as neutrals, all of which have surprising chemical complexity. These provide the source for Titan's haze. Ionospheric plasma is seen in Titan's tail, enabling ion escape to be estimated at 7 tonnes per day. Saturn's ring ionosphere was seen early in the mission, which was oxygen rich and produced photoelectrons; a return will be made in 2017. At Rhea, pickup positive and negative ions indicated weak atmospheres sustained by energetic particle impact, seen in the neutrals also. A weak atmosphere was also seen at Dione. The exosphere production process operates at Jupiter's moons also. Here we review some of the key new results, and discuss the implications for other solar system contexts.

  10. Measured Zero Net Energy Performance: Results, Lessons, and Surprises

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Carrie; LaRue, Anna; Pigman, Margaret; Roberts, Jon; Kaneda, David; Connelly, Dylan; Elliott, John; Pless, Shanti; Pande, Abhijeet; Dean, Edward; Anbarlilar, Can

    2016-08-26

    As more and more zero net energy (ZNE) buildings are built and monitored, we can learn from both careful case studies of individual projects as well as a broader perspective of trends over time. In a forum sponsored by Pacific Gas and Electric Company (PG&E), eight expert speakers discussed: results and lessons from monitoring occupied ZNE buildings; best practices for setting performance targets and getting actionable performance information, and; things that have surprised them about monitored ZNE buildings. This paper distills the content of the forum by laying out the most common hurdles that are encountered in setting up monitoring projects, frequent performance issues that the monitoring uncovers, and lessons learned that can be applied to future projects.

  11. Surprising hair analysis results following acute carbofuran intoxication.

    Science.gov (United States)

    Dulaurent, S; Gaulier, J M; Zouaoui, K; Moesch, C; François, B; Lachâtre, G

    2011-10-10

    We present two non fatal cases of intoxication with carbofuran (CBF) documented by hair analysis. Carbofuran and 3-hydroxycarbofuran (OHCBF, its main metabolite) hair concentrations were determined using a liquid chromatography-tandem mass spectrometry method. The obtained results were surprising if we consider several hair analyses previously published and based on a theory of the presence of xenobiotic in the only segment that comprised its intake. Among the two intoxication cases, we noticed the presence of CBF and OHCBF in hair segments corresponding to 45 days before, and more than 100 days after, the day of intoxication. Additionally, repeated hair samplings and subsequent analysis revealed a decrease of the carbofuran's concentration during the hair life.

  12. Physics Nobel prize 2004: Surprising theory wins physics Nobel

    CERN Multimedia

    2004-01-01

    From left to right: David Politzer, David Gross and Frank Wilczek. For their understanding of counter-intuitive aspects of the strong force, which governs quarks inside protons and neutrons, on 5 October three American physicists were awarded the 2004 Nobel Prize in Physics. David J. Gross (Kavli Institute of Theoretical Physics, University of California, Santa Barbara), H. David Politzer (California Institute of Technology), and Frank Wilczek (Massachusetts Institute of Technology) made a key theoretical discovery with a surprising result: the closer quarks are together, the weaker the force - opposite to what is seen with electromagnetism and gravity. Rather, the strong force is analogous to a rubber band stretching, where the force increases as the quarks get farther apart. These physicists discovered this property of quarks, known as asymptotic freedom, in 1976. It later became a key part of the theory of quantum chromodynamics (QCD) and the Standard Model, the current best theory to describe the interac...

  13. Probability and Surprisal in Auditory Comprehension of Morphologically Complex Words

    DEFF Research Database (Denmark)

    Balling, Laura Winther; Baayen, R. Harald

    2012-01-01

    Two auditory lexical decision experiments document for morphologically complex words two points at which the probability of a target word given the evidence shifts dramatically. The first point is reached when morphologically unrelated competitors are no longer compatible with the evidence....... Adapting terminology from Marslen-Wilson (1984), we refer to this as the word’s initial uniqueness point (UP1). The second point is the complex uniqueness point (CUP) introduced by Balling and Baayen (2008), at which morphologically related competitors become incompatible with the input. Later initial...... in the course of the word co-determines response latencies. The presence of effects of surprisal, both at the initial uniqueness point of complex words, and cumulatively throughout the word, challenges the Shortlist B model of Norris and McQueen (2008), and suggests that a Bayesian approach to auditory...

  14. 2014 Presidential elections in Romania – surprising result or strategy

    Directory of Open Access Journals (Sweden)

    Dan Mihalache

    2015-03-01

    Full Text Available The presidential elections in Romania which took place in November 2014 were won by Klaus Iohannis, who clearly defeated the incumbent prime-minister Victor Ponta by 10%. The result was considered by many a surprise, as none of the opinion polls were able to predict it. This article reveals a part of the strategy of Klaus Iohannis’s campaign and it offers a few clues about how this is result was possible, without having the aim to explain it fully. As the authors were accountable for strategy and political message in the electoral campaign for Klaus Iohannis, the scientific approach is combined with the inside view, to provide the reader a better understanding of the November 2014 events.

  15. Exploring the concept of climate surprises. A review of the literature on the concept of surprise and how it is related to climate change

    Energy Technology Data Exchange (ETDEWEB)

    Glantz, M.H.; Moore, C.M. [National Center for Atmospheric Research, Boulder, CO (United States); Streets, D.G.; Bhatti, N.; Rosa, C.H. [Argonne National Lab., IL (United States). Decision and Information Sciences Div.; Stewart, T.R. [State Univ. of New York, Albany, NY (United States)

    1998-01-01

    This report examines the concept of climate surprise and its implications for environmental policymaking. Although most integrated assessment models of climate change deal with average values of change, it is usually the extreme events or surprises that cause the most damage to human health and property. Current models do not help the policymaker decide how to deal with climate surprises. This report examines the literature of surprise in many aspects of human society: psychology, military, health care, humor, agriculture, etc. It draws together various ways to consider the concept of surprise and examines different taxonomies of surprise that have been proposed. In many ways, surprise is revealed to be a subjective concept, triggered by such factors as prior experience, belief system, and level of education. How policymakers have reacted to specific instances of climate change or climate surprise in the past is considered, particularly with regard to the choices they made between proactive and reactive measures. Finally, the report discusses techniques used in the current generation of assessment models and makes suggestions as to how climate surprises might be included in future models. The report concludes that some kinds of surprises are simply unpredictable, but there are several types that could in some way be anticipated and assessed, and their negative effects forestalled.

  16. The analysis of eight transcriptomes from all poriferan classes reveals surprising genetic complexity in sponges.

    Science.gov (United States)

    Riesgo, Ana; Farrar, Nathan; Windsor, Pamela J; Giribet, Gonzalo; Leys, Sally P

    2014-05-01

    Sponges (Porifera) are among the earliest evolving metazoans. Their filter-feeding body plan based on choanocyte chambers organized into a complex aquiferous system is so unique among metazoans that it either reflects an early divergence from other animals prior to the evolution of features such as muscles and nerves, or that sponges lost these characters. Analyses of the Amphimedon and Oscarella genomes support this view of uniqueness-many key metazoan genes are absent in these sponges-but whether this is generally true of other sponges remains unknown. We studied the transcriptomes of eight sponge species in four classes (Hexactinellida, Demospongiae, Homoscleromorpha, and Calcarea) specifically seeking genes and pathways considered to be involved in animal complexity. For reference, we also sought these genes in transcriptomes and genomes of three unicellular opisthokonts, two sponges (A. queenslandica and O. carmela), and two bilaterian taxa. Our analyses showed that all sponge classes share an unexpectedly large complement of genes with other metazoans. Interestingly, hexactinellid, calcareous, and homoscleromorph sponges share more genes with bilaterians than with nonbilaterian metazoans. We were surprised to find representatives of most molecules involved in cell-cell communication, signaling, complex epithelia, immune recognition, and germ-lineage/sex, with only a few, but potentially key, absences. A noteworthy finding was that some important genes were absent from all demosponges (transcriptomes and the Amphimedon genome), which might reflect divergence from main-stem lineages including hexactinellids, calcareous sponges, and homoscleromorphs. Our results suggest that genetic complexity arose early in evolution as shown by the presence of these genes in most of the animal lineages, which suggests sponges either possess cryptic physiological and morphological complexity and/or have lost ancestral cell types or physiological processes.

  17. The surprising diversity of clostridial hydrogenases: a comparative genomic perspective.

    Science.gov (United States)

    Calusinska, Magdalena; Happe, Thomas; Joris, Bernard; Wilmotte, Annick

    2010-06-01

    Among the large variety of micro-organisms capable of fermentative hydrogen production, strict anaerobes such as members of the genus Clostridium are the most widely studied. They can produce hydrogen by a reversible reduction of protons accumulated during fermentation to dihydrogen, a reaction which is catalysed by hydrogenases. Sequenced genomes provide completely new insights into the diversity of clostridial hydrogenases. Building on previous reports, we found that [FeFe] hydrogenases are not a homogeneous group of enzymes, but exist in multiple forms with different modular structures and are especially abundant in members of the genus Clostridium. This unusual diversity seems to support the central role of hydrogenases in cell metabolism. In particular, the presence of multiple putative operons encoding multisubunit [FeFe] hydrogenases highlights the fact that hydrogen metabolism is very complex in this genus. In contrast with [FeFe] hydrogenases, their [NiFe] hydrogenase counterparts, widely represented in other bacteria and archaea, are found in only a few clostridial species. Surprisingly, a heteromultimeric Ech hydrogenase, known to be an energy-converting [NiFe] hydrogenase and previously described only in methanogenic archaea and some sulfur-reducing bacteria, was found to be encoded by the genomes of four cellulolytic strains: Clostridum cellulolyticum, Clostridum papyrosolvens, Clostridum thermocellum and Clostridum phytofermentans.

  18. Atom Surprise: Using Theatre in Primary Science Education

    Science.gov (United States)

    Peleg, Ran; Baram-Tsabari, Ayelet

    2011-10-01

    Early exposure to science may have a lifelong effect on children's attitudes towards science and their motivation to learn science in later life. Out-of-class environments can play a significant role in creating favourable attitudes, while contributing to conceptual learning. Educational science theatre is one form of an out-of-class environment, which has received little research attention. This study aims to describe affective and cognitive learning outcomes of watching such a play and to point to connections between theatrical elements and specific outcomes. "Atom Surprise" is a play portraying several concepts on the topic of matter. A mixed methods approach was adopted to investigate the knowledge and attitudes of children (grades 1-6) from two different school settings who watched the play. Data were gathered using questionnaires and in-depth interviews. Analysis suggested that in both schools children's knowledge on the topic of matter increased after the play with younger children gaining more conceptual knowledge than their older peers. In the public school girls showed greater gains in conceptual knowledge than boys. No significant changes in students' general attitudes towards science were found, however, students demonstrated positive changes towards science learning. Theatrical elements that seemed to be important in children's recollection of the play were the narrative, props and stage effects, and characters. In the children's memory, science was intertwined with the theatrical elements. Nonetheless, children could distinguish well between scientific facts and the fictive narrative.

  19. Novelty biases attention and gaze in a surprise trial.

    Science.gov (United States)

    Horstmann, Gernot; Herwig, Arvid

    2016-01-01

    While the classical distinction between task-driven and stimulus-driven biasing of attention appears to be a dichotomy at first sight, there seems to be a third category that depends on the contrast or discrepancy between active representations and the upcoming stimulus, and may be termed novelty, surprise, or prediction failure. For previous demonstrations of the discrepancy-attention link, stimulus-driven components (saliency) may have played a decisive role. The present study was conducted to evaluate the discrepancy-attention link in a display where novel and familiar stimuli are equated for saliency. Eye tracking was used to determine fixations on novel and familiar stimuli as a proxy for attention. Results show a prioritization of attention by the novel color, and a de-prioritization of the familiar color, which is clearly present at the second fixation, and spans over the next couple of fixations. Saliency, on the other hand, did not prioritize items in the display. The results thus reinforce the notion that novelty captures and binds attention.

  20. A Well-Known But Still Surprising Generator

    Science.gov (United States)

    Haugland, Ole Anton

    2014-12-01

    The bicycle generator is often mentioned as an example of a method to produce electric energy. It is cheap and easily accessible, so it is a natural example to use in teaching. There are different types, but I prefer the old side-wall dynamo. The most common explanation of its working principle seems to be something like the illustration in Fig. 1. The illustration is taken from a popular textbook in the Norwegian junior high school.1 Typically it is explained as a system of a moving magnet or coils that directly results in a varying magnetic field through the coils. According to Faraday's law a voltage is induced in the coils. Simple and easy! A few times I have had a chance to glimpse into a bicycle generator, and I was somewhat surprised to sense that the magnet rotated parallel to the turns of the coil. How could the flux through the coil change and induce a voltage when the magnet rotated parallel to the turns of the coil? When teaching electromagnetic induction I have showed the students a dismantled generator and asked them how this could work. They naturally found that this was more difficult to understand than the principle illustrated in Fig. 1. Other authors in this journal have discussed even more challenging questions concerning electric generators.2,3

  1. Surprise disrupts cognition via a fronto-basal ganglia suppressive mechanism.

    Science.gov (United States)

    Wessel, Jan R; Jenkinson, Ned; Brittain, John-Stuart; Voets, Sarah H E M; Aziz, Tipu Z; Aron, Adam R

    2016-04-18

    Surprising events markedly affect behaviour and cognition, yet the underlying mechanism is unclear. Surprise recruits a brain mechanism that globally suppresses motor activity, ostensibly via the subthalamic nucleus (STN) of the basal ganglia. Here, we tested whether this suppressive mechanism extends beyond skeletomotor suppression and also affects cognition (here, verbal working memory, WM). We recorded scalp-EEG (electrophysiology) in healthy participants and STN local field potentials in Parkinson's patients during a task in which surprise disrupted WM. For scalp-EEG, surprising events engage the same independent neural signal component that indexes action stopping in a stop-signal task. Importantly, the degree of this recruitment mediates surprise-related WM decrements. Intracranially, STN activity is also increased post surprise, especially when WM is interrupted. These results suggest that surprise interrupts cognition via the same fronto-basal ganglia mechanism that interrupts action. This motivates a new neural theory of how cognition is interrupted, and how distraction arises after surprising events.

  2. Properties and Surprises of Solar Activity XXIII Cycle

    Science.gov (United States)

    Ishkov, V. N.

    2010-12-01

    The main properties of the 23rd cycle match almost completely those of average-magnitude solar cycles, and some of the features of the cycle may indicate a change in the generation mode of magnetic fields in the solar convection zone. If this is the case, the Sun enters a period of intermediate and weak cycles of solar activity (SA) in terms of the Wolf number, which may last for 3 to 6 solar cycles. The main development stages of solar cycle 23 are the following: minimum of solar cycle 22: April 1996 (W* = 8.0); maximum of the smoothed relative sunspot number: April 2000; global polarity reversal of the general solar magnetic field: July to December 2000; secondary maximum of the relative sunspot number: November 2001; maximum of the 10.7-cm radio flux: February 2002; phase of the cycle maximum: October 1999 to June 2002; beginning of the decrease phase: July 2002; the point of minimum of the current SA cycle: December 2008. Solar cycle 23 has presented two powerful flare-active sunspot groups, in September 2005 and December 2006 (+5.5 and +6.6 years from the maximum) which by flare potential occupy 4th and 20th place among the most flare-active regions for the last four solar cycles. The unprecedented duration of the relative sunspot numbers fall that has led to already record duration of the last solar cycle among authentic cycles (since 1849) became the next surprise of development of solar activity during the last cycle. The phase of the minimum began in May 2005 and lasted for 4.5 years. Thus, the new solar cycle 24 has begun in January 2009.

  3. Dracunculiasis eradication - Finishing the job before surprises arise

    Institute of Scientific and Technical Information of China (English)

    Benjamin Jelle Visser

    2012-01-01

    ABSTRACT Dracunculiasis(Guinea worm disease) is a preventable waterborne parasitic disease that affects the poorest people living in remote rural areas in sub-SaharanAfrican countries, who do not have access to safe drinking water.The Guinea Worm Eradication Program, a25-year old campaign to rid the world ofGuineaWorm disease has now reached its final stage accelerating to zero cases in all endemic countries.During the19th and20th centuries, dracunculiasis was common in much ofSouthernAsia and theAfrican continent.The overall number of cases has been reduced tremendously by≥99%, from the3.32 million cases estimated to have occurred in1986 inAfrica to only1797 cases reported in2010 reported in only five countries(Sudan,Mali,Ethiopia,Chad andGhana) andAsia free of the disease.This achievement is unique in its kind - the only previously eradicated disease is smallpox, a viral infection for which vaccination was possible - and it has been achieved through primary community-based prevention and health education programs.Most efforts need to be taken in two countries,SouthSudan(comprising94% or1698 out of1797 of the cases reported world-wide in2010) andMali because of frequent movements of nomads in a vast area inside and outsideMali’s borders.All factors favourable to dracunculiasis eradication are available including adequate financial resources, community and political support and high levels of advocacy.Thus there is no reason that this disabling parasitic disease cannot be eradicated soon before surprises arise such as new civil conflicts in currently endemic countries.

  4. Surprising Sensitivities in Simulations of Radiative Convective Equilibrium

    Science.gov (United States)

    Drotos, Gabor; Becker, Tobias; Mauritsen, Thorsten; Stevens, Bjorn

    2017-04-01

    The climate and climate-sensitivity of a global model run in radiative equilibrium is explored. Results from simulations with ECHAM6.3 coupled to a slab ocean and run in a wide range of configurations are presented. Simulations both with and without a parameterised representation of deep convection are conducted for CO2 concentrations ranging from one eighth of present day values to thirty-two times the present day, and for variations in the solar constant of more than a factor of two. Very long simulations, in some case more than a thousand years, are performed to adequately sample the attractor of the different climate states of the model, and provide robust estimates of the system's climate sensitivity parameter. For the standard configuration of the model the climate sensitivity progressively decreases from very large values (6-7K) for the coldest climates to well below 1 K for the warmest climates. For very high CO2 levels (16 and 32 times the present value) fluctuations of globally averaged temperature as large as 10 K arise on decadal time-scales. These fluctuations manifest as quasi-period coolings, driven by large and persistent global scale decks of stratiform low clouds, so that for a period of several years global temperatures drop to levels below the lowest temperatures of the climate with present day values of CO2. The same configuration of the model has more modest sensitivities when the insolation is reduced, but runaway warming results for small (10%) increases. Simulations without parameterised convection have colder (by roughly 10K) climates and smaller (1K) sensitivities, allowing a stable climate with earth-like temperatures even for insolation much (50%) larger than the present day. Such values of insolation are possible because over a large range of the insolation the climate sensitivity parameter is very near zero. The surprising sensitivities of the system, and the limit-cycle like behaviour of the very CO2 rich climates, can be traced to

  5. Transcription by the Numbers Redux: Experiments and Calculations that Surprise

    OpenAIRE

    Garcia, Hernan G.; Sanchez, Alvaro; Kuhlman, Thomas; Kondev, Jane'; Phillips, Rob

    2010-01-01

    The study of transcription has witnessed an explosion of quantitative effort both experimentally and theoretically. In this article, we highlight some of the exciting recent experimental efforts in the study of transcription with an eye to the demands that such experiments put on theoretical models of transcription. From a modeling perspective, we focus on two broad classes of models: the so-called thermodynamic models that use statistical mechanics to reckon the level of gene expression as p...

  6. Stars Form Surprisingly Close to Milky Way's Black Hole

    Science.gov (United States)

    2005-10-01

    The supermassive black hole at the center of the Milky Way has surprisingly helped spawn a new generation of stars, according to observations from NASA's Chandra X-ray Observatory. This novel mode of star formation may solve several mysteries about the supermassive black holes that reside at the centers of nearly all galaxies. "Massive black holes are usually known for violence and destruction," said Sergei Nayakshin of the University of Leicester, United Kingdom, and coauthor of a paper on this research in an upcoming issue of the Monthly Notices of the Royal Astronomical Society. "So it's remarkable that this black hole helped create new stars, not just destroy them." Black holes have earned their fearsome reputation because any material -- including stars -- that falls within the so-called event horizon is never seen again. However, these new results indicate that the immense disks of gas known to orbit many black holes at a "safe" distance from the event horizon can help nurture the formation of new stars. Animation of Stars Forming Around Black Hole Animation of Stars Forming Around Black Hole This conclusion came from new clues that could only be revealed in X-rays. Until the latest Chandra results, astronomers have disagreed about the origin of a mysterious group of massive stars discovered by infrared astronomers to be orbiting less than a light year from the Milky Way's central black hole, a.k.a. Sagittarius A*, or Sgr A*. At such close distances to Sgr A*, the standard model for star formation predicts that gas clouds from which stars form should have been ripped apart by tidal forces from the black hole. Two models to explain this puzzle have been proposed. In the disk model, the gravity of a dense disk of gas around Sgr A* offsets the tidal forces and allows stars to form; in the migration model, the stars formed in a star cluster far away from the black hole and migrated in to form the ring of massive stars. The migration scenario predicts about a

  7. Carbon Dioxide: Surprising Effects on Decision Making and Neurocognitive Performance

    Science.gov (United States)

    James, John T.

    2013-01-01

    The occupants of modern submarines and the International Space Station (ISS) have much in common as far as their air quality is concerned. Air is polluted by materials offgassing, use of utility compounds, leaks of systems chemicals, and anthropogenic sources. The primary anthropogenic compound of concern to submariners and astronauts has been carbon dioxide (CO2). NASA and the US Navy rely on the National Research Council Committee on Toxicology (NRC-COT) to help formulate exposure levels to CO2 that are thought to be safe for exposures of 3-6 months. NASA calls its limits Spacecraft Maximum Allowable Concentrations (SMACs). Years of experience aboard the ISS and a recent publication on deficits in decision making in ground-based subjects exposed briefly to 0.25% CO2 suggest that exposure levels that have been presumed acceptable to preserve health and performance need to be reevaluated. The current CO2 exposure limits for 3-6 months set by NASA and the UK Navy are 0.7%, and the limit for US submariners is 0.5%, although the NRC-COT recommended a 90-day level of 0.8% as safe a few years ago. NASA has set a 1000-day SMAC at 0.5% for exploration-class missions. Anecdotal experience with ISS operations approaching the current 180-day SMAC of 0.7% suggest that this limit is too high. Temporarily, NASA has limited exposures to 0.5% until further peer-reviewed data become available. In the meantime, a study published last year in the journal Environmental Health Perspectives (Satish U, et al. 2012) demonstrated that complexdecision- making performance is somewhat affected at 0.1% CO2 and becomes "dysfunctional" for at least half of the 9 indices of performance at concentrations approaching 0.25% CO2. The investigators used the Strategic Management Simulation (SMS) method of testing for decisionmaking ability, and the results were so surprising to the investigators that they declared that their findings need to be independently confirmed. NASA has responded to the

  8. Are seismic hazard assessment errors and earthquake surprises unavoidable?

    Science.gov (United States)

    Kossobokov, Vladimir

    2013-04-01

    Why earthquake occurrences bring us so many surprises? The answer seems evident if we review the relationships that are commonly used to assess seismic hazard. The time-span of physically reliable Seismic History is yet a small portion of a rupture recurrence cycle at an earthquake-prone site, which makes premature any kind of reliable probabilistic statements about narrowly localized seismic hazard. Moreover, seismic evidences accumulated to-date demonstrate clearly that most of the empirical relations commonly accepted in the early history of instrumental seismology can be proved erroneous when testing statistical significance is applied. Seismic events, including mega-earthquakes, cluster displaying behaviors that are far from independent or periodic. Their distribution in space is possibly fractal, definitely, far from uniform even in a single segment of a fault zone. Such a situation contradicts generally accepted assumptions used for analytically tractable or computer simulations and complicates design of reliable methodologies for realistic earthquake hazard assessment, as well as search and definition of precursory behaviors to be used for forecast/prediction purposes. As a result, the conclusions drawn from such simulations and analyses can MISLEAD TO SCIENTIFICALLY GROUNDLESS APPLICATION, which is unwise and extremely dangerous in assessing expected societal risks and losses. For example, a systematic comparison of the GSHAP peak ground acceleration estimates with those related to actual strong earthquakes, unfortunately, discloses gross inadequacy of this "probabilistic" product, which appears UNACCEPTABLE FOR ANY KIND OF RESPONSIBLE SEISMIC RISK EVALUATION AND KNOWLEDGEABLE DISASTER PREVENTION. The self-evident shortcomings and failures of GSHAP appeals to all earthquake scientists and engineers for an urgent revision of the global seismic hazard maps from the first principles including background methodologies involved, such that there becomes: (a) a

  9. Transcription by the numbers redux: experiments and calculations that surprise.

    Science.gov (United States)

    Garcia, Hernan G; Sanchez, Alvaro; Kuhlman, Thomas; Kondev, Jane; Phillips, Rob

    2010-12-01

    The study of transcription has witnessed an explosion of quantitative effort both experimentally and theoretically. In this article we highlight some of the exciting recent experimental efforts in the study of transcription with an eye to the demands that such experiments put on theoretical models of transcription. From a modeling perspective, we focus on two broad classes of models: the so-called thermodynamic models that use statistical mechanics to reckon the level of gene expression as probabilities of promoter occupancy, and rate-equation treatments that focus on the temporal evolution of the activity of a given promoter and that make it possible to compute the distributions of messenger RNA and proteins. We consider several appealing case studies to illustrate how quantitative models have been used to dissect transcriptional regulation. Copyright © 2010 Elsevier Ltd. All rights reserved.

  10. Supermagnetic Neutron Star Surprises Scientists, Forces Revision of Theories

    Science.gov (United States)

    2006-08-01

    magnetars because their magnetic fields are 100-1,000 times stronger than those of typical pulsars. It is the decay of those incredibly strong fields that powers their strange X-ray emission. "The magnetic field from a magnetar would make an aircraft carrier spin around and point north quicker than a compass needle moves on Earth," said David Helfand, of Columbia University. A magnetar's field is 1,000 trillion times stronger than Earth's, Helfand pointed out. The new object -- named XTE J1810-197 -- was first discovered by NASA's Rossi X-ray Timing Explorer when it emitted a strong burst of X-rays in 2003. While the X-rays were fading in 2004, Jules Halpern of Columbia University and collaborators identified the magnetar as a radio-wave emitter using the National Science Foundation's (NSF) Very Large Array (VLA) radio telescope in New Mexico. Any radio emission is highly unusual for a magnetar. Because magnetars had not been seen to regularly emit radio waves, the scientists presumed that the radio emission was caused by a cloud of particles thrown off the neutron star at the time of its X-ray outburst, an idea they soon would realize was wrong. With knowledge that the magnetar emitted some form of radio waves, Camilo and his colleagues observed it with the Parkes radio telescope in Australia in March and immediately detected astonishingly strong radio pulsations every 5.5 seconds, corresponding to the previously-determined rotation rate of the neutron star. As they continued to observe XTE J1810-197, the scientists got more surprises. Whereas most pulsars become weaker at higher radio frequencies, XTE J1810-197 does not, remaining a strong emitter at frequencies up to 140 GHz, the highest frequency ever detected from a radio pulsar. In addition, unlike normal pulsars, the object's radio emission fluctuates in strength from day to day, and the shape of the pulsations changes as well. These variations likely indicate that the magnetic fields around the pulsar are changing

  11. Chandra Finds Surprising Black Hole Activity In Galaxy Cluster

    Science.gov (United States)

    2002-09-01

    Scientists at the Carnegie Observatories in Pasadena, California, have uncovered six times the expected number of active, supermassive black holes in a single viewing of a cluster of galaxies, a finding that has profound implications for theories as to how old galaxies fuel the growth of their central black holes. The finding suggests that voracious, central black holes might be as common in old, red galaxies as they are in younger, blue galaxies, a surprise to many astronomers. The team made this discovery with NASA'S Chandra X-ray Observatory. They also used Carnegie's 6.5-meter Walter Baade Telescope at the Las Campanas Observatory in Chile for follow-up optical observations. "This changes our view of galaxy clusters as the retirement homes for old and quiet black holes," said Dr. Paul Martini, lead author on a paper describing the results that appears in the September 10 issue of The Astrophysical Journal Letters. "The question now is, how do these black holes produce bright X-ray sources, similar to what we see from much younger galaxies?" Typical of the black hole phenomenon, the cores of these active galaxies are luminous in X-ray radiation. Yet, they are obscured, and thus essentially undetectable in the radio, infrared and optical wavebands. "X rays can penetrate obscuring gas and dust as easily as they penetrate the soft tissue of the human body to look for broken bones," said co-author Dr. Dan Kelson. "So, with Chandra, we can peer through the dust and we have found that even ancient galaxies with 10-billion-year-old stars can have central black holes still actively pulling in copious amounts of interstellar gas. This activity has simply been hidden from us all this time. This means these galaxies aren't over the hill after all and our theories need to be revised." Scientists say that supermassive black holes -- having the mass of millions to billions of suns squeezed into a region about the size of our Solar System -- are the engines in the cores of

  12. Trait Anxiety Is Associated with Negative Interpretations When Resolving Valence Ambiguity of Surprised Faces.

    Science.gov (United States)

    Park, Gewnhi; Vasey, Michael W; Kim, Grace; Hu, Dixie D; Thayer, Julian F

    2016-01-01

    The current research examines whether trait anxiety is associated with negative interpretation bias when resolving valence ambiguity of surprised faces. To further isolate the neuro-cognitive mechanism, we presented angry, happy, and surprised faces at broad spatial frequency (BSF), high spatial frequency (HSF), and low spatial frequency (LSF) and asked participants to determine the valence of each face. High trait anxiety was associated with more negative interpretations of BSF (i.e., intact) surprised faces. However, the modulation of trait anxiety on the negative interpretation of surprised faces disappeared at HSF and LSF. The current study provides evidence that trait anxiety modulates negative interpretations of BSF surprised faces. However, the negative interpretation of LSF surprised faces appears to be a robust default response that occurs regardless of individual differences in trait anxiety.

  13. Trait anxiety is associated with negative interpretations when resolving valence ambiguity of surprised faces

    Directory of Open Access Journals (Sweden)

    Gewnhi Park

    2016-08-01

    Full Text Available The current research examines whether trait anxiety is associated with negative interpretation bias when resolving valence ambiguity of surprised faces. To further isolate the neuro-cognitive mechanism, we presented angry, happy, and surprised faces at broad, high, and low spatial frequency and asked participants to determine the valence of each face. High trait anxiety was associated with more negative interpretations of broad spatial frequency (i.e., intact surprised faces. However, the modulation of trait anxiety on the negative interpretation of surprised faces disappeared at high and low spatial frequencies. The current study provides evidence that trait anxiety modulates negative interpretations of broad spatial frequency surprised faces. However, the negative interpretation of low spatial frequency surprised faces appears to be a robust default response that occurs regardless of individual differences in trait anxiety.

  14. Effects of Surprisal and Locality on Danish Sentence Processing: An Eye-Tracking Investigation.

    Science.gov (United States)

    Balling, Laura Winther; Kizach, Johannes

    2017-03-22

    An eye-tracking experiment in Danish investigates two dominant accounts of sentence processing: locality-based theories that predict a processing advantage for sentences where the distance between the major syntactic heads is minimized, and the surprisal theory which predicts that processing time increases with big changes in the relative entropy of possible parses, sometimes leading to anti-locality effects. We consider both lexicalised surprisal, expressed in conditional trigram probabilities, and syntactic surprisal expressed in the manipulation of the expectedness of the second NP in Danish constructions with two postverbal NP-objects. An eye-tracking experiment showed a clear advantage for local syntactic relations, with only a marginal effect of lexicalised surprisal and no effect of syntactic surprisal. We conclude that surprisal has a relatively marginal effect, which may be clearest for verbs in verb-final languages, while locality is a robust predictor of sentence processing.

  15. Trait Anxiety Is Associated with Negative Interpretations When Resolving Valence Ambiguity of Surprised Faces

    OpenAIRE

    Gewnhi Park; Vasey, Michael W.; Grace Kim; Dixie D Hu; Thayer, Julian F

    2016-01-01

    The current research examines whether trait anxiety is associated with negative interpretation bias when resolving valence ambiguity of surprised faces. To further isolate the neuro-cognitive mechanism, we presented angry, happy, and surprised faces at broad, high, and low spatial frequency and asked participants to determine the valence of each face. High trait anxiety was associated with more negative interpretations of broad spatial frequency (i.e., intact) surprised faces. However, the mo...

  16. Carbon monoxide and bile pigments: surprising mediators of vascular function.

    Science.gov (United States)

    Durante, William

    2002-08-01

    Heme oxygenase (HO) catalyzes the degradation of heme to CO, iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although long considered irrelevant byproducts of heme catabolism, recent studies indicate that CO and the bile pigments biliverdin and bilirubin may play an important physiological role in the circulation. The release of CO by vascular cells may modulate blood flow and blood fluidity by inhibiting vasomotor tone, smooth muscle cell proliferation, and platelet aggregation. CO may also maintain the integrity of the vessel wall by directly blocking vascular cell apoptosis and by inhibiting the release of pro-apoptotic inflammatory cytokines from the vessel wall. These effects of CO are mediated via multiple pathways, including activation of soluble guanylate cyclase, potassium channels, p38 mitogen-activated protein kinase, or inhibition of cytochrome P450. In addition, the release of bile pigments may serve to sustain vascular homeostasis by protecting vascular cells from oxidative stress and by inhibiting the adhesion and infiltration of leukocytes into the vessel wall. Induction of HO-1 gene expression and the subsequent release of CO and bile pigments are observed in numerous vascular disorders and may provide an important adaptive mechanism to preserve homeostasis at sites of vascular injury. Thus, the HO-catalyzed formation of CO and bile pigments by vascular cells may function as a critical endogenous vasoprotective system. Moreover, pharmacological or genetic approaches targeting HO-1 to the vessel wall may represent a novel therapeutic approach in treating vascular disease.

  17. A Neural Mechanism for Surprise-related Interruptions of Visuospatial Working Memory.

    Science.gov (United States)

    Wessel, Jan R

    2016-11-30

    Surprising perceptual events recruit a fronto-basal ganglia mechanism for inhibition, which suppresses motor activity following surprise. A recent study found that this inhibitory mechanism also disrupts the maintenance of verbal working memory (WM) after surprising tones. However, it is unclear whether this same mechanism also relates to surprise-related interruptions of non-verbal WM. We tested this hypothesis using a change-detection task, in which surprising tones impaired visuospatial WM. Participants also performed a stop-signal task (SST). We used independent component analysis and single-trial scalp-electroencephalogram to test whether the same inhibitory mechanism that reflects motor inhibition in the SST relates to surprise-related visuospatial WM decrements, as was the case for verbal WM. As expected, surprising tones elicited activity of the inhibitory mechanism, and this activity correlated strongly with the trial-by-trial level of surprise. However, unlike for verbal WM, the activity of this mechanism was unrelated to visuospatial WM accuracy. Instead, inhibition-independent activity that immediately succeeded the inhibitory mechanism was increased when visuospatial WM was disrupted. This shows that surprise-related interruptions of visuospatial WM are not effected by the same inhibitory mechanism that interrupts verbal WM, and instead provides evidence for a 2-stage model of distraction.

  18. Surprisal-based comparison between a symbolic and a connectionist model of sentence processing

    NARCIS (Netherlands)

    Frank, S.L.; Taatgen, N.; van Rijn, H.

    2009-01-01

    The 'unlexicalized surprisal' of a word in sentence context is defined as the negative logarithm of the probability of the word's part-of-speech given the sequence of previous parts-of-speech of the sentence. Unlexicalized surprisal is known to correlate with word reading time. Here, it is shown

  19. The role of surprising events in a math game on proportional reasoning

    NARCIS (Netherlands)

    Wouters, P.; Oostendorp, van H.; Vrugte, ter J.; Jong, de T.; Vandercruysse, S.; Elen, J.

    2015-01-01

    This study examines whether surprising events can be used to stimulate students’ playful learning in a GBL environment in the domain of proportional reasoning. The assumed effect of surprise is that unexpected events interrupt an expectation and therefore triggers the player to evaluate the new situ

  20. Distinct medial temporal networks encode surprise during motivation by reward versus punishment.

    Science.gov (United States)

    Murty, Vishnu P; LaBar, Kevin S; Adcock, R Alison

    2016-10-01

    Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also impacts neural and mnemonic encoding of surprising events. During functional magnetic resonance imaging (fMRI), participants encountered perceptually unexpected events either during the pursuit of rewards or avoidance of punishments. Despite similar levels of motivation across groups, reward and punishment facilitated the processing of surprising events in different medial temporal lobe regions. Whereas during reward motivation, perceptual surprises enhanced activation in the hippocampus, during punishment motivation surprises instead enhanced activation in parahippocampal cortex. Further, we found that reward motivation facilitated hippocampal coupling with ventromedial PFC, whereas punishment motivation facilitated parahippocampal cortical coupling with orbitofrontal cortex. Behaviorally, post-scan testing revealed that reward, but not punishment, motivation resulted in greater memory selectivity for surprising events encountered during goal pursuit. Together these findings demonstrate that neuromodulatory systems engaged by anticipation of reward and punishment target separate components of the medial temporal lobe, modulating medial temporal lobe sensitivity and connectivity. Thus, reward and punishment motivation yield distinct neural contexts for learning, with distinct consequences for how surprises are incorporated into predictive mnemonic models of the environment.

  1. Previously seen and expected stimuli elicit surprise in the context of visual search.

    Science.gov (United States)

    Retell, James D; Becker, Stefanie I; Remington, Roger W

    2016-04-01

    In the context of visual search, surprise is the phenomenon by which a previously unseen and unexpected stimulus exogenously attracts spatial attention. Capture by such a stimulus occurs, by definition, independent of task goals and is thought to be dependent on the extent to which the stimulus deviates from expectations. However, the relative contributions of prior-exposure and explicit knowledge of an unexpected event to the surprise response have not yet been systematically investigated. Here observers searched for a specific color while ignoring irrelevant cues of different colors presented prior to the target display. After a brief familiarization period, we presented an irrelevant motion cue to elicit surprise. Across conditions we varied prior exposure to the motion stimulus - seen versus unseen - and top-down expectations of occurrence - expected versus unexpected - to assess the extent to which each of these factors contributes to surprise. We found no attenuation of the surprise response when observers were pre-exposed to the motion cue and or had explicit knowledge of its occurrence. Our results show that it is neither sufficient nor necessary that a stimulus be new and unannounced to elicit surprise and suggest that the expectations that determine the surprise response are highly context specific.

  2. A Statistical Analysis of the Relationship between Harmonic Surprise and Preference in Popular Music.

    Science.gov (United States)

    Miles, Scott A; Rosen, David S; Grzywacz, Norberto M

    2017-01-01

    Studies have shown that some musical pieces may preferentially activate reward centers in the brain. Less is known, however, about the structural aspects of music that are associated with this activation. Based on the music cognition literature, we propose two hypotheses for why some musical pieces are preferred over others. The first, the Absolute-Surprise Hypothesis, states that unexpected events in music directly lead to pleasure. The second, the Contrastive-Surprise Hypothesis, proposes that the juxtaposition of unexpected events and subsequent expected events leads to an overall rewarding response. We tested these hypotheses within the framework of information theory, using the measure of "surprise." This information-theoretic variable mathematically describes how improbable an event is given a known distribution. We performed a statistical investigation of surprise in the harmonic structure of songs within a representative corpus of Western popular music, namely, the McGill Billboard Project corpus. We found that chords of songs in the top quartile of the Billboard chart showed greater average surprise than those in the bottom quartile. We also found that the different sections within top-quartile songs varied more in their average surprise than the sections within bottom-quartile songs. The results of this study are consistent with both the Absolute- and Contrastive-Surprise Hypotheses. Although these hypotheses seem contradictory to one another, we cannot yet discard the possibility that both absolute and contrastive types of surprise play roles in the enjoyment of popular music. We call this possibility the Hybrid-Surprise Hypothesis. The results of this statistical investigation have implications for both music cognition and the human neural mechanisms of esthetic judgments.

  3. October Surprises.

    Science.gov (United States)

    2016-10-01

    Ushered in with the rampage of Hurricane Matthew, later days brightened in this month that has often been harbinger of both good and bad news for Cuba and the world. Hurricane Matthew ripped through Eastern Cuba, devastating the historic town of Baracoa (Cuba's first capital, founded in 1511) and the village of Maisí, where the morning sun first rises over Cuban territory. Wind and flood leveled hundreds of homes, brought down the power grid and destroyed crops. Yet there was no loss of human life, unlike in neighboring Haiti and other countries in Matthew's path, and unlike in Cuba in 1963, when Hurricane Flora caused more than 1200 deaths. In Haiti, efforts of health workers-including hundreds of Haitian graduates from Cuba's Latin American Medical School and 600 Cuban health professionals already there-were bolstered by dozens of specially trained Cuban disaster medical personnel in the wake of the storm.

  4. Surprising Resists

    Science.gov (United States)

    Morton, Stephie

    2007-01-01

    In this article, the author discusses an art adventure with her third, fourth, and fifth grade enrichment kids to the Fort Collins Museum of Contemporary Art in Colorado. The author demonstrates and teaches her students how to use the art tissue paper and oil pastel complementing the creative spirit of the Jaune Quick-to-See Smith work presented…

  5. The role of loudness in detection of surprising events in music recordings

    OpenAIRE

    Holonowicz, Piotr; Herrera, Perfecto; Purwins, Hendrik

    2009-01-01

    The abrupt change of loudness is a salient event that is not always expected by a music listener. Therefore loudness is an important cue when seeking for events in a music stream that could violate human expectations. The concept of expectation and surprise in music has become recently the subject of extensive research, however mostly using symbolic data. The aim of this work is to investigate the circumstances when a change of sound intensity could be surprising for a listener. Then, using t...

  6. A post-genomic surprise. The molecular reinscription of race in science, law and medicine.

    Science.gov (United States)

    Duster, Troy

    2015-03-01

    The completion of the first draft of the Human Genome Map in 2000 was widely heralded as the promise and future of genetics-based medicines and therapies - so much so that pundits began referring to the new century as 'The Century of Genetics'. Moreover, definitive assertions about the overwhelming similarities of all humans' DNA (99.9 per cent) by the leaders of the Human Genome Project were trumpeted as the end of racial thinking about racial taxonomies of human genetic differences. But the first decade of the new century brought unwelcomed surprises. First, gene therapies turned out to be far more complicated than any had anticipated - and instead the pharmaceutical industry turned to a focus on drugs that might be 'related' to population differences based upon genetic markers. While the language of 'personalized medicine' dominated this frame, research on racially and ethnically designated populations differential responsiveness to drugs dominated the empirical work in the field. Ancestry testing and 'admixture research' would play an important role in a new kind of molecular reification of racial categories. Moreover, the capacity of the super-computer to map differences reverberated into personal identification that would affect both the criminal justice system and forensic science, and generate new levels of concern about personal privacy. Social scientists in general, and sociologists in particular, have been caught short by these developments - relying mainly on assertions that racial categories are socially constructed, regionally and historically contingent, and politically arbitrary. While these assertions are true, the imprimatur of scientific legitimacy has shifted the burden, since now 'admixture research' can claim that its results get at the 'reality' of human differentiation, not the admittedly flawed social constructions of racial categories. Yet what was missing from this framing of the problem: 'admixture research' is itself based upon socially

  7. Efficient reduction of complex noise in passive millimeter-wavelength video utilizing Bayesian surprise

    Science.gov (United States)

    Mundhenk, T. Nathan; Baron, Josh; Matic, Roy M.

    2011-06-01

    Passive millimeter wavelength (PMMW) video holds great promise given its ability to see targets and obstacles through fog, smoke and rain. However, current imagers produce undesirable complex noise. This can come as a mixture of fast shot (snow like) noise and a slower forming circular fixed pattern. Shot noise can be removed by a simple gain style filter. However, this can produce blurring of objects in the scene. To alleviate this, we measure the amount of Bayesian surprise in videos. Bayesian surprise is feature change in time which is abrupt, but cannot be accounted for as shot noise. Surprise is used to attenuate the shot noise filter in locations of high surprise. Since high Bayesian surprise in videos is very salient to observers, this reduces blurring particularly in places where people visually attend. Fixed pattern noise is removed after the shot noise using a combination of Non-uniformity correction (NUC) and Eigen Image Wavelet Transformation. The combination allows for online removal of time varying fixed pattern noise even when background motion may be absent. It also allows for online adaptation to differing intensities of fixed pattern noise. The fixed pattern and shot noise filters are all efficient allowing for real time video processing of PMMW video. We show several examples of PMMW video with complex noise that is much cleaner as a result of the noise removal. Processed video clearly shows cars, houses, trees and utility poles at 20 frames per second.

  8. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  9. Conference of “Uncertainty and Surprise: Questions on Working with the Unexpected and Unknowable”

    CERN Document Server

    McDaniel, Reuben R; Uncertainty and Surprise in Complex Systems : Questions on Working with the Unexpected

    2005-01-01

    Complexity science has been a source of new insight in physical and social systems and has demonstrated that unpredictability and surprise are fundamental aspects of the world around us. This book is the outcome of a discussion meeting of leading scholars and critical thinkers with expertise in complex systems sciences and leaders from a variety of organizations sponsored by the Prigogine Center at The University of Texas at Austin and the Plexus Institute to explore strategies for understanding uncertainty and surprise. Besides distributions to the conference it includes a key digest by the editors as well as a commentary by the late nobel laureat Ilya Prigogine, "Surprises in half of a century". The book is intended for researchers and scientists in complexity science as well as for a broad interdisciplinary audience of both practitioners and scholars. It will well serve those interested in the research issues and in the application of complexity science to physical and social systems.

  10. What is a surprise earthquake? The example of the 2002, San Giuliano (Italy event

    Directory of Open Access Journals (Sweden)

    M. Mucciarelli

    2005-06-01

    Full Text Available Both in scientific literature and in the mass media, some earthquakes are defined as «surprise earthquakes». Based on his own judgment, probably any geologist, seismologist or engineer may have his own list of past «surprise earthquakes». This paper tries to quantify the underlying individual perception that may lead a scientist to apply such a definition to a seismic event. The meaning is different, depending on the disciplinary approach. For geologists, the Italian database of seismogenic sources is still too incomplete to allow for a quantitative estimate of the subjective degree of belief. For seismologists, quantification is possible defining the distance between an earthquake and its closest previous neighbor. Finally, for engineers, the San Giuliano quake could not be considered a surprise, since probabilistic site hazard estimates reveal that the change before and after the earthquake is just 4%.

  11. Salience and Attention in Surprisal-Based Accounts of Language Processing

    Science.gov (United States)

    Zarcone, Alessandra; van Schijndel, Marten; Vogels, Jorrig; Demberg, Vera

    2016-01-01

    The notion of salience has been singled out as the explanatory factor for a diverse range of linguistic phenomena. In particular, perceptual salience (e.g., visual salience of objects in the world, acoustic prominence of linguistic sounds) and semantic-pragmatic salience (e.g., prominence of recently mentioned or topical referents) have been shown to influence language comprehension and production. A different line of research has sought to account for behavioral correlates of cognitive load during comprehension as well as for certain patterns in language usage using information-theoretic notions, such as surprisal. Surprisal and salience both affect language processing at different levels, but the relationship between the two has not been adequately elucidated, and the question of whether salience can be reduced to surprisal / predictability is still open. Our review identifies two main challenges in addressing this question: terminological inconsistency and lack of integration between high and low levels of representations in salience-based accounts and surprisal-based accounts. We capitalize upon work in visual cognition in order to orient ourselves in surveying the different facets of the notion of salience in linguistics and their relation with models of surprisal. We find that work on salience highlights aspects of linguistic communication that models of surprisal tend to overlook, namely the role of attention and relevance to current goals, and we argue that the Predictive Coding framework provides a unified view which can account for the role played by attention and predictability at different levels of processing and which can clarify the interplay between low and high levels of processes and between predictability-driven expectation and attention-driven focus. PMID:27375525

  12. Salience and attention in surprisal-based accounts of language processing

    Directory of Open Access Journals (Sweden)

    Alessandra eZarcone

    2016-06-01

    Full Text Available The notion of salience has been singled out as the explanatory factor for a diverse range oflinguistic phenomena. In particular, perceptual salience (e.g. visual salience of objects in the world,acoustic prominence of linguistic sounds and semantic-pragmatic salience (e.g. prominence ofrecently mentioned or topical referents have been shown to influence language comprehensionand production. A different line of research has sought to account for behavioral correlates ofcognitive load during comprehension as well as for certain patterns in language usage usinginformation-theoretic notions, such as surprisal. Surprisal and salience both affect languageprocessing at different levels, but the relationship between the two has not been adequatelyelucidated, and the question of whether salience can be reduced to surprisal / predictability isstill open. Our review identifies two main challenges in addressing this question: terminologicalinconsistency and lack of integration between high and low levels of representations in salience-based accounts and surprisal-based accounts. We capitalise upon work in visual cognition inorder to orient ourselves in surveying the different facets of the notion of salience in linguisticsand their relation with models of surprisal. We find that work on salience highlights aspects oflinguistic communication that models of surprisal tend to overlook, namely the role of attentionand relevance to current goals, and we argue that the Predictive Coding framework provides aunified view which can account for the role played by attention and predictability at different levelsof processing and which can clarify the interplay between low and high levels of processes andbetween predictability-driven expectation and attention-driven focus.

  13. One In Five Inpatient Emergency Department Cases May Lead To Surprise Bills.

    Science.gov (United States)

    Garmon, Christopher; Chartock, Benjamin

    2017-01-01

    A surprise medical bill is a bill from an out-of-network provider that was not expected by the patient or that came from an out-of-network provider not chosen by the patient. In 2014, 20 percent of hospital inpatient admissions that originated in the emergency department (ED), 14 percent of outpatient visits to the ED, and 9 percent of elective inpatient admissions likely led to a surprise medical bill. Project HOPE—The People-to-People Health Foundation, Inc.

  14. Risk, surprises and black swans fundamental ideas and concepts in risk assessment and risk management

    CERN Document Server

    Aven, Terje

    2014-01-01

    Risk, Surprises and Black Swans provides an in depth analysis of the risk concept with a focus on the critical link to knowledge; and the lack of knowledge, that risk and probability judgements are based on.Based on technical scientific research, this book presents a new perspective to help you understand how to assess and manage surprising, extreme events, known as 'Black Swans'. This approach looks beyond the traditional probability-based principles to offer a broader insight into the important aspects of uncertain events and in doing so explores the ways to manage them.

  15. Did the FED Surprise the Markets in 2001? A Case Study for Vars with Sign Restrictions

    NARCIS (Netherlands)

    Uhlig, H.F.H.V.S.

    2001-01-01

    In 2001, the Fed has lowered interest rates in a series of cuts, starting from 6.5 % at the end of 2000 to 2.0 % by early November.This paper asks, whether the Federal Reserve Bank has been surprising the markets, taking as given the conventional view about the effect of monetary policy shocks.New

  16. Surprise Gift” Purchases of Small Electric Appliances: A Pilot Study

    NARCIS (Netherlands)

    J. Vanhamme (Joëlle); C.J.P.M. de Bont (Cees)

    2005-01-01

    textabstractUnderstanding decision-making processes for gifts is of strategic importance for companies selling small electrical appliances as gifts account for a large part of their sales. Among all gifts, the ones that are surprising are the most valued by recipients. However, research about

  17. Surprising convergence of the Monte Carlo renormalization group for the three-dimensional Ising model.

    Science.gov (United States)

    Ron, Dorit; Brandt, Achi; Swendsen, Robert H

    2017-05-01

    We present a surprisingly simple approach to high-accuracy calculations of the critical properties of the three-dimensional Ising model. The method uses a modified block-spin transformation with a tunable parameter to improve convergence in the Monte Carlo renormalization group. The block-spin parameter must be tuned differently for different exponents to produce optimal convergence.

  18. Bagpipes and Artichokes: Surprise as a Stimulus to Learning in the Elementary Music Classroom

    Science.gov (United States)

    Jacobi, Bonnie Schaffhauser

    2016-01-01

    Incorporating surprise into music instruction can stimulate student attention, curiosity, and interest. Novelty focuses attention in the reticular activating system, increasing the potential for brain memory storage. Elementary ages are ideal for introducing novel instruments, pieces, composers, or styles of music. Young children have fewer…

  19. The Educational Philosophies of Mordecai Kaplan and Michael Rosenak: Surprising Similarities and Illuminating Differences

    Science.gov (United States)

    Schein, Jeffrey; Caplan, Eric

    2014-01-01

    The thoughts of Mordecai Kaplan and Michael Rosenak present surprising commonalities as well as illuminating differences. Similarities include the perception that Judaism and Jewish education are in crisis, the belief that Jewish peoplehood must include commitment to meaningful content, the need for teachers to teach from a position of…

  20. Surprise, Memory, and Retrospective Judgment Making: Testing Cognitive Reconstruction Theories of the Hindsight Bias Effect

    Science.gov (United States)

    Ash, Ivan K.

    2009-01-01

    Hindsight bias has been shown to be a pervasive and potentially harmful decision-making bias. A review of 4 competing cognitive reconstruction theories of hindsight bias revealed conflicting predictions about the role and effect of expectation or surprise in retrospective judgment formation. Two experiments tested these predictions examining the…

  1. Did the FED Surprise the Markets in 2001? A Case Study for Vars with Sign Restrictions

    NARCIS (Netherlands)

    Uhlig, H.F.H.V.S.

    2001-01-01

    In 2001, the Fed has lowered interest rates in a series of cuts, starting from 6.5 % at the end of 2000 to 2.0 % by early November.This paper asks, whether the Federal Reserve Bank has been surprising the markets, taking as given the conventional view about the effect of monetary policy shocks.New e

  2. Surprising electronic structure of the BeH- dimer: a full-configuration-interaction study.

    Science.gov (United States)

    Verdicchio, Marco; Bendazzoli, Gian Luigi; Evangelisti, Stefano; Leininger, Thierry

    2013-01-10

    The electronic structure of the beryllium hydride anion, BeH(-), was investigated at valence full-configuration-interaction (FCI) level, using large cc-pV6Z basis sets. It appears that there is a deep change of the wave function nature as a function of the internuclear distance: the ion structure goes from a weakly bonded Be···H(-) complex, at long distance, to a rather strongly bonded system (more than 2 eV) at short distance, having a (:Be-H)(-) Lewis structure. In this case, it is the beryllium atom that formally bears the negative charge, a surprising result in view of the fact that it is the hydrogen atom that has a larger electronegativity. Even more surprisingly, at very short distances the average position of the total electronic charge is close to the beryllium atom but on the opposite side with respect to the hydrogen position.

  3. Investigating locality effects and surprisal in written English syntactic choice phenomena.

    Science.gov (United States)

    Rajkumar, Rajakrishnan; van Schijndel, Marten; White, Michael; Schuler, William

    2016-10-01

    We investigate the extent to which syntactic choice in written English is influenced by processing considerations as predicted by Gibson's (2000) Dependency Locality Theory (DLT) and Surprisal Theory (Hale, 2001; Levy, 2008). A long line of previous work attests that languages display a tendency for shorter dependencies, and in a previous corpus study, Temperley (2007) provided evidence that this tendency exerts a strong influence on constituent ordering choices. However, Temperley's study included no frequency-based controls, and subsequent work on sentence comprehension with broad-coverage eye-tracking corpora found weak or negative effects of DLT-based measures when frequency effects were statistically controlled for (Demberg & Keller, 2008; van Schijndel, Nguyen, & Schuler 2013; van Schijndel & Schuler, 2013), calling into question the actual impact of dependency locality on syntactic choice phenomena. Going beyond Temperley's work, we show that DLT integration costs are indeed a significant predictor of syntactic choice in written English even in the presence of competing frequency-based and cognitively motivated control factors, including n-gram probability and PCFG surprisal as well as embedding depth (Wu, Bachrach, Cardenas, & Schuler, 2010; Yngve, 1960). Our study also shows that the predictions of dependency length and surprisal are only moderately correlated, a finding which mirrors Dember & Keller's (2008) results for sentence comprehension. Further, we demonstrate that the efficacy of dependency length in predicting the corpus choice increases with increasing head-dependent distances. At the same time, we find that the tendency towards dependency locality is not always observed, and with pre-verbal adjuncts in particular, non-locality cases are found more often than not. In contrast, surprisal is effective in these cases, and the embedding depth measures further increase prediction accuracy. We discuss the implications of our findings for theories of

  4. Surprise and sense making: what newcomers experience in entering unfamiliar organizational settings.

    Science.gov (United States)

    Louis, M R

    1980-06-01

    Growing disillusionment among new members of organizations has been traced to inadequacies in approaches to organizational entry. Current directions of research on organizational entry and their limitations are described, and a new perspective is proposed. The new perspective identifies key features of newcomers' entry experiences, including surprise, contrast, and change, and describes the sense-making processes by which individuals cope with their entry experiences. Implications for research and practice on organizational entry are drawn.

  5. Each individual is a surprise: a conversation with Marianne Horney Eckardt.

    Science.gov (United States)

    Rubin, Jeffrey B

    2014-06-01

    "Each Individual is a Surprise" is a brief account of a dialogue between Marianne Horney Eckardt and myself about the state of psychoanalysis and the psychoanalytic process, the danger of idolatry, the damaging impact of psychoanalytic schools when they create a standardized and pathologizing approach to people, the value of curiosity and humility and retaining one's clinical creativity. The role of Rank, Horney, Sullivan, and Fromm in Dr. Eckardt's long life and rich work is touched upon.

  6. Surprise and Opportunity for Learning in Grand Canyon: the Glen Canyon Dam Adaptive Management Program

    Directory of Open Access Journals (Sweden)

    Theodore S. Melis

    2015-09-01

    Full Text Available With a focus on resources of the Colorado River ecosystem below Glen Canyon Dam, the Glen Canyon Dam Adaptive Management Program has included a variety of experimental policy tests, ranging from manipulation of water releases from the dam to removal of non-native fish within Grand Canyon National Park. None of these field-scale experiments has yet produced unambiguous results in terms of management prescriptions. But there has been adaptive learning, mostly from unanticipated or surprising resource responses relative to predictions from ecosystem modeling. Surprise learning opportunities may often be viewed with dismay by some stakeholders who might not be clear about the purpose of science and modeling in adaptive management. However, the experimental results from the Glen Canyon Dam program actually represent scientific successes in terms of revealing new opportunities for developing better river management policies. A new long-term experimental management planning process for Glen Canyon Dam operations, started in 2011 by the U.S. Department of the Interior, provides an opportunity to refocus management objectives, identify and evaluate key uncertainties about the influence of dam releases, and refine monitoring for learning over the next several decades. Adaptive learning since 1995 is critical input to this long-term planning effort. Embracing uncertainty and surprise outcomes revealed by monitoring and ecosystem modeling will likely continue the advancement of resource objectives below the dam, and may also promote efficient learning in other complex programs.

  7. Surprise and Uncertainty—Framing Regional Geohazards in the Theory of Complexity

    Directory of Open Access Journals (Sweden)

    Beate M. W. Ratter

    2013-01-01

    Full Text Available The paper analyzes the concepts of uncertainty and surprise as key variables of a socio-ecological system’s behavior in the context of the theory of complexity. Experiences from the past have shown that living with uncertainty is part of our daily life and surprises are only surprising because our perspective of system trajectories is basically linear and non-dynamic. The future of humanity is dependent on the understanding of the system’s behavior and needs a change in perspective of linearity to non-linearity and from the planning imperative to a management hedging uncertainty and surprise. In the context of humanity’s future, the theory of complexity offers a new perspective on system trajectories and their understanding of surprises and uncertainty. There is a need for a Gestaltwechsel—a change in perception—which helps to see things differently and fosters the search for new answers to emerging questions at the human-nature interface. Drawing on the case study of hazard management the paper will explain the necessity of analysis system’s behavior and the taking into account of multi-agent behavior on the micro level which led to emergent behavior on the macro-level of the system. Regional geohazards are explained as the regional impact of an uncontrolled risk based on a state of a natural feature that has a direct impact on a regional population being affected by the appearance of a hazard and its development into damage. By acting in space, time and connectivity, people construct hazardscapes and change risk into regional geohazards. This concept shows relevance for future mitigation and adaptation measures. The theory of complexity can help in engendering the necessary shift in perspective. What is non-linear dynamic thinking as suggested by the theory of complexity? Why is the consideration of the system’s behavior crucial and not just the number of system’s elements? What is the role of agents in these systems? In

  8. A strange and surprising debate: mountains, original sin and 'science' in seventeenth-century England.

    Science.gov (United States)

    Wragge-Morley, Alexander

    2009-06-01

    It could come as a shock to learn that some seventeenth-century men of science and learning thought that mountains were bad. Even more alarmingly, some thought that God had imposed them on the earth to punish man for his sins. By the end of the seventeenth century, surprisingly many English natural philosophers and theologians were engaged in a debate about whether mountains were 'good' or 'bad', useful or useless. At stake in this debate were not just the careers of its participants, but arguments about the best ways of looking at and reckoning with 'nature' itself.

  9. A new in vivo model of pantothenate kinase-associated neurodegeneration reveals a surprising role for transcriptional regulation in pathogenesis.

    Directory of Open Access Journals (Sweden)

    Varun ePandey

    2013-09-01

    Full Text Available Pantothenate Kinase-Associated Neurodegeneration (PKAN is a neurodegenerative disorder with a poorly understood molecular mechanism. It is caused by mutations in Pantothenate Kinase, the first enzyme in the Coenzyme A (CoA biosynthetic pathway. Here, we developed a Drosophila model of PKAN (tim-fbl flies that allows us to continuously monitor the modeled disease in the brain. In tim-fbl flies, downregulation of fumble, the Drosophila PanK homologue in the cells containing a circadian clock results in characteristic features of PKAN such as developmental lethality, hypersensitivity to oxidative stress, and diminished life span. Despite quasi-normal circadian transcriptional rhythms, tim-fbl flies display brain-specific aberrant circadian locomotor rhythms, and a unique transcriptional signature. Comparison with expression data from flies exposed to paraquat demonstrates that, as previously suggested, pathways others than oxidative stress are affected by PANK downregulation. Surprisingly we found a significant decrease in the expression of key components of the photoreceptor recycling pathways, which could lead to retinal degeneration, a hallmark of PKAN. Importantly, these defects are not accompanied by changes in structural components in eye genes suggesting that changes in gene expression in the eye precede and may cause the retinal degeneration. Indeed tim-fbl flies have diminished response to light transitions, and their altered day/night patterns of activity demonstrates defects in light perception. This suggest that retinal lesions are not solely due to oxidative stress and demonstrates a role for the transcriptional response to CoA deficiency underlying the defects observed in dPanK deficient flies. Moreover, in the present study we developed a new fly model that can be applied to other diseases and that allows the assessment of neurodegeneration in the brains of living flies.

  10. Expectation and surprise determine neural population responses in the ventral visual stream.

    Science.gov (United States)

    Egner, Tobias; Monti, Jim M; Summerfield, Christopher

    2010-12-08

    Visual cortex is traditionally viewed as a hierarchy of neural feature detectors, with neural population responses being driven by bottom-up stimulus features. Conversely, "predictive coding" models propose that each stage of the visual hierarchy harbors two computationally distinct classes of processing unit: representational units that encode the conditional probability of a stimulus and provide predictions to the next lower level; and error units that encode the mismatch between predictions and bottom-up evidence, and forward prediction error to the next higher level. Predictive coding therefore suggests that neural population responses in category-selective visual regions, like the fusiform face area (FFA), reflect a summation of activity related to prediction ("face expectation") and prediction error ("face surprise"), rather than a homogenous feature detection response. We tested the rival hypotheses of the feature detection and predictive coding models by collecting functional magnetic resonance imaging data from the FFA while independently varying both stimulus features (faces vs houses) and subjects' perceptual expectations regarding those features (low vs medium vs high face expectation). The effects of stimulus and expectation factors interacted, whereby FFA activity elicited by face and house stimuli was indistinguishable under high face expectation and maximally differentiated under low face expectation. Using computational modeling, we show that these data can be explained by predictive coding but not by feature detection models, even when the latter are augmented with attentional mechanisms. Thus, population responses in the ventral visual stream appear to be determined by feature expectation and surprise rather than by stimulus features per se.

  11. Infants’ Looking to Surprising Events: When Eye-Tracking Reveals More than Looking Time

    Science.gov (United States)

    Yeung, H. Henny; Denison, Stephanie; Johnson, Scott P.

    2016-01-01

    Research on infants’ reasoning abilities often rely on looking times, which are longer to surprising and unexpected visual scenes compared to unsurprising and expected ones. Few researchers have examined more precise visual scanning patterns in these scenes, and so, here, we recorded 8- to 11-month-olds’ gaze with an eye tracker as we presented a sampling event whose outcome was either surprising, neutral, or unsurprising: A red (or yellow) ball was drawn from one of three visible containers populated 0%, 50%, or 100% with identically colored balls. When measuring looking time to the whole scene, infants were insensitive to the likelihood of the sampling event, replicating failures in similar paradigms. Nevertheless, a new analysis of visual scanning showed that infants did spend more time fixating specific areas-of-interest as a function of the event likelihood. The drawn ball and its associated container attracted more looking than the other containers in the 0% condition, but this pattern was weaker in the 50% condition, and even less strong in the 100% condition. Results suggest that measuring where infants look may be more sensitive than simply how much looking there is to the whole scene. The advantages of eye tracking measures over traditional looking measures are discussed. PMID:27926920

  12. Surprises from the resummation of ladders in the ABJ(M) cusp anomalous dimension

    CERN Document Server

    Bonini, Marisa; Preti, Michelangelo; Seminara, Domenico

    2016-01-01

    We study the cusp anomalous dimension in N=6 ABJ(M) theory, identifying a scaling limit in which the ladder diagrams dominate. The resummation is encoded into a Bethe-Salpeter equation that is mapped to a Schroedinger problem, exactly solvable due to the surprising supersymmetry of the effective Hamiltonian. In the ABJ case the solution implies the diagonalization of the U(N) and U(M) building blocks, suggesting the existence of two independent cusp anomalous dimensions and an unexpected exponentiation structure for the related Wilson loops. While consistent with previous perturbative analysis, the strong coupling limit of our result does not agree with the string theory computation, emphasizing a difference with the analogous resummation in the N=4 case.

  13. Probing Critical Point Energies of Transition Metal Dichalcogenides: Surprising Indirect Gap of Single Layer WSe 2

    KAUST Repository

    Zhang, Chendong

    2015-09-21

    By using a comprehensive form of scanning tunneling spectroscopy, we have revealed detailed quasi-particle electronic structures in transition metal dichalcogenides, including the quasi-particle gaps, critical point energy locations, and their origins in the Brillouin zones. We show that single layer WSe surprisingly has an indirect quasi-particle gap with the conduction band minimum located at the Q-point (instead of K), albeit the two states are nearly degenerate. We have further observed rich quasi-particle electronic structures of transition metal dichalcogenides as a function of atomic structures and spin-orbit couplings. Such a local probe for detailed electronic structures in conduction and valence bands will be ideal to investigate how electronic structures of transition metal dichalcogenides are influenced by variations of local environment.

  14. OCEAN CIRCULATION. Observing the Atlantic Meridional Overturning Circulation yields a decade of inevitable surprises.

    Science.gov (United States)

    Srokosz, M A; Bryden, H L

    2015-06-19

    The importance of the Atlantic Meridional Overturning Circulation (AMOC) heat transport for climate is well acknowledged. Climate models predict that the AMOC will slow down under global warming, with substantial impacts, but measurements of ocean circulation have been inadequate to evaluate these predictions. Observations over the past decade have changed that situation, providing a detailed picture of variations in the AMOC. These observations reveal a surprising degree of AMOC variability in terms of the intraannual range, the amplitude and phase of the seasonal cycle, the interannual changes in strength affecting the ocean heat content, and the decline of the AMOC over the decade, both of the latter two exceeding the variations seen in climate models. Copyright © 2015, American Association for the Advancement of Science.

  15. Paroxysmal atrial fibrillation occurs often in cryptogenic ischaemic stroke. Final results from the SURPRISE study

    DEFF Research Database (Denmark)

    Christensen, Louisa; Krieger, D W; Højberg, S;

    2014-01-01

    BACKGROUND AND PURPOSE: Atrial fibrillation (AF) increases the risk of stroke fourfold and is associated with a poor clinical outcome. Despite work-up in compliance with guidelines, up to one-third of patients have cryptogenic stroke (CS). The prevalence of asymptomatic paroxysmal atrial...... fibrillation (PAF) in CS remains unknown. The SURPRISE project aimed at determining this rate using long-term cardiac monitoring. METHODS: Patients with CS after protocolled work-up including electrocardiography (ECG) and telemetry were included after informed consent. An implantable loop recorder (ILR...... patients (16.1%). In three patients PAF was detected by other methods before or after monitoring and was undiscovered due to device sensitivity in one case. The first event of PAF was documented at a mean of 109 days (SD ±48) after stroke onset. PAF was asymptomatic in all cases and occurred in episodes...

  16. Probing Critical Point Energies of Transition Metal Dichalcogenides: Surprising Indirect Gap of Single Layer WSe2.

    Science.gov (United States)

    Zhang, Chendong; Chen, Yuxuan; Johnson, Amber; Li, Ming-Yang; Li, Lain-Jong; Mende, Patrick C; Feenstra, Randall M; Shih, Chih-Kang

    2015-10-14

    By using a comprehensive form of scanning tunneling spectroscopy, we have revealed detailed quasi-particle electronic structures in transition metal dichalcogenides, including the quasi-particle gaps, critical point energy locations, and their origins in the Brillouin zones. We show that single layer WSe2 surprisingly has an indirect quasi-particle gap with the conduction band minimum located at the Q-point (instead of K), albeit the two states are nearly degenerate. We have further observed rich quasi-particle electronic structures of transition metal dichalcogenides as a function of atomic structures and spin-orbit couplings. Such a local probe for detailed electronic structures in conduction and valence bands will be ideal to investigate how electronic structures of transition metal dichalcogenides are influenced by variations of local environment.

  17. Beyond surprise: the puzzle of infants' expressive reactions to expectancy violation.

    Science.gov (United States)

    Scherer, Klaus R; Zentner, Marcel R; Stern, Daniel

    2004-12-01

    The reactions of 58 infants to expectancy violation by digitally filtering the experimenter's voice were studied in a cross-sectional design for ages 5, 7, 9, 11-12, and 14 months. The results show that behavioral freezing and changes in gaze direction, but not facial or vocal expression, are reliable responses to expectancy violation. The pattern suggests that a transition in the infant's capacity for cognitive evaluation of novel and discrepant events may occur around age 9 months. These findings confirm the consistent failure to find prototypical facial surprise reactions in research on novel or impossible situations. Componential theories of emotion, which predict adaptive behavior patterns from appraisal processes, may provide clues for underlying mechanisms and generate hypotheses on age-related changes in emotional expression. copyright (c) 2004 APA, all rights reserved.

  18. Surprising judgments about robot drivers: Experiments on rising expectations and blaming humans

    Directory of Open Access Journals (Sweden)

    Peter Danielson

    2015-05-01

    Full Text Available N-Reasons is an experimental Internet survey platform designed to enhance public participation in applied ethics and policy. N-Reasons encourages individuals to generate reasons to support their judgments, and groups to converge on a common set of reasons pro and con various issues.  In the Robot Ethics Survey some of the reasons contributed surprising judgments about autonomous machines. Presented with a version of the trolley problem with an autonomous train as the agent, participants gave unexpected answers, revealing high expectations for the autonomous machine and shifting blame from the automated device to the humans in the scenario. Further experiments with a standard pair of human-only trolley problems refine these results. While showing the high expectations even when no autonomous machine is involved, human bystanders are only blamed in the machine case. A third experiment explicitly aimed at responsibility for driverless cars confirms our findings about shifting blame in the case of autonomous machine agents. We conclude methodologically that both results point to the power of an experimental survey based approach to public participation to explore surprising assumptions and judgments in applied ethics. However, both results also support using caution when interpreting survey results in ethics, demonstrating the importance of qualitative data to provide further context for evaluating judgments revealed by surveys. On the ethics side, the result about shifting blame to humans interacting with autonomous machines suggests caution about the unintended consequences of intuitive principles requiring human responsibility.http://dx.doi.org/10.5324/eip.v9i1.1727

  19. Surprises in the maize pollen transcriptome: Inbred differences and developmental similarities

    Science.gov (United States)

    Pollen is the primary means of gene flow between plants and plant populations and plays a critical role in seed production. Our overall objective is to better understand the molecular and genetic basis of the pollen function. We compared gene expression levels in seedlings, mat...

  20. Two Genes Encoding Uracil Phosphoribosyltransferase Are Present in Bacillus subtilis

    DEFF Research Database (Denmark)

    Martinussen, Jan; Glaser, Philippe; Andersen, Paal S.

    1995-01-01

    Uracil phosphoribosyltransferase (UPRTase) catalyzes the key reaction in the salvage of uracil in many microorganisms. Surprisingly, two genes encoding UPRTase activity were cloned from Bacillus subtilis by complementation of an Escherichia coli mutant. The genes were sequenced, and the putative...

  1. The Nucleus of Comet 67P/Churyumov-Gerasimenko: Lots of Surprises

    Science.gov (United States)

    Weissman, Paul R.; Rosetta Science Working Team

    2016-10-01

    ESA's Rosetta mission has made many new and unexpected discoveries since its arrival at comet 67P/Churyumov-Gerasimenko in August 2014. The first of these was the unusual shape of the cometary nucleus. Although bilobate nuclei had been seen before, the extreme concavities on 67P were unexpected. Evidence gathered during the mission suggests that two independent bodies came together to form 67P, rather than the nucleus being a single body that was sculpted by sublimation and/or other processes. Although not a surprise, early observations showed that the nucleus rotation period had decreased by ~22 minutes since the previous aphelion passage. A similar rotation period decrease was seen post-perihelion during the encounter. These changes likely arise from asymmetric jetting forces from the irregular nucleus. Initially, Rosetta's instruments found little evidence for water ice on the surface; the presence of surface water ice increased substantially as the nucleus approached perihelion. The nucleus bulk density, 533 ± 6 kg/m3, was measured with Radio Science and OSIRIS imaging of the nucleus volume. This confirmed previous estimates based on indirect methods that the bulk density of cometary nuclei was on the order of 500-600 kg/m3 and on measurement of the density of 9P/Tempel 1's nucleus by Deep Impact. Nucleus topography proved to be highly varied, from smooth dust-covered plains to shallow circular basins, to the very rough terrain where the Philae lander came to rest. Evidence of thermal cracking is everywhere. The discovery of cylindrical pits on the surface, typically 100-200m in diameter with similar depths was a major surprise and has been interpreted as sinkholes. "Goose-bump" terrain consisting of apparently random piles of boulders 2-3 m in diameter was another unexpected discovery. Apparent layering with scales of meters to many tens of meters was seen but there was little or no evidence for impact features. Radar tomography of the interior of the "head

  2. Investigation of the heat source(s) of the Surprise Valley Geothermal System, Northern California

    Science.gov (United States)

    Tanner, N.; Holt, C. D.; Hawkes, S.; McClain, J. S.; Safford, L.; Mink, L. L.; Rose, C.; Zierenberg, R. A.

    2016-12-01

    Concerns about environmental impacts and energy security have led to an increased interest in sustainable and renewable energy resources, including geothermal systems. It is essential to know the permeability structure and possible heat source(s) of a geothermal area in order to assess the capacity and extent of the potential resource. We have undertaken geophysical surveys at the Surprise Valley Hot Springs in Cedarville, California to characterize essential parameters related to a fault-controlled geothermal system. At present, the heat source(s) for the system are unknown. Igneous bodies in the area are likely too old to have retained enough heat to supply the system, so it is probable that fracture networks provide heat from some deeper or more distributed heat sources. However, the fracture system and permeability structure remain enigmatic. The goal of our research is to identify the pathways for fluid transport within the Surprise Valley geothermal system using a combination of geophysical methods including active seismic surveys and short- and long-period magnetotelluric (MT) surveys. We have collected 14 spreads, consisting of 24 geophones each, of active-source seismic data. We used a "Betsy Gun" source at 8 to 12 locations along each spread and have collected and analyzed about 2800 shot-receiver pairs. Seismic velocities reveal shallow lake sediments, as well as velocities consistent with porous basalts. The latter, with velocities of greater than 3.0 km/s, lie along strike with known hot springs and faulted and tilted basalt outcrops outside our field area. This suggests that basalts may provide a permeable pathway through impermeable lake deposits. We conducted short-period (10Hz-60kHz) MT measurements at 33 stations. Our short-period MT models indicate shallow resistive blocks (>100Ωm) with a thin cover of more conductive sediments ( 10Ωm) at the surface. Hot springs are located in gaps between resistive blocks and are connected to deeper low

  3. Surprising results on phylogenetic tree building methods based on molecular sequences

    Directory of Open Access Journals (Sweden)

    Gonnet Gaston H

    2012-06-01

    Full Text Available Abstract Background We analyze phylogenetic tree building methods from molecular sequences (PTMS. These are methods which base their construction solely on sequences, coding DNA or amino acids. Results Our first result is a statistically significant evaluation of 176 PTMSs done by comparing trees derived from 193138 orthologous groups of proteins using a new measure of quality between trees. This new measure, called the Intra measure, is very consistent between different groups of species and strong in the sense that it separates the methods with high confidence. The second result is the comparison of the trees against trees derived from accepted taxonomies, the Taxon measure. We consider the NCBI taxonomic classification and their derived topologies as the most accepted biological consensus on phylogenies, which are also available in electronic form. The correlation between the two measures is remarkably high, which supports both measures simultaneously. Conclusions The big surprise of the evaluation is that the maximum likelihood methods do not score well, minimal evolution distance methods over MSA-induced alignments score consistently better. This comparison also allows us to rank different components of the tree building methods, like MSAs, substitution matrices, ML tree builders, distance methods, etc. It is also clear that there is a difference between Metazoa and the rest, which points out to evolution leaving different molecular traces. We also think that these measures of quality of trees will motivate the design of new PTMSs as it is now easier to evaluate them with certainty.

  4. Pooling designs with surprisingly high degree of error correction in a finite vector space

    CERN Document Server

    Guo, Jun

    2011-01-01

    Pooling designs are standard experimental tools in many biotechnical applications. It is well-known that all famous pooling designs are constructed from mathematical structures by the "containment matrix" method. In particular, Macula's designs (resp. Ngo and Du's designs) are constructed by the containment relation of subsets (resp. subspaces) in a finite set (resp. vector space). Recently, we generalized Macula's designs and obtained a family of pooling designs with more high degree of error correction by subsets in a finite set. In this paper, as a generalization of Ngo and Du's designs, we study the corresponding problems in a finite vector space and obtain a family of pooling designs with surprisingly high degree of error correction. Our designs and Ngo and Du's designs have the same number of items and pools, respectively, but the error-tolerant property is much better than that of Ngo and Du's designs, which was given by D'yachkov et al. \\cite{DF}, when the dimension of the space is large enough.

  5. IP Eri: A surprising long-period binary system hosting a He white dwarf

    CERN Document Server

    Merle, T; Masseron, T; Van Eck, S; Siess, L; Van Winckel, H

    2014-01-01

    We determine the orbital elements for the K0 IV + white dwarf (WD) system IP Eri, which appears to have a surprisingly long period of 1071 d and a significant eccentricity of 0.25. Previous spectroscopic analyses of the WD, based on a distance of 101 pc inferred from its Hipparcos parallax, yielded a mass of only 0.43 M$_\\odot$, implying it to be a helium-core WD. The orbital properties of IP Eri are similar to those of the newly discovered long-period subdwarf B star (sdB) binaries, which involve stars with He-burning cores surrounded by extremely thin H envelopes, and are therefore close relatives to He WDs. We performed a spectroscopic analysis of high-resolution spectra from the HERMES/Mercator spectrograph and concluded that the atmospheric parameters of the K0 component are $T_{\\rm eff} = 4960$ K, $\\log{g} = 3.3$, [Fe/H] = 0.09 and $\\xi = 1.5$ km/s. The detailed abundance analysis focuses on C, N, O abundances, carbon isotopic ratio, light (Na, Mg, Al, Si, Ca, Ti) and s-process (Sr, Y, Zr, Ba, La, Ce, N...

  6. Surprising dissimilarities in a newly formed pair of 'identical twin' stars.

    Science.gov (United States)

    Stassun, Keivan G; Mathieu, Robert D; Cargile, Phillip A; Aarnio, Alicia N; Stempels, Eric; Geller, Aaron

    2008-06-19

    The mass and chemical composition of a star are the primary determinants of its basic physical properties-radius, temperature and luminosity-and how those properties evolve with time. Accordingly, two stars born at the same time, from the same natal material and with the same mass, are 'identical twins,' and as such might be expected to possess identical physical attributes. We have discovered in the Orion nebula a pair of stellar twins in a newborn binary star system. Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to within 2 per cent. Here we report that these twin stars have surface temperatures differing by approximately 300 K ( approximately 10 per cent) and luminosities differing by approximately 50 per cent, both at high confidence level. Preliminary results indicate that the stars' radii also differ, by 5-10 per cent. These surprising dissimilarities suggest that one of the twins may have been delayed by several hundred thousand years in its formation relative to its sibling. Such a delay could only have been detected in a very young, definitively equal-mass binary system. Our findings reveal cosmic limits on the age synchronization of young binary stars, often used as tests for the age calibrations of star-formation models.

  7. The Surprising Composition of the Salivary Proteome of Preterm Human Newborn

    Science.gov (United States)

    Castagnola, Massimo; Inzitari, Rosanna; Fanali, Chiara; Iavarone, Federica; Vitali, Alberto; Desiderio, Claudia; Vento, Giovanni; Tirone, Chiara; Romagnoli, Costantino; Cabras, Tiziana; Manconi, Barbara; Teresa Sanna, Maria; Boi, Roberto; Pisano, Elisabetta; Olianas, Alessandra; Pellegrini, Mariagiuseppina; Nemolato, Sonia; Wilhelm Heizmann, Claus; Faa, Gavino; Messana, Irene

    2011-01-01

    Saliva is a body fluid of a unique composition devoted to protect the mouth cavity and the digestive tract. Our high performance liquid chromatography (HPLC)-electrospray ionization-MS analysis of the acidic soluble fraction of saliva from preterm human newborn surprisingly revealed more than 40 protein masses often undetected in adult saliva. We were able to identify the following proteins: stefin A and stefin B, S100A7 (two isoforms), S100A8, S100A9 (four isoforms), S100A11, S100A12, small proline-rich protein 3 (two isoforms), lysozyme C, thymosins β4 and β10, antileukoproteinase, histone H1c, and α and γ globins. The average mass value reported in international data banks was often incongruent with our experimental results mostly because of post-translational modifications of the proteins, e.g. acetylation of the N-terminal residue. A quantitative label-free MS analysis showed protein levels altered in relation to the postconceptional age and suggested coordinate and hierarchical functions for these proteins during development. In summary, this study shows for the first time that analysis of these proteins in saliva of preterm newborns might represent a noninvasive way to obtain precious information of the molecular mechanisms of development of human fetal oral structures. PMID:20943598

  8. Marine Protected Areas, Multiple-Agency Management, and Monumental Surprise in the Northwestern Hawaiian Islands

    Directory of Open Access Journals (Sweden)

    John N. Kittinger

    2011-01-01

    Full Text Available Large, regional-scale marine protected areas (MPAs and MPA networks face different challenges in governance systems than locally managed or community-based MPAs. An emerging theme in large-scale MPA management is the prevalence of governance structures that rely on institutional collaboration, presenting new challenges as agencies with differing mandates and cultures work together to implement ecosystem-based management. We analyzed qualitative interview data to investigate multi-level social interactions and institutional responses to the surprise establishment of the Papahānaumokuākea Marine National Monument (monument in the northwestern Hawaiian Islands (NWHI. The governance arrangement for the monument represents a new model in US MPA management, requiring two federal agencies and the State of Hawai‘i to collaboratively manage the NWHI. We elucidate the principal barriers to institutional cotrusteeship, characterize institutional transformations that have occurred among the partner agencies in the transition to collaborative management, and evaluate the governance arrangement for the monument as a model for MPAs. The lessons learned from the NWHI governance arrangement are critical as large-scale MPAs requiring multiple-agency management become a prevalent feature on the global seascape.

  9. You'll Never Guess Who Wrote That: 78 Surprising Authors of Psychological Publications.

    Science.gov (United States)

    Lilienfeld, Scott O; Lynn, Steven Jay

    2016-07-01

    One can find psychological authors in the most unexpected places. We present a capsule summary of scholarly publications of psychological interest authored or coauthored by 78 surprising individuals, most of whom are celebrities or relatives of celebrities, historical figures, or people who have otherwise achieved visibility in academic circles, politics, religion, art, and diverse realms of popular culture. Still other publications are authored by individuals who are far better known for their contributions to popular than to academic psychology. The publications, stretching across more than two centuries, encompass a wide swath of domains of psychological inquiry and highlight the intersection of psychology with fields that fall outside its traditional borders, including public health, economics, law, neurosurgery, and even magic. Many of these scholarly contributions have enriched psychology and its allied disciplines, such as psychiatry, in largely unappreciated ways, and they illustrate the penetration of psychological knowledge into multiple scientific disciplines and everyday life. At the same time, our author list demonstrates that remarkable intellectual accomplishments in one scientific domain, such as physics, do not necessarily translate into success in psychology and underscores the distinction between intelligence, on the one hand, and critical thinking and wisdom, on the other.

  10. Surprise responses in the human brain demonstrate statistical learning under high concurrent cognitive demand

    Science.gov (United States)

    Garrido, Marta Isabel; Teng, Chee Leong James; Taylor, Jeremy Alexander; Rowe, Elise Genevieve; Mattingley, Jason Brett

    2016-06-01

    The ability to learn about regularities in the environment and to make predictions about future events is fundamental for adaptive behaviour. We have previously shown that people can implicitly encode statistical regularities and detect violations therein, as reflected in neuronal responses to unpredictable events that carry a unique prediction error signature. In the real world, however, learning about regularities will often occur in the context of competing cognitive demands. Here we asked whether learning of statistical regularities is modulated by concurrent cognitive load. We compared electroencephalographic metrics associated with responses to pure-tone sounds with frequencies sampled from narrow or wide Gaussian distributions. We showed that outliers evoked a larger response than those in the centre of the stimulus distribution (i.e., an effect of surprise) and that this difference was greater for physically identical outliers in the narrow than in the broad distribution. These results demonstrate an early neurophysiological marker of the brain's ability to implicitly encode complex statistical structure in the environment. Moreover, we manipulated concurrent cognitive load by having participants perform a visual working memory task while listening to these streams of sounds. We again observed greater prediction error responses in the narrower distribution under both low and high cognitive load. Furthermore, there was no reliable reduction in prediction error magnitude under high-relative to low-cognitive load. Our findings suggest that statistical learning is not a capacity limited process, and that it proceeds automatically even when cognitive resources are taxed by concurrent demands.

  11. A surprisingly simple correlation between the classical and quantum structural networks in liquid water

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, Peter; Fanourgakis, George S.; Xantheas, Sotiris S.

    2017-08-14

    Nuclear quantum effects in liquid water have profound implications for several of its macroscopic properties related to structure, dynamics, spectroscopy and transport. Although several of water’s macroscopic properties can be reproduced by classical descriptions of the nuclei using potentials effectively parameterized for a narrow range of its phase diagram, a proper account of the nuclear quantum effects is required in order to ensure that the underlying molecular interactions are transferable across a wide temperature range covering different regions of that diagram. When performing an analysis of the hydrogen bonded structural networks in liquid water resulting from the classical (class.) and quantum (q.m.) descriptions of the nuclei with the transferable, flexible, polarizable TTM3-F interaction potential, we found that the two results can be superimposed over the temperature range of T=270-350 K using a surprisingly simple, linear scaling of the two temperatures according to T(q.m.)=aT(class)- T , where a=1.2 and T=51 K. The linear scaling and constant shift of the temperature scale can be considered as a generalization of the previously reported temperature shifts (corresponding to structural changes and the melting T) induced by quantum effects in liquid water.

  12. Polar F-layer model-observation comparisons: a neutral wind surprise

    Directory of Open Access Journals (Sweden)

    J. J. Sojka

    2005-01-01

    Full Text Available The existence of a month-long continuous database of incoherent scatter radar observations of the ionosphere from the EISCAT Savlbard Radar (ESR at Longyearbyen, Norway, provides an unprecedented opportunity for model/data comparisons. Physics-based ionospheric models, such as the Utah State University Time Dependent Ionospheric Model (TDIM, are usually only compared with observations over restricted one or two day events or against climatological averages. In this study, using the ESR observations, the daily weather, day-to-day variability, and month-long climatology can be simultaneously addressed to identify modeling shortcomings and successes. Since for this study the TDIM is driven by climatological representations of the magnetospheric convection, auroral oval, neutral atmosphere, and neutral winds, whose inputs are solar and geomagnetic indices, it is not surprising that the daily weather cannot be reproduced. What is unexpected is that the horizontal neutral wind has come to the forefront as a decisive model input parameter in matching the diurnal morphology of density structuring seen in the observations.

  13. Geophysical Investigation of the Lake City Fault Zone, Surprise Valley, California, and Implications for Geothermal Circulation

    Science.gov (United States)

    McPhee, D. K.; Glen, J. M.; Egger, A. E.; Chuchel, B. A.

    2009-12-01

    New audiomagnetotelluric (AMT), gravity, and magnetic data were collected in Surprise Valley, northwestern Basin and Range, in order to investigate the role that the Lake City Fault Zone (LCFZ) may play in controlling geothermal circulation in the area. Surprise Valley hosts an extensional geothermal system currently undergoing exploration for development on several scales. The focus of much of that exploration has been the LCFZ, a set of NW-SE-trending structures that has been suggested on the basis of (1) low-relief scarps in the NW portion of the zone, (2) dissolved mineral-rich groundwater chemistry along its length, and (3) parallelism with a strong regional fabric that includes the Brothers Fault Zone. The LCFZ extends across the valley at a topographic high, intersecting the N-S-trending basin-bounding faults where major hot springs occur. This relationship suggests that the LCFZ may be a zone of permeability for flow of hydrothermal fluids. Previous potential field data indicate that there is no vertical offset along this fault zone, and little signature at all in either the gravity or magnetic data; along with the lack of surface expression along most of its length, the subsurface geometry of the LCFZ and its influence on geothermal fluid circulation remains enigmatic. The LCFZ therefore provides an ideal opportunity to utilize AMT data, which measures subsurface resistivity and therefore - unlike potential field data - is highly sensitive to the presence of saline fluids. AMT data and additional gravity and magnetic data were collected in 2009 along 3 profiles perpendicular to the LCFZ in order to define the subsurface geometry and conductivity of the fault zone down to depths of ~ 500 m. AMT soundings were collected using the Geometrics Stratagem EH4 system, a four channel, natural and controlled-source tensor system recording in the range of 10 to 92,000 Hz. To augment the low signal in the natural field a transmitter of two horizontal-magnetic dipoles

  14. Surprise and Opportunity for Learning in Grand Canyon: the Glen Canyon Dam Adaptive Management Program

    Science.gov (United States)

    Melis, T. S.; Walters, C. J.; Korman, J.

    2013-12-01

    With a focus on resources of the Colorado River ecosystem downstream of Glen Canyon Dam in Glen Canyon National Recreation Area (GCNRA) and Grand Canyon National Park (GCNP) of northern Arizona, the Glen Canyon Dam Adaptive Management Program has evaluated experimental flow and nonflow policy tests since 1990. Flow experiments have consisted of a variety of water releases from the dam within pre-existing annual downstream delivery agreements. The daily experimental dam operation, termed the Modified Low Fluctuating Flow (MLFF), implemented in 1996 to increase daily low flows and decrease daily peaks were intended to limit daily flow range to conserve tributary sand inputs and improve navigation among other objectives, including hydropower energy. Other flow tests have included controlled floods with some larger releases bypassing the dam's hydropower plant to rebuild and maintain eroded sandbars in GCNP. Experimental daily hydropeaking tests beyond MLFF have also been evaluated for managing the exotic recreational rainbow trout fishery in the dam's GCNRA tailwater. Experimental nonflow policies, such as physical removal of exotic fish below the tailwater, and experimental translocation of endangered native humpback chub from spawning habitats in the Little Colorado River (the largest natal origin site for chub in the basin) to other tributaries within GCNP have also been monitored. None of these large-scale field experiments has yet produced unambiguous results in terms of management prescriptions, owing to inadequate monitoring programs and confounding of treatment effects with effects of ongoing natural changes; most notably, a persistent warming of the river resulting from reduced storage in the dam's reservoir after 2003. But there have been several surprising results relative to predictions from models developed to identify monitoring needs and evaluate experimental design options at the start of the adaptive ecosystem assessment and management program in 1997

  15. Lymphocytic alveolitis: A surprising index of poor prognosis in patients with primary Sjogren's syndrome.

    Science.gov (United States)

    Dalavanga, Y A; Voulgari, P V; Georgiadis, A N; Leontaridi, C; Katsenos, S; Vassiliou, M; Drosos, A A; Constantopoulos, S H

    2006-07-01

    Twelve years ago we reported that lymphocytic alveolitis [or bronchoalveolar lavage (BAL) lymphocytosis] correlates with clinical pulmonary involvement in primary Sjogren's syndrome (pSS). Our thesis was based on subtle clinical and functional evidence of interstitial lung disease (ILD) in pSS patients with "high lymphocytic alveolitis" (>15% lymphocytes in BAL). This report is a follow-up study of these patients. Basic clinical and functional re-evaluation of the 22 patients with pSS, studied in 1991, emphasized the differences between those with alveolitis and those without alveolitis. There was no significant functional decline. There were, however, two statistically significant differences between the two groups: (1) only patients with BAL lymphocytosis had to be treated with steroids (5/12 vs. 0/10, P < 0.05) and (2) only patients with BAL lymphocytosis had died in the mean time (6/12 vs. 0/10, P < 0.01). The causes of death were various. On only two occasions were they related to respiratory infections while there were no deaths from respiratory failure secondary to ILD. BAL lymphocytosis appears to be a surprisingly serious index of dismal prognosis in patients with pSS. We offer no unifying pathophysiologic mechanism for it and, therefore, all we propose is that BAL is performed early, in as many patients with pSS as possible. These patients should then be followed up systematically, in order to evaluate if BAL lymphocytosis has any pathophysiologic importance in the development of clinically serious pSS, which is serious enough to lead to death.

  16. Explanatory models of health and disease: surprises from within the former Soviet Union

    Directory of Open Access Journals (Sweden)

    Tatiana I Andreeva

    2013-06-01

    Full Text Available Extract The review of anthropological theories as applied to public health by Jennifer J. Carroll (Carroll, 2013 published in this issue of TCPHEE made me recollect my first and most surprising discoveries of how differently same things can be understood in different parts of the world. Probably less unexpectedly, these impressions concern substance abuse and addiction behaviors, similarly to many examples deployed by Jennifer J. Carroll. The first of these events happened soon after the break-up of the Soviet Union when some of the most active people from the West rushed to discover what was going on behind the opening iron curtain. A director of an addiction clinic, who had just come into contact with a Dutch counterpart, invited me to join the collaboration and the innovation process he planned to launch. Being a participant of the exchange program started within this collaboration, I had an opportunity to discover how addictive behaviors were understood and explained in books (English, 1961; Kooyman, 1992; Viorst, 1986 recommended by the colleagues in the Netherlands and, as I could observe with my own eyes, addressed in everyday practice. This was a jaw-dropping contrast to what I learnt at the soviet medical university and some post-graduate courses, where all the diseases related to alcohol, tobacco, or drug abuse were considered predominantly a result of the substance intake. In the Soviet discourse, the intake itself was understood as 'willful and deliberate' or immoral behavior which, in some cases, was to be rectified in prison-like treatment facilities. In the West, quite oppositely, substance abuse was seen rather as a consequence of a constellation of life-course adversities thoroughly considered by developmental psychology. This approach was obviously deeply ingrained in how practitioners diagnosed and treated their patients.

  17. The genome of Pelobacter carbinolicus reveals surprising metabolic capabilities and physiological features

    Directory of Open Access Journals (Sweden)

    Aklujkar Muktak

    2012-12-01

    Full Text Available Abstract Background The bacterium Pelobacter carbinolicus is able to grow by fermentation, syntrophic hydrogen/formate transfer, or electron transfer to sulfur from short-chain alcohols, hydrogen or formate; it does not oxidize acetate and is not known to ferment any sugars or grow autotrophically. The genome of P. carbinolicus was sequenced in order to understand its metabolic capabilities and physiological features in comparison with its relatives, acetate-oxidizing Geobacter species. Results Pathways were predicted for catabolism of known substrates: 2,3-butanediol, acetoin, glycerol, 1,2-ethanediol, ethanolamine, choline and ethanol. Multiple isozymes of 2,3-butanediol dehydrogenase, ATP synthase and [FeFe]-hydrogenase were differentiated and assigned roles according to their structural properties and genomic contexts. The absence of asparagine synthetase and the presence of a mutant tRNA for asparagine encoded among RNA-active enzymes suggest that P. carbinolicus may make asparaginyl-tRNA in a novel way. Catabolic glutamate dehydrogenases were discovered, implying that the tricarboxylic acid (TCA cycle can function catabolically. A phosphotransferase system for uptake of sugars was discovered, along with enzymes that function in 2,3-butanediol production. Pyruvate:ferredoxin/flavodoxin oxidoreductase was identified as a potential bottleneck in both the supply of oxaloacetate for oxidation of acetate by the TCA cycle and the connection of glycolysis to production of ethanol. The P. carbinolicus genome was found to encode autotransporters and various appendages, including three proteins with similarity to the geopilin of electroconductive nanowires. Conclusions Several surprising metabolic capabilities and physiological features were predicted from the genome of P. carbinolicus, suggesting that it is more versatile than anticipated.

  18. Virtual Volatility, an Elementary New Concept with Surprising Stock Market Consequences

    Science.gov (United States)

    Prange, Richard; Silva, A. Christian

    2006-03-01

    Textbook investors start by predicting the future price distribution, PDF, of a candidate stock (or portfolio) at horizon T, e.g. a year hence. A (log)normal PDF with center (=drift =expected return) μT and width (=volatility) σT is often assumed on Central Limit Theorem grounds, i.e. by a random walk of daily (log)price increments δs. The standard deviation, stdev, of historical (ex post) δs `s is usually a fair predictor of the coming year's (ex ante) stdev(δs) = σdaily, but the historical mean E(δs) at best roughly limits the true, to be predicted, drift by μtrueT˜ μhistT ± σhistT. Textbooks take a PDF with σ ˜ σdaily and μ as somehow known, as if accurate predictions of μ were possible. It is elementary and presumably new to argue that an average of PDF's over a range of μ values should be taken, e.g. an average over forecasts by different analysts. We estimate that this leads to a PDF with a `virtual' volatility σ ˜ 1.3σdaily. It is indeed clear that uncertainty in the value of the expected gain parameter increases the risk of investment in that security by most measures, e. g. Sharpe's ratio μT/σT will be 30% smaller because of this effect. It is significant and surprising that there are investments which benefit from this 30% virtual increase in the volatility

  19. Surprising results from abiotic enzyme digestion of dissolved organic matter at the molecular scale

    Science.gov (United States)

    Hess, N. J.; Tfaily, M. M.; Heredia-Langnar, A.; Rodriguez, L.; Purvine, E.; Todd-Brown, K. E.

    2016-12-01

    Sometimes even the simplest of experiments leads to unexpected results and new understanding. We extract dissolved organic matter using water from peat soil obtained from the S1 bog at the Marcell Experimental Forest in northern Minnesota. We characterized the dissolved organic matter in the water extract before and after adding glucosidase, peroxidase and β-N-Acetylglucosaminidase enzymes using electrospray Fourier transform ion cyclotron resonance mass spectrometry in negative ion mode. Based on mass measurement accuracy of less than 1 ppm for singly charged ions, we assigned putative chemical formula to greater than 80% of the measured mass spectrometry features. For each enzyme tested we are able to easily distinguish between the types and composition of dissolved organic molecules that are susceptible to enzyme degradation - and those that are not - based on the presence new compounds in reacted extracts and loss of compounds from the initial water extract. Next, we created a consensus molecular network analysis based on the neutral mass loss between the measured compounds for each enzyme. The connectivity within these networks suggested a unique, distinctive chemistry for each enzyme. Some results were expected, like the nondiscriminatory oxidation of organic molecules by peroxidase and preferential loss of lignin and tannin-like molecules by glucosidase. However, surprising results include the apparent reactivity of glucosidase enzymatic products to reassemble, forming larger mass organic molecules. While these experiments were conducted abiotically, these molecular-resolved results suggest that biotic enzymatic processes may result in product compounds with unexpected chemistry and reactivity, implying that our current conceptual model of microbial enzymatic activity may be overly simplistic.

  20. Young stars in old galaxies - surprising discovery with the world's leading telescopes

    Science.gov (United States)

    2002-06-01

    similar to the way a palaeontologist uses the skeletons of dinosaurs to deduce information about the era in which they lived. A surprising discovery The team combined images of a number of galaxies from Hubble's Wide Field and Planetary Camera 2 with infrared images obtained from the multi-mode ISAAC instrument on the 8.2m VLT Antu telescope at the ESO Paranal Observatory (Chile). To their great surprise, they discovered that many of the globular clusters in one of these galaxies, NGC 4365, a member of the large Virgo cluster of galaxies, were only a few thousand million years old, much younger than most of the other stars in this galaxy (roughly 12 thousand million years old). The astronomers were able to identify three major groups of stellar clusters. There is an old population of clusters of metal-poor stars, some clusters of old but metal-rich stars and now, seen for the first time, a population of clusters with young and metal-rich stars. These results have been fully confirmed by spectroscopic observations made with another of the world's giant telescopes, the 10-metre Keck on Hawaii. "It is a great pleasure to see two projects wholly or partly funded by Europe - VLT and Hubble - work in concert to produce such an important scientific result", says Piero Benvenuti, ESA Hubble Project Scientist. "The synergy between the most advanced ground and space telescopes continues to prove its effectiveness, paving the way to impressive new discoveries that would not otherwise be possible." The discovery of young globular clusters within old galaxies is surprising since the stars in the giant elliptical galaxies were until now believed to have formed during a single period early in the history of the Universe. It is now clear that some of the galaxies may be hiding their true nature and have indeed experienced much more recent periods of major star formation. Notes for editors This press release is issued in coordination between ESA and ESO. The Hubble Space Telescope project

  1. How to Produce a Surprise Ending for Readers---Writing Strategies in O. Henry’s The Last Leaf

    Institute of Scientific and Technical Information of China (English)

    姚雪莹

    2014-01-01

    “Twist ending”is well used by writers in a novel in order to leave readers a strong impression. In this essay, the author will focus on the narrative strategies that produce such a surprise ending in a short story, using as the example O. Henry’s The Last Leaf (1907). The author gives each of strategies O. Henry used in the novel a name and explains how it is used to produce a surprise ending, standing at the readers’perspective.

  2. Expression of Prothrombinase/fibroleukin Gene fg12 in Lung Impairment in a Murine Severe Acute Respiratory Syndrome Model

    Institute of Scientific and Technical Information of China (English)

    Wei-ming YAN; Jia-quan HUANG; Xiao-ping LUO; Qin NING

    2007-01-01

    To evaluate the role of murine fibrinogen like protein 2 (mfgl2) /fibroleukin in lung impairment in Severe acute respiratory syndrome (SARS), a murine SARS model induced by Murine hepatitis virus strain 3 (MHV-3) through trachea was established. Impressively, all the animals developed interstitial pneumonia with extensive hyaline membranes formation within alveoli, and presence of micro-vascular thrombosis in the pulmonary vessels. MHV-3 nucleocapsid gene transcripts were identified in multiple organs including lungs, spleen etc. As a representative proinflammatory gene, mfgl2 prothrombinase expression was evident in terminal and respiratory bronchioles, alveolar epithelia and infiltrated cells in the lungs associated with fibrin deposition and micro-vascular thrombosis. In summary, the established murine SARS model could mimic the pathologic characteristics of lungs in patients with SARS. Besides the physical damages due to virus replication in organs, the up-regulation of novel gene mfgl2 in lungs may play a vital role in the development of SARS associated lung damage.

  3. Common 5' beta-globin RFLP haplotypes harbour a surprising level of ancestral sequence mosaicism.

    Science.gov (United States)

    Webster, Matthew T; Clegg, John B; Harding, Rosalind M

    2003-07-01

    Blocks of linkage disequilibrium (LD) in the human genome represent segments of ancestral chromosomes. To investigate the relationship between LD and genealogy, we analysed diversity associated with restriction fragment length polymorphism (RFLP) haplotypes of the 5' beta-globin gene complex. Genealogical analyses were based on sequence alleles that spanned a 12.2-kb interval, covering 3.1 kb around the psibeta gene and 6.2 kb of the delta-globin gene and its 5' flanking sequence known as the R/T region. Diversity was sampled from a Kenyan Luo population where recent malarial selection has contributed to substantial LD. A single common sequence allele spanning the 12.2-kb interval exclusively identified the ancestral chromosome bearing the "Bantu" beta(s) (sickle-cell) RFLP haplotype. Other common 5' RFLP haplotypes comprised interspersed segments from multiple ancestral chromosomes. Nucleotide diversity was similar between psibeta and R/T-delta-globin but was non-uniformly distributed within the R/T-delta-globin region. High diversity associated with the 5' R/T identified two ancestral lineages that probably date back more than 2 million years. Within this genealogy, variation has been introduced into the 3' R/T by gene conversion from other ancestral chromosomes. Diversity in delta-globin was found to lead through parts of the main genealogy but to coalesce in a more recent ancestor. The well-known recombination hotspot is clearly restricted to the region 3' of delta-globin. Our analyses show that, whereas one common haplotype in a block of high LD represents a long segment from a single ancestral chromosome, others are mosaics of short segments from multiple ancestors related in genealogies of unsuspected complexity.

  4. Adult pallium transcriptomes surprise in not reflecting predicted homologies across diverse chicken and mouse pallial sectors.

    Science.gov (United States)

    Belgard, T Grant; Montiel, Juan F; Wang, Wei Zhi; García-Moreno, Fernando; Margulies, Elliott H; Ponting, Chris P; Molnár, Zoltán

    2013-08-01

    The thorniest problem in comparative neurobiology is the identification of the particular brain region of birds and reptiles that corresponds to the mammalian neocortex [Butler AB, Reiner A, Karten HJ (2011) Ann N Y Acad Sci 1225:14-27; Wang Y, Brzozowska-Prechtl A, Karten HJ (2010) Proc Natl Acad Sci USA 107(28):12676-12681]. We explored which genes are actively transcribed in the regions of controversial ancestry in a representative bird (chicken) and mammal (mouse) at adult stages. We conducted four analyses comparing the expression patterns of their 5,130 most highly expressed one-to-one orthologous genes that considered global patterns of expression specificity, strong gene markers, and coexpression networks. Our study demonstrates transcriptomic divergence, plausible convergence, and, in two exceptional cases, conservation between specialized avian and mammalian telencephalic regions. This large-scale study potentially resolves the complex relationship between developmental homology and functional characteristics on the molecular level and settles long-standing evolutionary debates.

  5. The Most Distant Mature Galaxy Cluster - Young, but surprisingly grown-up

    Science.gov (United States)

    2011-03-01

    Astronomers have used an armada of telescopes on the ground and in space, including the Very Large Telescope at ESO's Paranal Observatory in Chile to discover and measure the distance to the most remote mature cluster of galaxies yet found. Although this cluster is seen when the Universe was less than one quarter of its current age it looks surprisingly similar to galaxy clusters in the current Universe. "We have measured the distance to the most distant mature cluster of galaxies ever found", says the lead author of the study in which the observations from ESO's VLT have been used, Raphael Gobat (CEA, Paris). "The surprising thing is that when we look closely at this galaxy cluster it doesn't look young - many of the galaxies have settled down and don't resemble the usual star-forming galaxies seen in the early Universe." Clusters of galaxies are the largest structures in the Universe that are held together by gravity. Astronomers expect these clusters to grow through time and hence that massive clusters would be rare in the early Universe. Although even more distant clusters have been seen, they appear to be young clusters in the process of formation and are not settled mature systems. The international team of astronomers used the powerful VIMOS and FORS2 instruments on ESO's Very Large Telescope (VLT) to measure the distances to some of the blobs in a curious patch of very faint red objects first observed with the Spitzer space telescope. This grouping, named CL J1449+0856 [1], had all the hallmarks of being a very remote cluster of galaxies [2]. The results showed that we are indeed seeing a galaxy cluster as it was when the Universe was about three billion years old - less than one quarter of its current age [3]. Once the team knew the distance to this very rare object they looked carefully at the component galaxies using both the NASA/ESA Hubble Space Telescope and ground-based telescopes, including the VLT. They found evidence suggesting that most of the

  6. Mx1 and Mx2 key antiviral proteins are surprisingly lost in toothed whales.

    Science.gov (United States)

    Braun, Benjamin A; Marcovitz, Amir; Camp, J Gray; Jia, Robin; Bejerano, Gill

    2015-06-30

    Viral outbreaks in dolphins and other Delphinoidea family members warrant investigation into the integrity of the cetacean immune system. The dynamin-like GTPase genes Myxovirus 1 (Mx1) and Mx2 defend mammals against a broad range of viral infections. Loss of Mx1 function in human and mice enhances infectivity by multiple RNA and DNA viruses, including orthomyxoviruses (influenza A), paramyxoviruses (measles), and hepadnaviruses (hepatitis B), whereas loss of Mx2 function leads to decreased resistance to HIV-1 and other viruses. Here we show that both Mx1 and Mx2 have been rendered nonfunctional in Odontoceti cetaceans (toothed whales, including dolphins and orcas). We discovered multiple exon deletions, frameshift mutations, premature stop codons, and transcriptional evidence of decay in the coding sequence of both Mx1 and Mx2 in four species of Odontocetes. We trace the likely loss event for both proteins to soon after the divergence of Odontocetes and Mystocetes (baleen whales) ∼33-37 Mya. Our data raise intriguing questions as to what drove the loss of both Mx1 and Mx2 genes in the Odontoceti lineage, a double loss seen in none of 56 other mammalian genomes, and suggests a hitherto unappreciated fundamental genetic difference in the way these magnificent mammals respond to viral infections.

  7. Sermon and surprise: The meaning of scheduling in broadcast radio history - and - CBC Radio 3: A disquieting revolution

    OpenAIRE

    Sahota, Anu

    2006-01-01

    Essay 1 : 'Sermon & Surprise' explores the importance of scheduling to radio's communicative uses. The essay argues that its capacity for continuous transmission and promotion of shared listening is unique to terrestrial radio. The strengths of traditional radio relative to contemporary on-demand audio media are explored. Early Canadian and British broadcasting policies and scheduling practices demonstrate how radio's programming conceits may innovatively accommodate broadcasting philosop...

  8. Surprisal analysis characterizes the free energy time course of cancer cells undergoing epithelial-to-mesenchymal transition.

    Science.gov (United States)

    Zadran, Sohila; Arumugam, Rameshkumar; Herschman, Harvey; Phelps, Michael E; Levine, R D

    2014-09-09

    The epithelial-to-mesenchymal transition (EMT) initiates the invasive and metastatic behavior of many epithelial cancers. Mechanisms underlying EMT are not fully known. Surprisal analysis of mRNA time course data from lung and pancreatic cancer cells stimulated to undergo TGF-β1-induced EMT identifies two phenotypes. Examination of the time course for these phenotypes reveals that EMT reprogramming is a multistep process characterized by initiation, maturation, and stabilization stages that correlate with changes in cell metabolism. Surprisal analysis characterizes the free energy time course of the expression levels throughout the transition in terms of two state variables. The landscape of the free energy changes during the EMT for the lung cancer cells shows a stable intermediate state. Existing data suggest this is the previously proposed maturation stage. Using a single-cell ATP assay, we demonstrate that the TGF-β1-induced EMT for lung cancer cells, particularly during the maturation stage, coincides with a metabolic shift resulting in increased cytosolic ATP levels. Surprisal analysis also characterizes the absolute expression levels of the mRNAs and thereby examines the homeostasis of the transcription system during EMT.

  9. Comparative genomics reveals surprising divergence of two closely related strains of uncultivated UCYN-A cyanobacteria.

    Science.gov (United States)

    Bombar, Deniz; Heller, Philip; Sanchez-Baracaldo, Patricia; Carter, Brandon J; Zehr, Jonathan P

    2014-12-01

    Marine planktonic cyanobacteria capable of fixing molecular nitrogen (termed 'diazotrophs') are key in biogeochemical cycling, and the nitrogen fixed is one of the major external sources of nitrogen to the open ocean. Candidatus Atelocyanobacterium thalassa (UCYN-A) is a diazotrophic cyanobacterium known for its widespread geographic distribution in tropical and subtropical oligotrophic oceans, unusually reduced genome and symbiosis with a single-celled prymnesiophyte alga. Recently a novel strain of this organism was also detected in coastal waters sampled from the Scripps Institute of Oceanography pier. We analyzed the metagenome of this UCYN-A2 population by concentrating cells by flow cytometry. Phylogenomic analysis provided strong bootstrap support for the monophyly of UCYN-A (here called UCYN-A1) and UCYN-A2 within the marine Crocosphaera sp. and Cyanothece sp. clade. UCYN-A2 shares 1159 of the 1200 UCYN-A1 protein-coding genes (96.6%) with high synteny, yet the average amino-acid sequence identity between these orthologs is only 86%. UCYN-A2 lacks the same major pathways and proteins that are absent in UCYN-A1, suggesting that both strains can be grouped at the same functional and ecological level. Our results suggest that UCYN-A1 and UCYN-A2 had a common ancestor and diverged after genome reduction. These two variants may reflect adaptation of the host to different niches, which could be coastal and open ocean habitats.

  10. Gene Evolution: Getting Something from Nothing.

    Science.gov (United States)

    Weisman, Caroline M; Eddy, Sean R

    2017-07-10

    New genes arise from pre-existing genes, but some de novo origin from non-genic sequence also seems plausible. A new study has surprisingly concluded that 25% of random DNA sequences yield beneficial products when expressed in bacteria. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Communication Management and Trust: Their Role in Building Resilience to "Surprises" Such As Natural Disasters, Pandemic Flu, and Terrorism

    Directory of Open Access Journals (Sweden)

    P. H. Longstaff

    2008-06-01

    Full Text Available In times of public danger such as natural disasters and health emergencies, a country's communication systems will be some of its most important assets because access to information will make individuals and groups more resilient. Communication by those charged with dealing with the situation is often critical. We analyzed reports from a wide variety of crisis incidents and found a direct correlation between trust and an organization's preparedness and internal coordination of crisis communication and the effectiveness of its leadership. Thus, trust is one of the most important variables in effective communication management in times of "surprise."

  12. Gene Cluster Statistics with Gene Families

    Science.gov (United States)

    Durand, Dannie

    2009-01-01

    Identifying genomic regions that descended from a common ancestor is important for understanding the function and evolution of genomes. In distantly related genomes, clusters of homologous gene pairs are evidence of candidate homologous regions. Demonstrating the statistical significance of such “gene clusters” is an essential component of comparative genomic analyses. However, currently there are no practical statistical tests for gene clusters that model the influence of the number of homologs in each gene family on cluster significance. In this work, we demonstrate empirically that failure to incorporate gene family size in gene cluster statistics results in overestimation of significance, leading to incorrect conclusions. We further present novel analytical methods for estimating gene cluster significance that take gene family size into account. Our methods do not require complete genome data and are suitable for testing individual clusters found in local regions, such as contigs in an unfinished assembly. We consider pairs of regions drawn from the same genome (paralogous clusters), as well as regions drawn from two different genomes (orthologous clusters). Determining cluster significance under general models of gene family size is computationally intractable. By assuming that all gene families are of equal size, we obtain analytical expressions that allow fast approximation of cluster probabilities. We evaluate the accuracy of this approximation by comparing the resulting gene cluster probabilities with cluster probabilities obtained by simulating a realistic, power-law distributed model of gene family size, with parameters inferred from genomic data. Surprisingly, despite the simplicity of the underlying assumption, our method accurately approximates the true cluster probabilities. It slightly overestimates these probabilities, yielding a conservative test. We present additional simulation results indicating the best choice of parameter values for data

  13. No surprises, please!

    Science.gov (United States)

    Davis, Dena S

    2013-01-01

    This narrative symposium examines the relationship of bioethics practice to personal experiences of illness. A call for stories was developed by Tod Chambers, the symposium editor, and editorial staff and was sent to several commonly used bioethics listservs and posted on the Narrative Inquiry in Bioethics website. The call asked authors to relate a personal story of being ill or caring for a person who is ill, and to describe how this affected how they think about bioethical questions and the practice of medicine. Eighteen individuals were invited to submit full stories based on review of their proposals. Twelve stories are published in this symposium, and six supplemental stories are published online only through Project MUSE. Authors explore themes of vulnerability, suffering, communication, voluntariness, cultural barriers, and flaws in local healthcare systems through stories about their own illnesses or about caring for children, partners, parents and grandparents. Commentary articles by Arthur Frank, Bradley Lewis, and Carol Taylor follow the collection of personal narratives.

  14. Tohoku earthquake: a surprise?

    CERN Document Server

    Kagan, Yan Y

    2011-01-01

    We consider three issues related to the 2011 Tohoku mega-earthquake: (1) how to evaluate the earthquake maximum size in subduction zones, (2) what is the repeat time for the largest earthquakes in Tohoku area, and (3) what are the possibilities of short-term forecasts during the 2011 sequence. There are two quantitative methods which can be applied to estimate the maximum earthquake size: a statistical analysis of the available earthquake record and the moment conservation principle. The latter technique studies how much of the tectonic deformation rate is released by earthquakes. For the subduction zones, the seismic or historical record is not sufficient to provide a reliable statistical measure of the maximum earthquake. The moment conservation principle yields consistent estimates of maximum earthquake size: for all the subduction zones the magnitude is of the order 9.0--9.7, and for major subduction zones the maximum earthquake size is statistically indistinguishable. Starting in 1999 we have carried out...

  15. A Pleasant Goat Surprise

    Institute of Scientific and Technical Information of China (English)

    JING XIAOLEI

    2010-01-01

    @@ For decades,Chinese children have sat in front of television sets mesmerized as American cartoon cat Tom chased mouse rival Jerry,or as the Japanese manga robot feline Doraemon helped his schoolboy companion Nobita Nobi.Now,the animated tables are turning and foreign kids are able to enjoy Chinese cartoons from the comfort of their couches.

  16. More statistics, less surprise

    CERN Multimedia

    Antonella Del Rosso & the LHCb collaboration

    2013-01-01

    The LHCb collaboration has recently announced new results for a parameter that measures the CP violation effect in particles containing charm quarks. The new values obtained with a larger data set and with a new independent method are showing that the effect is smaller than previous measurements had  suggested. The parameter is back into the Standard Model picture.   CP violation signals – in particles containing charm quarks, such as the D0 particle, is a powerful probe of new physics. Indeed, such effects could result in unexpected values of parameters whose expectation values in the Standard Model are known. Although less precise than similar approaches used in particles made of b quarks, the investigation of the charm system has proven  to be intriguing. The LHCb collaboration has reported new measurements of ΔACP, the difference in CP violation between the D0→K+K– and D0→π+π– decays. The results are ob...

  17. Monotony and Surprise

    Science.gov (United States)

    Apostolico, Alberto

    This paper reviews models and tools emerged in recent years in the author’s work in connection with the discovery of interesting or anomalous patterns in sequences. Whereas customary approaches to pattern discovery proceed from either a statistical or a syntactic characterization alone, the approaches described here present the unifying feature of combining these two descriptors in a solidly intertwined, composite paradigm, whereby both syntactic structure and occurrence lists concur to define and identify a pattern in a subject. In turn, this supports a natural notion of pattern saturation, which enables one to partition patterns into equivalence classes over intervals of monotonicity of commonly adopted scores, in such a way that the subset of class representatives, consisting solely of saturated patterns, suffices to account for all patterns in the subject. The benefits at the outset consist not only of an increased descriptive power, but especially of a mitigation of the often unmanageable roster of candidates unearthed in a discovery attempt, and of the daunting computational burden that goes with it.

  18. Surprised by selectivity

    NARCIS (Netherlands)

    de Jong, Krijn P|info:eu-repo/dai/nl/06885580X

    2016-01-01

    Lower olefins, particularly ethylene (C2H4), propylene (C3H6), and butylene (C4H8), are important intermediates in the manufacture of products such as plastics, solvents, paints, and medicines. They are produced worldwide in amounts exceeding 200 million tons per year (see the photo) (1), mostly

  19. The surprising superconductor

    Directory of Open Access Journals (Sweden)

    Taner Yildirim

    2002-04-01

    The serendipitous discovery by Akimitsu’s group1 of the superconductivity of MgB2 at Tc=39 K, almost twice the temperature of other simple intermetallic compounds, has sparked a race to uncover its basic properties and to find other related diborides with even higher Tcs. After the first announcement, the number of preprints appearing on the Los Alamos preprint server (Fig. 1 grew almost exponentially, reaching a maximum of about 60 studies in March (two papers a day, then decreasing linearly down to a paper every other day in August, and staying steady at about this rate until now. During the first year of the MgB2 era, more than 300 studies were published, exploring both fundamental and practical issues, such as the mechanism of the superconductivity; synthesis of MgB2 in the form of powder, thin films, wires, and tapes; the effect on Tc of substitution with various elements and on critical current and fields.

  20. Surprises in aperiodic diffraction

    CERN Document Server

    Baake, Michael

    2009-01-01

    Mathematical diffraction theory is concerned with the diffraction image of a given structure and the corresponding inverse problem of structure determination. In recent years, the understanding of systems with continuous and mixed spectra has improved considerably. Moreover, the phenomenon of homometry shows various unexpected new facets. Here, we report on some of the recent results in an exemplary and informal fashion.

  1. Jordan: Surprisingly Stable

    OpenAIRE

    Ådnegard, Elisabeth

    2014-01-01

    Over the years, research has demonstrated that conflict spreads to the host country as a consequence of massive influx of refugees. Most studies gathered empirical evidence from African countries and focused on cases where conflict had already spread. In contrast to this literature, the main objective of this thesis is to examine the absence of conflict in Jordan after receiving Syrian refugees that amount to about 10 percent of Jordan s original population over the past three years, 2011-201...

  2. Surprising quantum bounces

    CERN Document Server

    Nesvizhevsky, Valery

    2015-01-01

    This unique book demonstrates the undivided unity and infinite diversity of quantum mechanics using a single phenomenon: quantum bounces of ultra-cold particles. Various examples of such "quantum bounces" are: gravitational quantum states of ultra-cold neutrons (the first observed quantum states of matter in a gravitational field), the neutron whispering gallery (an observed matter-wave analog of the whispering gallery effect well known in acoustics and for electromagnetic waves), and gravitational and whispering gallery states for anti-matter atoms that remain to be observed. These quantum states are an invaluable tool in the search for additional fundamental short-range forces, for exploring the gravitational interaction and quantum effects of gravity, for probing physics beyond the standard model, and for furthering studies into the foundations of quantum mechanics, quantum optics, and surface science.

  3. No More Surprises.

    Science.gov (United States)

    Sorrel, Amy

    2016-05-01

    Texas Medical Association research shows that health plans' shrinking networks, caps on payments for medical care, inaccurate directories, and other tactics - not physician billing - are bearing down on patients in the form of unexpected, out-of-network balance bills.

  4. Surprising radiation detectors

    CERN Document Server

    Fleischer, Robert

    2003-01-01

    Radiation doses received by the human body can be measured indirectly and retrospectively by counting the tracks left by particles in ordinary objects like pair of spectacles, glassware, compact disks...This method has been successfully applied to determine neutron radiation doses received 50 years ago on the Hiroshima site. Neutrons themselves do not leave tracks in bulk matter but glass contains atoms of uranium that may fission when hurt by a neutron, the recoil of the fission fragments generates a track that is detectable. The most difficult is to find adequate glass items and to evaluate the radiation shield they benefited at their initial place. The same method has been used to determine the radiation dose due to the pile-up of radon in houses. In that case the tracks left by alpha particles due to the radioactive decay of polonium-210 have been counted on the superficial layer of the window panes. Other materials like polycarbonate plastics have been used to determine the radiation dose due to heavy io...

  5. Neurotransmitter Switching? No Surprise.

    Science.gov (United States)

    Spitzer, Nicholas C

    2015-06-03

    Among the many forms of brain plasticity, changes in synaptic strength and changes in synapse number are particularly prominent. However, evidence for neurotransmitter respecification or switching has been accumulating steadily, both in the developing nervous system and in the adult brain, with observations of transmitter addition, loss, or replacement of one transmitter with another. Natural stimuli can drive these changes in transmitter identity, with matching changes in postsynaptic transmitter receptors. Strikingly, they often convert the synapse from excitatory to inhibitory or vice versa, providing a basis for changes in behavior in those cases in which it has been examined. Progress has been made in identifying the factors that induce transmitter switching and in understanding the molecular mechanisms by which it is achieved. There are many intriguing questions to be addressed.

  6. Surprise Trips 

    DEFF Research Database (Denmark)

    Korn, Matthias; Kawash, Raghid; Andersen, Lisbet Møller

    2010-01-01

    Little treasures in nature often go unnoticed by visitors when roaming about in a national park. Ubiquitous technology with its less intrusive character may be apt to enhance this natural experience of exploration. In this paper, we report on a system that augments this experience. It builds on t...

  7. Microhydrodynamics of deformable particles: surprising responses of drops and vesicles to uniform electric field or shear flow

    Science.gov (United States)

    Vlahovska, Petia

    2015-11-01

    Particle motion in a viscous fluid is a classic problem that continues to surprise researchers. In this talk, I will discuss some intriguing, experimentally-observed behaviors of droplets and giant vesicles (cell-size lipid membrane sacs) in electric or flow fields. In a uniform electric field, a droplet deforms into an ellipsoid that can either be steadily tilted relative to the applied field direction or undergo unsteady motions (periodic shape oscillations or irregular flipping); a spherical vesicle can adopt a transient square shape or reversibly porate. In a steady shear flow, a vesicle can tank-tread, tumble or swing. Theoretical models show that the nonlinear drop dynamics originates from the interplay of Quincke rotation and interface deformation, while the vesicle dynamics stems from the membrane inextensibility. The practical motivation for this research lies in an improved understanding of technologies that rely on the manipulation of drops and cells by flow or electric fields.

  8. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  9. The plant host can affect the encapsidation of brome mosaic virus (BMV) RNA: BMV virions are surprisingly heterogeneous.

    Science.gov (United States)

    Ni, Peng; Vaughan, Robert C; Tragesser, Brady; Hoover, Haley; Kao, C Cheng

    2014-03-01

    Brome mosaic virus (BMV) packages its genomic and subgenomic RNAs into three separate viral particles. BMV purified from barley, wheat, and tobacco have distinct relative abundances of the encapsidated RNAs. We seek to identify the basis for the host-dependent differences in viral RNA encapsidation. Sequencing of the viral RNAs revealed recombination events in the 3' untranslated region of RNA1 of BMV purified from barley and wheat, but not from tobacco. However, the relative amounts of the BMV RNAs that accumulated in barley and wheat are similar and RNA accumulation is not sufficient to account for the difference in RNA encapsidation. Virions purified from barley and wheat were found to differ in their isoelectric points, resistance to proteolysis, and contacts between the capsid residues and the RNA. Mass spectrometric analyses revealed that virions from the three hosts had different post-translational modifications that should impact the physiochemical properties of the virions. Another major source of variation in RNA encapsidation was due to the purification of BMV particles to homogeneity. Highly enriched BMV present in lysates had a surprising range of sizes, buoyant densities, and distinct relative amounts of encapsidated RNAs. These results show that the encapsidated BMV RNAs reflect a combination of host effects on the physiochemical properties of the viral capsids and the enrichment of a subset of virions. The previously unexpected heterogeneity in BMV should influence the timing of the infection and also the host innate immune responses.

  10. Benford's law predicted digit distribution of aggregated income taxes: the surprising conformity of Italian cities and regions

    Science.gov (United States)

    Mir, Tariq Ahmad; Ausloos, Marcel; Cerqueti, Roy

    2014-11-01

    The yearly aggregated tax income data of all, more than 8000, Italian municipalities are analyzed for a period of five years, from 2007 to 2011, to search for conformity or not with Benford's law, a counter-intuitive phenomenon observed in large tabulated data where the occurrence of numbers having smaller initial digits is more favored than those with larger digits. This is done in anticipation that large deviations from Benford's law will be found in view of tax evasion supposedly being widespread across Italy. Contrary to expectations, we show that the overall tax income data for all these years is in excellent agreement with Benford's law. Furthermore, we also analyze the data of Calabria, Campania and Sicily, the three Italian regions known for strong presence of mafia, to see if there are any marked deviations from Benford's law. Again, we find that all yearly data sets for Calabria and Sicily agree with Benford's law whereas only the 2007 and 2008 yearly data show departures from the law for Campania. These results are again surprising in view of underground and illegal nature of economic activities of mafia which significantly contribute to tax evasion. Some hypothesis for the found conformity is presented.

  11. Medial superior olivary neurons receive surprisingly few excitatory and inhibitory inputs with balanced strength and short-term dynamics.

    Science.gov (United States)

    Couchman, Kiri; Grothe, Benedikt; Felmy, Felix

    2010-12-15

    Neurons in the medial superior olive (MSO) process microsecond interaural time differences, the major cue for localizing low-frequency sounds, by comparing the relative arrival time of binaural, glutamatergic excitatory inputs. This coincidence detection mechanism is additionally shaped by highly specialized glycinergic inhibition. Traditionally, it is assumed that the binaural inputs are conveyed by many independent fibers, but such an anatomical arrangement may decrease temporal precision. Short-term depression on the other hand might enhance temporal fidelity during ongoing activity. For the first time we show that binaural coincidence detection in MSO neurons may require surprisingly few but strong inputs, challenging long-held assumptions about mammalian coincidence detection. This study exclusively uses adult gerbils for in vitro electrophysiology, single-cell electroporation and immunohistochemistry to characterize the size and short-term plasticity of inputs to the MSO. We find that the excitatory and inhibitory inputs to the MSO are well balanced both in strength and short-term dynamics, redefining this fastest of all mammalian coincidence detector circuits.

  12. Food insecurity and mental health: surprising trends among community health volunteers in Addis Ababa, Ethiopia during the 2008 food crisis.

    Science.gov (United States)

    Maes, Kenneth C; Hadley, Craig; Tesfaye, Fikru; Shifferaw, Selamawit

    2010-05-01

    The 2008 food crisis may have increased household food insecurity and caused distress among impoverished populations in low-income countries. Policy researchers have attempted to quantify the impact that a sharp rise in food prices might have on population wellbeing by asking what proportion of households would drop below conventional poverty lines given a set increase in prices. Our understanding of the impact of food crises can be extended by conducting micro-level ethnographic studies. This study examined self-reported household food insecurity (FI) and common mental disorders (CMD) among 110 community health AIDS care volunteers living in Addis Ababa, Ethiopia during the height of the 2008 food crisis. We used generalized estimating equations that account for associations between responses given by the same participants over 3 survey rounds during 2008, to model the longitudinal response profiles of FI, CMD symptoms, and socio-behavioral and micro-economic covariates. To help explain the patterns observed in the response profiles and regression results, we examine qualitative data that contextualize the cognition and reporting behavior of AIDS care volunteers, as well as potential observation biases inherent in longitudinal, community-based research. Our data show that food insecurity is highly prevalent, that is it associated with household economic factors, and that it is linked to mental health. Surprisingly, the volunteers in this urban sample did not report increasingly severe FI or CMD during the peak of the 2008 food crisis. This is a counter-intuitive result that would not be predicted in analyses of population-level data such as those used in econometrics simulations. But when these results are linked to real people in specific urban ecologies, they can improve our understanding of the psychosocial consequences of food price shocks.

  13. Surprisingly low compliance to local guidelines for risk factor based screening for gestational diabetes mellitus - A population-based study

    Directory of Open Access Journals (Sweden)

    Winkvist Anna

    2009-11-01

    Full Text Available Abstract Background Screening for gestational diabetes mellitus (GDM is routine during pregnancy in many countries in the world. The screening programs are either based on general screening offered to all pregnant women or risk factor based screening stipulated in local clinical guidelines. The aims of this study were to investigate: 1 the compliance with local guidelines of screening for GDM and 2 the outcomes of pregnancy and birth in relation to risk factors of GDM and whether or not exposed to oral glucose tolerance test (OGTT. Methods This study design was a population-based retrospective cross-sectional study of 822 women. A combination of questionnaire data and data collected from medical records was applied. Compliance to the local guidelines of risk factor based screening for GDM was examined and a comparison of outcomes of pregnancy and delivery in relation to risk factor groups for GDM was performed. Results Of the 822 participants, 257 (31.3% women fulfilled at least one criterion for being exposed to screening for GDM according to the local clinical guidelines. However, only 79 (30.7% of these women were actually exposed to OGTT and of those correctly exposed for screening, seven women were diagnosed with GDM. Women developing risk factors for GDM during pregnancy had a substantially increased risk of giving birth to an infant with macrosomia. Conclusion Surprisingly low compliance with the local clinical guidelines for screening for GDM during pregnancy was found. Furthermore, the prevalence of the risk factors of GDM in our study was almost doubled compared to previous Swedish studies. Pregnant women developing risk factors of GDM during pregnancy were found to be at substantially increased risk of giving birth to an infant with macrosomia. There is a need of actions improving compliance to the local guidelines.

  14. How do 'housekeeping' genes control organogenesis?--Unexpected new findings on the role of housekeeping genes in cell and organ differentiation.

    Science.gov (United States)

    Tsukaya, Hirokazu; Byrne, Mary E; Horiguchi, Gorou; Sugiyama, Munetaka; Van Lijsebettens, Mieke; Lenhard, Michael

    2013-01-01

    In recent years, an increasing number of mutations in what would appear to be 'housekeeping genes' have been identified as having unexpectedly specific defects in multicellular organogenesis. This is also the case for organogenesis in seed plants. Although it is not surprising that loss-of-function mutations in 'housekeeping' genes result in lethality or growth retardation, it is surprising when (1) the mutant phenotype results from the loss of function of a 'housekeeping' gene and (2) the mutant phenotype is specific. In this review, by defining housekeeping genes as those encoding proteins that work in basic metabolic and cellular functions, we discuss unexpected links between housekeeping genes and specific developmental processes. In a surprising number of cases housekeeping genes coding for enzymes or proteins with functions in basic cellular processes such as transcription, post-transcriptional modification, and translation affect plant development.

  15. A surprise at the bottom of the main sequence: Rapid rotation and NO H-alpha emission

    Science.gov (United States)

    Basri, Gibor; Marcy, Geoffrey W.

    1995-01-01

    We report Kech Observatory high-resolution echelle spectra from 640-850 nm for eight stars near the faint end of the main sequence. These spectra are the highest resolution spectra of such late-type stars, and clearly resolve the TiO, VO, and atomic lines. The sample includes the field brown-dwarf candidate, BRI 0021-0214 (M9.5+). Very unexpectedly, it shows the most rapid rotation in the entire samples, v sin i approximately 40 km/s, which is 20x faster than typical field nonemission M stars. Equally surprising is that BRI 0021 exhibits no emission or absorptionat H-alpha. We argue that this absence is not simply due to its cool photosphere, but that stellar activity declines in a fundamental way at the end of the main sequence. As it is the first very late M dwarf observed at high spectral resolution, BRI 0021 may be signaling a qualitative change in the angular momentum loss rate among the lowest mass stars. Conventionally, its rapid rotation would have marked BRI 0021 as very young, consistent with the selection effect which arises if the latest-type dwarfs are really brown dwarfs on cooling curves. In any case, it is unprecedented to find no sign of stellar activity in such a rapidly rotating convective star. We also discuss the possible conflict between this observation and the extremely strong H-alpha seen in another very cool star, PC 0025+0447. Extrapolation of M-L relations for BRI 0021 yields M approximately 0.065 solar mass, and the other sample objects have expected masses near the H-burning limit. These include two Pleiades brown-dwarf candidates, four field M6 dwarfs and one late-type T Tauri star. The two Pleiades M6 dwarfs have v sin i of 26 and 37 km/s, H-alpha in emission, and radial velocities consistent with Pleiades M6 dwarfs have v sin i of 26 and 37 km/s, H-alpha in emission, and radial velocities consistent with Pleiades membership. Similarly, the late-type T Tauri star has v sin i approximately 30 km/s and H alpha emission indicate of its

  16. Surprising Impact of Remote Groups on the Folding-Unfolding and Dimer-Chain Equilibria of Bifunctionl H-Bonding Unimers

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Rui; Cheng, Shuang; Baker, Erin Shammel; Smith, Richard D.; Zeng, Xiao Cheng; Gong, Bing

    2016-01-28

    Oligoamide 1, consisting of two H-bonding units linked by a trimethylene linker, was previously found to form a very stable, folded dimer. In this work, replacing the side chains and end groups of 1 led to derivatives that show the surprising impact of end groups on the folding and dimer-chain equilibria of the resultant molecules.

  17. Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

    2013-02-15

    Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

  18. Chromatin analysis of occluded genes

    Science.gov (United States)

    Lee, Jae Hyun; Gaetz, Jedidiah; Bugarija, Branimir; Fernandes, Croydon J.; Snyder, Gregory E.; Bush, Eliot C.; Lahn, Bruce T.

    2009-01-01

    We recently described two opposing states of transcriptional competency. One is termed ‘competent’ whereby a gene is capable of responding to trans-acting transcription factors of the cell, such that it is active if appropriate transcriptional activators are present, though it can also be silent if activators are absent or repressors are present. The other is termed ‘occluded’ whereby a gene is silenced by cis-acting, chromatin-based mechanisms in a manner that blocks it from responding to trans-acting factors, such that it is silent even when activators are present in the cellular milieu. We proposed that gene occlusion is a mechanism by which differentiated cells stably maintain their phenotypic identities. Here, we describe chromatin analysis of occluded genes. We found that DNA methylation plays a causal role in maintaining occlusion for a subset of occluded genes. We further examined a variety of other chromatin marks typically associated with transcriptional silencing, including histone variants, covalent histone modifications and chromatin-associated proteins. Surprisingly, we found that although many of these marks are robustly linked to silent genes (which include both occluded genes and genes that are competent but silent), none is linked specifically to occluded genes. Although the observation does not rule out a possible causal role of these chromatin marks in occlusion, it does suggest that these marks might be secondary effect rather than primary cause of the silent state in many genes. PMID:19380460

  19. Plant genetics: gene transfer from parasitic to host plants.

    Science.gov (United States)

    Mower, Jeffrey P; Stefanović, Sasa; Young, Gregory J; Palmer, Jeffrey D

    2004-11-11

    Plant mitochondrial genes are transmitted horizontally across mating barriers with surprising frequency, but the mechanism of transfer is unclear. Here we describe two new cases of horizontal gene transfer, from parasitic flowering plants to their host flowering plants, and present phylogenetic and biogeographic evidence that this occurred as a result of direct physical contact between the two. Our findings complement the discovery that genes can be transferred in the opposite direction, from host to parasite plant.

  20. Enlarged Multilocus Data set Provides Surprisingly Younger Time of Origin for the Plethodontidae, the Largest Family of Salamanders.

    Science.gov (United States)

    Shen, Xing-Xing; Liang, Dan; Chen, Meng-Yun; Mao, Rong-Li; Wake, David B; Zhang, Peng

    2016-01-01

    Deep phylogenetic relationships of the largest salamander family Plethodontidae have been difficult to resolve, probably reflecting a rapid diversification early in their evolutionary history. Here, data from 50 independent nuclear markers (total 48,582 bp) are used to reconstruct the phylogeny and divergence times for plethodontid salamanders, using both concatenation and coalescence-based species tree analyses. Our results robustly resolve the position of the enigmatic eastern North American four-toed salamander (Hemidactylium) as the sister taxon of Batrachoseps + Tribe Bolitoglossini, thus settling a long-standing question. Furthermore, we statistically reject sister taxon status of Karsenia and Hydromantes, the only plethodontids to occur outside the Americas, leading us to new biogeographic hypotheses. Contrary to previous long-standing arguments that plethodontid salamanders are an old lineage originating in the Cretaceous (more than 90 Ma), our analyses lead to the hypothesis that these salamanders are much younger, arising close to the K-T boundary (~66 Ma). These time estimates are highly stable using alternative calibration schemes and dating methods. Our data simulation highlights the potential risk of making strong arguments about phylogenetic timing based on inferences from a handful of nuclear genes, a common practice. Based on the newly obtained timetree and ancestral area reconstruction results, we argue that (i) the classic "Out of Appalachia" hypothesis of plethodontid origins is problematic; (ii) the common ancestor of extant plethodontids may have originated in northwestern North America in the early Paleocene; (iii) origins of Eurasian plethodontids likely result from two separate dispersal events from western North America via Beringia in the late Eocene (~42 Ma) and the early Miocene (~23 Ma), respectively.

  1. Transfer of engineered genes from crop to wild plants

    DEFF Research Database (Denmark)

    Bagger Jørgensen, Rikke; Hauser, T.P.; Mikkelsen, T.R.;

    1996-01-01

    The escape of engineered genes - genes inserted using recombinant DNA techniques - from cultivated plants to wild or weedy relatives has raised concern about possible risks to the environment or to health. The media have added considerably to public concern by suggesting that such gene escape...... is a new and rather unexpected phenomenon. However, transfer of engineered genes between plants is not at-all surprising, because it is mediated by exactly the same mechanisms as those responsible for transferring endogenous plant genes: it takes place by sexual crosses, with pollen as the carrier...

  2. DNA-energetics-based analyses suggest additional genes in prokaryotes

    Indian Academy of Sciences (India)

    Garima Khandelwal; Jalaj Gupta; B Jayaram

    2012-07-01

    We present here a novel methodology for predicting new genes in prokaryotic genomes on the basis of inherent energetics of DNA. Regions of higher thermodynamic stability were identified, which were filtered based on already known annotations to yield a set of potentially new genes. These were then processed for their compatibility with the stereo-chemical properties of proteins and tripeptide frequencies of proteins in Swissprot data, which results in a reliable set of new genes in a genome. Quite surprisingly, the methodology identifies new genes even in well-annotated genomes. Also, the methodology can handle genomes of any GC-content, size and number of annotated genes.

  3. Moderate rates of late Quaternary slip along the northwestern margin of the Basin and Range Province, Surprise Valley fault, northeastern California

    Science.gov (United States)

    Personius, Stephen F.; Crone, Anthony J.; Machette, Michael N.; Mahan, Shannon; Lidke, David J.

    2009-01-01

    The 86-km-long Surprise Valley normal fault forms part of the active northwestern margin of the Basin and Range province in northeastern California. We use trench mapping and radiocarbon, luminescence, and tephra dating to estimate displacements and timing of the past five surface-rupturing earthquakes on the central part of the fault near Cedarville. A Bayesian OxCal analysis of timing constraints indicates earthquake times of 18.2 ± 2.6, 10.9 ± 3.2, 8.5 ± 0.5, 5.8 ± 1.5, and 1.2 ± 0.1 ka. These data yield recurrence intervals of 7.3 ± 4.1, 2.5 ± 3.2, 2.7 ± 1.6, and 4.5 ± 1.5 ka and an elapsed time of 1.2 ± 0.1 ka since the latest surface-rupturing earthquake. Our best estimate of latest Quaternary vertical slip rate is 0.6 ?? 0.1 mm/a. This late Quaternary rate is remarkably similar to long-term (8-14 Ma) minimum vertical slip rates (>0.4-0.5 ± 0.3 mm/a) calculated from recently acquired seismic reflection and chronologic and structural data in Surprise Valley and the adjacent Warner Mountains. However, our slip rate yields estimates of extension that are lower than recent campaign GPS determinations by factors of 1.5-4 unless the fault has an unusually shallow (30°-35°) dip as suggested by recently acquired seismic reflection data. Coseismic displacements of 2-4.5 ± 1 m documented in the trench and probable rupture lengths of 53-65 km indicate a history of latest Quaternary earthquakes of M 6.8-7.3 on the central part of the. Surprise Valley fault.

  4. Surprisal analysis of transcripts expression levels in the presence of noise: a reliable determination of the onset of a tumor phenotype.

    Directory of Open Access Journals (Sweden)

    Ayelet Gross

    Full Text Available Towards a reliable identification of the onset in time of a cancer phenotype, changes in transcription levels in cell models were tested. Surprisal analysis, an information-theoretic approach grounded in thermodynamics, was used to characterize the expression level of mRNAs as time changed. Surprisal Analysis provides a very compact representation for the measured expression levels of many thousands of mRNAs in terms of very few - three, four - transcription patterns. The patterns, that are a collection of transcripts that respond together, can be assigned definite biological phenotypic role. We identify a transcription pattern that is a clear marker of eventual malignancy. The weight of each transcription pattern is determined by surprisal analysis. The weight of this pattern changes with time; it is never strictly zero but it is very low at early times and then rises rather suddenly. We suggest that the low weights at early time points are primarily due to experimental noise. We develop the necessary formalism to determine at what point in time the value of that pattern becomes reliable. Beyond the point in time when a pattern is deemed reliable the data shows that the pattern remain reliable. We suggest that this allows a determination of the presence of a cancer forewarning. We apply the same formalism to the weight of the transcription patterns that account for healthy cell pathways, such as apoptosis, that need to be switched off in cancer cells. We show that their weight eventually falls below the threshold. Lastly we discuss patient heterogeneity as an additional source of fluctuation and show how to incorporate it within the developed formalism.

  5. Genes, evolution and intelligence.

    Science.gov (United States)

    Bouchard, Thomas J

    2014-11-01

    I argue that the g factor meets the fundamental criteria of a scientific construct more fully than any other conception of intelligence. I briefly discuss the evidence regarding the relationship of brain size to intelligence. A review of a large body of evidence demonstrates that there is a g factor in a wide range of species and that, in the species studied, it relates to brain size and is heritable. These findings suggest that many species have evolved a general-purpose mechanism (a general biological intelligence) for dealing with the environments in which they evolved. In spite of numerous studies with considerable statistical power, we know of very few genes that influence g and the effects are very small. Nevertheless, g appears to be highly polygenic. Given the complexity of the human brain, it is not surprising that that one of its primary faculties-intelligence-is best explained by the near infinitesimal model of quantitative genetics.

  6. Studying Genes

    Science.gov (United States)

    ... NIGMS NIGMS Home > Science Education > Studying Genes Studying Genes Tagline (Optional) Middle/Main Content Area Other Fact Sheets What are genes? Genes are segments of DNA that contain instructions ...

  7. Aesthetic Surprise of Artistic Expression in Chinese Ancient Literature%审美惊奇在中国古代文学中的艺术表现

    Institute of Scientific and Technical Information of China (English)

    李潇云

    2015-01-01

    Aesthetic surprise is an appreciation of wonder beauty of literature, art and natural beauty. It is related with ideological content of expression, prefers to the artistic form and artistic expression, but also closely related with the aesthetic psychology and aesthetic experience. With the main identifications as aesthetic psychological effects which appeared as "surprising" "astonishing""touched"and so on, its reason can be roughly analyzed from four aspects:imagery, artistic conception, rhetoric and language.%审美惊奇是对具有奇异之美的文学艺术甚至奇特自然美的一种激赏,它和表现的思想内容有关,偏重于艺术形式、艺术表现,也和审美心理和审美经验密不可分,其主要标识为审美心理效果,体现为“惊人”“惊心动魄”“动心惊耳”等,其原因大致可以从四个方面来分析:语言、修辞、意象、意境。

  8. Small bowel obstruction- a surprise.

    Science.gov (United States)

    Mathew, Jeffrey Daniel; Cp, Ganesh Babu; M, Balachandar; M, Ramanathan

    2015-01-01

    Trans - omental hernia is very rare, accounting to 1-4% of all internal hernias which is an unusual cause of small bowel obstruction. Here we present a case report of a small bowel obstruction in a female due to trans - omental hernia presenting with central abdominal pain, distension and bilious vomiting. She had no previous history of trauma, surgery. Plain X-ray abdomen erect showed multiple air fluid levels with dilated small bowel loops. Emergency laparotomy revealed a segment of congested small bowel loop (ileum) through a defect in greater omentum. On table the herniated bowel loop was reduced and the defect in greater omentum was closed primarily. There was no necessity for bowel resection as it regained normal colour after reduction. Postoperative period was uneventful with complete resolution of symptoms. This case is presented for its rarity and its importance in clinical differential diagnosis of acute abdomen due to small bowel obstruction.

  9. Surprising Beauty in Technical Photography

    Science.gov (United States)

    Davidhazy, Andrew

    2009-01-01

    The Imaging and Photographic Technology area, in which the author teaches, is an applications- and technology-oriented photography program designed to prepare students for work in technical, corporate, industrial, and scientific environments. One day, the author received an e-mail message from an editor who had found his Web site and thought he…

  10. Surprised by the Parimutuel Odds?

    DEFF Research Database (Denmark)

    Ottaviani, Marco; Sørensen, Peter Norman

    2009-01-01

    Empirical analyses of parimutuel betting markets have documented that market probabilities of favorites (longshots) tend to underestimate (overestimate) the corresponding empirical probabilities. We argue that this favorite-longshot bias is consistent with bettors taking simultaneous positions...... on the basis of private information about the likelihood of different outcomes. The ex post realization of a high market probability indicates favorable information about the occurrence of an outcome -- and the opposite is true for longshots. This explanation for the bias relies on the bettors' inability...

  11. Conversation Simulation and Sensible Surprises

    Science.gov (United States)

    Hutchens, Jason L.

    I have entered the Loebner Prize five times, winning the "most humanlike program" category in 1996 with a surly ELIZA-clone named HeX, but failed to repeat the performance in subsequent years with more sophisticated techniques. Whether this is indicative of an unanticipated improvement in "conversation simulation" technology, or whether it highlights the strengths of ELIZA-style trickery, is as an exercise for the reader. In 2000, I was invited to assume the role of Chief Scientist at Artificial Intelligence Ltd. (Ai) on a project inspired by the advice given by Alan Turing in the final section of his classic paper - our quest was to build a "child machine" that could learn and use language from scratch. In this chapter, I will discuss both of these experiences, presenting my thoughts regarding the Chinese Room argument and Artificial Intelligence (AI) in between.

  12. Some new surprises in chaos

    Energy Technology Data Exchange (ETDEWEB)

    Bunimovich, Leonid A., E-mail: bunimovh@math.gatech.edu [ABC Program, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States); School of Mathematics, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States); Vela-Arevalo, Luz V., E-mail: luzvela@math.gatech.edu [School of Mathematics, Georgia Institute of Technology, Atlanta, Georgia 30332 (United States)

    2015-09-15

    A brief review is presented of some recent findings in the theory of chaotic dynamics. We also prove a statement that could be naturally considered as a dual one to the Poincaré theorem on recurrences. Numerical results demonstrate that some parts of the phase space of chaotic systems are more likely to be visited earlier than other parts. A new class of chaotic focusing billiards is discussed that clearly violates the main condition considered to be necessary for chaos in focusing billiards.

  13. Surprising results from cosmic rays

    Energy Technology Data Exchange (ETDEWEB)

    Wilk, G. [Soltan Institute for Nuclear Studies, Warsaw (Poland); Wlodarczyk, Z. [Institute for Physics, Pedagogical University, Kielce (Poland)

    1996-10-01

    A number of seemingly exotic phenomena seen in the highest cosmic-ray experiments are briefly discussed. We argue that they indicate existence of non-statistical fluctuations and strong correlations in the fragmentation region of multiparticle production processes unaccessible to the present accelerators. (author) 12 refs, 3 figs

  14. Education in Japan: Surprising Lessons.

    Science.gov (United States)

    Deasy, Richard J.

    1986-01-01

    Reports on an indepth probe of the Japanese educational system by American educators. This study shows that the United States cannot expect to achieve economic growth by copying the Japanese system, which has been shaped largely by its geography and culture and society. (MD)

  15. What is the mechanism of Ketamine's rapid-onset antidepressant effect? A concise overview of the surprisingly large number of possibilities.

    Science.gov (United States)

    Strasburger, S E; Bhimani, P M; Kaabe, J H; Krysiak, J T; Nanchanatt, D L; Nguyen, T N; Pough, K A; Prince, T A; Ramsey, N S; Savsani, K H; Scandlen, L; Cavaretta, M J; Raffa, R B

    2017-04-01

    Abundant clinical data now confirm that ketamine produces a remarkable rapid-onset antidepressant effect - hours or days - in contrast to the delayed onset (typically weeks) of current antidepressant drugs. This surprising and revolutionary finding may lead to the development of life-saving pharmacotherapy for depressive illness by reducing the high suicide risk associated with the delayed onset of effect of current drugs. As ketamine has serious self-limiting drawbacks that restrict its widespread use for this purpose, a safer alternative is needed. Our objective is to review the proposed mechanism(s) of ketamine's rapid-onset antidepressant action for new insights into the physiological basis of depressive illness that may lead to new and novel targets for antidepressant drug discovery. A search was conducted on published literature (e.g. PubMed) and Internet sources to identify information relevant to ketamine's rapid-acting antidepressant action and, specifically, to the possible mechanism(s) of this action. Key search words included 'ketamine', 'antidepressant', 'mechanism of action', 'depression' and 'rapid acting', either individually or in combination. Information was sought that would include less well-known, as well as well-known, basic pharmacologic properties of ketamine and that identified and evaluated the several hypotheses about ketamine's mechanism of antidepressant action. Whether the mechanistic explanation for ketamine's rapid-onset antidepressant action is related to its well-known antagonism of the NMDA (N-Methyl-d-aspartate) subtype of glutamate receptor or to something else has not yet been fully elucidated. The evidence from pharmacologic, medicinal chemistry, animal model and drug-discovery sources reveals a wide variety of postulated mechanisms. The surprising discovery of ketamine's rapid-onset antidepressant effect is a game-changer for the understanding and treatment of depressive illness. There is some convergence on NMDA receptor

  16. Immunoglobulin genes

    Energy Technology Data Exchange (ETDEWEB)

    Honjo, T. (Kyoto Univ. (Japan)); Alt, F.W. (Columbia Univ., Dobbs Ferry, NY (USA). Hudson Labs.); Rabbitts, T.H. (Medical Research Council, Cambridge (UK))

    1989-01-01

    This book reports on the structure, function, and expression of the genes encoding antibodies in normal and neoplastic cells. Topics covered are: B Cells; Organization and rearrangement of immunoglobin genes; Immunoglobin genes in disease; Immunoglobin gene expression; and Immunoglobin-related genes.

  17. Crystal structure of di-μ-chlorido-bis[dichloridobis(methanol-κOiridium(III] dihydrate: a surprisingly simple chloridoiridium(III dinuclear complex with methanol ligands

    Directory of Open Access Journals (Sweden)

    Joseph S. Merola

    2015-05-01

    Full Text Available The reaction between IrCl3·xH2O in methanol led to the formation of small amounts of the title compound, [Ir2Cl6(CH3OH4]·2H2O, which consists of two IrCl4O2 octahedra sharing an edge via chloride bridges. The molecule lies across an inversion center. Each octahedron can be envisioned as being comprised of four chloride ligands in the equatorial plane with methanol ligands in the axial positions. A lattice water molecule is strongly hydrogen-bonded to the coordinating methanol ligands and weak interactions with coordinating chloride ligands lead to the formation of a three-dimensional network. This is a surprising structure given that, while many reactions of iridium chloride hydrate are carried out in alcoholic solvents, especially methanol and ethanol, this is the first structure of a chloridoiridium compound with only methanol ligands.

  18. Evolution of mitochondrial gene orders in echinoderms.

    Science.gov (United States)

    Perseke, Marleen; Fritzsch, Guido; Ramsch, Kai; Bernt, Matthias; Merkle, Daniel; Middendorf, Martin; Bernhard, Detlef; Stadler, Peter F; Schlegel, Martin

    2008-05-01

    A comprehensive analysis of the mitochondrial gene orders of all previously published and two novel Antedon mediterranea (Crinoidea) and Ophiura albida (Ophiuroidea) complete echinoderm mitochondrial genomes shows that all major types of rearrangement operations are necessary to explain the evolution of mitochondrial genomes. In addition to protein coding genes we include all tRNA genes as well as the control region in our analysis. Surprisingly, 7 of the 16 genomes published in the GenBank database contain misannotations, mostly unannotated tRNAs and/or mistakes in the orientation of tRNAs, which we have corrected here. Although the gene orders of mt genomes appear very different, only 8 events are necessary to explain the evolutionary history of echinoderms with the exception of the ophiuroids. Only two of these rearrangements are inversions, while we identify three tandem-duplication-random-loss events and three transpositions.

  19. Expression of protein-coding genes embedded in ribosomal DNA

    DEFF Research Database (Denmark)

    Johansen, Steinar D; Haugen, Peik; Nielsen, Henrik

    2007-01-01

    Ribosomal DNA (rDNA) is a specialised chromosomal location that is dedicated to high-level transcription of ribosomal RNA genes. Interestingly, rDNAs are frequently interrupted by parasitic elements, some of which carry protein genes. These are non-LTR retrotransposons and group II introns...... that encode reverse transcriptase-like genes, and group I introns and archaeal introns that encode homing endonuclease genes (HEGs). Although rDNA-embedded protein genes are widespread in nuclei, organelles and bacteria, there is surprisingly little information available on how these genes are expressed....... Exceptions include a handful of HEGs from group I introns. Recent studies have revealed unusual and essential roles of group I and group I-like ribozymes in the endogenous expression of HEGs. Here we discuss general aspects of rDNA-embedded protein genes and focus on HEG expression from group I introns...

  20. A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Bustamente, Carlos; Clark, Andrew G.

    2005-01-01

    of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome...... such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved...... in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some...

  1. Golden age of RyR and GABA-R diamide and isoxazoline insecticides: common genesis, serendipity, surprises, selectivity, and safety.

    Science.gov (United States)

    Casida, John E

    2015-04-20

    The serendipitous observation of the insecticidal activity of a candidate herbicide was the first in a series of surprises that changed the course of insecticide research and opened the "Golden Age of Diamide and Isoxazoline Insecticides" which have a common genesis. Two novel modes of action were discovered, one involving the γ-aminobutyric acid (GABA) receptor of the chloride channel and the other the ryanodine receptor (RyR) of the calcium-activated calcium channel. These are old insecticide targets, but physiological assays and radioligand binding studies reveal that the new diamides and isoxazolines act at previously unrecognized sites without cross-resistance to other chemotypes and more important differing between insects and mammals resulting in selective toxicity and mechanistically based safety. The phthalic diamide flubendiamide and anthranilic diamides chlorantraniliprole and cyantraniliprole act at an allosteric site of the RyR to activate calcium release in insects but not mammals. They are the most important insecticide introductions of the past decade. Isoxazoline and meta-diamide insecticides and their previously unrecognized GABA-R target are more recent discoveries. Isoxazolines are currently important in flea and tick control in dogs and cats, and meta-diamides show promise for pest management and crop protection. These 21st century RyR and GABA-R diamides and isoxazolines were serendipitous discoveries and developments showing the importance of mechanism studies in maintaining the arsenal of safe and effective insecticides.

  2. A surprisingly poor correlation between in vitro and in vivo testing of biomaterials for bone regeneration: results of a multicentre analysis.

    Science.gov (United States)

    Hulsart-Billström, G; Dawson, J I; Hofmann, S; Müller, R; Stoddart, M J; Alini, M; Redl, H; El Haj, A; Brown, R; Salih, V; Hilborn, J; Larsson, S; Oreffo, R O

    2016-05-24

    New regenerative materials and approaches need to be assessed through reliable and comparable methods for rapid translation to the clinic. There is a considerable need for proven in vitro assays that are able to reduce the burden on animal testing, by allowing assessment of biomaterial utility predictive of the results currently obtained through in vivo studies. The purpose of this multicentre review was to investigate the correlation between existing in vitro results with in vivo outcomes observed for a range of biomaterials. Members from the European consortium BioDesign, comprising 8 universities in a European multicentre study, provided data from 36 in vivo studies and 47 in vitro assays testing 93 different biomaterials. The outcomes of the in vitro and in vivo experiments were scored according to commonly recognised measures of success relevant to each experiment. The correlation of in vitro with in vivo scores for each assay alone and in combination was assessed. A surprisingly poor correlation between in vitro and in vivo assessments of biomaterials was revealed indicating a clear need for further development of relevant in vitro assays. There was no significant overall correlation between in vitro and in vivo outcome. The mean in vitro scores revealed a trend of covariance to in vivo score with 58 %. The inadequacies of the current in vitro assessments highlighted here further stress the need for the development of novel approaches to in vitro biomaterial testing and validated pre-clinical pipelines.

  3. Collaborative Resilience to Episodic Shocks and Surprises: A Very Long-Term Case Study of Zanjera Irrigation in the Philippines 1979–2010

    Directory of Open Access Journals (Sweden)

    Ruth Yabes

    2015-07-01

    Full Text Available This thirty-year case study uses surveys, semi-structured interviews, and content analysis to examine the adaptive capacity of Zanjera San Marcelino, an indigenous irrigation management system in the northern Philippines. This common pool resource (CPR system exists within a turbulent social-ecological system (SES characterized by episodic shocks such as large typhoons as well as novel surprises, such as national political regime change and the construction of large dams. The Zanjera nimbly responded to these challenges, although sometimes in ways that left its structure and function substantially altered. While a partial integration with the Philippine National Irrigation Agency was critical to the Zanjera’s success, this relationship required on-going improvisation and renegotiation. Over time, the Zanjera showed an increasing capacity to learn and adapt. A core contribution of this analysis is the integration of a CPR study within an SES framework to examine resilience, made possible the occurrence of a wide range of challenges to the Zanjera’s function and survival over the long period of study. Long-term analyses like this one, however rare, are particularly useful for understanding the adaptive and transformative dimensions of resilience.

  4. A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

    Directory of Open Access Journals (Sweden)

    Daniel J Kliebenstein

    Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

  5. The Drosophila melanogaster methuselah gene: a novel gene with ancient functions.

    Directory of Open Access Journals (Sweden)

    Ana Rita Araújo

    Full Text Available The Drosophila melanogaster G protein-coupled receptor gene, methuselah (mth, has been described as a novel gene that is less than 10 million years old. Nevertheless, it shows a highly specific expression pattern in embryos, larvae, and adults, and has been implicated in larval development, stress resistance, and in the setting of adult lifespan, among others. Although mth belongs to a gene subfamily with 16 members in D. melanogaster, there is no evidence for functional redundancy in this subfamily. Therefore, it is surprising that a novel gene influences so many traits. Here, we explore the alternative hypothesis that mth is an old gene. Under this hypothesis, in species distantly related to D. melanogaster, there should be a gene with features similar to those of mth. By performing detailed phylogenetic, synteny, protein structure, and gene expression analyses we show that the D. virilis GJ12490 gene is the orthologous of mth in species distantly related to D. melanogaster. We also show that, in D. americana (a species of the virilis group of Drosophila, a common amino acid polymorphism at the GJ12490 orthologous gene is significantly associated with developmental time, size, and lifespan differences. Our results imply that GJ12490 orthologous genes are candidates for developmental time and lifespan differences in Drosophila in general.

  6. Drosophila X-Linked Genes Have Lower Translation Rates than Autosomal Genes.

    Science.gov (United States)

    Zhang, Zhenguo; Presgraves, Daven C

    2016-02-01

    In Drosophila, X-linked and autosomal genes achieve comparable expression at the mRNA level. Whether comparable X-autosome gene expression is realized at the translational and, ultimately, the protein levels is, however, unknown. Previous studies suggest the possibility of higher translation rates for X-linked genes owing to stronger usage of preferred codons. In this study, we use public ribosome profiling data from Drosophila melanogaster to infer translation rates on the X chromosome versus the autosomes. We find that X-linked genes have consistently lower ribosome densities than autosomal genes in S2 cells, early embryos, eggs, and mature oocytes. Surprisingly, the lower ribosome densities of X-linked genes are not consistent with faster translation elongation but instead imply slower translation initiation. In particular, X-linked genes have sequence features known to slow translation initiation such as stronger mRNA structure near start codons and longer 5'-UTRs. Comparison to outgroup species suggests that stronger mRNA structure is an evolved feature of Drosophila X chromosomes. Finally, we find that the magnitude of the X-autosome difference in ribosome densities is smaller for genes encoding members of protein complexes, suggesting that stoichiometry constrains the evolution of translation rates. In sum, our analyses suggest that Drosophila X-linked genes have evolved lower translation rates than autosomal genes despite stronger usage of preferred codons.

  7. Syntheses and surprising regioselectivity of 5- and 6-substituted decaboranyl ethers via the nucleophilic attack of alcohols on 6- and 5-halodecaboranes.

    Science.gov (United States)

    Ewing, William C; Carroll, Patrick J; Sneddon, Larry G

    2011-05-02

    The selective syntheses of new classes of decaboranyl ethers containing a range of functional groups substituted at the B5 or B6 positions were achieved through the reaction of alcohols with halodecaboranes. The surprising regioselectivity of the reaction, where the reaction of the 6-halodecaboranes (6-X-B(10)H(13)) with alcohols yielded the 5-substituted decaboranyl ethers (5-RO-B(10)H(13)) and the reaction with 5-halodecaboranes (5-X-B(10)H(13)) gave the 6-substituted decaboranyl ethers (6-RO-B(10)H(13)), was confirmed by NMR and X-ray crystallographic analyses. The crystallographic determinations also showed that the decaboranyl ethers had shortened B-O bonds and apparent sp(2) hybridization at oxygen indicating significant π-backbonding from oxygen to the cage boron. A possible substitution mechanism was computationally identified involving: (1) initial nucleophilic attack by the alcohol-oxygen at a site adjacent to the 5- or 6-halo-substituted boron, (2) movement of the terminal hydrogen at the point of attack to a bridging position, (3) formation of a 5-membered (B-O-H-Cl-B) cyclic transition state allowing the acidic methanolic-hydrogen to bond to the halogen, (4) release of HX, and finally (5) movement of a bridging hydrogen into the vacated terminal position. Deuterium labeling studies confirmed the movement of hydrogen from a bridging position of the halodecaborane into the halogen-vacated terminal position on the decaboranyl ether product. The relative reaction rates of the 6-X-B(10)H(13) compounds (X = F, Cl, Br, I) with alcohols were likewise found to be consistent with this mechanism.

  8. Accurate reaction barrier heights of pericyclic reactions: Surprisingly large deviations for the CBS-QB3 composite method and their consequences in DFT benchmark studies.

    Science.gov (United States)

    Karton, Amir; Goerigk, Lars

    2015-04-05

    Accurate barrier heights are obtained for the 26 pericyclic reactions in the BHPERI dataset by means of the high-level Wn-F12 thermochemical protocols. Very often, the complete basis set (CBS)-type composite methods are used in similar situations, but herein it is shown that they in fact result in surprisingly large errors with root mean square deviations (RMSDs) of about 2.5 kcal mol(-1). In comparison, other composite methods, particularly G4-type and estimated coupled cluster with singles, doubles, and quasiperturbative triple excitations [CCSD(T)/CBS] approaches, show deviations well below the chemical-accuracy threshold of 1 kcal mol(-1). With the exception of SCS-MP2 and the herein newly introduced MP3.5 approach, all other tested Møller-Plesset perturbative procedures give poor performance with RMSDs of up to 8.0 kcal mol(-1). The finding that CBS-type methods fail for barrier heights of these reactions is unexpected and it is particularly troublesome given that they are often used to obtain reference values for benchmark studies. Significant differences are identified in the interpretation and final ranking of density functional theory (DFT) methods when using the original CBS-QB3 rather than the new Wn-F12 reference values for BHPERI. In particular, it is observed that the more accurate Wn-F12 benchmark results in lower statistical errors for those methods that are generally considered to be robust and accurate. Two examples are the PW6B95-D3(BJ) hybrid-meta-general-gradient approximation and the PWPB95-D3(BJ) double-hybrid functionals, which result in the lowest RMSDs of the entire DFT study (1.3 and 1.0 kcal mol(-1), respectively). These results indicate that CBS-QB3 should be applied with caution in computational modeling and benchmark studies involving related systems.

  9. Task-Irrelevant Expectation Violations in Sequential Manual Actions: Evidence for a "Check-after-Surprise" Mode of Visual Attention and Eye-Hand Decoupling.

    Science.gov (United States)

    Foerster, Rebecca M

    2016-01-01

    When performing sequential manual actions (e.g., cooking), visual information is prioritized according to the task determining where and when to attend, look, and act. In well-practiced sequential actions, long-term memory (LTM)-based expectations specify which action targets might be found where and when. We have previously demonstrated (Foerster and Schneider, 2015b) that violations of such expectations that are task-relevant (e.g., target location change) cause a regression from a memory-based mode of attentional selection to visual search. How might task-irrelevant expectation violations in such well-practiced sequential manual actions modify attentional selection? This question was investigated by a computerized version of the number-connection test. Participants clicked on nine spatially distributed numbered target circles in ascending order while eye movements were recorded as proxy for covert attention. Target's visual features and locations stayed constant for 65 prechange-trials, allowing practicing the manual action sequence. Consecutively, a task-irrelevant expectation violation occurred and stayed for 20 change-trials. Specifically, action target number 4 appeared in a different font. In 15 reversion-trials, number 4 returned to the original font. During the first task-irrelevant change trial, manual clicking was slower and eye scanpaths were larger and contained more fixations. The additional fixations were mainly checking fixations on the changed target while acting on later targets. Whereas the eyes repeatedly revisited the task-irrelevant change, cursor-paths remained completely unaffected. Effects lasted for 2-3 change trials and did not reappear during reversion. In conclusion, an unexpected task-irrelevant change on a task-defining feature of a well-practiced manual sequence leads to eye-hand decoupling and a "check-after-surprise" mode of attentional selection.

  10. ‘Surprise’: Outbreak of Campylobacter infection associated with chicken liver pâté at a surprise birthday party, Adelaide, Australia, 2012

    Directory of Open Access Journals (Sweden)

    Emma Denehy

    2012-11-01

    Full Text Available Objective: In July 2012, an outbreak of Campylobacter infection was investigated by the South Australian Communicable Disease Control Branch and Food Policy and Programs Branch. The initial notification identified illness at a surprise birthday party held at a restaurant on 14 July 2012. The objective of the investigation was to identify the potential source of infection and institute appropriate intervention strategies to prevent further illness.Methods: A guest list was obtained and a retrospective cohort study undertaken. A combination of paper-based and telephone questionnaires were used to collect exposure and outcome information. An environmental investigation was conducted by Food Policy and Programs Branch at the implicated premises.Results: All 57 guests completed the questionnaire (100% response rate, and 15 met the case definition. Analysis showed a significant association between illness and consumption of chicken liver pâté (relative risk: 16.7, 95% confidence interval: 2.4–118.6. No other food or beverage served at the party was associated with illness. Three guests submitted stool samples; all were positive for Campylobacter. The environmental investigation identified that the cooking process used in the preparation of chicken liver pâté may have been inconsistent, resulting in some portions not cooked adequately to inactivate potential Campylobacter contamination.Discussion: Chicken liver products are a known source of Campylobacter infection; therefore, education of food handlers remains a high priority. To better identify outbreaks among the large number of Campylobacter notifications, routine typing of Campylobacter isolates is recommended.

  11. Gene expression profiling of placentas affected by pre-eclampsia

    DEFF Research Database (Denmark)

    Hoegh, Anne Mette; Borup, Rehannah; Nielsen, Finn Cilius;

    2010-01-01

    Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA...... expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000) were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia...... as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events...

  12. Gene expression profiling of placentas affected by pre-eclampsia

    DEFF Research Database (Denmark)

    Hoegh, Anne Mette; Borup, Rehannah; Nielsen, Finn Cilius

    2010-01-01

    Several studies point to the placenta as the primary cause of pre-eclampsia. Our objective was to identify placental genes that may contribute to the development of pre-eclampsia. RNA was purified from tissue biopsies from eleven pre-eclamptic placentas and eighteen normal controls. Messenger RNA...... expression from pooled samples was analysed by microarrays. Verification of the expression of selected genes was performed using real-time PCR. A surprisingly low number of genes (21 out of 15,000) were identified as differentially expressed. Among these were genes not previously associated with pre-eclampsia...... as bradykinin B1 receptor and a 14-3-3 protein, but also genes that have already been connected with pre-eclampsia, for example, inhibin beta A subunit and leptin. A low number of genes were repeatedly identified as differentially expressed, because they may represent the endpoint of a cascade of events...

  13. The Vision and Challenges of the Gene Ontology.

    Science.gov (United States)

    Lewis, Suzanna E

    2017-01-01

    The overarching goal of the Gene Ontology (GO) Consortium is to provide researchers in biology and biomedicine with all current functional information concerning genes and the cellular context under which these occur. When the GO was started in the 1990s surprisingly little attention had been given to how functional information about genes was to be uniformly captured, structured in a computable form, and made accessible to biologists. Because knowledge of gene, protein, ncRNA, and molecular complex roles is continuously accumulating and changing, the GO needed to be a dynamic resource, accurately tracking ongoing research results over time. Here I describe the progress that has been made over the years towards this goal, and the work that still remains to be done, to make of the Gene Ontology (GO) Consortium realize its goal of offering the most comprehensive and up-to-date resource for information on gene function.

  14. Genes under positive selection in Escherichia coli

    DEFF Research Database (Denmark)

    Petersen, Lise; Bollback, Jonathan P; Dimmic, Matt

    2007-01-01

    We used a comparative genomics approach to identify genes that are under positive selection in six strains of Escherichia coli and Shigella flexneri, including five strains that are human pathogens. We find that positive selection targets a wide range of different functions in the E. coli genome......, including cell surface proteins such as beta barrel porins, presumably because of the involvement of these genes in evolutionary arms races with other bacteria, phages, and/or the host immune system. Structural mapping of positively selected sites on trans-membrane beta barrel porins reveals...... that the residues under positive selection occur almost exclusively in the extracellular region of the proteins that are enriched with sites known to be targets of phages, colicins, or the host immune system. More surprisingly, we also find a number of other categories of genes that show very strong evidence...

  15. Histone Deacetylase Genes in Arabidopsis Development

    Institute of Scientific and Technical Information of China (English)

    Courtney Hollender; Zhongchi Liu

    2008-01-01

    Histone acetylatlon and deacetylation are directly connected with transcriptional activation and silencing in eukaryotas.Gene families for enzymes that accomplish these histone modifications show surprising complexity in domain organization,tissue-specific expression, and function. This review is focused on the family of histone deacetylases (HDACs) that remove the acetyl group from core histone tails, resulting in a "closed" chromatin and transcriptional repression. In Arabidopsis,18 HDAC genes are divided in to three different types - RPD3-1ike, HD-tuin and sirtuin - with two or more members ineach type. The structural feature of each HDAC class, the expression profile of each HDAC gene during development and functional insights of important family members are summarized here. It is clear that HDACs are an important class of global transcriptional regulators that play crucial roles in plant development, defense, and adaptation.

  16. Investor Reaction to Market Surprises on the Istanbul Stock Exchange Investor Reaction to Market Surprises on the Istanbul Stock Exchange = İstanbul Menkul Kıymetler Borsasında Piyasa Sürprizlerine Yatırımcı Tepkisi

    Directory of Open Access Journals (Sweden)

    Yaman Ömer ERZURUMLU

    2011-08-01

    Full Text Available This paper examines the reaction of investors to the arrival of unexpected information on the Istanbul Stock Exchange. The empirical results suggest that the investor reaction following unexpected news on the ISE100 is consistent with Overreaction Hypothesis especially after unfavorable market surprises. Interestingly such pattern does not exist for ISE30 index which includes more liquid and informationally efficient securities. A possible implication of this study for investors is that employing a semi contrarian investment strategy of buying losers in ISE100 may generate superior returns. Moreover, results are supportive of the last regulation change of Capital Market Board of Turkey which mandates more disclosure regarding the trading of less liquid stocks with lower market capitalization.

  17. Gene expression profile analysis of type 2 diabetic mouse liver.

    Directory of Open Access Journals (Sweden)

    Fang Zhang

    Full Text Available Liver plays a key role in glucose metabolism and homeostasis, and impaired hepatic glucose metabolism contributes to the development of type 2 diabetes. However, the precise gene expression profile of diabetic liver and its association with diabetes and related diseases are yet to be further elucidated. In this study, we detected the gene expression profile by high-throughput sequencing in 9-week-old normal and type 2 diabetic db/db mouse liver. Totally 12132 genes were detected, and 2627 genes were significantly changed in diabetic mouse liver. Biological process analysis showed that the upregulated genes in diabetic mouse liver were mainly enriched in metabolic processes. Surprisingly, the downregulated genes in diabetic mouse liver were mainly enriched in immune-related processes, although all the altered genes were still mainly enriched in metabolic processes. Similarly, KEGG pathway analysis showed that metabolic pathways were the major pathways altered in diabetic mouse liver, and downregulated genes were enriched in immune and cancer pathways. Analysis of the key enzyme genes in fatty acid and glucose metabolism showed that some key enzyme genes were significantly increased and none of the detected key enzyme genes were decreased. In addition, FunDo analysis showed that liver cancer and hepatitis were most likely to be associated with diabetes. Taken together, this study provides the digital gene expression profile of diabetic mouse liver, and demonstrates the main diabetes-associated hepatic biological processes, pathways, key enzyme genes in fatty acid and glucose metabolism and potential hepatic diseases.

  18. Electroporation-mediated gene delivery.

    Science.gov (United States)

    Young, Jennifer L; Dean, David A

    2015-01-01

    Electroporation has been used extensively to transfer DNA to bacteria, yeast, and mammalian cells in culture for the past 30 years. Over this time, numerous advances have been made, from using fields to facilitate cell fusion, delivery of chemotherapeutic drugs to cells and tissues, and most importantly, gene and drug delivery in living tissues from rodents to man. Electroporation uses electrical fields to transiently destabilize the membrane allowing the entry of normally impermeable macromolecules into the cytoplasm. Surprisingly, at the appropriate field strengths, the application of these fields to tissues results in little, if any, damage or trauma. Indeed, electroporation has even been used successfully in human trials for gene delivery for the treatment of tumors and for vaccine development. Electroporation can lead to between 100 and 1000-fold increases in gene delivery and expression and can also increase both the distribution of cells taking up and expressing the DNA as well as the absolute amount of gene product per cell (likely due to increased delivery of plasmids into each cell). Effective electroporation depends on electric field parameters, electrode design, the tissues and cells being targeted, and the plasmids that are being transferred themselves. Most importantly, there is no single combination of these variables that leads to greatest efficacy in every situation; optimization is required in every new setting. Electroporation-mediated in vivo gene delivery has proven highly effective in vaccine production, transgene expression, enzyme replacement, and control of a variety of cancers. Almost any tissue can be targeted with electroporation, including muscle, skin, heart, liver, lung, and vasculature. This chapter will provide an overview of the theory of electroporation for the delivery of DNA both in individual cells and in tissues and its application for in vivo gene delivery in a number of animal models.

  19. Association of SARS susceptibility with single nucleic acid polymorphisms of OAS1 and MxA genes: a case-control study

    Directory of Open Access Journals (Sweden)

    Yang Hong

    2006-07-01

    Full Text Available Abstract Background Host genetic factors may play a role in susceptibility and resistance to SARS associated coronavirus (SARS-CoV infection. The study was carried out to investigate the association between the genetic polymorphisms of 2',5'-oligoadenylate synthetase 1 (OAS1 gene as well as myxovirus resistance 1 (MxA gene and susceptibility to SARS in Chinese Han population. Methods A hospital-based case-control study was conducted. A collective of 66 SARS cases and 64 close contact uninfected controls were enrolled in this study. End point real time polymerase chain reaction (PCR and PCR-based Restriction Fragment Length Polymorphism (RFLP analysis were used to detect the single nucleic polymorphisms (SNPs in OAS1 and MxA genes. Information on other factors associated with SARS infection was collected using a pre-tested questionnaire. Univariate and multivariate logistic analyses were conducted. Results One polymorphism in the 3'-untranslated region (3'-UTR of the OAS1 gene was associated with SARS infection. Compared to AA genotype, AG and GG genotypes were found associated with a protective effect on SARS infection with ORs (95% CI of 0.42 (0.20~0.89 and 0.30 (0.09~0.97, respectively. Also, a GT genotype at position 88 in the MxA gene promoter was associated with increased susceptibility to SARS infection compared to a GG genotype (OR = 3.06, 95% CI: 1.25~7.50. The associations of AG genotype in OAS1 and GT genotype in MxA remained significant in multivariate analyses after adjusting for SARS protective measures (OR = 0.38, 95% CI: 0.14~0.98 and OR = 3.22, 95% CI: 1.13~9.18, respectively. Conclusion SNPs in the OAS1 3'-UTR and MxA promoter region appear associated with host susceptibility to SARS in Chinese Han population.

  20. Engineering genes for predictable protein expression.

    Science.gov (United States)

    Gustafsson, Claes; Minshull, Jeremy; Govindarajan, Sridhar; Ness, Jon; Villalobos, Alan; Welch, Mark

    2012-05-01

    The DNA sequence used to encode a polypeptide can have dramatic effects on its expression. Lack of readily available tools has until recently inhibited meaningful experimental investigation of this phenomenon. Advances in synthetic biology and the application of modern engineering approaches now provide the tools for systematic analysis of the sequence variables affecting heterologous expression of recombinant proteins. We here discuss how these new tools are being applied and how they circumvent the constraints of previous approaches, highlighting some of the surprising and promising results emerging from the developing field of gene engineering.

  1. Metabolic analysis of the soil microbe Dechloromonas aromatica str. RCB: indications of a surprisingly complex life-style and cryptic anaerobic pathways for aromatic degradation

    Directory of Open Access Journals (Sweden)

    Feil Helene

    2009-08-01

    Full Text Available Abstract Background Initial interest in Dechloromonas aromatica strain RCB arose from its ability to anaerobically degrade benzene. It is also able to reduce perchlorate and oxidize chlorobenzoate, toluene, and xylene, creating interest in using this organism for bioremediation. Little physiological data has been published for this microbe. It is considered to be a free-living organism. Results The a priori prediction that the D. aromatica genome would contain previously characterized "central" enzymes to support anaerobic aromatic degradation of benzene proved to be false, suggesting the presence of novel anaerobic aromatic degradation pathways in this species. These missing pathways include the benzylsuccinate synthase (bssABC genes (responsible for fumarate addition to toluene and the central benzoyl-CoA pathway for monoaromatics. In depth analyses using existing TIGRfam, COG, and InterPro models, and the creation of de novo HMM models, indicate a highly complex lifestyle with a large number of environmental sensors and signaling pathways, including a relatively large number of GGDEF domain signal receptors and multiple quorum sensors. A number of proteins indicate interactions with an as yet unknown host, as indicated by the presence of predicted cell host remodeling enzymes, effector enzymes, hemolysin-like proteins, adhesins, NO reductase, and both type III and type VI secretory complexes. Evidence of biofilm formation including a proposed exopolysaccharide complex and exosortase (epsH are also present. Annotation described in this paper also reveals evidence for several metabolic pathways that have yet to be observed experimentally, including a sulphur oxidation (soxFCDYZAXB gene cluster, Calvin cycle enzymes, and proteins involved in nitrogen fixation in other species (including RubisCo, ribulose-phosphate 3-epimerase, and nif gene families, respectively. Conclusion Analysis of the D. aromatica genome indicates there is much to be

  2. Metabolic analysis of the soil microbe Dechloromonas aromatica str. RCB: indications of a surprisingly complex life-style and cryptic anaerobic pathways for aromatic degradation

    Energy Technology Data Exchange (ETDEWEB)

    Salinero, Kennan Kellaris; Keller, Keith; Feil, William S.; Feil, Helene; Trong, Stephan; Di Bartolo, Genevieve; Lapidus, Alla

    2008-11-17

    Initial interest in Dechloromonas aromatica strain RCB arose from its ability to anaerobically degrade benzene. It is also able to reduce perchlorate and oxidize chlorobenzoate, toluene, and xylene, creating interest in using this organism for bioremediation. Little physiological data has been published for this microbe. It is considered to be a free-living organism. The a priori prediction that the D. aromatica genome would contain previously characterized 'central' enzymes involved in anaerobic aromatic degradation proved to be false, suggesting the presence of novel anaerobic aromatic degradation pathways in this species. These missing pathways include the benzyl succinyl synthase (bssABC) genes (responsible for formate addition to toluene) and the central benzoylCoA pathway for monoaromatics. In depth analyses using existing TIGRfam, COG, and InterPro models, and the creation of de novo HMM models, indicate a highly complex lifestyle with a large number of environmental sensors and signaling pathways, including a relatively large number of GGDEF domain signal receptors and multiple quorum sensors. A number of proteins indicate interactions with an as yet unknown host, as indicated by the presence of predicted cell host remodeling enzymes, effector enzymes, hemolysin-like proteins, adhesins, NO reductase, and both type III and type VI secretory complexes. Evidence of biofilm formation including a proposed exopolysaccharide complex with the somewhat rare exosortase (epsH), is also present. Annotation described in this paper also reveals evidence for several metabolic pathways that have yet to be observed experimentally, including a sulphur oxidation (soxFCDYZAXB) gene cluster, Calvin cycle enzymes, and nitrogen fixation (including RubisCo, ribulose-phosphate 3-epimerase, and nif gene families, respectively). Analysis of the D. aromatica genome indicates there is much to be learned regarding the metabolic capabilities, and life-style, for this microbial

  3. The surprisingly small but increasing role of international agricultural trade on the European Union’s dependence on mineral phosphorus fertiliser

    Science.gov (United States)

    Nesme, Thomas; Roques, Solène; Metson, Geneviève S.; Bennett, Elena M.

    2016-02-01

    Phosphorus (P) is subject to global management challenges due to its importance to both food security and water quality. The European Union (EU) has promoted policies to limit fertiliser over-application and protect water quality for more than 20 years, helping to reduce European P use. Over this time period, the EU has, however, become more reliant on imported agricultural products. These imported products require fertiliser to be used in distant countries to grow crops that will ultimately feed European people and livestock. As such, these imports represent a displacement of European P demand, possibly allowing Europe to decrease its apparent P footprint by moving P use to locations outside the EU. We investigated the effect of EU imports on the European P fertiliser footprint to better understand whether the EU’s decrease in fertiliser use over time resulted from P demand being ‘outsourced’ to other countries or whether it truly represented a decline in P demand. To do this, we quantified the ‘virtual P flow’ defined as the amount of mineral P fertiliser applied to agricultural soils in non-EU countries to support agricultural product imports to the EU. We found that the EU imported a virtual P flow of 0.55 Tg P/yr in 1995 that, surprisingly, decreased to 0.50 Tg P/yr in 2009. These results were contrary to our hypothesis that trade increases would be used to help the EU reduce its domestic P fertiliser use by outsourcing its P footprint abroad. Still, the contribution of virtual P flows to the total P footprint of the EU has increased by 40% from 1995 to 2009 due to a dramatic decrease in domestic P fertiliser use in Europe: in 1995, virtual P was equivalent to 32% of the P used as fertiliser domestically to support domestic consumption but jumped to 53% in 2009. Soybean and palm tree products from South America and South East Asia contributed most to the virtual P flow. These results demonstrate that, although policies in the EU have successfully

  4. Multiscale Modeling of Gene-Behavior Associations in an Artificial Neural Network Model of Cognitive Development

    Science.gov (United States)

    Thomas, Michael S. C.; Forrester, Neil A.; Ronald, Angelica

    2016-01-01

    In the multidisciplinary field of developmental cognitive neuroscience, statistical associations between levels of description play an increasingly important role. One example of such associations is the observation of correlations between relatively common gene variants and individual differences in behavior. It is perhaps surprising that such…

  5. Gene therapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005147 CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer. WANG Wei-guo(王伟国),et al. Viral & Gene Ther Center, Eastern Hepatobilli Surg Instit 2nd Milit Univ, Shanghai 200438. Chin J Oncol,2005:27(2):69-72. Objective: To develop a novel vector system, which combines the advantages of the gene therapy,

  6. The Origin of Carbon-bearing Volatiles in Surprise Valley Hot Springs in the Great Basin: Carbon Isotope and Water Chemistry Characterizations

    Science.gov (United States)

    Fu, Q.; Socki, R.; Niles, P. B.; Romanek, C. S.; Datta, S.; Darnell, M.; Bissada, A. K.

    2013-12-01

    There are numerous hydrothermal fields within the Great Basin of North America, some of which have been exploited for geothermal resources. With methane and other carbon-bearing compounds being observed, however, their origins and formation conditions remain unknown. Thus, studying hydrothermal springs in this area provides us an opportunity to understand subsurface (bio)chemical processes that generate organic compounds, and aid in future development and exploration of potential energy resources as well. While isotope measurement has long been used for identification of their origins, there are secondary processes that may generate variations in isotopic compositions: oxidation, re-equilibration of methane and other alkanes with CO2, mixing with compounds of other sources, etc. Therefore, in addition to isotopic analysis, other lines of evidence, including water chemistry and rock compositions, are necessary to identify origins of volatile compounds. Surprise Valley Hot Springs (SVHS, 41°32'N, 120°5'W), located in a typical basin and range province in northeastern California, is a terrestrial hydrothermal spring system of the Great Basin. Previous geophysical studies indicated the presence of clay-rich volcanic and sedimentary rocks of Tertiary age beneath the lava flows during late Tertiary and Quaternary. Water and gas samples were collected for a variety of chemical and isotope composition analyses, including in-situ pH, alkalinity, oxidation reduction potential (ORP), major and trace elements, and C and H isotope measurements. Fluids issuing from SVHS can be classified as Na-(Cl)-SO4 type, with the major cation and anion being Na+ and SO42-, respectively. Thermodynamic calculation using ORP and major element data indicated that sulfate is the most dominant sulfur species, which is consistent with anion analysis results. Aquifer temperatures at depth estimated by both dissolved SiO2 and Na-K-Ca geothermometers are in the range of 125.0 to 135.4 °C, and

  7. The Origin of Carbon-bearing Volatiles in Surprise Valley Hot Springs in the Great Basin: Carbon Isotope and Water Chemistry Characterizations

    Science.gov (United States)

    Fu, Qi; Socki, Richard A.; Niles, Paul B.; Romanek, Christopher; Datta, Saugata; Darnell, Mike; Bissada, Adry K.

    2013-01-01

    There are numerous hydrothermal fields within the Great Basin of North America, some of which have been exploited for geothermal resources. With methane and other carbon-bearing compounds being observed, in some cases with high concentrations, however, their origins and formation conditions remain unknown. Thus, studying hydrothermal springs in this area provides us an opportunity to expand our knowledge of subsurface (bio)chemical processes that generate organic compounds in hydrothermal systems, and aid in future development and exploration of potential energy resources as well. While isotope measurement has long been used for recognition of their origins, there are several secondary processes that may generate variations in isotopic compositions: oxidation, re-equilibration of methane and other alkanes with CO2, mixing with compounds of other sources, etc. Therefore, in addition to isotopic analysis, other evidence, including water chemistry and rock compositions, are necessary to identify volatile compounds of different sources. Surprise Valley Hot Springs (SVHS, 41 deg 32'N, 120 deg 5'W), located in a typical basin and range province valley in northeastern California, is a terrestrial hydrothermal spring system of the Great Basin. Previous geophysical studies indicated the presence of clay-rich volcanic and sedimentary rocks of Tertiary age beneath the lava flows in late Tertiary and Quaternary. Water and gas samples were collected for a variety of chemical and isotope composition analyses, including in-situ pH, alkalinity, conductivity, oxidation reduction potential (ORP), major and trace elements, and C and H isotope measurements. Fluids issuing from SVHS can be classified as Na-(Cl)-SO4 type, with the major cation and anion being Na+ and SO4(2-), respectively. Thermodynamic calculation using ORP and major element data indicated that sulfate is the most dominant sulfur species, which is consistent with anion analysis results. Aquifer temperatures at depth

  8. The Origin of Carbon-bearing Volatiles in Surprise Valley Hot Springs in the Great Basin: Carbon Isotope aud Water Chemistry Characterizations

    Science.gov (United States)

    Fu, Qi; Socki, Richard A.; Niles, Paul B.; Romanek, Christopher; Datta, Saugata; Darnell, Mike; Bissada, Adry K.

    2013-01-01

    There are numerous hydrothermal fields within the Great Basin of North America, some of which have been exploited for geothermal resources. With methane and other carbon-bearing compounds being observed, in some cases with high concentrations, however, their origins and formation conditions remain unknown. Thus, studying hydrothermal springs in this area provides us an opportunity to expand our knowledge of subsurface (bio)chemical processes that generate organic compounds in hydrothermal systems, and aid in future development and exploration of potential energy resources as well. While isotope measurement has long been used for recognition of their origins, there are several secondary processes that may generate variations in isotopic compositions: oxidation, re-equilibration of methane and other alkanes with CO2, mixing with compounds of other sources, etc. Therefore, in addition to isotopic analysis, other evidence, including water chemistry and rock compositions, are necessary to identify volatile compounds of different sources. Surprise Valley Hot Springs (SVHS, 41º32'N, 120º5'W), located in a typical basin and range province valley in northeastern California, is a terrestrial hydrothermal spring system of the Great Basin. Previous geophysical studies indicated the presence of clay-rich volcanic and sedimentary rocks of Tertiary age beneath the lava flows in late Tertiary and Quaternary. Water and gas samples were collected for a variety of chemical and isotope composition analyses, including in-situ pH, alkalinity, conductivity, oxidation reduction potential (ORP), major and trace elements, and C and H isotope measurements. Fluids issuing from SVHS can be classified as Na-(Cl)-SO4 type, with the major cation and anion being Na+ and SO4 2-, respectively. Thermodynamic calculation using ORP and major element data indicated that sulfate is the most dominant sulfur species, which is consistent with anion analysis results. Aquifer temperatures at depth estimated

  9. Both msa Genes in Renibacterium salmoninarum Are Needed for Full Virulence in Bacterial Kidney Disease

    OpenAIRE

    Coady, Alison M; Murray, Anthony L.; Elliott, Diane G.; Rhodes, Linda D.

    2006-01-01

    Renibacterium salmoninarum, a gram-positive diplococcobacillus that causes bacterial kidney disease among salmon and trout, has two chromosomal loci encoding the major soluble antigen (msa) gene. Because the MSA protein is widely suspected to be an important virulence factor, we used insertion-duplication mutagenesis to generate disruptions of either the msa1 or msa2 gene. Surprisingly, expression of MSA protein in broth cultures appeared unaffected. However, the virulence of either mutant in...

  10. Depletion of the non-coding regulatory 6S RNA in E. coli causes a surprising reduction in the expression of the translation machinery

    Directory of Open Access Journals (Sweden)

    Wagner Rolf

    2010-03-01

    Full Text Available Abstract Background 6S RNA from E. coli is known to bind to RNA polymerase interfering with transcription initiation. Because 6S RNA concentrations are maximal at stationary phase and binding occurs preferentially to the holoenzyme associated with σ70 (Eσ70 it is believed that 6S RNA supports adjustment to stationary phase transcription. Previous studies have also suggested that inhibition is specific for σ70-dependent promoters characterized by a weak -35 recognition motif or extended -10 promoters. There are many exceptions to this precept, showing that other types of promoters, including stationary phase-specific (σ38-dependent promoters are inhibited. Results To solve this apparent ambiguity and to better understand the role of 6S RNA in stationary phase transition we have performed a genome-wide transcriptional analysis of wild-type and 6S RNA deficient cells growing to mid-log or early stationary phase. We found 245 genes at the exponential growth phase and 273 genes at the early stationary phase to be ≥ 1.5-fold differentially expressed. Up- and down-regulated genes include many transcriptional regulators, stress-related proteins, transporters and several enzymes involved in purine metabolism. As the most striking result during stationary phase, however, we obtained in the 6S RNA deficient strain a concerted expression reduction of genes constituting the translational apparatus. In accordance, primer extension analysis showed that transcription of ribosomal RNAs, representing the key molecules for ribosome biogenesis, is also significantly reduced under the same conditions. Consistent with this finding biochemical analysis of the 6S RNA deficient strain indicates that the lack of 6S RNA is apparently compensated by an increase of the basal ppGpp concentration, known to affect growth adaptation and ribosome biogenesis. Conclusions The analysis demonstrated that the effect of 6S RNA on transcription is not strictly confined to σ70

  11. Trichoderma genes

    Science.gov (United States)

    Foreman, Pamela [Los Altos, CA; Goedegebuur, Frits [Vlaardingen, NL; Van Solingen, Pieter [Naaldwijk, NL; Ward, Michael [San Francisco, CA

    2012-06-19

    Described herein are novel gene sequences isolated from Trichoderma reesei. Two genes encoding proteins comprising a cellulose binding domain, one encoding an arabionfuranosidase and one encoding an acetylxylanesterase are described. The sequences, CIP1 and CIP2, contain a cellulose binding domain. These proteins are especially useful in the textile and detergent industry and in pulp and paper industry.

  12. The gene identification problem: An overview for developers

    Energy Technology Data Exchange (ETDEWEB)

    Fickett, J.W.

    1995-03-27

    The gene identification problem is the problem of interpreting nucleotide sequences by computer, in order to provide tentative annotation on the location, structure, and functional class of protein-coding genes. This problem is of self-evident importance, and is far from being fully solved, particularly for higher eukaryotes, Thus it is not surprising that the number of algorithm and software developers working in this area is rapidly increasing. The present paper is an overview of the field, with an emphasis on eukaryotes, for such developers.

  13. Horizontal acquisition of multiple mitochondrial genes from a parasitic plant followed by gene conversion with host mitochondrial genes

    Directory of Open Access Journals (Sweden)

    Hao Weilong

    2010-12-01

    mitochondrial copies suggests that transferred genes may be evolutionarily important in generating mitochondrial genetic diversity. Finally, the complex relationships within each lineage of transferred genes imply a surprisingly complicated history of these genes in Plantago subsequent to their acquisition via HGT and this history probably involves some combination of additional transfers (including intracellular transfer, gene duplication, differential loss and mutation-rate variation. Unravelling this history will probably require sequencing multiple mitochondrial and nuclear genomes from Plantago. See Commentary: http://www.biomedcentral.com/1741-7007/8/147.

  14. Construction and characterization of single-chain variable fragment antibody library derived from germline rearranged immunoglobulin variable genes.

    Directory of Open Access Journals (Sweden)

    Man Cheng

    Full Text Available Antibody repertoires for library construction are conventionally harvested from mRNAs of immune cells. To examine whether germline rearranged immunoglobulin (Ig variable region genes could be used as source of antibody repertoire, an immunized phage-displayed scFv library was prepared using splenocytic genomic DNA as template. In addition, a novel frame-shifting PCR (fsPCR step was introduced to rescue stop codon and to enhance diversity of the complementarity-determining region 3 (CDR3. The germline scFv library was initially characterized against the hapten antigen phenyloxazolone (phOx. Sequence analysis of the phOx-selective scFvs indicated that the CDRs consisted of novel as well as conserved motifs. In order to illustrate that the diversity of CDR3 was increased by the fsPCR step, a second scFv library was constructed using a single scFv clone L3G7C as a template. Despite showing similar binding characteristics towards phOx, the scFv clones that were obtained from the L3G7C-derived antibody library gave a lower non-specific binding than that of the parental L3G7C clone. To determine whether germline library represented the endogenous immune status, specific scFv clones for nucleocapsid (N protein of SARS-associated coronavirus (SCoV were obtained both from naïve and immunized germline scFv libraries. Both libraries yielded specific anti-N scFvs that exhibited similar binding characteristics towards recombinant N protein, except the immunized library gave a larger number of specific anti-N scFv, and clones with identical nucleotide sequences were found. In conclusion, highly diversified antibody library can be efficiently constructed using germline rearranged immunoglobulin variable genes as source of antibody repertoires and fsPCR to diversify the CDR3.

  15. Gene Therapy.

    Science.gov (United States)

    Thorne, Barb; Takeya, Ryan; Vitelli, Francesca; Swanson, Xin

    2017-03-14

    Gene therapy refers to a rapidly growing field of medicine in which genes are introduced into the body to treat or prevent diseases. Although a variety of methods can be used to deliver the genetic materials into the target cells and tissues, modified viral vectors represent one of the more common delivery routes because of its transduction efficiency for therapeutic genes. Since the introduction of gene therapy concept in the 1970s, the field has advanced considerably with notable clinical successes being demonstrated in many clinical indications in which no standard treatment options are currently available. It is anticipated that the clinical success the field observed in recent years can drive requirements for more scalable, robust, cost effective, and regulatory-compliant manufacturing processes. This review provides a brief overview of the current manufacturing technologies for viral vectors production, drawing attention to the common upstream and downstream production process platform that is applicable across various classes of viral vectors and their unique manufacturing challenges as compared to other biologics. In addition, a case study of an industry-scale cGMP production of an AAV-based gene therapy product performed at 2,000 L-scale is presented. The experience and lessons learned from this largest viral gene therapy vector production run conducted to date as discussed and highlighted in this review should contribute to future development of commercial viable scalable processes for vial gene therapies.

  16. Candidate genes in ocular dominance plasticity

    Directory of Open Access Journals (Sweden)

    M. Liset Rietman

    2012-02-01

    Full Text Available The objective of this study was to identify new candidate genes involved in experience-dependent plasticity. To this aim, we combined previously obtained data from recombinant inbred BXD strains on ocular dominance (OD plasticity and gene expression levels in the neocortex. We validated our approach using a list of genes which alter OD plasticity when inactivated. The expression levels of one fifth of these genes correlated with the amount of OD plasticity. Moreover, the two genes with the highest relative inter-strain differences were among the correlated genes. This suggests that correlation between gene expression levels and OD plasticity is indeed likely to point to genes with a causal role in modulating or generating plasticity in the visual cortex. After this validation on known plasticity genes, we identified new candidate genes by a multi-step approach. First, a list was compiled of all genes of which the expression level in BXD strains correlate with the amount of OD plasticity. To narrow this list to the more promising candidates, we took its cross-section with a list of genes co-regulated with the sensitive period for OD plasticity and a list of genes associated with pathways implicated in OD plasticity. This analysis resulted in a list of 32 candidate genes. The list contained unproven, but not surprising, candidates, such as the genes for IGF-1, NCAM1, NOGO-A, the gamma2 subunit of the GABA(A receptor, acetylcholine esterase and the catalytic subunit of cAMP-dependent protein kinase A. This was indicative of the viability of our approach, but more interesting were the novel candidate genes: Akap7, Akt1, Camk2d, Cckbr, Cd44, Crim1, Ctdsp2, Dnajc5, Gnai1, Itpka, Mapk8, Nbea, Nfatc3, Nlk, Npy5r, Phf21a, Phip, Ppm1l, Ppp1r1b, Rbbp4, Slc1a3, Slit2, Socs2, Spock3, St8sia1, Zfp207. The possible role of some of these candidates is discussed in the article.

  17. Gene Therapy

    Science.gov (United States)

    ... or improve your body's ability to fight disease. Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Researchers are still studying how and ...

  18. Genes V.

    Energy Technology Data Exchange (ETDEWEB)

    Lewin, B.

    1994-12-31

    This fifth edition book encompasses a wide range of topics covering 1,272 pages. The book is arranged into nine parts with a total of 36 chapters. These nine parts include Introduction; DNA as a Store of Information; Translation; Constructing Cells; Control of Prokaryotypic Gene Expression; Perpetuation of DNA; Organization of the Eukaryotypic Genome; Eukaryotypic Transcription and RNA Processing; The Dynamic Genome; and Genes in Development.

  19. Surprising abundance of Gallionella-related iron oxidizers in creek sediments at pH 4.4 or at high heavy metal concentrations.

    Science.gov (United States)

    Fabisch, Maria; Beulig, Felix; Akob, Denise M; Küsel, Kirsten

    2013-01-01

    We identified and quantified abundant iron-oxidizing bacteria (FeOB) at three iron-rich, metal-contaminated creek sites with increasing sediment pH from extremely acidic (R1, pH 2.7), to moderately acidic (R2, pH 4.4), to slightly acidic (R3, pH 6.3) in a former uranium-mining district. The geochemical parameters showed little variations over the 1.5 year study period. The highest metal concentrations found in creek sediments always coincided with the lowest metal concentrations in creek water at the slightly acidic site R3. Sequential extractions of R3 sediment revealed large portions of heavy metals (Ni, Cu, Zn, Pb, U) bound to the iron oxide fraction. Light microscopy of glass slides exposed in creeks detected twisted stalks characteristic of microaerobic FeOB of the family Gallionellaceae at R3 but also at the acidic site R2. Sequences related to FeOB such as Gallionella ferruginea, Sideroxydans sp. CL21, Ferritrophicum radicicola, and Acidovorax sp. BrG1 were identified in the sediments. The highest fraction of clone sequences similar to the acidophilic "Ferrovum myxofaciens" was detected in R1. Quantitative PCR using primer sets specific for Gallionella spp., Sideroxydans spp., and "Ferrovum myxofaciens" revealed that ~72% (R2 sediment) and 37% (R3 sediment) of total bacterial 16S rRNA gene copies could be assigned to groups of FeOB with dominance of microaerobic Gallionella spp. at both sites. Gallionella spp. had similar and very high absolute and relative gene copy numbers in both sediment communities. Thus, Gallionella-like organisms appear to exhibit a greater acid and metal tolerance than shown before. Microaerobic FeOB from R3 creek sediment enriched in newly developed metal gradient tubes tolerated metal concentrations of 35 mM Co, 24 mM Ni, and 1.3 mM Cd, higher than those in sediments. Our results will extend the limited knowledge of FeOB at contaminated, moderately to slightly acidic environments.

  20. Surprising abundance of Gallionella-related iron oxidizers in creek sediments at pH 4.4 or at high heavy metal concentrations

    Directory of Open Access Journals (Sweden)

    Maria eFabisch

    2013-12-01

    Full Text Available We identified and quantified abundant iron-oxidizing bacteria (FeOB at three iron-rich, metal-contaminated creek sites with increasing sediment pH from extremely acidic (R1, pH 2.7, to moderately acidic (R2, pH 4.4, to slightly acidic (R3, pH 6.3 in a former uranium-mining district. The geochemical parameters showed little variations over the 1.5 year study period. The highest metal concentrations found in creek sediments always coincided with the lowest metal concentrations in creek water at the slightly acidic site R3. Sequential extractions of R3 sediment revealed large portions of heavy metals (Ni, Cu, Zn, Pb, U bound to the iron oxide fraction. Light microscopy of glass slides exposed in creeks detected twisted stalks characteristic of microaerobic FeOB of the family Gallionellaceae at R3 but also at the acidic site R2. Sequences related to FeOB such as Gallionella ferruginea, Sideroxydans sp. CL21, Ferritrophicum radicicola, and Acidovorax sp. BrG1 were identified in the sediments. The highest fraction of clone sequences similar to the acidophilic ‘Ferrovum myxofaciens’ was detected in R1. Quantitative PCR using primer sets specific for Gallionella spp., Sideroxydans spp., and ‘Ferrovum myxofaciens’ revealed that approximately 72% (R2 sediment and 37% (R3 sediment of total bacterial 16S rRNA gene copies could be assigned to groups of FeOB with dominance of microaerobic Gallionella spp. at both sites. Gallionella spp. had similar and very high absolute and relative gene copy numbers in both sediment communities. Thus, Gallionella-like organisms appear to exhibit a greater acid and metal tolerance than shown before. Microaerobic FeOB from R3 creek sediment enriched in newly developed metal gradient tubes tolerated metal concentrations of 35 mM Co, 24 mM Ni, and 1.3 mM Cd, higher than those in sediments. Our results will extend the limited knowledge of FeOB at contaminated, moderately to slightly acidic environments.

  1. Surprising abundance of Gallionella-related iron oxidizers in creek sediments at pH 4.4 or at high heavy metal concentrations

    Science.gov (United States)

    Fabisch, Maria; Beulig, Felix; Akob, Denise M.; Küsel, Kirsten

    2013-01-01

    We identified and quantified abundant iron-oxidizing bacteria (FeOB) at three iron-rich, metal-contaminated creek sites with increasing sediment pH from extremely acidic (R1, pH 2.7), to moderately acidic (R2, pH 4.4), to slightly acidic (R3, pH 6.3) in a former uranium-mining district. The geochemical parameters showed little variations over the 1.5 year study period. The highest metal concentrations found in creek sediments always coincided with the lowest metal concentrations in creek water at the slightly acidic site R3. Sequential extractions of R3 sediment revealed large portions of heavy metals (Ni, Cu, Zn, Pb, U) bound to the iron oxide fraction. Light microscopy of glass slides exposed in creeks detected twisted stalks characteristic of microaerobic FeOB of the family Gallionellaceae at R3 but also at the acidic site R2. Sequences related to FeOB such as Gallionella ferruginea, Sideroxydans sp. CL21, Ferritrophicum radicicola, and Acidovorax sp. BrG1 were identified in the sediments. The highest fraction of clone sequences similar to the acidophilic “Ferrovum myxofaciens” was detected in R1. Quantitative PCR using primer sets specific for Gallionella spp., Sideroxydans spp., and “Ferrovum myxofaciens” revealed that ~72% (R2 sediment) and 37% (R3 sediment) of total bacterial 16S rRNA gene copies could be assigned to groups of FeOB with dominance of microaerobic Gallionella spp. at both sites. Gallionella spp. had similar and very high absolute and relative gene copy numbers in both sediment communities. Thus, Gallionella-like organisms appear to exhibit a greater acid and metal tolerance than shown before. Microaerobic FeOB from R3 creek sediment enriched in newly developed metal gradient tubes tolerated metal concentrations of 35 mM Co, 24 mM Ni, and 1.3 mM Cd, higher than those in sediments. Our results will extend the limited knowledge of FeOB at contaminated, moderately to slightly acidic environments.

  2. Voltage-gated sodium channel gene repertoire of lampreys: gene duplications, tissue-specific expression and discovery of a long-lost gene.

    Science.gov (United States)

    Zakon, Harold H; Li, Weiming; Pillai, Nisha E; Tohari, Sumanty; Shingate, Prashant; Ren, Jianfeng; Venkatesh, Byrappa

    2017-09-27

    Studies of the voltage-gated sodium (Nav) channels of extant gnathostomes have made it possible to deduce that ancestral gnathostomes possessed four voltage-gated sodium channel genes derived from a single ancestral chordate gene following two rounds of genome duplication early in vertebrates. We investigated the Nav gene family in two species of lampreys (the Japanese lamprey Lethenteron japonicum and sea lamprey Petromyzon marinus) (jawless vertebrates-agnatha) and compared them with those of basal vertebrates to better understand the origin of Nav genes in vertebrates. We noted six Nav genes in both lamprey species, but orthology with gnathostome (jawed vertebrate) channels was inconclusive. Surprisingly, the Nav2 gene, ubiquitously found in invertebrates and believed to have been lost in vertebrates, is present in lampreys, elephant shark (Callorhinchus milii) and coelacanth (Latimeria chalumnae). Despite repeated duplication of the Nav1 family in vertebrates, Nav2 is only in single copy in those vertebrates in which it is retained, and was independently lost in ray-finned fishes and tetrapods. Of the other five Nav channel genes, most were expressed in brain, one in brain and heart, and one exclusively in skeletal muscle. Invertebrates do not express Nav channel genes in muscle. Thus, early in the vertebrate lineage Nav channels began to diversify and different genes began to express in heart and muscle. © 2017 The Author(s).

  3. Simultaneous integration of multiple genes into the Kluyveromyces marxianus chromosome.

    Science.gov (United States)

    Heo, Paul; Yang, Tae-Jun; Chung, Soon-Chun; Cheon, Yuna; Kim, Jun-Seob; Park, Jun-Bum; Koo, Hyun Min; Cho, Kwang Myung; Seo, Jin-Ho; Park, Jae Chan; Kweon, Dae-Hyuk

    2013-09-10

    While Kluyveromyces marxianus is a promising yeast strain for biotechnological applications, genetic engineering of this strain is still challenging, especially when multiple genes are to be transformed. Sequential gene integration, which takes advantage of repetitive insertion/excision of the URA3 gene as a marker, has been the best option until now, because the URA3-deletion mutant is the only precondition for this method. However, we found that the introduced gene is co-excised during the URA3 excision step for next gene introduction, resulting in a very low cumulative probability (<1.57×10⁻⁶ % for 4 genes) of integrating all genes of interest. To overcome this extremely low probability, and to reduce labor and time, all 4 genes were simultaneously transformed. Surprisingly, the infamously high 'non-homologous end joining' activity of K. marxianus enabled simultaneous integration of all 4 genes in a single step, with a probability of 7.9%. Various K. marxianus strains could also be similarly transformed. Our finding not only reduces the labor and time required for such procedures, but also removes a number of preconditions, such as pre-made vectors, selection markers and knockout mutants, which are needed to introduce many genes into K. marxianus.

  4. Cryptosporidiosis in Haiti: surprisingly low level of species diversity revealed by molecular characterization of Cryptosporidium oocysts from surface water and groundwater

    Science.gov (United States)

    Damiani, Céline; Balthazard-Accou, Ketty; Clervil, Elmyre; Diallo, Aïssata; Da Costa, Cécilia; Emmanuel, Evens; Totet, Anne; Agnamey, Patrice

    2013-01-01

    The protozoan parasite Cryptosporidium sp. has emerged as one of the most important water contaminants, causing waterborne outbreaks of diarrhoeal diseases worldwide. In Haiti, cryptosporidiosis is a frequent cause of diarrhoea in children under the age of five years, HIV-infected individuals, and people living in low socioeconomic conditions, mainly due to the consumption of water or food polluted by Cryptosporidium oocysts. The aim of this study was to detect and identify Cryptosporidium oocysts present in 12 water samples collected in Port-au-Prince and 4 water samples collected in Cap Haïtien. Initial detection consisted of immunomagnetic separation – immunofluorescence assay (IMS-IFA), which was confirmed by nested PCR, targeting the most polymorphic region of the 18S rRNA gene in 15/16 samples. Genotyping was performed by PCR-restriction fragment length polymorphism (RFLP) analysis and DNA sequencing. Under our working conditions, neither nested PCR-RFLP nor direct DNA sequencing revealed the expected species diversity, as only Cryptosporidium parvum was identified in the water samples studied. This study highlights the difficulty of detecting mixed populations of Cryptosporidium species in environmental samples. PMID:24252814

  5. Gene/Environment Interaction in Atherosclerosis: An Example of Clinical Medicine as Seen from the Evolutionary Perspective

    Directory of Open Access Journals (Sweden)

    Gerhard Mertens

    2010-01-01

    The chronic multifactorial disease of atherosclerosis clearly illustrates the Darwinian paradigm. Recent research, combining the effects of genes and environment, has provided surprising clues to the pathogenesis of this major public health problem. This example makes a strong case for recognizing evolution biology as a basic science for medicine.

  6. Isolation of Hox cluster genes from insects reveals an accelerated sequence evolution rate.

    Directory of Open Access Journals (Sweden)

    Heike Hadrys

    Full Text Available Among gene families it is the Hox genes and among metazoan animals it is the insects (Hexapoda that have attracted particular attention for studying the evolution of development. Surprisingly though, no Hox genes have been isolated from 26 out of 35 insect orders yet, and the existing sequences derive mainly from only two orders (61% from Hymenoptera and 22% from Diptera. We have designed insect specific primers and isolated 37 new partial homeobox sequences of Hox cluster genes (lab, pb, Hox3, ftz, Antp, Scr, abd-a, Abd-B, Dfd, and Ubx from six insect orders, which are crucial to insect phylogenetics. These new gene sequences provide a first step towards comparative Hox gene studies in insects. Furthermore, comparative distance analyses of homeobox sequences reveal a correlation between gene divergence rate and species radiation success with insects showing the highest rate of homeobox sequence evolution.

  7. DREB genes

    African Journals Online (AJOL)

    Unipar

    2015-03-12

    Mar 12, 2015 ... to AP2/ERF family, dehydration-responsive element-binding protein (DREB) genes, (CitsERF01 to ... Protein sequences of DREB subfamilies belonging to group I, .... position 37, and it was present in consensus in all protein.

  8. Horizontal gene transfer and the evolution of transcriptionalregulation in Escherichia coli

    Energy Technology Data Exchange (ETDEWEB)

    Price, Morgan N.; Dehal, Paramvir S.; Arkin, Adam P.

    2007-12-20

    Background: Most bacterial genes were acquired by horizontalgene transfer from other bacteria instead of being inherited bycontinuous vertical descent from an ancient ancestor}. To understand howthe regulation of these {acquired} genes evolved, we examined theevolutionary histories of transcription factors and of regulatoryinteractions from the model bacterium Escherichia coli K12. Results:Although most transcription factors have paralogs, these usually arose byhorizontal gene transfer rather than by duplication within the E. colilineage, as previously believed. In general, most neighbor regulators --regulators that are adjacent to genes that they regulate -- were acquiredby horizontal gene transfer, while most global regulators evolvedvertically within the gamma-Proteobacteria. Neighbor regulators wereoften acquired together with the adjacent operon that they regulate, sothe proximity might be maintained by repeated transfers (like "selfishoperons"). Many of the as-yet-uncharacterized (putative) regulators havealso been acquired together with adjacent genes, so we predict that theseare neighbor regulators as well. When we analyzed the histories ofregulatory interactions, we found that the evolution of regulation byduplication was rare, and surprisingly, many of the regulatoryinteractions that are shared between paralogs result from convergentevolution. Another surprise was that horizontally transferred genes aremore likely than other genes to be regulated by multiple regulators, andmost of this complex regulation probably evolved after the transfer.Conclusions: Our results highlight the rapid evolution of niche-specificgene regulation in bacteria.

  9. Extreme expansion of the olfactory receptor gene repertoire in African elephants and evolutionary dynamics of orthologous gene groups in 13 placental mammals.

    Science.gov (United States)

    Niimura, Yoshihito; Matsui, Atsushi; Touhara, Kazushige

    2014-09-01

    Olfactory receptors (ORs) detect odors in the environment, and OR genes constitute the largest multigene family in mammals. Numbers of OR genes vary greatly among species--reflecting the respective species' lifestyles--and this variation is caused by frequent gene gains and losses during evolution. However, whether the extent of gene gains/losses varies among individual gene lineages and what might generate such variation is unknown. To answer these questions, we used a newly developed phylogeny-based method to classify >10,000 intact OR genes from 13 placental mammal species into 781 orthologous gene groups (OGGs); we then compared the OGGs. Interestingly, African elephants had a surprisingly large repertoire (∼ 2000) of functional OR genes encoded in enlarged gene clusters. Additionally, OR gene lineages that experienced more gene duplication had weaker purifying selection, and Class II OR genes have evolved more dynamically than those in Class I. Some OGGs were highly expanded in a lineage-specific manner, while only three OGGs showed complete one-to-one orthology among the 13 species without any gene gains/losses. These three OGGs also exhibited highly conserved amino acid sequences; therefore, ORs in these OGGs may have physiologically important functions common to every placental mammal. This study provides a basis for inferring OR functions from evolutionary trajectory. © 2014 Niimura et al.; Published by Cold Spring Harbor Laboratory Press.

  10. Both msa genes in Renibacterium salmoninarum are needed for full virulence in bacterial kidney disease

    Science.gov (United States)

    Coady, A.M.; Murray, A.L.; Elliott, D.G.; Rhodes, L.D.

    2006-01-01

    Renibacterium salmoninarum, a gram-positive diplococcobacillus that causes bacterial kidney disease among salmon and trout, has two chromosomal loci encoding the major soluble antigen (msa) gene. Because the MSA protein is widely suspected to be an important virulence factor, we used insertion-duplication mutagenesis to generate disruptions of either the msa1 or msa2 gene. Surprisingly, expression of MSA protein in broth cultures appeared unaffected. However, the virulence of either mutant in juvenile Chinook salmon (Oncorhynchus tshawytscha) by intraperitoneal challenge was severely attenuated, suggesting that disruption of the msa1 or msa2 gene affected in vivo expression. Copyright ?? 2006, American Society for Microbiology. All Rights Reserved.

  11. Limnology in El Dorado: some surprising aspects of the regulation of phytoplankton productive capacity in a high-altitude Andean lake (Laguna de Guatavita, Colombia

    Directory of Open Access Journals (Sweden)

    Jhon Donato

    2012-09-01

    are sufficiently rare to justify the presentation of the data from Laguna de Guatavita that our studies have revealed so far.Los factores que regulan la producción primaria en un lago remoto, pequeño, ecuatorial y de elevada altitud en la región Oriental de los Andes Colombianos (4°58’50” N - 73°46’43” W, altura 2 935m.s.n.m., área 0.11km² y profundidad máxima 30m, que también tuvo importancia cultural para los indígenas precolombinos y los orígenes de la leyenda de El Dorado, fueron investigados. La relativa lejanía del lugar requirió una serie de tres campañas intensivas de estudio, en un periodo de un año (2003-2004. Durante cada campaña se realizaron perfiles temperatura, concentración de oxígeno e intensidad de luz. Se recolectaron muestras para medir la concentración de clorofila y de solutos de significado biológico en agua filtrada GF/F. Cada día de la campaña se llevaron a cabo mediciones de la producción primaria, como se indica por la producción de oxígeno. Estas demostraron que el potencial productivo es particularmente modesto (promedio de campañas de 45-90mgC/m².h, pero casi todos los aspectos de su regulación fueron sorprendentes y contrarios al sentido común. El lago es meromíctico, reminiscencia de dolinas kársticas de latitudes más altas y la estratificación se mantiene por los solutos. La penetración de luz es pobre, atribuible a la alta turbidez debida a la calcita fina y a otras partículas en suspensión. La producción primaria neta del mixolimnion de la Laguna de Guatavita es sensible a las variaciones del día a día de la radiación superficial. Deficiencias en la disponibilidad de nutrientes, sobre todo, del nitrógeno, también limitaron la capacidad productiva del fitoplancton. La laguna de Guatavita es una especie de enigma limnológico: aunque sin duda, no es el único, las descripciones de sitios similares en otras partes son lo suficientemente raras para justificar la presentación de los datos

  12. Recurrent DCC gene losses during bird evolution

    Science.gov (United States)

    Friocourt, François; Lafont, Anne-Gaelle; Kress, Clémence; Pain, Bertrand; Manceau, Marie; Dufour, Sylvie; Chédotal, Alain

    2017-01-01

    During development, midline crossing by axons brings into play highly conserved families of receptors and ligands. The interaction between the secreted ligand Netrin-1 and its receptor Deleted in Colorectal Carcinoma (DCC) is thought to control midline attraction of crossing axons. Here, we studied the evolution of this ligand/receptor couple in birds taking advantage of a wealth of newly sequenced genomes. From phylogeny and synteny analyses we can infer that the DCC gene has been conserved in most extant bird species, while two independent events have led to its loss in two avian groups, passeriformes and galliformes. These convergent accidental gene loss events are likely related to chromosome Z rearrangement. We show, using whole-mount immunostaining and 3Disco clearing, that in the nervous system of all birds that have a DCC gene, DCC protein expression pattern is similar to other vertebrates. Surprisingly, we show that the early developmental pattern of commissural tracts is comparable in all birds, whether or not they have a DCC receptor. Interestingly, only 4 of the 5 genes encoding secreted netrins, the DCC ligands in vertebrates, were found in birds, but Netrin-5 was absent. Together, these results support a remarkable plasticity of commissural axon guidance mechanisms in birds. PMID:28240285

  13. Automated discovery of functional generality of human gene expression programs.

    Directory of Open Access Journals (Sweden)

    Georg K Gerber

    2007-08-01

    Full Text Available An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-kappaB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal

  14. Modulation of R-gene expression across environments.

    Science.gov (United States)

    MacQueen, Alice; Bergelson, Joy

    2016-03-01

    Some environments are more conducive to pathogen growth than others, and, as a consequence, plants might be expected to invest more in resistance when pathogen growth is favored. Resistance (R-) genes in Arabidopsis thaliana have unusually extensive variation in basal expression when comparing the same R-gene among accessions collected from different environments. R-gene expression variation was characterized to explore whether R-gene expression is up-regulated in environments favoring pathogen proliferation and down-regulated when risks of infection are low; down-regulation would follow if costs of R-gene expression negatively impact plant fitness in the absence of disease. Quantitative reverse transcription-PCR was used to quantify the expression of 13 R-gene loci in plants grown in eight environmental conditions for each of 12 A. thaliana accessions, and large effects of the environment on R-gene expression were found. Surprisingly, almost every change in the environment--be it a change in biotic or abiotic conditions--led to an increase in R-gene expression, a response that was distinct from the average transcriptome response and from that of other stress response genes. These changes in expression are functional in that environmental change prior to infection affected levels of specific disease resistance to isolates of Pseudomonas syringae. In addition, there are strong latitudinal clines in basal R-gene expression and clines in R-gene expression plasticity correlated with drought and high temperatures. These results suggest that variation in R-gene expression across environments may be shaped by natural selection to reduce fitness costs of R-gene expression in permissive or predictable environments.

  15. Endothelial Genes

    Science.gov (United States)

    2005-06-01

    8217Department of Surgery, Division of Oncology , and 2Department of BRCA-l and BRCA-2 (breast cancer susceptibility genes), Pathology, University of...Suppression subtractive hybridization re- Cancer: principles and practice of oncology . Philadelphia: Lippincott- vealed an RNA sequence (GenBank accession...Lippman ME. Cancer of the breast: molecular biology angiogenesis in sarcomas and carcinomas. Clin Cancer Res 1999;5: of breast cancer. In: DeVita VT

  16. Different level of population differentiation among human genes

    Directory of Open Access Journals (Sweden)

    Zhang Ya-Ping

    2011-01-01

    Full Text Available Abstract Background During the colonization of the world, after dispersal out of African, modern humans encountered changeable environments and substantial phenotypic variations that involve diverse behaviors, lifestyles and cultures, were generated among the different modern human populations. Results Here, we study the level of population differentiation among different populations of human genes. Intriguingly, genes involved in osteoblast development were identified as being enriched with higher FST SNPs, a result consistent with the proposed role of the skeletal system in accounting for variation among human populations. Genes involved in the development of hair follicles, where hair is produced, were also found to have higher levels of population differentiation, consistent with hair morphology being a distinctive trait among human populations. Other genes that showed higher levels of population differentiation include those involved in pigmentation, spermatid, nervous system and organ development, and some metabolic pathways, but few involved with the immune system. Disease-related genes demonstrate excessive SNPs with lower levels of population differentiation, probably due to purifying selection. Surprisingly, we find that Mendelian-disease genes appear to have a significant excessive of SNPs with high levels of population differentiation, possibly because the incidence and susceptibility of these diseases show differences among populations. As expected, microRNA regulated genes show lower levels of population differentiation due to purifying selection. Conclusion Our analysis demonstrates different level of population differentiation among human populations for different gene groups.

  17. Gene Ontology

    Directory of Open Access Journals (Sweden)

    Gaston K. Mazandu

    2012-01-01

    Full Text Available The wide coverage and biological relevance of the Gene Ontology (GO, confirmed through its successful use in protein function prediction, have led to the growth in its popularity. In order to exploit the extent of biological knowledge that GO offers in describing genes or groups of genes, there is a need for an efficient, scalable similarity measure for GO terms and GO-annotated proteins. While several GO similarity measures exist, none adequately addresses all issues surrounding the design and usage of the ontology. We introduce a new metric for measuring the distance between two GO terms using the intrinsic topology of the GO-DAG, thus enabling the measurement of functional similarities between proteins based on their GO annotations. We assess the performance of this metric using a ROC analysis on human protein-protein interaction datasets and correlation coefficient analysis on the selected set of protein pairs from the CESSM online tool. This metric achieves good performance compared to the existing annotation-based GO measures. We used this new metric to assess functional similarity between orthologues, and show that it is effective at determining whether orthologues are annotated with similar functions and identifying cases where annotation is inconsistent between orthologues.

  18. Cartilage-selective genes identified in genome-scale analysis of non-cartilage and cartilage gene expression

    Directory of Open Access Journals (Sweden)

    Cohn Zachary A

    2007-06-01

    Full Text Available Abstract Background Cartilage plays a fundamental role in the development of the human skeleton. Early in embryogenesis, mesenchymal cells condense and differentiate into chondrocytes to shape the early skeleton. Subsequently, the cartilage anlagen differentiate to form the growth plates, which are responsible for linear bone growth, and the articular chondrocytes, which facilitate joint function. However, despite the multiplicity of roles of cartilage during human fetal life, surprisingly little is known about its transcriptome. To address this, a whole genome microarray expression profile was generated using RNA isolated from 18–22 week human distal femur fetal cartilage and compared with a database of control normal human tissues aggregated at UCLA, termed Celsius. Results 161 cartilage-selective genes were identified, defined as genes significantly expressed in cartilage with low expression and little variation across a panel of 34 non-cartilage tissues. Among these 161 genes were cartilage-specific genes such as cartilage collagen genes and 25 genes which have been associated with skeletal phenotypes in humans and/or mice. Many of the other cartilage-selective genes do not have established roles in cartilage or are novel, unannotated genes. Quantitative RT-PCR confirmed the unique pattern of gene expression observed by microarray analysis. Conclusion Defining the gene expression pattern for cartilage has identified new genes that may contribute to human skeletogenesis as well as provided further candidate genes for skeletal dysplasias. The data suggest that fetal cartilage is a complex and transcriptionally active tissue and demonstrate that the set of genes selectively expressed in the tissue has been greatly underestimated.

  19. NF-Y activates genes of metabolic pathways altered in cancer cells.

    Science.gov (United States)

    Benatti, Paolo; Chiaramonte, Maria Luisa; Lorenzo, Mariangela; Hartley, John A; Hochhauser, Daniel; Gnesutta, Nerina; Mantovani, Roberto; Imbriano, Carol; Dolfini, Diletta

    2016-01-12

    The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells.

  20. Gene doping: gene delivery for olympic victory

    OpenAIRE

    2012-01-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called ‘gene doping’. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted...

  1. GTOs and HGT: genes are older than expected and can be installed by horizontal gene transfer, especially with help from viruses

    Science.gov (United States)

    Klyce, Brig

    2012-10-01

    The origin of life on Earth took a puzzlingly short time. Panspermia is appealing because it means that the origin of life need not be confined to a few million years on one planet. Similar puzzles arise in the evolution of higher life forms. Punctuated equilibrium, for example, seems to violate the darwinian account of gradual evolution by trial-and-error, a few DNA nucleotides at a time. The strong version of panspermia alleviates this puzzle as well. If all of life comes ultimately from space, genes may appear to be older than necessary, evolution by the acquisition of whole genes or suites of genes, by horizontal gene transfer (HGT), becomes much more important, and punctuated equilibrium is not surprising. Does evidence support this supposition? How common are old genes? How important is HGT versus the gradual composition of genetic programs? We will look at these questions.

  2. The "fourth dimension" of gene transcription.

    Science.gov (United States)

    O'Malley, Bert W

    2009-05-01

    The three dimensions of space provide our relationship to position on the earth, but the fourth dimension of time has an equally profound influence on our lives. Everything from light and sound to weather and biology operate on the principle of measurable temporal periodicity. Consequently, a wide variety of time clocks affect all aspects of our existence. The annual (and biannual) cycles of activity, metabolism, and mating, the monthly physiological clocks of women and men, and the 24-h diurnal rhythms of humans are prime examples. Should it be surprising to us that the fourth dimension also impinges upon gene expression and that the genome itself is regulated by the fastest running of all biological clocks? Recent evidence substantiates the existence of such a ubiquitin-dependent transcriptional clock that is based upon the activation and destruction of transcriptional coactivators.

  3. A scan for positively selected genes in the genomes of humans and chimpanzees.

    Directory of Open Access Journals (Sweden)

    Rasmus Nielsen

    2005-06-01

    Full Text Available Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

  4. Impact of Institutional Care on Attachment Disorganization and Insecurity of Ukrainian Preschoolers: Protective Effect of the Long Variant of the Serotonin Transporter Gene (5HTT)

    Science.gov (United States)

    Bakermans-Kranenburg, Marian J.; Dobrova-Krol, Natasha; van IJzendoorn, Marinus

    2012-01-01

    Institutional care has been shown to lead to insecure and disorganized attachments and indiscriminate friendliness. Some children, however, are surprisingly resilient to the adverse environment. Here the protective role of the long variant of the serotonin receptor gene (5HTT) is explored in a small hypothesis-generating study of 37 Ukrainian…

  5. The Orion Nebula: Still Full of Surprises

    Science.gov (United States)

    2011-01-01

    This ethereal-looking image of the Orion Nebula was captured using the Wide Field Imager on the MPG/ESO 2.2-metre telescope at the La Silla Observatory, Chile. This nebula is much more than just a pretty face, offering astronomers a close-up view of a massive star-forming region to help advance our understanding of stellar birth and evolution. The data used for this image were selected by Igor Chekalin (Russia), who participated in ESO's Hidden Treasures 2010 astrophotography competition. Igor's composition of the Orion Nebula was the seventh highest ranked entry in the competition, although another of Igor's images was the eventual overall winner. The Orion Nebula, also known as Messier 42, is one of the most easily recognisable and best-studied celestial objects. It is a huge complex of gas and dust where massive stars are forming and is the closest such region to the Earth. The glowing gas is so bright that it can be seen with the unaided eye and is a fascinating sight through a telescope. Despite its familiarity and closeness there is still much to learn about this stellar nursery. It was only in 2007, for instance, that the nebula was shown to be closer to us than previously thought: 1350 light-years, rather than about 1500 light-years. Astronomers have used the Wide Field Imager on the MPG/ESO 2.2-metre telescope at ESO's La Silla Observatory in Chile to observe the stars within Messier 42. They found that the faint red dwarfs in the star cluster associated with the glowing gas radiate much more light than had previously been thought, giving us further insights into this famous object and the stars that it hosts. The data collected for this science project, with no original intention to make a colour image, have now been reused to create the richly detailed picture of Messier 42 shown here. The image is a composite of several exposures taken through a total of five different filters. Light that passed through a red filter as well as light from a filter that shows the glowing hydrogen gas, were coloured red. Light in the yellow-green part of the spectrum is coloured green, blue light is coloured blue and light that passed through an ultraviolet filter has been coloured purple. The exposure times were about 52 minutes through each filter. This image was processed by ESO using the observational data found by Igor Chekalin (Russia) [1], who participated in ESO's Hidden Treasures 2010 astrophotography competition [2], organised by ESO in October-November 2010, for everyone who enjoys making beautiful images of the night sky using real astronomical data. Notes [1] Igor searched through ESO's archive and identified datasets that he used to compose his image of Messier 42, which was the seventh highest ranked entry in the competition, out of almost 100 entries. His original work can be seen here. Igor Chekalin was awarded the first prize of the competition for his composition of Messier 78, and he also submitted an image of NGC3169, NGC3166 and SN 2003cg, which was ranked second highest. [2] ESO's Hidden Treasures 2010 competition gave amateur astronomers the opportunity to search through ESO's vast archives of astronomical data, hoping to find a well-hidden gem that needed polishing by the entrants. Participants submitted nearly 100 entries and ten skilled people were awarded some extremely attractive prizes, including an all expenses paid trip for the overall winner to ESO's Very Large Telescope (VLT) on Cerro Paranal, in Chile, the world's most advanced optical telescope. The ten winners submitted a total of 20 images that were ranked as the highest entries in the competition out of the near 100 images. More information ESO, the European Southern Observatory, is the foremost intergovernmental astronomy organisation in Europe and the world's most productive astronomical observatory. It is supported by 15 countries: Austria, Belgium, Brazil, the Czech Republic, Denmark, France, Finland, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, Switzerland and the United Kingdom. ESO carries out an ambitious programme focused on the design, construction and operation of powerful ground-based observing facilities enabling astronomers to make important scientific discoveries. ESO also plays a leading role in promoting and organising cooperation in astronomical research. ESO operates three unique world-class observing sites in Chile: La Silla, Paranal and Chajnantor. At Paranal, ESO operates the Very Large Telescope, the world's most advanced visible-light astronomical observatory and VISTA, the world's largest survey telescope. ESO is the European partner of a revolutionary astronomical telescope ALMA, the largest astronomical project in existence. ESO is currently planning a 42-metre European Extremely Large optical/near-infrared Telescope, the E-ELT, which will become "the world's biggest eye on the sky".

  6. Summer Student takes ISOLDE by surprise

    CERN Multimedia

    Katarina Anthony

    2012-01-01

    Two weeks ago, the Collinear Resonant Ionization Spectroscopy (CRIS) experiment at ISOLDE performed some of the world’s most sensitive measurements of the nuclear structure of francium, one of the rarest and least-understood elements. Gathered in record time and with excellent background resolution, the results are in good agreement with model predictions. The developer of their model? 2012 Summer Student, Ruben de Groote.   When student Ruben de Groote arrived at CERN this June, he joined one of CERN’s smallest experiments: CRIS. With a team of just 8 people at CERN, the CRIS experiment has become the world’s best facility to study the nuclear structure of light francium isotopes. By using a combination of resonant ionization spectroscopy and collinear laser spectroscopy, the experiment can select francium beams in a specific nuclear state with little background noise. As part of his thesis, Ruben has been developing a model – based on work by his Univers...

  7. Comment exploiter les 'corpus-surprise' ?

    Directory of Open Access Journals (Sweden)

    Rittaud-Hutinet, Chantal

    2009-01-01

    Full Text Available To what extent non-recorded oral corpora may constitute objects of analysis of pragmatic meaning?These corpora are heard by chance: on the radio, on television, in the street, a shop, a means of transport or generally in any conversational interaction in which the linguist participates, but had not previously planned to record for his research. The problem of the use of these corpora in linguistics is all the more crucial since the aim, in phonopragmatics, is to discover the functions and significations of their phonic part. I shall attempt to answer the following questions:–The accuracy of the transcription with respect to the original. To what extent can we ignore our own phonological code, our regional variants, mastered/partly known styles of speech?–The reliability of the oral reproduction carried out by the linguist – for example, during a talk at a conference. What is his capacity for deferred mimicry?–The relation between a significant discrepancy and the elocutionary habits of the speaker.–The relation between the comprehension of the external auditors and the effect produced on the 'real' person addressed.Considering that transparency is (sometimes? often? an illusion, I shall also examine what precautions should be taken so that these corpora offer guarantees as to the veracity.

  8. Mesocosms Reveal Ecological Surprises from Climate Change.

    Science.gov (United States)

    Fordham, Damien A

    2015-12-01

    Understanding, predicting, and mitigating the impacts of climate change on biodiversity poses one of the most crucial challenges this century. Currently, we know more about how future climates are likely to shift across the globe than about how species will respond to these changes. Two recent studies show how mesocosm experiments can hasten understanding of the ecological consequences of climate change on species' extinction risk, community structure, and ecosystem functions. Using a large-scale terrestrial warming experiment, Bestion et al. provide the first direct evidence that future global warming can increase extinction risk for temperate ectotherms. Using aquatic mesocosms, Yvon-Durocher et al. show that human-induced climate change could, in some cases, actually enhance the diversity of local communities, increasing productivity. Blending these theoretical and empirical results with computational models will improve forecasts of biodiversity loss and altered ecosystem processes due to climate change.

  9. Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

    Directory of Open Access Journals (Sweden)

    Anders Lyngvi Fougner

    2016-04-01

    Full Text Available Rapid, accurate and robust glucose measurements are needed to make a safe artificial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP sensor sites, as an alternative to the SC location. Intraarterial (IA and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70--360 mg/dL (approximately 3.8--20 mmol/L. Optical interferometric sensors were used for IA and IP measurements. A first-order dynamic model with time delay was fitted to the data after compensating for sensor dynamics. Additionally, off-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing. The time delay in glucose excursions from central circulation (IA to IP sensor location was found to be in the range 0--26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s, and the time constant was found to be 0.5--10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min. IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal fluid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies. This study may provide a benchmark for future, rapid IP glucose sensors.

  10. Primary Renal Synovial Sarcoma: An Oncologic Surprise

    Directory of Open Access Journals (Sweden)

    H. Krishna Moorthy

    2014-09-01

    Full Text Available Primary renal synovial sarcoma is a rare tumor having a specific chromosomal translocation t(X; 18 (p11.2; q11.2. The clinical features of this tumor and radiologic appearances are quite similar to those of renal cell carcinoma. Confirmatory diagnosis requires fluorescent in situ hybridization or reverse transcriptase polymerase chain reaction validation for differentiating the tumors from sarcomatoid renal cell carcinoma. We present a case of primary renal synovial sarcoma that was diagnosed in a middle-aged man.

  11. A SURGICAL SURPRISE: A RARE CASE REPORT

    Directory of Open Access Journals (Sweden)

    Jaya Shree

    2014-08-01

    Full Text Available Implantation of the blastocyst anywhere else other than the uterine cavity is ectopic pregnancy. Ovarian Pregnancy is one of the rare forms of an ectopic pregnancy. The incidence of ovarian pregnancy is 0.15 to 3 % 1 of all ectopic pregnancies. Here we present a case of ruptured ovarian pregnancy, which was preoperatively diagnosed as ruptured tubal pregnancy and later found to be an ovarian pregnancy at laparotomy.

  12. The Energetic Universe: a Nobel Surprise

    Science.gov (United States)

    Kirshner, Robert P.

    2015-01-01

    he history of cosmic expansion can be accurately traced using Type Ia supernovae (SN Ia) as standard candles. Over the past 40 years, this effort has improved its precision and extended its reach in redshift. Recently, the distances to SN Ia have been measured to a precision of ~5% using luminosity information that is encoded in the shape of the supernova's rest frame optical light curve. By combining observations of supernova distances as measured from their light curves and redshifts measured from spectra, we can detect changes in the cosmic expansion rate. This empirical approach was successfully exploited by the High-Z Supernova Team and by the Supernova Cosmology Project to detect cosmic expansion and to infer the presence of dark energy. The 2011 Nobel Prize in Physics was awarded to Perlmutter, Schmidt and Riess for this discovery. The world's sample of well-observed SN Ia light curves at high redshift and low, approaching 1000 objects, is now large enough to make statistical errors due to sample size a thing of the past. Systematic errors are now the challenge. To learn the properties of dark energy and determine, for example, whether it has an equation-of-state that is different from the cosmological constant demands higher precision and better accuracy. The largest systematic uncertainties come from light curve fitters, photometric calibration errors, and from uncertain knowledge of the scattering properties of dust along the line of sight. Efforts to use SN Ia spectra as luminosity indicators have had some success, but have not yet produced a big step forward. Fortunately, observations of SN Ia in the near infrared (NIR), from 1 to 2 microns, offer a very promising path to better knowledge of the Hubble constant and to improved constraints on dark energy. In the NIR, SN Ia are better standard candles and the effects of dust absorption are smaller. We have begun an HST program dubbed RAISIN (SN IA in the IR) to tighten our grip on dark energy properties

  13. Synecdoche and Surprise: Transdisciplinary Knowledge Production

    Science.gov (United States)

    Dalke, Anne; McCormack, Elizabeth F.

    2007-01-01

    Using contemporary insights from feminist critical theory and the literary device of synecdoche, we argue that transdisciplinary knowledge is productive because it maximizes serendipity. We draw on student learning experiences in a course on "Gender and Science" to illustrate how the dichotomous frameworks and part-whole correspondences that are…

  14. Taken with Surprise: Critical Incidents in Teaching

    Science.gov (United States)

    Pui-Lan, Kwok; Brown, William P.; Delamarter, Steve; Frank, Thomas E.; Marshall, Joretta L.; Menn, Esther; Riggs, Marcia Y.

    2005-01-01

    This collection of essays tackles thorny questions related to critical incidents in teaching. By using different pedagogical methods and techniques, each author provokes creative thinking about how to address specific concerns common to teaching. The authors demonstrate that the teaching and learning process must make room for--if not…

  15. Serendipity: A Delightful Surprise that Requires Insight.

    Science.gov (United States)

    Florczak, Kristine L

    2015-10-01

    Since serendipity is the focus of this column, its definition is explored first. Then, qualitative and quantitative research methodologies are compared as to how they handle such unexpected findings. Next, the nature of complex adaptive systems is discussed. Here it is suggested that modifications to extant quantitative methodologies, including the incorporation of serendipitous findings, are requisite to explain the nature of dynamic ever-evolving systems.

  16. Psychosurgery: National Commission Issues Surprisingly Favorable Report

    Science.gov (United States)

    Culliton, Barbara J.

    1976-01-01

    Presents results of a national commission's investigation of psychosurgery. Results indicate the procedure to be effective in the cure of patients suffering from pain accompanied by depression, while avoiding the destruction caused by prefrontal lobotomies. (SL)

  17. The surprising inefficiency of dwarf satellite quenching

    CERN Document Server

    Wheeler, Coral; Cooper, Michael C; Boylan-Kolchin, Mike; Bullock, James S

    2014-01-01

    We study dwarf satellite galaxy quenching using observations from the Geha et al. (2012) NSA/SDSS catalog together with LCDM cosmological simulations to facilitate selection and interpretation. We show that fewer than 30% of dwarfs (M* ~ 10^8.5-10^9.5 Msun) identified as satellites within massive host halos (Mhost ~ 10^12.5-10^14 Msun) are quenched, in spite of the expectation from simulations that half of them should have been accreted more than 6 Gyr ago. We conclude that whatever the action triggering environmental quenching of dwarf satellites, the process must be highly inefficient. We investigate a series of simple, one-parameter quenching models in order understand what is required to explain the low quenched fraction and conclude that either the quenching timescale is very long (> 9.5 Gyr, a "slow starvation" scenario) or that the environmental trigger is not well matched to accretion within the virial volume. We discuss these results in light of the fact that most of the low mass dwarf satellites in ...

  18. Mesocosms Reveal Ecological Surprises from Climate Change.

    Directory of Open Access Journals (Sweden)

    Damien A Fordham

    2015-12-01

    Full Text Available Understanding, predicting, and mitigating the impacts of climate change on biodiversity poses one of the most crucial challenges this century. Currently, we know more about how future climates are likely to shift across the globe than about how species will respond to these changes. Two recent studies show how mesocosm experiments can hasten understanding of the ecological consequences of climate change on species' extinction risk, community structure, and ecosystem functions. Using a large-scale terrestrial warming experiment, Bestion et al. provide the first direct evidence that future global warming can increase extinction risk for temperate ectotherms. Using aquatic mesocosms, Yvon-Durocher et al. show that human-induced climate change could, in some cases, actually enhance the diversity of local communities, increasing productivity. Blending these theoretical and empirical results with computational models will improve forecasts of biodiversity loss and altered ecosystem processes due to climate change.

  19. Methanogenesis: surprising molecules, microorganisms and ecosystems.

    Science.gov (United States)

    Vogels, G D; van der Drift, C; Stumm, C K; Keltjens, J T; Zwart, K B

    1984-01-01

    Methanogenesis involves a novel set of coenzymes as one-carbon and electron carriers. Consequently, metabolic processes of methanogens deviate from those present in non-methanogenic bacteria. Methanogenic bacteria can be classified on the basis of substrate utilization. Group I (24 species) grows at the expense of hydrogen plus CO2 and/or formate and group II (7 species) uses methanol and/or acetate. Hydrogen-consuming methanogens are found as epi- or endosymbionts of anaerobic ciliates.

  20. Synecdoche and Surprise: Transdisciplinary Knowledge Production

    Directory of Open Access Journals (Sweden)

    Anne Dalke

    2007-01-01

    Full Text Available Using contemporary insights from feminist critical theory and the literary device of synecdoche, we argue that transdisciplinary knowledge is productive because it maximizes serendipity. We draw on student learning experiences in a course on “Gender and Science” to illustrate how the dichotomous frameworks and part-whole correspondences that are predominant in much disciplinary discourse must be dismantled for innovative intellectual work to take place. In such a process, disciplinary presumptions interrogate and unsettle one another to produce novel questions and answers.

  1. Plant Breeding: Surprisingly, Less Sex Is Better.

    Science.gov (United States)

    van Dijk, Peter J; Rigola, Diana; Schauer, Stephen E

    2016-02-01

    Introduction of apomixis, asexual reproduction through seeds, into crop species has the potential to dramatically transform plant breeding. A new study demonstrates that traits can be stably transferred between generations in newly produced apomictic lines, and heralds a breeding revolution needed to increase food production for the growing planet.

  2. A rice Stowaway MITE for gene transfer in yeast.

    Directory of Open Access Journals (Sweden)

    Isam Fattash

    Full Text Available Miniature inverted repeat transposable elements (MITEs lack protein coding capacity and often share very limited sequence similarity with potential autonomous elements. Their capability of efficient transposition and dramatic amplification led to the proposition that MITEs are an untapped rich source of materials for transposable element (TE based genetic tools. To test the concept of using MITE sequence in gene transfer, a rice Stowaway MITE previously shown to excise efficiently in yeast was engineered to carry cargo genes (neo and gfp for delivery into the budding yeast genome. Efficient excision of the cargo gene cassettes was observed even though the excision frequency generally decreases with the increase of the cargo sizes. Excised elements insert into new genomic loci efficiently, with about 65% of the obtained insertion sites located in genes. Elements at the primary insertion sites can be remobilized, frequently resulting in copy number increase of the element. Surprisingly, the orientation of a cargo gene (neo on a construct bearing dual reporter genes (gfp and neo was found to have a dramatic effect on transposition frequency. These results demonstrated the concept that MITE sequences can be useful in engineering genetic tools to deliver cargo genes into eukaryotic genomes.

  3. GeneEd -- A Genetics Educational Resource

    Science.gov (United States)

    ... Javascript on. Feature: Genetics 101 GeneEd — A Genetics Educational Resource Past Issues / Summer 2013 Table of Contents Science ... The Hereditary Material of Life / GeneEd — A Genetics Educational Resource / Using The Genetics Home Reference Website / Understanding the ...

  4. A single gene defect causing claustrophobia.

    Science.gov (United States)

    El-Kordi, A; Kästner, A; Grube, S; Klugmann, M; Begemann, M; Sperling, S; Hammerschmidt, K; Hammer, C; Stepniak, B; Patzig, J; de Monasterio-Schrader, P; Strenzke, N; Flügge, G; Werner, H B; Pawlak, R; Nave, K-A; Ehrenreich, H

    2013-04-30

    Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3'untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia.

  5. Genome-wide identification and mapping of NBS-encoding resistance genes in Solanum tuberosum group phureja.

    Directory of Open Access Journals (Sweden)

    Roberto Lozano

    Full Text Available The majority of disease resistance (R genes identified to date in plants encode a nucleotide-binding site (NBS and leucine-rich repeat (LRR domain containing protein. Additional domains such as coiled-coil (CC and TOLL/interleukin-1 receptor (TIR domains can also be present. In the recently sequenced Solanum tuberosum group phureja genome we used HMM models and manual curation to annotate 435 NBS-encoding R gene homologs and 142 NBS-derived genes that lack the NBS domain. Highly similar homologs for most previously documented Solanaceae R genes were identified. A surprising ∼41% (179 of the 435 NBS-encoding genes are pseudogenes primarily caused by premature stop codons or frameshift mutations. Alignment of 81.80% of the 577 homologs to S. tuberosum group phureja pseudomolecules revealed non-random distribution of the R-genes; 362 of 470 genes were found in high density clusters on 11 chromosomes.

  6. Utility of the NECPAL CCOMS-ICO(©) tool and the Surprise Question as screening tools for early palliative care and to predict mortality in patients with advanced chronic conditions: A cohort study.

    Science.gov (United States)

    Gómez-Batiste, Xavier; Martínez-Muñoz, Marisa; Blay, Carles; Amblàs, Jordi; Vila, Laura; Costa, Xavier; Espaulella, Joan; Villanueva, Alicia; Oller, Ramon; Martori, Joan Carles; Constante, Carles

    2017-09-01

    The Surprise Question (SQ) identifies patients with palliative care needs. The NECPAL CCOMS-ICO(©) (NECPAL) tool combines the Surprise Question with additional clinical parameters for a more comprehensive assessment. The capacity of these screening tools to predict mortality is still unknown. To explore the predictive validity of the NECPAL and SQ to determine 12- to 24-month mortality. Longitudinal, prospective and observational cohort study. Three primary care centres, one general hospital, one intermediate care centre, and four nursing homes. Population cohort with advanced chronic conditions and limited life prognosis. Patients were classified according to SQ and NECPAL criteria and followed for 24 months. Data available to assess 1059 of 1064 recruited patients (99.6%) at 12 and 24 months: 837 patients were SQ+ and 780 were NECPAL+. Mortality rates at 24 months were as follows: 44.6% (SQ+) versus 15.8% (SQ-) and 45.8% (NECPAL+) versus 18.3% (NECPAL-) ( p = 0.000). SQ+ and NECPAL+ identification was significantly correlated with 24-month mortality risk (hazard ratios: 2.719 and 2.398, respectively). Both tools were highly sensitive (91.4, CI: 88.7-94.1 and 87.5, CI: 84.3-90.7) with high negative predictive values (84.2, CI: 79.4-89.0 and 81.7, CI: 77.2-86.2), with low specificity and positive predictive value. The prognostic accuracy of SQ and NECPAL was 52.9% and 55.2%, respectively. The predictive validity was slightly better for NECPAL. SQ and NECPAL are valuable screening instruments to identify patients with limited life prognosis who may require palliative care. More research is needed to increase its prognostic utility in combination with other parameters.

  7. A structural study of [CpM(CO)3H] (M = Cr, Mo and W) by single-crystal X-ray diffraction and DFT calculations: sterically crowded yet surprisingly flexible molecules.

    Science.gov (United States)

    Burchell, Richard P L; Sirsch, Peter; Decken, Andreas; McGrady, G Sean

    2009-08-14

    The single-crystal X-ray structures of the complexes [CpCr(CO)3H] 1, [CpMo(CO)3H] 2 and [CpW(CO)3H] 3 are reported. The results indicate that 1 adopts a structure close to a distorted three-legged piano stool geometry, whereas a conventional four-legged piano stool arrangement is observed for 2 and 3. Further insight into the equilibrium geometries and potential energy surfaces of all three complexes was obtained by DFT calculations. These show that in the gas phase complex 1 also prefers a geometry close to a four-legged piano stool in line with its heavier congeners, and implying strong packing forces at work for 1 in the solid state. Comparison with their isolelectronic group 7 tricarbonyl counterparts [CpM(CO)3] (M = Mn 4 and Re 5) illustrates that 1, 2 and 3 are sterically crowded complexes. However, a surprisingly soft bending potential is evident for the M-H moiety, whose order (1 approximately = 2 < 3) correlates with the M-H bond strength rather than with the degree of congestion at the metal centre, indicating electronic rather than steric control of the potential. The calculations also reveal cooperative motions of the hydride and carbonyl ligands in the M(CO)3H unit, which allow the M-H moiety to move freely, in spite of the closeness of the four basal ligands, helping to explain the surprising flexibility of the crowded coordination sphere observed for this family of high CN complexes.

  8. Early events in the evolution of spider silk genes.

    Directory of Open Access Journals (Sweden)

    James Starrett

    Full Text Available Silk spinning is essential to spider ecology and has had a key role in the expansive diversification of spiders. Silk is composed primarily of proteins called spidroins, which are encoded by a multi-gene family. Spidroins have been studied extensively in the derived clade, Orbiculariae (orb-weavers, from the suborder Araneomorphae ('true spiders'. Orbicularians produce a suite of different silks, and underlying this repertoire is a history of duplication and spidroin gene divergence. A second class of silk proteins, Egg Case Proteins (ECPs, is known only from the orbicularian species, Lactrodectus hesperus (Western black widow. In L. hesperus, ECPs bond with tubuliform spidroins to form egg case silk fibers. Because most of the phylogenetic diversity of spiders has not been sampled for their silk genes, there is limited understanding of spidroin gene family history and the prevalence of ECPs. Silk genes have not been reported from the suborder Mesothelae (segmented spiders, which diverged from all other spiders >380 million years ago, and sampling from Mygalomorphae (tarantulas, trapdoor spiders and basal araneomorph lineages is sparse. In comparison to orbicularians, mesotheles and mygalomorphs have a simpler silk biology and thus are hypothesized to have less diversity of silk genes. Here, we present cDNAs synthesized from the silk glands of six mygalomorph species, a mesothele, and a non-orbicularian araneomorph, and uncover a surprisingly rich silk gene diversity. In particular, we find ECP homologs in the mesothele, suggesting that ECPs were present in the common ancestor of extant spiders, and originally were not specialized to complex with tubuliform spidroins. Furthermore, gene-tree/species-tree reconciliation analysis reveals that numerous spidroin gene duplications occurred after the split between Mesothelae and Opisthothelae (Mygalomorphae plus Araneomorphae. We use the spidroin gene tree to reconstruct the evolution of amino acid

  9. Early events in the evolution of spider silk genes.

    Science.gov (United States)

    Starrett, James; Garb, Jessica E; Kuelbs, Amanda; Azubuike, Ugochi O; Hayashi, Cheryl Y

    2012-01-01

    Silk spinning is essential to spider ecology and has had a key role in the expansive diversification of spiders. Silk is composed primarily of proteins called spidroins, which are encoded by a multi-gene family. Spidroins have been studied extensively in the derived clade, Orbiculariae (orb-weavers), from the suborder Araneomorphae ('true spiders'). Orbicularians produce a suite of different silks, and underlying this repertoire is a history of duplication and spidroin gene divergence. A second class of silk proteins, Egg Case Proteins (ECPs), is known only from the orbicularian species, Lactrodectus hesperus (Western black widow). In L. hesperus, ECPs bond with tubuliform spidroins to form egg case silk fibers. Because most of the phylogenetic diversity of spiders has not been sampled for their silk genes, there is limited understanding of spidroin gene family history and the prevalence of ECPs. Silk genes have not been reported from the suborder Mesothelae (segmented spiders), which diverged from all other spiders >380 million years ago, and sampling from Mygalomorphae (tarantulas, trapdoor spiders) and basal araneomorph lineages is sparse. In comparison to orbicularians, mesotheles and mygalomorphs have a simpler silk biology and thus are hypothesized to have less diversity of silk genes. Here, we present cDNAs synthesized from the silk glands of six mygalomorph species, a mesothele, and a non-orbicularian araneomorph, and uncover a surprisingly rich silk gene diversity. In particular, we find ECP homologs in the mesothele, suggesting that ECPs were present in the common ancestor of extant spiders, and originally were not specialized to complex with tubuliform spidroins. Furthermore, gene-tree/species-tree reconciliation analysis reveals that numerous spidroin gene duplications occurred after the split between Mesothelae and Opisthothelae (Mygalomorphae plus Araneomorphae). We use the spidroin gene tree to reconstruct the evolution of amino acid compositions of

  10. Increased incidence of rare codon clusters at 5' and 3' gene termini:implications for function

    Directory of Open Access Journals (Sweden)

    Clark Patricia L

    2010-02-01

    Full Text Available Abstract Background The process of translation can be affected by the use of rare versus common codons within the mRNA transcript. Results Here, we show that rare codons are enriched at the 5' and 3' termini of genes from E. coli and other prokaryotes. Genes predicted to be secreted show significant enrichment in 5' rare codon clusters, but not 3' rare codon clusters. Surprisingly, no correlation between 5' mRNA structure and rare codon usage was observed. Conclusions Potential functional roles for the enrichment of rare codons at terminal positions are explored.

  11. Antisense transcription as a tool to tune gene expression.

    Science.gov (United States)

    Brophy, Jennifer A N; Voigt, Christopher A

    2016-01-14

    A surprise that has emerged from transcriptomics is the prevalence of genomic antisense transcription, which occurs counter to gene orientation. While frequent, the roles of antisense transcription in regulation are poorly understood. We built a synthetic system in Escherichia coli to study how antisense transcription can change the expression of a gene and tune the response characteristics of a regulatory circuit. We developed a new genetic part that consists of a unidirectional terminator followed by a constitutive antisense promoter and demonstrate that this part represses gene expression proportionally to the antisense promoter strength. Chip-based oligo synthesis was applied to build a large library of 5,668 terminator-promoter combinations that was used to control the expression of three repressors (PhlF, SrpR, and TarA) in a simple genetic circuit (NOT gate). Using the library, we demonstrate that antisense promoters can be used to tune the threshold of a regulatory circuit without impacting other properties of its response function. Finally, we determined the relative contributions of antisense RNA and transcriptional interference to repressing gene expression and introduce a biophysical model to capture the impact of RNA polymerase collisions on gene repression. This work quantifies the role of antisense transcription in regulatory networks and introduces a new mode to control gene expression that has been previously overlooked in genetic engineering.

  12. Effects of stretch and shortening on gene expression in intact myocardium.

    Science.gov (United States)

    Haggart, Charles R; Ames, Elizabeth G; Lee, Jae K; Holmes, Jeffrey W

    2014-01-15

    Multiple cues have been suggested as the mechanical stimulus for the heart's hypertrophic response. Our work has previously suggested that the amount of cyclic shortening in cardiomyocytes controls myocyte shape and the amount of stretch controls myocyte size. To identify gene expression changes that occur in response to these mechanical perturbations, we used microarray analysis of papillary muscles cultured for 12 h at physiological or reduced levels of cyclic shortening and physiological or reduced mean stretch. Overall, genes related to extracellular matrix (ECM) were surprisingly prominent in our analysis. Connective tissue growth factor was among a small group of genes regulated by the amount of cyclic shortening regardless of the level of mean stretch, and many more ECM genes were regulated by shortening with reduced amounts of stretch. When we compared our results to gene expression data from an in vivo model of pressure overload (PO), which also decreases myocyte shortening, we found the genes that were commonly regulated in PO and our decreased shortening groups were most significantly enriched for ontology terms related to the ECM, followed by genes associated with mechanosensing and the cytoskeleton. The list of genes regulated in PO and our decreased shortening groups also includes genes known to change early in hypertrophy, such as myosin heavy chain 7, brain natriuretic peptide, and myosin binding protein C. We conclude that in intact myocardium, the amount of cyclic shortening may be an important regulator not only of myocyte genes classically associated with hypertrophy but also of ECM genes.

  13. Special Issue: Gene Conversion in Duplicated Genes

    Directory of Open Access Journals (Sweden)

    Hideki Innan

    2011-06-01

    Full Text Available Gene conversion is an outcome of recombination, causing non-reciprocal transfer of a DNA fragment. Several decades later than the discovery of crossing over, gene conversion was first recognized in fungi when non-Mendelian allelic distortion was observed. Gene conversion occurs when a double-strand break is repaired by using homologous sequences in the genome. In meiosis, there is a strong preference to use the orthologous region (allelic gene conversion, which causes non-Mendelian allelic distortion, but paralogous or duplicated regions can also be used for the repair (inter-locus gene conversion, also referred to as non-allelic and ectopic gene conversion. The focus of this special issue is the latter, interlocus gene conversion; the rate is lower than allelic gene conversion but it has more impact on phenotype because more drastic changes in DNA sequence are involved.

  14. Gene-expression signatures of Atlantic salmon's plastic life cycle

    Science.gov (United States)

    Aubin-Horth, N.; Letcher, B.H.; Hofmann, H.A.

    2009-01-01

    How genomic expression differs as a function of life history variation is largely unknown. Atlantic salmon exhibits extreme alternative life histories. We defined the gene-expression signatures of wild-caught salmon at two different life stages by comparing the brain expression profiles of mature sneaker males and immature males, and early migrants and late migrants. In addition to life-stage-specific signatures, we discovered a surprisingly large gene set that was differentially regulated-at similar magnitudes, yet in opposite direction-in both life history transitions. We suggest that this co-variation is not a consequence of many independent cellular and molecular switches in the same direction but rather represents the molecular equivalent of a physiological shift orchestrated by one or very few master regulators. ?? 2009 Elsevier Inc. All rights reserved.

  15. An Epigenetic Perspective on Developmental Regulation of Seed Genes

    Institute of Scientific and Technical Information of China (English)

    Heng Zhang; Joe Ogas

    2009-01-01

    The developmental program of seeds is promoted by master regulators that are expressed in a seed-specific manner.Ectopic expression studies reveal that expression of these master regulators and other transcriptional regulators is sufficient to promote seed-associated traits,including generation of somatic embryos.Recent work highlights the importance of chromatin-associated factors in restricting expression of seed-specific genes,in particular PcG proteins and ATP-dependent remodelers.This review summarizes what is known regarding factors that promote zygotic and/or somatic embryogenesis and the chromatin machinery that represses their expression.Characterization of the regulation of seedspecific genes reveals that plant chromatin-based repression systems exhibit broad conservation with and surprising differences from animal repression systems.

  16. Principles of gene therapy

    OpenAIRE

    Mammen Biju; Ramakrishnan T; Sudhakar Uma; Vijayalakshmi

    2007-01-01

    Genes are specific sequences of bases that encode instructions to make proteins. When genes are altered so that encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. This article reviews the fundamentals in gene therapy and its various modes of administration with an insight into the role of gene therapy in Periodontics an...

  17. Organization of immunoglobulin genes.

    Science.gov (United States)

    Tonegawa, S; Brack, C; Hozumi, N; Pirrotta, V

    1978-01-01

    The nucleotide-sequence determination of a cloned, embryonic Vlambda gene directly demonstrated that V genes are separate from a corresponding C gene in embryonic cells. Analysis by restriction enzymes of total cellular DNA from various sources strongly suggested that the two separate immunoglobulin genes become continuous during differentiation of B lymphocytes. There seems to be a strict correlation between the joining event and activation of the joined genes. Cloning of more immunoglobulin genes from embryo and plasma cells will not only provide direct demonstration of such a gene-joining event but also help in the elucidation of a possible relationship of the event to gene activation mechanisms.

  18. Locus- and Site-Specific DNA Methylation of 19 kDa Zein Genes in Maize.

    Directory of Open Access Journals (Sweden)

    Jian-Hong Xu

    Full Text Available An interesting question in maize development is why only a single zein gene is highly expressed in each of the 19-kDa zein gene clusters (A and B types, z1A2-1 and z1B4, in the immature endosperm. For instance, epigenetic marks could provide a structural difference. Therefore, we investigated the DNA methylation of the arrays of gene copies in both promoter and gene body regions of leaf (non-expressing tissue as a control, normal endosperm, and cultured endosperm. Although we could show that expressed genes have much lower methylation levels in promoter regions than silent ones in both leaf and normal endosperm, there was surprisingly also a difference in the pattern of the z1A and z1B gene clusters. The expression of z1B gene is suppressed by increased DNA methylation and activated with reduced DNA methylation, whereas z1A gene expression is not. DNA methylation in gene coding regions is higher in leaf than in endosperm, whereas no significant difference is observed in gene bodies between expressed and non-expressed gene copies. A median CHG methylation (25-30% appears to be optimal for gene expression. Moreover, tissue-cultured endosperm can reset the DNA methylation pattern and tissue-specific gene expression. These results reveal that DNA methylation changes of the 19-kDa zein genes is subject to plant development and tissue culture treatment, but varies in different chromosomal locations, indicating that DNA methylation changes do not apply to gene expression in a uniform fashion. Because tissue culture is used to produce transgenic plants, these studies provide new insights into variation of gene expression of integrated sequences.

  19. Harmonics of circadian gene transcription in mammals.

    Directory of Open Access Journals (Sweden)

    Michael E Hughes

    2009-04-01

    Full Text Available The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology and behavior. Numerous investigations have addressed the contribution of circadian rhythmicity to cellular, organ, and organismal physiology. We recently developed a method to look at transcriptional oscillations with unprecedented precision and accuracy using high-density time sampling. Here, we report a comparison of oscillating transcription from mouse liver, NIH3T3, and U2OS cells. Several surprising observations resulted from this study, including a 100-fold difference in the number of cycling transcripts in autonomous cellular models of the oscillator versus tissues harvested from intact mice. Strikingly, we found two clusters of genes that cycle at the second and third harmonic of circadian rhythmicity in liver, but not cultured cells. Validation experiments show that 12-hour oscillatory transcripts occur in several other peripheral tissues as well including heart, kidney, and lungs. These harmonics are lost ex vivo, as well as under restricted feeding conditions. Taken in sum, these studies illustrate the importance of time sampling with respect to multiple testing, suggest caution in use of autonomous cellular models to study clock output, and demonstrate the existence of harmonics of circadian gene expression in the mouse.

  20. Harmonics of circadian gene transcription in mammals.

    Science.gov (United States)

    Hughes, Michael E; DiTacchio, Luciano; Hayes, Kevin R; Vollmers, Christopher; Pulivarthy, S; Baggs, Julie E; Panda, Satchidananda; Hogenesch, John B

    2009-04-01

    The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology and behavior. Numerous investigations have addressed the contribution of circadian rhythmicity to cellular, organ, and organismal physiology. We recently developed a method to look at transcriptional oscillations with unprecedented precision and accuracy using high-density time sampling. Here, we report a comparison of oscillating transcription from mouse liver, NIH3T3, and U2OS cells. Several surprising observations resulted from this study, including a 100-fold difference in the number of cycling transcripts in autonomous cellular models of the oscillator versus tissues harvested from intact mice. Strikingly, we found two clusters of genes that cycle at the second and third harmonic of circadian rhythmicity in liver, but not cultured cells. Validation experiments show that 12-hour oscillatory transcripts occur in several other peripheral tissues as well including heart, kidney, and lungs. These harmonics are lost ex vivo, as well as under restricted feeding conditions. Taken in sum, these studies illustrate the importance of time sampling with respect to multiple testing, suggest caution in use of autonomous cellular models to study clock output, and demonstrate the existence of harmonics of circadian gene expression in the mouse.

  1. Gene doping: gene delivery for olympic victory.

    Science.gov (United States)

    Gould, David

    2013-08-01

    With one recently recommended gene therapy in Europe and a number of other gene therapy treatments now proving effective in clinical trials it is feasible that the same technologies will soon be adopted in the world of sport by unscrupulous athletes and their trainers in so called 'gene doping'. In this article an overview of the successful gene therapy clinical trials is provided and the potential targets for gene doping are highlighted. Depending on whether a doping gene product is secreted from the engineered cells or is retained locally to, or inside engineered cells will, to some extent, determine the likelihood of detection. It is clear that effective gene delivery technologies now exist and it is important that detection and prevention plans are in place.

  2. A comparison of reptilian and avian olfactory receptor gene repertoires: Species-specific expansion of group γ genes in birds

    Directory of Open Access Journals (Sweden)

    Kempenaers Bart

    2009-09-01

    Full Text Available Abstract Background The detection of odorants is mediated by olfactory receptors (ORs. ORs are G-protein coupled receptors that form a remarkably large protein superfamily in vertebrate genomes. We used data that became available through recent sequencing efforts of reptilian and avian genomes to identify the complete OR gene repertoires in a lizard, the green anole (Anolis carolinensis, and in two birds, the chicken (Gallus gallus and the zebra finch (Taeniopygia guttata. Results We identified 156 green anole OR genes, including 42 pseudogenes. The OR gene repertoire of the two bird species was substantially larger with 479 and 553 OR gene homologs in the chicken and zebra finch, respectively (including 111 and 221 pseudogenes, respectively. We show that the green anole has a higher fraction of intact OR genes (~72% compared with the chicken (~66% and the zebra finch (~38%. We identified a larger number and a substantially higher proportion of intact OR gene homologs in the chicken genome than previously reported (214 versus 82 genes and 66% versus 15%, respectively. Phylogenetic analysis showed that lizard and bird OR gene repertoires consist of group α, θ and γ genes. Interestingly, the vast majority of the avian OR genes are confined to a large expansion of a single branch (the so called γ-c clade. An analysis of the selective pressure on the paralogous genes of each γ-c clade revealed that they have been subjected to adaptive evolution. This expansion appears to be bird-specific and not sauropsid-specific, as it is lacking from the lizard genome. The γ-c expansions of the two birds do not intermix, i.e., they are lineage-specific. Almost all (group γ-c OR genes mapped to the unknown chromosome. The remaining OR genes mapped to six homologous chromosomes plus three to four additional chromosomes in the zebra finch and chicken. Conclusion We identified a surprisingly large number of potentially functional avian OR genes. Our data

  3. A Caenorhabditis motif compendium for studying transcriptional gene regulation

    Science.gov (United States)

    Dieterich, Christoph; Sommer, Ralf J

    2008-01-01

    Background Controlling gene expression is fundamental to biological complexity. The nematode Caenorhabditis elegans is an important model for studying principles of gene regulation in multi-cellular organisms. A comprehensive parts list of putative regulatory motifs was yet missing for this model system. In this study, we compile a set of putative regulatory motifs by combining evidence from conservation and expression data. Description We present an unbiased comparative approach to a regulatory motif compendium for Caenorhabditis species. This involves the assembly of a new nematode genome, whole genome alignments and assessment of conserved k-mers counts. Candidate motifs are selected from a set of 9,500 randomly picked genes by three different motif discovery strategies. Motif candidates have to pass a conservation enrichment filter. Motif degeneracy and length are optimized. Retained motif descriptions are evaluated by expression data using a non-parametric test, which assesses expression changes due to the presence/absence of individual motifs. Finally, we also provide condition-specific motif ensembles by conditional tree analysis. Conclusion The nematode genomes align surprisingly well despite high neutral substitution rates. Our pipeline delivers motif sets by three alternative strategies. Each set contains less than 400 motifs, which are significantly conserved and correlated with 214 out of 270 tested gene expression conditions. This motif compendium is an entry point to comprehensive studies on nematode gene regulation. The website: http://corg.eb.tuebingen.mpg.de/CMC has extensive query capabilities, supplements this article and supports the experimental list. PMID:18215260

  4. Developmental gene expression provides clues to relationships between sponge and eumetazoan body plans.

    Science.gov (United States)

    Leininger, Sven; Adamski, Marcin; Bergum, Brith; Guder, Corina; Liu, Jing; Laplante, Mary; Bråte, Jon; Hoffmann, Friederike; Fortunato, Sofia; Jordal, Signe; Rapp, Hans Tore; Adamska, Maja

    2014-05-20

    Elucidation of macroevolutionary transitions between diverse animal body plans remains a major challenge in evolutionary biology. We address the sponge-eumetazoan transition by analyzing expression of a broad range of eumetazoan developmental regulatory genes in Sycon ciliatum (Calcispongiae). Here we show that many members of surprisingly numerous Wnt and Tgfβ gene families are expressed higher or uniquely in the adult apical end and the larval posterior end. Genes involved in formation of the eumetazoan endomesoderm, such as β-catenin, Brachyury and Gata, as well as germline markers Vasa and Pl10, are expressed during formation and maintenance of choanoderm, the feeding epithelium of sponges. Similarity in developmental gene expression between sponges and eumetazoans, especially cnidarians, is consistent with Haeckel's view that body plans of sponges and cnidarians are homologous. These results provide a framework for further studies aimed at deciphering ancestral developmental regulatory networks and their modifications during animal body plans evolution.

  5. Effect of zearalenone on reproductive parameters and expression of selected testicular genes in mice.

    Science.gov (United States)

    Zatecka, E; Ded, L; Elzeinova, F; Kubatova, A; Dorosh, A; Margaryan, H; Dostalova, P; Korenkova, V; Hoskova, K; Peknicova, J

    2014-06-01

    We tested the effect of two different concentrations (150μg/l and 0.15μg/l) of mycotoxin zearalenone (ZEA) on the reproductive parameters and expression of testicular genes in male mice. In adult males, no reduction of body or reproductive organ weight was observed, and the seminiferous tubules were morphologically normal with ongoing spermatogenesis. However, we found decreased sperm concentration, increase of morphologically abnormal spermatozoa and increased binding of apoptotic marker annexin V. This study was also focused on the evaluation of gene expression profiles of 28 genes playing important roles during the processes occurring in the testicular tissue. We detected changes in the expression of genes important for proper spermatogenesis. Surprisingly, we observed a stronger effect after exposure to the lower dose of ZEA.

  6. Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors.

    Science.gov (United States)

    Kemmeren, Patrick; Sameith, Katrin; van de Pasch, Loes A L; Benschop, Joris J; Lenstra, Tineke L; Margaritis, Thanasis; O'Duibhir, Eoghan; Apweiler, Eva; van Wageningen, Sake; Ko, Cheuk W; van Heesch, Sebastiaan; Kashani, Mehdi M; Ampatziadis-Michailidis, Giannis; Brok, Mariel O; Brabers, Nathalie A C H; Miles, Anthony J; Bouwmeester, Diane; van Hooff, Sander R; van Bakel, Harm; Sluiters, Erik; Bakker, Linda V; Snel, Berend; Lijnzaad, Philip; van Leenen, Dik; Groot Koerkamp, Marian J A; Holstege, Frank C P

    2014-04-24

    To understand regulatory systems, it would be useful to uniformly determine how different components contribute to the expression of all other genes. We therefore monitored mRNA expression genome-wide, for individual deletions of one-quarter of yeast genes, focusing on (putative) regulators. The resulting genetic perturbation signatures reflect many different properties. These include the architecture of protein complexes and pathways, identification of expression changes compatible with viability, and the varying responsiveness to genetic perturbation. The data are assembled into a genetic perturbation network that shows different connectivities for different classes of regulators. Four feed-forward loop (FFL) types are overrepresented, including incoherent type 2 FFLs that likely represent feedback. Systematic transcription factor classification shows a surprisingly high abundance of gene-specific repressors, suggesting that yeast chromatin is not as generally restrictive to transcription as is often assumed. The data set is useful for studying individual genes and for discovering properties of an entire regulatory system.

  7. Analysis of mammalian gene function through broad based phenotypic screens across a consortium of mouse clinics

    Science.gov (United States)

    Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Mike; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; El Fertak, Lahcen; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl MJ; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Ed; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie

    2015-01-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse ES cell knockout resource provides a basis for characterisation of relationships between gene and phenotype. The EUMODIC consortium developed and validated robust methodologies for broad-based phenotyping of knockouts through a pipeline comprising 20 disease-orientated platforms. We developed novel statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no prior functional annotation. We captured data from over 27,000 mice finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. Novel phenotypes were uncovered for many genes with unknown function providing a powerful basis for hypothesis generation and further investigation in diverse systems. PMID:26214591

  8. An H1 histone gene from rainbow trout (Salmo gairdnerii).

    Science.gov (United States)

    Mezquita, J; Connor, W; Winkfein, R J; Dixon, G H

    A 1.7-kbp DNA region from the 10.2-kb cluster containing the five rainbow trout histone genes has been subcloned in pBR322 and completely sequenced. It contains a trout histone H1 gene together with its 5' and 3' flanking sequences. This H1 gene codes for a H1 variant different from the major trout testis H1 previously sequenced by Macleod et al. (1977). Northern blots of total RNA from trout testis, kidney, and liver indicate that this H1 gene is expressed in all three tissues but that the level of H1 mRNA is much higher in testis than in other tissues. The lack of heterogeneity in the sizes and 5' initiation sites of trout H1 mRNAs is surprising in view of the substantial heterogeneity of H1 variant proteins observed previously. The coding sequence of the H1 gene shows strong evidence of repeated partial duplications of a hexapeptide motif of the form Ala.Ala.Ala.Lys.Lys.Pro and of a pentapeptide phosphorylation-site sequence, Lys.Ser.Pro.Lys.Lys, during its evolution. Comparisons are drawn between this gene and the coding sequences of other vertebrate H1 genes from chicken and Xenopus, and a strong homology is seen in the region of amino acids 22-101, which form the hydrophobic "head" of the H1 molecule. The 5' and 3' regulatory signals in the trout H1 are also compared with those of H1 genes from other sequences.

  9. Genome-wide identification and expression analysis of NBS-encoding genes in Malus x domestica and expansion of NBS genes family in Rosaceae.

    Directory of Open Access Journals (Sweden)

    Preeti Arya

    Full Text Available Nucleotide binding site leucine-rich repeats (NBS-LRR disease resistance proteins play an important role in plant defense against pathogen attack. A number of recent studies have been carried out to identify and characterize NBS-LRR gene families in many important plant species. In this study, we identified NBS-LRR gene family comprising of 1015 NBS-LRRs using highly stringent computational methods. These NBS-LRRs were characterized on the basis of conserved protein motifs, gene duplication events, chromosomal locations, phylogenetic relationships and digital gene expression analysis. Surprisingly, equal distribution of Toll/interleukin-1 receptor (TIR and coiled coil (CC (1 ∶ 1 was detected in apple while the unequal distribution was reported in majority of all other known plant genome studies. Prediction of gene duplication events intriguingly revealed that not only tandem duplication but also segmental duplication may equally be responsible for the expansion of the apple NBS-LRR gene family. Gene expression profiling using expressed sequence tags database of apple and quantitative real-time PCR (qRT-PCR revealed the expression of these genes in wide range of tissues and disease conditions, respectively. Taken together, this study will provide a blueprint for future efforts towards improvement of disease resistance in apple.

  10. Molecular evolution of the keratin associated protein gene family in mammals, role in the evolution of mammalian hair

    Directory of Open Access Journals (Sweden)

    Irwin David M

    2008-08-01

    Full Text Available Abstract Background Hair is unique to mammals. Keratin associated proteins (KRTAPs, which contain two major groups: high/ultrahigh cysteine and high glycine-tyrosine, are one of the major components of hair and play essential roles in the formation of rigid and resistant hair shafts. Results The KRTAP family was identified as being unique to mammals, and near-complete KRTAP gene repertoires for eight mammalian genomes were characterized in this study. An expanded KRTAP gene repertoire was found in rodents. Surprisingly, humans have a similar number of genes as other primates despite the relative hairlessness of humans. We identified several new subfamilies not previously reported in the high/ultrahigh cysteine KRTAP genes. Genes in many subfamilies of the high/ultrahigh cysteine KRTAP genes have evolved by concerted evolution with frequent gene conversion events, yielding a higher GC base content for these gene sequences. In contrast, the high glycine-tyrosine KRTAP genes have evolved more dynamically, with fewer gene conversion events and thus have a lower GC base content, possibly due to positive selection. Conclusion Most of the subfamilies emerged early in the evolution of mammals, thus we propose that the mammalian ancestor should have a diverse KRTAP gene repertoire. We propose that hair content characteristics have evolved and diverged rapidly among mammals because of rapid divergent evolution of KRTAPs between species. In contrast, subfamilies of KRTAP genes have been homogenized within each species due to concerted evolution.

  11. Industrial melanism in the peppered moth is not associated with genetic variation in canonical melanisation gene candidates.

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    Arjen E van't Hof

    Full Text Available Industrial melanism in the peppered moth (Biston betularia is an iconic case study of ecological genetics but the molecular identity of the gene determining the difference between the typical and melanic (carbonaria morphs is entirely unknown. We applied the candidate gene approach to look for associations between genetic polymorphisms within sixteen a priori melanisation gene candidates and the carbonaria morph. The genes were isolated and sequence characterised in B. betularia using degenerate PCR and from whole-transcriptome sequence. The list of candidates contains all the genes previously implicated in melanisation pattern differences in other insects, including aaNAT, DOPA-decarboxylase, ebony, tan, tyrosine hydroxylase, yellow and yellow2 (yellow-fa. Co-segregation of candidate gene alleles and carbonaria morph was tested in 73 offspring of a carbonaria male-typical female backcross. Surprisingly, none of the sixteen candidate genes was in close linkage with the locus controlling the carbonaria-typical polymorphism. Our study demonstrates that the 'carbonaria gene' is not a structural variant of a canonical melanisation pathway gene, neither is it a cis-regulatory element of these enzyme-coding genes. The implication is either that we have failed to characterize an unknown enzyme-coding gene in the melanisation pathway, or more likely, that the 'carbonaria gene' is a higher level trans-acting factor which regulates the spatial expression of one or more of the melanisation candidates in this study to alter the pattern of melanin production.

  12. Lateral gene transfer, rearrangement, reconciliation

    NARCIS (Netherlands)

    Patterson, M.D.; Szollosi, G.; Daubin, V.; Tannier, E.

    2013-01-01

    Background. Models of ancestral gene order reconstruction have progressively integrated different evolutionary patterns and processes such as unequal gene content, gene duplications, and implicitly sequence evolution via reconciled gene trees. These models have so far ignored lateral gene transfer,

  13. Parallel retention of Pdx2 genes in cartilaginous fish and coelacanths.

    Science.gov (United States)

    Mulley, John F; Holland, Peter W H

    2010-10-01

    The Pdx1 or Ipf1 gene encodes an important homeodomain-containing protein with key roles in pancreas development and function. Mutations in human PDX1 are implicated in developmental defects and disease of the pancreas. Extensive research, including genome sequencing, has indicated that Pdx1 is the only member of its gene family in mammals, birds, amphibians, and ray-finned fish, and with the exception of teleost fish, this gene forms part of the ParaHox gene cluster along with Gsx1 and Cdx2. The ParaHox cluster, however, is a remnant of a 4-fold genome duplication; the three other ParaHox paralogues lack a Pdx-like gene in all vertebrate genomes examined to date. We have used bacterial artificial chromosome cloning and synteny analysis to show that the ancestor of living jawed vertebrates in fact had more ParaHox genes, including two Pdx genes (Pdx1 and Pdx2). Surprisingly, the two Pdx genes have been retained in parallel in two quite distantly related lineages, the cartilaginous fish (sharks, skates, and chimeras) and the Indonesian coelacanth, Latimeria menadoensis. The Pdx2 gene has been lost independently in ray-finned fish and in tetrapods.

  14. Integrating Diverse Types of Genomic Data to Identify Genes that Underlie Adverse Pregnancy Phenotypes.

    Directory of Open Access Journals (Sweden)

    Jibril Hirbo

    Full Text Available Progress in understanding complex genetic diseases has been bolstered by synthetic approaches that overlay diverse data types and analyses to identify functionally important genes. Pre-term birth (PTB, a major complication of pregnancy, is a leading cause of infant mortality worldwide. A major obstacle in addressing PTB is that the mechanisms controlling parturition and birth timing remain poorly understood. Integrative approaches that overlay datasets derived from comparative genomics with function-derived ones have potential to advance our understanding of the genetics of birth timing, and thus provide insights into the genes that may contribute to PTB. We intersected data from fast evolving coding and non-coding gene regions in the human and primate lineage with data from genes expressed in the placenta, from genes that show enriched expression only in the placenta, as well as from genes that are differentially expressed in four distinct PTB clinical subtypes. A large fraction of genes that are expressed in placenta, and differentially expressed in PTB clinical subtypes (23-34% are fast evolving, and are associated with functions that include adhesion neurodevelopmental and immune processes. Functional categories of genes that express fast evolution in coding regions differ from those linked to fast evolution in non-coding regions. Finally, there is a surprising lack of overlap between fast evolving genes that are differentially expressed in four PTB clinical subtypes. Integrative approaches, especially those that incorporate evolutionary perspectives, can be successful in identifying potential genetic contributions to complex genetic diseases, such as PTB.

  15. Molecular characterization of genes encoding leucoanthocyanidin reductase involved in proanthocyanidin biosynthesis in apple

    Directory of Open Access Journals (Sweden)

    Yuepeng eHan

    2015-04-01

    Full Text Available Proanthocyanidins (PAs are the major component of phenolics in apple, but mechanisms involved in PA biosynthesis remain unclear. Here, the relationship between the PA biosynthesis and the expression of genes encoding leucoanthocyanidin reductase (LAR and anthocyanidin reductase (ANR was investigated in fruit skin of one apple cultivar and three crabapples. Transcript levels of LAR1 and ANR2 genes were significantly correlated with the contents of catechin and epicatechin, respectively, which suggests their active roles in PA synthesis. Surprisingly, transcript levels for both LAR1 and LAR2 genes were almost undetectable in two crabapples that accumulated both flavan-3-ols and PAs. This contradicts the previous finding that LAR1 gene is a strong candidate regulating the accumulation of metabolites such as epicatechin and PAs in apple. Ectopic expression of apple MdLAR1 gene in tobacco suppresses expression of the late genes in anthocyanin biosynthetic pathway, resulting in loss of anthocyanin in flowers. Interestingly, a decrease in PA biosynthesis was also observed in flowers of transgenic tobacco plants overexpressing the MdLAR1 gene, which could be attributed to decreased expression of both the NtANR1 and NtANR2 genes. Our study not only confirms the in vivo function of apple LAR1 gene, but it is also helpful for understanding the mechanism of PA biosynthesis.

  16. 'Specific' oligonucleotides often recognize more than one gene: the limits of in situ hybridization applied to GABA receptors.

    Science.gov (United States)

    Mladinic, M; Didelon, F; Cherubini, E; Bradbury, A

    2000-05-15

    As exquisite probes for gene sequences, oligonucleotides are one of the most powerful tools of recombinant molecular biology. In studying the GABA receptor subunits in the neonatal hippocampus we have used oligonucleotide probes in in situ hybridization and cloning techniques. The oligonucleotides used and assumed to be specific for the target gene, actually recognized more than one gene, leading to surprising and contradictory results. In particular, we found that a GABA(A)-rho specific oligonucleotide recognized an abundant, previously unknown, transcription factor in both in situ and library screening, while oligos 'specific' for GABA(A) subunits were able to recognize 30 additional unrelated genes in library screening. This suggests that positive results obtained with oligonucleotides should be interpreted with caution unless confirmed by identical results with oligonucleotides from different parts of the same gene, or cDNA library screening excludes the presence of other hybridizing species.

  17. Gene doping in sports.

    Science.gov (United States)

    Unal, Mehmet; Ozer Unal, Durisehvar

    2004-01-01

    Gene or cell doping is defined by the World Anti-Doping Agency (WADA) as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". New research in genetics and genomics will be used not only to diagnose and treat disease, but also to attempt to enhance human performance. In recent years, gene therapy has shown progress and positive results that have highlighted the potential misuse of this technology and the debate of 'gene doping'. Gene therapies developed for the treatment of diseases such as anaemia (the gene for erythropoietin), muscular dystrophy (the gene for insulin-like growth factor-1) and peripheral vascular diseases (the gene for vascular endothelial growth factor) are potential doping methods. With progress in gene technology, many other genes with this potential will be discovered. For this reason, it is important to develop timely legal regulations and to research the field of gene doping in order to develop methods of detection. To protect the health of athletes and to ensure equal competitive conditions, the International Olympic Committee, WADA and International Sports Federations have accepted performance-enhancing substances and methods as being doping, and have forbidden them. Nevertheless, the desire to win causes athletes to misuse these drugs and methods. This paper reviews the current status of gene doping and candidate performance enhancement genes, and also the use of gene therapy in sports medicine and ethics of genetic enhancement.

  18. Comparative genomic analysis of the arthropod muscle myosin heavy chain genes allows ancestral gene reconstruction and reveals a new type of 'partially' processed pseudogene

    Directory of Open Access Journals (Sweden)

    Kollmar Martin

    2008-02-01

    Full Text Available Abstract Background Alternative splicing of mutually exclusive exons is an important mechanism for increasing protein diversity in eukaryotes. The insect Mhc (myosin heavy chain gene produces all different muscle myosins as a result of alternative splicing in contrast to most other organisms of the Metazoa lineage, that have a family of muscle genes with each gene coding for a protein specialized for a functional niche. Results The muscle myosin heavy chain genes of 22 species of the Arthropoda ranging from the waterflea to wasp and Drosophila have been annotated. The analysis of the gene structures allowed the reconstruction of an ancient muscle myosin heavy chain gene and showed that during evolution of the arthropods introns have mainly been lost in these genes although intron gain might have happened in a few cases. Surprisingly, the genome of Aedes aegypti contains another and that of Culex pipiens quinquefasciatus two further muscle myosin heavy chain genes, called Mhc3 and Mhc4, that contain only one variant of the corresponding alternative exons of the Mhc1 gene. Mhc3 transcription in Aedes aegypti is documented by EST data. Mhc3 and Mhc4 inserted in the Aedes and Culex genomes either by gene duplication followed by the loss of all but one variant of the alternative exons, or by incorporation of a transcript of which all other variants have been spliced out retaining the exon-intron structure. The second and more likely possibility represents a new type of a 'partially' processed pseudogene. Conclusion Based on the comparative genomic analysis of the alternatively spliced arthropod muscle myosin heavy chain genes we propose that the splicing process operates sequentially on the transcript. The process consists of the splicing of the mutually exclusive exons until one exon out of the cluster remains while retaining surrounding intronic sequence. In a second step splicing of introns takes place. A related mechanism could be responsible for

  19. Human Gene Therapy: Genes without Frontiers?

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  20. Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray

    Directory of Open Access Journals (Sweden)

    Shin Minkyu

    2010-11-01

    Full Text Available Abstract Background The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. Results We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine. a selective serotonin reuptake inhibitor (fluoxetine, a monoamine oxidase inhibitor (phenelzine and psychoactive herbal extracts of Nelumbinis Semen (NS. To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFβ, was significantly enhanced. Conclusions These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.

  1. Paternity and gene dispersal in limber pine (Pinus flexilis James).

    Science.gov (United States)

    Schuster, W S; Mitton, J B

    2000-03-01

    This study provides empirical information on intrapopulation gene dispersal via pollen, the size of genetic 'neighbourhoods', and interpopulation gene flow in a long-lived conifer, limber pine (Pinus flexilis). We used allozyme loci for a paternity analysis of 518 seeds produced in an isolated population of limber pine located in north-eastern Colorado, U.S.A., separated by 2 km from the nearest conspecific trees and nearly 100 km from populations in the Rocky Mountains. We also used indirect techniques (FST analyses) to estimate gene flow rates among subdivisions of the study population and among five widely separated populations. Within the main study population limber pine exhibited a polymorphism level of 50%, observed heterozygosity of 0.159, and 2.36 alleles per polymorphic locus. Mountain populations were slightly more variable. The main study population showed significant differentiation in allozymes among neighbouring subpopulations. The mean FST was 0.031 and the gene flow rate among subpopulations was estimated as 7.8 migrants per generation. Among widely separated populations the mean FST was 0.035 and the gene flow rate was estimated as 6.9 migrants per generation. The paternity analysis indicated a best estimate of 6.5% pollen immigration (minimum 1.1%) from populations 2 km to 100+ km away. For 4% of the seeds examined, paternity could be ascribed to a single tree in the study population. Fractional paternity and likelihood methods were used to estimate pollen dispersal distances for the remainder of the seeds. Mean pollen dispersal distance was estimated at 140 m using the fractional method, similar to results from the other techniques. This compares with a mean distance of 172 m between potential mates. These results suggest near-panmictic pollen dispersal over this population, which covers about 15 ha. The observed allozyme differences and surprisingly low estimates of among-subpopulation gene flow are ascribed to a probable restriction of gene

  2. Contrasting evolutionary histories of MHC class I and class II loci in grouse—Effects of selection and gene conversion

    Science.gov (United States)

    Minias, Piotr; Bateson, Zachary W; Whittingham, Linda A; Johnson, Jeff A.; Oyler-McCance, Sara J.; Dunn, Peter O

    2016-01-01

    Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens.

  3. Variation in the Genetic Repertoire of Viruses Infecting Micromonas pusilla Reflects Horizontal Gene Transfer and Links to Their Environmental Distribution

    Science.gov (United States)

    Finke, Jan F.; Winget, Danielle M.; Chan, Amy M.; Suttle, Curtis A.

    2017-01-01

    Prasinophytes, a group of eukaryotic phytoplankton, has a global distribution and is infected by large double-stranded DNA viruses (prasinoviruses) in the family Phycodnaviridae. This study examines the genetic repertoire, phylogeny, and environmental distribution of phycodnaviruses infecting Micromonas pusilla, other prasinophytes and chlorophytes. Based on comparisons among the genomes of viruses infecting M. pusilla and other phycodnaviruses, as well as the genome from a host isolate of M. pusilla, viruses infecting M. pusilla (MpVs) share a limited set of core genes, but vary strongly in their flexible pan-genome that includes numerous metabolic genes, such as those associated with amino acid synthesis and sugar manipulation. Surprisingly, few of these presumably host-derived genes are shared with M. pusilla, but rather have their closest non-viral homologue in bacteria and other eukaryotes, indicating horizontal gene transfer. A comparative analysis of full-length DNA polymerase (DNApol) genes from prasinoviruses with their overall gene content, demonstrated that the phylogeny of DNApol gene fragments reflects the gene content of the viruses; hence, environmental DNApol gene sequences from prasinoviruses can be used to infer their overall genetic repertoire. Thus, the distribution of virus ecotypes across environmental samples based on DNApol sequences implies substantial underlying differences in gene content that reflect local environmental conditions. Moreover, the high diversity observed in the genetic repertoire of prasinoviruses has been driven by horizontal gene transfer throughout their evolutionary history, resulting in a broad suite of functional capabilities and a high diversity of prasinovirus ecotypes. PMID:28534829

  4. Quasispecies theory for horizontal gene transfer and recombination

    Science.gov (United States)

    Muñoz, Enrique; Park, Jeong-Man; Deem, Michael W.

    2008-12-01

    We introduce a generalization of the parallel, or Crow-Kimura, and Eigen models of molecular evolution to represent the exchange of genetic information between individuals in a population. We study the effect of different schemes of genetic recombination on the steady-state mean fitness and distribution of individuals in the population, through an analytic field theoretic mapping. We investigate both horizontal gene transfer from a population and recombination between pairs of individuals. Somewhat surprisingly, these nonlinear generalizations of quasispecies theory to modern biology are analytically solvable. For two-parent recombination, we find two selected phases, one of which is spectrally rigid. We present exact analytical formulas for the equilibrium mean fitness of the population, in terms of a maximum principle, which are generally applicable to any permutation invariant replication rate function. For smooth fitness landscapes, we show that when positive epistatic interactions are present, recombination or horizontal gene transfer introduces a mild load against selection. Conversely, if the fitness landscape exhibits negative epistasis, horizontal gene transfer or recombination introduces an advantage by enhancing selection towards the fittest genotypes. These results prove that the mutational deterministic hypothesis holds for quasispecies models. For the discontinuous single sharp peak fitness landscape, we show that horizontal gene transfer has no effect on the fitness, while recombination decreases the fitness, for both the parallel and the Eigen models. We present numerical and analytical results as well as phase diagrams for the different cases.

  5. Genes and Hearing Loss

    Science.gov (United States)

    ... Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient Health Information News media interested in covering ... One of the most common birth defects is hearing loss or deafness (congenital), which can affect as many ...

  6. Essential Bacillus subtilis genes

    DEFF Research Database (Denmark)

    Kobayashi, K.; Ehrlich, S.D.; Albertini, A.

    2003-01-01

    To estimate the minimal gene set required to sustain bacterial life in nutritious conditions, we carried out a systematic inactivation of Bacillus subtilis genes. Among approximate to4,100 genes of the organism, only 192 were shown to be indispensable by this or previous work. Another 79 genes were...... predicted to be essential. The vast majority of essential genes were categorized in relatively few domains of cell metabolism, with about half involved in information processing, one-fifth involved in the synthesis of cell envelope and the determination of cell shape and division, and one-tenth related...... to cell energetics. Only 4% of essential genes encode unknown functions. Most essential genes are present throughout a wide range of Bacteria, and almost 70% can also be found in Archaea and Eucarya. However, essential genes related to cell envelope, shape, division, and respiration tend to be lost from...

  7. Cochlear Gene Therapy

    OpenAIRE

    2012-01-01

    The purpose of this review is to highlight recent advances in cochlear gene therapy over the past several years. Cochlear gene therapy has undergone tremendous advances over the past decade. Beginning with some groundbreaking work in 2005 documenting hair cell regeneration using virallymediated delivery of the mouse atonal 1 gene, gene therapy is now being explored as a possible treatment for a variety of causes of hearing loss.

  8. The human desmin promoter drives robust gene expression for skeletal muscle stem cell-mediated gene therapy.

    Science.gov (United States)

    Jonuschies, Jacqueline; Antoniou, Michael; Waddington, Simon; Boldrin, Luisa; Muntoni, Francesco; Thrasher, Adrian; Morgan, Jennifer

    2014-01-01

    Lentiviral vectors (LVs) represent suitable candidates to mediate gene therapy for muscular dystrophies as they infect dividing and non-dividing cells and integrate their genetic material into the host genome, thereby theoretically mediating longterm expression. We evaluated the ability of LVs where a GFP reporter gene was under the control of five different promoters, to transduce and mediate expression in myogenic and non-myogenic cells in vitro and in skeletal muscle fibres and stem (satellite) cells in vivo. We further analysed lentivirally-transduced satellite cell-derived myoblasts following their transplantation into dystrophic, immunodeficient mouse muscles. The spleen focus-forming virus promoter mediated the highest gene expression in all cell types; the CBX3-HNRPA2B1 ubiquitously-acting chromatin opening element (UCOE) promoter was also active in all cells, whereas the human desmin promoter in isolation or fused with UCOE had lower activity in non-muscle cells. Surprisingly, the human skeletal muscle actin promoter was also active in immune cells. The human desmin promoter mediated robust, persistent reporter gene expression in myogenic cells in vitro, and satellite cells and muscle fibres in vivo. The human desmin promoter combined with UCOE did not significantly increase transgene expression. Therefore, our data indicate that the desmin promoter is suitable for the development of therapeutic purposes.

  9. Comparative genomics of rhizobia nodulating soybean suggests extensive recruitment of lineage-specific genes in adaptations.

    Science.gov (United States)

    Tian, Chang Fu; Zhou, Yuan Jie; Zhang, Yan Ming; Li, Qin Qin; Zhang, Yun Zeng; Li, Dong Fang; Wang, Shuang; Wang, Jun; Gilbert, Luz B; Li, Ying Rui; Chen, Wen Xin

    2012-05-29

    The rhizobium-legume symbiosis has been widely studied as the model of mutualistic evolution and the essential component of sustainable agriculture. Extensive genetic and recent genomic studies have led to the hypothesis that many distinct strategies, regardless of rhizobial phylogeny, contributed to the varied rhizobium-legume symbiosis. We sequenced 26 genomes of Sinorhizobium and Bradyrhizobium nodulating soybean to test this hypothesis. The Bradyrhizobium core genome is disproportionally enriched in lipid and secondary metabolism, whereas several gene clusters known to be involved in osmoprotection and adaptation to alkaline pH are specific to the Sinorhizobium core genome. These features are consistent with biogeographic patterns of these bacteria. Surprisingly, no genes are specifically shared by these soybean microsymbionts compared with other legume microsymbionts. On the other hand, phyletic patterns of 561 known symbiosis genes of rhizobia reflected the species phylogeny of these soybean microsymbionts and other rhizobia. Similar analyses with 887 known functional genes or the whole pan genome of rhizobia revealed that only the phyletic distribution of functional genes was consistent with the species tree of rhizobia. Further evolutionary genetics revealed that recombination dominated the evolution of core genome. Taken together, our results suggested that faithfully vertical genes were rare compared with those with history of recombination including lateral gene transfer, although rhizobial adaptations to symbiotic interactions and other environmental conditions extensively recruited lineage-specific shell genes under direct or indirect control through the speciation process.

  10. Discovering genes underlying QTL

    Energy Technology Data Exchange (ETDEWEB)

    Vanavichit, Apichart [Kasetsart University, Kamphaengsaen, Nakorn Pathom (Thailand)

    2002-02-01

    A map-based approach has allowed scientists to discover few genes at a time. In addition, the reproductive barrier between cultivated rice and wild relatives has prevented us from utilizing the germ plasm by a map-based approach. Most genetic traits important to agriculture or human diseases are manifested as observable, quantitative phenotypes called Quantitative Trait Loci (QTL). In many instances, the complexity of the phenotype/genotype interaction and the general lack of clearly identifiable gene products render the direct molecular cloning approach ineffective, thus additional strategies like genome mapping are required to identify the QTL in question. Genome mapping requires no prior knowledge of the gene function, but utilizes statistical methods to identify the most likely gene location. To completely characterize genes of interest, the initially mapped region of a gene location will have to be narrowed down to a size that is suitable for cloning and sequencing. Strategies for gene identification within the critical region have to be applied after the sequencing of a potentially large clone or set of clones that contains this gene(s). Tremendous success of positional cloning has been shown for cloning many genes responsible for human diseases, including cystic fibrosis and muscular dystrophy as well as plant disease resistance genes. Genome and QTL mapping, positional cloning: the pre-genomics era, comparative approaches to gene identification, and positional cloning: the genomics era are discussed in the report. (M. Suetake)

  11. Reading and Generalist Genes

    Science.gov (United States)

    Haworth, Claire M. A.; Meaburn, Emma L.; Harlaar, Nicole; Plomin, Robert

    2007-01-01

    Twin-study research suggests that many (but not all) of the same genes contribute to genetic influence on diverse learning abilities and disabilities, a hypothesis called "generalist genes". This generalist genes hypothesis was tested using a set of 10 DNA markers (single nucleotide polymorphisms [SNPs]) found to be associated with early reading…

  12. Replication-associated gene dosage effects shape the genomes of fast-growing bacteria but only for transcription and translation genes.

    Science.gov (United States)

    Couturier, Etienne; Rocha, Eduardo P C

    2006-03-01

    The bidirectional replication of bacterial genomes leads to transient gene dosage effects. Here, we show that such effects shape the chromosome organisation of fast-growing bacteria and that they correlate strongly with maximal growth rate. Surprisingly the predicted maximal number of replication rounds shows little if any phylogenetic inertia, suggesting that it is a very labile trait. Yet, a combination of theoretical and statistical analyses predicts that dozens of replication forks may be simultaneously present in the cells of certain species. This suggests a strikingly efficient management of the replication apparatus, of replication fork arrests and of chromosome segregation in such cells. Gene dosage effects strongly constrain the position of genes involved in translation and transcription, but not other highly expressed genes. The relative proximity of the former genes to the origin of replication follows the regulatory dependencies observed under exponential growth, as the bias is stronger for RNA polymerase, then rDNA, then ribosomal proteins and tDNA. Within tDNAs we find that only the positions of the previously proposed 'ubiquitous' tRNA, which translate the most frequent codons in highly expressed genes, show strong signs of selection for gene dosage effects. Finally, we provide evidence for selection acting upon genome organisation to take advantage of gene dosage effects by identifying a positive correlation between genome stability and the number of simultaneous replication rounds. We also show that gene dosage effects can explain the over-representation of highly expressed genes in the largest replichore of genomes containing more than one chromosome. Together, these results demonstrate that replication-associated gene dosage is an important determinant of chromosome organisation and dynamics, especially among fast-growing bacteria.

  13. Symbiotic Burkholderia Species Show Diverse Arrangements of nif/fix and nod Genes and Lack Typical High-Affinity Cytochrome cbb3 Oxidase Genes.

    Science.gov (United States)

    De Meyer, Sofie E; Briscoe, Leah; Martínez-Hidalgo, Pilar; Agapakis, Christina M; de-Los Santos, Paulina Estrada; Seshadri, Rekha; Reeve, Wayne; Weinstock, George; O'Hara, Graham; Howieson, John G; Hirsch, Ann M

    2016-08-01

    Genome analysis of fourteen mimosoid and four papilionoid beta-rhizobia together with fourteen reference alpha-rhizobia for both nodulation (nod) and nitrogen-fixing (nif/fix) genes has shown phylogenetic congruence between 16S rRNA/MLSA (combined 16S rRNA gene sequencing and multilocus sequence analysis) and nif/fix genes, indicating a free-living diazotrophic ancestry of the beta-rhizobia. However, deeper genomic analysis revealed a complex symbiosis acquisition history in the beta-rhizobia that clearly separates the mimosoid and papilionoid nodulating groups. Mimosoid-nodulating beta-rhizobia have nod genes tightly clustered in the nodBCIJHASU operon, whereas papilionoid-nodulating Burkholderia have nodUSDABC and nodIJ genes, although their arrangement is not canonical because the nod genes are subdivided by the insertion of nif and other genes. Furthermore, the papilionoid Burkholderia spp. contain duplications of several nod and nif genes. The Burkholderia nifHDKEN and fixABC genes are very closely related to those found in free-living diazotrophs. In contrast, nifA is highly divergent between both groups, but the papilionoid species nifA is more similar to alpha-rhizobia nifA than to other groups. Surprisingly, for all Burkholderia, the fixNOQP and fixGHIS genes required for cbb3 cytochrome oxidase production and assembly are missing. In contrast, symbiotic Cupriavidus strains have fixNOQPGHIS genes, revealing a divergence in the evolution of two distinct electron transport chains required for nitrogen fixation within the beta-rhizobia.

  14. Shutoff of Host Gene Expression in Influenza A Virus and Herpesviruses: Similar Mechanisms and Common Themes.

    Science.gov (United States)

    Rivas, Hembly G; Schmaling, Summer K; Gaglia, Marta M

    2016-04-16

    The ability to shut off host gene expression is a shared feature of many viral infections, and it is thought to promote viral replication by freeing host cell machinery and blocking immune responses. Despite the molecular differences between viruses, an emerging theme in the study of host shutoff is that divergent viruses use similar mechanisms to enact host shutoff. Moreover, even viruses that encode few proteins often have multiple mechanisms to affect host gene expression, and we are only starting to understand how these mechanisms are integrated. In this review we discuss the multiplicity of host shutoff mechanisms used by the orthomyxovirus influenza A virus and members of the alpha- and gamma-herpesvirus subfamilies. We highlight the surprising similarities in their mechanisms of host shutoff and discuss how the different mechanisms they use may play a coordinated role in gene regulation.

  15. Cloning and expression of swine myostatin gene and its application in animal immunization trial

    Institute of Scientific and Technical Information of China (English)

    MA; Xianyong; CAO; Yongchang; SHU; Dingming; BI; Yingzuo

    2005-01-01

    We have amplified swine myostatin (MSTN) gene by reverse transcription polymerase chain reaction (RT-PCR) and cloned it into pGEM-T Easy vector. The cloned swine MSTN gene consists of 1128 nucleotides, which has been submitted to GenBank (acquired registered code- AY448008). The cloned swine MSTN gene was successfully expressed in E. coli without the first 25 amino acids. Crude extraction of the expressed recombinant MSTN protein was used to immunize mice to investigate the effects on their bodyweights. We show here that the body weights of the immunized mice were higher than that of the controls, even though the difference was not significant. Surprisingly, the progenies of the immunized mice also were heavier than the controls. Especially at day 3, the average body weight of the immunized mice was 10.5% higher than that of the controls , which is significant (p < 0.05).

  16. Shutoff of Host Gene Expression in Influenza A Virus and Herpesviruses: Similar Mechanisms and Common Themes

    Directory of Open Access Journals (Sweden)

    Hembly G. Rivas

    2016-04-01

    Full Text Available The ability to shut off host gene expression is a shared feature of many viral infections, and it is thought to promote viral replication by freeing host cell machinery and blocking immune responses. Despite the molecular differences between viruses, an emerging theme in the study of host shutoff is that divergent viruses use similar mechanisms to enact host shutoff. Moreover, even viruses that encode few proteins often have multiple mechanisms to affect host gene expression, and we are only starting to understand how these mechanisms are integrated. In this review we discuss the multiplicity of host shutoff mechanisms used by the orthomyxovirus influenza A virus and members of the alpha- and gamma-herpesvirus subfamilies. We highlight the surprising similarities in their mechanisms of host shutoff and discuss how the different mechanisms they use may play a coordinated role in gene regulation.

  17. ISWI and CHD chromatin remodelers bind promoters but act in gene bodies.

    Directory of Open Access Journals (Sweden)

    Gabriel E Zentner

    Full Text Available ATP-dependent nucleosome remodelers influence genetic processes by altering nucleosome occupancy, positioning, and composition. In vitro, Saccharomyces cerevisiae ISWI and CHD remodelers require ∼30-85 bp of extranucleosomal DNA to reposition nucleosomes, but linker DNA in S. cerevisiae averages <20 bp. To address this discrepancy between in vitro and in vivo observations, we have mapped the genomic distributions of the yeast Isw1, Isw2, and Chd1 remodelers at base-pair resolution on native chromatin. Although these remodelers act in gene bodies, we find that they are also highly enriched at nucleosome-depleted regions (NDRs, where they bind to extended regions of DNA adjacent to particular transcription factors. Surprisingly, catalytically inactive remodelers show similar binding patterns. We find that remodeler occupancy at NDRs and gene bodies is associated with nucleosome turnover and transcriptional elongation rate, suggesting that remodelers act on regions of transient nucleosome unwrapping or depletion within gene bodies subsequent to transcriptional elongation.

  18. Mutation analysis of codons 345 and 347 of rhodopsin gene in Indian retinitis pigmentosa patients

    Indian Academy of Sciences (India)

    Madhurima Dikshit; Rakhi Agarwal

    2001-08-01

    More than 100 mutations have been reported till date in the rhodopsin gene in patients with retinitis pigmentosa. The present study was undertaken to detect the reported rhodopsin gene point mutations in Indian retinitis pigmentosa patients. We looked for presence or absence of codon 345 and 347 mutations in exon 5 of the gene using the technique of allele-specific polymerase chain reaction by designing primers for each mutation. We have examined 100 patients from 76 families irrespective of genetic categories. Surprisingly, in our sample the very widely reported highly frequent mutations of codon 347 (P → S/A/R/Q/L/T) were absent while the codon 345 mutation V → M was seen in three cases in one family (autosomal dominant form) and in one sporadic case (total two families). This is the first report on codon 345 and 347 mutation in Indian retinitis pigmentosa subjects.

  19. Disruption of ubiquitin-related genes in laboratory yeast strains enhances ethanol production during sake brewing.

    Science.gov (United States)

    Wu, Hong; Watanabe, Tomoko; Araki, Yoshio; Kitagaki, Hiroshi; Akao, Takeshi; Takagi, Hiroshi; Shimoi, Hitoshi

    2009-06-01

    Sake yeast can produce high levels of ethanol in concentrated rice mash. While both sake and laboratory yeast strains belong to the species Saccharomyces cerevisiae, the laboratory strains produce much less ethanol. This disparity in fermentation activity may be due to the strains' different responses to environmental stresses, including ethanol accumulation. To obtain more insight into the stress response of yeast cells under sake brewing conditions, we carried out small-scale sake brewing tests using laboratory yeast strains disrupted in specific stress-related genes. Surprisingly, yeast strains with disrupted ubiquitin-related genes produced more ethanol than the parental strain during sake brewing. The elevated fermentation ability conferred by disruption of the ubiquitin-coding gene UBI4 was confined to laboratory strains, and the ubi4 disruptant of a sake yeast strain did not demonstrate a comparable increase in ethanol production. These findings suggest different roles for ubiquitin in sake and laboratory yeast strains.

  20. Ancient Duplications and Expression Divergence in the Globin Gene Superfamily of Vertebrates: Insights from the Elephant Shark Genome and Transcriptome.

    Science.gov (United States)

    Opazo, Juan C; Lee, Alison P; Hoffmann, Federico G; Toloza-Villalobos, Jessica; Burmester, Thorsten; Venkatesh, Byrappa; Storz, Jay F

    2015-07-01

    Comparative analyses of vertebrate genomes continue to uncover a surprising diversity of genes in the globin gene superfamily, some of which have very restricted phyletic distributions despite their antiquity. Genomic analysis of the globin gene repertoire of cartilaginous fish (Chondrichthyes) should be especially informative about the duplicative origins and ancestral functions of vertebrate globins, as divergence between Chondrichthyes and bony vertebrates represents the most basal split within the jawed vertebrates. Here, we report a comparative genomic analysis of the vertebrate globin gene family that includes the complete globin gene repertoire of the elephant shark (Callorhinchus milii). Using genomic sequence data from representatives of all major vertebrate classes, integrated analyses of conserved synteny and phylogenetic relationships revealed that the last common ancestor of vertebrates possessed a repertoire of at least seven globin genes: single copies of androglobin and neuroglobin, four paralogous copies of globin X, and the single-copy progenitor of the entire set of vertebrate-specific globins. Combined with expression data, the genomic inventory of elephant shark globins yielded four especially surprising findings: 1) there is no trace of the neuroglobin gene (a highly conserved gene that is present in all other jawed vertebrates that have been examined to date), 2) myoglobin is highly expressed in heart, but not in skeletal muscle (reflecting a possible ancestral condition in vertebrates with single-circuit circulatory systems), 3) elephant shark possesses two highly divergent globin X paralogs, one of which is preferentially expressed in gonads, and 4) elephant shark possesses two structurally distinct α-globin paralogs, one of which is preferentially expressed in the brain. Expression profiles of elephant shark globin genes reveal distinct specializations of function relative to orthologs in bony vertebrates and suggest hypotheses about

  1. Journey from Jumping Genes to Gene Therapy.

    Science.gov (United States)

    Whartenby, Katharine A

    2015-01-01

    Gene therapy for cancer is a still evolving approach that resulted from a long history of studies into genetic modification of organisms. The fascination with manipulating gene products has spanned hundreds if not thousands of years, beginning with observations of the hereditary nature of traits in plants and culminating to date in the alteration of genetic makeup in humans via modern technology. From early discoveries noting the potential for natural mobility of genetic material to the culmination of clinical trials in a variety of disease, gene transfer has had an eventful and sometimes tumultuous course. Within the present review is a brief history of the biology of gene transfer, how it came to be applied to genetic diseases, and its early applications to cancer therapies. Some of the different types of methods used to modify cells, the theories behind the approaches, and some of the limitations encountered along the way are reviewed.

  2. Gene conversion in human rearranged immunoglobulin genes.

    Science.gov (United States)

    Darlow, John M; Stott, David I

    2006-07-01

    Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V(H) segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V(H) replacements with no addition of untemplated nucleotides at the V(H)-V(H) joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V(H) replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion.

  3. Gene therapy in periodontics

    Directory of Open Access Journals (Sweden)

    Anirban Chatterjee

    2013-01-01

    Full Text Available GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person′s genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is ′the use of genes as medicine′. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

  4. Regulated Gene Therapy.

    Science.gov (United States)

    Breger, Ludivine; Wettergren, Erika Elgstrand; Quintino, Luis; Lundberg, Cecilia

    2016-01-01

    Gene therapy represents a promising approach for the treatment of monogenic and multifactorial neurological disorders. It can be used to replace a missing gene and mutated gene or downregulate a causal gene. Despite the versatility of gene therapy, one of the main limitations lies in the irreversibility of the process: once delivered to target cells, the gene of interest is constitutively expressed and cannot be removed. Therefore, efficient, safe and long-term gene modification requires a system allowing fine control of transgene expression.Different systems have been developed over the past decades to regulate transgene expression after in vivo delivery, either at transcriptional or post-translational levels. The purpose of this chapter is to give an overview on current regulatory system used in the context of gene therapy for neurological disorders. Systems using external regulation of transgenes using antibiotics are commonly used to control either gene expression using tetracycline-controlled transcription or protein levels using destabilizing domain technology. Alternatively, specific promoters of genes that are regulated by disease mechanisms, increasing expression as the disease progresses or decreasing expression as disease regresses, are also examined. Overall, this chapter discusses advantages and drawbacks of current molecular methods for regulated gene therapy in the central nervous system.

  5. Gene therapy: An overview

    Directory of Open Access Journals (Sweden)

    Sudip Indu

    2013-01-01

    Full Text Available Gene therapy "the use of genes as medicine" involves the transfer of a therapeutic or working copy of a gene into specific cells of an individual in order to repair a faulty gene copy. The technique may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. The objective of gene therapy is to introduce new genetic material into target cells while causing no damage to the surrounding healthy cells and tissues, hence the treatment related morbidity is decreased. The delivery system includes a vector that delivers a therapeutic gene into the patient′s target cell. Functional proteins are created from the therapeutic gene causing the cell to return to a normal stage. The vectors used in gene therapy can be viral and non-viral. Gene therapy, an emerging field of biomedicine, is still at infancy and much research remains to be done before this approach to the treatment of condition will realize its full potential.

  6. Gene therapy in periodontics.

    Science.gov (United States)

    Chatterjee, Anirban; Singh, Nidhi; Saluja, Mini

    2013-03-01

    GENES are made of DNA - the code of life. They are made up of two types of base pair from different number of hydrogen bonds AT, GC which can be turned into instruction. Everyone inherits genes from their parents and passes them on in turn to their children. Every person's genes are different, and the changes in sequence determine the inherited differences between each of us. Some changes, usually in a single gene, may cause serious diseases. Gene therapy is 'the use of genes as medicine'. It involves the transfer of a therapeutic or working gene copy into specific cells of an individual in order to repair a faulty gene copy. Thus it may be used to replace a faulty gene, or to introduce a new gene whose function is to cure or to favorably modify the clinical course of a condition. It has a promising era in the field of periodontics. Gene therapy has been used as a mode of tissue engineering in periodontics. The tissue engineering approach reconstructs the natural target tissue by combining four elements namely: Scaffold, signaling molecules, cells and blood supply and thus can help in the reconstruction of damaged periodontium including cementum, gingival, periodontal ligament and bone.

  7. Cyanobacterial signature genes.

    Science.gov (United States)

    Martin, Kirt A; Siefert, Janet L; Yerrapragada, Sailaja; Lu, Yue; McNeill, Thomas Z; Moreno, Pedro A; Weinstock, George M; Widger, William R; Fox, George E

    2003-01-01

    A comparison of 8 cyanobacterial genomes reveals that there are 181 shared genes that do not have obvious orthologs in other bacteria. These signature genes define aspects of the genotype that are uniquely cyanobacterial. Approximately 25% of these genes have been associated with some function. These signature genes may or may not be involved in photosynthesis but likely they will be in many cases. In addition, several examples of widely conserved gene order involving two or more signature genes were observed. This suggests there may be regulatory processes that have been preserved throughout the long history of the cyanobacterial phenotype. The results presented here will be especially useful because they identify which of the many genes of unassigned function are likely to be of the greatest interest.

  8. Comparison and Validation of Putative Pathogenicity-Related Genes Identified by T-DNA Insertional Mutagenesis and Microarray Expression Profiling in Magnaporthe oryzae

    Science.gov (United States)

    Wáng, Ying; Tan, Qi; Gao, Ying Nv; Li, Yan

    2017-01-01

    High-throughput technologies of functional genomics such as T-DNA insertional mutagenesis and microarray expression profiling have been employed to identify genes related to pathogenicity in Magnaporthe oryzae. However, validation of the functions of individual genes identified by these high-throughput approaches is laborious. In this study, we compared two published lists of genes putatively related to pathogenicity in M. oryzae identified by T-DNA insertional mutagenesis (comprising 1024 genes) and microarray expression profiling (comprising 236 genes), respectively, and then validated the functions of some overlapped genes between the two lists by knocking them out using the method of target gene replacement. Surprisingly, only 13 genes were overlapped between the two lists, and none of the four genes selected from the overlapped genes exhibited visible phenotypic changes on vegetative growth, asexual reproduction, and infection ability in their knockout mutants. Our results suggest that both of the lists might contain large proportions of unrelated genes to pathogenicity and therefore comparing the two gene lists is hardly helpful for the identification of genes that are more likely to be involved in pathogenicity as we initially expected.

  9. The highly recombinogenic bz locus lies in an unusually gene-rich region of the maize genome.

    Science.gov (United States)

    Fu, H; Park, W; Yan, X; Zheng, Z; Shen, B; Dooner, H K

    2001-07-17

    The bronze (bz) locus exhibits the highest rate of recombination of any gene in higher plants. To investigate the possible basis of this high rate of recombination, we have analyzed the physical organization of the region around the bz locus. Two adjacent bacterial artificial chromosome clones, comprising a 240-kb contig centered around the Bz-McC allele, were isolated, and 60 kb of contiguous DNA spanning the two bacterial artificial chromosome clones was sequenced. We find that the bz locus lies in an unusually gene-rich region of the maize genome. Ten genes, at least eight of which are shown to be transcribed, are contained in a 32-kb stretch of DNA that is uninterrupted by retrotransposons. We have isolated nearly full length cDNAs corresponding to the five proximal genes in the cluster. The average intertranscript distance between them is just 1 kb, revealing a surprisingly compact packaging of adjacent genes in this part of the genome. At least 11 small insertions, including several previously described miniature inverted repeat transposable elements, were detected in the introns and 3' untranslated regions of genes and between genes. The gene-rich region is flanked at the proximal and distal ends by retrotransposon blocks. Thus, the maize genome appears to have scattered regions of high gene density similar to those found in other plants. The unusually high rate of intragenic recombination seen in bz may be related to the very high gene density of the region.

  10. Comparison of methods for genomic localization of gene trap sequences

    Directory of Open Access Journals (Sweden)

    Ferrin Thomas E

    2006-09-01

    Full Text Available Abstract Background Gene knockouts in a model organism such as mouse provide a valuable resource for the study of basic biology and human disease. Determining which gene has been inactivated by an untargeted gene trapping event poses a challenging annotation problem because gene trap sequence tags, which represent sequence near the vector insertion site of a trapped gene, are typically short and often contain unresolved residues. To understand better the localization of these sequences on the mouse genome, we compared stand-alone versions of the alignment programs BLAT, SSAHA, and MegaBLAST. A set of 3,369 sequence tags was aligned to build 34 of the mouse genome using default parameters for each algorithm. Known genome coordinates for the cognate set of full-length genes (1,659 sequences were used to evaluate localization results. Results In general, all three programs performed well in terms of localizing sequences to a general region of the genome, with only relatively subtle errors identified for a small proportion of the sequence tags. However, large differences in performance were noted with regard to correctly identifying exon boundaries. BLAT correctly identified the vast majority of exon boundaries, while SSAHA and MegaBLAST missed the majority of exon boundaries. SSAHA consistently reported the fewest false positives and is the fastest algorithm. MegaBLAST was comparable to BLAT in speed, but was the most susceptible to localizing sequence tags incorrectly to pseudogenes. Conclusion The differences in performance for sequence tags and full-length reference sequences were surprisingly small. Characteristic variations in localization results for each program were noted that affect the localization of sequence at exon boundaries, in particular.

  11. Lateral Gene Transfer Dynamics in the Ancient Bacterial Genus Streptomyces.

    Science.gov (United States)

    McDonald, Bradon R; Currie, Cameron R

    2017-06-06

    Lateral gene transfer (LGT) profoundly shapes the evolution of bacterial lineages. LGT across disparate phylogenetic groups and genome content diversity between related organisms suggest a model of bacterial evolution that views LGT as rampant and promiscuous. It has even driven the argument that species concepts and tree-based phylogenetics cannot be applied to bacteria. Here, we show that acquisition and retention of genes through LGT are surprisingly rare in the ubiquitous and biomedically important bacterial genus Streptomyces Using a molecular clock, we estimate that the Streptomyces bacteria are ~380 million years old, indicating that this bacterial genus is as ancient as land vertebrates. Calibrating LGT rate to this geologic time span, we find that on average only 10 genes per million years were acquired and subsequently maintained. Over that same time span, Streptomyces accumulated thousands of point mutations. By explicitly incorporating evolutionary timescale into our analyses, we provide a dramatically different view on the dynamics of LGT and its impact on bacterial evolution.IMPORTANCE Tree-based phylogenetics and the use of species as units of diversity lie at the foundation of modern biology. In bacteria, these pillars of evolutionary theory have been called into question due to the observation of thousands of lateral gene transfer (LGT) events within and between lineages. Here, we show that acquisition and retention of genes through LGT are exceedingly rare in the bacterial genus Streptomyces, with merely one gene acquired in Streptomyces lineages every 100,000 years. These findings stand in contrast to the current assumption of rampant genetic exchange, which has become the dominant hypothesis used to explain bacterial diversity. Our results support a more nuanced understanding of genetic exchange, with LGT impacting evolution over short timescales but playing a significant role over long timescales. Deeper understanding of LGT provides new

  12. Drosophila germline invasion by the endogenous retrovirus gypsy: involvement of the viral env gene.

    Science.gov (United States)

    Pelisson, A; Mejlumian, L; Robert, V; Terzian, C; Bucheton, A

    2002-10-01

    The endogenous retrovirus gypsy is expressed at high levels in mutant flamenco female flies. Gypsy viral particles extracted from such flies can infect naive flamenco individuals raised in the presence of these extracts mixed into their food. This results in the integration of new proviruses into the germline genome. These proviruses can then increase their copy number by (1) expression in the flamenco female somatic cells, (2) transfer into the oocyte and (3) integration into the genome of the progeny. Surprisingly, unlike the infection observed in the feeding experiments, this strategy of endogenous proviral multiplication does not seem to involve the expression of the viral env gene.

  13. Spontaneous silencing of humanized green fluorescent protein (hGFP) gene expression from a retroviral vector by DNA methylation

    DEFF Research Database (Denmark)

    Gram, G J; Nielsen, S D; Hansen, J E

    1998-01-01

    We have constructed a functional murine leukemia virus (MLV)-derived retroviral vector transducing two genes encoding the autofluorescent humanized green fluorescent protein (hGFP) and neomycin phosphotransferase (Neo). This was done to determine whether hGFP could function as a marker gene...... in a retroviral vector and to investigate the expression of genes in a retroviral vector. Surprisingly, clonal vector packaging cell lines showed variable levels of hGFP expression, and expression was detected in as few as 49% of the cells in a clonally derived culture. This indicated that hGFP expression...... was shown to increase the hGFP-expressing MT4 cells from either 10.4% to 11.6% or 3.7% to 4.8%, corresponding to an increase in observed transduction efficiencies of 12% and 30%, respectively. These results indicate that silencing of gene expression from a retroviral vector may result from DNA methylation...

  14. Analysis of mammalian gene function through broad-based phenotypic screens across a consortium of mouse clinics.

    Science.gov (United States)

    Hrabě de Angelis, Martin; Nicholson, George; Selloum, Mohammed; White, Jacqueline K; Morgan, Hugh; Ramirez-Solis, Ramiro; Sorg, Tania; Wells, Sara; Fuchs, Helmut; Fray, Martin; Adams, David J; Adams, Niels C; Adler, Thure; Aguilar-Pimentel, Antonio; Ali-Hadji, Dalila; Amann, Gregory; André, Philippe; Atkins, Sarah; Auburtin, Aurelie; Ayadi, Abdel; Becker, Julien; Becker, Lore; Bedu, Elodie; Bekeredjian, Raffi; Birling, Marie-Christine; Blake, Andrew; Bottomley, Joanna; Bowl, Michael R; Brault, Véronique; Busch, Dirk H; Bussell, James N; Calzada-Wack, Julia; Cater, Heather; Champy, Marie-France; Charles, Philippe; Chevalier, Claire; Chiani, Francesco; Codner, Gemma F; Combe, Roy; Cox, Roger; Dalloneau, Emilie; Dierich, André; Di Fenza, Armida; Doe, Brendan; Duchon, Arnaud; Eickelberg, Oliver; Esapa, Chris T; Fertak, Lahcen El; Feigel, Tanja; Emelyanova, Irina; Estabel, Jeanne; Favor, Jack; Flenniken, Ann; Gambadoro, Alessia; Garrett, Lilian; Gates, Hilary; Gerdin, Anna-Karin; Gkoutos, George; Greenaway, Simon; Glasl, Lisa; Goetz, Patrice; Da Cruz, Isabelle Goncalves; Götz, Alexander; Graw, Jochen; Guimond, Alain; Hans, Wolfgang; Hicks, Geoff; Hölter, Sabine M; Höfler, Heinz; Hancock, John M; Hoehndorf, Robert; Hough, Tertius; Houghton, Richard; Hurt, Anja; Ivandic, Boris; Jacobs, Hughes; Jacquot, Sylvie; Jones, Nora; Karp, Natasha A; Katus, Hugo A; Kitchen, Sharon; Klein-Rodewald, Tanja; Klingenspor, Martin; Klopstock, Thomas; Lalanne, Valerie; Leblanc, Sophie; Lengger, Christoph; le Marchand, Elise; Ludwig, Tonia; Lux, Aline; McKerlie, Colin; Maier, Holger; Mandel, Jean-Louis; Marschall, Susan; Mark, Manuel; Melvin, David G; Meziane, Hamid; Micklich, Kateryna; Mittelhauser, Christophe; Monassier, Laurent; Moulaert, David; Muller, Stéphanie; Naton, Beatrix; Neff, Frauke; Nolan, Patrick M; Nutter, Lauryl M J; Ollert, Markus; Pavlovic, Guillaume; Pellegata, Natalia S; Peter, Emilie; Petit-Demoulière, Benoit; Pickard, Amanda; Podrini, Christine; Potter, Paul; Pouilly, Laurent; Puk, Oliver; Richardson, David; Rousseau, Stephane; Quintanilla-Fend, Leticia; Quwailid, Mohamed M; Racz, Ildiko; Rathkolb, Birgit; Riet, Fabrice; Rossant, Janet; Roux, Michel; Rozman, Jan; Ryder, Edward; Salisbury, Jennifer; Santos, Luis; Schäble, Karl-Heinz; Schiller, Evelyn; Schrewe, Anja; Schulz, Holger; Steinkamp, Ralf; Simon, Michelle; Stewart, Michelle; Stöger, Claudia; Stöger, Tobias; Sun, Minxuan; Sunter, David; Teboul, Lydia; Tilly, Isabelle; Tocchini-Valentini, Glauco P; Tost, Monica; Treise, Irina; Vasseur, Laurent; Velot, Emilie; Vogt-Weisenhorn, Daniela; Wagner, Christelle; Walling, Alison; Wattenhofer-Donze, Marie; Weber, Bruno; Wendling, Olivia; Westerberg, Henrik; Willershäuser, Monja; Wolf, Eckhard; Wolter, Anne; Wood, Joe; Wurst, Wolfgang; Yildirim, Ali Önder; Zeh, Ramona; Zimmer, Andreas; Zimprich, Annemarie; Holmes, Chris; Steel, Karen P; Herault, Yann; Gailus-Durner, Valérie; Mallon, Ann-Marie; Brown, Steve D M

    2015-09-01

    The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline comprising 20 disease-oriented platforms. We developed new statistical methods for pipeline design and data analysis aimed at detecting reproducible phenotypes with high power. We acquired phenotype data from 449 mutant alleles, representing 320 unique genes, of which half had no previous functional annotation. We captured data from over 27,000 mice, finding that 83% of the mutant lines are phenodeviant, with 65% demonstrating pleiotropy. Surprisingly, we found significant differences in phenotype annotation according to zygosity. New phenotypes were uncovered for many genes with previously unknown function, providing a powerful basis for hypothesis generation and further investigation in diverse systems.

  15. Identification of interleukin genes in Pogona vitticeps using a de novo transcriptome assembly from RNA-seq data.

    Science.gov (United States)

    Livernois, Alexandra; Hardy, Kristine; Domaschenz, Renae; Papanicolaou, Alexie; Georges, Arthur; Sarre, Stephen D; Rao, Sudha; Ezaz, Tariq; Deakin, Janine E

    2016-10-01

    Interleukins are a group of cytokines with complex immunomodulatory functions that are important for regulating immunity in vertebrate species. Reptiles and mammals last shared a common ancestor more than 350 million years ago, so it is not surprising that low sequence identity has prevented divergent interleukin genes from being identified in the central bearded dragon lizard, Pogona vitticeps, in its genome assembly. To determine the complete nucleotide sequences of key interleukin genes, we constructed full-length transcripts, using the Trinity platform, from short paired-end read RNA sequences from stimulated spleen cells. De novo transcript reconstruction and analysis allowed us to identify interleukin genes that are missing from the published P. vitticeps assembly. Identification of key cytokines in P. vitticeps will provide insight into the essential molecular mechanisms and evolution of interleukin gene families and allow for characterization of the immune response in a lizard for comparison with mammals.

  16. Identification of target genes of synovial sarcoma-associated fusion oncoprotein using human pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, Kazuo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ikeya, Makoto [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Fukuta, Makoto [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Woltjen, Knut [Department of Reprogramming Sciences, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Tamaki, Sakura; Takahara, Naoko; Kato, Tomohisa; Sato, Shingo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Otsuka, Takanobu [Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Toguchida, Junya, E-mail: togjun@frontier.kyoto-u.ac.jp [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

    2013-03-22

    Highlights: ► We tried to identify targets of synovial sarcoma (SS)-associated SYT–SSX fusion gene. ► We established pluripotent stem cell (PSC) lines with inducible SYT–SSX gene. ► SYT–SSX responsive genes were identified by the induction of SYT–SSX in PSC. ► SS-related genes were selected from database by in silico analyses. ► 51 genes were finally identified among SS-related genes as targets of SYT–SSX in PSC. -- Abstract: Synovial sarcoma (SS) is a malignant soft tissue tumor harboring chromosomal translocation t(X; 18)(p11.2; q11.2), which produces SS-specific fusion gene, SYT–SSX. Although precise function of SYT–SSX remains to be investigated, accumulating evidences suggest its role in gene regulation via epigenetic mechanisms, and the product of SYT–SSX target genes may serve as biomarkers of SS. Lack of knowledge about the cell-of-origin of SS, however, has placed obstacle in the way of target identification. Here we report a novel approach to identify SYT–SSX2 target genes using human pluripotent stem cells (hPSCs) containing a doxycycline-inducible SYT–SSX2 gene. SYT–SSX2 was efficiently induced both at mRNA and protein levels within three hours after doxycycline administration, while no morphological change of hPSCs was observed until 24 h. Serial microarray analyses identified genes of which the expression level changed more than twofold within 24 h. Surprisingly, the majority (297/312, 95.2%) were up-regulated genes and a result inconsistent with the current concept of SYT–SSX as a transcriptional repressor. Comparing these genes with SS-related genes which were selected by a series of in silico analyses, 49 and 2 genes were finally identified as candidates of up- and down-regulated target of SYT–SSX, respectively. Association of these genes with SYT–SSX in SS cells was confirmed by knockdown experiments. Expression profiles of SS-related genes in hPSCs and human mesenchymal stem cells (hMSCs) were strikingly

  17. Primetime for Learning Genes

    Science.gov (United States)

    Keifer, Joyce

    2017-01-01

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be “poised” for rapid response to activate or repress gene expression depending on environmental stimuli. PMID:28208656

  18. Primetime for Learning Genes.

    Science.gov (United States)

    Keifer, Joyce

    2017-02-11

    Learning genes in mature neurons are uniquely suited to respond rapidly to specific environmental stimuli. Expression of individual learning genes, therefore, requires regulatory mechanisms that have the flexibility to respond with transcriptional activation or repression to select appropriate physiological and behavioral responses. Among the mechanisms that equip genes to respond adaptively are bivalent domains. These are specific histone modifications localized to gene promoters that are characteristic of both gene activation and repression, and have been studied primarily for developmental genes in embryonic stem cells. In this review, studies of the epigenetic regulation of learning genes in neurons, particularly the brain-derived neurotrophic factor gene (BDNF), by methylation/demethylation and chromatin modifications in the context of learning and memory will be highlighted. Because of the unique function of learning genes in the mature brain, it is proposed that bivalent domains are a characteristic feature of the chromatin landscape surrounding their promoters. This allows them to be "poised" for rapid response to activate or repress gene expression depending on environmental stimuli.

  19. Cloning and sequence analysis of Sox genes in a tetraploid cyprinid fish, Tor douronensis

    Institute of Scientific and Technical Information of China (English)

    GUO BaoCheng; LI JunBing; TONG ChaoBo; HE ShunPing

    2008-01-01

    A PCR survey for Sox genes in a young tetraploid fish Tor douronensis (Teleostei: Cyprinidae) was per-formed to access the evolutionary fates of important functional genes after genome duplication caused by polyploidization event. Totally 13 Sox genes were obtained in Tor douronensis, which represent SoxB, SoxC and SoxE groups. Phylogenetic analysis of Sox genes in Tor douronensis provided evidence for fish-specific genome duplication, and suggested that Sox19 might be a teleost specific Sox gene member. Sequence analysis revealed most of the nucleotide substitutions between duplicated copies of Sox genes caused by tetraploidization event or their orthologues in other species are silent substitutions. It would appear that the sequences are under purifying selective pressure, strongly suggesting that they repre- sent functional genes and supporting selection against all null allele at either of two duplicated loci of Sox4a, Sox9a and Sox9b. Surprising variations of the intron length and similarities of two duplicated copies of Sox9a and Sox9b, suggest that Tor douronensis might be an allotetraploidy.

  20. Unique chimeric composition of the trehalase gene from brine shrimp, Artemia franciscana.

    Science.gov (United States)

    Tanaka, Shin; Nambu, Fumiko; Nambu, Ziro

    2010-03-01

    To investigate the exon/intron structure of the Artemia trehalase gene, four overlapping clones were isolated from a genome library derived from an inbred strain of crustacean Artemia franciscana, and a 49 kb genetic area was re-constructed. The re-constructed area contained eight exons corresponding to the trehalase cDNA sequence that we had previously reported [1]. Comparative analysis of the Artemia trehalase gene with other animal trehalase genes revealed the existence of conserved exon/intron boundaries among different phyla. Comparison of the 5' UTR region of trehalase mRNA obtained by the 5' RACE method with the trehalase genes indicated the existence of a novel exon/intron boundary in the region designated "Exon I". Surprisingly, a part of a mitochondrial ribosomal protein gene (MRP-S33) was found to be inserted in the 5' UTR region of the trehalase gene. This sequence had the same polyadenylation signal that the Artemia MRP-S33 cDNAs did. Using the 3' RACE method, it was demonstrated that the poly (A) additional signal is still functional and that the chimeric mRNAs composed of the 5' UTR of the trehalase mRNA and of the 3' end derived from the MRP-S33 gene are transcribed.

  1. Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom phospholipase A2 genes

    Directory of Open Access Journals (Sweden)

    Lynch Vincent J

    2007-01-01

    Full Text Available Abstract Background Gene duplication followed by functional divergence has long been hypothesized to be the main source of molecular novelty. Convincing examples of neofunctionalization, however, remain rare. Snake venom phospholipase A2 genes are members of large multigene families with many diverse functions, thus they are excellent models to study the emergence of novel functions after gene duplications. Results Here, I show that positive Darwinian selection and neofunctionalization is common in snake venom phospholipase A2 genes. The pattern of gene duplication and positive selection indicates that adaptive molecular evolution occurs immediately after duplication events as novel functions emerge and continues as gene families diversify and are refined. Surprisingly, adaptive evolution of group-I phospholipases in elapids is also associated with speciation events, suggesting adaptation of the phospholipase arsenal to novel prey species after niche shifts. Mapping the location of sites under positive selection onto the crystal structure of phospholipase A2 identified regions evolving under diversifying selection are located on the molecular surface and are likely protein-protein interactions sites essential for toxin functions. Conclusion These data show that increases in genomic complexity (through gene duplications can lead to phenotypic complexity (venom composition and that positive Darwinian selection is a common evolutionary force in snake venoms. Finally, regions identified under selection on the surface of phospholipase A2 enzymes are potential candidate sites for structure based antivenin design.

  2. Genome-wide analysis of the p53 gene regulatory network in the developing mouse kidney.

    Science.gov (United States)

    Li, Yuwen; Liu, Jiao; McLaughlin, Nathan; Bachvarov, Dimcho; Saifudeen, Zubaida; El-Dahr, Samir S

    2013-10-16

    Despite mounting evidence that p53 senses and responds to physiological cues in vivo, existing knowledge regarding p53 function and target genes is largely derived from studies in cancer or stressed cells. Herein we utilize p53 transcriptome and ChIP-Seq (chromatin immunoprecipitation-high throughput sequencing) analyses to identify p53 regulated pathways in the embryonic kidney, an organ that develops via mesenchymal-epithelial interactions. This integrated approach allowed identification of novel genes that are possible direct p53 targets during kidney development. We find the p53-regulated transcriptome in the embryonic kidney is largely composed of genes regulating developmental, morphogenesis, and metabolic pathways. Surprisingly, genes in cell cycle and apoptosis pathways account for kidney lie within proximal promoters of annotated genes compared with 7% in a representative cancer cell line; 25% of the differentially expressed p53-bound genes are present in nephron progenitors and nascent nephrons, including key transcriptional regulators, components of Fgf, Wnt, Bmp, and Notch pathways, and ciliogenesis genes. The results indicate widespread p53 binding to the genome in vivo and context-dependent differences in the p53 regulon between cancer, stress, and development. To our knowledge, this is the first comprehensive analysis of the p53 transcriptome and cistrome in a developing mammalian organ, substantiating the role of p53 as a bona fide developmental regulator. We conclude p53 targets transcriptional networks regulating nephrogenesis and cellular metabolism during kidney development.

  3. High efficiency TALENs enable F0 functional analysis by targeted gene disruption in Xenopus laevis embryos

    Directory of Open Access Journals (Sweden)

    Ken-ichi T. Suzuki

    2013-03-01

    Recently, gene editing with transcription activator-like effector nucleases (TALENs has been used in the life sciences. TALENs can be easily customized to recognize a specific DNA sequence and efficiently introduce double-strand breaks at the targeted genomic locus. Subsequent non-homologous end-joining repair leads to targeted gene disruption by base insertion, deletion, or both. Here, to readily evaluate the efficacy of TALENs in Xenopus laevis embryos, we performed the targeted gene disruption of tyrosinase (tyr and pax6 genes that are involved in pigmentation and eye formation, respectively. We constructed TALENs targeting tyr and pax6 and injected their mRNAs into fertilized eggs at the one-cell stage. Expectedly, introduction of tyr TALEN mRNA resulted in drastic loss of pigmentation with high efficiency. Similarly, for pax6, TALENs led to deformed eyes in the injected embryos. We confirmed mutations of the target alleles by restriction enzyme digestion and sequence analyses of genomic PCR products. Surprisingly, not only biallelic but also paralogous, gene disruption was observed. Our results demonstrate that targeted gene disruption by TALENs provides a method comparable to antisense morpholinos in analyzing gene function in Xenopus F0 embryos, but also applies beyond embryogenesis to any life stage.

  4. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shang-Lang [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chao, Chuck C.-K., E-mail: cckchao@mail.cgu.edu.tw [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan (China)

    2015-06-16

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug.

  5. A circadian gene expression atlas in mammals: implications for biology and medicine.

    Science.gov (United States)

    Zhang, Ray; Lahens, Nicholas F; Ballance, Heather I; Hughes, Michael E; Hogenesch, John B

    2014-11-11

    To characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional "rush hours" preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.

  6. Association study of interferon gamma (IFN-γ) +874T/A gene polymorphism in patients with paranoid schizophrenia.

    Science.gov (United States)

    Paul-Samojedny, Monika; Owczarek, Aleksander; Suchanek, Renata; Kowalczyk, Malgorzata; Fila-Danilow, Anna; Borkowska, Paulina; Kucia, Krzysztof; Kowalski, Jan

    2011-03-01

    Schizophrenia is a multifactorial disease with changes affecting the immune system. Dysregulation of the cytokine network in schizophrenia has been well documented. Such changes may occur due to disturbances in cytokine levels that are linked to polymorphisms of cytokine genes. However, research in the role of cytokine gene polymorphisms in schizophrenia has been surprisingly scanty. The aim of this study was to identify, in a case control study, whether polymorphism of IFN-γ gene is a risk factor for the development of paranoid schizophrenia. To the best of our knowledge, this is the first study that examines the association between the IFN-γ gene polymorphism and psychopathological symptoms in patients with paranoid schizophrenia. Polymorphism of IFN-γ (+874T/A, rs 62559044) in schizophrenic patients (n=179), as well as healthy individuals (n=196), both Polish residents, was genotyped using AS-PCR method. Of note, when analyzing the results, we took into consideration the gender of studied individuals. Surprisingly, a single-nucleotide polymorphism in the first intron of the IFN-γ gene was found to be associated with paranoid schizophrenia in males, but not in females. The presence of allele A at position +874 in the IFN-γ gene correlates with 1.66-fold higher risk of paranoid schizophrenia development in males. Differences in the genotypes may have an important role in determining the level of I gene transcription. Because other polymorphisms have been demonstrated to influence IFN-γ transcription, further analysis is necessary to clarify the role of this gene in the pathogenesis of paranoid schizophrenia.

  7. Integrating murine gene expression studies to understand obstructive lung disease due to chronic inhaled endotoxin.

    Directory of Open Access Journals (Sweden)

    Peggy S Lai

    Full Text Available RATIONALE: Endotoxin is a near ubiquitous environmental exposure that that has been associated with both asthma and chronic obstructive pulmonary disease (COPD. These obstructive lung diseases have a complex pathophysiology, making them difficult to study comprehensively in the context of endotoxin. Genome-wide gene expression studies have been used to identify a molecular snapshot of the response to environmental exposures. Identification of differentially expressed genes shared across all published murine models of chronic inhaled endotoxin will provide insight into the biology underlying endotoxin-associated lung disease. METHODS: We identified three published murine models with gene expression profiling after repeated low-dose inhaled endotoxin. All array data from these experiments were re-analyzed, annotated consistently, and tested for shared genes found to be differentially expressed. Additional functional comparison was conducted by testing for significant enrichment of differentially expressed genes in known pathways. The importance of this gene signature in smoking-related lung disease was assessed using hierarchical clustering in an independent experiment where mice were exposed to endotoxin, smoke, and endotoxin plus smoke. RESULTS: A 101-gene signature was detected in three murine models, more than expected by chance. The three model systems exhibit additional similarity beyond shared genes when compared at the pathway level, with increasing enrichment of inflammatory pathways associated with longer duration of endotoxin exposure. Genes and pathways important in both asthma and COPD were shared across all endotoxin models. Mice exposed to endotoxin, smoke, and smoke plus endotoxin were accurately classified with the endotoxin gene signature. CONCLUSIONS: Despite the differences in laboratory, duration of exposure, and strain of mouse used in three experimental models of chronic inhaled endotoxin, surprising similarities in gene

  8. Gene expression profiling of U12-type spliceosome mutant Drosophila reveals widespread changes in metabolic pathways.

    Directory of Open Access Journals (Sweden)

    Heli K J Pessa

    Full Text Available BACKGROUND: The U12-type spliceosome is responsible for the removal of a subset of introns from eukaryotic mRNAs. U12-type introns are spliced less efficiently than normal U2-type introns, which suggests a rate-limiting role in gene expression. The Drosophila genome contains about 20 U12-type introns, many of them in essential genes, and the U12-type spliceosome has previously been shown to be essential in the fly. METHODOLOGY/PRINCIPAL FINDINGS: We have used a Drosophila line with a P-element insertion in U6atac snRNA, an essential component of the U12-type spliceosome, to investigate the impact of U12-type introns on gene expression at the organismal level during fly development. This line exhibits progressive accumulation of unspliced U12-type introns during larval development and the death of larvae at the third instar stage. Surprisingly, microarray and RT-PCR analyses revealed that most genes containing U12-type introns showed only mild perturbations in the splicing of U12-type introns. In contrast, we detected widespread downstream effects on genes that do not contain U12-type introns, with genes related to various metabolic pathways constituting the largest group. CONCLUSIONS/SIGNIFICANCE: U12-type intron-containing genes exhibited variable gene-specific responses to the splicing defect, with some genes showing up- or downregulation, while most did not change significantly. The observed residual U12-type splicing activity could be explained with the mutant U6atac allele having a low level of catalytic activity. Detailed analysis of all genes suggested that a defect in the splicing of the U12-type intron of the mitochondrial prohibitin gene may be the primary cause of the various downstream effects detected in the microarray analysis.

  9. An Ontology of Gene

    OpenAIRE

    Masuya, Hiroshi; Mizoguchi, Riichiro

    2012-01-01

    The concept of a gene was established in the era of classical genetics and is now essential for life science for elucidating the molecular basis of the coding of genetic information necessary to realize the body of an organism and its biological functions. However, an ontology fully representing multiple aspects of a gene is still not available. In this study, we dissected the biological and ontological definitions of bearers of genetic information, including genes and alleles. Based on this ...

  10. Placental gene therapy

    OpenAIRE

    David, A. L.; Ashcroft, R

    2009-01-01

    Gene therapy uses genetic material as a drug delivery vehicle to express therapeutic proteins. Placental gene therapy may be useful for correction of two important obstetric conditions, foetal growth restriction and pre-eclampsia in which there is a failure of the physiological trophoblast remodelling of the uterine spiral arteries in early pregnancy. The patient in this scenario is the foetus. Placental gene therapy might be justifiable when: there is reasonable certainty that the foetus wil...

  11. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to mammal......Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...

  12. History of gene therapy.

    Science.gov (United States)

    Wirth, Thomas; Parker, Nigel; Ylä-Herttuala, Seppo

    2013-08-10

    Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the concern that has persisted in society. Despite the setbacks gene therapy has faced, success stories have increasingly emerged. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, our knowledge continues to grow and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors which are now producing clinical results. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and address some concerns that have been connected with gene therapy as an important therapeutic modality.

  13. Performance of single and concatenated sets of mitochondrial genes at inferring metazoan relationships relative to full mitogenome data.

    Directory of Open Access Journals (Sweden)

    Justin C Havird

    Full Text Available Mitochondrial (mt genes are some of the most popular and widely-utilized genetic loci in phylogenetic studies of metazoan taxa. However, their linked nature has raised questions on whether using the entire mitogenome for phylogenetics is overkill (at best or pseudoreplication (at worst. Moreover, no studies have addressed the comparative phylogenetic utility of mitochondrial genes across individual lineages within the entire Metazoa. To comment on the phylogenetic utility of individual mt genes as well as concatenated subsets of genes, we analyzed mitogenomic data from 1865 metazoan taxa in 372 separate lineages spanning genera to subphyla. Specifically, phylogenies inferred from these datasets were statistically compared to ones generated from all 13 mt protein-coding (PC genes (i.e., the "supergene" set to determine which single genes performed "best" at, and the minimum number of genes required to, recover the "supergene" topology. Surprisingly, the popular marker COX1 performed poorest, while ND5, ND4, and ND2 were most likely to reproduce the "supergene" topology. Averaged across all lineages, the longest ∼2 mt PC genes were sufficient to recreate the "supergene" topology, although this average increased to ∼5 genes for datasets with 40 or more taxa. Furthermore, concatenation of the three "best" performing mt PC genes outperformed that of the three longest mt PC genes (i.e, ND5, COX1, and ND4. Taken together, while not all mt PC genes are equally interchangeable in phylogenetic studies of the metazoans, some subset can serve as a proxy for the 13 mt PC genes. However, the exact number and identity of these genes is specific to the lineage in question and cannot be applied indiscriminately across the Metazoa.

  14. The genomic distribution of sex-biased genes in drosophila serrata: X chromosome demasculinization, feminization, and hyperexpression in both sexes.

    Science.gov (United States)

    Allen, Scott L; Bonduriansky, Russell; Chenoweth, Stephen F

    2013-01-01

    The chromosomal distribution of genes with sex-biased expression is often nonrandom, and in species with XY sex chromosome systems, it is common to observe a deficit of X-linked male-biased genes and an excess of X-linked female-biased genes. One explanation for this pattern is that sex-specific selection has shaped the gene content of the X. Alternatively, the deficit of male-biased and excess of female-biased genes could be an artifact of differences between the sexes in the global expression level of their X chromosome(s), perhaps brought about by a lack of dosage compensation in males and hyperexpression in females. In the montium fruit fly, Drosophila serrata, both these explanations can account for a deficit of male-biased and excess of female-biased X-linked genes. Using genome-wide expression data from multiple male and female tissues (n = 176 hybridizations), we found that testis- and accessory gland-specific genes are underrepresented whereas female ovary-specific genes are overrepresented on the X chromosome, suggesting that X-linkage is disfavored for male function genes but favored for female function genes. However, genes with such sex-specific functions did not fully account for the deficit of male-biased and excess of female-biased X-linked genes. We did, however, observe sex differences in the global expression level of the X chromosome and autosomes. Surprisingly, and in contrast to other species where a lack of dosage compensation in males is responsible, we found that hyperexpression of X-linked genes in both sexes leads to this imbalance in D. serrata. Our results highlight how common genomic distributions of sex-biased genes, even among closely related species, may arise via quite different evolutionary processes.

  15. Delivery Systems in Gene Therapy

    Institute of Scientific and Technical Information of China (English)

    Liu Hu; Anas El-Aneed; Cui Guohui

    2005-01-01

    1 Gene therapy Gene therapy includes the treatment of both genetically based and infectious diseases by introducing genetic materials which have therapeutic effects[1~3]. In its simplest terms, a wild type gene (which is non-functional in the cell leading to disease development) is introduced into the somatic cell lacking this gene to restore the normal gene function in this cell. Many gene therapy strategies, however, utilize genes to destroy specific cells.

  16. Gene promoters dictate histone occupancy within genes.

    Science.gov (United States)

    Perales, Roberto; Erickson, Benjamin; Zhang, Lian; Kim, Hyunmin; Valiquett, Elan; Bentley, David

    2013-10-01

    Spt6 is a transcriptional elongation factor and histone chaperone that reassembles transcribed chromatin. Genome-wide H3 mapping showed that Spt6 preferentially maintains nucleosomes within the first 500 bases of genes and helps define nucleosome-depleted regions in 5' and 3' flanking sequences. In Spt6-depleted cells, H3 loss at 5' ends correlates with reduced pol II density suggesting enhanced transcription elongation. Consistent with its 'Suppressor of Ty' (Spt) phenotype, Spt6 inactivation caused localized H3 eviction over 1-2 nucleosomes at 5' ends of Ty elements. H3 displacement differed between genes driven by promoters with 'open'/DPN and 'closed'/OPN chromatin conformations with similar pol II densities. More eviction occurred on genes with 'closed' promoters, associated with 'noisy' transcription. Moreover, swapping of 'open' and 'closed' promoters showed that they can specify distinct downstream patterns of histone eviction/deposition. These observations suggest a novel function for promoters in dictating histone dynamics within genes possibly through effects on transcriptional bursting or elongation rate.

  17. Smart Genes, Stupid Science.

    Science.gov (United States)

    Randerson, Sherman; Mahadeva, Madhu N.

    1983-01-01

    Because many people still believe that specific, identifiable genes dictate the level of human intelligence and that the number/quality of these genes can be evaluated, presents evidence from human genetics (related to nervous system development) to counter this view. Also disputes erroneous assumptions made in "heritability studies" of human…

  18. XLMR genes: update 2000.

    NARCIS (Netherlands)

    Chiurazzi, P.; Hamel, B.C.J.; Neri, G.

    2001-01-01

    This is the sixth edition of the catalogue of XLMR genes, ie X-linked genes whose malfunctioning causes mental retardation. The cloning era is not yet concluded, actually much remains to be done to account for the 202 XLMR conditions listed in this update. Many of these may eventually prove to be du

  19. Glaucoma Genes and Mechanisms.

    Science.gov (United States)

    Wiggs, Janey L

    2015-01-01

    Genetic studies have yielded important genes contributing to both early-onset and adult-onset forms of glaucoma. The proteins encoded by the current collection of glaucoma genes participate in a broad range of cellular processes and biological systems. Approximately half the glaucoma-related genes function in the extracellular matrix, however proteins involved in cytokine signaling, lipid metabolism, membrane biology, regulation of cell division, autophagy, and ocular development also contribute to the disease pathogenesis. While the function of these proteins in health and disease are not completely understood, recent studies are providing insight into underlying disease mechanisms, a critical step toward the development of gene-based therapies. In this review, genes known to cause early-onset glaucoma or contribute to adult-onset glaucoma are organized according to the cell processes or biological systems that are impacted by the function of the disease-related protein product.

  20. The Genome-Wide Interaction Network of Nutrient Stress Genes in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Côtôé

    2016-11-01

    Full Text Available Conventional efforts to describe essential genes in bacteria have typically emphasized nutrient-rich growth conditions. Of note, however, are the set of genes that become essential when bacteria are grown under nutrient stress. For example, more than 100 genes become indispensable when the model bacterium Escherichia coli is grown on nutrient-limited media, and many of these nutrient stress genes have also been shown to be important for the growth of various bacterial pathogens in vivo. To better understand the genetic network that underpins nutrient stress in E. coli, we performed a genome-scale cross of strains harboring deletions in some 82 nutrient stress genes with the entire E. coli gene deletion collection (Keio to create 315,400 double deletion mutants. An analysis of the growth of the resulting strains on rich microbiological media revealed an average of 23 synthetic sick or lethal genetic interactions for each nutrient stress gene, suggesting that the network defining nutrient stress is surprisingly complex. A vast majority of these interactions involved genes of unknown function or genes of unrelated pathways. The most profound synthetic lethal interactions were between nutrient acquisition and biosynthesis. Further, the interaction map reveals remarkable metabolic robustness in E. coli through pathway redundancies. In all, the genetic interaction network provides a powerful tool to mine and identify missing links in nutrient synthesis and to further characterize genes of unknown function in E. coli. Moreover, understanding of bacterial growth under nutrient stress could aid in the development of novel antibiotic discovery platforms.

  1. Decoding the nucleoid organisation of Bacillus subtilis and Escherichia coli through gene expression data

    Directory of Open Access Journals (Sweden)

    Grossmann Alex

    2005-06-01

    Full Text Available Abstract Background Although the organisation of the bacterial chromosome is an area of active research, little is known yet on that subject. The difficulty lies in the fact that the system is dynamic and difficult to observe directly. The advent of massive hybridisation techniques opens the way to further studies of the chromosomal structure because the genes that are co-expressed, as identified by microarray experiments, probably share some spatial relationship. The use of several independent sets of gene expression data should make it possible to obtain an exhaustive view of the genes co-expression and thus a more accurate image of the structure of the chromosome. Results For both Bacillus subtilis and Escherichia coli the co-expression of genes varies as a function of the distance between the genes along the chromosome. The long-range correlations are surprising: the changes in the level of expression of any gene are correlated (positively or negatively to the changes in the expression level of other genes located at well-defined long-range distances. This property is true for all the genes, regardless of their localisation on the chromosome. We also found short-range correlations, which suggest that the location of these co-expressed genes corresponds to DNA turns on the nucleoid surface (14–16 genes. Conclusion The long-range correlations do not correspond to the domains so far identified in the nucleoid. We explain our results by a model of the nucleoid solenoid structure based on two types of spirals (short and long. The long spirals are uncoiled expressed DNA while the short ones correspond to coiled unexpressed DNA.

  2. A relative variation-based method to unraveling gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Yali Wang

    Full Text Available Gene regulatory network (GRN reconstruction is essential in understanding the functioning and pathology of a biological system. Extensive models and algorithms have been developed to unravel a GRN. The DREAM project aims to clarify both advantages and disadvantages of these methods from an application viewpoint. An interesting yet surprising observation is that compared with complicated methods like those based on nonlinear differential equations, etc., methods based on a simple statistics, such as the so-called Z-score, usually perform better. A fundamental problem with the Z-score, however, is that direct and indirect regulations can not be easily distinguished. To overcome this drawback, a relative expression level variation (RELV based GRN inference algorithm is suggested in this paper, which consists of three major steps. Firstly, on the basis of wild type and single gene knockout/knockdown experimental data, the magnitude of RELV of a gene is estimated. Secondly, probability for the existence of a direct regulation from a perturbed gene to a measured gene is estimated, which is further utilized to estimate whether a gene can be regulated by other genes. Finally, the normalized RELVs are modified to make genes with an estimated zero in-degree have smaller RELVs in magnitude than the other genes, which is used afterwards in queuing possibilities of the existence of direct regulations among genes and therefore leads to an estimate on the GRN topology. This method can in principle avoid the so-called cascade errors under certain situations. Computational results with the Size 100 sub-challenges of DREAM3 and DREAM4 show that, compared with the Z-score based method, prediction performances can be substantially improved, especially the AUPR specification. Moreover, it can even outperform the best team of both DREAM3 and DREAM4. Furthermore, the high precision of the obtained most reliable predictions shows that the suggested algorithm may be

  3. miRNA-mediated functional changes through co-regulating function related genes.

    Directory of Open Access Journals (Sweden)

    Jie He

    Full Text Available BACKGROUND: MicroRNAs play important roles in various biological processes involving fairly complex mechanism. Analysis of genome-wide miRNA microarray demonstrate that a single miRNA can regulate hundreds of genes, but the regulative extent on most individual genes is surprisingly mild so that it is difficult to understand how a miRNA provokes detectable functional changes with such mild regulation. RESULTS: To explore the internal mechanism of miRNA-mediated regulation, we re-analyzed the data collected from genome-wide miRNA microarray with bioinformatics assay, and found that the transfection of miR-181b and miR-34a in Hela and HCT-116 tumor cells regulated large numbers of genes, among which, the genes related to cell growth and cell death demonstrated high Enrichment scores, suggesting that these miRNAs may be important in cell growth and cell death. MiR-181b induced changes in protein expression of most genes that were seemingly related to enhancing cell growth and decreasing cell death, while miR-34a mediated contrary changes of gene expression. Cell growth assays further confirmed this finding. In further study on miR-20b-mediated osteogenesis in hMSCs, miR-20b was found to enhance osteogenesis by activating BMPs/Runx2 signaling pathway in several stages by co-repressing of PPARγ, Bambi and Crim1. CONCLUSIONS: With its multi-target characteristics, miR-181b, miR-34a and miR-20b provoked detectable functional changes by co-regulating functionally-related gene groups or several genes in the same signaling pathway, and thus mild regulation from individual miRNA targeting genes could have contributed to an additive effect. This might also be one of the modes of miRNA-mediated gene regulation.

  4. Identification of genes involved in cold-shock response in rainbow trout (Oncorhynchus mykiss)

    Indian Academy of Sciences (India)

    ANDREAS BORCHEL; MARIEKE VERLEIH; ALEXANDER REBL; TOM GOLDAMMER

    2017-09-01

    A rapid decline in temperature poses a major challenge for poikilothermic fish, as their entire metabolism depends on ambient temperature. The gene expression of rainbow trout Oncorhynchus mykiss having undergone such a cold shock (0◦C) was compared to a control (5◦C) in a microarray and quantitative real-time PCR based study. The tissues of gill, kidney and liver were examined. The most differently expressed genes were found in liver, many of them contributing to the network ‘cellular compromise, cellular growth and proliferation’.However, the number of genes found to be regulated at 0◦Cwas surprisingly low. Instead of classical genes involved in temperature shock, the three genes encoding fibroblast growth factor 1 (fgf1), growth arrest and DNA-damageinducible,alpha (gadd45a) and sclerostin domain-containing protein 1 (sostdc1) were upregulated in the liver upon cold shock in two different rainbow trout strains, suggesting that these genes may be considered as general biomarkers for cold shock in rainbow trout.

  5. NF-Y activates genes of metabolic pathways altered in cancer cells

    Science.gov (United States)

    Benatti, Paolo; Chiaramonte, Maria Luisa; Lorenzo, Mariangela; Hartley, John A.; Hochhauser, Daniel; Gnesutta, Nerina; Mantovani, Roberto; Imbriano, Carol; Dolfini, Diletta

    2016-01-01

    The trimeric transcription factor NF-Y binds to the CCAAT box, an element enriched in promoters of genes overexpressed in tumors. Previous studies on the NF-Y regulome identified the general term metabolism as significantly enriched. We dissect here in detail the targeting of metabolic genes by integrating analysis of NF-Y genomic binding and profilings after inactivation of NF-Y subunits in different cell types. NF-Y controls de novo biosynthetic pathways of lipids, teaming up with the master SREBPs regulators. It activates glycolytic genes, but, surprisingly, is neutral or represses mitochondrial respiratory genes. NF-Y targets the SOCG (Serine, One Carbon, Glycine) and Glutamine pathways, as well as genes involved in the biosynthesis of polyamines and purines. Specific cancer-driving nodes are generally under NF-Y control. Altogether, these data delineate a coherent strategy to promote expression of metabolic genes fuelling anaerobic energy production and other anabolic pathways commonly altered in cancer cells. PMID:26646448

  6. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.

    Science.gov (United States)

    Kononenko, Olga; Galatenko, Vladimir; Andersson, Malin; Bazov, Igor; Watanabe, Hiroyuki; Zhou, Xing Wu; Iatsyshyna, Anna; Mityakina, Irina; Yakovleva, Tatiana; Sarkisyan, Daniil; Ponomarev, Igor; Krishtal, Oleg; Marklund, Niklas; Tonevitsky, Alex; Adkins, DeAnna L; Bakalkin, Georgy

    2017-01-25

    Regulation of the formation and rewiring of neural circuits by neuropeptides may require coordinated production of these signaling molecules and their receptors that may be established at the transcriptional level. Here, we address this hypothesis by comparing absolute expression levels of opioid peptides with their receptors, the largest neuropeptide family, and by characterizing coexpression (transcriptionally coordinated) patterns of these genes. We demonstrated that expression patterns of opioid genes highly correlate within and across functionally and anatomically different areas. Opioid peptide genes, compared with their receptor genes, are transcribed at much greater absolute levels, which suggests formation of a neuropeptide cloud that covers the receptor-expressed circuits. Surprisingly, we found that both expression levels and the proportion of opioid receptors are strongly lateralized in the spinal cord, interregional coexpression patterns are side-specific, and intraregional coexpression profiles are affected differently by left- and right-side unilateral body injury. We propose that opioid genes are regulated as interconnected components of the same molecular system distributed between distinct anatomic regions. The striking feature of this system is its asymmetric coexpression patterns, which suggest side-specific regulation of selective neural circuits by opioid neurohormones.-Kononenko, O., Galatenko, V., Andersson, M., Bazov, I., Watanabe, H., Zhou, X. W., Iatsyshyna, A., Mityakina, I., Yakovleva, T., Sarkisyan, D., Ponomarev, I., Krishtal, O., Marklund, N., Tonevitsky, A., Adkins, D. L., Bakalkin, G. Intra- and interregional coregulation of opioid genes: broken symmetry in spinal circuits.

  7. Evidence that plasmid-borne botulinum neurotoxin type B genes are widespread among Clostridium botulinum serotype B strains.

    Directory of Open Access Journals (Sweden)

    Giovanna Franciosa

    Full Text Available BACKGROUND: Plasmids that encode certain subtypes of the botulinum neurotoxin type B have recently been detected in some Clostridium botulinum strains. The objective of the present study was to investigate the frequency with which plasmid carriage of the botulinum neurotoxin type B gene (bont/B occurs in strains of C. botulinum type B, Ab, and A(B, and whether plasmid carriage is bont/B subtype-related. METHODOLOGY/PRINCIPAL FINDINGS: PCR-Restriction fragment length polymorphism was employed to identify subtypes of the bont/B gene. Pulsed-field gel electrophoresis and Southern blot hybridization with specific probes were performed to analyze the genomic location of the bont/B subtype genes. All five known bont/B subtype genes were detected among the strains; the most frequently detected subtype genes were bont/B1 and /B2. Surprisingly, the bont/B subtype gene was shown to be plasmid-borne in >50% of the total strains. The same bont/B subtype gene was associated with the chromosome in some strains, whereas it was associated with a plasmid in others. All five known bont/B subtype genes were in some cases found to reside on plasmids, though with varying frequency (e.g., most of the bont/B1 subtype genes were located on plasmids, whereas all but one of the bont/B2 subtypes were chromosomally-located. Three bivalent isolates carried both bont/A and /B genes on the same plasmid. The plasmids carrying the bont gene were five different sizes, ranging from approximately 55 kb to approximately 245 kb. CONCLUSIONS/SIGNIFICANCE: The unexpected finding of the widespread distribution of plasmids harboring the bont/B gene among C. botulinum serotype B strains provides a chance to examine their contribution to the dissemination of the bont genes among heterogeneous clostridia, with potential implications on issues related to pathogenesis and food safety.

  8. The role of population size, pleiotropy and fitness effects of mutations in the evolution of overlapping gene functions.

    Science.gov (United States)

    Wagner, A

    2000-03-01

    Sheltered from deleterious mutations, genes with overlapping or partially redundant functions may be important sources of novel gene functions. While most partially redundant genes originated in gene duplications, it is much less clear why genes with overlapping functions have been retained, in some cases for hundreds of millions of years. A case in point is the many partially redundant genes in vertebrates, the result of ancient gene duplications in primitive chordates. Their persistence and ubiquity become surprising when it is considered that duplicate and original genes often diversify very rapidly, especially if the action of natural selection is involved. Are overlapping gene functions perhaps maintained because of their protective role against otherwise deleterious mutations? There are two principal objections against this hypothesis, which are the main subject of this article. First, because overlapping gene functions are maintained in populations by a slow process of "second order" selection, population sizes need to be very high for this process to be effective. It is shown that even in small populations, pleiotropic mutations that affect more than one of a gene's functions simultaneously can slow the mutational decay of functional overlap after a gene duplication by orders of magnitude. Furthermore, brief and transient increases in population size may be sufficient to maintain functional overlap. The second objection regards the fact that most naturally occurring mutations may have much weaker fitness effects than the rather drastic "knock-out" mutations that lead to detection of partially redundant functions. Given weak fitness effects of most mutations, is selection for the buffering effect of functional overlap strong enough to compensate for the diversifying force exerted by mutations? It is shown that the extent of functional overlap maintained in a population is not only independent of the mutation rate, but also independent of the average fitness

  9. Gene therapy for hemophilia.

    Science.gov (United States)

    Chuah, M K; Evens, H; VandenDriessche, T

    2013-06-01

    Hemophilia A and B are X-linked monogenic disorders resulting from deficiencies of factor VIII and FIX, respectively. Purified clotting factor concentrates are currently intravenously administered to treat hemophilia, but this treatment is non-curative. Therefore, gene-based therapies for hemophilia have been developed to achieve sustained high levels of clotting factor expression to correct the clinical phenotype. Over the past two decades, different types of viral and non-viral gene delivery systems have been explored for hemophilia gene therapy research with a variety of target cells, particularly hepatocytes, hematopoietic stem cells, skeletal muscle cells, and endothelial cells. Lentiviral and adeno-associated virus (AAV)-based vectors are among the most promising vectors for hemophilia gene therapy. In preclinical hemophilia A and B animal models, the bleeding phenotype was corrected with these vectors. Some of these promising preclinical results prompted clinical translation to patients suffering from a severe hemophilic phenotype. These patients receiving gene therapy with AAV vectors showed long-term expression of therapeutic FIX levels, which is a major step forwards in this field. Nevertheless, the levels were insufficient to prevent trauma or injury-induced bleeding episodes. Another challenge that remains is the possible immune destruction of gene-modified cells by effector T cells, which are directed against the AAV vector antigens. It is therefore important to continuously improve the current gene therapy approaches to ultimately establish a real cure for hemophilia. © 2013 International Society on Thrombosis and Haemostasis.

  10. Gene amplification in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lucimari Bizari

    2006-01-01

    Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

  11. Sex-biased expression of sex-differentiating genes FOXL2 and FGF9 in American alligators, Alligator mississippiensis

    Science.gov (United States)

    Janes, Daniel E.; Elsey, Ruth M.; Langan, Esther M.; Valenzuela, Nicole; Edwards, Scott V.

    2013-01-01

    Across amniotes, sex-determining mechanisms exhibit great variation yet the genes that govern sexual differentiation are largely conserved. Studies of evolution of sex-determining and sex-differentiating genes require an exhaustive characterization of functions of those genes such as FOXL2 and FGF9. FOXL2 is associated with ovarian development and FGF9 is known to play a role in testicular organogenesis in mammals and other amniotes. As a step toward characterization of the evolutionary history of sexual development, we measured expression of FOXL2 and FGF9 across three developmental stages and eight juvenile tissue types in male and female American alligators, Alligator mississippiensis. We report surprisingly high expression of FOXL2 before the stage of embryonic development when sex is determined in response to temperature and sustained and variable expression of FGF9 in juvenile male but not female tissue types. Novel characterization of gene expression in reptiles with temperature-dependent sex determination such as American alligators may inform the evolution of sex-determining and sex-differentiating gene networks as they suggest alternative functions from which the genes may have been exapted. Future functional profiling of sex-differentiating genes should similarly follow other genes and other species to enable a broad comparison across sex-determining mechanisms. PMID:23689672

  12. RNA Sequence Analysis of Human Huntington Disease Brain Reveals an Extensive Increase in Inflammatory and Developmental Gene Expression.

    Directory of Open Access Journals (Sweden)

    Adam Labadorf

    Full Text Available Huntington's Disease (HD is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480 of the 28,087 confidently detected genes are differentially expressed (FDR<0.05 and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes, that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD.

  13. Human genes for U2 small nuclear RNA map to a major adenovirus 12 modification site on chromosome 17.

    Science.gov (United States)

    Lindgren, V; Ares, M; Weiner, A M; Francke, U

    U2 RNA is one of the abundant, highly conserved species of small nuclear RNA (snRNA) molecules implicated in RNA processing. As is typical of mammalian snRNAs, human U1 and U2 are each encoded by a multigene family. In the human genome, defective copies of the genes (pseudogenes) far outnumber the authentic genes. The majority or all of the 35 to 100 bona fide U1 genes have at least 20 kilobases (kb) of nearly perfect 5' and 3' flanking homology in common with each other; these U1 genes are clustered loosely in chromosome band 1p36 (refs 5, 7) with intergenic distances exceeding 44 kb. In contrast, the 10 to 20 U2 genes are clustered tightly in a virtually perfect tandem array which has a strict 6-kb repeating unit. We report here the assignment, by in situ hybridization, of the U2 gene cluster to chromosome 17, bands q21-q22. Surprisingly, this region is one of three major adenovirus 12 modification sites which undergo chromosome decondensation ('uncoiling') in permissive human cells infected by highly oncogenic strains of adenovirus. The two other major modification sites, 1p36 and 1q21, coincide with the locations of U1 genes and class I U1 pseudogenes, respectively. We suggest that snRNA genes are the major targets of viral chromosome modification.

  14. Antisense gene silencing

    DEFF Research Database (Denmark)

    Nielsen, Troels T; Nielsen, Jørgen E

    2013-01-01

    Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied...... to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how...

  15. Decoding sORF translation - from small proteins to gene regulation.

    Science.gov (United States)

    Cabrera-Quio, Luis Enrique; Herberg, Sarah; Pauli, Andrea

    2016-11-01

    Translation is best known as the fundamental mechanism by which the ribosome converts a sequence of nucleotides into a string of amino acids. Extensive research over many years has elucidated the key principles of translation, and the majority of translated regions were thought to be known. The recent discovery of wide-spread translation outside of annotated protein-coding open reading frames (ORFs) came therefore as a surprise, raising the intriguing possibility that these newly discovered translated regions might have unrecognized protein-coding or gene-regulatory functions. Here, we highlight recent findings that provide evidence that some of these newly discovered translated short ORFs (sORFs) encode functional, previously missed small proteins, while others have regulatory roles. Based on known examples we will also speculate about putative additional roles and the potentially much wider impact that these translated regions might have on cellular homeostasis and gene regulation.

  16. Inhibitory effect of Ca2+ on in vivo gene transfer by electroporation

    Institute of Scientific and Technical Information of China (English)

    Yong-gang ZHAO; Hui-li LU; Jin-liang PENG; Yu-hong XU

    2006-01-01

    Aim:To investigate the specific effects of Ca2+ on transgene expression during electroporation-mediated gene transfer in mice.Methods:Skeletal muscle and skin were subjected to in vivo electroporation with a luciferase reporter plasmid,with or Without Ca2+ and various other ions.Resuits:For in vivo electroporation,the presence of just 10 mmol/L Ca2+ in the DNA solution drastically reduced the resulting transgene expression,to less than 5% of control values.Only Ca2+,not other ions,caused inhibition,and the effect was not tissue specific.More surprisingly.even when Ca2+ ions were delivered by electroporation before or after DNA administration,similar effects were still observed.Conelusion:The inhibitory effect of Ca2+ on in vivo gene transfer by electroporation is specific,ie,the inhibitory effect may be related to the cell membrane properties after electroporation and the subsequent resealing event.

  17. DNA methylation changes in plasticity genes accompany the formation and maintenance of memory.

    Science.gov (United States)

    Halder, Rashi; Hennion, Magali; Vidal, Ramon O; Shomroni, Orr; Rahman, Raza-Ur; Rajput, Ashish; Centeno, Tonatiuh Pena; van Bebber, Frauke; Capece, Vincenzo; Garcia Vizcaino, Julio C; Schuetz, Anna-Lena; Burkhardt, Susanne; Benito, Eva; Navarro Sala, Magdalena; Javan, Sanaz Bahari; Haass, Christian; Schmid, Bettina; Fischer, Andre; Bonn, Stefan

    2016-01-01

    The ability to form memories is a prerequisite for an organism's behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring.

  18. Phylogenetic conservation of immunoglobulin heavy chains: direct comparison of hamster and mouse Cmu genes.

    Science.gov (United States)

    McGuire, K L; Duncan, W R; Tucker, P W

    1985-08-12

    We have analyzed the JH-Cmu locus of the Syrian hamster by DNA cloning and sequencing. The single Cmu gene is highly homologous to that of the mouse. The hamster equivalents of the JH and switch (S) recombination regions are arranged as in the mouse, but surprisingly are not highly conserved. Also unlike its close murine relative, the Smu regions among inbred hamster strains are not polymorphic. The complete nucleotide sequence of hamster and mouse Cmu genes have been compared to partial Cmu sequences of other species. Conservation within a portion of the 3' untranslated region may signify functional requirements for 3' end processing. Mutational frequencies within exons and introns of hamster and mouse do not support the theory that the rate of DNA transitions to transversions decreases with evolutionary distance.

  19. Gene Therapy of Cancerous Diseases

    OpenAIRE

    Valenčáková, A.; Dziaková, A.; Hatalová, E.

    2015-01-01

    Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purp...

  20. Exogenous Camp upregulates the expression of glnII and glnK-amtB genes in Sinorhizobium meliloti 1021

    Institute of Scientific and Technical Information of China (English)

    TIAN Zhexian; MAO Xianjun; SU Wei; LI Jian; BECKER Anke; WANG Yiping

    2006-01-01

    The existence of multiple adenylate cyclase encoding genes implies the importance of Camp in Sinorhizobium meliloti 1021. In this study, as a pioneer step of understanding Camp roles, microarray analysis on S. Meliloti was carried out for the function of exogenous Camp. To our surprise, the result showed that the transcriptions of glnII and glnK genes were significantly upshifted in the presence of exogenous Camp in S. Meliloti. This phenomenon is further confirmed in S. Meliloti that the expression of either glnII or glnK promoter-lacZ translational fusion is higher in the presence of exogenous Camp.Therefore, for the first time, we have identified genes from S. Meliloti whose expression is activated by Camp. The potential physiological role of upregulation of glnII and glnK by Camp is discussed.

  1. Antagonistic changes in sensitivity to antifungal drugs by mutations of an important ABC transporter gene in a fungal pathogen.

    Directory of Open Access Journals (Sweden)

    Wenjun Guan

    Full Text Available Fungal pathogens can be lethal, especially among immunocompromised populations, such as patients with AIDS and recipients of tissue transplantation or chemotherapy. Prolonged usage of antifungal reagents can lead to drug resistance and treatment failure. Understanding mechanisms that underlie drug resistance by pathogenic microorganisms is thus vital for dealing with this emerging issue. In this study, we show that dramatic sequence changes in PDR5, an ABC (ATP-binding cassette efflux transporter protein gene in an opportunistic fungal pathogen, caused the organism to become hypersensitive to azole, a widely used antifungal drug. Surprisingly, the same mutations conferred growth advantages to the organism on polyenes, which are also commonly used antimycotics. Our results indicate that Pdr5p might be important for ergosterol homeostasis. The observed remarkable sequence divergence in the PDR5 gene in yeast strain YJM789 may represent an interesting case of adaptive loss of gene function with significant clinical implications.

  2. "Bad genes" & criminal responsibility.

    Science.gov (United States)

    González-Tapia, María Isabel; Obsuth, Ingrid

    2015-01-01

    The genetics of the accused is trying to break into the courts. To date several candidate genes have been put forward and their links to antisocial behavior have been examined and documented with some consistency. In this paper, we focus on the so called "warrior gene", or the low-activity allele of the MAOA gene, which has been most consistently related to human behavior and specifically to violence and antisocial behavior. In preparing this paper we had two objectives. First, to summarize and analyze the current scientific evidence, in order to gain an in depth understanding of the state of the issue and determine whether a dominant line of generally accepted scientific knowledge in this field can be asserted. Second, to derive conclusions and put forward recommendations related to the use of genetic information, specifically the presence of the low-activity genotype of the MAOA gene, in modulation of criminal responsibility in European and US courts.

  3. Gene Expression Omnibus (GEO)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene Expression Omnibus is a public functional genomics data repository supporting MIAME-compliant submissions of array- and sequence-based data. Tools are provided...

  4. Gene therapy in ophthalmology.

    Science.gov (United States)

    Uthra, Satagopan; Kumaramanickavel, Govindasamy

    2009-09-01

    It has been more than a year since ophthalmologists and scientists under Dr. Robin Ali's team at the Moorsfield Eye Hospital and the Institute of Ophthalmology, University College London, successfully treated patients with a severely blinding disease, Leber's congenital amaurosis (LCA) using gene therapy. This success does not look to be transient, and this achievement in gene replacement therapy clinical trial for LCA has instilled hope in numerous families with patients suffering from this and similar retinal degenerative diseases, for whom restoration of lost vision has remained a distant dream so far. The encouragement that this success has given is expected to also lead to start of clinical trials for other blinding ocular diseases for which gene therapy experiments at the laboratory and animal levels have been successful. This article reviews the various studies that have led to the understanding of gene therapy outcomes in human ocular diseases and attempts to provide a brief sketch of successful clinical trials.

  5. A systematic survey of expression and function of zebrafish frizzled genes.

    Science.gov (United States)

    Nikaido, Masataka; Law, Edward W P; Kelsh, Robert N

    2013-01-01

    Wnt signaling is crucial for the regulation of numerous processes in development. Consistent with this, the gene families for both the ligands (Wnts) and receptors (Frizzleds) are very large. Surprisingly, while we have a reasonable understanding of the Wnt ligands likely to mediate specific Wnt-dependent processes, the corresponding receptors usually remain to be elucidated. Taking advantage of the zebrafish model's excellent genomic and genetic properties, we undertook a comprehensive analysis of the expression patterns of frizzled (fzd) genes in zebrafish. To explore their functions, we focused on testing their requirement in several developmental events known to be regulated by Wnt signaling, convergent extension movements of gastrulation, neural crest induction, and melanocyte specification. We found fourteen distinct fzd genes in the zebrafish genome. Systematic analysis of their expression patterns between 1-somite and 30 hours post-fertilization revealed complex, dynamic and overlapping expression patterns. This analysis demonstrated that only fzd3a, fzd9b, and fzd10 are expressed in the dorsal neural tube at stages corresponding to the timing of melanocyte specification. Surprisingly, however, morpholino knockdown of these, alone or in combination, gave no indication of reduction of melanocytes, suggesting the important involvement of untested fzds or another type of Wnt receptor in this process. Likewise, we found only fzd7b and fzd10 expressed at the border of the neural plate at stages appropriate for neural crest induction. However, neural crest markers were not reduced by knockdown of these receptors. Instead, these morpholino knockdown studies showed that fzd7a and fzd7b work co-operatively to regulate convergent extension movement during gastrulation. Furthermore, we show that the two fzd7 genes function together with fzd10 to regulate epiboly movements and mesoderm differentiation.

  6. A systematic survey of expression and function of zebrafish frizzled genes.

    Directory of Open Access Journals (Sweden)

    Masataka Nikaido

    Full Text Available Wnt signaling is crucial for the regulation of numerous processes in development. Consistent with this, the gene families for both the ligands (Wnts and receptors (Frizzleds are very large. Surprisingly, while we have a reasonable understanding of the Wnt ligands likely to mediate specific Wnt-dependent processes, the corresponding receptors usually remain to be elucidated. Taking advantage of the zebrafish model's excellent genomic and genetic properties, we undertook a comprehensive analysis of the expression patterns of frizzled (fzd genes in zebrafish. To explore their functions, we focused on testing their requirement in several developmental events known to be regulated by Wnt signaling, convergent extension movements of gastrulation, neural crest induction, and melanocyte specification. We found fourteen distinct fzd genes in the zebrafish genome. Systematic analysis of their expression patterns between 1-somite and 30 hours post-fertilization revealed complex, dynamic and overlapping expression patterns. This analysis demonstrated that only fzd3a, fzd9b, and fzd10 are expressed in the dorsal neural tube at stages corresponding to the timing of melanocyte specification. Surprisingly, however, morpholino knockdown of these, alone or in combination, gave no indication of reduction of melanocytes, suggesting the important involvement of untested fzds or another type of Wnt receptor in this process. Likewise, we found only fzd7b and fzd10 expressed at the border of the neural plate at stages appropriate for neural crest induction. However, neural crest markers were not reduced by knockdown of these receptors. Instead, these morpholino knockdown studies showed that fzd7a and fzd7b work co-operatively to regulate convergent extension movement during gastrulation. Furthermore, we show that the two fzd7 genes function together with fzd10 to regulate epiboly movements and mesoderm differentiation.

  7. Combinatorial Gene Regulation Using Auto-Regulation

    Science.gov (United States)

    Hermsen, Rutger; Ursem, Bas; ten Wolde, Pieter Rein

    2010-01-01

    As many as 59% of the transcription factors in Escherichia coli regulate the transcription rate of their own genes. This suggests that auto-regulation has one or more important functions. Here, one possible function is studied. Often the transcription rate of an auto-regulator is also controlled by additional transcription factors. In these cases, the way the expression of the auto-regulator responds to changes in the concentrations of the “input” regulators (the response function) is obviously affected by the auto-regulation. We suggest that, conversely, auto-regulation may be used to optimize this response function. To test this hypothesis, we use an evolutionary algorithm and a chemical–physical model of transcription regulation to design model cis-regulatory constructs with predefined response functions. In these simulations, auto-regulation can evolve if this provides a functional benefit. When selecting for a series of elementary response functions—Boolean logic gates and linear responses—the cis-regulatory regions resulting from the simulations indeed often exploit auto-regulation. Surprisingly, the resulting constructs use auto-activation rather than auto-repression. Several design principles show up repeatedly in the simulation results. They demonstrate how auto-activation can be used to generate sharp, switch-like activation and repression circuits and how linearly decreasing response functions can be obtained. Auto-repression, on the other hand, resulted only when a high response speed or a suppression of intrinsic noise was also selected for. The results suggest that, while auto-repression may primarily be valuable to improve the dynamical properties of regulatory circuits, auto-activation is likely to evolve even when selection acts on the shape of response function only. PMID:20548950

  8. Aggressiveness of human melanoma xenograft models is promoted by aneuploidy-driven gene expression deregulation.

    Science.gov (United States)

    Mathieu, Véronique; Pirker, Christine; Schmidt, Wolfgang M; Spiegl-Kreinecker, Sabine; Lötsch, Daniela; Heffeter, Petra; Hegedus, Balazs; Grusch, Michael; Kiss, Robert; Berger, Walter

    2012-04-01

    Melanoma is a devastating skin cancer characterized by distinct biological subtypes. Besides frequent mutations in growth- and survival-promoting genes like BRAF and NRAS, melanomas additionally harbor complex non-random genomic alterations. Using an integrative approach, we have analysed genomic and gene expression changes in human melanoma cell lines (N=32) derived from primary tumors and various metastatic sites and investigated the relation to local growth aggressiveness as xenografts in immuno-compromised mice (N=22). Although the vast majority >90% of melanoma models harbored mutations in either BRAF or NRAS, significant differences in subcutaneous growth aggressiveness became obvious. Unsupervised clustering revealed that genomic alterations rather than gene expression data reflected this aggressive phenotype, while no association with histology, stage or metastatic site of the original melanoma was found. Genomic clustering allowed separation of melanoma models into two subgroups with differing local growth aggressiveness in vivo. Regarding genes expressed at significantly altered levels between these subgroups, a surprising correlation with the respective gene doses (>85% accordance) was found. Genes deregulated at the DNA and mRNA level included well-known cancer genes partly already linked to melanoma (RAS genes, PTEN, AURKA, MAPK inhibitors Sprouty/Spred), but also novel candidates like SIPA1 (a Rap1GAP). Pathway mining further supported deregulation of Rap1 signaling in the aggressive subgroup e.g. by additional repression of two Rap1GEFs. Accordingly, siRNA-mediated down-regulation of SIPA1 exerted significant effects on clonogenicity, adherence and migration in aggressive melanoma models. Together our data suggest that an aneuploidy-driven gene expression deregulation drives local aggressiveness in human melanoma.

  9. Comprehensive gene expression profiling reveals synergistic functional networks in cerebral vessels after hypertension or hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Wei-Yi Ong

    Full Text Available Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin, P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein; and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of 'common genes' (21 and 7% between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD.

  10. Comparative Analysis of Gene Regulation by the Transcription Factor PPARα between Mouse and Human

    Science.gov (United States)

    Rakhshandehroo, Maryam; Hooiveld, Guido; Müller, Michael; Kersten, Sander

    2009-01-01

    Background Studies in mice have shown that PPARα is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARα in human liver. Here we set out to compare the function of PPARα in mouse and human hepatocytes via analysis of target gene regulation. Methodology/Principal Findings Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARα agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARα expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362–672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPARα in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARα targets, including CPT1A, HMGCS2, FABP1, ACSL1, and ADFP. Several genes were identified that were specifically induced by PPARα in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPARα targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Conclusions/Significance Our results suggest that PPARα activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPARα as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPARα regulates a mostly divergent set of genes in mouse and human hepatocytes. PMID:19710929

  11. Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.

    Directory of Open Access Journals (Sweden)

    Maryam Rakhshandehroo

    Full Text Available BACKGROUND: Studies in mice have shown that PPARalpha is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPARalpha in human liver. Here we set out to compare the function of PPARalpha in mouse and human hepatocytes via analysis of target gene regulation. METHODOLOGY/PRINCIPAL FINDINGS: Primary hepatocytes from 6 human and 6 mouse donors were treated with PPARalpha agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPARalpha expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPARalpha in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPARalpha targets, including CPT1A, HMGCS2, FABP1, ACSL1, and ADFP. Several genes were identified that were specifically induced by PPARalpha in human (MBL2, ALAS1, CYP1A1, TSKU or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4. Furthermore, several putative novel PPARalpha targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. CONCLUSIONS/SIGNIFICANCE: Our results suggest that PPARalpha activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPARalpha as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPARalpha regulates a mostly divergent set of genes in mouse and

  12. Diverse flavonoids stimulate NodD1 binding to nod gene promoters in Sinorhizobium meliloti.

    Science.gov (United States)

    Peck, Melicent C; Fisher, Robert F; Long, Sharon R

    2006-08-01

    NodD1 is a member of the NodD family of LysR-type transcriptional regulators that mediates the expression of nodulation (nod) genes in the soil bacterium Sinorhizobium meliloti. Each species of rhizobia establishes a symbiosis with a limited set of leguminous plants. This host specificity results in part from a NodD-dependent upregulation of nod genes in response to a cocktail of flavonoids in the host plant's root exudates. To demonstrate that NodD is a key determinant of host specificity, we expressed nodD genes from different species of rhizobia in a strain of S. meliloti lacking endogenous NodD activity. We observed that nod gene expression was initiated in response to distinct sets of flavonoid inducers depending on the source of NodD. To better understand the effects of flavonoids on NodD, we assayed the DNA binding activity of S. meliloti NodD1 treated with the flavonoid inducer luteolin. In the presence of luteolin, NodD1 exhibited increased binding to nod gene promoters compared to binding in the absence of luteolin. Surprisingly, although they do not stimulate nod gene expression in S. meliloti, the flavonoids naringenin, eriodictyol, and daidzein also stimulated an increase in the DNA binding affinity of NodD1 to nod gene promoters. In vivo competition assays demonstrate that noninducing flavonoids act as competitive inhibitors of luteolin, suggesting that both inducing and noninducing flavonoids are able to directly bind to NodD1 and mediate conformational changes at nod gene promoters but that only luteolin is capable of promoting the downstream changes necessary for nod gene induction.

  13. Massive losses of taste receptor genes in toothed and baleen whales.

    Science.gov (United States)

    Feng, Ping; Zheng, Jinsong; Rossiter, Stephen J; Wang, Ding; Zhao, Huabin

    2014-05-06

    Taste receptor genes are functionally important in animals, with a surprising exception in the bottlenose dolphin, which shows extensive losses of sweet, umami, and bitter taste receptor genes. To examine the generality of taste gene loss, we examined seven toothed whales and five baleen whales and sequenced the complete repertoire of three sweet/umami (T1Rs) and ten bitter (T2Rs) taste receptor genes. We found all amplified T1Rs and T2Rs to be pseudogenes in all 12 whales, with a shared premature stop codon in 10 of the 13 genes, which demonstrated massive losses of taste receptor genes in the common ancestor of whales. Furthermore, we analyzed three genome sequences from two toothed whales and one baleen whale and found that the sour taste marker gene Pkd2l1 is a pseudogene, whereas the candidate salty taste receptor genes are intact and putatively functional. Additionally, we examined three genes that are responsible for taste signal transduction and found the relaxation of functional constraints on taste signaling pathways along the ancestral branch leading to whales. Together, our results strongly suggest extensive losses of sweet, umami, bitter, and sour tastes in whales, and the relaxation of taste function most likely arose in the common ancestor of whales between 36 and 53 Ma. Therefore, whales represent the first animal group to lack four of five primary tastes, probably driven by the marine environment with high concentration of sodium, the feeding behavior of swallowing prey whole, and the dietary switch from plants to meat in the whale ancestor. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. RpoS regulation of gene expression during exponential growth of Escherichia coli K12.

    Science.gov (United States)

    Dong, Tao; Kirchhof, Mark G; Schellhorn, Herb E

    2008-03-01

    RpoS is a major regulator of genes required for adaptation to stationary phase in E. coli. However, the exponential phase expression of some genes is affected by rpoS mutation, suggesting RpoS may also have an important physiological role in growing cells. To test this hypothesis, we examined the regulatory role of RpoS in exponential phase using both genomic and biochemical approaches. Microarray expression data revealed that, in the rpoS mutant, the expression of 268 genes was attenuated while the expression of 24 genes was enhanced. Genes responsible for carbon source transport (the mal operon for maltose), protein folding (dnaK and mopAB), and iron acquisition (fepBD, entCBA, fecI, and exbBD) were positively controlled by RpoS. The importance of RpoS-mediated control of iron acquisition was confirmed by cellular metal analysis which revealed that the intracellular iron content of wild type cells was two-fold higher than in rpoS mutant cells. Surprisingly, many previously identified RpoS stationary-phase dependent genes were not controlled by RpoS in exponential phase and several genes were RpoS-regulated only in exponential phase, suggesting the involvement of other regulators. The expression of RpoS-dependent genes osmY, tnaA and malK was controlled by Crl, a transcriptional regulator that modulates RpoS activity. In summary, the identification of a group of exponential phase genes controlled by RpoS reveals a novel aspect of RpoS function.

  15. Evaluation of gene association methods for coexpression network construction and biological knowledge discovery.

    Directory of Open Access Journals (Sweden)

    Sapna Kumari

    Full Text Available BACKGROUND: Constructing coexpression networks and performing network analysis using large-scale gene expression data sets is an effective way to uncover new biological knowledge; however, the methods used for gene association in constructing these coexpression networks have not been thoroughly evaluated. Since different methods lead to structurally different coexpression networks and provide different information, selecting the optimal gene association method is critical. METHODS AND RESULTS: In this study, we compared eight gene association methods - Spearman rank correlation, Weighted Rank Correlation, Kendall, Hoeffding's D measure, Theil-Sen, Rank Theil-Sen, Distance Covariance, and Pearson - and focused on their true knowledge discovery rates in associating pathway genes and construction coordination networks of regulatory genes. We also examined the behaviors of different methods to microarray data with different properties, and whether the biological processes affect the efficiency of different methods. CONCLUSIONS: We found that the Spearman, Hoeffding and Kendall methods are effective in identifying coexpressed pathway genes, whereas the Theil-sen, Rank Theil-Sen, Spearman, and Weighted Rank methods perform well in identifying coordinated transcription factors that control the same biological processes and traits. Surprisingly, the widely used Pearson method is generally less efficient, and so is the Distance Covariance method that can find gene pairs of multiple relationships. Some analyses we did clearly show Pearson and Distance Covariance methods have distinct behaviors as compared to all other six methods. The efficiencies of different methods vary with the data properties to some degree and are largely contingent upon the biological processes, which necessitates the pre-analysis to identify the best performing method for gene association and coexpression network construction.

  16. Cross-species comparison of biological themes and underlying genes on a global gene expression scale in a mouse model of colorectal liver metastasis and in clinical specimens

    Directory of Open Access Journals (Sweden)

    Schirmacher Peter

    2008-09-01

    Full Text Available Abstract Background Invasion-related genes over-expressed by tumor cells as well as by reacting host cells represent promising drug targets for anti-cancer therapy. Such candidate genes need to be validated in appropriate animal models. Results This study examined the suitability of a murine model (CT26/Balb/C of colorectal liver metastasis to represent clinical liver metastasis specimens using a global gene expression approach. Cross-species similarity was examined between pure liver, liver invasion, tumor invasion and pure tumor compartments through overlap of up-regulated genes and gene ontology (GO-based biological themes on the level of single GO-terms and of condensed GO-term families. Three out of four GO-term families were conserved in a compartment-specific way between the species: secondary metabolism (liver, invasion (invasion front, and immune response (invasion front and liver. Among the individual GO-terms over-represented in the invasion compartments in both species were "extracellular matrix", "cell motility", "cell adhesion" and "antigen presentation" indicating that typical invasion related processes are operating in both species. This was reflected on the single gene level as well, as cross-species overlap of potential target genes over-expressed in the combined invasion front compartments reached up to 36.5%. Generally, histopathology and gene expression correlated well as the highest single gene overlap was found to be 44% in syn-compartmental comparisons (liver versus liver whereas cross-compartmental overlaps were much lower (e.g. liver versus tumor: 9.7%. However, single gene overlap was surprisingly high in some cross-compartmental comparisons (e.g. human liver invasion compartment and murine tumor invasion compartment: 9.0% despite little histolopathologic similarity indicating that invasion relevant genes are not necessarily confined to histologically defined compartments. Conclusion In summary, cross

  17. Gene therapy for hemophilia.

    Science.gov (United States)

    Hortelano, G; Chang, P L

    2000-01-01

    Hemophilia A and B are X-linked genetic disorders caused by deficiency of the coagulation factors VIII and IX, respectively. Because of the health hazards and costs of current product replacement therapy, much effort is devoted to the development of gene therapy for these disorders. Approaches to gene therapy for the hemophilias include: ex vivo gene therapy in which cells from the intended recipients are explanted, genetically modified to secrete Factor VIII or IX, and reimplanted into the donor; in vivo gene therapy in which Factor VIII or IX encoding vectors are directly injected into the recipient; and non-autologous gene therapy in which universal cell lines engineered to secrete Factor VIII or IX are enclosed in immuno-protective devices before implantation into recipients. Research into these approaches is aided by the many murine and canine models available. While problems of achieving high and sustained levels of factor delivery, and issues related to efficacy, safety and cost are still to be resolved, progress in gene therapy for the hemophilias has been encouraging and is likely to reach human clinical trial in the foreseeable future.

  18. Evidence for homosexuality gene

    Energy Technology Data Exchange (ETDEWEB)

    Pool, R.

    1993-07-16

    A genetic analysis of 40 pairs of homosexual brothers has uncovered a region on the X chromosome that appears to contain a gene or genes for homosexuality. When analyzing the pedigrees of homosexual males, the researcheres found evidence that the trait has a higher likelihood of being passed through maternal genes. This led them to search the X chromosome for genes predisposing to homosexuality. The researchers examined the X chromosomes of pairs of homosexual brothers for regions of DNA that most or all had in common. Of the 40 sets of brothers, 33 shared a set of five markers in the q28 region of the long arm of the X chromosome. The linkage has a LOD score of 4.0, which translates into a 99.5% certainty that there is a gene or genes in this area that predispose males to homosexuality. The chief researcher warns, however, that this one site cannot explain all instances of homosexuality, since there were some cases where the trait seemed to be passed paternally. And even among those brothers where there was no evidence that the trait was passed paternally, seven sets of brothers did not share the Xq28 markers. It seems likely that homosexuality arises from a variety of causes.

  19. Gene-gene, gene-environment, gene-nutrient interactionsand single nucleotide polymorphisms of inflammatorycytokines

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Inflammation plays a significant role in the etiologyof type 2 diabetes mellitus (T2DM). The rise in thepro-inflammatory cytokines is the essential step inglucotoxicity and lipotoxicity induced mitochondrialinjury, oxidative stress and beta cell apoptosis inT2DM. Among the recognized markers are interleukin(IL)-6, IL-1, IL-10, IL-18, tissue necrosis factor-alpha(TNF-α), C-reactive protein, resistin, adiponectin, tissueplasminogen activator, fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strongenvironmental influence; exhibiting a polygenic modeof inheritance. Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatorycytokines have been reported as a riskfor T2DM. Not all the SNPs have been confirmed byunifying results in different studies and wide variationshave been reported in various ethnic groups. Theinter-ethnic variations can be explained by the factthat gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions. Thisreview highlights the impact of these interactions ondetermining the role of single nucleotide polymorphismof IL-6, TNF-α, resistin and adiponectin in pathogenesisof T2DM.

  20. Tolerance of Deregulated G1/S Transcription Depends on Critical G1/S Regulon Genes to Prevent Catastrophic Genome Instability

    Directory of Open Access Journals (Sweden)

    Catia Caetano

    2014-12-01

    Full Text Available Expression of a G1/S regulon of genes that are required for DNA replication is a ubiquitous mechanism for controlling cell proliferation; moreover, the pathological deregulated expression of E2F-regulated G1/S genes is found in every type of cancer. Cellular tolerance of deregulated G1/S transcription is surprising because this regulon includes many dosage-sensitive proteins. Here, we used the fission yeast Schizosaccharomyces pombe to investigate this issue. We report that deregulating the MBF G1/S regulon by eliminating the Nrm1 corepressor increases replication errors. Homology-directed repair proteins, including MBF-regulated Ctp1CtIP, are essential to prevent catastrophic genome instability. Surprisingly, the normally inconsequential MBF-regulated S-phase cyclin Cig2 also becomes essential in the absence of Nrm1. This requirement was traced to cyclin-dependent kinase inhibition of the MBF-regulated Cdc18Cdc6 replication origin-licensing factor. Collectively, these results establish that, although deregulation of G1/S transcription is well tolerated by cells, nonessential G1/S target genes become crucial for preventing catastrophic genome instability.

  1. How to decide? Different methods of calculating gene expression from short oligonucleotide array data will give different results

    Directory of Open Access Journals (Sweden)

    Voesenek Laurentius ACJ

    2006-03-01

    Full Text Available Abstract Background Short oligonucleotide arrays for transcript profiling have been available for several years. Generally, raw data from these arrays are analysed with the aid of the Microarray Analysis Suite or GeneChip Operating Software (MAS or GCOS from Affymetrix. Recently, more methods to analyse the raw data have become available. Ideally all these methods should come up with more or less the same results. We set out to evaluate the different methods and include work on our own data set, in order to test which method gives the most reliable results. Results Calculating gene expression with 6 different algorithms (MAS5, dChip PMMM, dChip PM, RMA, GC-RMA and PDNN using the same (Arabidopsis data, results in different calculated gene expression levels. Consequently, depending on the method used, different genes will be identified as differentially regulated. Surprisingly, there was only 27 to 36% overlap between the different methods. Furthermore, 47.5% of the genes/probe sets showed good correlation between the mismatch and perfect match intensities. Conclusion After comparing six algorithms, RMA gave the most reproducible results and showed the highest correlation coefficients with Real Time RT-PCR data on genes identified as differentially expressed by all methods. However, we were not able to verify, by Real Time RT-PCR, the microarray results for most genes that were solely calculated by RMA. Furthermore, we conclude that subtraction of the mismatch intensity from the perfect match intensity results most likely in a significant underestimation for at least 47.5% of the expression values. Not one algorithm produced significant expression values for genes present in quantities below 1 pmol. If the only purpose of the microarray experiment is to find new candidate genes, and too many genes are found, then mutual exclusion of the genes predicted by contrasting methods can be used to narrow down the list of new candidate genes by 64 to 73%.

  2. Loss aversion and 5HTT gene variants in adolescent anxiety

    Directory of Open Access Journals (Sweden)

    Monique Ernst

    2014-04-01

    Full Text Available Loss aversion, a well-documented behavioral phenomenon, characterizes decisions under risk in adult populations. As such, loss aversion may provide a reliable measure of risky behavior. Surprisingly, little is known about loss aversion in adolescents, a group who manifests risk-taking behavior, or in anxiety disorders, which are associated with risk-avoidance. Finally, loss aversion is expected to be modulated by genotype, particularly the serotonin transporter (SERT gene variant, based on its role in anxiety and impulsivity. This genetic modulation may also differ between anxious and healthy adolescents, given their distinct propensities for risk taking. The present work examines the modulation of loss aversion, an index of risk-taking, and reaction-time to decision, an index of impulsivity, by the serotonin-transporter-gene-linked polymorphisms (5HTTLPR in healthy and clinically anxious adolescents. Findings show that loss aversion (1 does manifest in adolescents, (2 does not differ between healthy and clinically anxious participants, and (3, when stratified by SERT genotype, identifies a subset of anxious adolescents who are high SERT-expressers, and show excessively low loss-aversion and high impulsivity. This last finding may serve as preliminary evidence for 5HTTLPR as a risk factor for the development of comorbid disorders associated with risk-taking and impulsivity in clinically anxious adolescents.

  3. Evolution of the HIV-1 nef gene in HLA-B*57 Positive Elite Suppressors

    OpenAIRE

    Siliciano Robert F; Ray Stuart C; Bailey Justin R; O'Connell Karen A; Brennan Timothy P; Salgado Maria; Blankson Joel N

    2010-01-01

    Abstract Elite controllers or suppressors (ES) are HIV-1 infected patients who maintain viral loads of < 50 copies/ml without antiretroviral therapy. CD8+ T cells are thought to play a key role in the control of viral replication and exert selective pressure on gag and nef in HLA-B*57 positive ES. We previously showed evolution in the gag gene of ES which surprisingly was mostly due to synonymous mutations rather than non-synonymous mutation in targeted CTL epitopes. This finding could be the...

  4. Genome-Wide Association Studies Candidate Gene to Dual Modifier of Nonalcoholic Steatohepatitis and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Clint L. Miller, PhD

    2016-12-01

    Full Text Available Nonalcoholic steatohepatitis is a common disease involving chronic accumulation of fat and inflammation in the liver, often leading to advanced fibrosis, cirrhosis, and cancer. It is known that nonalcoholic steatohepatitis shares many features with atherosclerosis; however, there are still no effective therapeutics. In a recent study published in Nature, investigators demonstrated that mice lacking a high-density lipoprotein–associated gene were surprisingly protected from both steatohepatitis and atherosclerosis through the stabilization of the liver X receptor. This work reveals a timely candidate target for 2 highly prevalent cardiovascular diseases.

  5. Identification of four soybean reference genes for gene expression normalization

    Science.gov (United States)

    Gene expression analysis requires the use of reference genes stably expressed independently of specific tissues or environmental conditions. Housekeeping genes (e.g., actin, tubulin, ribosomal, polyubiquitin and elongation factor 1-alpha) are commonly used as reference genes with the assumption tha...

  6. The Mycoplasma hominis vaa gene displays a mosaic gene structure

    DEFF Research Database (Denmark)

    Boesen, Thomas; Emmersen, Jeppe M. G.; Jensen, Lise T.;

    1998-01-01

    Mycoplasma hominis contains a variable adherence-associated (vaa) gene. To classify variants of the vaa genes, we examined 42 M. hominis isolated by PCR, DNA sequencing and immunoblotting. This uncovered the existence of five gene categories. Comparison of the gene types revealed a modular compos...

  7. Nucleofection of Rat Pheochromocytoma PC-12 Cells with Human Mutated Beta-Amyloid Precursor Protein Gene (APP-sw) Leads to Reduced Viability, Autophagy-Like Process, and Increased Expression and Secretion of Beta Amyloid

    OpenAIRE

    Beata Pająk; Elżbieta Kania; Arkadiusz Orzechowski

    2015-01-01

    Pheochromocytoma PC-12 cells are immune to physiological stimuli directed to evoke programmed cell death. Besides, metabolic inhibitors are incapable of sensitizing PC-12 cells to extrinsic or intrinsic apoptosis unless they are used in toxic concentrations. Surprisingly, these cells become receptive to cell deletion after human APP-sw gene expression. We observed reduced cell viability in GFP vector + APP-sw-nucleofected cells (drop by 36%) but not in GFP vector − or GFP vector + APP-wt-nucl...

  8. Hox genes and study of Hox genes in crustacean

    Institute of Scientific and Technical Information of China (English)

    HOU Lin; CHEN Zhijuan; XU Mingyu; LIN Shengguo; WANG Lu

    2004-01-01

    Homeobox genes have been discovered in many species. These genes are known to play a major role in specifying regional identity along the anterior-posterior axis of animals from a wide range of phyla.The products of the homeotic genes are a set of evolutionarily conserved transcription factors that control elaborate developmental processes and specify cell fates in metazoans. Crustacean, presenting a variety of body plans not encountered in any other class or phylum of the Metazoa, has been shown to possess a single set of homologous Hox genes like insect. The ancestral crustacean Hox gene complex comprised ten genes: eight homologous to the hometic Hox genes and two related to nonhomeotic genes presented within the insect Hox complexes. The crustacean in particular exhibits an abundant diversity segment specialization and tagmosis. This morphological diversity relates to the Hox genes. In crustacean body plan, different Hox genes control different segments and tagmosis.

  9. Transcription variants of SLA-7, a swine non classical MHC class I gene.

    Science.gov (United States)

    Hu, Rui; Lemonnier, Gaëtan; Bourneuf, Emmanuelle; Vincent-Naulleau, Silvia; Rogel-Gaillard, Claire

    2011-06-03

    In pig, very little information is available on the non classical class I (Ib) genes of the Major Histocompatibility Complex (MHC) i.e. SLA-6, -7 and -8. Our aim was to focus on the transcription pattern of the SLA-7 gene. RT-PCR experiments were carried out with SLA-7 specific primers targeting either the full coding sequence (CDS) from exon 1 to the 3 prime untranslated region (3UTR) or a partial CDS from exon 4 to the 3UTR. We show that the SLA-7 gene expresses a full length transcript not yet identified that refines annotation of the gene with eight exons instead of seven as initially described from the existing RefSeq RNA. These two RNAs encode molecules that differ in cytoplasmic tail length. In this study, another SLA-7 transcript variant was characterized, which encodes a protein with a shorter alpha 3 domain, as a consequence of a splicing site within exon 4. Surprisingly, a cryptic non canonical GA-AG splicing site is used to generate this transcript variant. An additional SLA-7 variant was also identified in the 3UTR with a splicing site occurring 31 nucleotides downstream to the stop codon. In conclusion, the pig SLA-7 MHC class Ib gene presents a complex transcription pattern with two transcripts encoding various molecules and transcripts that do not alter the CDS and may be subject to post-transcriptional regulation.

  10. Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Milène Catoire

    Full Text Available Regular physical activity positively influences whole body energy metabolism and substrate handling in exercising muscle. While it is recognized that the effects of exercise extend beyond exercising muscle, it is unclear to what extent exercise impacts non-exercising muscles. Here we investigated the effects of an acute endurance exercise bouts on gene expression in exercising and non-exercising human muscle. To that end, 12 male subjects aged 44-56 performed one hour of one-legged cycling at 50% W(max. Muscle biopsies were taken from the exercising and non-exercising leg before and immediately after exercise and analyzed by microarray. One-legged cycling raised plasma lactate, free fatty acids, cortisol, noradrenalin, and adrenalin levels. Surprisingly, acute endurance exercise not only caused pronounced gene expression changes in exercising muscle but also in non-exercising muscle. In the exercising leg the three most highly induced genes were all part of the NR4A family. Remarkably, many genes induced in non-exercising muscle were PPAR targets or related to PPAR signalling, including PDK4, ANGPTL4 and SLC22A5. Pathway analysis confirmed this finding. In conclusion, our data indicate that acute endurance exercise elicits pronounced changes in gene expression in non-exercising muscle, which are likely mediated by changes in circulating factors such as free fatty acids. The study points to a major influence of exercise beyond the contracting muscle.

  11. Long-term effect of systemic RNA interference on circadian clock genes in hemimetabolous insects.

    Science.gov (United States)

    Uryu, Outa; Kamae, Yuichi; Tomioka, Kenji; Yoshii, Taishi

    2013-04-01

    RNA interference (RNAi) strategy, which enables gene-specific knock-down of transcripts, has been spread across a wide area of insect studies for investigating gene function without regard to model and non-model insects. This technique is of particular benefit to promote molecular studies on non-model insects. However, the optimal conditions for RNAi are still not well understood because of its variable efficiency depending on the species, target genes, and experimental conditions. To apply RNAi technique to long-running experiments such as chronobiological studies, the effects of RNAi have to persist throughout the experiment. In this study, we attempted to determine the optimal concentration of double-stranded RNA (dsRNA) for systemic RNAi and its effective period in two different insect species, the cricket Gryllus bimaculatus and the firebrat Thermobia domestica. In both species, higher concentrations of dsRNA principally yielded a more efficient knock-down of mRNA levels of tested clock genes, although the effect depended on the gene and the species. Surprisingly, the effect of the RNAi reached its maximum effect 1-2 weeks and 1 month after the injection of dsRNA in the crickets and the firebrats, respectively, suggesting a slow but long-term effect of RNAi. Our study provides fundamental information for utilizing RNAi technique in any long-running experiment.

  12. Common gene therapy viral vectors do not efficiently penetrate sputum from cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Kaoru Hida

    Full Text Available Norwalk virus and human papilloma virus, two viruses that infect humans at mucosal surfaces, have been found capable of rapidly penetrating human mucus secretions. Viral vectors for gene therapy of Cystic Fibrosis (CF must similarly penetrate purulent lung airway mucus (sputum to deliver DNA to airway epithelial cells. However, surprisingly little is known about the rates at which gene delivery vehicles penetrate sputum, including viral vectors used in clinical trials for CF gene therapy. We find that sputum spontaneously expectorated by CF patients efficiently traps two viral vectors commonly used in CF gene therapy trials, adenovirus (d∼80 nm and adeno-associated virus (AAV serotype 5; d∼20 nm, leading to average effective diffusivities that are ∼3,000-fold and 12,000-fold slower than their theoretical speeds in water, respectively. Both viral vectors are slowed by adhesion, as engineered muco-inert nanoparticles with diameters as large as 200 nm penetrate the same sputum samples at rates only ∼40-fold reduced compared to in pure water. A limited fraction of AAV exhibit sufficiently fast mobility to penetrate physiologically thick sputum layers, likely because of the lower viscous drag and smaller surface area for adhesion to sputum constituents. Nevertheless, poor penetration of CF sputum is likely a major contributor to the ineffectiveness of viral vector based gene therapy in the lungs of CF patients observed to date.

  13. Entrez Gene: gene-centered information at NCBI

    OpenAIRE

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2006-01-01

    Entrez Gene () is NCBI's database for gene-specific information. Entrez Gene includes records from genomes that have been completely sequenced, that have an active research community to contribute gene-specific information or that are scheduled for intense sequence analysis. The content of Entrez Gene represents the result of both curation and automated integration of data from NCBI's Reference Sequence project (RefSeq), from collaborating model organism databases and from other databases wit...

  14. The nuclear receptor genes HR3 and E75 are required for the circadian rhythm in a primitive insect.

    Directory of Open Access Journals (Sweden)

    Yuichi Kamae

    Full Text Available Insect circadian rhythms are generated by a circadian clock consisting of transcriptional/translational feedback loops, in which CYCLE and CLOCK are the key elements in activating the transcription of various clock genes such as timeless (tim and period (per. Although the transcriptional regulation of Clock (Clk has been profoundly studied, little is known about the regulation of cycle (cyc. Here, we identify the orphan nuclear receptor genes HR3 and E75, which are orthologs of mammalian clock genes, Rorα and Rev-erbα, respectively, as factors involved in the rhythmic expression of the cyc gene in a primitive insect, the firebrat Thermobia domestica. Our results show that HR3 and E75 are rhythmically expressed, and their normal, rhythmic expression is required for the persistence of locomotor rhythms. Their RNAi considerably altered the rhythmic transcription of not only cyc but also tim. Surprisingly, the RNAi of HR3 revealed the rhythmic expression of Clk, suggesting that this ancestral insect species possesses the mechanisms for rhythmic expression of both cyc and Clk genes. When either HR3 or E75 was knocked down, tim, cyc, and Clk or tim and cyc, respectively, oscillated in phase, suggesting that the two genes play an important role in the regulation of the phase relationship among the clock genes. Interestingly, HR3 and E75 were also found to be involved in the regulation of ecdysis, suggesting that they interconnect the circadian clock and developmental processes.

  15. The nuclear receptor genes HR3 and E75 are required for the circadian rhythm in a primitive insect.

    Science.gov (United States)

    Kamae, Yuichi; Uryu, Outa; Miki, Taiki; Tomioka, Kenji

    2014-01-01

    Insect circadian rhythms are generated by a circadian clock consisting of transcriptional/translational feedback loops, in which CYCLE and CLOCK are the key elements in activating the transcription of various clock genes such as timeless (tim) and period (per). Although the transcriptional regulation of Clock (Clk) has been profoundly studied, little is known about the regulation of cycle (cyc). Here, we identify the orphan nuclear receptor genes HR3 and E75, which are orthologs of mammalian clock genes, Rorα and Rev-erbα, respectively, as factors involved in the rhythmic expression of the cyc gene in a primitive insect, the firebrat Thermobia domestica. Our results show that HR3 and E75 are rhythmically expressed, and their normal, rhythmic expression is required for the persistence of locomotor rhythms. Their RNAi considerably altered the rhythmic transcription of not only cyc but also tim. Surprisingly, the RNAi of HR3 revealed the rhythmic expression of Clk, suggesting that this ancestral insect species possesses the mechanisms for rhythmic expression of both cyc and Clk genes. When either HR3 or E75 was knocked down, tim, cyc, and Clk or tim and cyc, respectively, oscillated in phase, suggesting that the two genes play an important role in the regulation of the phase relationship among the clock genes. Interestingly, HR3 and E75 were also found to be involved in the regulation of ecdysis, suggesting that they interconnect the circadian clock and developmental processes.

  16. Somatic polyploidy is associated with the upregulation of c-MYC interacting genes and EMT-like signature.

    Science.gov (United States)

    Vazquez-Martin, Alejandro; Anatskaya, Olga V; Giuliani, Alessandro; Erenpreisa, Jekaterina; Huang, Sui; Salmina, Kristine; Inashkina, Inna; Huna, Anda; Nikolsky, Nikolai N; Vinogradov, Alexander E

    2016-11-15

    The dependence of cancer on overexpressed c-MYC and its predisposition for polyploidy represents a double puzzle. We address this conundrum by cross-species transcription analysis of c-MYC interacting genes in polyploid vs. diploid tissues and cells, including human vs. mouse heart, mouse vs. human liver and purified 4n vs. 2n mouse decidua cells. Gene-by-gene transcriptome comparison and principal component analysis indicated that c-MYC interactants are significantly overrepresented among ploidy-associated genes. Protein interaction networks and gene module analysis revealed that the most upregulated genes relate to growth, stress response, proliferation, stemness and unicellularity, as well as to the pathways of cancer supported by MAPK and RAS coordinated pathways. A surprising feature was the up-regulation of epithelial-mesenchymal transition (EMT) modules embodied by the N-cadherin pathway and EMT regulators from SNAIL and TWIST families. Metabolic pathway analysis also revealed the EMT-linked features, such as global proteome remodeling, oxidative stress, DNA repair and Warburg-like energy metabolism. Genes associated with apoptosis, immunity, energy demand and tumour suppression were mostly down-regulated. Noteworthy, despite the association between polyploidy and ample features of cancer, polyploidy does not trigger it. Possibly it occurs because normal polyploidy does not go that far in embryonalisation and linked genome destabilisation. In general, the analysis of polyploid transcriptome explained the evolutionary relation of c-MYC and polyploidy to cancer.

  17. Differential expression of the TMV resistance gene N prevents a hypersensitive response in seeds and during germination.

    Science.gov (United States)

    Niemeyer, Julia; Ruhe, Jonas; Machens, Fabian; Hehl, Reinhard

    2013-03-01

    The dominant tobacco mosaic virus (TMV) resistance gene N confers a hypersensitive response (HR) at the site of TMV infection and protects tobacco against systemic spread of the virus. To study N gene activity in seeds and early seedling development, the avirulence gene of N, the helicase domain (p50) of the TMV replicase, was constitutively expressed in a tobacco genotype without N (nn). Transgenic F1 expressing N and p50 were generated by crossing with an NN genotype. Surprisingly, Nn F1 seeds expressing p50 are viable and germinate. Only about 5 days after sowing, seedlings started to show an HR. This paralleled the upregulation of several pathogenesis-related and HR genes. The timing of the HR is consistent with the upregulation of N gene transcript 4-6 days after sowing. The expression of p50 has a stimulating effect on the N gene transcript level during germination. These results show that tobacco seeds and very young seedlings do not express a functional N gene product.

  18. Pathogenic mutations and sequence variants within mitofusin 2 gene in Polish patients with different hereditary motor-sensory neuropathies.

    Science.gov (United States)

    Kotruchow, Katarzyna; Kabzińska, Dagmara; Kochański, Andrzej

    2015-01-01

    At the time of its first description in 2004, MFN2 was considered the most frequently mutated gene in hereditary motor and sensory neuropathy type 2 (HMSN 2). However recent studies have shown that the frequency of MFN2 gene mutations in HMSN II patients is surprisingly low. To date, no systematic studies devoted to HMSN IIa in Poland have been carried out. In this study, we searched for MFN2 gene mutations in Polish patients representing the population of nearly 40 million. We decided to include a wide spectrum of clinical phenotypes in the study, proving able to detect, in a group of 67 affected patients: 1) 3 pathogenic mutations; 2) 3 sequence variants of unknown pathogenic status; 3) 9 rare MFN2 gene sequence variants; 4) 6 common polymorphisms. The frequency of MFN2 gene mutations in the whole group of patients is 4.5%. Due to the high frequency of MFN2 gene sequence variants within single patients we could not definitely exclude the cumulative effect of these contributing to the HMSN II phenotype. The MFN2 gene should therefore be considered in Polish HMSN II patients, though it is still not possible to determine its position in HMSN II molecular diagnostics.

  19. Signatures of functional constraint at aye-aye opsin genes: the potential of adaptive color vision in a nocturnal primate.

    Science.gov (United States)

    Perry, George H; Martin, Robert D; Verrelli, Brian C

    2007-09-01

    While color vision perception is thought to be adaptively correlated with foraging efficiency for diurnal mammals, those that forage exclusively at night may not need color vision nor have the capacity for it. Indeed, although the basic condition for mammals is dichromacy, diverse nocturnal mammals have only monochromatic vision, resulting from functional loss of the short-wavelength sensitive opsin gene. However, many nocturnal primates maintain intact two opsin genes and thus have dichromatic capacity. The evolutionary significance of this surprising observation has not yet been elucidated. We used a molecular population genetics approach to test evolutionary hypotheses for the two intact opsin genes of the fully nocturnal aye-aye (Daubentonia madagascariensis), a highly unusual and endangered Madagascar primate. No evidence of gene degradation in either opsin gene was observed for any of 8 aye-aye individuals examined. Furthermore, levels of nucleotide diversity for opsin gene functional sites were lower than those for 15 neutrally evolving intergenic regions (>25 kb in total), which is consistent with a history of purifying selection on aye-aye opsin genes. The most likely explanation for these findings is that dichromacy is advantageous for aye-ayes despite their nocturnal activity pattern. We speculate that dichromatic nocturnal primates may be able to perceive color while foraging under moonlight conditions, and suggest that behavioral and ecological comparisons among dichromatic and monochromatic nocturnal primates will help to elucidate the specific activities for which color vision perception is advantageous.

  20. Gene therapy for brain tumors.

    Science.gov (United States)

    Bansal, K; Engelhard, H H

    2000-09-01

    "Gene therapy" can be defined as the transfer of genetic material into a patient's cells for therapeutic purposes. To date, a diverse and creative assortment of treatment strategies utilizing gene therapy have been devised, including gene transfer for modulating the immune system, enzyme prodrug ("suicide gene") therapy, oncolytic therapy, replacement/therapeutic gene transfer, and antisense therapy. For malignant glioma, gene-directed prodrug therapy using the herpes simplex virus thymidine kinase gene was the first gene therapy attempted clinically. A variety of different strategies have now been pursued experimentally and in clinical trials. Although, to date, gene therapy for brain tumors has been found to be reasonably safe, concerns still exist regarding issues related to viral delivery, transduction efficiency, potential pathologic response of the brain, and treatment efficacy. Improved viral vectors are being sought, and potential use of gene therapy in combination with other treatments is being investigated.

  1. Introns in higher plant genes

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The intron is an important component of eukaryotic gene. Extensive studies have been conducted to get a better understanding of its structure and function. This paper presents a brief review of the structure and function of introns in higher plant genes. It is shown that higher plant introns possess structural properties shared by all eukaryotic introns, however, they also exhibit a striking degree of diversity. The process of intron splicing in higher plant genes involves interaction between multiple cis-acting elements and trans-acting factors, such as 5′ splicing site, 3′ splicing site and many protein factors. The process of intron splicing is an important level at which gene expression is regulated. Especially alternative splicing of intron can regulate time and space of gene expression. In addition, some introns in higher plant genes also regulate gene expression by affecting the pattern of gene expression, enhancing the level of gene expression and driving the gene expression.

  2. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  3. FunGene: the Functional Gene Pipeline and Repository

    Directory of Open Access Journals (Sweden)

    Jordan A. Fish

    2013-10-01

    Full Text Available Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer.While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/ offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.

  4. Comprehensive Gene Expression Profiling Reveals Synergistic Functional Networks in Cerebral Vessels after Hypertension or Hypercholesterolemia

    Science.gov (United States)

    Ong, Wei-Yi; Ng, Mary Pei-Ern; Loke, Sau-Yeen; Jin, Shalai; Wu, Ya-Jun; Tanaka, Kazuhiro; Wong, Peter Tsun-Hon

    2013-01-01

    Atherosclerotic stenosis of cerebral arteries or intracranial large artery disease (ICLAD) is a major cause of stroke especially in Asians, Hispanics and Africans, but relatively little is known about gene expression changes in vessels at risk. This study compares comprehensive gene expression profiles in the middle cerebral artery (MCA) of New Zealand White rabbits exposed to two stroke risk factors i.e. hypertension and/or hypercholesterolemia, by the 2-Kidney-1-Clip method, or dietary supplementation with cholesterol. Microarray and Ingenuity Pathway Analyses of the MCA of the hypertensive rabbits showed up-regulated genes in networks containing the node molecules: UBC (ubiquitin), P38 MAPK, ERK, NFkB, SERPINB2, MMP1 and APP (amyloid precursor protein); and down-regulated genes related to MAPK, ERK 1/2, Akt, 26 s proteasome, histone H3 and UBC. The MCA of hypercholesterolemic rabbits showed differentially expressed genes that are surprisingly, linked to almost the same node molecules as the hypertensive rabbits, despite a relatively low percentage of ‘common genes’ (21 and 7%) between the two conditions. Up-regulated common genes were related to: UBC, SERPINB2, TNF, HNF4A (hepatocyte nuclear factor 4A) and APP, and down-regulated genes, related to UBC. Increased HNF4A message and protein were verified in the aorta. Together, these findings reveal similar nodal molecules and gene pathways in cerebral vessels affected by hypertension or hypercholesterolemia, which could be a basis for synergistic action of risk factors in the pathogenesis of ICLAD. PMID:23874591

  5. The Effect of Genetic and Environmental Variation on Metabolic Gene Expression

    Science.gov (United States)

    Scott, Cinda P.; Williams, Dean A.; Crawford, Douglas L.

    2009-01-01

    What is the relationship between genetic or environmental variation and the variation in mRNA expression? To address this, microarrays were used to examine the effect of genetic and environmental variation on cardiac mRNA expression for metabolic genes in three groups of Fundulus heteroclitus: (1) individuals sampled in the field (field), (2) field individuals acclimated for six months to laboratory conditions (acclimated) or (3) individuals bred for ten successive generations in a laboratory environment (G10). The G10 individuals have significantly less genetic variation than individuals obtained in the field and had a significantly lower variation in mRNA expression across all genes in comparison to the other two groups (p ≤ 0.001). When examining the gene specific variation, twenty-two genes had variation in expression that was significantly different among groups with lower variation in G10 individuals than in acclimated individuals. Additionally, there were fewer genes with significant differences in expression among G10 individuals versus either acclimated or field individuals: 66 genes have statistically different levels of expression versus 107 or 97 for Acclimated or Field groups. Based on the permutation of the data, these differences in the number of genes with significant differences among individuals within a group are unlikely to occur by chance (p < 0.01). Surprisingly, variation in mRNA expression in field individuals is lower than in acclimated individuals. Relative to the variation among individual within a group, few genes have significant differences in expression among groups (seven, 2.3%) and none of these are different between acclimated and field individuals. The results support the concept that genetic variation affects variation in mRNA expression and also suggests that temporal environmental variation associated with estuarine environments does not increase the variation among individuals or add to the differences among groups. PMID

  6. Identification and engineering of regulation-related genes toward improved kasugamycin production.

    Science.gov (United States)

    Zhu, Chenchen; Kang, Qianjin; Bai, Linquan; Cheng, Lin; Deng, Zixin

    2016-02-01

    Kasugamycin, produced by Streptomyces kasugaensis and Streptomyces microaureus, is an important amino-glycoside family antibiotic and widely used for veterinary and agricultural applications. In the left flanking region of the previously reported kasugamycin gene cluster, four additional genes (two-component system kasW and kasX, MerR-family kasV, and isoprenylcysteine carboxyl methyltransferase kasS) were identified both in the low-yielding S. kasugaensis BCRC12349 and high-yielding S. microaureus XM301. Deletion of regulatory gene kasT abolished kasugamycin production, and its overexpression in BCRC12349 resulted in an increased titer by 186 %. Deletion of kasW, kasX, kasV, and kasS improved kasugamycin production by 12, 19, 194, and 22 %, respectively. qRT-PCR analysis demonstrated that the transcription of kas genes was significantly increased in all the four mutants. Similar gene inactivation was performed in the high-yielding strain S. microaureus XM301. As expected, the deletion of kasW/X resulted in a 58 % increase of the yield from 6 to 9.5 g/L. However, the deletion of kasV and over-expression of kasT had no obvious effect, and the disruption of kasS surprisingly decreased kasugamycin production. In addition, trans-complementation of the kasS mutant with a TTA codon-mutated kasS increased the kasugamycin yield by 20 %. A much higher transcription of kas genes was detected in the high-yielding XM301 than in the low-yielding BCRC12349, which may partially account for the discrepancy of gene inactivation effects between them. Our work not only generated engineered strains with improved kasugamycin yield, but also pointed out that different strategies on manipulating regulatory-related genes should be considered for low-yielding or high-yielding strains.

  7. Novel mutations of PRSS1 gene in patients with pancreatic cancer among Han population

    Institute of Scientific and Technical Information of China (English)

    ZENG Kai; LIU Qi-cai; LIN Jian-hua; LIN Xin-hua; ZHUANG Ze-hao; GAO Feng; OU Qi-shui

    2011-01-01

    Background A high mortality rate of pancreatic cancer becomes a bottleneck for further treatment with long-term efficacy. It is urgent to find a new mean to predict the early onset of pancreatic cancer accurately. The authors hypothesized that genetic variants of cationic trypsinogen (PRSS1) gene could affect trypsin expression/function and result in abnormal activation of protease activated receptor-2 (PAR-2), then lead to pancreatic cancer. The aim of this study was to elaborate some novel mutations of PRSS1 gene in the patients with pancreatic cancer.Methods Totally 156 patients with pancreatic cancer and 220 unrelated individuals as controls were enrolled in this study. The mutations of PRSS1 gene were analyzed by direct sequencing. K-ras Mutation Detection Kit was used to find the general k-ras gene disorder in the pancreatic cancer tissue. Then the clinical data were collected and analyzed simultaneously.Results There were two patients who carried novel mutations which was IVS 3 +157 G>C of PRSS1 gene in peripheral blood specimens and pancreatic cancer tissue. What's more, it was surprising to find a novel complicated mutation of exon 3 in PRSS1 gene (c.409 A>G and c.416 C>T) in another young patient. The complicated mutation made No. 135 and No.137 amino acid transfer from Thr to Ala and Thr to Met respectively. No any mutation was found in the normal controls while no mutations of k-ras gene were detected in the three patients.Conclusion Mutations of PRSS1 gene may be an important factor of pancreatic cancer.

  8. Diversity of ABC transporter genes across the plant kingdom and their potential utility in biotechnology.

    Science.gov (United States)

    Lane, Thomas S; Rempe, Caroline S; Davitt, Jack; Staton, Margaret E; Peng, Yanhui; Soltis, Douglas Edward; Melkonian, Michael; Deyholos, Michael; Leebens-Mack, James H; Chase, Mark; Rothfels, Carl J; Stevenson, Dennis; Graham, Sean W; Yu, Jun; Liu, Tao; Pires, J Chris; Edger, Patrick P; Zhang, Yong; Xie, Yinlong; Zhu, Ying; Carpenter, Eric; Wong, Gane Ka-Shu; Stewart, C Neal

    2016-05-31

    The ATP-binding cassette (ABC) transporter gene superfamily is ubiquitous among extant organisms and prominently represented in plants. ABC transporters act to transport compounds across cellular membranes and are involved in a diverse range of biological processes. Thus, the applicability to biotechnology is vast, including cancer resistance in humans, drug resistance among vertebrates, and herbicide and other xenobiotic resistance in plants. In addition, plants appear to harbor the highest diversity of ABC transporter genes compared with any other group of organisms. This study applied transcriptome analysis to survey the kingdom-wide ABC transporter diversity in plants and suggest biotechnology applications of this diversity. We utilized sequence similarity-based informatics techniques to infer the identity of ABC transporter gene candidates from 1295 phylogenetically-diverse plant transcriptomes. A total of 97,149 putative (approximately 25 % were full-length) ABC transporter gene members were identified; each RNA-Seq library (plant sample) had 88 ± 30 gene members. As expected, simpler organisms, such as algae, had fewer unique members than vascular land plants. Differences were also noted in the richness of certain ABC transporter subfamilies. Land plants had more unique ABCB, ABCC, and ABCG transporter gene members on average (p plant groups (p plant groups. An increase in the number of gene family members present in the ABCB, ABCC, and ABCD transporter subfamilies may indicate an expansion of the ABC transporter superfamily among green land plants, which include all crop species. The striking difference between the number of ABCA subfamily transporter gene members between ferns and other plant taxa is surprising and merits further investigation. Discussed is the potential exploitation of ABC transporters in plant biotechnology, with an emphasis on crops.

  9. Gene decay in archaea

    Directory of Open Access Journals (Sweden)

    M. W. J. van Passel

    2007-01-01

    Full Text Available The gene-dense chromosomes of archaea and bacteria were long thought to be devoid of pseudogenes, but with the massive increase in available genome sequences, whole genome comparisons between closely related species have identified mutations that have rendered numerous genes inactive. Comparative analyses of sequenced archaeal genomes revealed numerous pseudogenes, which can constitute up to 8.6% of the annotated coding sequences in some genomes. The largest proportion of pseudogenes is created by gene truncations, followed by frameshift mutations. Within archaeal genomes, large numbers of pseudogenes contain more than one inactivating mutation, suggesting that pseudogenes are deleted from the genome more slowly in archaea than in bacteria. Although archaea seem to retain pseudogenes longer than do bacteria, most archaeal genomes have unique repertoires of pseudogenes.

  10. A review on microcephaly genes

    Directory of Open Access Journals (Sweden)

    Irshad S.

    2012-06-01

    Full Text Available This review aims to summarize the recent findings regarding microcephaly genes. We have discussed the molecular genetics studies of microcephaly genes including a comprehensive appraisal of the seven mapped loci (MCPH1–MCPH7, their corresponding genes and protein products of the genes, their likely role in normal brain development and the details of the mutations reported in these genes.

  11. Gene therapy for skin diseases.

    Science.gov (United States)

    Gorell, Emily; Nguyen, Ngon; Lane, Alfred; Siprashvili, Zurab

    2014-04-01

    The skin possesses qualities that make it desirable for gene therapy, and studies have focused on gene therapy for multiple cutaneous diseases. Gene therapy uses a vector to introduce genetic material into cells to alter gene expression, negating a pathological process. This can be accomplished with a variety of viral vectors or nonviral administrations. Although results are promising, there are several potential pitfalls that must be addressed to improve the safety profile to make gene therapy widely available clinically.

  12. Gene Therapy for Skin Diseases

    OpenAIRE

    2014-01-01

    The skin possesses qualities that make it desirable for gene therapy, and studies have focused on gene therapy for multiple cutaneous diseases. Gene therapy uses a vector to introduce genetic material into cells to alter gene expression, negating a pathological process. This can be accomplished with a variety of viral vectors or nonviral administrations. Although results are promising, there are several potential pitfalls that must be addressed to improve the safety profile to make gene thera...

  13. Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma.

    Science.gov (United States)

    Ellis, Leigh; Pan, Yan; Smyth, Gordon K; George, Daniel J; McCormack, Chris; Williams-Truax, Roxanne; Mita, Monica; Beck, Joachim; Burris, Howard; Ryan, Gail; Atadja, Peter; Butterfoss, Dale; Dugan, Margaret; Culver, Kenneth; Johnstone, Ricky W; Prince, H Miles

    2008-07-15

    Histone deacetylase inhibitors can alter gene expression and mediate diverse antitumor activities. Herein, we report the safety and activity of the histone deacetylase inhibitor panobinostat (LBH589) in cutaneous T-cell lymphoma (CTCL) and identify genes commonly regulated by panobinostat. Panobinostat was administered orally to patients with CTCL on Monday, Wednesday, and Friday of each week on a 28-day cycle. A dose of 30 mg was considered excessively toxic, and subsequent patients were treated at the expanded maximum tolerated dose of 20 mg. Biopsies from six patients taken 0, 4, 8, and 24 h after administration were subjected to microarray gene expression profiling and real-time quantitative PCR of selected genes. Patients attained a complete response (n = 2), attained a partial response (n = 4), achieved stable disease with ongoing improvement (n = 1), and progressed on treatment (n = 2). Microarray data showed distinct gene expression response profiles over time following panobinostat treatment, with the majority of genes being repressed. Twenty-three genes were commonly regulated by panobinostat in all patients tested. Panobinostat is well tolerated and induces clinical responses in CTCL patients. Microarray analyses of tumor samples indicate that panobinostat induces rapid changes in gene expression, and surprisingly more genes are repressed than are activated. A unique set of genes that can mediate biological responses such as apoptosis, immune regulation, and angiogenesis were commonly regulated in response to panobinostat. These genes are potential molecular biomarkers for panobinostat activity and are strong candidates for the future assessment of their functional role(s) in mediating the antitumor responses of panobinostat.

  14. Correlating Expression Data with Gene Function Using Gene Ontology

    Institute of Scientific and Technical Information of China (English)

    LIU,Qi; DENG,Yong; WANG,Chuan; SHI,Tie-Liu; LI,Yi-Xue

    2006-01-01

    Clustering is perhaps one of the most widely used tools for microarray data analysis. Proposed roles for genes of unknown function are inferred from clusters of genes similarity expressed across many biological conditions.However, whether function annotation by similarity metrics is reliable or not and to what extent the similarity in gene expression patterns is useful for annotation of gene functions, has not been evaluated. This paper made a comprehensive research on the correlation between the similarity of expression data and of gene functions using Gene Ontology. It has been found that although the similarity in expression patterns and the similarity in gene functions are significantly dependent on each other, this association is rather weak. In addition, among the three categories of Gene Ontology, the similarity of expression data is more useful for cellular component annotation than for biological process and molecular function. The results presented are interesting for the gene functions prediction research area.

  15. The gene tree delusion.

    Science.gov (United States)

    Springer, Mark S; Gatesy, John

    2016-01-01

    Higher-level relationships among placental mammals are mostly resolved, but several polytomies remain contentious. Song et al. (2012) claimed to have resolved three of these using shortcut coalescence methods (MP-EST, STAR) and further concluded that these methods, which assume no within-locus recombination, are required to unravel deep-level phylogenetic problems that have stymied concatenation. Here, we reanalyze Song et al.'s (2012) data and leverage these re-analyses to explore key issues in systematics including the recombination ratchet, gene tree stoichiometry, the proportion of gene tree incongruence that results from deep coalescence versus other factors, and simulations that compare the performance of coalescence and concatenation methods in species tree estimation. Song et al. (2012) reported an average locus length of 3.1 kb for the 447 protein-coding genes in their phylogenomic dataset, but the true mean length of these loci (start codon to stop codon) is 139.6 kb. Empirical estimates of recombination breakpoints in primates, coupled with consideration of the recombination ratchet, suggest that individual coalescence genes (c-genes) approach ∼12 bp or less for Song et al.'s (2012) dataset, three to four orders of magnitude shorter than the c-genes reported by these authors. This result has general implications for the application of coalescence methods in species tree estimation. We contend that it is illogical to apply coalescence methods to complete protein-coding sequences. Such analyses amalgamate c-genes with different evolutionary histories (i.e., exons separated by >100,000 bp), distort true gene tree stoichiometry that is required for accurate species tree inference, and contradict the central rationale for applying coalescence methods to difficult phylogenetic problems. In addition, Song et al.'s (2012) dataset of 447 genes includes 21 loci with switched taxonomic names, eight duplicated loci, 26 loci with non-homologous sequences that are

  16. Neighboring Genes Show Correlated Evolution in Gene Expression

    Science.gov (United States)

    Ghanbarian, Avazeh T.; Hurst, Laurence D.

    2015-01-01

    When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

  17. Integrative genomic analysis in K562 chronic myelogenous leukemia cells reveals that proximal NCOR1 binding positively regulates genes that govern erythroid differentiation and Imatinib sensitivity.

    Science.gov (United States)

    Long, Mark D; van den Berg, Patrick R; Russell, James L; Singh, Prashant K; Battaglia, Sebastiano; Campbell, Moray J

    2015-09-01

    To define the functions of NCOR1 we developed an integrative analysis that combined ENCODE and NCI-60 data, followed by in vitro validation. NCOR1 and H3K9me3 ChIP-Seq, FAIRE-seq and DNA CpG methylation interactions were related to gene expression using bootstrapping approaches. Most NCOR1 combinations (24/44) were associated with significantly elevated level expression of protein coding genes and only very few combinations related to gene repression. DAVID's biological process annotation revealed that elevated gene expression was uniquely associated with acetylation and ETS binding. A matrix of gene and drug interactions built on NCI-60 data identified that Imatinib significantly targeted the NCOR1 governed transcriptome. Stable knockdown of NCOR1 in K562 cells slowed growth and significantly repressed genes associated with NCOR1 cistrome, again, with the GO terms acetylation and ETS binding, and significantly dampened sensitivity to Imatinib-induced erythroid differentiation. Mining public microarray data revealed that NCOR1-targeted genes were significantly enriched in Imatinib response gene signatures in cell lines and chronic myelogenous leukemia (CML) patients. These approaches integrated cistrome, transcriptome and drug sensitivity relationships to reveal that NCOR1 function is surprisingly most associated with elevated gene expression, and that these targets, both in CML cell lines and patients, associate with sensitivity to Imatinib.

  18. Identification and Regulation of c-Myb Target Genes in MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    O'Rourke John P

    2011-01-01

    Full Text Available Abstract Background The c-Myb transcription factor regulates differentiation and proliferation in hematopoietic cells, stem cells and epithelial cells. Although oncogenic versions of c-Myb were first associated with leukemias, over expression or rearrangement of the c-myb gene is common in several types of solid tumors, including breast cancers. Expression of the c-myb gene in human breast cancer cells is dependent on estrogen stimulation, but little is known about the activities of the c-Myb protein or what genes it regulates in estrogen-stimulated cells. Methods We used chromatin immunoprecipitation coupled with whole genome promoter tiling microarrays to identify endogenous c-Myb target genes in human MCF-7 breast cancer cells and characterized the activity of c-Myb at a panel of target genes during different stages of estrogen deprivation and stimulation. Results By using different antibodies and different growth conditions, the c-Myb protein was found associated with over 10,000 promoters in MCF-7 cells, including many genes that encode cell cycle regulators or transcription factors and more than 60 genes that encode microRNAs. Several previously identified c-Myb target genes were identified, including CCNB1, MYC and CXCR4 and novel targets such as JUN, KLF4, NANOG and SND1. By studying a panel of these targets to validate the results, we found that estradiol stimulation triggered the association of c-Myb with promoters and that association correlated with increased target gene expression. We studied one target gene, CXCR4, in detail, showing that c-Myb associated with the CXCR4 gene promoter and activated a CXCR4 reporter gene in transfection assays. Conclusions Our results show that c-Myb associates with a surprisingly large number of promoters in human cells. The results also suggest that estradiol stimulation leads to large-scale, genome-wide changes in c-Myb activity and subsequent changes in gene expression in human breast cancer

  19. Searching for speciation genes

    DEFF Research Database (Denmark)

    Holt, Benjamin George; Côté, Isabelle M; Emerson, Brent C

    2011-01-01

    Closely related species that show clear phenotypic divergence, but without obvious geographic barriers, can provide opportunities to study how diversification can occur when opportunities for allopatric speciation are limited. We examined genetic divergence in the coral reef fish genus Hypoplectr...... evidence for genes that may be associated with colour morphotype in the genus Hypoplectrus....

  20. Gene therapy in ophthalmology

    Directory of Open Access Journals (Sweden)

    Satagopan Uthra

    2009-01-01

    Full Text Available It has been more than a year since ophthalmologists and scientists under Dr. Robin Ali′s team at the Moorsfield Eye Hospital and the Institute of Ophthalmology, University College London, successfully treated patients with a severely blinding disease, Leber′s congenital amaurosis (LCA using gene therapy. This success does not look to be transient, and this achievement in gene replacement therapy clinical trial for LCA has instilled hope in numerous families with patients suffering from this and similar retinal degenerative diseases, for whom restoration of lost vision has remained a distant dream so far. The encouragement that this success has given is expected to also lead to start of clinical trials for other blinding ocular diseases for which gene therapy experiments at the laboratory and animal levels have been successful. This article reviews the various studies that have led to the understanding of gene therapy outcomes in human ocular diseases and attempts to provide a brief sketch of successful clinical trials.

  1. Old genes experience stronger translational selection than young genes.

    Science.gov (United States)

    Yin, Hongyan; Ma, Lina; Wang, Guangyu; Li, Mengwei; Zhang, Zhang

    2016-09-15

    Selection on synonymous codon usage for translation efficiency and/or accuracy has been identified as a widespread mechanism in many living organisms. However, it remains unknown whether translational selection associates closely with gene age and acts differentially on genes with different evolutionary ages. To address this issue, here we investigate the strength of translational selection acting on different aged genes in human. Our results show that old genes present stronger translational selection than young genes, demonstrating that translational selection correlates positively with gene age. We further explore the difference of translational selection in duplicates vs. singletons and in housekeeping vs. tissue-specific genes. We find that translational selection acts comparably in old singletons and old duplicates and stronger translational selection in old genes is contributed primarily by housekeeping genes. For young genes, contrastingly, singletons experience stronger translational selection than duplicates, presumably due to redundant function of duplicated genes during their early evolutionary stage. Taken together, our results indicate that translational selection acting on a gene would not be constant during all stages of evolution, associating closely with gene age. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Genes2FANs: connecting genes through functional association networks

    Directory of Open Access Journals (Sweden)

    Dannenfelser Ruth

    2012-07-01

    Full Text Available Abstract Background Protein-protein, cell signaling, metabolic, and transcriptional interaction networks are useful for identifying connections between lists of experimentally identified genes/proteins. However, besides physical or co-expression interactions there are many ways in which pairs of genes, or their protein products, can be associated. By systematically incorporating knowledge on shared properties of genes from diverse sources to build functional association networks (FANs, researchers may be able to identify additional functional interactions between groups of genes that are not readily apparent. Results Genes2FANs is a web based tool and a database that utilizes 14 carefully constructed FANs and a large-scale protein-protein interaction (PPI network to build subnetworks that connect lists of human and mouse genes. The FANs are created from mammalian gene set libraries where mouse genes are converted to their human orthologs. The tool takes as input a list of human or mouse Entrez gene symbols to produce a subnetwork and a ranked list of intermediate genes that are used to connect the query input list. In addition, users can enter any PubMed search term and then the system automatically converts the returned results to gene lists using GeneRIF. This gene list is then used as input to generate a subnetwork from the user’s PubMed query. As a case study, we applied Genes2FANs to connect disease genes from 90 well-studied disorders. We find an inverse correlation between the counts of links connecting disease genes through PPI and links connecting diseases genes through FANs, separating diseases into two categories. Conclusions Genes2FANs is a useful tool for interpreting the relationships between gene/protein lists in the context of their various functions and networks. Combining functional association interactions with physical PPIs can be useful for revealing new biology and help form hypotheses for further experimentation. Our

  3. Industrial scale gene synthesis.

    Science.gov (United States)

    Notka, Frank; Liss, Michael; Wagner, Ralf

    2011-01-01

    The most recent developments in the area of deep DNA sequencing and downstream quantitative and functional analysis are rapidly adding a new dimension to understanding biochemical pathways and metabolic interdependencies. These increasing insights pave the way to designing new strategies that address public needs, including environmental applications and therapeutic inventions, or novel cell factories for sustainable and reconcilable energy or chemicals sources. Adding yet another level is building upon nonnaturally occurring networks and pathways. Recent developments in synthetic biology have created economic and reliable options for designing and synthesizing genes, operons, and eventually complete genomes. Meanwhile, high-throughput design and synthesis of extremely comprehensive DNA sequences have evolved into an enabling technology already indispensable in various life science sectors today. Here, we describe the industrial perspective of modern gene synthesis and its relationship with synthetic biology. Gene synthesis contributed significantly to the emergence of synthetic biology by not only providing the genetic material in high quality and quantity but also enabling its assembly, according to engineering design principles, in a standardized format. Synthetic biology on the other hand, added the need for assembling complex circuits and large complexes, thus fostering the development of appropriate methods and expanding the scope of applications. Synthetic biology has also stimulated interdisciplinary collaboration as well as integration of the broader public by addressing socioeconomic, philosophical, ethical, political, and legal opportunities and concerns. The demand-driven technological achievements of gene synthesis and the implemented processes are exemplified by an industrial setting of large-scale gene synthesis, describing production from order to delivery.

  4. Endovascular Gene Delivery from a Stent Platform: Gene- Eluting Stents.

    Science.gov (United States)

    Fishbein, Ilia; Chorny, Michael; Adamo, Richard F; Forbes, Scott P; Corrales, Ricardo A; Alferiev, Ivan S; Levy, Robert J

    A synergistic impact of research in the fields of post-angioplasty restenosis, drug-eluting stents and vascular gene therapy over the past 15 years has shaped the concept of gene-eluting stents. Gene-eluting stents hold promise of overcoming some biological and technical problems inherent to drug-eluting stent technology. As the field of gene-eluting stents matures it becomes evident that all three main design modules of a gene-eluting stent: a therapeutic transgene, a vector and a delivery system are equally important for accomplishing sustained inhibition of neointimal formation in arteries treated with gene delivery stents. This review summarizes prior work on stent-based gene delivery and discusses the main optimization strategies required to move the field of gene-eluting stents to clinical translation.

  5. Tumor-specific gene expression patterns with gene expression profiles

    Institute of Scientific and Technical Information of China (English)

    RUAN Xiaogang; LI Yingxin; LI Jiangeng; GONG Daoxiong; WANG Jinlian

    2006-01-01

    Gene expression profiles of 14 common tumors and their counterpart normal tissues were analyzed with machine learning methods to address the problem of selection of tumor-specific genes and analysis of their differential expressions in tumor tissues. First, a variation of the Relief algorithm, "RFE_Relief algorithm" was proposed to learn the relations between genes and tissue types. Then, a support vector machine was employed to find the gene subset with the best classification performance for distinguishing cancerous tissues and their counterparts. After tissue-specific genes were removed, cross validation experiments were employed to demonstrate the common deregulated expressions of the selected gene in tumor tissues. The results indicate the existence of a specific expression fingerprint of these genes that is shared in different tumor tissues, and the hallmarks of the expression patterns of these genes in cancerous tissues are summarized at the end of this paper.

  6. Entrez Gene: gene-centered information at NCBI.

    Science.gov (United States)

    Maglott, Donna; Ostell, Jim; Pruitt, Kim D; Tatusova, Tatiana

    2011-01-01

    Entrez Gene (http://www.ncbi.nlm.nih.gov/gene) is National Center for Biotechnology Information (NCBI)'s database for gene-specific information. Entrez Gene maintains records from genomes which have been completely sequenced, which have an active research community to submit gene-specific information, or which are scheduled for intense sequence analysis. The content represents the integration of curation and automated processing from NCBI's Reference Sequence project (RefSeq), collaborating model organism databases, consortia such as Gene Ontology and other databases within NCBI. Records in Entrez Gene are assigned unique, stable and tracked integers as identifiers. The content (nomenclature, genomic location, gene products and their attributes, markers, phenotypes and links to citations, sequences, variation details, maps, expression, homologs, protein domains and external databases) is available via interactive browsing through NCBI's Entrez system, via NCBI's Entrez programming utilities (E-Utilities) and for bulk transfer by FTP.

  7. Ultra high-resolution gene centric genomic structural analysis of a non-syndromic congenital heart defect, Tetralogy of Fallot.

    Directory of Open Access Journals (Sweden)

    Douglas C Bittel

    Full Text Available Tetralogy of Fallot (TOF is one of the most common severe congenital heart malformations. Great progress has been made in identifying key genes that regulate heart development, yet approximately 70% of TOF cases are sporadic and nonsyndromic with no known genetic cause. We created an ultra high-resolution gene centric comparative genomic hybridization (gcCGH microarray based on 591 genes with a validated association with cardiovascular development or function. We used our gcCGH array to analyze the genomic structure of 34 infants with sporadic TOF without a deletion on chromosome 22q11.2 (n male = 20; n female = 14; age range of 2 to 10 months. Using our custom-made gcCGH microarray platform, we identified a total of 613 copy number variations (CNVs ranging in size from 78 base pairs to 19.5 Mb. We identified 16 subjects with 33 CNVs that contained 13 different genes which are known to be directly associated with heart development. Additionally, there were 79 genes from the broader list of genes that were partially or completely contained in a CNV. All 34 individuals examined had at least one CNV involving these 79 genes. Furthermore, we had available whole genome exon arrays from right ventricular tissue in 13 of our subjects. We analyzed these for correlations between copy number and gene expression level. Surprisingly, we could detect only one clear association between CNVs and expression (GSTT1 for any of the 591 focal genes on the gcCGH array. The expression levels of GSTT1 were correlated with copy number in all cases examined (r = 0.95, p = 0.001. We identified a large number of small CNVs in genes with varying associations with heart development. Our results illustrate the complexity of human genome structural variation and underscore the need for multifactorial assessment of potential genetic/genomic factors that contribute to congenital heart defects.

  8. Gene set analysis for longitudinal gene expression data

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    Piepho Hans-Peter

    2011-07-01

    Full Text Available Abstract Background Gene set analysis (GSA has become a successful tool to interpret gene expression profiles in terms of biological functions, molecular pathways, or genomic locations. GSA performs statistical tests for independent microarray samples at the level of gene sets rather than individual genes. Nowadays, an increasing number of microarray studies are conducted to explore the dynamic changes of gene expression in a variety of species and biological scenarios. In these longitudinal studies, gene expression is repeatedly measured over time such that a GSA needs to take into account the within-gene correlations in addition to possible between-gene correlations. Results We provide a robust nonparametric approach to compare the expressions of longitudinally measured sets of genes under multiple treatments or experimental conditions. The limiting distributions of our statistics are derived when the number of genes goes to infinity while the number of replications can be small. When the number of genes in a gene set is small, we recommend permutation tests based on our nonparametric test statistics to achieve reliable type I error and better power while incorporating unknown correlations between and within-genes. Simulation results demonstrate that the proposed method has a greater power than other methods for various data distributions and heteroscedastic correlation structures. This method was used for an IL-2 stimulation study and significantly altered gene sets were identified. Conclusions The simulation study and the real data application showed that the proposed gene set analysis provides a promising tool for longitudinal microarray analysis. R scripts for simulating longitudinal data and calculating the nonparametric statistics are posted on the North Dakota INBRE website http://ndinbre.org/programs/bioinformatics.php. Raw microarray data is available in Gene Expression Omnibus (National Center for Biotechnology Information with

  9. Optimal Reference Genes for Gene Expression Normalization in Trichomonas vaginalis.

    Science.gov (United States)

    dos Santos, Odelta; de Vargas Rigo, Graziela; Frasson, Amanda Piccoli; Macedo, Alexandre José; Tasca, Tiana

    2015-01-01

    Trichomonas vaginalis is the etiologic agent of trichomonosis, the most common non-viral sexually transmitted disease worldwide. This infection is associated with several health consequences, including cervical and prostate cancers and HIV acquisition. Gene expression analysis has been facilitated because of available genome sequences and large-scale transcriptomes in T. vaginalis, particularly using quantitative real-time polymerase chain reaction (qRT-PCR), one of the most used methods for molecular studies. Reference genes for normalization are crucial to ensure the accuracy of this method. However, to the best of our knowledge, a systematic validation of reference genes has not been performed for T. vaginalis. In this study, the transcripts of nine candidate reference genes were quantified using qRT-PCR under different cultivation conditions, and the stability of these genes was compared using the geNorm and NormFinder algorithms. The most stable reference genes were α-tubulin, actin and DNATopII, and, conversely, the widely used T. vaginalis reference genes GAPDH and β-tubulin were less stable. The PFOR gene was used to validate the reliability of the use of these candidate reference genes. As expected, the PFOR gene was upregulated when the trophozoites were cultivated with ferrous ammonium sulfate when the DNATopII, α-tubulin and actin genes were used as normalizing gene. By contrast, the PFOR gene was downregulated when the GAPDH gene was used as an internal control, leading to misinterpretation of the data. These results provide an important starting point for reference gene selection and gene expression analysis with qRT-PCR studies of T. vaginalis.

  10. Dominance from the perspective of gene-gene and gene-chemical interactions.

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    Gladki, Arkadiusz; Zielenkiewicz, Piotr; Kaczanowski, Szymon

    2016-02-01

    In this study, we used genetic interaction (GI) and gene-chemical interaction (GCI) data to compare mutations with different dominance phenotypes. Our analysis focused primarily on Saccharomyces cerevisiae, where haploinsufficient genes (HI; genes with dominant loss-of-function mutations) were found to be participating in gene expression processes, namely, the translation and regulation of gene transcription. Non-ribosomal HI genes (mainly regulators of gene transcription) were found to have more GIs and GCIs than haplosufficient (HS) genes. Several properties seem to lead to the enrichment of interactions, most notably, the following: importance, pleiotropy, gene expression level and gene expression variation. Importantly, after these properties were appropriately considered in the analysis, the correlation between dominance and GI/GCI degrees was still observed. Strikingly, for the GCIs of heterozygous strains, haploinsufficiency was the only property significantly correlated with the number of GCIs. We found ribosomal HI genes to be depleted in GIs/GCIs. This finding can be explained by their high variation in gene expression under different genetic backgrounds and environmental conditions. We observed the same distributions of GIs among non-ribosomal HI, ribosomal HI and HS genes in three other species: Schizosaccharomyces pombe, Drosophila melanogaster and Homo sapiens. One potentially interesting exception was the lack of significant differences in the degree of GIs between non-ribosomal HI and HS genes in Schizosaccharomyces pombe.

  11. Gene-gene interaction between tuberculosis candidate genes in a South African population.

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    de Wit, Erika; van der Merwe, Lize; van Helden, Paul D; Hoal, Eileen G

    2011-02-01

    In a complex disease such as tuberculosis (TB) it is increasingly evident that gene-gene interactions play a far more important role in an individual's susceptibility to develop the disease than single polymorphisms on their own, as one gene can enhance or hinder the expression of another gene. Gene-gene interaction analysis is a new approach to elucidate susceptibility to TB. The possibility of gene-gene interactions was assessed, focusing on 11 polymorphisms in nine genes (DC-SIGN, IFN-γ, IFNGR1, IL-8, IL-1Ra, MBL, NRAMP1, RANTES, and SP-D) that have been associated with TB, some repeatedly. An optimal model, which best describes and predicts TB case-control status, was constructed. Significant interactions were detected between eight pairs of variants. The models fitted the observed data extremely well, with p activation is greatly enhanced by IFN-γ and IFN-γ response elements that are present in the human NRAMP1 promoter region, providing further evidence for their interaction. This study enabled us to test the theory that disease outcome may be due to interaction of several gene effects. With eight instances of statistically significant gene-gene interactions, the importance of epistasis is clearly identifiable in this study. Methods for studying gene-gene interactions are based on a multilocus and multigene approach, consistent with the nature of complex-trait diseases, and may provide the paradigm for future genetic studies of TB.

  12. Contribution of six flagellin genes to the flagellum biogenesis of Vibrio vulnificus and in vivo invasion.

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    Kim, Soo Young; Thanh, Xuan Tran Thi; Jeong, Kwangjoon; Kim, Seong Bin; Pan, Sang O; Jung, Che Hun; Hong, Seol Hee; Lee, Shee Eun; Rhee, Joon Haeng

    2014-01-01

    Vibrio vulnificus is a halophilic pathogenic bacterium that is motile due to the presence of a single polar flagellum. V. vulnificus possesses a total of six flagellin genes organized into two loci (flaFBA and flaCDE). We proved that all six of the flagellin genes were transcribed, whereas only five (FlaA, -B, -C, -D, and -F) of the six flagellin proteins were detected. To understand roles of the six V. vulnificus flagellins in motility and virulence, mutants with single and multiple flagellin deletions were constructed. Mutations in flaB or flaC or the flaCDE locus resulted in a significant decrease in motility, adhesion, and cytotoxicity, whereas single mutations in the other flagellin genes or the flaFBA locus showed little or no effect. The motility was completely abolished only in the mutant lacking all six flagellin genes (flaFBA flaCDE). Surprisingly, a double mutation of flaB and flaD, a gene sharing 99% identity with the flaB at the amino acid level, resulted in the largest decrease in motility, adhesion, and cytotoxicity except for the mutant in which all six genes were deleted (the hexa mutant). Additionally, the 50% lethal doses (LD50s) of the flaB flaD and the flaFBA flaCDE mutants increased 23- and 91-fold in a mouse model, respectively, and the in vitro and in vivo invasiveness of the mutants was significantly decreased compared to that of the wild type. Taken together, the multiple flagellin subunits differentially contribute to the flagellum biogenesis and the pathogenesis of V. vulnificus, and among the six flagellin genes, flaB, flaD, and flaC were the most influential components.

  13. Comparative gene expression analysis of avian embryonic facial structures reveals new candidates for human craniofacial disorders.

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    Brugmann, S A; Powder, K E; Young, N M; Goodnough, L H; Hahn, S M; James, A W; Helms, J A; Lovett, M

    2010-03-01

    Mammals and birds have common embryological facial structures, and appear to employ the same molecular genetic developmental toolkit. We utilized natural variation found in bird beaks to investigate what genes drive vertebrate facial morphogenesis. We employed cross-species microarrays to describe the molecular genetic signatures, developmental signaling pathways and the spectrum of transcription factor (TF) gene expression changes that differ between cranial neural crest cells in the developing beaks of ducks, quails and chickens. Surprisingly, we observed that the neural crest cells established a species-specific TF gene expression profile that predates morphological differences between the species. A total of 232 genes were differentially expressed between the three species. Twenty-two of these genes, including Fgfr2, Jagged2, Msx2, Satb2 and Tgfb3, have been previously implicated in a variety of mammalian craniofacial defects. Seventy-two of the differentially expressed genes overlap with un-cloned loci for human craniofacial disorders, suggesting that our data will provide a valuable candidate gene resource for human craniofacial genetics. The most dramatic changes between species were in the Wnt signaling pathway, including a 20-fold up-regulation of Dkk2, Fzd1 and Wnt1 in the duck compared with the other two species. We functionally validated these changes by demonstrating that spatial domains of Wnt activity differ in avian beaks, and that Wnt signals regulate Bmp pathway activity and promote regional growth in facial prominences. This study is the first of its kind, extending on previous work in Darwin's finches and provides the first large-scale insights into cross-species facial morphogenesis.

  14. Expanded functional diversity of shaker K(+ channels in cnidarians is driven by gene expansion.

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    Timothy Jegla

    Full Text Available The genome of the cnidarian Nematostella vectensis (starlet sea anemone provides a molecular genetic view into the first nervous systems, which appeared in a late common ancestor of cnidarians and bilaterians. Nematostella has a surprisingly large and diverse set of neuronal signaling genes including paralogs of most neuronal signaling molecules found in higher metazoans. Several ion channel gene families are highly expanded in the sea anemone, including three subfamilies of the Shaker K(+ channel gene family: Shaker (Kv1, Shaw (Kv3 and Shal (Kv4. In order to better understand the physiological significance of these voltage-gated K(+ channel expansions, we analyzed the function of 18 members of the 20 gene Shaker subfamily in Nematostella. Six of the Nematostella Shaker genes express functional homotetrameric K(+ channels in vitro. These include functional orthologs of bilaterian Shakers and channels with an unusually high threshold for voltage activation. We identified 11 Nematostella Shaker genes with a distinct "silent" or "regulatory" phenotype; these encode subunits that function only in heteromeric channels and serve to further diversify Nematostella Shaker channel gating properties. Subunits with the regulatory phenotype have not previously been found in the Shaker subfamily, but have evolved independently in the Shab (Kv2 family in vertebrates and the Shal family in a cnidarian. Phylogenetic analysis indicates that regulatory subunits were present in ancestral cnidarians, but have continued to diversity at a high rate after the split between anthozoans and hydrozoans. Comparison of Shaker family gene complements from diverse metazoan species reveals frequent, large scale duplication has produced highly unique sets of Shaker channels in the major metazoan lineages.

  15. Identification of genes associated with resilience/vulnerability to sleep deprivation and starvation in Drosophila.

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    Thimgan, Matthew S; Seugnet, Laurent; Turk, John; Shaw, Paul J

    2015-05-01

    Flies mutant for the canonical clock protein cycle (cyc(01)) exhibit a sleep rebound that is ∼10 times larger than wild-type flies and die after only 10 h of sleep deprivation. Surprisingly, when starved, cyc(01) mutants can remain awake for 28 h without demonstrating negative outcomes. Thus, we hypothesized that identifying transcripts that are differentially regulated between waking induced by sleep deprivation and waking induced by starvation would identify genes that underlie the deleterious effects of sleep deprivation and/or protect flies from the negative consequences of waking. We used partial complementary DNA microarrays to identify transcripts that are differentially expressed between cyc(01) mutants that had been sleep deprived or starved for 7 h. We then used genetics to determine whether disrupting genes involved in lipid metabolism would exhibit alterations in their response to sleep deprivation. Laboratory. Drosophila melanogaster. Sleep deprivation and starvation. We identified 84 genes with transcript levels that were differentially modulated by 7 h of sleep deprivation and starvation in cyc(01) mutants and were confirmed in independent samples using quantitative polymerase chain reaction. Several of these genes were predicted to be lipid metabolism genes, including bubblegum, cueball, and CG4500, which based on our data we have renamed heimdall (hll). Using lipidomics we confirmed that knockdown of hll using RNA interference significantly decreased lipid stores. Importantly, genetically modifying bubblegum, cueball, or hll resulted in sleep rebound alterations following sleep deprivation compared to genetic background controls. We have identified a set of genes that may confer resilience/vulnerability to sleep deprivation and demonstrate that genes involved in lipid metabolism modulate sleep homeostasis. © 2015 Associated Professional Sleep Societies, LLC.

  16. Expression of Root Genes in Arabidopsis Seedlings Grown by Standard and Improved Growing Methods

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    Yanli Qu

    2017-05-01

    Full Text Available Roots of Arabidopsis thaliana seedlings grown in the laboratory using the traditional plant-growing culture system (TPG were covered to maintain them in darkness. This new method is based on a dark chamber and is named the improved plant-growing method (IPG. We measured the light conditions in dark chambers, and found that the highest light intensity was dramatically reduced deeper in the dark chamber. In the bottom and side parts of dark chambers, roots were almost completely shaded. Using the high-throughput RNA sequencing method on the whole RNA extraction from roots, we compared the global gene expression levels in roots of seedlings from these two conditions and identified 141 differently expressed genes (DEGs between them. According to the KEGG (Kyoto Encyclopedia of Genes and Genomes enrichment, the flavone and flavonol biosynthesis and flavonoid biosynthesis pathways were most affected among all annotated pathways. Surprisingly, no genes of known plant photoreceptors were identified as DEGs by this method. Considering that the light intensity was decreased in the IPG system, we collected four sections (1.5 cm for each of Arabidopsis roots grown in TPG and IPG conditions, and the spatial-related differential gene expression levels of plant photoreceptors and polar auxin transporters, including CRY1, CRY2, PHYA, PHYB, PHOT1, PHOT2, and UVR8 were analyzed by qRT-PCR. Using these results, we generated a map of the spatial-related expression patterns of these genes under IPG and TPG conditions. The expression levels of light-related genes in roots is highly sensitive to illumination and it provides a background reference for selecting an improved culture method for laboratory-maintained Arabidopsis seedlings.

  17. Expression of Root Genes in Arabidopsis Seedlings Grown by Standard and Improved Growing Methods.

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    Qu, Yanli; Liu, Shuai; Bao, Wenlong; Xue, Xian; Ma, Zhengwen; Yokawa, Ken; Baluška, František; Wan, Yinglang

    2017-05-03

    Roots of Arabidopsis thaliana seedlings grown in the laboratory using the traditional plant-growing culture system (TPG) were covered to maintain them in darkness. This new method is based on a dark chamber and is named the improved plant-growing method (IPG). We measured the light conditions in dark chambers, and found that the highest light intensity was dramatically reduced deeper in the dark chamber. In the bottom and side parts of dark chambers, roots were almost completely shaded. Using the high-throughput RNA sequencing method on the whole RNA extraction from roots, we compared the global gene expression levels in roots of seedlings from these two conditions and identified 141 differently expressed genes (DEGs) between them. According to the KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment, the flavone and flavonol biosynthesis and flavonoid biosynthesis pathways were most affected among all annotated pathways. Surprisingly, no genes of known plant photoreceptors were identified as DEGs by this method. Considering that the light intensity was decreased in the IPG system, we collected four sections (1.5 cm for each) of Arabidopsis roots grown in TPG and IPG conditions, and the spatial-related differential gene expression levels of plant photoreceptors and polar auxin transporters, including CRY1, CRY2, PHYA, PHYB, PHOT1, PHOT2, and UVR8 were analyzed by qRT-PCR. Using these results, we generated a map of the spatial-related expression patterns of these genes under IPG and TPG conditions. The expression levels of light-related genes in roots is highly sensitive to illumination and it provides a background reference for selecting an improved culture method for laboratory-maintained Arabidopsis seedlings.

  18. New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen.

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    2005-07-01

    Full Text Available Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

  19. Stress tolerances of nullmutants of function-unknown genes encoding menadione stress-responsive proteins in Aspergillus nidulans.

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    Leiter, Éva; Bálint, Mihály; Miskei, Márton; Orosz, Erzsébet; Szabó, Zsuzsa; Pócsi, István

    2016-07-01

    A group of menadione stress-responsive function-unkown genes of Aspergillus nidulans (Locus IDs ANID_03987.1, ANID_06058.1, ANID_10219.1, and ANID_10260.1) was deleted and phenotypically characterized. Importantly, comparative and phylogenetic analyses of the tested A. nidulans genes and their orthologs shed light only on the presence of a TANGO2 domain with NRDE protein motif in the translated ANID_06058.1 gene but did not reveal any recognizable protein-encoding domains in other protein sequences. The gene deletion strains were subjected to oxidative, osmotic, and metal ion stress and, surprisingly, only the ΔANID_10219.1 mutant showed an increased sensitivity to 0.12 mmol l(-1) menadione sodium bisulfite. The gene deletions affected the stress sensitivities (tolerances) irregularly, for example, some strains grew more slowly when exposed to various oxidants and/or osmotic stress generating agents, meanwhile the ΔANID_10260.1 mutant possessed a wild-type tolerance to all stressors tested. Our results are in line with earlier studies demonstrating that the deletions of stress-responsive genes do not confer necessarily any stress-sensitivity phenotypes, which can be attributed to compensatory mechanisms based on other elements of the stress response system with overlapping functions.

  20. Transcriptional profiling of epidermal keratinocytes: comparison of genes expressed in skin, cultured keratinocytes, and reconstituted epidermis, using large DNA microarrays.

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    Gazel, Alix; Ramphal, Patricia; Rosdy, Martin; De Wever, Bart; Tornier, Carine; Hosein, Nadia; Lee, Brian; Tomic-Canic, Marjana; Blumenberg, Miroslav

    2003-12-01

    Epidermal keratinocytes are complex cells that create a unique three-dimensional (3-D) structure, differentiate through a multistage process, and respond to extracellular stimuli from nearby cells. Consequently, keratinocytes express many genes, i.e., have a relatively large "transcriptome." To determine which of the expressed genes are innate to keratinocytes, which are specific for the differentiation and 3-D architecture, and which are induced by other cell types, we compared the transcriptomes of skin from human subjects, differentiating 3-D reconstituted epidermis, cultured keratinocytes, and nonkeratinocyte cell types. Using large oligonucleotide microarrays, we analyzed five or more replicates of each, which yielded statistically consistent data and allowed identification of the differentially expressed genes. Epidermal keratinocytes, unlike other cells, express many proteases and protease inhibitors and genes that protect from UV light. Skin specifically expresses a higher number of receptors, secreted proteins, and transcription factors, perhaps influenced by the presence of nonkeratinocyte cell types. Surprisingly, mitochondrial proteins were significantly suppressed in skin, suggesting a low metabolic rate. Three-dimensional samples, skin and reconstituted epidermis, are similar to each other, expressing epidermal differentiation markers. Cultured keratinocytes express many cell-cycle and DNA replication genes, as well as integrins and extracellular matrix proteins. These results define innate, architecture-specific, and cell-type-regulated genes in epidermis.