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Sample records for sar-associated genes surprisingly

  1. Invited Commentary: More Surprises From a Gene Desert

    OpenAIRE

    Wacholder, Sholom; Yeager, Meredith; Liao, Linda M.

    2012-01-01

    Pleiotropy across the 8q24 region is perhaps the most intriguing of the genome-wide association findings relating to cancer. This region of chromosome 8 is a gene desert, far from any recognized genes. Guarrera et al., whose work is reported in this issue (Am J Epidemiol. 2012;175(6):479–487), took an epidemiologic approach to learn more about the 8q24 region. They capitalized on their ascertainment of other endpoints in members of the cohort at the Turin site of the European Prospective Inve...

  2. Ontological Surprises

    DEFF Research Database (Denmark)

    Leahu, Lucian

    2016-01-01

    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.......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...

  3. Surprise Trips

    DEFF Research Database (Denmark)

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

    2010-01-01

    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 as notification tokens to alert users when they are within proximity of a surprise. To evaluate the concept, we developed mock-ups, a video prototype and conducted a wizard-of-oz user test for a national park in Denmark....

  4. Fancy a gene? A surprisingly complex evolutionary history/nof peroxiredoxins

    Czech Academy of Sciences Publication Activity Database

    Zíková, Alena; Oborník, Miroslav; Lukeš, Julius

    2015-01-01

    Roč. 2, č. 2 (2015), s. 33-37 E-ISSN 2311-2638 EU Projects: European Commission(XE) 316304 Institutional support: RVO:60077344 Keywords : horizontal gene transfer * Apicomplexa * endosymbiont * Plasmodium * Chromera * peroxiredoxin * oxidative stress Subject RIV: EB - Genetics ; Molecular Biology

  5. 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...

  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. Surprise, Recipes for Surprise, and Social Influence.

    Science.gov (United States)

    Loewenstein, Jeffrey

    2018-02-07

    Surprising people can provide an opening for influencing them. Surprises garner attention, are arousing, are memorable, and can prompt shifts in understanding. Less noted is that, as a result, surprises can serve to persuade others by leading them to shifts in attitudes. Furthermore, because stories, pictures, and music can generate surprises and those can be widely shared, surprise can have broad social influence. People also tend to share surprising items with others, as anyone on social media has discovered. This means that in addition to broadcasting surprising information, surprising items can also spread through networks. The joint result is that surprise not only has individual effects on beliefs and attitudes but also collective effects on the content of culture. Items that generate surprise need not be random or accidental. There are predictable methods or recipes for generating surprise. One such recipe is discussed, the repetition-break plot structure, to explore the psychological and social possibilities of examining surprise. Recipes for surprise offer a useful means for understanding how surprise works and offer prospects for harnessing surprise to a wide array of ends. Copyright © 2017 Cognitive Science Society, Inc.

  8. 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

  9. 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

  10. 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…

  11. The role of surprise in satisfaction judgements

    NARCIS (Netherlands)

    Vanhamme, J.; Snelders, H.M.J.J.

    2001-01-01

    Empirical findings suggest that surprise plays an important role in consumer satisfaction, but there is a lack of theory to explain why this is so. The present paper provides explanations for the process through which positive (negative) surprise might enhance (reduce) consumer satisfaction. First,

  12. Climate Change as a Predictable Surprise

    International Nuclear Information System (INIS)

    Bazerman, M.H.

    2006-01-01

    In this article, I analyze climate change as a 'predictable surprise', an event that leads an organization or nation to react with surprise, despite the fact that the information necessary to anticipate the event and its consequences was available (Bazerman and Watkins, 2004). I then assess the cognitive, organizational, and political reasons why society fails to implement wise strategies to prevent predictable surprises generally and climate change specifically. Finally, I conclude with an outline of a set of response strategies to overcome barriers to change

  13. 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.

  14. Surprise: a belief or an emotion?

    Science.gov (United States)

    Mellers, Barbara; Fincher, Katrina; Drummond, Caitlin; Bigony, Michelle

    2013-01-01

    Surprise is a fundamental link between cognition and emotion. It is shaped by cognitive assessments of likelihood, intuition, and superstition, and it in turn shapes hedonic experiences. We examine this connection between cognition and emotion and offer an explanation called decision affect theory. Our theory predicts the affective consequences of mistaken beliefs, such as overconfidence and hindsight. It provides insight about why the pleasure of a gain can loom larger than the pain of a comparable loss. Finally, it explains cross-cultural differences in emotional reactions to surprising events. By changing the nature of the unexpected (from chance to good luck), one can alter the emotional reaction to surprising events. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Viral marketing: the use of surprise

    NARCIS (Netherlands)

    Lindgreen, A.; Vanhamme, J.; Clarke, I.; Flaherty, T.B.

    2005-01-01

    Viral marketing involves consumers passing along a company's marketing message to their friends, family, and colleagues. This chapter reviews viral marketing campaigns and argues that the emotion of surprise often is at work and that this mechanism resembles that of word-of-mouth marketing.

  16. Exploration, Novelty, Surprise and Free Energy Minimisation

    Directory of Open Access Journals (Sweden)

    Philipp eSchwartenbeck

    2013-10-01

    Full Text Available This paper reviews recent developments under the free energy principle that introduce a normative perspective on classical economic (utilitarian decision-making based on (active Bayesian inference. It has been suggested that the free energy principle precludes novelty and complexity, because it assumes that biological systems – like ourselves - try to minimise the long-term average of surprise to maintain their homeostasis. However, recent formulations show that minimising surprise leads naturally to concepts such as exploration and novelty bonuses. In this approach, agents infer a policy that minimises surprise by minimising the difference (or relative entropy between likely and desired outcomes, which involves both pursuing the goal-state that has the highest expected utility (often termed ‘exploitation’ and visiting a number of different goal-states (‘exploration’. Crucially, the opportunity to visit new states increases the value of the current state. Casting decision-making problems within a variational framework, therefore, predicts that our behaviour is governed by both the entropy and expected utility of future states. This dissolves any dialectic between minimising surprise and exploration or novelty seeking.

  17. Glial heterotopia of maxilla: A clinical surprise

    Directory of Open Access Journals (Sweden)

    Santosh Kumar Mahalik

    2011-01-01

    Full Text Available Glial heterotopia is a rare congenital mass lesion which often presents as a clinical surprise. We report a case of extranasal glial heterotopia in a neonate with unusual features. The presentation, management strategy, etiopathogenesis and histopathology of the mass lesion has been reviewed.

  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. 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. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  20. A surprising palmar nevus: A case report

    Directory of Open Access Journals (Sweden)

    Rana Rafiei

    2018-02-01

    Full Text Available Raised palmar or plantar nevus especially in white people is an unusual feature. We present an uncommon palmar compound nevus in a 26-year-old woman with a large diameter (6 mm which had a collaret-shaped margin. In histopathologic evaluation intralymphatic protrusions of nevic nests were noted. This case was surprising to us for these reasons: size, shape, location and histopathology of the lesion. Palmar nevi are usually junctional (flat and below 3 mm diameter and intra lymphatic protrusion or invasion in nevi is an extremely rare phenomenon.

  1. Primary Care Practice: Uncertainty and Surprise

    Science.gov (United States)

    Crabtree, Benjamin F.

    I will focus my comments on uncertainty and surprise in primary care practices. I am a medical anthropologist by training, and have been a full-time researcher in family medicine for close to twenty years. In this talk I want to look at primary care practices as complex systems, particularly taking the perspective of translating evidence into practice. I am going to discuss briefly the challenges we have in primary care, and in medicine in general, of translating new evidence into the everyday care of patients. To do this, I will look at two studies that we have conducted on family practices, then think about how practices can be best characterized as complex adaptive systems. Finally, I will focus on the implications of this portrayal for disseminating new knowledge into practice.

  2. Surprises and counterexamples in real function theory

    CERN Document Server

    Rajwade, A R

    2007-01-01

    This book presents a variety of intriguing, surprising and appealing topics and nonroutine theorems in real function theory. It is a reference book to which one can turn for finding that arise while studying or teaching analysis.Chapter 1 is an introduction to algebraic, irrational and transcendental numbers and contains the Cantor ternary set. Chapter 2 contains functions with extraordinary properties; functions that are continuous at each point but differentiable at no point. Chapters 4 and intermediate value property, periodic functions, Rolle's theorem, Taylor's theorem, points of tangents. Chapter 6 discusses sequences and series. It includes the restricted harmonic series, of alternating harmonic series and some number theoretic aspects. In Chapter 7, the infinite peculiar range of convergence is studied. Appendix I deal with some specialized topics. Exercises at the end of chapters and their solutions are provided in Appendix II.This book will be useful for students and teachers alike.

  3. 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

  4. 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...

  5. X rays and radioactivity: a complete surprise

    International Nuclear Information System (INIS)

    Radvanyi, P.; Bordry, M.

    1995-01-01

    The discoveries of X rays and of radioactivity came as complete experimental surprises; the physicists, at that time, had no previous hint of a possible structure of atoms. It is difficult now, knowing what we know, to replace ourselves in the spirit, astonishment and questioning of these years, between 1895 and 1903. The nature of X rays was soon hypothesized, but the nature of the rays emitted by uranium, polonium and radium was much more difficult to disentangle, as they were a mixture of different types of radiations. The origin of the energy continuously released in radioactivity remained a complete mystery for a few years. The multiplicity of the radioactive substances became soon a difficult matter: what was real and what was induced ? Isotopy was still far ahead. It appeared that some radioactive substances had ''half-lifes'': were they genuine radioactive elements or was it just a transitory phenomenon ? Henri Becquerel (in 1900) and Pierre and Marie Curie (in 1902) hesitated on the correct answer. Only after Ernest Rutherford and Frederick Soddy established that radioactivity was the transmutation of one element into another, could one understand that a solid element transformed into a gaseous element, which in turn transformed itself into a succession of solid radioactive elements. It was only in 1913 - after the discovery of the atomic nucleus -, through precise measurements of X ray spectra, that Henry Moseley showed that the number of electrons of a given atom - and the charge of its nucleus - was equal to its atomic number in the periodic table. (authors)

  6. X rays and radioactivity: a complete surprise

    Energy Technology Data Exchange (ETDEWEB)

    Radvanyi, P. [Laboratoire National Saturne, Centre d`Etudes de Saclay, 91 - Gif-sur-Yvette (France); Bordry, M. [Institut du Radium, 75 - Paris (France)

    1995-12-31

    The discoveries of X rays and of radioactivity came as complete experimental surprises; the physicists, at that time, had no previous hint of a possible structure of atoms. It is difficult now, knowing what we know, to replace ourselves in the spirit, astonishment and questioning of these years, between 1895 and 1903. The nature of X rays was soon hypothesized, but the nature of the rays emitted by uranium, polonium and radium was much more difficult to disentangle, as they were a mixture of different types of radiations. The origin of the energy continuously released in radioactivity remained a complete mystery for a few years. The multiplicity of the radioactive substances became soon a difficult matter: what was real and what was induced ? Isotopy was still far ahead. It appeared that some radioactive substances had ``half-lifes``: were they genuine radioactive elements or was it just a transitory phenomenon ? Henri Becquerel (in 1900) and Pierre and Marie Curie (in 1902) hesitated on the correct answer. Only after Ernest Rutherford and Frederick Soddy established that radioactivity was the transmutation of one element into another, could one understand that a solid element transformed into a gaseous element, which in turn transformed itself into a succession of solid radioactive elements. It was only in 1913 - after the discovery of the atomic nucleus -, through precise measurements of X ray spectra, that Henry Moseley showed that the number of electrons of a given atom - and the charge of its nucleus - was equal to its atomic number in the periodic table. (authors).

  7. 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

  8. Surprise: Dwarf Galaxy Harbors Supermassive Black Hole

    Science.gov (United States)

    2011-01-01

    The surprising discovery of a supermassive black hole in a small nearby galaxy has given astronomers a tantalizing look at how black holes and galaxies may have grown in the early history of the Universe. Finding a black hole a million times more massive than the Sun in a star-forming dwarf galaxy is a strong indication that supermassive black holes formed before the buildup of galaxies, the astronomers said. The galaxy, called Henize 2-10, 30 million light-years from Earth, has been studied for years, and is forming stars very rapidly. Irregularly shaped and about 3,000 light-years across (compared to 100,000 for our own Milky Way), it resembles what scientists think were some of the first galaxies to form in the early Universe. "This galaxy gives us important clues about a very early phase of galaxy evolution that has not been observed before," said Amy Reines, a Ph.D. candidate at the University of Virginia. Supermassive black holes lie at the cores of all "full-sized" galaxies. In the nearby Universe, there is a direct relationship -- a constant ratio -- between the masses of the black holes and that of the central "bulges" of the galaxies, leading them to conclude that the black holes and bulges affected each others' growth. Two years ago, an international team of astronomers found that black holes in young galaxies in the early Universe were more massive than this ratio would indicate. This, they said, was strong evidence that black holes developed before their surrounding galaxies. "Now, we have found a dwarf galaxy with no bulge at all, yet it has a supermassive black hole. This greatly strengthens the case for the black holes developing first, before the galaxy's bulge is formed," Reines said. Reines, along with Gregory Sivakoff and Kelsey Johnson of the University of Virginia and the National Radio Astronomy Observatory (NRAO), and Crystal Brogan of the NRAO, observed Henize 2-10 with the National Science Foundation's Very Large Array radio telescope and

  9. Old Star's "Rebirth" Gives Astronomers Surprises

    Science.gov (United States)

    2005-04-01

    Astronomers using the National Science Foundation's Very Large Array (VLA) radio telescope are taking advantage of a once-in-a-lifetime opportunity to watch an old star suddenly stir back into new activity after coming to the end of its normal life. Their surprising results have forced them to change their ideas of how such an old, white dwarf star can re-ignite its nuclear furnace for one final blast of energy. Sakurai's Object Radio/Optical Images of Sakurai's Object: Color image shows nebula ejected thousands of years ago. Contours indicate radio emission. Inset is Hubble Space Telescope image, with contours indicating radio emission; this inset shows just the central part of the region. CREDIT: Hajduk et al., NRAO/AUI/NSF, ESO, StSci, NASA Computer simulations had predicted a series of events that would follow such a re-ignition of fusion reactions, but the star didn't follow the script -- events moved 100 times more quickly than the simulations predicted. "We've now produced a new theoretical model of how this process works, and the VLA observations have provided the first evidence supporting our new model," said Albert Zijlstra, of the University of Manchester in the United Kingdom. Zijlstra and his colleagues presented their findings in the April 8 issue of the journal Science. The astronomers studied a star known as V4334 Sgr, in the constellation Sagittarius. It is better known as "Sakurai's Object," after Japanese amateur astronomer Yukio Sakurai, who discovered it on February 20, 1996, when it suddenly burst into new brightness. At first, astronomers thought the outburst was a common nova explosion, but further study showed that Sakurai's Object was anything but common. The star is an old white dwarf that had run out of hydrogen fuel for nuclear fusion reactions in its core. Astronomers believe that some such stars can undergo a final burst of fusion in a shell of helium that surrounds a core of heavier nuclei such as carbon and oxygen. However, the

  10. 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.

  11. A Dichotomic Analysis of the Surprise Examination Paradox

    OpenAIRE

    Franceschi, Paul

    2002-01-01

    This paper presents a dichotomic analysis of the surprise examination paradox. In section 1, I analyse the surprise notion in detail. I introduce then in section 2, the distinction between a monist and dichotomic analysis of the paradox. I also present there a dichotomy leading to distinguish two basically and structurally different versions of the paradox, respectively based on a conjoint and a disjoint definition of the surprise. In section 3, I describe the solution to SEP corresponding to...

  12. The Value of Surprising Findings for Research on Marketing

    OpenAIRE

    JS Armstrong

    2004-01-01

    In the work of Armstrong (Journal of Business Research, 2002), I examined empirical research on the scientific process and related these to marketing science. The findings of some studies were surprising. In this reply, I address surprising findings and other issues raised by commentators.

  13. Corrugator Activity Confirms Immediate Negative Affect in Surprise

    Directory of Open Access Journals (Sweden)

    Sascha eTopolinski

    2015-02-01

    Full Text Available The emotion of surprise entails a complex of immediate responses, such as cognitive interruption, attention allocation to, and more systematic processing of the surprising stimulus. All these processes serve the ultimate function to increase processing depth and thus cognitively master the surprising stimulus. The present account introduces phasic negative affect as the underlying mechanism responsible for these consequences. Surprising stimuli are schema-discrepant and thus entail cognitive disfluency, which elicits immediate negative affect. This affect in turn works like a phasic cognitive tuning switching the current processing mode from more automatic and heuristic to more systematic and reflective processing. Directly testing the initial elicitation of negative affect by suprising events, the present experiment presented high and low surprising neutral trivia statements to N = 28 participants while assessing their spontaneous facial expressions via facial electromyography. High compared to low suprising trivia elicited higher corrugator activity, indicative of negative affect and mental effort, while leaving zygomaticus (positive affect and frontalis (cultural surprise expression activity unaffected. Future research shall investigate the mediating role of negative affect in eliciting surprise-related outcomes.

  14. Managing Uncertainity: Soviet Views on Deception, Surprise, and Control

    National Research Council Canada - National Science Library

    Hull, Andrew

    1989-01-01

    .... In the first two cases (deception and surprise), the emphasis is on how the Soviets seek to sow uncertainty in the minds of the enemy and how the Soviets then plan to use that uncertainty to gain military advantage...

  15. Dividend announcements reconsidered: Dividend changes versus dividend surprises

    OpenAIRE

    Andres, Christian; Betzer, André; van den Bongard, Inga; Haesner, Christian; Theissen, Erik

    2012-01-01

    This paper reconsiders the issue of share price reactions to dividend announcements. Previous papers rely almost exclusively on a naive dividend model in which the dividend change is used as a proxy for the dividend surprise. We use the difference between the actual dividend and the analyst consensus forecast as obtained from I/B/E/S as a proxy for the dividend surprise. Using data from Germany, we find significant share price reactions after dividend announcements. Once we control for analys...

  16. The Surprise Examination Paradox and the Second Incompleteness Theorem

    OpenAIRE

    Kritchman, Shira; Raz, Ran

    2010-01-01

    We give a new proof for Godel's second incompleteness theorem, based on Kolmogorov complexity, Chaitin's incompleteness theorem, and an argument that resembles the surprise examination paradox. We then go the other way around and suggest that the second incompleteness theorem gives a possible resolution of the surprise examination paradox. Roughly speaking, we argue that the flaw in the derivation of the paradox is that it contains a hidden assumption that one can prove the consistency of the...

  17. An efficient community detection algorithm using greedy surprise maximization

    International Nuclear Information System (INIS)

    Jiang, Yawen; Jia, Caiyan; Yu, Jian

    2014-01-01

    Community detection is an important and crucial problem in complex network analysis. Although classical modularity function optimization approaches are widely used for identifying communities, the modularity function (Q) suffers from its resolution limit. Recently, the surprise function (S) was experimentally proved to be better than the Q function. However, up until now, there has been no algorithm available to perform searches to directly determine the maximal surprise values. In this paper, considering the superiority of the S function over the Q function, we propose an efficient community detection algorithm called AGSO (algorithm based on greedy surprise optimization) and its improved version FAGSO (fast-AGSO), which are based on greedy surprise optimization and do not suffer from the resolution limit. In addition, (F)AGSO does not need the number of communities K to be specified in advance. Tests on experimental networks show that (F)AGSO is able to detect optimal partitions in both simple and even more complex networks. Moreover, algorithms based on surprise maximization perform better than those algorithms based on modularity maximization, including Blondel–Guillaume–Lambiotte–Lefebvre (BGLL), Clauset–Newman–Moore (CNM) and the other state-of-the-art algorithms such as Infomap, order statistics local optimization method (OSLOM) and label propagation algorithm (LPA). (paper)

  18. Surprise and Memory as Indices of Concrete Operational Development

    Science.gov (United States)

    Achenbach, Thomas M.

    1973-01-01

    Normal and retarded children's use of color, number, length and continuous quantity as attributes of identification was assessed by presenting them with contrived changes in three properties. Surprise and correct memory responses for color preceded those to number, which preceded logical verbal responses to a conventional number-conservation task.…

  19. 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...

  20. Surprisal analysis and probability matrices for rotational energy transfer

    International Nuclear Information System (INIS)

    Levine, R.D.; Bernstein, R.B.; Kahana, P.; Procaccia, I.; Upchurch, E.T.

    1976-01-01

    The information-theoretic approach is applied to the analysis of state-to-state rotational energy transfer cross sections. The rotational surprisal is evaluated in the usual way, in terms of the deviance of the cross sections from their reference (''prior'') values. The surprisal is found to be an essentially linear function of the energy transferred. This behavior accounts for the experimentally observed exponential gap law for the hydrogen halide systems. The data base here analyzed (taken from the literature) is largely computational in origin: quantal calculations for the hydrogenic systems H 2 +H, He, Li + ; HD+He; D 2 +H and for the N 2 +Ar system; and classical trajectory results for H 2 +Li + ; D 2 +Li + and N 2 +Ar. The surprisal analysis not only serves to compact a large body of data but also aids in the interpretation of the results. A single surprisal parameter theta/subR/ suffices to account for the (relative) magnitude of all state-to-state inelastic cross sections at a given energy

  1. Things may not be as expected: Surprising findings when updating ...

    African Journals Online (AJOL)

    2015-05-14

    May 14, 2015 ... Things may not be as expected: Surprising findings when updating .... (done at the end of three months after the first review month) ..... Allen G. Getting beyond form filling: The role of institutional governance in human research ...

  2. Automation surprise : results of a field survey of Dutch pilots

    NARCIS (Netherlands)

    de Boer, R.J.; Hurts, Karel

    2017-01-01

    Automation surprise (AS) has often been associated with aviation safety incidents. Although numerous laboratory studies have been conducted, few data are available from routine flight operations. A survey among a representative sample of 200 Dutch airline pilots was used to determine the prevalence

  3. 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...

  4. 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.

  5. ORMS IN SURPRISING PLACES: CLINICAL AND MORPHOLOGICAL FEATURES

    Directory of Open Access Journals (Sweden)

    Myroshnychenko MS

    2013-06-01

    Full Text Available Helminthes are the most common human diseases, which are characterized by involvement in the pathological process of all organs and systems. In this article, the authors discuss a few cases of typical and atypical localizations for parasitic worms such as filarial and pinworms which were recovered from surprising places in the bodies of patients in Kharkiv region. This article will allow the doctors of practical health care to pay special attention to the timely prevention and diagnostics of this pathology.

  6. On the surprising rigidity of the Pauli exclusion principle

    International Nuclear Information System (INIS)

    Greenberg, O.W.

    1989-01-01

    I review recent attempts to construct a local quantum field theory of small violations of the Pauli exclusion principle and suggest a qualitative reason for the surprising rigidity of the Pauli principle. I suggest that small violations can occur in our four-dimensional world as a consequence of the compactification of a higher-dimensional theory in which the exclusion principle is exactly valid. I briefly mention a recent experiment which places a severe limit on possible violations of the exclusion principle. (orig.)

  7. Teacher Supply and Demand: Surprises from Primary Research

    Directory of Open Access Journals (Sweden)

    Andrew J. Wayne

    2000-09-01

    Full Text Available An investigation of primary research studies on public school teacher supply and demand revealed four surprises. Projections show that enrollments are leveling off. Relatedly, annual hiring increases should be only about two or three percent over the next few years. Results from studies of teacher attrition also yield unexpected results. Excluding retirements, only about one in 20 teachers leaves each year, and the novice teachers who quit mainly cite personal and family reasons, not job dissatisfaction. Each of these findings broadens policy makers' options for teacher supply.

  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. 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...

  10. Surprises in the suddenly-expanded infinite well

    International Nuclear Information System (INIS)

    Aslangul, Claude

    2008-01-01

    I study the time evolution of a particle prepared in the ground state of an infinite well after the latter is suddenly expanded. It turns out that the probability density |Ψ(x, t)| 2 shows up quite a surprising behaviour: for definite times, plateaux appear for which |Ψ(x, t)| 2 is constant on finite intervals for x. Elements of theoretical explanation are given by analysing the singular component of the second derivative ∂ xx Ψ(x, t). Analytical closed expressions are obtained for some specific times, which easily allow us to show that, at these times, the density organizes itself into regular patterns provided the size of the box is large enough; more, above some critical size depending on the specific time, the density patterns are independent of the expansion parameter. It is seen how the density at these times simply results from a construction game with definite rules acting on the pieces of the initial density

  11. Hepatobiliary fascioliasis in non-endemic zones: a surprise diagnosis.

    Science.gov (United States)

    Jha, Ashish Kumar; Goenka, Mahesh Kumar; Goenka, Usha; Chakrabarti, Amrita

    2013-03-01

    Fascioliasis is a zoonotic infection caused by Fasciola hepatica. Because of population migration and international food trade, human fascioliasis is being an increasingly recognised entity in nonendemic zones. In most parts of Asia, hepatobiliary fascioliasis is sporadic. Human hepatobiliary infection by this trematode has two distinct phases: an acute hepatic phase and a chronic biliary phase. Hepatobiliary infection is mostly associated with intense peripheral eosinophilia. In addition to classically defined hepatic phase and biliary phase fascioliasis, some cases may have an overlap of these two phases. Chronic liver abscess formation is a rare presentation. We describe a surprise case of hepatobiliary fascioliasis who presented to us with liver abscess without intense peripheral eosinophilia, a rare presentation of human fascioliasis especially in non-endemic zones. Copyright © 2013 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.

  12. The Value of Change: Surprises and Insights in Stellar Evolution

    Science.gov (United States)

    Bildsten, Lars

    2018-01-01

    Astronomers with large-format cameras regularly scan the sky many times per night to detect what's changing, and telescopes in space such as Kepler and, soon, TESS obtain very accurate brightness measurements of nearly a million stars over time periods of years. These capabilities, in conjunction with theoretical and computational efforts, have yielded surprises and remarkable new insights into the internal properties of stars and how they end their lives. I will show how asteroseismology reveals the properties of the deep interiors of red giants, and highlight how astrophysical transients may be revealing unusual thermonuclear outcomes from exploding white dwarfs and the births of highly magnetic neutron stars. All the while, stellar science has been accelerated by the availability of open source tools, such as Modules for Experiments in Stellar Astrophysics (MESA), and the nearly immediate availability of observational results.

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

    International Nuclear Information System (INIS)

    Glantz, M.H.; Moore, C.M.; Streets, D.G.; Bhatti, N.; Rosa, C.H.

    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

  14. 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.

  15. 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.

  16. X-rays from comets - a surprising discovery

    CERN Document Server

    CERN. Geneva

    2000-01-01

    Comets are kilometre-size aggregates of ice and dust, which remained from the formation of the solar system. It was not obvious to expect X-ray emission from such objects. Nevertheless, when comet Hyakutake (C/1996 B2) was observed with the ROSAT X-ray satellite during its close approach to Earth in March 1996, bright X-ray emission from this comet was discovered. This finding triggered a search in archival ROSAT data for comets, which might have accidentally crossed the field of view during observations of unrelated targets. To increase the surprise even more, X-ray emission was detected from four additional comets, which were optically 300 to 30 000 times fainter than Hyakutake. For one of them, comet Arai (C/1991 A2), X-ray emission was even found in data which were taken six weeks before the comet was optically discovered. These findings showed that comets represent a new class of celestial X-ray sources. The subsequent detection of X-ray emission from several other comets in dedicated observations confir...

  17. Beyond surprise : A longitudinal study on the experience of visual-tactual incongruities in products

    NARCIS (Netherlands)

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

    2012-01-01

    When people encounter products with visual-tactual incongruities, they are likely to be surprised because the product feels different than expected. In this paper, we investigate (1) the relationship between surprise and the overall liking of the products, (2) the emotions associated with surprise,

  18. Surprising Incentive: An Instrument for Promoting Safety Performance of Construction Employees

    Directory of Open Access Journals (Sweden)

    Fakhradin Ghasemi

    2015-09-01

    Conclusion: The results of this study proved that the surprising incentive would improve the employees' safety performance just in the short term because the surprising value of the incentives dwindle over time. For this reason and to maintain the surprising value of the incentive system, the amount and types of incentives need to be evaluated and modified annually or biannually.

  19. The Role of Surprise in Game-Based Learning for Mathematics

    NARCIS (Netherlands)

    Wouters, Pieter; van Oostendorp, Herre; ter Vrugte, Judith; Vandercruysse, Sylke; de Jong, Anthonius J.M.; Elen, Jan; De Gloria, Alessandro; Veltkamp, Remco

    2016-01-01

    In this paper we investigate the potential of surprise on learning with prevocational students in the domain of proportional reasoning. Surprise involves an emotional reaction, but it also serves a cognitive goal as it directs attention to explain why the surprising event occurred and to learn for

  20. Human amygdala response to dynamic facial expressions of positive and negative surprise.

    Science.gov (United States)

    Vrticka, Pascal; Lordier, Lara; Bediou, Benoît; Sander, David

    2014-02-01

    Although brain imaging evidence accumulates to suggest that the amygdala plays a key role in the processing of novel stimuli, only little is known about its role in processing expressed novelty conveyed by surprised faces, and even less about possible interactive encoding of novelty and valence. Those investigations that have already probed human amygdala involvement in the processing of surprised facial expressions either used static pictures displaying negative surprise (as contained in fear) or "neutral" surprise, and manipulated valence by contextually priming or subjectively associating static surprise with either negative or positive information. Therefore, it still remains unresolved how the human amygdala differentially processes dynamic surprised facial expressions displaying either positive or negative surprise. Here, we created new artificial dynamic 3-dimensional facial expressions conveying surprise with an intrinsic positive (wonderment) or negative (fear) connotation, but also intrinsic positive (joy) or negative (anxiety) emotions not containing any surprise, in addition to neutral facial displays either containing ("typical surprise" expression) or not containing ("neutral") surprise. Results showed heightened amygdala activity to faces containing positive (vs. negative) surprise, which may either correspond to a specific wonderment effect as such, or to the computation of a negative expected value prediction error. Findings are discussed in the light of data obtained from a closely matched nonsocial lottery task, which revealed overlapping activity within the left amygdala to unexpected positive outcomes. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  1. 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,...

  2. 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

  3. 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

  4. 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

  5. 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

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

    Science.gov (United States)

    Wessel, Jan R

    2018-01-01

    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. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. 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

    2016-01-01

    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. PMID:26854903

  8. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. A Contrast-Based Computational Model of Surprise and Its Applications.

    Science.gov (United States)

    Macedo, Luis; Cardoso, Amílcar

    2017-11-19

    We review our work on a contrast-based computational model of surprise and its applications. The review is contextualized within related research from psychology, philosophy, and particularly artificial intelligence. Influenced by psychological theories of surprise, the model assumes that surprise-eliciting events initiate a series of cognitive processes that begin with the appraisal of the event as unexpected, continue with the interruption of ongoing activity and the focusing of attention on the unexpected event, and culminate in the analysis and evaluation of the event and the revision of beliefs. It is assumed that the intensity of surprise elicited by an event is a nonlinear function of the difference or contrast between the subjective probability of the event and that of the most probable alternative event (which is usually the expected event); and that the agent's behavior is partly controlled by actual and anticipated surprise. We describe applications of artificial agents that incorporate the proposed surprise model in three domains: the exploration of unknown environments, creativity, and intelligent transportation systems. These applications demonstrate the importance of surprise for decision making, active learning, creative reasoning, and selective attention. Copyright © 2017 Cognitive Science Society, Inc.

  10. 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.

  11. Summit surprises.

    Science.gov (United States)

    Myers, N

    1994-01-01

    A New Delhi Population Summit, organized by the Royal Society, the US National Academy of Sciences, the Royal Swedish Academy of Sciences, and the Indian National Science Academy, was convened with representation of 120 (only 10% women) scientists from 50 countries and about 12 disciplines and 43 national scientific academies. Despite the common assumption that scientists never agree, a 3000 word statement was signed by 50 prominent national figures and supported by 25 professional papers on diverse subjects. The statement proclaimed that stable world population and "prodigious planning efforts" are required for dealing with global social, economic, and environmental problems. The target should be zero population growth by the next generation. The statement, although containing many uncompromising assertions, was not as strong as a statement by the Royal Society and the US National Academy of Sciences released last year: that, in the future, science and technology may not be able to prevent "irreversible degradation of the environment and continued poverty," and that the capacity to sustain life on the planet may be permanently jeopardized. The Delhi statement was backed by professional papers highlighting several important issues. Dr Mahmoud Fathalla of the Rockefeller Foundation claimed that the 500,000 annual maternal deaths worldwide, of which perhaps 33% are due to "coathanger" abortions, are given far less attention than a one-day political event of 500 deaths would receive. Although biologically women have been given a greater survival advantage, which is associated with their reproductive capacity, socially disadvantaged females are relegated to low status. There is poorer nutrition and overall health care for females, female infanticide, and female fetuses are increasingly aborted in China, India, and other countries. The sex ratio in developed countries is 95-97 males to every 100 females, but in developing Asian countries the ratio is 105 males to 100 females. There are reports of 60-100 million missing females. The human species 12,000 years ago had a population of 6 million, a life expectancy of 20 years, and a doubling time of 8000 years; high birth rates were important for preservation of the species. Profertility attitudes are still prevalent today. Insufficient funds go to contraceptive research.

  12. Metaproteomics of cellulose methanisation under thermophilic conditions reveals a surprisingly high proteolytic activity.

    Science.gov (United States)

    Lü, Fan; Bize, Ariane; Guillot, Alain; Monnet, Véronique; Madigou, Céline; Chapleur, Olivier; Mazéas, Laurent; He, Pinjing; Bouchez, Théodore

    2014-01-01

    Cellulose is the most abundant biopolymer on Earth. Optimising energy recovery from this renewable but recalcitrant material is a key issue. The metaproteome expressed by thermophilic communities during cellulose anaerobic digestion was investigated in microcosms. By multiplying the analytical replicates (65 protein fractions analysed by MS/MS) and relying solely on public protein databases, more than 500 non-redundant protein functions were identified. The taxonomic community structure as inferred from the metaproteomic data set was in good overall agreement with 16S rRNA gene tag pyrosequencing and fluorescent in situ hybridisation analyses. Numerous functions related to cellulose and hemicellulose hydrolysis and fermentation catalysed by bacteria related to Caldicellulosiruptor spp. and Clostridium thermocellum were retrieved, indicating their key role in the cellulose-degradation process and also suggesting their complementary action. Despite the abundance of acetate as a major fermentation product, key methanogenesis enzymes from the acetoclastic pathway were not detected. In contrast, enzymes from the hydrogenotrophic pathway affiliated to Methanothermobacter were almost exclusively identified for methanogenesis, suggesting a syntrophic acetate oxidation process coupled to hydrogenotrophic methanogenesis. Isotopic analyses confirmed the high dominance of the hydrogenotrophic methanogenesis. Very surprising was the identification of an abundant proteolytic activity from Coprothermobacter proteolyticus strains, probably acting as scavenger and/or predator performing proteolysis and fermentation. Metaproteomics thus appeared as an efficient tool to unravel and characterise metabolic networks as well as ecological interactions during methanisation bioprocesses. More generally, metaproteomics provides direct functional insights at a limited cost, and its attractiveness should increase in the future as sequence databases are growing exponentially.

  13. 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

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

    OpenAIRE

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

    2016-01-01

    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...

  15. Ignorance, Vulnerability and the Occurrence of "Radical Surprises": Theoretical Reflections and Empirical Findings

    Science.gov (United States)

    Kuhlicke, C.

    2009-04-01

    By definition natural disasters always contain a moment of surprise. Their occurrence is mostly unforeseen and unexpected. They hit people unprepared, overwhelm them and expose their helplessness. Yet, there is surprisingly little known on the reasons for their being surprised. Aren't natural disasters expectable and foreseeable after all? Aren't the return rates of most hazards well known and shouldn't people be better prepared? The central question of this presentation is hence: Why do natural disasters so often radically surprise people at all (and how can we explain this being surprised)? In the first part of the presentation, it is argued that most approaches to vulnerability are not able to grasp this moment of surprise. On the contrary, they have their strength in unravelling the expectable: A person who is marginalized or even oppressed in everyday life is also vulnerable during times of crisis and stress, at least this is the central assumption of most vulnerability studies. In the second part, an understanding of vulnerability is developed, which allows taking into account such radical surprises. First, two forms of the unknown are differentiated: An area of the unknown an actor is more or less aware of (ignorance), and an area, which is not even known to be not known (nescience). The discovery of the latter is mostly associated with a "radical surprise", since it is per definition impossible to prepare for it. Second, a definition of vulnerability is proposed, which allows capturing the dynamics of surprises: People are vulnerable when they discover their nescience exceeding by definition previously established routines, stocks of knowledge and resources—in a general sense their capacities—to deal with their physical and/or social environment. This definition explicitly takes the view of different actors serious and departs from their being surprised. In the third part findings of a case study are presented, the 2002 flood in Germany. It is shown

  16. 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%.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Dealing with unexpected events on the flight deck : A conceptual model of startle and surprise

    NARCIS (Netherlands)

    Landman, H.M.; Groen, E.L.; Paassen, M.M. van; Bronkhorst, A.W.; Mulder, M.

    2017-01-01

    Objective: A conceptual model is proposed in order to explain pilot performance in surprising and startling situations. Background: Today’s debate around loss of control following in-flight events and the implementation of upset prevention and recovery training has highlighted the importance of

  4. 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…

  5. 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…

  6. Models of Automation surprise : results of a field survey in aviation

    NARCIS (Netherlands)

    De Boer, Robert; Dekker, Sidney

    2017-01-01

    Automation surprises in aviation continue to be a significant safety concern and the community’s search for effective strategies to mitigate them are ongoing. The literature has offered two fundamentally divergent directions, based on different ideas about the nature of cognition and collaboration

  7. Decision-making under surprise and uncertainty: Arsenic contamination of water supplies

    Science.gov (United States)

    Randhir, Timothy O.; Mozumder, Pallab; Halim, Nafisa

    2018-05-01

    With ignorance and potential surprise dominating decision making in water resources, a framework for dealing with such uncertainty is a critical need in hydrology. We operationalize the 'potential surprise' criterion proposed by Shackle, Vickers, and Katzner (SVK) to derive decision rules to manage water resources under uncertainty and ignorance. We apply this framework to managing water supply systems in Bangladesh that face severe, naturally occurring arsenic contamination. The uncertainty involved with arsenic in water supplies makes the application of conventional analysis of decision-making ineffective. Given the uncertainty and surprise involved in such cases, we find that optimal decisions tend to favor actions that avoid irreversible outcomes instead of conventional cost-effective actions. We observe that a diversification of the water supply system also emerges as a robust strategy to avert unintended outcomes of water contamination. Shallow wells had a slight higher optimal level (36%) compare to deep wells and surface treatment which had allocation levels of roughly 32% under each. The approach can be applied in a variety of other cases that involve decision making under uncertainty and surprise, a frequent situation in natural resources management.

  8. Surprising results: HIV testing and changes in contraceptive practices among young women in Malawi

    Science.gov (United States)

    Sennott, Christie; Yeatman, Sara

    2015-01-01

    This study uses eight waves of data from the population-based Tsogolo la Thanzi study (2009–2011) in rural Malawi to examine changes in young women’s contraceptive practices, including the use of condoms, non-barrier contraceptive methods, and abstinence, following positive and negative HIV tests. The analysis factors in women’s prior perceptions of their HIV status that may already be shaping their behaviour and separates surprise HIV test results from those that merely confirm what was already believed. Fixed effects logistic regression models show that HIV testing frequently affects the contraceptive practices of young Malawian women, particularly when the test yields an unexpected result. Specifically, women who are surprised to test HIV positive increase their condom use and are more likely to use condoms consistently. Following an HIV negative test (whether a surprise or expected), women increase their use of condoms and decrease their use of non-barrier contraceptives; the latter may be due to an increase in abstinence following a surprise negative result. Changes in condom use following HIV testing are robust to the inclusion of potential explanatory mechanisms including fertility preferences, relationship status, and the perception that a partner is HIV positive. The results demonstrate that both positive and negative tests can influence women’s sexual and reproductive behaviours, and emphasise the importance of conceptualizing of HIV testing as offering new information only insofar as results deviate from prior perceptions of HIV status. PMID:26160156

  9. 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…

  10. 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...

  11. Models of Automation Surprise: Results of a Field Survey in Aviation

    Directory of Open Access Journals (Sweden)

    Robert De Boer

    2017-09-01

    Full Text Available Automation surprises in aviation continue to be a significant safety concern and the community’s search for effective strategies to mitigate them are ongoing. The literature has offered two fundamentally divergent directions, based on different ideas about the nature of cognition and collaboration with automation. In this paper, we report the results of a field study that empirically compared and contrasted two models of automation surprises: a normative individual-cognition model and a sensemaking model based on distributed cognition. Our data prove a good fit for the sense-making model. This finding is relevant for aviation safety, since our understanding of the cognitive processes that govern human interaction with automation drive what we need to do to reduce the frequency of automation-induced events.

  12. Human Amygdala Tracks a Feature-Based Valence Signal Embedded within the Facial Expression of Surprise.

    Science.gov (United States)

    Kim, M Justin; Mattek, Alison M; Bennett, Randi H; Solomon, Kimberly M; Shin, Jin; Whalen, Paul J

    2017-09-27

    Human amygdala function has been traditionally associated with processing the affective valence (negative vs positive) of an emotionally charged event, especially those that signal fear or threat. However, this account of human amygdala function can be explained by alternative views, which posit that the amygdala might be tuned to either (1) general emotional arousal (activation vs deactivation) or (2) specific emotion categories (fear vs happy). Delineating the pure effects of valence independent of arousal or emotion category is a challenging task, given that these variables naturally covary under many circumstances. To circumvent this issue and test the sensitivity of the human amygdala to valence values specifically, we measured the dimension of valence within the single facial expression category of surprise. Given the inherent valence ambiguity of this category, we show that surprised expression exemplars are attributed valence and arousal values that are uniquely and naturally uncorrelated. We then present fMRI data from both sexes, showing that the amygdala tracks these consensus valence values. Finally, we provide evidence that these valence values are linked to specific visual features of the mouth region, isolating the signal by which the amygdala detects this valence information. SIGNIFICANCE STATEMENT There is an open question as to whether human amygdala function tracks the valence value of cues in the environment, as opposed to either a more general emotional arousal value or a more specific emotion category distinction. Here, we demonstrate the utility of surprised facial expressions because exemplars within this emotion category take on valence values spanning the dimension of bipolar valence (positive to negative) at a consistent level of emotional arousal. Functional neuroimaging data showed that amygdala responses tracked the valence of surprised facial expressions, unconfounded by arousal. Furthermore, a machine learning classifier identified

  13. Prediction, Expectation, and Surprise: Methods, Designs, and Study of a Deployed Traffic Forecasting Service

    OpenAIRE

    Horvitz, Eric J.; Apacible, Johnson; Sarin, Raman; Liao, Lin

    2012-01-01

    We present research on developing models that forecast traffic flow and congestion in the Greater Seattle area. The research has led to the deployment of a service named JamBayes, that is being actively used by over 2,500 users via smartphones and desktop versions of the system. We review the modeling effort and describe experiments probing the predictive accuracy of the models. Finally, we present research on building models that can identify current and future surprises, via efforts on mode...

  14. The effect of emotionally valenced eye region images on visuocortical processing of surprised faces.

    Science.gov (United States)

    Li, Shuaixia; Li, Ping; Wang, Wei; Zhu, Xiangru; Luo, Wenbo

    2018-05-01

    In this study, we presented pictorial representations of happy, neutral, and fearful expressions projected in the eye regions to determine whether the eye region alone is sufficient to produce a context effect. Participants were asked to judge the valence of surprised faces that had been preceded by a picture of an eye region. Behavioral results showed that affective ratings of surprised faces were context dependent. Prime-related ERPs with presentation of happy eyes elicited a larger P1 than those for neutral and fearful eyes, likely due to the recognition advantage provided by a happy expression. Target-related ERPs showed that surprised faces in the context of fearful and happy eyes elicited dramatically larger C1 than those in the neutral context, which reflected the modulation by predictions during the earliest stages of face processing. There were larger N170 with neutral and fearful eye contexts compared to the happy context, suggesting faces were being integrated with contextual threat information. The P3 component exhibited enhanced brain activity in response to faces preceded by happy and fearful eyes compared with neutral eyes, indicating motivated attention processing may be involved at this stage. Altogether, these results indicate for the first time that the influence of isolated eye regions on the perception of surprised faces involves preferential processing at the early stages and elaborate processing at the late stages. Moreover, higher cognitive processes such as predictions and attention can modulate face processing from the earliest stages in a top-down manner. © 2017 Society for Psychophysiological Research.

  15. Analysis of physiological signals for recognition of boredom, pain, and surprise emotions.

    Science.gov (United States)

    Jang, Eun-Hye; Park, Byoung-Jun; Park, Mi-Sook; Kim, Sang-Hyeob; Sohn, Jin-Hun

    2015-06-18

    The aim of the study was to examine the differences of boredom, pain, and surprise. In addition to that, it was conducted to propose approaches for emotion recognition based on physiological signals. Three emotions, boredom, pain, and surprise, are induced through the presentation of emotional stimuli and electrocardiography (ECG), electrodermal activity (EDA), skin temperature (SKT), and photoplethysmography (PPG) as physiological signals are measured to collect a dataset from 217 participants when experiencing the emotions. Twenty-seven physiological features are extracted from the signals to classify the three emotions. The discriminant function analysis (DFA) as a statistical method, and five machine learning algorithms (linear discriminant analysis (LDA), classification and regression trees (CART), self-organizing map (SOM), Naïve Bayes algorithm, and support vector machine (SVM)) are used for classifying the emotions. The result shows that the difference of physiological responses among emotions is significant in heart rate (HR), skin conductance level (SCL), skin conductance response (SCR), mean skin temperature (meanSKT), blood volume pulse (BVP), and pulse transit time (PTT), and the highest recognition accuracy of 84.7% is obtained by using DFA. This study demonstrates the differences of boredom, pain, and surprise and the best emotion recognizer for the classification of the three emotions by using physiological signals.

  16. Spatiotemporal neural characterization of prediction error valence and surprise during reward learning in humans.

    Science.gov (United States)

    Fouragnan, Elsa; Queirazza, Filippo; Retzler, Chris; Mullinger, Karen J; Philiastides, Marios G

    2017-07-06

    Reward learning depends on accurate reward associations with potential choices. These associations can be attained with reinforcement learning mechanisms using a reward prediction error (RPE) signal (the difference between actual and expected rewards) for updating future reward expectations. Despite an extensive body of literature on the influence of RPE on learning, little has been done to investigate the potentially separate contributions of RPE valence (positive or negative) and surprise (absolute degree of deviation from expectations). Here, we coupled single-trial electroencephalography with simultaneously acquired fMRI, during a probabilistic reversal-learning task, to offer evidence of temporally overlapping but largely distinct spatial representations of RPE valence and surprise. Electrophysiological variability in RPE valence correlated with activity in regions of the human reward network promoting approach or avoidance learning. Electrophysiological variability in RPE surprise correlated primarily with activity in regions of the human attentional network controlling the speed of learning. Crucially, despite the largely separate spatial extend of these representations our EEG-informed fMRI approach uniquely revealed a linear superposition of the two RPE components in a smaller network encompassing visuo-mnemonic and reward areas. Activity in this network was further predictive of stimulus value updating indicating a comparable contribution of both signals to reward learning.

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

    Science.gov (United States)

    Parry, Amy; Fearnley, Emily; Denehy, Emma

    2012-10-01

    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. 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. 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. 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.

  18. 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.

  19. The influence of the surprising decay properties of element 108 on search experiments for new elements

    International Nuclear Information System (INIS)

    Hofmann, S.; Armbruster, P.; Muenzenberg, G.; Reisdorf, W.; Schmidt, K.H.; Burkhard, H.G.; Hessberger, F.P.; Schoett, H.J.; Agarwal, Y.K.; Berthes, G.; Gollerthan, U.; Folger, H.; Hingmann, J.G.; Keller, J.G.; Leino, M.E.; Lemmertz, P.; Montoya, M.; Poppensieker, K.; Quint, B.; Zychor, I.

    1986-01-01

    Results of experiments to synthesize the heaviest elements are reported. Surprising is the high stability against fission not only of the odd and odd-odd nuclei but also of even isotopes of even elements. Alpha decay data gave an increasing stability of nuclei by shell effects up to 266 109, the heaviest known element. Theoretically, the high stability is explained by an island of nuclei with big quadrupole and hexadecapole deformations around Z=109 and N=162. Future experiments will be planned to prove the island character of these heavy nuclei. (orig.)

  20. Surprisal analysis of Glioblastoma Multiform (GBM) microRNA dynamics unveils tumor specific phenotype.

    Science.gov (United States)

    Zadran, Sohila; Remacle, Francoise; Levine, Raphael

    2014-01-01

    Gliomablastoma multiform (GBM) is the most fatal form of all brain cancers in humans. Currently there are limited diagnostic tools for GBM detection. Here, we applied surprisal analysis, a theory grounded in thermodynamics, to unveil how biomolecule energetics, specifically a redistribution of free energy amongst microRNAs (miRNAs), results in a system deviating from a non-cancer state to the GBM cancer -specific phenotypic state. Utilizing global miRNA microarray expression data of normal and GBM patients tumors, surprisal analysis characterizes a miRNA system response capable of distinguishing GBM samples from normal tissue biopsy samples. We indicate that the miRNAs contributing to this system behavior is a disease phenotypic state specific to GBM and is therefore a unique GBM-specific thermodynamic signature. MiRNAs implicated in the regulation of stochastic signaling processes crucial in the hallmarks of human cancer, dominate this GBM-cancer phenotypic state. With this theory, we were able to distinguish with high fidelity GBM patients solely by monitoring the dynamics of miRNAs present in patients' biopsy samples. We anticipate that the GBM-specific thermodynamic signature will provide a critical translational tool in better characterizing cancer types and in the development of future therapeutics for GBM.

  1. Cloud Surprises in Moving NASA EOSDIS Applications into Amazon Web Services

    Science.gov (United States)

    Mclaughlin, Brett

    2017-01-01

    NASA ESDIS has been moving a variety of data ingest, distribution, and science data processing applications into a cloud environment over the last 2 years. As expected, there have been a number of challenges in migrating primarily on-premises applications into a cloud-based environment, related to architecture and taking advantage of cloud-based services. What was not expected is a number of issues that were beyond purely technical application re-architectures. We ran into surprising network policy limitations, billing challenges in a government-based cost model, and difficulty in obtaining certificates in an NASA security-compliant manner. On the other hand, this approach has allowed us to move a number of applications from local hosting to the cloud in a matter of hours (yes, hours!!), and our CMR application now services 95% of granule searches and an astonishing 99% of all collection searches in under a second. And most surprising of all, well, you'll just have to wait and see the realization that caught our entire team off guard!

  2. Vascular legacy: HOPE ADVANCEs to EMPA-REG and LEADER: A Surprising similarity

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2017-01-01

    Full Text Available Recently reported cardiovascular outcome studies on empagliflozin (EMPA-REG and liraglutide (LEADER have spurred interest in this field of diabetology. This commentary compares and contrasts these studies with two equally important outcome trials conducted using blood pressure lowering agents. A comparison with MICROHOPE (using ramipril and ADVANCE (using perindopril + indapamide blood pressure arms throws up interesting facts. The degree of blood pressure lowering, dissociation between cardiovascular and cerebrovascular benefits, and discordance between renal and retinal outcomes are surprisingly similar in these trials, conducted using disparate molecules. The time taken to achieve such benefits is similar for all drugs except empagliflozin. Such discussion helps inform rational and evidence-based choice of therapy and forms the framework for future research.

  3. Self-organizing weights for Internet AS-graphs and surprisingly simple routing metrics

    DEFF Research Database (Denmark)

    Scholz, Jan Carsten; Greiner, Martin

    2011-01-01

    The transport capacity of Internet-like communication networks and hence their efficiency may be improved by a factor of 5–10 through the use of highly optimized routing metrics, as demonstrated previously. The numerical determination of such routing metrics can be computationally demanding...... to an extent that prohibits both investigation of and application to very large networks. In an attempt to find a numerically less expensive way of constructing a metric with a comparable performance increase, we propose a local, self-organizing iteration scheme and find two surprisingly simple and efficient...... metrics. The new metrics have negligible computational cost and result in an approximately 5-fold performance increase, providing distinguished competitiveness with the computationally costly counterparts. They are applicable to very large networks and easy to implement in today's Internet routing...

  4. 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.

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

    KAUST Repository

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

    2015-01-01

    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.

  6. 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

  7. Hillslope, river, and Mountain: some surprises in Landscape evolution (Ralph Alger Bagnold Medal Lecture)

    Science.gov (United States)

    Tucker, G. E.

    2012-04-01

    Geomorphology, like the rest of geoscience, has always had two major themes: a quest to understand the earth's history and 'products' - its landscapes and seascapes - and, in parallel, a quest to understand its formative processes. This dualism is manifest in the remarkable career of R. A. Bagnold, who was inspired by landforms such as dunes, and dedicated to understanding the physical processes that shaped them. His legacy inspires us to emulate two principles at the heart of his contributions: the benefits of rooting geomorphic theory in basic physics, and the importance of understanding geomorphic systems in terms of simple equations framed around energy or force. Today, following Bagnold's footsteps, the earth-surface process community is engaged in a quest to build, test, and refine an ever-improving body of theory to describe our planet's surface and its evolution. In this lecture, I review a small sample of some of the fruits of that quest, emphasizing the value of surprises encountered along the way. The first example involves models of long-term river incision into bedrock. When the community began to grapple with how to represent this process mathematically, several different ideas emerged. Some were based on the assumption that sediment transport is the limiting factor; others assumed that hydraulic stress on rock is the key, while still others treated rivers as first-order 'reactors.' Thanks in part to advances in digital topography and numerical computing, the predictions of these models can be tested using natural-experiment case studies. Examples from the King Range, USA, the Central Apennines, Italy, and the fold-thrust belt of Taiwan, illustrate that independent knowledge of history and/or tectonics makes it possible to quantify how the rivers have responded to external forcing. Some interesting surprises emerge, such as: that the relief-uplift relationship can be highly nonlinear in a steady-state landscape because of grain-entrainment thresholds

  8. Cerebral metastasis masquerading as cerebritis: A case of misguiding history and radiological surprise!

    Directory of Open Access Journals (Sweden)

    Ashish Kumar

    2013-01-01

    Full Text Available Cerebral metastases usually have a characteristic radiological appearance. They can be differentiated rather easily from any infective etiology. Similarly, positive medical history also guides the neurosurgeon towards the possible diagnosis and adds to the diagnostic armamentarium. However, occasionally, similarities on imaging may be encountered where even history could lead us in the wrong direction and tends to bias the clinician. We report a case of a 40-year-old female with a history of mastoidectomy for otitis media presenting to us with a space occupying lesion in the right parietal region, which was thought pre-operatively as an abscess along with the cerebritis. Surprisingly, the histopathology proved it to be a metastatic adenocarcinoma. Hence, a ring enhancing lesion may be a high grade neoplasm/metastasis/abscess, significant gyral enhancement; a feature of cerebritis is not linked with a neoplastic etiology more often. This may lead to delayed diagnosis, incorrect prognostication and treatment in patients having coincidental suggestive history of infection. We review the literature and highlight the key points helping to differentiate an infective from a neoplastic pathology which may look similar at times.

  9. Beyond interests and institutions: US health policy reform and the surprising silence of big business.

    Science.gov (United States)

    Smyrl, Marc E

    2014-02-01

    Interest-based arguments do not provide satisfying explanations for the surprising reticence of major US employers to take a more active role in the debate surrounding the 2010 Patient Protection and Affordable Care Act (ACA). Through focused comparison with the Bismarckian systems of France and Germany, on the one hand, and with the 1950s and 1960s in the United States, on the other, this article concludes that while institutional elements do account for some of the observed behavior of big business, a necessary complement to this is a fuller understanding of the historically determined legitimating ideology of US firms. From the era of the "corporate commonwealth," US business inherited the principles of private welfare provision and of resistance to any expansion of government control. Once complementary, these principles are now mutually exclusive: employer-provided health insurance increasingly is possible only at the cost of ever-increasing government subsidy and regulation. Paralyzed by the uncertainty that followed from this clash of legitimate ideas, major employers found themselves unable to take a coherent and unified stand for or against the law. As a consequence, they failed either to oppose it successfully or to secure modifications to it that would have been useful to them.

  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. Pseudohalide (SCN(-))-Doped MAPbI3 Perovskites: A Few Surprises.

    Science.gov (United States)

    Halder, Ansuman; Chulliyil, Ramya; Subbiah, Anand S; Khan, Tuhin; Chattoraj, Shyamtanu; Chowdhury, Arindam; Sarkar, Shaibal K

    2015-09-03

    Pseudohalide thiocyanate anion (SCN(-)) has been used as a dopant in a methylammonium lead tri-iodide (MAPbI3) framework, aiming for its use as an absorber layer for photovoltaic applications. The substitution of SCN(-) pseudohalide anion, as verified using Fourier transform infrared (FT-IR) spectroscopy, results in a comprehensive effect on the optical properties of the original material. Photoluminescence measurements at room temperature reveal a significant enhancement in the emission quantum yield of MAPbI3-x(SCN)x as compared to MAPbI3, suggestive of suppression of nonradiative channels. This increased intensity is attributed to a highly edge specific emission from MAPbI3-x(SCN)x microcrystals as revealed by photoluminescence microscopy. Fluoresence lifetime imaging measurements further established contrasting carrier recombination dynamics for grain boundaries and the bulk of the doped material. Spatially resolved emission spectroscopy on individual microcrystals of MAPbI3-x(SCN)x reveals that the optical bandgap and density of states at various (local) nanodomains are also nonuniform. Surprisingly, several (local) emissive regions within MAPbI3-x(SCN)x microcrystals are found to be optically unstable under photoirradiation, and display unambiguous temporal intermittency in emission (blinking), which is extremely unusual and intriguing. We find diverse blinking behaviors for the undoped MAPbI3 crystals as well, which leads us to speculate that blinking may be a common phenomenon for most hybrid perovskite materials.

  12. Surprises from a Deep ASCA Spectrum of the Broad Absorption Line Quasar PHL 5200

    Science.gov (United States)

    Mathur, Smita; Matt, G.; Green, P. J.; Elvis, M.; Singh, K. P.

    2002-01-01

    We present a deep (approx. 85 ks) ASCA observation of the prototype broad absorption line quasar (BALQSO) PHL 5200. This is the best X-ray spectrum of a BALQSO yet. We find the following: (1) The source is not intrinsically X-ray weak. (2) The line-of-sight absorption is very strong, with N(sub H) = 5 x 10(exp 23)/sq cm. (3) The absorber does not cover the source completely; the covering fraction is approx. 90%. This is consistent with the large optical polarization observed in this source, implying multiple lines of sight. The most surprising result of this observation is that (4) the spectrum of this BALQSO is not exactly similar to other radio-quiet quasars. The hard X-ray spectrum of PHL 5200 is steep, with the power-law spectral index alpha approx. 1.5. This is similar to the steepest hard X-ray slopes observed so far. At low redshifts, such steep slopes are observed in narrow-line Seyfert 1 (NLS1) galaxies, believed to be accreting at a high Eddington rate. This observation strengthens the analogy between BALQSOs and NLS1 galaxies and supports the hypothesis that BALQSOs represent an early evolutionary state of quasars. It is well accepted that the orientation to the line of sight determines the appearance of a quasar: age seems to play a significant role as well.

  13. From Lithium-Ion to Sodium-Ion Batteries: Advantages, Challenges, and Surprises.

    Science.gov (United States)

    Nayak, Prasant Kumar; Yang, Liangtao; Brehm, Wolfgang; Adelhelm, Philipp

    2018-01-02

    Mobile and stationary energy storage by rechargeable batteries is a topic of broad societal and economical relevance. Lithium-ion battery (LIB) technology is at the forefront of the development, but a massively growing market will likely put severe pressure on resources and supply chains. Recently, sodium-ion batteries (SIBs) have been reconsidered with the aim of providing a lower-cost alternative that is less susceptible to resource and supply risks. On paper, the replacement of lithium by sodium in a battery seems straightforward at first, but unpredictable surprises are often found in practice. What happens when replacing lithium by sodium in electrode reactions? This review provides a state-of-the art overview on the redox behavior of materials when used as electrodes in lithium-ion and sodium-ion batteries, respectively. Advantages and challenges related to the use of sodium instead of lithium are discussed. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Effect of Temperature Shock and Inventory Surprises on Natural Gas and Heating Oil Futures Returns

    Science.gov (United States)

    Hu, John Wei-Shan; Lin, Chien-Yu

    2014-01-01

    The aim of this paper is to examine the impact of temperature shock on both near-month and far-month natural gas and heating oil futures returns by extending the weather and storage models of the previous study. Several notable findings from the empirical studies are presented. First, the expected temperature shock significantly and positively affects both the near-month and far-month natural gas and heating oil futures returns. Next, significant temperature shock has effect on both the conditional mean and volatility of natural gas and heating oil prices. The results indicate that expected inventory surprises significantly and negatively affects the far-month natural gas futures returns. Moreover, volatility of natural gas futures returns is higher on Thursdays and that of near-month heating oil futures returns is higher on Wednesdays than other days. Finally, it is found that storage announcement for natural gas significantly affects near-month and far-month natural gas futures returns. Furthermore, both natural gas and heating oil futures returns are affected more by the weighted average temperature reported by multiple weather reporting stations than that reported by a single weather reporting station. PMID:25133233

  15. Surprises from the resolution of operator mixing in N=4 SYM

    International Nuclear Information System (INIS)

    Bianchi, Massimo; Rossi, Giancarlo; Stanev, Yassen S.

    2004-01-01

    We reexamine the problem of operator mixing in N=4 SYM. Particular attention is paid to the correct definition of composite gauge invariant local operators, which is necessary for the computation of their anomalous dimensions beyond lowest order. As an application we reconsider the case of operators with naive dimension Δ 0 =4, already studied in the literature. Stringent constraints from the resummation of logarithms in power behaviours are exploited and the role of the generalized N=4 Konishi anomaly in the mixing with operators involving fermions is discussed. A general method for the explicit (numerical) resolution of the operator mixing and the computation of anomalous dimensions is proposed. We then resolve the order g 2 mixing for the 15 (purely scalar) singlet operators of naive dimension Δ 0 =6. Rather surprisingly we find one isolated operator which has a vanishing anomalous dimension up to order g 4 , belonging to an apparently long multiplet. We also solve the order g 2 mixing for the 26 operators belonging to the representation 20' of SU(4). We find an operator with the same one-loop anomalous dimension as the Konishi multiplet

  16. The Ultraviolet Surprise. Efficient Soft X-Ray High Harmonic Generation in Multiply-Ionized Plasmas

    International Nuclear Information System (INIS)

    Popmintchev, Dimitar; Hernandez-Garcia, Carlos; Dollar, Franklin; Mancuso, Christopher; Perez-Hernandez, Jose A.; Chen, Ming-Chang; Hankla, Amelia; Gao, Xiaohui; Shim, Bonggu; Gaeta, Alexander L.; Tarazkar, Maryam; Romanov, Dmitri A.; Levis, Robert J.; Gaffney, Jim A.; Foord, Mark; Libby, Stephen B.; Jaron-Becker, Agnieskzka; Becker, Andreas; Plaja, Luis; Muranane, Margaret M.; Kapteyn, Henry C.; Popmintchev, Tenio

    2015-01-01

    High-harmonic generation is a universal response of matter to strong femtosecond laser fields, coherently upconverting light to much shorter wavelengths. Optimizing the conversion of laser light into soft x-rays typically demands a trade-off between two competing factors. Reduced quantum diffusion of the radiating electron wave function results in emission from each species which is highest when a short-wavelength ultraviolet driving laser is used. But, phase matching - the constructive addition of x-ray waves from a large number of atoms - favors longer-wavelength mid-infrared lasers. We identified a regime of high-harmonic generation driven by 40-cycle ultraviolet lasers in waveguides that can generate bright beams in the soft x-ray region of the spectrum, up to photon energies of 280 electron volts. Surprisingly, the high ultraviolet refractive indices of both neutral atoms and ions enabled effective phase matching, even in a multiply ionized plasma. We observed harmonics with very narrow linewidths, while calculations show that the x-rays emerge as nearly time-bandwidt-limited pulse trains of ~100 attoseconds

  17. Gene cluster statistics with gene families.

    Science.gov (United States)

    Raghupathy, Narayanan; Durand, Dannie

    2009-05-01

    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

  18. A conceptual geochemical model of the geothermal system at Surprise Valley, CA

    Science.gov (United States)

    Fowler, Andrew P. G.; Ferguson, Colin; Cantwell, Carolyn A.; Zierenberg, Robert A.; McClain, James; Spycher, Nicolas; Dobson, Patrick

    2018-03-01

    Characterizing the geothermal system at Surprise Valley (SV), northeastern California, is important for determining the sustainability of the energy resource, and mitigating hazards associated with hydrothermal eruptions that last occurred in 1951. Previous geochemical studies of the area attempted to reconcile different hot spring compositions on the western and eastern sides of the valley using scenarios of dilution, equilibration at low temperatures, surface evaporation, and differences in rock type along flow paths. These models were primarily supported using classical geothermometry methods, and generally assumed that fluids in the Lake City mud volcano area on the western side of the valley best reflect the composition of a deep geothermal fluid. In this contribution, we address controls on hot spring compositions using a different suite of geochemical tools, including optimized multicomponent geochemistry (GeoT) models, hot spring fluid major and trace element measurements, mineralogical observations, and stable isotope measurements of hot spring fluids and precipitated carbonates. We synthesize the results into a conceptual geochemical model of the Surprise Valley geothermal system, and show that high-temperature (quartz, Na/K, Na/K/Ca) classical geothermometers fail to predict maximum subsurface temperatures because fluids re-equilibrated at progressively lower temperatures during outflow, including in the Lake City area. We propose a model where hot spring fluids originate as a mixture between a deep thermal brine and modern meteoric fluids, with a seasonally variable mixing ratio. The deep brine has deuterium values at least 3 to 4‰ lighter than any known groundwater or high-elevation snow previously measured in and adjacent to SV, suggesting it was recharged during the Pleistocene when meteoric fluids had lower deuterium values. The deuterium values and compositional characteristics of the deep brine have only been identified in thermal springs and

  19. 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.

  20. [Fall from height--surprising autopsy diagnosis in primarily unclear initial situations].

    Science.gov (United States)

    Schyma, Christian; Doberentz, Elke; Madea, Burkhard

    2012-01-01

    External post-mortem examination and first police assessments are often not consistent with subsequent autopsy results. This is all the more surprising the more serious the injuries found at autopsy are. Such discrepancies result especially from an absence of gross external injuries, as demonstrated by four examples. A 42-year-old, externally uninjured male was found at night time in a helpless condition in the street and died in spite of resuscitation. Autopsy showed severe polytrauma with traumatic brain injury and lesions of the thoracic and abdominal organs. A jump from the third floor was identified as the cause. At dawn, a twenty-year-old male was found dead on the grounds of the adjacent house. Because of the blood-covered head the police assumed a traumatic head injury by strike impact. The external examination revealed only abrasions on the forehead and to a minor extent on the back. At autopsy a midfacial fracture, a trauma of the thorax and abdomen and fractures of the spine and pelvis were detected. Afterwards investigations showed that the man, intoxicated by alcohol, had fallen from the flat roof of a multistoried house. A 77-year-old man was found unconscious on his terrace at day time; a cerebral seizure was assumed. He was transferred to emergency care where he died. The corpse was externally inconspicuous. Autopsy revealed serious traumatic injuries of the brain, thorax, abdomen and pelvis, which could be explained by a fall from the balcony. A 47-year-old homeless person without any external injuries was found dead in a barn. An alcohol intoxication was assumed. At autopsy severe injuries of the brain and cervical spine were found which were the result of a fall from a height of 5 m. On the basis of an external post-mortem examination alone gross blunt force trauma cannot be reliably excluded.

  1. 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

  2. Technological monitoring radar: a weak signals interpretation tool for the identification of strategic surprises

    Directory of Open Access Journals (Sweden)

    Adalton Ozaki

    2011-07-01

    Full Text Available In the current competitive scenario, marked by rapid and constant changes, it is vital that companies actively monitor the business environment, in search of signs which might anticipate changes. This study poses to propose and discuss a tool called Technological Monitoring Radar, which endeavours to address the following query: “How can a company systematically monitor the environment and capture signs that anticipate opportunities and threats concerning a particular technology?”. The literature review covers Competitive Intelligence, Technological Intelligence, Environmental Analysis and Anticipative Monitoring. Based on the critical analysis of the literature, a tool called Technological Monitoring Radar is proposed comprising five environments to be monitored (political, economical, technological, social and competition each of which with key topics for analysis. To exemplify the use of the tool, it is applied to the smartphone segment in an exclusively reflexive manner, and without the participation of a specific company. One of the suggestions for future research is precisely the application of the proposed methodology in an actual company. Despite the limitation of this being a theoretical study, the example demonstrated the tool´s applicability. The radar prove to be very useful for a company that needs to monitor the environment in search of signs of change. This study´s main contribution is to relate different fields of study (technological intelligence, environmental analysis and anticipative monitoring and different approaches to provide a practical tool that allows a manager to identify and better visualize opportunities and threats, thus avoiding strategic surprises in the technological arena.Key words: Technological monitoring. Technological intelligence. Competitive intelligence. Weak signals.

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

    Energy Technology Data Exchange (ETDEWEB)

    Aklujkar, Muktak [University of Massachusetts, Amherst; Haveman, Shelley [University of Massachusetts, Amherst; DiDonatoJr, Raymond [University of Massachusetts, Amherst; Chertkov, Olga [Los Alamos National Laboratory (LANL); Han, Cliff [Los Alamos National Laboratory (LANL); Land, Miriam L [ORNL; Brown, Peter [University of Massachusetts, Amherst; Lovley, Derek [University of Massachusetts, Amherst

    2012-01-01

    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.

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

    Science.gov (United States)

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

    2017-08-01

    Nuclear quantum effects in liquid water have profound implications for several of its macroscopic properties related to the structure, dynamics, spectroscopy, and transport. Although several of water's macroscopic properties can be reproduced by classical descriptions of the nuclei using interaction potentials effectively parameterized for a narrow range of its phase diagram, a proper account of the nuclear quantum effects is required 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 (qm) descriptions of the nuclei with two interaction potentials that are at the two opposite ends of the range in describing quantum effects, namely the flexible, pair-wise additive q-TIP4P/F, and the flexible, polarizable TTM3-F, we found that the (class) and (qm) results can be superimposed over the temperature range T = 250-350 K using a surprisingly simple, linear scaling of the two temperatures according to T(qm) = α T(class) + ΔT, where α = 0.99 and ΔT = -6 K for q-TIP4P/F and α = 1.24 and ΔT = -64 K for TTM3-F. This simple relationship suggests that the structural networks resulting from the quantum and classical treatment of the nuclei with those two very different interaction potentials are essentially similar to each other over this extended temperature range once a model-dependent linear temperature scaling law is applied.

  5. 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 ...

  6. Modern Sedimentation along the SE Bangladesh Coast Reveal Surprisingly Low Accumulation Rates

    Science.gov (United States)

    McHugh, C.; Mustaque, S.; Mondal, D. R.; Akhter, S. H.; Iqbal, M.

    2016-12-01

    Recent sediments recovered along the SE coast of Bangladesh, from Teknaf to Cox's Bazar and drainage basin analyses reveal sediment sources and very low sedimentation rates of 1mm/year. These low rates are surprisingly low given that this coast is adjacent to the Ganges-Brahmaputra Delta with a yearly discharge of 1GT. The Teknaf anticline (elevation 200 m), part of the western Burma fold-thrust belt dominates the topography extending across and along the Teknaf peninsula. It is thought to have begun evolving since the Miocene (Alam et al. 2003 & Allen et al. 2008). Presently the anticline foothills on the west are flanked by uplifted terraces, the youngest linked to coseismic displacement during the 1762 earthquake (Mondal et al. 2015), and a narrow beach 60-200 m in width. Petrography, semi-quantitative bulk mineralogy and SEM/EDX analyses were conducted on sediments recovered along the west coast from 1-4 m deep trenches and three 4-8 m deep drill holes. GIS mapping of drainage basins and quartz-feldspar-lithic (QFL) ternary plots based on grain counting show mixing of sediments from multiple sources: Himalayan provenance of metamorphic and igneous origin (garnet-mostly almandine, tourmaline, rutile, kyanite, zircon, sillimanite and clinopyroxene) similar to Uddin et al. (2007); Brahmaputra provenance of igneous and metamorphic origin (amphibole, epidote, plagioclase 40% Na and 60% Ca, apatite, ilmenite, magnetite, Cr-spinel and garnet-mostly grossular,) as indicated by Garzanti et al. (2010) & Rahman et al. (2016) and Burmese sources (cassiterite and wolframite) (Zaw 1990 & Searle et al. 2007). Low sedimentation rates are the result of two main factors: 1. Strong longshore currents from the south-east that interact with high tidal ranges as evidenced by the morphology of sand waves and ridge and runnel landforms along the beach. 2. Streams draining the Teknaf anticline are dry during the winter and during summer monsoon rains, the sediments bypass the narrow

  7. 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

  8. Cloud Surprises Discovered in Moving NASA EOSDIS Applications into Amazon Web Services… and #6 Will Shock You!

    Science.gov (United States)

    McLaughlin, B. D.; Pawloski, A. W.

    2017-12-01

    NASA ESDIS has been moving a variety of data ingest, distribution, and science data processing applications into a cloud environment over the last 2 years. As expected, there have been a number of challenges in migrating primarily on-premises applications into a cloud-based environment, related to architecture and taking advantage of cloud-based services. What was not expected is a number of issues that were beyond purely technical application re-architectures. From surprising network policy limitations, billing challenges in a government-based cost model, and obtaining certificates in an NASA security-compliant manner to working with multiple applications in a shared and resource-constrained AWS account, these have been the relevant challenges in taking advantage of a cloud model. And most surprising of all… well, you'll just have to wait and see the "gotcha" that caught our entire team off guard!

  9. The influence of psychological resilience on the relation between automatic stimulus evaluation and attentional breadth for surprised faces.

    Science.gov (United States)

    Grol, Maud; De Raedt, Rudi

    2015-01-01

    The broaden-and-build theory relates positive emotions to resilience and cognitive broadening. The theory proposes that the broadening effects underly the relation between positive emotions and resilience, suggesting that resilient people can benefit more from positive emotions at the level of cognitive functioning. Research has investigated the influence of positive emotions on attentional broadening, but the stimulus in the target of attention may also influence attentional breadth, depending on affective stimulus evaluation. Surprised faces are particularly interesting as they are valence ambiguous, therefore, we investigated the relation between affective evaluation--using an affective priming task--and attentional breadth for surprised faces, and how this relation is influenced by resilience. Results show that more positive evaluations are related to more attentional broadening at high levels of resilience, while this relation is reversed at low levels. This indicates that resilient individuals can benefit more from attending to positively evaluated stimuli at the level of attentional broadening.

  10. Team play with a powerful and independent agent: operational experiences and automation surprises on the Airbus A-320

    Science.gov (United States)

    Sarter, N. B.; Woods, D. D.

    1997-01-01

    Research and operational experience have shown that one of the major problems with pilot-automation interaction is a lack of mode awareness (i.e., the current and future status and behavior of the automation). As a result, pilots sometimes experience so-called automation surprises when the automation takes an unexpected action or fails to behave as anticipated. A lack of mode awareness and automation surprises can he viewed as symptoms of a mismatch between human and machine properties and capabilities. Changes in automation design can therefore he expected to affect the likelihood and nature of problems encountered by pilots. Previous studies have focused exclusively on early generation "glass cockpit" aircraft that were designed based on a similar automation philosophy. To find out whether similar difficulties with maintaining mode awareness are encountered on more advanced aircraft, a corpus of automation surprises was gathered from pilots of the Airbus A-320, an aircraft characterized by high levels of autonomy, authority, and complexity. To understand the underlying reasons for reported breakdowns in human-automation coordination, we also asked pilots about their monitoring strategies and their experiences with and attitude toward the unique design of flight controls on this aircraft.

  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. Surprising finding on colonoscopy.

    Science.gov (United States)

    Griglione, Nicole; Naik, Jahnavi; Christie, Jennifer

    2010-02-01

    A 48-year-old man went to his primary care physician for his annual physical. He told his physician that for the past few years, he had intermittent, painless rectal bleeding consisting of small amounts of blood on the toilet paper after defecation. He also mentioned that he often spontaneously awoke, very early in the morning. His past medical history was unremarkable. The patient was born in Cuba but had lived in the United States for more than 30 years. He was divorced, lived alone, and had no children. He had traveled to Latin America-including Mexico, Brazil, and Cuba-off and on over the past 10 years. His last trip was approximately 2 years ago. His physical exam was unremarkable. Rectal examination revealed no masses or external hemorrhoids; stool was brown and Hemoccult negative. Labs were remarkable for eosinophilia ranging from 10% to 24% over the past several years (the white blood cell count ranged from 5200 to 5900/mcL). A subsequent colonoscopy revealed many white, thin, motile organisms dispersed throughout the colon. The organisms were most densely populated in the cecum. Of note, the patient also had nonbleeding internal hemorrhoids. An aspiration of the organisms was obtained and sent to the microbiology lab for further evaluation. What is your diagnosis? How would you manage this condition?

  13. 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.

  14. More Supernova Surprises

    Science.gov (United States)

    2010-09-24

    originated in South America. E veryone appreciates the beauty of dai- sies, chrysanthemums, and sunfl ow- ers, and many of us enjoy eating lettuce ...few fossils. On page 1621 of this issue, Barreda et al. ( 1) describe an unusually well-preserved new fossil that sheds light on the history of

  15. 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...

  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. Gene Therapy

    Science.gov (United States)

    Gene therapy Overview Gene therapy involves altering the genes inside your body's cells in an effort to treat or stop disease. Genes contain your ... that don't work properly can cause disease. Gene therapy replaces a faulty gene or adds a new ...

  18. Surprisingly high specificity of the PPD skin test for M. tuberculosis infection from recent exposure in The Gambia.

    Science.gov (United States)

    Hill, Philip C; Brookes, Roger H; Fox, Annette; Jackson-Sillah, Dolly; Lugos, Moses D; Jeffries, David J; Donkor, Simon A; Adegbola, Richard A; McAdam, Keith P W J

    2006-12-20

    Options for intervention against Mycobacterium tuberculosis infection are limited by the diagnostic tools available. The Purified Protein Derivative (PPD) skin test is thought to be non-specific, especially in tropical settings. We compared the PPD skin test with an ELISPOT test in The Gambia. Household contacts over six months of age of sputum smear positive TB cases and community controls were recruited. They underwent a PPD skin test and an ELISPOT test for the T cell response to PPD and ESAT-6/CFP10 antigens. Responsiveness to M. tuberculosis exposure was analysed according to sleeping proximity to an index case using logistic regression. 615 household contacts and 105 community controls were recruited. All three tests assessed increased significantly in positivity with increasing M. tuberculosis exposure, the PPD skin test most dramatically (OR 15.7; 95% CI 6.6-35.3). While the PPD skin test positivity continued to trend downwards in the community with increasing distance from a known case (61.9% to 14.3%), the PPD and ESAT-6/CFP-10 ELISPOT positivity did not. The PPD skin test was more in agreement with ESAT-6/CFP-10 ELISPOT (75%, p = 0.01) than the PPD ELISPOT (53%, pPPD skin test positive increased (pPPD skin test negative decreased (pPPD skin test has surprisingly high specificity for M. tuberculosis infection from recent exposure in The Gambia. In this setting, anti-tuberculous prophylaxis in PPD skin test positive individuals should be revisited.

  19. Surprising transformation of a block copolymer into a high performance polystyrene ultrafiltration membrane with a hierarchically organized pore structure

    KAUST Repository

    Shevate, Rahul

    2018-02-08

    We describe the preparation of hierarchical polystyrene nanoporous membranes with a very narrow pore size distribution and an extremely high porosity. The nanoporous structure is formed as a result of unusual degradation of the poly(4-vinyl pyridine) block from self-assembled poly(styrene)-b-poly(4-vinyl pyridine) (PS-b-P4VP) membranes through the formation of an unstable pyridinium intermediate in an alkaline medium. During this process, the confined swelling and controlled degradation produced a tunable pore size. We unequivocally confirmed the successful elimination of the P4VP block from a PS-b-P4VPVP membrane using 1D/2D NMR spectroscopy and other characterization techniques. Surprisingly, the long range ordered surface porosity was preserved even after degradation of the P4VP block from the main chain of the diblock copolymer, as revealed by SEM. Aside from a drastically improved water flux (∼67% increase) compared to the PS-b-P4VP membrane, the hydraulic permeability measurements validated pH independent behaviour of the isoporous PS membrane over a wide pH range from 3 to 10. The effect of the pore size on protein transport rate and selectivity (a) was investigated for lysozyme (Lys), bovine serum albumin (BSA) and globulin-γ (IgG). A high selectivity of 42 (Lys/IgG) and 30 (BSA/IgG) was attained, making the membranes attractive for size selective separation of biomolecules from their synthetic model mixture solutions.

  20. How to reach clients of female sex workers: a survey by surprise in brothels in Dakar, Senegal.

    Science.gov (United States)

    Espirito Santo, M. E. Gomes do; Etheredge, G. D.

    2002-01-01

    OBJECTIVE: To describe the sampling techniques and survey procedures used in identifying male clients who frequent brothels to buy sexual services from female sex workers in Dakar, Senegal, with the aim of measuring the prevalence of human immunodeficiency virus (HIV) infection and investigating related risk behaviours. METHODS: Surveys were conducted in seven brothels in Dakar, Senegal. Clients were identified "by surprise" and interviewed and requested to donate saliva for HIV testing. RESULTS: Of the 1450 clients of prostitutes who were solicited to enter the study, 1140 (79.8%) agreed to be interviewed; 1083 (95%) of these clients provided saliva samples for testing. Of the samples tested, 47 were positive for HIV-1 or HIV-2, giving an HIV prevalence of 4.4%. CONCLUSION: The procedures adopted were successful in reaching the target population. Men present in the brothels could not deny being there, and it proved possible to explain the purpose of the study and to gain their confidence. Collection of saliva samples was shown to be an excellent method for performing HIV testing in difficult field conditions where it is hard to gain access to the population under study. The surveying of prostitution sites is recommended as a means of identifying core groups for HIV infection with a view to targeting education programmes more effectively. In countries such as Senegal, where the prevalence of HIV infection is still low, interventions among commercial sex workers and their clients may substantially delay the onset of a larger epidemic in the general population. PMID:12378288

  1. The Impact of a Surprise Dividend Increase on a Stocks Performance : the Analysis of Companies Listed on the Warsaw Stock Exchange

    Directory of Open Access Journals (Sweden)

    Tomasz Słoński

    2012-01-01

    Full Text Available The reaction of marginal investors to the announcement of a surprise dividend increase has been measured. Although field research is performed on companies listed on the Warsaw Stock Exchange, the paper has important theoretical implications. Valuation theory gives many clues for the interpretation of changes in dividends. At the start of the literature review, the assumption of the irrelevance of dividends (to investment decisions is described. This assumption is the basis for up-to-date valuation procedures leading to fundamental and fair market valuation of equity (shares. The paper is designed to verify whether the market value of stock is immune to the surprise announcement of a dividend increase. This study of the effect of a surprise dividend increase gives the chance to partially isolate such an event from dividend changes based on long-term expectations. The result of the research explicitly shows that a surprise dividend increase is on average welcomed by investors (an average abnormal return of 2.24% with an associated p-value of 0.001. Abnormal returns are realized by investors when there is a surprise increase in a dividend payout. The subsample of relatively high increases in a dividend payout enables investors to gain a 3.2% return on average. The results show that valuation models should be revised to take into account a possible impact of dividend changes on investors behavior. (original abstract

  2. 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...

  3. 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.

  4. BEEF CATTLE MUSCULARITY CANDIDATE GENES

    Directory of Open Access Journals (Sweden)

    Irida Novianti

    2010-04-01

    Full Text Available Muscularity is a potential indicator for the selection of more productive cattle. Mapping quantitative trait loci (QTL for traits related to muscularity is useful to identify the genomic regions where the genes affecting muscularity reside. QTL analysis from a Limousin-Jersey double backcross herd was conducted using QTL Express software with cohort and breed as the fixed effects. Nine QTL suggested to have an association with muscularity were identified on cattle chromosomes BTA 1, 2, 3, 4, 5, 8, 12, 14 and 17. The myostatin gene is located at the centromeric end of chromosome 2 and not surprisingly, the Limousin myostatin F94L variant accounted for the QTL on BTA2. However, when the myostatin F94L genotype was included as an additional fixed effect, the QTL on BTA17 was also no longer significant. This result suggests that there may be gene(s that have epistatic effects with myostatin located on cattle chromosome 17. Based on the position of the QTL in base pairs, all the genes that reside in the region were determined using the Ensembl data base (www.ensembl.org. There were two potential candidate genes residing within these QTL regions were selected. They were Smad nuclear interacting protein 1 (SNIP1 and similar to follistatin-like 5 (FSTL5. (JIIPB 2010 Vol 20 No 1: 1-10

  5. Semantic relation vs. surprise: the differential effects of related and unrelated co-verbal gestures on neural encoding and subsequent recognition.

    Science.gov (United States)

    Straube, Benjamin; Meyer, Lea; Green, Antonia; Kircher, Tilo

    2014-06-03

    Speech-associated gesturing leads to memory advantages for spoken sentences. However, unexpected or surprising events are also likely to be remembered. With this study we test the hypothesis that different neural mechanisms (semantic elaboration and surprise) lead to memory advantages for iconic and unrelated gestures. During fMRI-data acquisition participants were presented with video clips of an actor verbalising concrete sentences accompanied by iconic gestures (IG; e.g., circular gesture; sentence: "The man is sitting at the round table"), unrelated free gestures (FG; e.g., unrelated up down movements; same sentence) and no gestures (NG; same sentence). After scanning, recognition performance for the three conditions was tested. Videos were evaluated regarding semantic relation and surprise by a different group of participants. The semantic relationship between speech and gesture was rated higher for IG (IG>FG), whereas surprise was rated higher for FG (FG>IG). Activation of the hippocampus correlated with subsequent memory performance of both gesture conditions (IG+FG>NG). For the IG condition we found activation in the left temporal pole and middle cingulate cortex (MCC; IG>FG). In contrast, for the FG condition posterior thalamic structures (FG>IG) as well as anterior and posterior cingulate cortices were activated (FG>NG). Our behavioral and fMRI-data suggest different mechanisms for processing related and unrelated co-verbal gestures, both of them leading to enhanced memory performance. Whereas activation in MCC and left temporal pole for iconic co-verbal gestures may reflect semantic memory processes, memory enhancement for unrelated gestures relies on the surprise response, mediated by anterior/posterior cingulate cortex and thalamico-hippocampal structures. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. 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.

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

    International Nuclear Information System (INIS)

    Xia, Xiaojun; Park, Eunmi; Fischer, Susan M.; Hu, Yinling

    2013-01-01

    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

  8. Codon usage and amino acid usage influence genes expression level.

    Science.gov (United States)

    Paul, Prosenjit; Malakar, Arup Kumar; Chakraborty, Supriyo

    2018-02-01

    Highly expressed genes in any species differ in the usage frequency of synonymous codons. The relative recurrence of an event of the favored codon pair (amino acid pairs) varies between gene and genomes due to varying gene expression and different base composition. Here we propose a new measure for predicting the gene expression level, i.e., codon plus amino bias index (CABI). Our approach is based on the relative bias of the favored codon pair inclination among the genes, illustrated by analyzing the CABI score of the Medicago truncatula genes. CABI showed strong correlation with all other widely used measures (CAI, RCBS, SCUO) for gene expression analysis. Surprisingly, CABI outperforms all other measures by showing better correlation with the wet-lab data. This emphasizes the importance of the neighboring codons of the favored codon in a synonymous group while estimating the expression level of a gene.

  9. Would you be surprised if this patient died?: Preliminary exploration of first and second year residents' approach to care decisions in critically ill patients

    Directory of Open Access Journals (Sweden)

    Armstrong John D

    2003-01-01

    Full Text Available Abstract Background How physicians approach decision-making when caring for critically ill patients is poorly understood. This study aims to explore how residents think about prognosis and approach care decisions when caring for seriously ill, hospitalized patients. Methods Qualitative study where we conducted structured discussions with first and second year internal medicine residents (n = 8 caring for critically ill patients during Medical Intensive Care Unit Ethics and Discharge Planning Rounds. Residents were asked to respond to questions beginning with "Would you be surprised if this patient died?" Results An equal number of residents responded that they would (n = 4 or would not (n = 4 be surprised if their patient died. Reasons for being surprised included the rapid onset of an acute illness, reversible disease, improving clinical course and the patient's prior survival under similar circumstances. Residents reported no surprise with worsening clinical course. Based on the realization that their patient might die, residents cited potential changes in management that included clarifying treatment goals, improving communication with families, spending more time with patients and ordering fewer laboratory tests. Perceived or implied barriers to changes in management included limited time, competing clinical priorities, "not knowing" a patient, limited knowledge and experience, presence of diagnostic or prognostic uncertainty and unclear treatment goals. Conclusions These junior-level residents appear to rely on clinical course, among other factors, when assessing prognosis and the possibility for death in severely ill patients. Further investigation is needed to understand how these factors impact decision-making and whether perceived barriers to changes in patient management influence approaches to care.

  10. On predicting quantal cross sections by interpolation: Surprisal analysis of j/sub z/CCS and statistical j/sub z/ results

    International Nuclear Information System (INIS)

    Goldflam, R.; Kouri, D.J.

    1976-01-01

    New methods for predicting the full matrix of integral cross sections are developed by combining the surprisal analysis of Bernstein and Levine with the j/sub z/-conserving coupled states method (j/sub z/CCS) of McGuire, Kouri, and Pack and with the statistical j/sub z/ approximation (Sj/sub z/) of Kouri, Shimoni, and Heil. A variety of approaches is possible and only three are studied in the present work. These are (a) a surprisal fit of the j=0→j' column of the j/sub z/CCS cross section matrix (thereby requiring only a solution of the lambda=0 set of j/sub z/CCS equations), (b) a surprisal fit of the lambda-bar=0 Sj/sub z/ cross section matrix (again requiring solution of the lambda=0 set of j/sub z/CCS equations only), and (c) a surprisal fit of a lambda-bar not equal to 0 Sj/sub z/ submatrix (involving input cross sections for j,j'> or =lambda-bar transitions only). The last approach requires the solution of the lambda=lambda-bar set of j/sub z/CCS equations only, which requires less computation effort than the effective potential method. We explore three different choices for the prior and two-parameter (i.e., linear) and three-parameter (i.e., parabolic) fits as applied to Ar--N 2 collisions. The results are in general very encouraging and for one choice of prior give results which are within 20% of the exact j/sub z/CCS results

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

    OpenAIRE

    Emma Denehy; Amy Parry; Emily Fearnley

    2012-01-01

    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 retro...

  12. Gene expression

    International Nuclear Information System (INIS)

    Hildebrand, C.E.; Crawford, B.D.; Walters, R.A.; Enger, M.D.

    1983-01-01

    We prepared probes for isolating functional pieces of the metallothionein locus. The probes enabled a variety of experiments, eventually revealing two mechanisms for metallothionein gene expression, the order of the DNA coding units at the locus, and the location of the gene site in its chromosome. Once the switch regulating metallothionein synthesis was located, it could be joined by recombinant DNA methods to other, unrelated genes, then reintroduced into cells by gene-transfer techniques. The expression of these recombinant genes could then be induced by exposing the cells to Zn 2+ or Cd 2+ . We would thus take advantage of the clearly defined switching properties of the metallothionein gene to manipulate the expression of other, perhaps normally constitutive, genes. Already, despite an incomplete understanding of how the regulatory switch of the metallothionein locus operates, such experiments have been performed successfully

  13. 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.

  14. Methylation of cancer-stem-cell-associated Wnt target genes predicts poor prognosis in colorectal cancer patients

    NARCIS (Netherlands)

    de Sousa E Melo, Felipe; Colak, Selcuk; Buikhuisen, Joyce; Koster, Jan; Cameron, Kate; de Jong, Joan H.; Tuynman, Jurriaan B.; Prasetyanti, Pramudita R.; Fessler, Evelyn; van den Bergh, Saskia P.; Rodermond, Hans; Dekker, Evelien; van der Loos, Chris M.; Pals, Steven T.; van de Vijver, Marc J.; Versteeg, Rogier; Richel, Dick J.; Vermeulen, Louis; Medema, Jan Paul

    2011-01-01

    Gene signatures derived from cancer stem cells (CSCs) predict tumor recurrence for many forms of cancer. Here, we derived a gene signature for colorectal CSCs defined by high Wnt signaling activity, which in agreement with previous observations predicts poor prognosis. Surprisingly, however, we

  15. 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.

  16. Surpresa refrativa pós-facoemulsificação em distrofia corneana posterior amorfa Post-phacoemulsification refractive surprise in a posterior amorphous corneal dystrophy patient

    Directory of Open Access Journals (Sweden)

    Giuliano de Oliveira Freitas

    2010-02-01

    Full Text Available Relato de um caso de surpresa refracional pós-operatória não pretendida em paciente portador de distrofia corneana posterior amorfa submetida à facoemulsificação. A provável causa do erro, bem como a conduta tomada a partir do reconhecimento da mesma, são discutidas neste relato.One case of post-phacoemulsification refractive surprise in a posterior amorphous corneal dystrophy patient is reported herein. Its likely causative factor, as well as our approach once it was recognized are discussed in this report.

  17. 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...

  18. 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...

  19. Genes misregulated in C. elegans deficient in Dicer, RDE-4, or RDE-1 are enriched for innate immunity genes.

    Science.gov (United States)

    Welker, Noah C; Habig, Jeffrey W; Bass, Brenda L

    2007-07-01

    We describe the first microarray analysis of a whole animal containing a mutation in the Dicer gene. We used adult Caenorhabditis elegans and, to distinguish among different roles of Dicer, we also performed microarray analyses of animals with mutations in rde-4 and rde-1, which are involved in silencing by siRNA, but not miRNA. Surprisingly, we find that the X chromosome is greatly enriched for genes regulated by Dicer. Comparison of all three microarray data sets indicates the majority of Dicer-regulated genes are not dependent on RDE-4 or RDE-1, including the X-linked genes. However, all three data sets are enriched in genes important for innate immunity and, specifically, show increased expression of innate immunity genes.

  20. 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.

  1. Centrifugal force: a few surprises

    International Nuclear Information System (INIS)

    Abramowicz, M.A.; Max-Planck-Institut fuer Physik und Astrophysik, Garching

    1990-01-01

    The need for a rather fundamental revision in understanding of the nature of the centrifugal force is discussed. It is shown that in general relativity (and contrary to the situation in Newtonian theory) rotation of a reference frame is a necessary but not sufficient condition for the centrifugal force to appear. A sufficient condition for its appearance, in the instantaneously corotating reference frame of a particle, is that the particle motion in space (observed in the global rest frame) differs from a photon trajectory. The direction of the force is the same as that of the gradient of the effective potential for photon motion. In some cases, the centrifugal force will attract towards the axis of rotation. (author)

  2. Cartel surprised by quota reduction

    International Nuclear Information System (INIS)

    Debnar, M.

    2003-01-01

    Development of world prices of petroleum in April - September 2003 are analysed. OPEC accepted a decision to lower oil production in 900 thousands barrels per day to 24.5 millions barrels per day from 1 November 2003. Although Russian Federation reports higher oil production every month, it does not represent danger for OPEC for the present. Problem is to import the oil. Situation will change dramatically from 2008. Russian Federation plans anyway to build gigantic pipeline to Murmansk port in Barents Sea. Thanks to it Russian oil export to USA should sharply extend. It was reported by Russian Minister of economy German Gref with note that construction of pipeline is priority for Russian Federation, which wants to diversification its oil export from traditional Europe. Project of pipeline construction from Western Siberia to deep water of Murmansk terminal was published by five oil companies leaded by Lukoil and Yukos already at the end of last year. Pipeline should cost 4 billions USD and it should transport up to 2.4 millions barrels of oil per day. In the meantime Caspian oil should start to flow to Europe

  3. 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.

  4. Some new surprises in chaos.

    Science.gov (United States)

    Bunimovich, Leonid A; Vela-Arevalo, Luz V

    2015-09-01

    "Chaos is found in greatest abundance wherever order is being sought.It always defeats order, because it is better organized"Terry PratchettA 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.

  5. Experimental results surprise quantum theory

    International Nuclear Information System (INIS)

    White, C.

    1986-01-01

    Interest in results from Darmstadt that positron-electron pairs are created in nuclei with high atomic numbers (in the Z range from 180-188) lies in the occurrence of a quantized positron kinetic energy peak at 300. The results lend substance to the contention of Erich Bagge that the traditionally accepted symmetries in positron-electron emission do not exist and, therefore, there is no need to posit the existence of the neutrino. The search is on for the decay of a previously unknown boson to account for the findings, which also points to the need for a major revision in quantum theory. 1 figure

  6. Surprises and omissions in toxicology

    Czech Academy of Sciences Publication Activity Database

    Rašková, H.; Zídek, Zdeněk

    2004-01-01

    Roč. 12, - (2004), S94-S96 ISSN 1210-7778. [Inderdisciplinary Czech-Slovak Toxicological Conference /8./. Praha, 03.09.2004-05.09.2004] Institutional research plan: CEZ:AV0Z5008914 Keywords : bacterial toxins Subject RIV: FR - Pharmacology ; Medidal Chemistry

  7. Ageing genes

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2018-01-01

    The idea of gerontogenes is in line with the evolutionary explanation of ageing as being an emergent phenomenon as a result of the imperfect maintenance and repair systems. Although evolutionary processes did not select for any specific ageing genes that restrict and determine the lifespan...... of an individual, the term ‘gerontogenes’ primarily refers to any genes that may seem to influence ageing and longevity, without being specifically selected for that role. Such genes can also be called ‘virtual gerontogenes’ by virtue of their indirect influence on the rate and process of ageing. More than 1000...... virtual gerontogenes have been associated with ageing and longevity in model organisms and humans. The ‘real’ genes, which do influence the essential lifespan of a species, and have been selected for in accordance with the evolutionary life history of the species, are known as the longevity assurance...

  8. A review of the Nearctic genus Prostoia (Ricker) (Plecoptera, Nemouridae), with the description of a new species and a surprising range extension for P. hallasi Kondratieff & Kirchner.

    Science.gov (United States)

    Grubbs, Scott A; Baumann, Richard W; DeWalt, R Edward; Tweddale, Tari

    2014-01-01

    The Nearctic genus Prostoia (Plecoptera: Nemouridae) is reviewed. Prostoia ozarkensis sp. n. is described from the male and female adult stages mainly from the Interior Highland region encompassing portions of Arkansas, Missouri, and Oklahoma. Prostoia ozarkensis sp. n. appears most closely related to two species, one distributed broadly across the western Nearctic region, P. besametsa (Ricker), and one found widely throughout the central and eastern Nearctic regions, P. completa (Walker). A surprising range extension is noted for P. hallasi Kondratieff & Kirchner, a species once known only from the Great Dismal Swamp, from small upland streams in southern Illinois. Additional new state records are documented for P. besametsa, P. completa, P. hallasi and P. similis (Hagen). Taxonomic keys to Prostoia males and females are provided, and scanning electron micrographs of adult genitalia of all species are given.

  9. 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.

  10. Analogies and surprising differences between recombinant nitric oxide synthase-like proteins from Staphylococcus aureus and Bacillus anthracis in their interactions with l-arginine analogs and iron ligands.

    Science.gov (United States)

    Salard, Isabelle; Mercey, Emilie; Rekka, Eleni; Boucher, Jean-Luc; Nioche, Pierre; Mikula, Ivan; Martasek, Pavel; Raman, C S; Mansuy, Daniel

    2006-12-01

    Genome sequencing has recently shown the presence of genes coding for NO-synthase (NOS)-like proteins in bacteria. The roles of these proteins remain unclear. The interactions of a series of l-arginine (l-arg) analogs and iron ligands with two recombinant NOS-like proteins from Staphylococcus aureus (saNOS) and Bacillus anthracis (baNOS) have been studied by UV-visible spectroscopy. SaNOS and baNOS in their ferric native state, as well as their complexes with l-arg analogs and with various ligands, exhibit spectral characteristics highly similar to the corresponding complexes of heme-thiolate proteins such as cytochromes P450 and NOSs. However, saNOS greatly differs from baNOS at the level of three main properties: (i) native saNOS mainly exists under an hexacoordinated low-spin ferric state whereas native baNOS is mainly high-spin, (ii) the addition of tetrahydrobiopterin (H4B) or H4B analogs leads to an increase of the affinity of l-arg for saNOS but not for baNOS, and (iii) saNOS Fe(II), contrary to baNOS, binds relatively bulky ligands such as nitrosoalkanes and tert-butylisocyanide. Thus, saNOS exhibits properties very similar to those of the oxygenase domain of inducible NOS (iNOS(oxy)) not containing H4B, as expected for a NOSoxy-like protein that does not contain H4B. By contrast, the properties of baNOS which look like those of H4B-containing iNOS(oxy) are unexpected for a NOS-like protein not containing H4B. The origin of these surprising properties of baNOS remains to be determined.

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

    Science.gov (United States)

    2010-01-01

    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. PMID:21176201

  12. 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.

  13. A Resource of Quantitative Functional Annotation for Homo sapiens Genes.

    Science.gov (United States)

    Taşan, Murat; Drabkin, Harold J; Beaver, John E; Chua, Hon Nian; Dunham, Julie; Tian, Weidong; Blake, Judith A; Roth, Frederick P

    2012-02-01

    The body of human genomic and proteomic evidence continues to grow at ever-increasing rates, while annotation efforts struggle to keep pace. A surprisingly small fraction of human genes have clear, documented associations with specific functions, and new functions continue to be found for characterized genes. Here we assembled an integrated collection of diverse genomic and proteomic data for 21,341 human genes and make quantitative associations of each to 4333 Gene Ontology terms. We combined guilt-by-profiling and guilt-by-association approaches to exploit features unique to the data types. Performance was evaluated by cross-validation, prospective validation, and by manual evaluation with the biological literature. Functional-linkage networks were also constructed, and their utility was demonstrated by identifying candidate genes related to a glioma FLN using a seed network from genome-wide association studies. Our annotations are presented-alongside existing validated annotations-in a publicly accessible and searchable web interface.

  14. 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…

  15. Exploring the Optimal Strategy to Predict Essential Genes in Microbes

    Directory of Open Access Journals (Sweden)

    Yao Lu

    2011-12-01

    Full Text Available Accurately predicting essential genes is important in many aspects of biology, medicine and bioengineering. In previous research, we have developed a machine learning based integrative algorithm to predict essential genes in bacterial species. This algorithm lends itself to two approaches for predicting essential genes: learning the traits from known essential genes in the target organism, or transferring essential gene annotations from a closely related model organism. However, for an understudied microbe, each approach has its potential limitations. The first is constricted by the often small number of known essential genes. The second is limited by the availability of model organisms and by evolutionary distance. In this study, we aim to determine the optimal strategy for predicting essential genes by examining four microbes with well-characterized essential genes. Our results suggest that, unless the known essential genes are few, learning from the known essential genes in the target organism usually outperforms transferring essential gene annotations from a related model organism. In fact, the required number of known essential genes is surprisingly small to make accurate predictions. In prokaryotes, when the number of known essential genes is greater than 2% of total genes, this approach already comes close to its optimal performance. In eukaryotes, achieving the same best performance requires over 4% of total genes, reflecting the increased complexity of eukaryotic organisms. Combining the two approaches resulted in an increased performance when the known essential genes are few. Our investigation thus provides key information on accurately predicting essential genes and will greatly facilitate annotations of microbial genomes.

  16. Gene doping.

    Science.gov (United States)

    Haisma, H J; de Hon, O

    2006-04-01

    Together with the rapidly increasing knowledge on genetic therapies as a promising new branch of regular medicine, the issue has arisen whether these techniques might be abused in the field of sports. Previous experiences have shown that drugs that are still in the experimental phases of research may find their way into the athletic world. Both the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) have expressed concerns about this possibility. As a result, the method of gene doping has been included in the list of prohibited classes of substances and prohibited methods. This review addresses the possible ways in which knowledge gained in the field of genetic therapies may be misused in elite sports. Many genes are readily available which may potentially have an effect on athletic performance. The sporting world will eventually be faced with the phenomena of gene doping to improve athletic performance. A combination of developing detection methods based on gene arrays or proteomics and a clear education program on the associated risks seems to be the most promising preventive method to counteract the possible application of gene doping.

  17. Motif analysis unveils the possible co-regulation of chloroplast genes and nuclear genes encoding chloroplast proteins.

    Science.gov (United States)

    Wang, Ying; Ding, Jun; Daniell, Henry; Hu, Haiyan; Li, Xiaoman

    2012-09-01

    Chloroplasts play critical roles in land plant cells. Despite their importance and the availability of at least 200 sequenced chloroplast genomes, the number of known DNA regulatory sequences in chloroplast genomes are limited. In this paper, we designed computational methods to systematically study putative DNA regulatory sequences in intergenic regions near chloroplast genes in seven plant species and in promoter sequences of nuclear genes in Arabidopsis and rice. We found that -35/-10 elements alone cannot explain the transcriptional regulation of chloroplast genes. We also concluded that there are unlikely motifs shared by intergenic sequences of most of chloroplast genes, indicating that these genes are regulated differently. Finally and surprisingly, we found five conserved motifs, each of which occurs in no more than six chloroplast intergenic sequences, are significantly shared by promoters of nuclear-genes encoding chloroplast proteins. By integrating information from gene function annotation, protein subcellular localization analyses, protein-protein interaction data, and gene expression data, we further showed support of the functionality of these conserved motifs. Our study implies the existence of unknown nuclear-encoded transcription factors that regulate both chloroplast genes and nuclear genes encoding chloroplast protein, which sheds light on the understanding of the transcriptional regulation of chloroplast genes.

  18. Acyl-CoA-binding protein/diazepam-binding inhibitor gene and pseudogenes

    DEFF Research Database (Denmark)

    Mandrup, S; Hummel, R; Ravn, S

    1992-01-01

    Acyl-CoA-binding protein (ACBP) is a 10 kDa protein isolated from bovine liver by virtue of its ability to bind and induce the synthesis of medium-chain acyl-CoA esters. Surprisingly, it turned out to be identical to a protein named diazepam-binding Inhibitor (DBI) claimed to be an endogenous mod...... have molecularly cloned and characterized the ACBP/DBI gene family in rat. The rat ACBP/DBI gene family comprises one expressed gene and four processed pseudogenes of which one was shown to exist in two allelic forms. The expressed gene is organized into four exons and three introns...

  19. 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.

  20. Gene Locater

    DEFF Research Database (Denmark)

    Anwar, Muhammad Zohaib; Sehar, Anoosha; Rehman, Inayat-Ur

    2012-01-01

    software's for calculating recombination frequency is mostly limited to the range and flexibility of this type of analysis. GENE LOCATER is a fully customizable program for calculating recombination frequency, written in JAVA. Through an easy-to-use interface, GENE LOCATOR allows users a high degree...... of flexibility in calculating genetic linkage and displaying linkage group. Among other features, this software enables user to identify linkage groups with output visualized graphically. The program calculates interference and coefficient of coincidence with elevated accuracy in sample datasets. AVAILABILITY...

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

    Science.gov (United States)

    Fearnley, Emily; Denehy, Emma

    2012-01-01

    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. PMID:23908933

  2. 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.

  3. 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.

  4. Orientation, distance, regulation and function of neighbouring genes

    Directory of Open Access Journals (Sweden)

    Gherman Adrian

    2009-01-01

    Full Text Available Abstract The sequencing of the human genome has allowed us to observe globally and in detail the arrangement of genes along the chromosomes. There are multiple lines of evidence that this arrangement is not random, both in terms of intergenic distances and orientation of neighbouring genes. We have undertaken a systematic evaluation of the spatial distribution and orientation of known genes across the human genome. We used genome-level information, including phylogenetic conservation, single nucleotide polymorphism density and correlation of gene expression to assess the importance of this distribution. In addition to confirming and extending known properties of the genome, such as the significance of gene deserts and the importance of 'head to head' orientation of gene pairs in proximity, we provide significant new observations that include a smaller average size for intervals separating the 3' ends of neighbouring genes, a correlation of gene expression across tissues for genes as far as 100 kilobases apart and signatures of increasing positive selection with decreasing interval size surprisingly relaxing for intervals smaller than ~500 base pairs. Further, we provide extensive graphical representations of the genome-wide data to allow for observations and comparisons beyond what we address.

  5. 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.

  6. Surprisingly different star-spot distributions on the near equal-mass equal-rotation-rate stars in the M dwarf binary GJ 65 AB

    Science.gov (United States)

    Barnes, J. R.; Jeffers, S. V.; Haswell, C. A.; Jones, H. R. A.; Shulyak, D.; Pavlenko, Ya. V.; Jenkins, J. S.

    2017-10-01

    We aim to understand how stellar parameters such as mass and rotation impact the distribution of star-spots on the stellar surface. To this purpose, we have used Doppler imaging to reconstruct the surface brightness distributions of three fully convective M dwarfs with similar rotation rates. We secured high cadence spectral time series observations of the 5.5 au separation binary GJ 65, comprising GJ 65A (M5.5V, Prot = 0.24 d) and GJ 65B (M6V, Prot = 0.23 d). We also present new observations of GJ 791.2A (M4.5V, Prot = 0.31 d). Observations of each star were made on two nights with UVES, covering a wavelength range from 0.64 - 1.03μm. The time series spectra reveal multiple line distortions that we interpret as cool star-spots and which are persistent on both nights suggesting stability on the time-scale of 3 d. Spots are recovered with resolutions down to 8.3° at the equator. The global spot distributions for GJ 791.2A are similar to observations made a year earlier. Similar high latitude and circumpolar spot structure is seen on GJ 791.2A and GJ 65A. However, they are surprisingly absent on GJ 65B, which instead reveals more extensive, larger, spots concentrated at intermediate latitudes. All three stars show small amplitude latitude-dependent rotation that is consistent with solid body rotation. We compare our measurements of differential rotation with previous Doppler imaging studies and discuss the results in the wider context of other observational estimates and recent theoretical predictions.

  7. ‘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.

  8. Gene doping: gene delivery for olympic victory

    OpenAIRE

    Gould, David

    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...

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. Genes and Hearing Loss

    Science.gov (United States)

    ... ENTCareers Marketplace Find an ENT Doctor Near You Genes and Hearing Loss Genes and Hearing Loss Patient ... mutation may only have dystopia canthorum. How Do Genes Work? Genes are a road map for the ...

  14. Evolutionarily Conserved TCR Binding Sites, Identification of T Cells in Primary Lymphoid Tissues, and Surprising Trans-Rearrangements in Nurse Shark

    OpenAIRE

    Criscitiello, Michael F.; Ohta, Yuko; Saltis, Mark; McKinney, E. Churchill; Flajnik, Martin F.

    2010-01-01

    Cartilaginous fish are the oldest animals that generate RAG-based Ag receptor diversity. We have analyzed the genes and expressed transcripts of the four TCR chains for the first time in a cartilaginous fish, the nurse shark (Ginglymostoma cirratum). Northern blotting found TCR mRNA expression predominantly in lymphoid and mucosal tissues. Southern blotting suggested translocon-type loci encoding all four chains. Based on diversity of V and J segments, the expressed combinatorial diversity fo...

  15. 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

  16. 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.

  17. 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

  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. 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.

  20. Different level of population differentiation among human genes.

    Science.gov (United States)

    Wu, Dong-Dong; Zhang, Ya-Ping

    2011-01-14

    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. 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. Our analysis demonstrates different level of population differentiation among human populations for different gene groups.

  1. Gene expression and gene therapy imaging

    International Nuclear Information System (INIS)

    Rome, Claire; Couillaud, Franck; Moonen, Chrit T.W.

    2007-01-01

    The fast growing field of molecular imaging has achieved major advances in imaging gene expression, an important element of gene therapy. Gene expression imaging is based on specific probes or contrast agents that allow either direct or indirect spatio-temporal evaluation of gene expression. Direct evaluation is possible with, for example, contrast agents that bind directly to a specific target (e.g., receptor). Indirect evaluation may be achieved by using specific substrate probes for a target enzyme. The use of marker genes, also called reporter genes, is an essential element of MI approaches for gene expression in gene therapy. The marker gene may not have a therapeutic role itself, but by coupling the marker gene to a therapeutic gene, expression of the marker gene reports on the expression of the therapeutic gene. Nuclear medicine and optical approaches are highly sensitive (detection of probes in the picomolar range), whereas MRI and ultrasound imaging are less sensitive and require amplification techniques and/or accumulation of contrast agents in enlarged contrast particles. Recently developed MI techniques are particularly relevant for gene therapy. Amongst these are the possibility to track gene therapy vectors such as stem cells, and the techniques that allow spatiotemporal control of gene expression by non-invasive heating (with MRI guided focused ultrasound) and the use of temperature sensitive promoters. (orig.)

  2. Imaging reporter gene for monitoring gene therapy

    International Nuclear Information System (INIS)

    Beco, V. de; Baillet, G.; Tamgac, F.; Tofighi, M.; Weinmann, P.; Vergote, J.; Moretti, J.L.; Tamgac, G.

    2002-01-01

    Scintigraphic images can be obtained to document gene function at cellular level. This approach is presented here and the use of a reporter gene to monitor gene therapy is described. Two main ways are presented: either the use of a reporter gene coding for an enzyme the action of which will be monitored by radiolabeled pro-drug, or a cellular receptor gene, the action of which is documented by a radio labeled cognate receptor ligand. (author)

  3. Functionally enigmatic genes: a case study of the brain ignorome.

    Directory of Open Access Journals (Sweden)

    Ashutosh K Pandey

    Full Text Available What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed--the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum--a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases--ELMOD1, TMEM88B, and DZANK1--we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes.

  4. Functionally enigmatic genes: a case study of the brain ignorome.

    Science.gov (United States)

    Pandey, Ashutosh K; Lu, Lu; Wang, Xusheng; Homayouni, Ramin; Williams, Robert W

    2014-01-01

    What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed--the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum--a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases--ELMOD1, TMEM88B, and DZANK1--we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes.

  5. Identification of metastasis driver genes by massive parallel sequencing of successive steps of breast cancer progression

    DEFF Research Database (Denmark)

    Krøigård, Anne Bruun; Larsen, Martin Jakob; Lænkholm, Anne-Vibeke

    2018-01-01

    Cancer results from alterations at essential genomic sites and is characterized by uncontrolled cell proliferation, invasion and metastasis. Identification of driver genes of metastatic progression is essential, as metastases, not primary tumors, are fatal. To gain insight into the mutational......-synonymous to synonymous mutations, a surprisingly large number of cancer driver genes, ranging between 3 and 145, were estimated to confer a selective advantage in the studied primary tumors. We report a substantial amount of metastasis specific mutations and a number of novel putative metastasis driver genes. Most...... notable are the DCC, ABCA13, TIAM2, CREBBP, BCL6B and ZNF185 genes, mainly mutated exclusively in metastases and highly likely driver genes of metastatic progression. We find different genes and pathways to be affected at different steps of malignant progression. The Adherens junction pathway is affected...

  6. 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.

  7. Evolutionarily conserved TCR binding sites, identification of T cells in primary lymphoid tissues, and surprising trans-rearrangements in nurse shark.

    Science.gov (United States)

    Criscitiello, Michael F; Ohta, Yuko; Saltis, Mark; McKinney, E Churchill; Flajnik, Martin F

    2010-06-15

    Cartilaginous fish are the oldest animals that generate RAG-based Ag receptor diversity. We have analyzed the genes and expressed transcripts of the four TCR chains for the first time in a cartilaginous fish, the nurse shark (Ginglymostoma cirratum). Northern blotting found TCR mRNA expression predominantly in lymphoid and mucosal tissues. Southern blotting suggested translocon-type loci encoding all four chains. Based on diversity of V and J segments, the expressed combinatorial diversity for gamma is similar to that of human, alpha and beta may be slightly lower, and delta diversity is the highest of any organism studied to date. Nurse shark TCRdelta have long CDR3 loops compared with the other three chains, creating binding site topologies comparable to those of mammalian TCR in basic paratope structure; additionally, nurse shark TCRdelta CDR3 are more similar to IgH CDR3 in length and heterogeneity than to other TCR chains. Most interestingly, several cDNAs were isolated that contained IgM or IgW V segments rearranged to other gene segments of TCRdelta and alpha. Finally, in situ hybridization experiments demonstrate a conservation of both alpha/beta and gamma/delta T cell localization in the thymus across 450 million years of vertebrate evolution, with gamma/delta TCR expression especially high in the subcapsular region. Collectively, these data make the first cellular identification of TCR-expressing lymphocytes in a cartilaginous fish.

  8. 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

  9. 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

  10. 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.

  11. Conditions for the evolution of gene clusters in bacterial genomes.

    Directory of Open Access Journals (Sweden)

    Sara Ballouz

    2010-02-01

    Full Text Available Genes encoding proteins in a common pathway are often found near each other along bacterial chromosomes. Several explanations have been proposed to account for the evolution of these structures. For instance, natural selection may directly favour gene clusters through a variety of mechanisms, such as increased efficiency of coregulation. An alternative and controversial hypothesis is the selfish operon model, which asserts that clustered arrangements of genes are more easily transferred to other species, thus improving the prospects for survival of the cluster. According to another hypothesis (the persistence model, genes that are in close proximity are less likely to be disrupted by deletions. Here we develop computational models to study the conditions under which gene clusters can evolve and persist. First, we examine the selfish operon model by re-implementing the simulation and running it under a wide range of conditions. Second, we introduce and study a Moran process in which there is natural selection for gene clustering and rearrangement occurs by genome inversion events. Finally, we develop and study a model that includes selection and inversion, which tracks the occurrence and fixation of rearrangements. Surprisingly, gene clusters fail to evolve under a wide range of conditions. Factors that promote the evolution of gene clusters include a low number of genes in the pathway, a high population size, and in the case of the selfish operon model, a high horizontal transfer rate. The computational analysis here has shown that the evolution of gene clusters can occur under both direct and indirect selection as long as certain conditions hold. Under these conditions the selfish operon model is still viable as an explanation for the evolution of gene clusters.

  12. Conditions for the Evolution of Gene Clusters in Bacterial Genomes

    Science.gov (United States)

    Ballouz, Sara; Francis, Andrew R.; Lan, Ruiting; Tanaka, Mark M.

    2010-01-01

    Genes encoding proteins in a common pathway are often found near each other along bacterial chromosomes. Several explanations have been proposed to account for the evolution of these structures. For instance, natural selection may directly favour gene clusters through a variety of mechanisms, such as increased efficiency of coregulation. An alternative and controversial hypothesis is the selfish operon model, which asserts that clustered arrangements of genes are more easily transferred to other species, thus improving the prospects for survival of the cluster. According to another hypothesis (the persistence model), genes that are in close proximity are less likely to be disrupted by deletions. Here we develop computational models to study the conditions under which gene clusters can evolve and persist. First, we examine the selfish operon model by re-implementing the simulation and running it under a wide range of conditions. Second, we introduce and study a Moran process in which there is natural selection for gene clustering and rearrangement occurs by genome inversion events. Finally, we develop and study a model that includes selection and inversion, which tracks the occurrence and fixation of rearrangements. Surprisingly, gene clusters fail to evolve under a wide range of conditions. Factors that promote the evolution of gene clusters include a low number of genes in the pathway, a high population size, and in the case of the selfish operon model, a high horizontal transfer rate. The computational analysis here has shown that the evolution of gene clusters can occur under both direct and indirect selection as long as certain conditions hold. Under these conditions the selfish operon model is still viable as an explanation for the evolution of gene clusters. PMID:20168992

  13. Developmental transitions in Arabidopsis are regulated by antisense RNAs resulting from bidirectionally transcribed genes.

    Science.gov (United States)

    Krzyczmonik, Katarzyna; Wroblewska-Swiniarska, Agata; Swiezewski, Szymon

    2017-07-03

    Transcription terminators are DNA elements located at the 3' end of genes that ensure efficient cleavage of nascent RNA generating the 3' end of mRNA, as well as facilitating disengagement of elongating DNA-dependent RNA polymerase II. Surprisingly, terminators are also a potent source of antisense transcription. We have recently described an Arabidopsis antisense transcript originating from the 3' end of a master regulator of Arabidopsis thaliana seed dormancy DOG1. In this review, we discuss the broader implications of our discovery in light of recent developments in yeast and Arabidopsis. We show that, surprisingly, the key features of terminators that give rise to antisense transcription are preserved between Arabidopsis and yeast, suggesting a conserved mechanism. We also compare our discovery to known antisense-based regulatory mechanisms, highlighting the link between antisense-based gene expression regulation and major developmental transitions in plants.

  14. Combinatorial explosion in model gene networks

    Science.gov (United States)

    Edwards, R.; Glass, L.

    2000-09-01

    The explosive growth in knowledge of the genome of humans and other organisms leaves open the question of how the functioning of genes in interacting networks is coordinated for orderly activity. One approach to this problem is to study mathematical properties of abstract network models that capture the logical structures of gene networks. The principal issue is to understand how particular patterns of activity can result from particular network structures, and what types of behavior are possible. We study idealized models in which the logical structure of the network is explicitly represented by Boolean functions that can be represented by directed graphs on n-cubes, but which are continuous in time and described by differential equations, rather than being updated synchronously via a discrete clock. The equations are piecewise linear, which allows significant analysis and facilitates rapid integration along trajectories. We first give a combinatorial solution to the question of how many distinct logical structures exist for n-dimensional networks, showing that the number increases very rapidly with n. We then outline analytic methods that can be used to establish the existence, stability and periods of periodic orbits corresponding to particular cycles on the n-cube. We use these methods to confirm the existence of limit cycles discovered in a sample of a million randomly generated structures of networks of 4 genes. Even with only 4 genes, at least several hundred different patterns of stable periodic behavior are possible, many of them surprisingly complex. We discuss ways of further classifying these periodic behaviors, showing that small mutations (reversal of one or a few edges on the n-cube) need not destroy the stability of a limit cycle. Although these networks are very simple as models of gene networks, their mathematical transparency reveals relationships between structure and behavior, they suggest that the possibilities for orderly dynamics in such

  15. 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.

  16. 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.

  17. Imaging gene expression in gene therapy

    International Nuclear Information System (INIS)

    Wiebe, Leonard I.

    1997-01-01

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on 'suicide gene therapy' of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k + ) has been use for 'suicide' in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k + gene expression where the H S V-1 t k + gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([ 18 F]F H P G; [ 18 F]-A C V), and pyrimidine- ([ 123 / 131 I]I V R F U; [ 124 / 131I ]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [ 123 / 131I ]I V R F U imaging with the H S V-1 t k + reporter gene will be presented

  18. Imaging gene expression in gene therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I. [Alberta Univ., Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-12-31

    Full text. Gene therapy can be used to introduce new genes, or to supplement the function of indigenous genes. At the present time, however, there is non-invasive test to demonstrate efficacy of the gene transfer and expression processes. It has been postulated that scintigraphic imaging can offer unique information on both the site at which the transferred gene is expressed, and the degree of expression, both of which are critical issue for safety and clinical efficacy. Many current studies are based on `suicide gene therapy` of cancer. Cells modified to express these genes commit metabolic suicide in the presence of an enzyme encoded by the transferred gene and a specifically-convertible pro drug. Pro drug metabolism can lead to selective metabolic trapping, required for scintigraphy. Herpes simplex virus type-1 thymidine kinase (H S V-1 t k{sup +}) has been use for `suicide` in vivo tumor gene therapy. It has been proposed that radiolabelled nucleosides can be used as radiopharmaceuticals to detect H S V-1 t k{sup +} gene expression where the H S V-1 t k{sup +} gene serves a reporter or therapeutic function. Animal gene therapy models have been studied using purine-([{sup 18} F]F H P G; [{sup 18} F]-A C V), and pyrimidine- ([{sup 123}/{sup 131} I]I V R F U; [{sup 124}/{sup 131I}]) antiviral nucleosides. Principles of gene therapy and gene therapy imaging will be reviewed and experimental data for [{sup 123}/{sup 131I}]I V R F U imaging with the H S V-1 t k{sup +} reporter gene will be presented

  19. 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

  20. 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. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  1. The Epstein-Barr virus BILF1 gene encodes a G protein-coupled receptor that inhibits phosphorylation of RNA-dependent protein kinase

    NARCIS (Netherlands)

    Beisser, P.S.; Verzijl, D.; Gruijthuijsen, Y.K.; Beuken, E.V.; Smit, M.J.; Leurs, R.; Bruggeman, C.A.; Vink, C.

    2005-01-01

    Epstein-Barr vires (EBV) infection is associated with many lymphoproliferative diseases, such as infectious mononucleosis and Burkitt's lymphoma. Consequently, EBV is one of the most extensively studied herpesvirases. Surprisingly, a putative G protein-coupled receptor (GPCR) gene of EBV, BILF1, has

  2. 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…

  3. A novel gene of Kalanchoe daigremontiana confers plant drought resistance.

    Science.gov (United States)

    Wang, Li; Zhu, Chen; Jin, Lin; Xiao, Aihua; Duan, Jie; Ma, Luyi

    2018-02-07

    Kalanchoe (K.) daigremontiana is important for studying asexual reproduction under different environmental conditions. Here, we describe a novel KdNOVEL41 (KdN41) gene that may confer drought resistance and could thereby affect K. daigremontiana development. The detected subcellular localization of a KdN41/Yellow Fluorescent Protein (YFP) fusion protein was in the nucleus and cell membrane. Drought, salt, and heat stress treatment in tobacco plants containing the KdN41 gene promoter driving β-glucuronidase (GUS) gene transcription revealed that only drought stress triggered strong GUS staining in the vascular tissues. Overexpression (OE) of the KdN41 gene conferred improved drought resistance in tobacco plants compared to wild-type and transformed with empty vector plants by inducing higher antioxidant enzyme activities, decreasing cell membrane damage, increasing abscisic acid (ABA) content, causing reinforced drought resistance related gene expression profiles. The 3,3'-diaminobenzidine (DAB) and nitroblue tetrazolium (NBT) staining results also showed less relative oxygen species (ROS) content in KdN41-overexpressing tobacco leaf during drought stress. Surprisingly, by re-watering after drought stress, KdN41-overexpressing tobacco showed earlier flowering. Overall, the KdN41 gene plays roles in ROS scavenging and osmotic damage reduction to improve tobacco drought resistance, which may increase our understanding of the molecular network involved in developmental manipulation under drought stress in K. daigremontiana.

  4. Evolution of homeobox genes.

    Science.gov (United States)

    Holland, Peter W H

    2013-01-01

    Many homeobox genes encode transcription factors with regulatory roles in animal and plant development. Homeobox genes are found in almost all eukaryotes, and have diversified into 11 gene classes and over 100 gene families in animal evolution, and 10 to 14 gene classes in plants. The largest group in animals is the ANTP class which includes the well-known Hox genes, plus other genes implicated in development including ParaHox (Cdx, Xlox, Gsx), Evx, Dlx, En, NK4, NK3, Msx, and Nanog. Genomic data suggest that the ANTP class diversified by extensive tandem duplication to generate a large array of genes, including an NK gene cluster and a hypothetical ProtoHox gene cluster that duplicated to generate Hox and ParaHox genes. Expression and functional data suggest that NK, Hox, and ParaHox gene clusters acquired distinct roles in patterning the mesoderm, nervous system, and gut. The PRD class is also diverse and includes Pax2/5/8, Pax3/7, Pax4/6, Gsc, Hesx, Otx, Otp, and Pitx genes. PRD genes are not generally arranged in ancient genomic clusters, although the Dux, Obox, and Rhox gene clusters arose in mammalian evolution as did several non-clustered PRD genes. Tandem duplication and genome duplication expanded the number of homeobox genes, possibly contributing to the evolution of developmental complexity, but homeobox gene loss must not be ignored. Evolutionary changes to homeobox gene expression have also been documented, including Hox gene expression patterns shifting in concert with segmental diversification in vertebrates and crustaceans, and deletion of a Pitx1 gene enhancer in pelvic-reduced sticklebacks. WIREs Dev Biol 2013, 2:31-45. doi: 10.1002/wdev.78 For further resources related to this article, please visit the WIREs website. The author declares that he has no conflicts of interest. Copyright © 2012 Wiley Periodicals, Inc.

  5. Carboxylesterase 1 genes

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Madsen, Majbritt Busk

    2018-01-01

    The carboxylesterase 1 gene (CES1) encodes a hydrolase that metabolizes commonly used drugs. The CES1-related pseudogene, carboxylesterase 1 pseudogene 1 (CES1P1), has been implicated in gene exchange with CES1 and in the formation of hybrid genes including the carboxylesterase 1A2 gene (CES1A2...

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

    Science.gov (United States)

    Aubin-Horth, Nadia; Letcher, Benjamin H; Hofmann, Hans A

    2009-09-15

    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.

  7. 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.

  8. Intermediate filaments and gene regulation.

    Science.gov (United States)

    Traub, P

    1995-01-01

    way specify different chromatin organizations and thus the expression of distinct sets of cell- or tissue-specific proteins. In support of this, different type III IFs have been shown to preferentially interact with guanine-rich, highly repetitive, double-stranded fragments of total genomic DNA, including chromosomal telomere sequences. Surprisingly, they also bound AT-rich, centromeric satellite DNA sequences with high efficiency. Since most of the affinity-isolated, non-telomeric and -centromeric DNA fragments contain regulatory elements that are normally located in 5'/3'-flanking and intron regions of genes, cIFs may activate gene expression or repress it as the result of telomeric and centromeric position effects. However, the nucleotide sequences of the cIF-bound, genomic DNA fragments also predict the involvement of cIF(protein)s in recombination and hence in evolutionary processes. Based on these observations, the initially observed minor effects of cIF protein knock-out mutations on the phenotype of transgenic mice may be interpreted as a redundancy phenomenon operating at the levels of the cytoskeleton and gene expression, whereas the capacity of the mutated animals to adapt to new environments via recombination processes may be severely disturbed and, as such, perceivable only after many generations of less favorable living conditions.

  9. 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. Copyright 2004 Adis Data Information BV

  10. 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

  11. 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…

  12. A targeted resequencing gene panel for focal epilepsy.

    Science.gov (United States)

    Hildebrand, Michael S; Myers, Candace T; Carvill, Gemma L; Regan, Brigid M; Damiano, John A; Mullen, Saul A; Newton, Mark R; Nair, Umesh; Gazina, Elena V; Milligan, Carol J; Reid, Christopher A; Petrou, Steven; Scheffer, Ingrid E; Berkovic, Samuel F; Mefford, Heather C

    2016-04-26

    We report development of a targeted resequencing gene panel for focal epilepsy, the most prevalent phenotypic group of the epilepsies. The targeted resequencing gene panel was designed using molecular inversion probe (MIP) capture technology and sequenced using massively parallel Illumina sequencing. We demonstrated proof of principle that mutations can be detected in 4 previously genotyped focal epilepsy cases. We searched for both germline and somatic mutations in 251 patients with unsolved sporadic or familial focal epilepsy and identified 11 novel or very rare missense variants in 5 different genes: CHRNA4, GRIN2B, KCNT1, PCDH19, and SCN1A. Of these, 2 were predicted to be pathogenic or likely pathogenic, explaining ∼0.8% of the cohort, and 8 were of uncertain significance based on available data. We have developed and validated a targeted resequencing panel for focal epilepsies, the most important clinical class of epilepsies, accounting for about 60% of all cases. Our application of MIP technology is an innovative approach that will be advantageous in the clinical setting because it is highly sensitive, efficient, and cost-effective for screening large patient cohorts. Our findings indicate that mutations in known genes likely explain only a small proportion of focal epilepsy cases. This is not surprising given the established clinical and genetic heterogeneity of these disorders and underscores the importance of further gene discovery studies in this complex syndrome. © 2016 American Academy of Neurology.

  13. Characterization and expression of the calpastatin gene in Cyprinus carpio.

    Science.gov (United States)

    Chen, W X; Ma, Y

    2015-07-03

    Calpastatin, an important protein used to regulate meat quality traits in animals, is encoded by the CAST gene. The aim of the present study was to clone the cDNA sequence of the CAST gene and detect the expression of CAST in the tissues of Cyprinus carpio. The cDNA of the C. carpio CAST gene, amplified using rapid amplification of cDNA ends PCR, is 2834 bp in length (accession No. JX275386), contains a 2634-bp open reading frame, and encodes a protein with 877 amino acid residues. The amino acid sequence of the C. carpio CAST gene was 88, 80, and 59% identical to the sequences observed in grass carp, zebrafish, and other fish, respectively. The C. carpio CAST was observed to contain four conserved domains with 54 serine phosphorylation loci, 28 threonine phosphorylation loci, 1 tyrosine phosphorylation loci, and 6 specific protein kinase C phosphorylation loci. The CAST gene showed widespread expression in different tissues of C. carpio. Surprisingly, the relative expression of the CAST transcript in the muscle and heart tissues of C. carpio was significantly higher than in other tissues (P < 0.01).

  14. The evolutionary fate of the genes encoding the purine catabolic enzymes in hominoids, birds, and reptiles.

    Science.gov (United States)

    Keebaugh, Alaine C; Thomas, James W

    2010-06-01

    Gene loss has been proposed to play a major role in adaptive evolution, and recent studies are beginning to reveal its importance in human evolution. However, the potential consequence of a single gene-loss event upon the fates of functionally interrelated genes is poorly understood. Here, we use the purine metabolic pathway as a model system in which to explore this important question. The loss of urate oxidase (UOX) activity, a necessary step in this pathway, has occurred independently in the hominoid and bird/reptile lineages. Because the loss of UOX would have removed the functional constraint upon downstream genes in this pathway, these downstream genes are generally assumed to have subsequently deteriorated. In this study, we used a comparative genomics approach to empirically determine the fate of UOX itself and the downstream genes in five hominoids, two birds, and a reptile. Although we found that the loss of UOX likely triggered the genetic deterioration of the immediate downstream genes in the hominoids, surprisingly in the birds and reptiles, the UOX locus itself and some of the downstream genes were present in the genome and predicted to encode proteins. To account for the variable pattern of gene retention and loss after the inactivation of UOX, we hypothesize that although gene loss is a common fate for genes that have been rendered obsolete due to the upstream loss of an enzyme a metabolic pathway, it is also possible that same lack of constraint will foster the evolution of new functions or allow the optimization of preexisting alternative functions in the downstream genes, thereby resulting in gene retention. Thus, adaptive single-gene losses have the potential to influence the long-term evolutionary fate of functionally interrelated genes.

  15. Can subtle changes in gene expression be consistently detected with different microarray platforms?

    Directory of Open Access Journals (Sweden)

    Kuiper Rowan

    2008-03-01

    Full Text Available Abstract Background The comparability of gene expression data generated with different microarray platforms is still a matter of concern. Here we address the performance and the overlap in the detection of differentially expressed genes for five different microarray platforms in a challenging biological context where differences in gene expression are few and subtle. Results Gene expression profiles in the hippocampus of five wild-type and five transgenic δC-doublecortin-like kinase mice were evaluated with five microarray platforms: Applied Biosystems, Affymetrix, Agilent, Illumina, LGTC home-spotted arrays. Using a fixed false discovery rate of 10% we detected surprising differences between the number of differentially expressed genes per platform. Four genes were selected by ABI, 130 by Affymetrix, 3,051 by Agilent, 54 by Illumina, and 13 by LGTC. Two genes were found significantly differentially expressed by all platforms and the four genes identified by the ABI platform were found by at least three other platforms. Quantitative RT-PCR analysis confirmed 20 out of 28 of the genes detected by two or more platforms and 8 out of 15 of the genes detected by Agilent only. We observed improved correlations between platforms when ranking the genes based on the significance level than with a fixed statistical cut-off. We demonstrate significant overlap in the affected gene sets identified by the different platforms, although biological processes were represented by only partially overlapping sets of genes. Aberrances in GABA-ergic signalling in the transgenic mice were consistently found by all platforms. Conclusion The different microarray platforms give partially complementary views on biological processes affected. Our data indicate that when analyzing samples with only subtle differences in gene expression the use of two different platforms might be more attractive than increasing the number of replicates. Commercial two-color platforms seem to

  16. 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

  17. Evolution of the HIV-1 nef gene in HLA-B*57 Positive Elite Suppressors

    Directory of Open Access Journals (Sweden)

    Siliciano Robert F

    2010-11-01

    Full Text Available Abstract Elite controllers or suppressors (ES are HIV-1 infected patients who maintain viral loads of 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 result of structural constraints on Gag, and we therefore examined the less conserved nef gene. We found slow evolution of nef in plasma virus in some ES. This evolution is mostly due to synonymous mutations and occurs at a rate similar to that seen in the gag gene in the same patients. The results provide further evidence of ongoing viral replication in ES and suggest that the nef and gag genes in these patients respond similarly to selective pressure from the host.

  18. Tumor targeted gene therapy

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2006-01-01

    Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment had led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest in suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner

  19. 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...

  20. 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.

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

    Science.gov (United States)

    Arya, Preeti; Kumar, Gulshan; Acharya, Vishal; Singh, Anil K

    2014-01-01

    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.

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

    Science.gov (United States)

    Wu, Dong-Dong; Irwin, David M; Zhang, Ya-Ping

    2008-08-23

    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. 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. 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.

  3. Radiotechnologies and gene therapy

    International Nuclear Information System (INIS)

    Xia Jinsong

    2001-01-01

    Gene therapy is an exciting frontier in medicine today. Radiologist will make an uniquely contribution to these exciting new technologies at every level by choosing sites for targeting therapy, perfecting and establishing routes of delivery, developing imaging strategies to monitor therapy and assess gene expression, developing radiotherapeutic used of gene therapy

  4. 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)

  5. 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.

  6. Ecological Divergence and the Origins of Intrinsic Postmating Isolation with Gene Flow

    Directory of Open Access Journals (Sweden)

    Aneil F. Agrawal

    2011-01-01

    Full Text Available The evolution of intrinsic postmating isolation has received much attention, both historically and in recent studies of speciation genes. Intrinsic isolation often stems from between-locus genetic incompatibilities, where alleles that function well within species are incompatible with one another when brought together in the genome of a hybrid. It can be difficult for such incompatibilities to originate when populations diverge with gene flow, because deleterious genotypic combinations will be created and then purged by selection. However, it has been argued that if genes underlying incompatibilities are themselves subject to divergent selection, then they might overcome gene flow to diverge between populations, resulting in the origin of incompatibilities. Nonetheless, there has been little explicit mathematical exploration of such scenarios for the origin of intrinsic incompatibilities during ecological speciation with gene flow. Here we explore theoretical models for the origin of intrinsic isolation where genes subject to divergent natural selection also affect intrinsic isolation, either directly or via linkage disequilibrium with other loci. Such genes indeed overcome gene flow, diverge between populations, and thus result in the evolution of intrinsic isolation. We also examine barriers to neutral gene flow. Surprisingly, we find that intrinsic isolation sometimes weakens this barrier, by impeding differentiation via ecologically based divergent selection.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Leishmaniasis — Surprise from the East

    Directory of Open Access Journals (Sweden)

    I.V. Bogadelnikov

    2012-03-01

    Full Text Available The clinical case of cutaneous leishmaniasis in a 4-year-old child is presented in the article. The child came to the Crimea from area where leishmaniasis is endemic — Republic of Uzbekistan. Clinical case is interesting for consideration in terms of differential diagnosis of specific rash.

  12. Cyber Deterrence by Engagement and Surprise

    Science.gov (United States)

    2017-12-21

    Stability Through Strength,” Military and Strategic Affairs, vol. 4, no. 3, (2012), 3–23; Martin Libicki, Cyberdeterrence and Cyberwar, (RAND...Defense, May 2015). 6 The levels of severity are based on the levels of bellig- erence as outlined by Martin Libicki in Cyberdeterrence and Cyberwar...See: Martin Libicki, Cyberdeterrence and Cyberwar, (RAND Corporation, Project Air Force, 2009), 8.

  13. Fundamental surprise in the application of airpower

    Science.gov (United States)

    2017-05-25

    explain transformations in scientific research proposed by Thomas Kuhn in his book “The Structure of Scientific Revolutions." Kuhn proposed the idea...that the accepted traditions of scientific research within a particular community, known as a paradigm, provide the tools to perform "normal science...the large-scale attacks on Lebanese infrastructure would have on the regime, this concept was a non- starter . The order issued to the IDF on 12 July

  14. Office gossip: a surprising source of liability.

    Science.gov (United States)

    Gregg, Robert E

    2003-01-01

    Rumors and gossip are inevitable ingredients of work life. Within limits, they may have some beneficial functions. Still, practitioners and managers must be aware of the dangers inherent in defamation of character and harassment. This article defines workplace comments and activities that should be avoided and the employer's legal liability when situations get out of hand. It also outlines the manager's responsibilities and lists privacy rights that are codified by state and federal laws.

  15. The surprising power of neighborly advice.

    Science.gov (United States)

    Gilbert, Daniel T; Killingsworth, Matthew A; Eyre, Rebecca N; Wilson, Timothy D

    2009-03-20

    Two experiments revealed that (i) people can more accurately predict their affective reactions to a future event when they know how a neighbor in their social network reacted to the event than when they know about the event itself and (ii) people do not believe this. Undergraduates made more accurate predictions about their affective reactions to a 5-minute speed date (n = 25) and to a peer evaluation (n = 88) when they knew only how another undergraduate had reacted to these events than when they had information about the events themselves. Both participants and independent judges mistakenly believed that predictions based on information about the event would be more accurate than predictions based on information about how another person had reacted to it.

  16. 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.

  17. Older Galaxy Pair Has Surprisingly Youthful Glow

    Science.gov (United States)

    2007-01-01

    [figure removed for brevity, see original site] Poster Version A pair of interacting galaxies might be experiencing the galactic equivalent of a mid-life crisis. For some reason, the pair, called Arp 82, didn't make their stars early on as is typical of most galaxies. Instead, they got a second wind later in life -- about 2 billion years ago -- and started pumping out waves of new stars as if they were young again. Arp 82 is an interacting pair of galaxies with a strong bridge and a long tail. NGC 2535 is the big galaxy and NGC 2536 is its smaller companion. The disk of the main galaxy looks like an eye, with a bright 'pupil' in the center and oval-shaped 'eyelids.' Dramatic 'beads on a string' features are visible as chains of evenly spaced star-formation complexes along the eyelids. These are presumably the result of large-scale gaseous shocks from a grazing encounter. The colors of this galaxy indicate that the observed stars are young to intermediate in age, around 2 million to 2 billion years old, much less than the age of the universe (13.7 billion years). The puzzle is: why didn't Arp 82 form many stars earlier, like most galaxies of that mass range? Scientifically, it is an oddball and provides a relatively nearby lab for studying the age of intermediate-mass galaxies. This picture is a composite captured by Spitzer's infrared array camera with light at wavelength 8 microns shown in red, NASA's Galaxy Evolution Explorer combined 1530 and 2310 Angstroms shown in blue, and the Southeastern Association for Research in Astronomy Observatory light at 6940 Angstroms shown in green.

  18. 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.

  19. 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...

  20. An undiagnosed pleural effusion with surprising consequences

    Directory of Open Access Journals (Sweden)

    A.G. Casalini

    2017-01-01

    With this case report, we would like to underline the importance of making a correct diagnosis of any pleural effusion as soon as possible by at least a thoracocentesis. If untreated, tuberculosis may easily disseminate to other organs. Some considerations and suggestions for antibiotic treatment of pleural effusion will also be given, since many antibiotics have some anti-tuberculosis effect and may delay the diagnosis of this infectious disease.

  1. A surprise case of colonic interposition

    International Nuclear Information System (INIS)

    Law, Robert

    2006-01-01

    Blind nasogastric intubation failure as a result of changes to the normal anatomical pathway is not uncommon. This case report is of fluoroscopically guided intubation in a patient in whom blind intubation failed as a result of what was subsequently found to be a colonic interposition with associated late complications. Fluroscopically guided nasogastric intubation is a safe and effective procedure that should always be considered when blind intubation has failed

  2. Resilience to Surprises through Communicative Planning

    Directory of Open Access Journals (Sweden)

    Bruce Evan. Goldstein

    2009-12-01

    Full Text Available Resilience thinkers share an interest in collaborative deliberation with communicative planners, who aim to accommodate different forms of knowledge and styles of reasoning to promote social learning and yield creative and equitable agreements. Members of both fields attended a symposium at Virginia Tech in late 2008, where communicative planners considered how social-ecological resilience informed new possibilities for planning practice beyond disaster mitigation and response. In turn, communicative planners offered resilience scholars ideas about how collaboration could accomplish more than enhance rational decision making of the commons. Through these exchanges, the symposium fostered ideas about collaborative governance and the critical role of expertise in fostering communicative resilience.

  3. Latest Surprises from Mira the Wonderful

    Science.gov (United States)

    Karovska, Margarita; Marengo, Massimo; Wood, Brian

    We report the latest results from our long-term study of Mira A and its companion Mira B. These include a study of the dust environment in mid-IR wavelengths (Marengo et al. 2001), and of the accretion processes in the Mira AB interacting system (Wood, Karovska, and Raymond 2002).

  4. Surprise Ultraviolet Party in the Sky

    Science.gov (United States)

    2005-01-01

    Galaxies aren't the only objects filling up the view of NASA's Galaxy Evolution Explorer. Since its launch in 2003, the space telescope -- originally designed to observe galaxies across the universe in ultraviolet light -- has discovered a festive sky blinking with flaring and erupting stars, as well as streaking asteroids, satellites and space debris. A group of six streaking objects -- the identities of which remain unknown -- can be seen here flying across the telescope's sight in this sped-up movie. The two brightest objects appear to perform a sharp turn then travel in the reverse direction. This illusion is most likely the result of the Galaxy Evolution Explorer overtaking the objects as it orbits around Earth. Careful inspection reveals four additional faint objects with the same timing and behavior. These faint objects are easiest to see during the retrograde portion of their paths. Three appear between the two bright sources, and one is above them, near the edge of the field of view. These bonus objects are being collected in to public catalogues for other astronomers to study.

  5. Equilibrium deuterium isotope effect of surprising magnitude

    International Nuclear Information System (INIS)

    Goldstein, M.J.; Pressman, E.J.

    1981-01-01

    Seemingly large deuterium isotope effects are reported for the preference of deuterium for the α-chloro site to the bridgehead or to the vinyl site in samples of anti-7-chlorobicyclo[4.3.2]undecatetraene-d 1 . Studies of molecular models did not provide a basis for these large equilibrium deuterium isotope effects. The possibility is proposed that these isotope effects only appear to be large for want of comparison with isotope effects measured for molecules that might provide even greater contrasts in local force fields

  6. Identification and Regulation of c-Myb Target Genes in MCF-7 Cells

    International Nuclear Information System (INIS)

    Quintana, Anita M; Liu, Fan; O'Rourke, John P; Ness, Scott A

    2011-01-01

    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. 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. 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. 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 cells

  7. 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.

  8. A review of the Nearctic genus Prostoia (Ricker (Plecoptera, Nemouridae, with the description of a new species and a surprising range extension for P. hallasi Kondratieff & Kirchner

    Directory of Open Access Journals (Sweden)

    Scott Grubbs

    2014-04-01

    Full Text Available The Nearctic genus Prostoia (Plecoptera: Nemouridae is reviewed. Prostoia ozarkensis sp. n. is described from the male and female adult stages mainly from the Interior Highland region encompassing portions of Arkansas, Missouri, and Oklahoma. Prostoia ozarkensis sp. n. appears most closely related to two species, one distributed broadly across the western Nearctic region, P. besametsa (Ricker, and one found widely throughout the central and eastern Nearctic regions, P. completa (Walker. A surprising range extension is noted for P. hallasi Kondratieff & Kirchner, a species once known only from the Great Dismal Swamp, from small upland streams in southern Illinois. Additional new state records are documented for P. besametsa, P. completa, P. hallasi and P. similis (Hagen. Taxonomic keys to Prostoia males and females are provided, and scanning electron micrographs of adult genitalia of all species are given.

  9. 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.

  10. 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.

  11. Genes and Social Behavior

    OpenAIRE

    Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

    2008-01-01

    What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence beh...

  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. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Refining discordant gene trees.

    Science.gov (United States)

    Górecki, Pawel; Eulenstein, Oliver

    2014-01-01

    Evolutionary studies are complicated by discordance between gene trees and the species tree in which they evolved. Dealing with discordant trees often relies on comparison costs between gene and species trees, including the well-established Robinson-Foulds, gene duplication, and deep coalescence costs. While these costs have provided credible results for binary rooted gene trees, corresponding cost definitions for non-binary unrooted gene trees, which are frequently occurring in practice, are challenged by biological realism. We propose a natural extension of the well-established costs for comparing unrooted and non-binary gene trees with rooted binary species trees using a binary refinement model. For the duplication cost we describe an efficient algorithm that is based on a linear time reduction and also computes an optimal rooted binary refinement of the given gene tree. Finally, we show that similar reductions lead to solutions for computing the deep coalescence and the Robinson-Foulds costs. Our binary refinement of Robinson-Foulds, gene duplication, and deep coalescence costs for unrooted and non-binary gene trees together with the linear time reductions provided here for computing these costs significantly extends the range of trees that can be incorporated into approaches dealing with discordance.

  14. 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

  15. 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.

  16. Protists and the Wild, Wild West of Gene Expression: New Frontiers, Lawlessness, and Misfits.

    Science.gov (United States)

    Smith, David Roy; Keeling, Patrick J

    2016-09-08

    The DNA double helix has been called one of life's most elegant structures, largely because of its universality, simplicity, and symmetry. The expression of information encoded within DNA, however, can be far from simple or symmetric and is sometimes surprisingly variable, convoluted, and wantonly inefficient. Although exceptions to the rules exist in certain model systems, the true extent to which life has stretched the limits of gene expression is made clear by nonmodel systems, particularly protists (microbial eukaryotes). The nuclear and organelle genomes of protists are subject to the most tangled forms of gene expression yet identified. The complicated and extravagant picture of the underlying genetics of eukaryotic microbial life changes how we think about the flow of genetic information and the evolutionary processes shaping it. Here, we discuss the origins, diversity, and growing interest in noncanonical protist gene expression and its relationship to genomic architecture.

  17. 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

  18. Chromatin loops, gene positioning, and gene expression

    NARCIS (Netherlands)

    Holwerda, S.; de Laat, W.

    2012-01-01

    Technological developments and intense research over the last years have led to a better understanding of the 3D structure of the genome and its influence on genome function inside the cell nucleus. We will summarize topological studies performed on four model gene loci: the alpha- and beta-globin

  19. Your Genes, Your Choices

    Science.gov (United States)

    Table of Contents Your Genes, Your Choices describes the Human Genome Project, the science behind it, and the ethical, legal, and social issues that are ... Nothing could be further from the truth. Your Genes, Your Choices points out how the progress of ...

  20. DNA repair genes

    International Nuclear Information System (INIS)

    Morimyo, Mitsuoki

    1995-01-01

    Fission yeast S. pombe is assumed to be a good model for cloning of human DNA repair genes, because human gene is normally expressed in S. pombe and has a very similar protein sequence to yeast protein. We have tried to elucidate the DNA repair mechanisms of S. pombe as a model system for those of mammals. (J.P.N.)

  1. 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...

  2. The “Fourth Dimension” of Gene Transcription

    Science.gov (United States)

    O'Malley, Bert W.

    2009-01-01

    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. PMID:19221049

  3. Complete genes may pass from food to human blood

    DEFF Research Database (Denmark)

    Spisák, Sándor; Solymosi, Norbert; Ittzés, Péter

    2013-01-01

    Our bloodstream is considered to be an environment well separated from the outside world and the digestive tract. According to the standard paradigm large macromolecules consumed with food cannot pass directly to the circulatory system. During digestion proteins and DNA are thought to be degraded...... into small constituents, amino acids and nucleic acids, respectively, and then absorbed by a complex active process and distributed to various parts of the body through the circulation system. Here, based on the analysis of over 1000 human samples from four independent studies, we report evidence that meal......-derived DNA fragments which are large enough to carry complete genes can avoid degradation and through an unknown mechanism enter the human circulation system. In one of the blood samples the relative concentration of plant DNA is higher than the human DNA. The plant DNA concentration shows a surprisingly...

  4. Radionuclide reporter gene imaging

    International Nuclear Information System (INIS)

    Min, Jung Joon

    2004-01-01

    Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studies published to date demonstrate that reporter gene imaging technologies will help to accelerate model validation as well as allow for clinical monitoring of human diseases

  5. Radionuclide reporter gene imaging

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Joon [School of Medicine, Chonnam National Univ., Gwangju (Korea, Republic of)

    2004-04-01

    Recent progress in the development of non-invasive imaging technologies continues to strengthen the role of molecular imaging biological research. These tools have been validated recently in variety of research models, and have been shown to provide continuous quantitative monitoring of the location(s), magnitude, and time-variation of gene expression. This article reviews the principles, characteristics, categories and the use of radionuclide reporter gene imaging technologies as they have been used in imaging cell trafficking, imaging gene therapy, imaging endogenous gene expression and imaging molecular interactions. The studies published to date demonstrate that reporter gene imaging technologies will help to accelerate model validation as well as allow for clinical monitoring of human diseases.

  6. Dissecting the organ specificity of insecticide resistance candidate genes in Anopheles gambiae: known and novel candidate genes.

    Science.gov (United States)

    Ingham, Victoria A; Jones, Christopher M; Pignatelli, Patricia; Balabanidou, Vasileia; Vontas, John; Wagstaff, Simon C; Moore, Jonathan D; Ranson, Hilary

    2014-11-25

    The elevated expression of enzymes with insecticide metabolism activity can lead to high levels of insecticide resistance in the malaria vector, Anopheles gambiae. In this study, adult female mosquitoes from an insecticide susceptible and resistant strain were dissected into four different body parts. RNA from each of these samples was used in microarray analysis to determine the enrichment patterns of the key detoxification gene families within the mosquito and to identify additional candidate insecticide resistance genes that may have been overlooked in previous experiments on whole organisms. A general enrichment in the transcription of genes from the four major detoxification gene families (carboxylesterases, glutathione transferases, UDP glucornyltransferases and cytochrome P450s) was observed in the midgut and malpighian tubules. Yet the subset of P450 genes that have previously been implicated in insecticide resistance in An gambiae, show a surprisingly varied profile of tissue enrichment, confirmed by qPCR and, for three candidates, by immunostaining. A stringent selection process was used to define a list of 105 genes that are significantly (p ≤0.001) over expressed in body parts from the resistant versus susceptible strain. Over half of these, including all the cytochrome P450s on this list, were identified in previous whole organism comparisons between the strains, but several new candidates were detected, notably from comparisons of the transcriptomes from dissected abdomen integuments. The use of RNA extracted from the whole organism to identify candidate insecticide resistance genes has a risk of missing candidates if key genes responsible for the phenotype have restricted expression within the body and/or are over expression only in certain tissues. However, as transcription of genes implicated in metabolic resistance to insecticides is not enriched in any one single organ, comparison of the transcriptome of individual dissected body parts cannot

  7. 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.

  8. Brassica villosa, a system for studying non-glandular trichomes and genes in the Brassicas.

    Science.gov (United States)

    Nayidu, Naghabushana K; Tan, Yifang; Taheri, Ali; Li, Xiang; Bjorndahl, Trent C; Nowak, Jacek; Wishart, David S; Hegedus, Dwayne; Gruber, Margaret Y

    2014-07-01

    Brassica villosa is a wild Brassica C genome species with very dense trichome coverage and strong resistance to many insect pests of Brassica oilseeds and vegetables. Transcriptome analysis of hairy B. villosa leaves indicated higher expression of several important trichome initiation genes compared with glabrous B. napus leaves and consistent with the Arabidopsis model of trichome development. However, transcripts of the TRY inhibitory gene in hairy B. villosa were surprisingly high relative to B. napus and relative transcript levels of SAD2, EGL3, and several XIX genes were low, suggesting potential ancillary or less important trichome-related roles for these genes in Brassica species compared with Arabidopsis. Several antioxidant, calcium, non-calcium metal and secondary metabolite genes also showed differential expression between these two species. These coincided with accumulation of two alkaloid-like compounds, high levels of calcium, and other metals in B. villosa trichomes that are correlated with the known tolerance of B. villosa to high salt and the calcium-rich natural habitat of this wild species. This first time report on the isolation of large amounts of pure B. villosa trichomes, on trichome content, and on relative gene expression differences in an exceptionally hairy Brassica species compared with a glabrous species opens doors for the scientific community to understand trichome gene function in the Brassicas and highlights the potential of B. villosa as a trichome research platform.

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

    International Nuclear Information System (INIS)

    Huang, Shang-Lang; Chao, Chuck C.-K.

    2015-01-01

    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

  10. 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.

  11. A maize resistance gene functions against bacterial streak disease in rice.

    Science.gov (United States)

    Zhao, Bingyu; Lin, Xinghua; Poland, Jesse; Trick, Harold; Leach, Jan; Hulbert, Scot

    2005-10-25

    Although cereal crops all belong to the grass family (Poacea), most of their diseases are specific to a particular species. Thus, a given cereal species is typically resistant to diseases of other grasses, and this nonhost resistance is generally stable. To determine the feasibility of transferring nonhost resistance genes (R genes) between distantly related grasses to control specific diseases, we identified a maize R gene that recognizes a rice pathogen, Xanthomonas oryzae pv. oryzicola, which causes bacterial streak disease. Bacterial streak is an important disease of rice in Asia, and no simply inherited sources of resistance have been identified in rice. Although X. o. pv. oryzicola does not cause disease on maize, we identified a maize gene, Rxo1, that conditions a resistance reaction to a diverse collection of pathogen strains. Surprisingly, Rxo1 also controls resistance to the unrelated pathogen Burkholderia andropogonis, which causes bacterial stripe of sorghum and maize. The same gene thus controls resistance reactions to both pathogens and nonpathogens of maize. Rxo1 has a nucleotide-binding site-leucine-rich repeat structure, similar to many previously identified R genes. Most importantly, Rxo1 functions after transfer as a transgene to rice, demonstrating the feasibility of nonhost R gene transfer between cereals and providing a valuable tool for controlling bacterial streak disease.

  12. 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.

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

    Science.gov (United States)

    de Angelis, Martin Hrabě; Nicholson, George; Selloum, Mohammed; White, Jacqui; 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, 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; Holmes, Chris; Steel, Karen P; Herault, Yann; Gailus-Durner, Valérie; Mallon, Ann-Marie; Brown, Steve Dm

    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.

  14. What's in a Gene? Pseudoexfoliation Syndrome and Pigment Dispersion Syndrome in the Same Patient.

    Science.gov (United States)

    Pokrovskaya, Olya; O'Brien, Colm

    2016-01-01

    Pseudoexfoliation syndrome (PXS) and pigment dispersion syndrome (PDS) are two of the commonest disorders to produce secondary open-angle glaucoma through trabecular meshwork blockage. Each is a defined clinical entity, and while genetics likely play a significant role in the pathogenesis of both, the specific genes involved appear to be distinct. There is surprisingly little published in the literature regarding the coexistence of PDS and PXS in the same patient. We present the intriguing case of a patient who developed PDS in one eye and PXS in the other. This unusual case acts as a platform for an interesting discussion of the genomics of PXS and PDS.

  15. What's in a Gene Pseudoexfoliation Syndrome and Pigment Dispersion Syndrome in the Same Patient

    Directory of Open Access Journals (Sweden)

    Olya Pokrovskaya

    2016-01-01

    Full Text Available Pseudoexfoliation syndrome (PXS and pigment dispersion syndrome (PDS are two of the commonest disorders to produce secondary open-angle glaucoma through trabecular meshwork blockage. Each is a defined clinical entity, and while genetics likely play a significant role in the pathogenesis of both, the specific genes involved appear to be distinct. There is surprisingly little published in the literature regarding the coexistence of PDS and PXS in the same patient. We present the intriguing case of a patient who developed PDS in one eye and PXS in the other. This unusual case acts as a platform for an interesting discussion of the genomics of PXS and PDS.

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

    Directory of Open Access Journals (Sweden)

    Bradon R. McDonald

    2017-06-01

    Full Text Available 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.

  17. 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.

  18. Methanogenesis and methane genes

    International Nuclear Information System (INIS)

    Reeve, J.N.; Shref, B.A.

    1991-01-01

    An overview of the pathways leading to methane biosynthesis is presented. The steps investigated to date by gene cloning and DNA sequencing procedures are identified and discussed. The primary structures of component C of methyl coenzyme M reductase encoded by mcr operons in different methanogens are compared. Experiments to detect the primary structure of the genes encoding F420 reducing hydrogenase (frhABG) and methyl hydrogen reducing hydrogenase (mvhDGA) in methanobacterium thermoautotrophicum strain H are compared with each other and with eubacterial hydrogenase encoding genes. A biotechnological use for hydrogenases from hypermorphillic archaebacteria is suggested. (author)

  19. 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.

  20. Presentation of an umbilical cord cyst with a surprising jet: a case report of a patent urachus [v1; ref status: indexed, http://f1000r.es/xx

    Directory of Open Access Journals (Sweden)

    John Svigos

    2013-02-01

    Full Text Available We report a baby with an unusual true umbilical cord cyst detected at 12 weeks gestation which as the pregnancy progressed became increasingly difficult to distinguish from a pseudocyst of the umbilical cord. Concern of the possibility of cord compression/cord accident led to an elective caesarean section being performed at 35+ week’s gestation with delivery of a healthy female infant weighing 2170g. At birth the cyst ruptured and the resultant thickened elongated cord was clamped accordingly. After the cord clamp fell off at 5 days post delivery an elongated umbilical stump was left behind from which a stream of urine surprisingly jetted out from the umbilicus each time the baby cried. A patent urachus was confirmed on ultrasound and the umbilical jet of urine resolved at 4 weeks post delivery after treatment of an Escherichia coli urinary tract infection. At 11 weeks post delivery a laparoscopic excision of the urachus was successfully performed. The baby, now 18 months of age, continues to thrive without incident.

  1. 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.

  2. Evolution and Diversity of Biosynthetic Gene Clusters in Fusarium

    Directory of Open Access Journals (Sweden)

    Koen Hoogendoorn

    2018-06-01

    Full Text Available Plant pathogenic fungi in the Fusarium genus cause severe damage to crops, resulting in great financial losses and health hazards. Specialized metabolites synthesized by these fungi are known to play key roles in the infection process, and to provide survival advantages inside and outside the host. However, systematic studies of the evolution of specialized metabolite-coding potential across Fusarium have been scarce. Here, we apply a combination of bioinformatic approaches to identify biosynthetic gene clusters (BGCs across publicly available genomes from Fusarium, to group them into annotated families and to study gain/loss events of BGC families throughout the history of the genus. Comparison with MIBiG reference BGCs allowed assignment of 29 gene cluster families (GCFs to pathways responsible for the production of known compounds, while for 57 GCFs, the molecular products remain unknown. Comparative analysis of BGC repertoires using ancestral state reconstruction raised several new hypotheses on how BGCs contribute to Fusarium pathogenicity or host specificity, sometimes surprisingly so: for example, a gene cluster for the biosynthesis of hexadehydro-astechrome was identified in the genome of the biocontrol strain Fusarium oxysporum Fo47, while being absent in that of the tomato pathogen F. oxysporum f.sp. lycopersici. Several BGCs were also identified on supernumerary chromosomes; heterologous expression of genes for three terpene synthases encoded on the Fusarium poae supernumerary chromosome and subsequent GC/MS analysis showed that these genes are functional and encode enzymes that each are able to synthesize koraiol; this observed functional redundancy supports the hypothesis that localization of copies of BGCs on supernumerary chromosomes provides freedom for evolutionary innovations to occur, while the original function remains conserved. Altogether, this systematic overview of biosynthetic diversity in Fusarium paves the way for

  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. Finding Genes for Schizophrenia

    OpenAIRE

    Åberg, Karolina

    2005-01-01

    Schizophrenia is one of our most common psychiatric diseases. It severely affects all aspects of psychological functions and results in loss of contact with reality. No cure exists and the treatments available today produce only partial relief for disease symptoms. The aim of this work is to better understand the etiology of schizophrenia by identification of candidate genes and gene pathways involved in the development of the disease. In a preliminarily study, the effects of medication and g...

  5. Epigenetics: beyond genes

    CSIR Research Space (South Africa)

    Fossey, A

    2009-06-01

    Full Text Available in forestry breeding. Keywords Gene regulation; chromatin; histone code hyporthesis; RNA silencing; post transcriptional gene silencing; forestry. Introduction to epigenetic phenomena Most living organisms share a vast amount of genetic information... (Rapp and Wendel, 2005). Epigenetic phenomena pervade all aspects of cell proliferation and plant development and are often in conflict with Mendelian models of genetics (Grant-Downton and Dickinson, 2005). A key element in many epigenetic effects...

  6. Gene-Gene and Gene-Environment Interactions in the Etiology of Breast Cancer

    National Research Council Canada - National Science Library

    Adegoke, Olufemi

    2003-01-01

    The objective of this CDA is to evaluate the gene-gene and gene-environment interactions in the etiology of breast cancer in two ongoing case-control studies, the Shanghai Breast Cancer Study (SBCS...

  7. Radiosensitivity and genes

    Energy Technology Data Exchange (ETDEWEB)

    Qiyue, Hu; Mingyue, Lun [Suzhou Medical Coll., JS (China)

    1995-07-01

    Reported effects of some oncogenes, tumour suppressor genes and DNA repair genes on sensitivity of cells to ionizing radiation are reviewed. The role of oncogenes in cellular response to irradiation is discussed, especially the extensively studied oncogenes such as the ras gene family. For tumour suppressor genes, mainly the p53, which is increasingly implicated as a gene affecting radiosensitivity, is reviewed. It is considered that there is a cell cycle checkpoint determinant which is postulated to be able to arrest the irradiated cells in G{sub 1} phase to allow them to repair damage before they undergo DNA synthesis. So far there are six DNA repair genes which have been cloned in mammalian cells, but only one, XRCC1, appears to be involved in repair of human X-ray damage. XRCC1 can correct high sisterchromatid exchange levels when transferred into EM{sub 9} cells, but its expression seems to have no correlation with radiosensitivity of human neck and head tumour cells. Radiosensitivity is an intricate issue which may involve many factors. A scheme of cellular reactions after exposure to irradiation is proposed to indicate a possible sequence of events initiated by ionizing radiation.

  8. Radiosensitivity and genes

    International Nuclear Information System (INIS)

    Hu Qiyue; Lun Mingyue

    1995-07-01

    Reported effects of some oncogenes, tumour suppressor genes and DNA repair genes on sensitivity of cells to ionizing radiation are reviewed. The role of oncogenes in cellular response to irradiation is discussed, especially the extensively studied oncogenes such as the ras gene family. For tumour suppressor genes, mainly the p53, which is increasingly implicated as a gene affecting radiosensitivity, is reviewed. It is considered that there is a cell cycle checkpoint determinant which is postulated to be able to arrest the irradiated cells in G 1 phase to allow them to repair damage before they undergo DNA synthesis. So far there are six DNA repair genes which have been cloned in mammalian cells, but only one, XRCC1, appears to be involved in repair of human X-ray damage. XRCC1 can correct high sisterchromatid exchange levels when transferred into EM 9 cells, but its expression seems to have no correlation with radiosensitivity of human neck and head tumour cells. Radiosensitivity is an intricate issue which may involve many factors. A scheme of cellular reactions after exposure to irradiation is proposed to indicate a possible sequence of events initiated by ionizing radiation

  9. 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.

  10. 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

  11. 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.

  12. Oxidative stress gene expression profile in inbred mouse after ischemia/reperfusion small bowel injury.

    Science.gov (United States)

    Bertoletto, Paulo Roberto; Ikejiri, Adauto Tsutomu; Somaio Neto, Frederico; Chaves, José Carlos; Teruya, Roberto; Bertoletto, Eduardo Rodrigues; Taha, Murched Omar; Fagundes, Djalma José

    2012-11-01

    To determine the profile of gene expressions associated with oxidative stress and thereby contribute to establish parameters about the role of enzyme clusters related to the ischemia/reperfusion intestinal injury. Twelve male inbred mice (C57BL/6) were randomly assigned: Control Group (CG) submitted to anesthesia, laparotomy and observed by 120 min; Ischemia/reperfusion Group (IRG) submitted to anesthesia, laparotomy, 60 min of small bowel ischemia and 60 min of reperfusion. A pool of six samples was submitted to the qPCR-RT protocol (six clusters) for mouse oxidative stress and antioxidant defense pathways. On the 84 genes investigated, 64 (76.2%) had statistic significant expression and 20 (23.8%) showed no statistical difference to the control group. From these 64 significantly expressed genes, 60 (93.7%) were up-regulated and 04 (6.3%) were down-regulated. From the group with no statistical significantly expression, 12 genes were up-regulated and 8 genes were down-regulated. Surprisingly, 37 (44.04%) showed a higher than threefold up-regulation and then arbitrarily the values was considered as a very significant. Thus, 37 genes (44.04%) were expressed very significantly up-regulated. The remained 47 (55.9%) genes were up-regulated less than three folds (35 genes - 41.6%) or down-regulated less than three folds (12 genes - 14.3%). The intestinal ischemia and reperfusion promote a global hyper-expression profile of six different clusters genes related to antioxidant defense and oxidative stress.

  13. 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...

  14. An exceptional horizontal gene transfer in plastids: gene replacement by a distant bacterial paralog and evidence that haptophyte and cryptophyte plastids are sisters

    Directory of Open Access Journals (Sweden)

    Palmer Jeffrey D

    2006-09-01

    Full Text Available Abstract Background Horizontal gene transfer (HGT to the plant mitochondrial genome has recently been shown to occur at a surprisingly high rate; however, little evidence has been found for HGT to the plastid genome, despite extensive sequencing. In this study, we analyzed all genes from sequenced plastid genomes to unearth any neglected cases of HGT and to obtain a measure of the overall extent of HGT to the plastid. Results Although several genes gave strongly supported conflicting trees under certain conditions, we are confident of HGT in only a single case beyond the rubisco HGT already reported. Most of the conflicts involved near neighbors connected by long branches (e.g. red algae and their secondary hosts, where phylogenetic methods are prone to mislead. However, three genes – clpP, ycf2, and rpl36 – provided strong support for taxa moving far from their organismal position. Further taxon sampling of clpP and ycf2 resulted in rejection of HGT due to long-branch attraction and a serious error in the published plastid genome sequence of Oenothera elata, respectively. A single new case, a bacterial rpl36 gene transferred into the ancestor of the cryptophyte and haptophyte plastids, appears to be a true HGT event. Interestingly, this rpl36 gene is a distantly related paralog of the rpl36 type found in other plastids and most eubacteria. Moreover, the transferred gene has physically replaced the native rpl36 gene, yet flanking genes and intergenic regions show no sign of HGT. This suggests that gene replacement somehow occurred by recombination at the very ends of rpl36, without the level and length of similarity normally expected to support recombination. Conclusion The rpl36 HGT discovered in this study is of considerable interest in terms of both molecular mechanism and phylogeny. The plastid acquisition of a bacterial rpl36 gene via HGT provides the first strong evidence for a sister-group relationship between haptophyte and

  15. An exceptional horizontal gene transfer in plastids: gene replacement by a distant bacterial paralog and evidence that haptophyte and cryptophyte plastids are sisters

    Science.gov (United States)

    Rice, Danny W; Palmer, Jeffrey D

    2006-01-01

    Background Horizontal gene transfer (HGT) to the plant mitochondrial genome has recently been shown to occur at a surprisingly high rate; however, little evidence has been found for HGT to the plastid genome, despite extensive sequencing. In this study, we analyzed all genes from sequenced plastid genomes to unearth any neglected cases of HGT and to obtain a measure of the overall extent of HGT to the plastid. Results Although several genes gave strongly supported conflicting trees under certain conditions, we are confident of HGT in only a single case beyond the rubisco HGT already reported. Most of the conflicts involved near neighbors connected by long branches (e.g. red algae and their secondary hosts), where phylogenetic methods are prone to mislead. However, three genes – clpP, ycf2, and rpl36 – provided strong support for taxa moving far from their organismal position. Further taxon sampling of clpP and ycf2 resulted in rejection of HGT due to long-branch attraction and a serious error in the published plastid genome sequence of Oenothera elata, respectively. A single new case, a bacterial rpl36 gene transferred into the ancestor of the cryptophyte and haptophyte plastids, appears to be a true HGT event. Interestingly, this rpl36 gene is a distantly related paralog of the rpl36 type found in other plastids and most eubacteria. Moreover, the transferred gene has physically replaced the native rpl36 gene, yet flanking genes and intergenic regions show no sign of HGT. This suggests that gene replacement somehow occurred by recombination at the very ends of rpl36, without the level and length of similarity normally expected to support recombination. Conclusion The rpl36 HGT discovered in this study is of considerable interest in terms of both molecular mechanism and phylogeny. The plastid acquisition of a bacterial rpl36 gene via HGT provides the first strong evidence for a sister-group relationship between haptophyte and cryptophyte plastids to the

  16. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system.

    Science.gov (United States)

    Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Heimberg, Alysha M; Jansen, Hans J; McCleary, Ryan J R; Kerkkamp, Harald M E; Vos, Rutger A; Guerreiro, Isabel; Calvete, Juan J; Wüster, Wolfgang; Woods, Anthony E; Logan, Jessica M; Harrison, Robert A; Castoe, Todd A; de Koning, A P Jason; Pollock, David D; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S; Ribeiro, José M C; Arntzen, Jan W; van den Thillart, Guido E E J M; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P; Spaink, Herman P; Duboule, Denis; McGlinn, Edwina; Kini, R Manjunatha; Richardson, Michael K

    2013-12-17

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection.

  17. Microarray labeling extension values: laboratory signatures for Affymetrix GeneChips

    Science.gov (United States)

    Lee, Yun-Shien; Chen, Chun-Houh; Tsai, Chi-Neu; Tsai, Chia-Lung; Chao, Angel; Wang, Tzu-Hao

    2009-01-01

    Interlaboratory comparison of microarray data, even when using the same platform, imposes several challenges to scientists. RNA quality, RNA labeling efficiency, hybridization procedures and data-mining tools can all contribute variations in each laboratory. In Affymetrix GeneChips, about 11–20 different 25-mer oligonucleotides are used to measure the level of each transcript. Here, we report that ‘labeling extension values (LEVs)’, which are correlation coefficients between probe intensities and probe positions, are highly correlated with the gene expression levels (GEVs) on eukayotic Affymetrix microarray data. By analyzing LEVs and GEVs in the publicly available 2414 cel files of 20 Affymetrix microarray types covering 13 species, we found that correlations between LEVs and GEVs only exist in eukaryotic RNAs, but not in prokaryotic ones. Surprisingly, Affymetrix results of the same specimens that were analyzed in different laboratories could be clearly differentiated only by LEVs, leading to the identification of ‘laboratory signatures’. In the examined dataset, GSE10797, filtering out high-LEV genes did not compromise the discovery of biological processes that are constructed by differentially expressed genes. In conclusion, LEVs provide a new filtering parameter for microarray analysis of gene expression and it may improve the inter- and intralaboratory comparability of Affymetrix GeneChips data. PMID:19295132

  18. Complementary striped expression patterns of NK homeobox genes during segment formation in the annelid Platynereis.

    Science.gov (United States)

    Saudemont, Alexandra; Dray, Nicolas; Hudry, Bruno; Le Gouar, Martine; Vervoort, Michel; Balavoine, Guillaume

    2008-05-15

    NK genes are related pan-metazoan homeobox genes. In the fruitfly, NK genes are clustered and involved in patterning various mesodermal derivatives during embryogenesis. It was therefore suggested that the NK cluster emerged in evolution as an ancestral mesodermal patterning cluster. To test this hypothesis, we cloned and analysed the expression patterns of the homologues of NK cluster genes Msx, NK4, NK3, Lbx, Tlx, NK1 and NK5 in the marine annelid Platynereis dumerilii, a representative of trochozoans, the third great branch of bilaterian animals alongside deuterostomes and ecdysozoans. We found that most of these genes are involved, as they are in the fly, in the specification of distinct mesodermal derivatives, notably subsets of muscle precursors. The expression of the homologue of NK4/tinman in the pulsatile dorsal vessel of Platynereis strongly supports the hypothesis that the vertebrate heart derived from a dorsal vessel relocated to a ventral position by D/V axis inversion in a chordate ancestor. Additionally and more surprisingly, NK4, Lbx, Msx, Tlx and NK1 orthologues are expressed in complementary sets of stripes in the ectoderm and/or mesoderm of forming segments, suggesting an involvement in the segment formation process. A potentially ancient role of the NK cluster genes in segment formation, unsuspected from vertebrate and fruitfly studies so far, now deserves to be investigated in other bilaterian species, especially non-insect arthropods and onychophorans.

  19. The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

    Science.gov (United States)

    Vonk, Freek J.; Casewell, Nicholas R.; Henkel, Christiaan V.; Heimberg, Alysha M.; Jansen, Hans J.; McCleary, Ryan J. R.; Kerkkamp, Harald M. E.; Vos, Rutger A.; Guerreiro, Isabel; Calvete, Juan J.; Wüster, Wolfgang; Woods, Anthony E.; Logan, Jessica M.; Harrison, Robert A.; Castoe, Todd A.; de Koning, A. P. Jason; Pollock, David D.; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B.; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S.; Ribeiro, José M. C.; Arntzen, Jan W.; van den Thillart, Guido E. E. J. M.; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P.; Spaink, Herman P.; Duboule, Denis; McGlinn, Edwina; Kini, R. Manjunatha; Richardson, Michael K.

    2013-01-01

    Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection. PMID:24297900

  20. The Role of Cell Adhesion Molecule Genes Regulating Neuroplasticity in Addiction

    Directory of Open Access Journals (Sweden)

    Dawn E. Muskiewicz

    2018-01-01

    Full Text Available A variety of genetic approaches, including twin studies, linkage studies, and candidate gene studies, has established a firm genetic basis for addiction. However, there has been difficulty identifying the precise genes that underlie addiction liability using these approaches. This situation became especially clear in genome-wide association studies (GWAS of addiction. Moreover, the results of GWAS brought into clarity many of the shortcomings of those early genetic approaches. GWAS studies stripped away those preconceived notions, examining genes that would not previously have been considered in the study of addiction, consequently creating a shift in our understanding. Most importantly, those studies implicated a class of genes that had not previously been considered in the study of addiction genetics: cell adhesion molecules (CAMs. Considering the well-documented evidence supporting a role for various CAMs in synaptic plasticity, axonal growth, and regeneration, it is not surprising that allelic variation in CAM genes might also play a role in addiction liability. This review focuses on the role of various cell adhesion molecules in neuroplasticity that might contribute to addictive processes and emphasizes the importance of ongoing research on CAM genes that have been implicated in addiction by GWAS.

  1. Guided genetic screen to identify genes essential in the regeneration of hair cells and other tissues.

    Science.gov (United States)

    Pei, Wuhong; Xu, Lisha; Huang, Sunny C; Pettie, Kade; Idol, Jennifer; Rissone, Alberto; Jimenez, Erin; Sinclair, Jason W; Slevin, Claire; Varshney, Gaurav K; Jones, MaryPat; Carrington, Blake; Bishop, Kevin; Huang, Haigen; Sood, Raman; Lin, Shuo; Burgess, Shawn M

    2018-01-01

    Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury. To understand the mechanism of hair cell regeneration and its association with regeneration of other tissues, we performed a guided mutagenesis screen using zebrafish lateral line hair cells as a screening platform to identify genes that are essential for hair cell regeneration, and further investigated how genes essential for hair cell regeneration were involved in the regeneration of other tissues. We created genetic mutations either by retroviral insertion or CRISPR/Cas9 approaches, and developed a high-throughput screening pipeline for analyzing hair cell development and regeneration. We screened 254 gene mutations and identified 7 genes specifically affecting hair cell regeneration. These hair cell regeneration genes fell into distinct and somewhat surprising functional categories. By examining the regeneration of caudal fin and liver, we found these hair cell regeneration genes often also affected other types of tissue regeneration. Therefore, our results demonstrate guided screening is an effective approach to discover regeneration candidates, and hair cell regeneration is associated with other tissue regeneration.

  2. Different gene-specific mechanisms determine the 'revised-response' memory transcription patterns of a subset of A. thaliana dehydration stress responding genes.

    Science.gov (United States)

    Liu, Ning; Ding, Yong; Fromm, Michael; Avramova, Zoya

    2014-05-01

    Plants that have experienced several exposures to dehydration stress show increased resistance to future exposures by producing faster and/or stronger reactions, while many dehydration stress responding genes in Arabidopsis thaliana super-induce their transcription as a 'memory' from the previous encounter. A previously unknown, rather unusual, memory response pattern is displayed by a subset of the dehydration stress response genes. Despite robustly responding to a first stress, these genes return to their initial, pre-stressed, transcript levels during the watered recovery; surprisingly, they do not respond further to subsequent stresses of similar magnitude and duration. This transcriptional behavior defines the 'revised-response' memory genes. Here, we investigate the molecular mechanisms regulating this transcription memory behavior. Potential roles of abscisic acid (ABA), of transcription factors (TFs) from the ABA signaling pathways (ABF2/3/4 and MYC2), and of histone modifications (H3K4me3 and H3K27me3) as factors in the revised-response transcription memory patterns are elucidated. We identify the TF MYC2 as the critical component for the memory behavior of a specific subset of MYC2-dependent genes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Genome-wide identification of physically clustered genes suggests chromatin-level co-regulation in male reproductive development in Arabidopsis thaliana.

    Science.gov (United States)

    Reimegård, Johan; Kundu, Snehangshu; Pendle, Ali; Irish, Vivian F; Shaw, Peter; Nakayama, Naomi; Sundström, Jens F; Emanuelsson, Olof

    2017-04-07

    Co-expression of physically linked genes occurs surprisingly frequently in eukaryotes. Such chromosomal clustering may confer a selective advantage as it enables coordinated gene regulation at the chromatin level. We studied the chromosomal organization of genes involved in male reproductive development in Arabidopsis thaliana. We developed an in-silico tool to identify physical clusters of co-regulated genes from gene expression data. We identified 17 clusters (96 genes) involved in stamen development and acting downstream of the transcriptional activator MS1 (MALE STERILITY 1), which contains a PHD domain associated with chromatin re-organization. The clusters exhibited little gene homology or promoter element similarity, and largely overlapped with reported repressive histone marks. Experiments on a subset of the clusters suggested a link between expression activation and chromatin conformation: qRT-PCR and mRNA in situ hybridization showed that the clustered genes were up-regulated within 48 h after MS1 induction; out of 14 chromatin-remodeling mutants studied, expression of clustered genes was consistently down-regulated only in hta9/hta11, previously associated with metabolic cluster activation; DNA fluorescence in situ hybridization confirmed that transcriptional activation of the clustered genes was correlated with open chromatin conformation. Stamen development thus appears to involve transcriptional activation of physically clustered genes through chromatin de-condensation. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Plastid Transcriptomics and Translatomics of Tomato Fruit Development and Chloroplast-to-Chromoplast Differentiation: Chromoplast Gene Expression Largely Serves the Production of a Single Protein[W][OA

    Science.gov (United States)

    Kahlau, Sabine; Bock, Ralph

    2008-01-01

    Plastid genes are expressed at high levels in photosynthetically active chloroplasts but are generally believed to be drastically downregulated in nongreen plastids. The genome-wide changes in the expression patterns of plastid genes during the development of nongreen plastid types as well as the contributions of transcriptional versus translational regulation are largely unknown. We report here a systematic transcriptomics and translatomics analysis of the tomato (Solanum lycopersicum) plastid genome during fruit development and chloroplast-to-chromoplast conversion. At the level of RNA accumulation, most but not all plastid genes are strongly downregulated in fruits compared with leaves. By contrast, chloroplast-to-chromoplast differentiation during fruit ripening is surprisingly not accompanied by large changes in plastid RNA accumulation. However, most plastid genes are translationally downregulated during chromoplast development. Both transcriptional and translational downregulation are more pronounced for photosynthesis-related genes than for genes involved in gene expression, indicating that some low-level plastid gene expression must be sustained in chromoplasts. High-level expression during chromoplast development identifies accD, the only plastid-encoded gene involved in fatty acid biosynthesis, as the target gene for which gene expression activity in chromoplasts is maintained. In addition, we have determined the developmental patterns of plastid RNA polymerase activities, intron splicing, and RNA editing and report specific developmental changes in the splicing and editing patterns of plastid transcripts. PMID:18441214

  5. Symmetry breaking and spectral considerations of the surprisingly floppy c-C3H radical and the related dipole-bound excited state of c-C3H-

    Science.gov (United States)

    Bassett, Matthew K.; Fortenberry, Ryan C.

    2017-06-01

    The C3H radical is believed to be prevalent throughout the interstellar medium and may be involved in the formation of polycyclic aromatic hydrocarbons. C3H exists as both a linear and a cyclic isomer. The C2 v cyclopropenylidenyl radical isomer was detected in the dark molecular cloud TMC-1, and the linear propenylidenyl radical isomer has been observed in various dark molecular clouds. Even though the c-C3H radical has been classified rotationally, the vibrational frequencies of this seemingly important interstellar molecule have never been directly observed. Established, highly accurate quartic force field methodologies are employed here to compute useful geometrical data, spectroscopic constants, and vibrational frequencies. The computed rotational constants are consistent with the experimental results. Consequently, the three a1 (ν1, ν2, and ν3) and one b1 (ν6) anharmonic vibrational frequencies at 3117.7 cm-1, 1564.3 cm-1, 1198.5 cm-1, and 826.7 cm-1, respectively, are reliable predictions for these, as of yet unseen, observables. Unfortunately, the two b2 fundamentals (ν4 and ν5) cannot be treated adequately in the current approach due to a flat and possible double-well potential described in detail herein. The dipole-bound excited state of the anion suffers from the same issues and may not even be bound. However, the trusted fundamental vibrational frequencies described for the neutral radical should not be affected by this deformity and are the first robustly produced for c-C3H. The insights gained here will also be applicable to other structures containing three-membered bare and exposed carbon rings that are surprisingly floppy in nature.

  6. Gene coexpression network analysis of fruit transcriptomes uncovers a possible mechanistically distinct class of sugar/acid ratio-associated genes in sweet orange.

    Science.gov (United States)

    Qiao, Liang; Cao, Minghao; Zheng, Jian; Zhao, Yihong; Zheng, Zhi-Liang

    2017-10-30

    The ratio of sugars to organic acids, two of the major metabolites in fleshy fruits, has been considered the most important contributor to fruit sweetness. Although accumulation of sugars and acids have been extensively studied, whether plants evolve a mechanism to maintain, sense or respond to the fruit sugar/acid ratio remains a mystery. In a prior study, we used an integrated systems biology tool to identify a group of 39 acid-associated genes from the fruit transcriptomes in four sweet orange varieties (Citrus sinensis L. Osbeck) with varying fruit acidity, Succari (acidless), Bingtang (low acid), and Newhall and Xinhui (normal acid). We reanalyzed the prior sweet orange fruit transcriptome data, leading to the identification of 72 genes highly correlated with the fruit sugar/acid ratio. The majority of these sugar/acid ratio-related genes are predicted to be involved in regulatory functions such as transport, signaling and transcription or encode enzymes involved in metabolism. Surprisingly, only three of these sugar/acid ratio-correlated genes are weakly correlated with sugar level and none of them overlaps with the acid-associated genes. Weighted Gene Coexpression Network Analysis (WGCNA) has revealed that these genes belong to four modules, Blue, Grey, Brown and Turquoise, with the former two modules being unique to the sugar/acid ratio control. Our results indicate that orange fruits contain a possible mechanistically distinct class of genes that may potentially be involved in maintaining fruit sugar/acid ratios and/or responding to the cellular sugar/acid ratio status. Therefore, our analysis of orange transcriptomes provides an intriguing insight into the potentially novel genetic or molecular mechanisms controlling the sugar/acid ratio in fruits.

  7. Isoflurane is a suitable alternative to ether for anesthetizing rats prior to euthanasia for gene expression analysis.

    Science.gov (United States)

    Nakatsu, Noriyuki; Igarashi, Yoshinobu; Aoshi, Taiki; Hamaguchi, Isao; Saito, Masumichi; Mizukami, Takuo; Momose, Haruka; Ishii, Ken J; Yamada, Hiroshi

    2017-01-01

    Diethyl ether (ether) had been widely used in Japan for anesthesia, despite its explosive properties and toxicity to both humans and animals. We also had used ether as an anesthetic for euthanizing rats for research in the Toxicogenomics Project (TGP). Because the use of ether for these purposes will likely cease, it is required to select an alternative anesthetic which is validated for consistency with existing TGP data acquired under ether anesthesia. We therefore compared two alternative anesthetic candidates, isoflurane and pentobarbital, with ether in terms of hematological findings, serum biochemical parameters, and gene expressions. As a result, few differences among the three agents were observed. In hematological and serum biochemistry analysis, no significant changes were found. In gene expression analysis, four known genes were extracted as differentially expressed genes in the liver of rats anesthetized with ether, isoflurane, or pentobarbital. However, no significant relationships were detected using gene ontology, pathway, or gene enrichment analyses by DAVID and TargetMine. Surprisingly, although it was expected that the lung would be affected by administration via inhalation, only one differentially expressed gene was extracted in the lung. Taken together, our data indicate that there are no significant differences among ether, isoflurane, and pentobarbital with respect to effects on hematological parameters, serum biochemistry parameters, and gene expression. Based on its smallest affect to existing data and its safety profile for humans and animals, we suggest isoflurane as a suitable alternative anesthetic for use in rat euthanasia in toxicogenomics analysis.

  8. FunGene: the functional gene pipeline and repository.

    Science.gov (United States)

    Fish, Jordan A; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C Titus; Tiedje, James M; Cole, James R

    2013-01-01

    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.

  9. 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.

  10. 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.

  11. Radionuclide reporter gene imaging for cardiac gene therapy

    International Nuclear Information System (INIS)

    Inubushi, Masayuki; Tamaki, Nagara

    2007-01-01

    In the field of cardiac gene therapy, angiogenic gene therapy has been most extensively investigated. The first clinical trial of cardiac angiogenic gene therapy was reported in 1998, and at the peak, more than 20 clinical trial protocols were under evaluation. However, most trials have ceased owing to the lack of decisive proof of therapeutic effects and the potential risks of viral vectors. In order to further advance cardiac angiogenic gene therapy, remaining open issues need to be resolved: there needs to be improvement of gene transfer methods, regulation of gene expression, development of much safer vectors and optimisation of therapeutic genes. For these purposes, imaging of gene expression in living organisms is of great importance. In radionuclide reporter gene imaging, ''reporter genes'' transferred into cell nuclei encode for a protein that retains a complementary ''reporter probe'' of a positron or single-photon emitter; thus expression of the reporter genes can be imaged with positron emission tomography or single-photon emission computed tomography. Accordingly, in the setting of gene therapy, the location, magnitude and duration of the therapeutic gene co-expression with the reporter genes can be monitored non-invasively. In the near future, gene therapy may evolve into combination therapy with stem/progenitor cell transplantation, so-called cell-based gene therapy or gene-modified cell therapy. Radionuclide reporter gene imaging is now expected to contribute in providing evidence on the usefulness of this novel therapeutic approach, as well as in investigating the molecular mechanisms underlying neovascularisation and safety issues relevant to further progress in conventional gene therapy. (orig.)

  12. GoGene: gene annotation in the fast lane.

    Science.gov (United States)

    Plake, Conrad; Royer, Loic; Winnenburg, Rainer; Hakenberg, Jörg; Schroeder, Michael

    2009-07-01

    High-throughput screens such as microarrays and RNAi screens produce huge amounts of data. They typically result in hundreds of genes, which are often further explored and clustered via enriched GeneOntology terms. The strength of such analyses is that they build on high-quality manual annotations provided with the GeneOntology. However, the weakness is that annotations are restricted to process, function and location and that they do not cover all known genes in model organisms. GoGene addresses this weakness by complementing high-quality manual annotation with high-throughput text mining extracting co-occurrences of genes and ontology terms from literature. GoGene contains over 4,000,000 associations between genes and gene-related terms for 10 model organisms extracted from more than 18,000,000 PubMed entries. It does not cover only process, function and location of genes, but also biomedical categories such as diseases, compounds, techniques and mutations. By bringing it all together, GoGene provides the most recent and most complete facts about genes and can rank them according to novelty and importance. GoGene accepts keywords, gene lists, gene sequences and protein sequences as input and supports search for genes in PubMed, EntrezGene and via BLAST. Since all associations of genes to terms are supported by evidence in the literature, the results are transparent and can be verified by the user. GoGene is available at http://gopubmed.org/gogene.

  13. 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

  14. Genes in food--why the furore?

    Science.gov (United States)

    Dixon, Bernard

    2003-04-01

    Although unprecedented and perhaps unique in its irrationality, the recent furore over genetically modified (GM) food holds extremely important lessons for scientists. Some sections of the media undoubtedly bear a heavy responsibility for giving the expression 'GM' threatening connotations that are quite unwarranted. However, influential contributions to the hysteria have come from a surprising range of other sources, including some scientists. The research community has failed in its responsibility to society in three ways. Firstly, plant scientists did not appreciate that certain techniques (such as the use of antibiotic resistance genes as markers during plant transformation) would inevitably provoke public consternation. As a result, they took no steps to address such concerns. Secondly, researchers overlooked, minimized or in some cases simply dismissed the significance of public fears that they were 'interfering with Nature' or 'playing God'. Thirdly, plant breeders apparently saw no need to take pro-active measures with regard to the media and public in placing potential environmental and nutritional benefits of GM crops on the agenda in a positive fashion. Partly because of this failure, GM food is now firmly established in the public mind as wholly objectionable. One measure of how far we have travelled down that road is that it hardly matters any more whether objections are based on alleged environmental risks of cultivating GM crops or alleged toxicological hazards of eating them. 'Genetically modified organism', like 'radioactivity', has become an odious, generic shibboleth. Given that millions of people throughout the world are already benefiting from pharmaceuticals made by GM organisms, this is bizarre.

  15. 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.

  16. Mitogen activated protein kinases selectively regulate palytoxin-stimulated gene expression in mouse keratinocytes

    International Nuclear Information System (INIS)

    Zeliadt, Nicholette A.; Warmka, Janel K.; Wattenberg, Elizabeth V.

    2003-01-01

    We have been investigating how the novel skin tumor promoter palytoxin transmits signals through mitogen activated protein kinases (MAPKs). Palytoxin activates three major MAPKs, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, in a keratinocyte cell line derived from initiated mouse skin (308). We previously showed that palytoxin requires ERK to increase matrix metalloproteinase-13 (MMP-13) gene expression, an enzyme implicated in carcinogenesis. Diverse stimuli require JNK and p38 to increase MMP-13 gene expression, however. We therefore used the JNK and p38 inhibitors SP 600125 and SB 202190, respectively, to investigate the role of these MAPKs in palytoxin-induced MMP-13 gene expression. Surprisingly, palytoxin does not require JNK and p38 to increase MMP-13 gene expression. Accordingly, ERK activation, independent of palytoxin and in the absence of JNK and p38 activation, is sufficient to induce MMP-13 gene expression in 308 keratinocytes. Dexamethasone, a synthetic glucocorticoid that inhibits activator protein-1 (AP-1), blocked palytoxin-stimulated MMP-13 gene expression. Therefore, the AP-1 site present in the promoter of the MMP-13 gene appears to be functional and to play a key role in palytoxin-stimulated gene expression. Previous studies showed that palytoxin simulates an ERK-dependent selective increase in the c-Fos content of AP-1 complexes that bind to the promoter of the MMP-13 gene. JNK and p38 can also modulate c-Fos. Palytoxin does not require JNK or p38 to increase c-Fos binding, however. Altogether, these studies indicate that ERK plays a distinctly essential role in transmitting palytoxin-stimulated signals to specific nuclear targets in keratinocytes derived from initiated mouse skin

  17. 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.

  18. Genes and inheritance.

    Science.gov (United States)

    Middelton, L A; Peters, K F

    2001-10-01

    The information gained from the Human Genome Project and related genetic research will undoubtedly create significant changes in healthcare practice. It is becoming increasingly clear that nurses in all areas of clinical practice will require a fundamental understanding of basic genetics. This article provides the oncology nurse with an overview of basic genetic concepts, including inheritance patterns of single gene conditions, pedigree construction, chromosome aberrations, and the multifactorial basis underlying the common diseases of adulthood. Normal gene structure and function are introduced and the biochemistry of genetic errors is described.

  19. 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

  20. Fatty acid represses insulin receptor gene expression by impairing HMGA1 through protein kinase Cε

    International Nuclear Information System (INIS)

    Dey, Debleena; Bhattacharya, Anirban; Roy, SibSankar; Bhattacharya, Samir

    2007-01-01

    It is known that free fatty acid (FFA) contributes to the development of insulin resistance and type2 diabetes. However, the underlying mechanism in FFA-induced insulin resistance is still unclear. In the present investigation we have demonstrated that palmitate significantly (p < 0.001) inhibited insulin-stimulated phosphorylation of PDK1, the key insulin signaling molecule. Consequently, PDK1 phosphorylation of plasma membrane bound PKCε was also inhibited. Surprisingly, phosphorylation of cytosolic PKCε was greatly stimulated by palmitate; this was then translocated to the nuclear region and associated with the inhibition of insulin receptor (IR) gene transcription. A PKCε translocation inhibitor peptide, εV1, suppressed this inhibitory effect of palmitate, suggesting requirement of phospho-PKCε migration to implement palmitate effect. Experimental evidences indicate that phospho-PKCε adversely affected HMGA1. Since HMGA1 regulates IR promoter activity, expression of IR gene was impaired causing reduction of IR on cell surface and that compromises with insulin sensitivity

  1. Gene-expression signatures of Atlantic salmon’s plastic life cycle

    Science.gov (United States)

    Aubin-Horth, Nadia; Letcher, Benjamin H.; Hofmann, Hans 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. PMID:19401203

  2. Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa

    DEFF Research Database (Denmark)

    Gao, Shan; Nielsen, Boye Schnack; Krogdahl, Annelise

    2010-01-01

    , 17 of 20 patients with oral carcinoma were found to have between 2.5- and 50-fold increased tumor PAI-1 mRNA level, as compared with the matched tumor-adjacent normal tissues. The PAI-1 mRNA level in connective tissues from 15 healthy volunteers was similar to the level in tumor-adjacent normal...... tissues, but the level in epithelium was 5- to 10-fold lower. Analyzing DNA methylation of 25 CpG sites within 960 bp around the transcription initiation site of the SERPINE1 gene by bisulfite sequencing, we did the surprising observation that both tumors and tumor-adjacent normal tissue had a significant...... level of methylation, whereas there was very little methylation in tissue from healthy volunteers, suggesting that tumor-adjacent normal tissue already contains transformation-associated epigenetic changes. However, there was no general inverse correlation between PAI-1 mRNA levels and SERPINE1 gene...

  3. Genes involved in meso-diaminopimelate synthesis in Bacillus subtilis: identification of the gene encoding aspartokinase I.

    Science.gov (United States)

    Roten, C A; Brandt, C; Karamata, D

    1991-04-01

    Thermosensitive mutants of Bacillus subtilis deficient in peptidoglycan synthesis were screened for mutations in the meso-diaminopimelate (LD-A2pm) metabolic pathway. Mutations in two out of five relevant linkage groups, lssB and lssD, were shown to induce, at the restrictive temperature, a deficiency in LD-A2pm synthesis and accumulation of UDP-MurNAc-dipeptide. Group lssB is heterogeneous; it encompasses mutations that confer deficiency in the deacylation of N-acetyl-LL-A2pm and accumulation of this precursor. Accordingly, these mutations are assigned to the previously identified locus dapE. Mutations in linkage group lssD entail a thermosensitive aspartokinase 1. Therefore, they are most likely to affect the structural gene of this enzyme, which we propose to designate dapG. Mutation pyc-1476, previously reported to affect the pyruvate carboxylase, was shown to confer a deficiency in aspartokinase 1, not in the carboxylase, and to belong to the dapG locus, dapG is closely linked to spoVF, the putative gene of dipicolinate synthase. In conclusion, mutations affecting only two out of eight steps known to be involved in LD-A2pm synthesis were uncovered in a large collection of thermosensitive mutants obtained by indirect selection. We propose that this surprisingly restricted distribution of the thermosensitive dap mutations isolated so far is due to the existence, in each step of the pathway, of isoenzymes encoded by separate genes. The biological role of different aspartokinases was investigated with mutants deficient in dapE and dapG genes. Growth characteristics of these mutants in the presence of various combinations of aspartate family amino acids allow a reassessment of a metabolic channel hypothesis, i.e. the proposed existence of multienzyme complexes, each specific for a given end product.

  4. Norrie disease gene is distinct from the monoamine oxidase genes

    OpenAIRE

    Sims, Katherine B.; Ozelius, Laurie; Corey, Timothy; Rinehart, William B.; Liberfarb, Ruth; Haines, Jonathan; Chen, Wei Jane; Norio, Reijo; Sankila, Eeva; de la Chapelle, Albert; Murphy, Dennis L.; Gusella, James; Breakefield, Xandra O.

    1989-01-01

    The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and /or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in “classic” Norrie disease patients. Genomic DNA from these “nondelet...

  5. Loss aversion and 5HTT gene variants in adolescent anxiety.

    Science.gov (United States)

    Ernst, Monique; Plate, Rista C; Carlisi, Christina O; Gorodetsky, Elena; Goldman, David; Pine, Daniel S

    2014-04-01

    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. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Invasion and persistence of a selfish gene in the Cnidaria.

    Directory of Open Access Journals (Sweden)

    Matthew R Goddard

    Full Text Available BACKGROUND: Homing endonuclease genes (HEGs are superfluous, but are capable of invading populations that mix alleles by biasing their inheritance patterns through gene conversion. One model suggests that their long-term persistence is achieved through recurrent invasion. This circumvents evolutionary degeneration, but requires reasonable rates of transfer between species to maintain purifying selection. Although HEGs are found in a variety of microbes, we found the previous discovery of this type of selfish genetic element in the mitochondria of a sea anemone surprising. METHODS/PRINCIPAL FINDINGS: We surveyed 29 species of Cnidaria for the presence of the COXI HEG. Statistical analyses provided evidence for HEG invasion. We also found that 96 individuals of Metridium senile, from five different locations in the UK, had identical HEG sequences. This lack of sequence divergence illustrates the stable nature of Anthozoan mitochondria. Our data suggests this HEG conforms to the recurrent invasion model of evolution. CONCLUSIONS: Ordinarily such low rates of HEG transfer would likely be insufficient to enable major invasion. However, the slow rate of Anthozoan mitochondrial change lengthens greatly the time to HEG degeneration: this significantly extends the periodicity of the HEG life-cycle. We suggest that a combination of very low substitution rates and rare transfers facilitated metazoan HEG invasion.

  7. Invasion and persistence of a selfish gene in the Cnidaria.

    Science.gov (United States)

    Goddard, Matthew R; Leigh, Jessica; Roger, Andrew J; Pemberton, Andrew J

    2006-12-20

    Homing endonuclease genes (HEGs) are superfluous, but are capable of invading populations that mix alleles by biasing their inheritance patterns through gene conversion. One model suggests that their long-term persistence is achieved through recurrent invasion. This circumvents evolutionary degeneration, but requires reasonable rates of transfer between species to maintain purifying selection. Although HEGs are found in a variety of microbes, we found the previous discovery of this type of selfish genetic element in the mitochondria of a sea anemone surprising. We surveyed 29 species of Cnidaria for the presence of the COXI HEG. Statistical analyses provided evidence for HEG invasion. We also found that 96 individuals of Metridium senile, from five different locations in the UK, had identical HEG sequences. This lack of sequence divergence illustrates the stable nature of Anthozoan mitochondria. Our data suggests this HEG conforms to the recurrent invasion model of evolution. Ordinarily such low rates of HEG transfer would likely be insufficient to enable major invasion. However, the slow rate of Anthozoan mitochondrial change lengthens greatly the time to HEG degeneration: this significantly extends the periodicity of the HEG life-cycle. We suggest that a combination of very low substitution rates and rare transfers facilitated metazoan HEG invasion.

  8. Learning abilities and disabilities: generalist genes in early adolescence.

    Science.gov (United States)

    Davis, Oliver S P; Haworth, Claire M A; Plomin, Robert

    2009-01-01

    The new view of cognitive neuropsychology that considers not just case studies of rare severe disorders but also common disorders, as well as normal variation and quantitative traits, is more amenable to recent advances in molecular genetics, such as genome-wide association studies, and advances in quantitative genetics, such as multivariate genetic analysis. A surprising finding emerging from multivariate quantitative genetic studies across diverse learning abilities is that most genetic influences are shared: they are "generalist", rather than "specialist". We exploited widespread access to inexpensive and fast Internet connections in the United Kingdom to assess over 5000 pairs of 12-year-old twins from the Twins Early Development Study (TEDS) on four distinct batteries: reading, mathematics, general cognitive ability (g) and, for the first time, language. Genetic correlations remain high among all of the measured abilities, with language as highly correlated genetically with g as reading and mathematics. Despite developmental upheaval, generalist genes remain important into early adolescence, suggesting optimal strategies for molecular genetic studies seeking to identify the genes of small effect that influence learning abilities and disabilities.

  9. Horizontal gene transfer and mobile genetic elements in marine systems.

    Science.gov (United States)

    Sobecky, Patricia A; Hazen, Tracy H

    2009-01-01

    The pool of mobile genetic elements (MGE) in microbial communities consists of viruses, plasmids, and associated elements (insertion sequences, transposons, and integrons) that are either self-transmissible or use mobile plasmids and viruses as vehicles for their dissemination. This mobilome facilitates the horizontal transfer of genes that promote the evolution and adaptation of microbial communities. Efforts to characterize MGEs from microbial populations resident in a variety of ecological habitats have revealed a surprisingly novel and seemingly untapped biodiversity. To better understand the impact of horizontal gene transfer (HGT), as well as the agents that promote HGT in marine ecosystems and to determine whether or not environmental parameters can effect the composition and structure of the mobilome in marine microbial communities, information on the distribution, diversity, and ecological traits of the marine mobilome is presented. In this chapter we discuss recent insights gained from different methodological approaches used to characterize the biodiversity and ecology of MGE in marine environments and their contributions to HGT. In addition, we present case studies that highlight specific HGT examples in coastal, open-ocean, and deep-sea marine ecosystems.

  10. Natural gene therapy in monozygotic twins with Fanconi anemia.

    Science.gov (United States)

    Mankad, Anuj; Taniguchi, Toshiyasu; Cox, Barbara; Akkari, Yassmine; Rathbun, R Keaney; Lucas, Lora; Bagby, Grover; Olson, Susan; D'Andrea, Alan; Grompe, Markus

    2006-04-15

    Monozygotic twin sisters, with nonhematologic symptoms of Fanconi anemia (FA), were discovered to be somatic mosaics for mutations in the FANCA gene. Skin fibroblasts, but not lymphocytes or committed hematopoietic progenitors, were sensitive to DNA cross-linking agents. Molecular analysis revealed, in skin cells of both twins, a frameshift causing deletion in exon 27 (2555deltaT) and an exon 28 missense mutation (2670G>A/R880Q). The latter resulted in primarily cytoplasmic expression and reduced function of the mutant FANCA (R880Q) protein. Surprisingly, the same acquired exon 30 missense change (2927G>A/E966K) was detected in the hematopoietic cells of both sisters, but not in their fibroblasts, nor in either parent. This compensatory mutation existed in cis with the maternal exon 28 mutation, and it restored function and nuclear localization of the resulting protein. Both sisters have been free of hematologic symptoms for more than 2 decades, suggesting that this de novo mutation occurred prenatally in a single hematopoietic stem cell (HSC) in one twin and that descendants of this functionally corrected HSC, via intra-uterine circulation, repopulated the blood lineages of both sisters. This finding suggests that treating FA patients with gene therapy might require transduction of only a few hematopoietic stem cells.

  11. 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.

  12. The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein-coding genes

    DEFF Research Database (Denmark)

    Pantano, Lorena; Jodar, Meritxell; Bak, Mads

    2015-01-01

    -specific genes. The most abundant class of small noncoding RNAs in sperm are PIWI-interacting RNAs (piRNAs). Surprisingly, we found that human sperm cells contain piRNAs processed from pseudogenes. Clusters of piRNAs from human testes contain pseudogenes transcribed in the antisense strand and processed...... into small RNAs. Several human protein-coding genes contain antisense predicted targets of pseudogene-derived piRNAs in the male germline and these piRNAs are still found in mature sperm. Our study provides the most extensive data set and annotation of human sperm small RNAs to date and is a resource...... for further functional studies on the roles of sperm small RNAs. In addition, we propose that some of the pseudogene-derived human piRNAs may regulate expression of their parent gene in the male germline....

  13. Hidden genes in birds

    Czech Academy of Sciences Publication Activity Database

    Hron, Tomáš; Pajer, Petr; Pačes, Jan; Bartůněk, Petr; Elleder, Daniel

    2015-01-01

    Roč. 16, August 18 (2015) ISSN 1465-6906 R&D Projects: GA MŠk(CZ) LK11215; GA MŠk LO1419 Grant - others:GA MŠk(CZ) LM2010005 Institutional support: RVO:68378050 Keywords : REPETITIVE SEQUENCES * G/C stretches * avian genes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.313, year: 2015

  14. Rhabdovirus accessory genes.

    Science.gov (United States)

    Walker, Peter J; Dietzgen, Ralf G; Joubert, D Albert; Blasdell, Kim R

    2011-12-01

    The Rhabdoviridae is one of the most ecologically diverse families of RNA viruses with members infecting a wide range of organisms including placental mammals, marsupials, birds, reptiles, fish, insects and plants. The availability of complete nucleotide sequences for an increasing number of rhabdoviruses has revealed that their ecological diversity is reflected in the diversity and complexity of their genomes. The five canonical rhabdovirus structural protein genes (N, P, M, G and L) that are shared by all rhabdoviruses are overprinted, overlapped and interspersed with a multitude of novel and diverse accessory genes. Although not essential for replication in cell culture, several of these genes have been shown to have roles associated with pathogenesis and apoptosis in animals, and cell-to-cell movement in plants. Others appear to be secreted or have the characteristics of membrane-anchored glycoproteins or viroporins. However, most encode proteins of unknown function that are unrelated to any other known proteins. Understanding the roles of these accessory genes and the strategies by which rhabdoviruses use them to engage, divert and re-direct cellular processes will not only present opportunities to develop new anti-viral therapies but may also reveal aspects of cellar function that have broader significance in biology, agriculture and medicine. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  15. Targeting fumonisin biosynthetic genes

    Science.gov (United States)

    The fungus Fusarium is an agricultural problem because it can cause disease on most crop plants and can contaminate crops with mycotoxins. There is considerable variation in the presence/absence and genomic location of gene clusters responsible for synthesis of mycotoxins and other secondary metabol...

  16. Radio-induced genes

    International Nuclear Information System (INIS)

    Rigaud, O.; Kazmaier, M.

    2000-01-01

    The monitoring system of the DNA integrity of an irradiated cell does not satisfy oneself to recruit the enzymes allowing the repair of detected damages. It sends an alarm signal whom transmission leads to the activation of specific genes in charge of stopping the cell cycle, the time to make the repair works, or to lead to the elimination of a too much damaged cell. Among the numerous genes participating to the monitoring of cell response to irradiation, the target genes of the mammalian P53 protein are particularly studied. Caretaker of the genome, this protein play a central part in the cell response to ionizing radiations. this response is less studied among plants. A way to tackle it is to be interested in the radioinduced genes identification in the vegetal cell, while taking advantage of knowledge got in the animal field. The knowledge of the complete genome of the arabette (arabidopsis thaliana), the model plant and the arising of new techniques allow to lead this research at a previously unknown rhythm in vegetal biology. (N.C.)

  17. The Gene Guessing Game

    OpenAIRE

    Dunham, Ian

    2000-01-01

    A recent flurry of publications and media attention has revived interest in the question of how many genes exist in the human genome. Here, I review the estimates and use genomic sequence data from human chromosomes 21 and 22 to establish my own prediction.

  18. Targeting trichothecene biosynthetic genes

    NARCIS (Netherlands)

    Wei, Songhong; Lee, van der Theo; Verstappen, Els; Gent, van Marga; Waalwijk, Cees

    2017-01-01

    Biosynthesis of trichothecenes requires the involvement of at least 15 genes, most of which have been targeted for PCR. Qualitative PCRs are used to assign chemotypes to individual isolates, e.g., the capacity to produce type A and/or type B trichothecenes. Many regions in the core cluster

  19. Silence of the Genes

    Indian Academy of Sciences (India)

    Srimath

    a gene in the opposite orientation in a cultured plant cell line and observed that the ..... started emerging in early 1990s from the work carried out by the. It is believed that ... cause human diseases such as cervical cancer, hepatitis, measles.

  20. Silence of the Genes

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 12; Issue 4. Silence of the Genes - 2006 Nobel Prize in Physiology or Medicine. Utpal Nath Saumitra Das. General Article Volume 12 Issue 4 April 2007 pp 6-18. Fulltext. Click here to view fulltext PDF. Permanent link:

  1. Suicide genes or p53 gene and p53 target genes as targets for cancer gene therapy by ionizing radiation

    International Nuclear Information System (INIS)

    Liu Bing; Chinese Academy of Sciences, Beijing; Zhang Hong

    2005-01-01

    Radiotherapy has some disadvantages due to the severe side-effect on the normal tissues at a curative dose of ionizing radiation (IR). Similarly, as a new developing approach, gene therapy also has some disadvantages, such as lack of specificity for tumors, limited expression of therapeutic gene, potential biological risk. To certain extent, above problems would be solved by the suicide genes or p53 gene and its target genes therapies targeted by ionizing radiation. This strategy not only makes up the disadvantage from radiotherapy or gene therapy alone, but also promotes success rate on the base of lower dose. By present, there have been several vectors measuring up to be reaching clinical trials. This review focused on the development of the cancer gene therapy through suicide genes or p53 and its target genes mediated by IR. (authors)

  2. Genes2FANs: connecting genes through functional association networks

    Science.gov (United States)

    2012-01-01

    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 finding that disease genes in

  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. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Genes contributing to prion pathogenesis

    DEFF Research Database (Denmark)

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V

    2008-01-01

    incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1...

  5. Pronounced effects of acute endurance exercise on gene expression in resting and exercising human skeletal muscle.

    Science.gov (United States)

    Catoire, Milène; Mensink, Marco; Boekschoten, Mark V; Hangelbroek, Roland; Müller, Michael; Schrauwen, Patrick; Kersten, Sander

    2012-01-01

    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.

  6. Aquilegia B gene homologs promote petaloidy of the sepals and maintenance of the C domain boundary

    Directory of Open Access Journals (Sweden)

    Bharti Sharma

    2017-11-01

    Full Text Available Abstract The model Aquilegia coerulea x “Origami” possesses several interesting floral features, including petaloid sepals that are morphologically distinct from the true petals and a broad domain containing many whorls of stamens. We undertook the current study in an effort to understand the former trait, but additionally uncovered data that inform on the latter. The Aquilegia B gene homolog AqPI is shown to contribute to the production of anthocyanin in the first whorl sepals, although it has no major role in their morphology. Surprisingly, knockdown of AqPI in Aquilegia coerulea x “Origami” also reveals a role for the B class genes in maintaining the expression of the C gene homolog AqAG1 in the outer whorls of stamens. These findings suggest that the transference of pollinator function to the first whorl sepals included a non-homeotic recruitment of the B class genes to promote aspects of petaloidy. They also confirm results in several other Ranunculales that have revealed an unexpected regulatory connection between the B and C class genes.

  7. 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.

  8. Cyclooxygenase and lipoxygenase gene expression in the inflammogenesis of breast cancer.

    Science.gov (United States)

    Kennedy, Brian M; Harris, Randall E

    2018-05-07

    We examined the expression of major inflammatory genes, cyclooxygenase-1 and 2 (COX1, COX2) and arachidonate 5-lipoxygenase (ALOX5) in 1090 tumor samples of invasive breast cancer from The Cancer Genome Atlas (TCGA). Mean cyclooxygenase expression (COX1 + COX2) ranked in the upper 99th percentile of all 20,531 genes and surprisingly, the mean expression of COX1 was more than tenfold higher than COX2. Highly significant correlations were observed between COX2 with eight tumor-promoting genes (EGR2, IL6, RGS2, B3GNT5, SGK1, SLC2A3, SFRP1 and ETS2) and between ALOX5 and ten tumor promoter genes (CD33, MYOF1, NLRP1, GAB3, CD4, IFR8, CYTH4, BTK, FGR, CD37). Expression of CYP19A1 (aromatase) was significantly correlated with COX2, but only in tumors positive for ER, PR and HER2. Tumor-promoting genes correlated with the expression of COX1, COX2, and ALOX5 are known to effectively increase mitogenesis, mutagenesis, angiogenesis, cell survival, immunosuppression and metastasis in the pathogenesis of breast cancer.

  9. Using gene expression noise to understand gene regulation

    NARCIS (Netherlands)

    Munsky, B.; Neuert, G.; van Oudenaarden, A.

    2012-01-01

    Phenotypic variation is ubiquitous in biology and is often traceable to underlying genetic and environmental variation. However, even genetically identical cells in identical environments display variable phenotypes. Stochastic gene expression, or gene expression "noise," has been suggested as a

  10. Patenting human genes: Chinese academic articles' portrayal of gene patents.

    Science.gov (United States)

    Du, Li

    2018-04-24

    The patenting of human genes has been the subject of debate for decades. While China has gradually come to play an important role in the global genomics-based testing and treatment market, little is known about Chinese scholars' perspectives on patent protection for human genes. A content analysis of academic literature was conducted to identify Chinese scholars' concerns regarding gene patents, including benefits and risks of patenting human genes, attitudes that researchers hold towards gene patenting, and any legal and policy recommendations offered for the gene patent regime in China. 57.2% of articles were written by law professors, but scholars from health sciences, liberal arts, and ethics also participated in discussions on gene patent issues. While discussions of benefits and risks were relatively balanced in the articles, 63.5% of the articles favored gene patenting in general and, of the articles (n = 41) that explored gene patents in the Chinese context, 90.2% supported patent protections for human genes in China. The patentability of human genes was discussed in 33 articles, and 75.8% of these articles reached the conclusion that human genes are patentable. Chinese scholars view the patent regime as an important legal tool to protect the interests of inventors and inventions as well as the genetic resources of China. As such, many scholars support a gene patent system in China. These attitudes towards gene patents remain unchanged following the court ruling in the Myriad case in 2013, but arguments have been raised about the scope of gene patents, in particular that the increasing numbers of gene patents may negatively impact public health in China.

  11. 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. PMID:26393928

  12. Dynamics of immediate early gene and neuropeptide gene response to prolonged immobilization stress: evidence against a critical role of the termination of exposure to the stressor.

    Science.gov (United States)

    Trnecková, Lenka; Rotllant, David; Klenerová, Vera; Hynie, Sixtus; Armario, Antonio

    2007-02-01

    Stress-induced expression of immediate early genes (IEGs) appears to be transient even if the exposure to the stressor persists. However, there are some exceptions which suggest that particular characteristics of stressors can affect the dynamics of IEG expression. We studied in selected telencephalic, diencephalic and brainstem regions the mRNA levels of two clearly distinct IEGs (c-fos and arc) during prolonged exposure to a severe stressor such as immobilization (IMO) and after releasing the rats from the situation. Although regional differences were observed with the two IEGs, overall, c-fos mRNA levels progressively declined over the course of 4 h of continuous exposure to IMO, whereas arc mRNA levels were maintained at high levels in the brain regions that express this gene under stress (telencephalon). Levels of CRF hnRNA in the hypothalamus paraventricular nucleus only slightly declined during prolonged exposure to IMO. Surprisingly, termination of exposure to IMO did not modify CRF gene expression in the paraventricular nucleus or the pattern of IEGs expression, with the exception of c-fos in the lateral septum. Thus, putative signals associated to the termination of exposure to IMO were unable to modify either IEG expression in most brain areas or CRF gene expression in the paraventricular nucleus.

  13. 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.

  14. Genes, stress, and depression.

    Science.gov (United States)

    Wurtman, Richard J

    2005-05-01

    A relationship between genetic makeup and susceptibility to major depressive disorder (MDD) has long been suspected on the basis of family and twin studies. A metaanalysis of reports on the basis of twin studies has estimated MDD's degree of heritability to be 0.33 (confidence interval, 0.26-0.39). Among families exhibiting an increased prevalence of MDD, risk of developing the illness was enhanced in members exposed to a highly stressful environment. Aberrant genes can predispose to depression in a number of ways, for example, by diminishing production of growth factors that act during brain development. An aberrant gene could also increase or decrease a neurotransmitter's release into synapses, its actions, or its duration of activity. The gene products of greatest interest at present are those involved in the synthesis and actions of serotonin; among them, the serotonin-uptake protein localized within the terminals and dendrites of serotonin-releasing neurons. It has been found that the Vmax of platelet serotonin uptake is low in some patients with MDD; also, Vmax is highly correlated in twins. Antidepressant drugs such as the selective serotonin reuptake inhibitors act on this uptake protein. The specific genetic locus causing serotonin uptake to be lower in some patients with major depression involves a polymorphic region (5-HTTLPR) in the promoter region of the gene for the uptake protein. The gene itself exists as several alleles, the short "S" allele and the long "L" allele. The S variant is associated with less, and the L variant with more, of the uptake protein. The effect of stressful life events on depressive symptoms in young adults was found to be significantly stronger among SS or SL subjects than among LL subjects. Neuroimaging studies showed that people with the SS or SL alleles exhibited a greater activation of the amygdala in response to fearful stimuli than those with LL. It has been reported recently that mutations in the gene that controls

  15. Vertebrate gene predictions and the problem of large genes

    DEFF Research Database (Denmark)

    Wang, Jun; Li, ShengTing; Zhang, Yong

    2003-01-01

    To find unknown protein-coding genes, annotation pipelines use a combination of ab initio gene prediction and similarity to experimentally confirmed genes or proteins. Here, we show that although the ab initio predictions have an intrinsically high false-positive rate, they also have a consistent...

  16. The evolution of multiple isotypic IgM heavy chain genes in the shark.

    Science.gov (United States)

    Lee, Victor; Huang, Jing Li; Lui, Ming Fai; Malecek, Karolina; Ohta, Yuko; Mooers, Arne; Hsu, Ellen

    2008-06-01

    The IgM H chain gene organization of cartilaginous fishes consists of 15-200 miniloci, each with a few gene segments (V(H)-D1-D2-J(H)) and one C gene. This is a gene arrangement ancestral to the complex IgH locus that exists in all other vertebrate classes. To understand the molecular evolution of this system, we studied the nurse shark, which has relatively fewer loci, and characterized the IgH isotypes for organization, functionality, and the somatic diversification mechanisms that act upon them. Gene numbers differ slightly between individuals ( approximately 15), but five active IgM subclasses are always present. Each gene undergoes rearrangement that is strictly confined within the minilocus; in B cells there is no interaction between adjacent loci located > or =120 kb apart. Without combinatorial events, the shark IgM H chain repertoire is based on junctional diversity and, subsequently, somatic hypermutation. We suggest that the significant contribution by junctional diversification reflects the selected novelty introduced by RAG in the early vertebrate ancestor, whereas combinatorial diversity coevolved with the complex translocon organization. Moreover, unlike other cartilaginous fishes, there are no germline-joined VDJ at any nurse shark mu locus, and we suggest that such genes, when functional, are species-specific and may have specialized roles. With an entire complement of IgM genes available for the first time, phylogenetic analyses were performed to examine how the multiple Ig loci evolved. We found that all domains changed at comparable rates, but V(H) appears to be under strong positive selection for increased amino acid sequence diversity, and surprisingly, so does Cmicro2.

  17. 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

  18. 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.

  19. Plant gene technology: social considerations

    African Journals Online (AJOL)

    Administrator

    The genetic modification of plants by gene technology is of immense potential benefits, but there may be possible risks. ... As a new endeavour, however, people have a mixed ... reality by gene biotechnology (Watson, 1997). Industrial ...

  20. Brains, Genes and Primates

    Science.gov (United States)

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  1. Gene Porter Bridwell

    Science.gov (United States)

    1994-01-01

    Gene Porter Bridwell served as the director of the Marshall Space Flight Center from January 6, 1994 until February 3, 1996, when he retired from NASA after thirty-four years service. Bridwell, a Marshall employee since 1962, had been Marshall's Space Shuttle Projects Office Director and Space Station Redesign Team deputy manager. Under Bridwell, Marshall worked to develop its role as a Center of Excellence for propulsion and for providing access to space.

  2. Mutant genes in pea breeding

    International Nuclear Information System (INIS)

    Swiecicki, W.K.

    1990-01-01

    Full text: Mutations of genes Dpo (dehiscing pods) and A (anthocyanin synthesis) played a role in pea domestication. A number of other genes were important in cultivar development for 3 types of usage (dry seeds, green vegetable types, fodder), e.g. fn, fna, le, p, v, fas and af. New genes (induced and spontaneous), are important for present ideotypes and are registered by the Pisum Genetics Association (PGA). Comparison of a pea variety ideotype with the variation available in gene banks shows that breeders need 'new' features. In mutation induction experiments, genotype, mutagen and method of treatment (e.g. combined or fractionated doses) are varied for broadening the mutation spectrum and selecting more genes of agronomic value. New genes are genetically analysed. In Poland, some mutant varieties with the gene afila were registered, controlling lodging by a shorter stem and a higher number of internodes. Really non-lodging pea varieties could strongly increase seed yield. But the probability of detecting a major gene for lodging resistance is low. Therefore, mutant genes with smaller influence on plant architecture are sought, to combine their effect by crossing. Promising seem to be the genes rogue, reductus and arthritic as well as a number of mutant genes not yet genetically identified. The gene det for terminal inflorescence - similarly to Vicia faba - changes plant development. Utilisation of assimilates and ripening should be better. Improvement of harvest index should give higher seed yield. A number of genes controlling disease resistance are well known (eg. Fw, Fnw, En, mo and sbm). Important in mass screening of resistance are closely linked gene markers. Pea gene banks collect respective lines, but mutants induced in highly productive cultivars would be better. Inducing gene markers sometimes seems to be easier than transfer by crossing. Mutation induction in pea breeding is probably more important because a high number of monogenic features are

  3. Gene doping in modern sport.

    OpenAIRE

    MAREK SAWCZUK; AGNIESZKA MACIEJEWSKA; PAWEL CIESZCZYK,

    2009-01-01

    Background: The subject of this paper is gene doping, which should be understood as "he non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to improve athletic performance". The authors of this work, based on the review of literature and previous research, make an attempt at wider characterization of gene doping and the discussion of related potential threats.Methods: This is a comprehensive survey of literature on the latest app...

  4. Regulation of eucaryotic gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Brent, R.; Ptashne, M.S

    1989-05-23

    This patent describes a method of regulating the expression of a gene in a eucaryotic cell. The method consists of: providing in the eucaryotic cell, a peptide, derived from or substantially similar to a peptide of a procaryotic cell able to bind to DNA upstream from or within the gene, the amount of the peptide being sufficient to bind to the gene and thereby control expression of the gene.

  5. 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

  6. Genealogy and gene trees.

    Science.gov (United States)

    Rasmuson, Marianne

    2008-02-01

    Heredity can be followed in persons or in genes. Persons can be identified only a few generations back, but simplified models indicate that universal ancestors to all now living persons have occurred in the past. Genetic variability can be characterized as variants of DNA sequences. Data are available only from living persons, but from the pattern of variation gene trees can be inferred by means of coalescence models. The merging of lines backwards in time leads to a MRCA (most recent common ancestor). The time and place of living for this inferred person can give insights in human evolutionary history. Demographic processes are incorporated in the model, but since culture and customs are known to influence demography the models used ought to be tested against available genealogy. The Icelandic data base offers a possibility to do so and points to some discrepancies. Mitochondrial DNA and Y chromosome patterns give a rather consistent view of human evolutionary history during the latest 100 000 years but the earlier epochs of human evolution demand gene trees with longer branches. The results of such studies reveal as yet unsolved problems about the sources of our genome.

  7. Gene therapy of cancer and development of therapeutic target gene

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene.

  8. Gene therapy of cancer and development of therapeutic target gene

    International Nuclear Information System (INIS)

    Kim, Chang Min; Kwon, Hee Chung

    1998-04-01

    We applied HSV-tk/GCV strategy to orthotopic rat hepatoma model and showed anticancer effects of hepatoma. The increased expression of Lac Z gene after adenovirus-mediated gene delivery throughout hepatic artery was thought that is increased the possibility of gene therapy for curing hepatoma. With the construction of kGLP-laboratory, it is possible to produce a good quantity and quality of adenovirus in lage-scale production and purification of adenovirus vector. Also, the analysis of hepatoma related genes by PCR-LOH could be used for the diagnosis of patients and the development of therapeutic gene

  9. Gene electrotransfer in clinical trials

    DEFF Research Database (Denmark)

    Gehl, Julie

    2014-01-01

    Electroporation is increasingly being used for delivery of chemotherapy to tumors. Likewise, gene delivery by electroporation is rapidly gaining momentum for both vaccination purposes and for delivery of genes coding for other therapeutic molecules, such as chronic diseases or cancer. This chapter...... describes how gene therapy may be performed using electric pulses to enhance uptake and expression....

  10. Gene probes: principles and protocols

    National Research Council Canada - National Science Library

    Aquino de Muro, Marilena; Rapley, Ralph

    2002-01-01

    ... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

  11. Compositional gradients in Gramineae genes

    DEFF Research Database (Denmark)

    Wong, Gane Ka-Shu; Wang, Jun; Tao, Lin

    2002-01-01

    In this study, we describe a property of Gramineae genes, and perhaps all monocot genes, that is not observed in eudicot genes. Along the direction of transcription, beginning at the junction of the 5'-UTR and the coding region, there are gradients in GC content, codon usage, and amino-acid usage...

  12. Independent Gene Discovery and Testing

    Science.gov (United States)

    Palsule, Vrushalee; Coric, Dijana; Delancy, Russell; Dunham, Heather; Melancon, Caleb; Thompson, Dennis; Toms, Jamie; White, Ashley; Shultz, Jeffry

    2010-01-01

    A clear understanding of basic gene structure is critical when teaching molecular genetics, the central dogma and the biological sciences. We sought to create a gene-based teaching project to improve students' understanding of gene structure and to integrate this into a research project that can be implemented by instructors at the secondary level…

  13. Gene function prediction based on Gene Ontology Hierarchy Preserving Hashing.

    Science.gov (United States)

    Zhao, Yingwen; Fu, Guangyuan; Wang, Jun; Guo, Maozu; Yu, Guoxian

    2018-02-23

    Gene Ontology (GO) uses structured vocabularies (or terms) to describe the molecular functions, biological roles, and cellular locations of gene products in a hierarchical ontology. GO annotations associate genes with GO terms and indicate the given gene products carrying out the biological functions described by the relevant terms. However, predicting correct GO annotations for genes from a massive set of GO terms as defined by GO is a difficult challenge. To combat with this challenge, we introduce a Gene Ontology Hierarchy Preserving Hashing (HPHash) based semantic method for gene function prediction. HPHash firstly measures the taxonomic similarity between GO terms. It then uses a hierarchy preserving hashing technique to keep the hierarchical order between GO terms, and to optimize a series of hashing functions to encode massive GO terms via compact binary codes. After that, HPHash utilizes these hashing functions to project the gene-term association matrix into a low-dimensional one and performs semantic similarity based gene function prediction in the low-dimensional space. Experimental results on three model species (Homo sapiens, Mus musculus and Rattus norvegicus) for interspecies gene function prediction show that HPHash performs better than other related approaches and it is robust to the number of hash functions. In addition, we also take HPHash as a plugin for BLAST based gene function prediction. From the experimental results, HPHash again significantly improves the prediction performance. The codes of HPHash are available at: http://mlda.swu.edu.cn/codes.php?name=HPHash. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Alternaria Toxins: Potential Virulence Factors and Genes Related to Pathogenesis

    Directory of Open Access Journals (Sweden)

    Mukesh Meena

    2017-08-01

    Full Text Available Alternaria is an important fungus to study due to their different life style from saprophytes to endophytes and a very successful fungal pathogen that causes diseases to a number of economically important crops. Alternaria species have been well-characterized for the production of different host-specific toxins (HSTs and non-host specific toxins (nHSTs which depend upon their physiological and morphological stages. The pathogenicity of Alternaria species depends on host susceptibility or resistance as well as quantitative production of HSTs and nHSTs. These toxins are chemically low molecular weight secondary metabolites (SMs. The effects of toxins are mainly on different parts of cells like mitochondria, chloroplast, plasma membrane, Golgi complex, nucleus, etc. Alternaria species produce several nHSTs such as brefeldin A, tenuazonic acid, tentoxin, and zinniol. HSTs that act in very low concentrations affect only certain plant varieties or genotype and play a role in determining the host range of specificity of plant pathogens. The commonly known HSTs are AAL-, AK-, AM-, AF-, ACR-, and ACT-toxins which are named by their host specificity and these toxins are classified into different family groups. The HSTs are differentiated on the basis of bio-statistical and other molecular analyses. All these toxins have different mode of action, biochemical reactions and signaling mechanisms to cause diseases. Different species of Alternaria produced toxins which reveal its biochemical and genetic effects on itself as well as on its host cells tissues. The genes responsible for the production of HSTs are found on the conditionally dispensable chromosomes (CDCs which have been well characterized. Different bio-statistical methods like basic local alignment search tool (BLAST data analysis used for the annotation of gene prediction, pathogenicity-related genes may provide surprising knowledge in present and future.

  15. Immunoglobulin gene usage in the human anti-pathogen response.

    Science.gov (United States)

    Newkirk, M M; Rioux, J D

    1995-09-01

    The human antibody response to foreign pathogens is generated to a relatively small number of target surface proteins and carbohydrates that nonetheless have an extensive array of epitopes. The study of human monoclonal antibodies to different pathogens shows that there are a diversity of mechanisms used to generate a sufficient repertoire of antibodies to combat the invading pathogens. Although many different immunoglobulin gene elements are used to construct the anti-pathogen response, some elements are used more often than would be expected if all elements were used randomly. For example, the immune response to Haemophilus influenzae polysaccharide appears to be quite narrow, being restricted primarily to a specific heavy-chain gene, 3-15, and a lambda light-chain family II member, 4A. In contrast, for the immune response to cytomegalovirus proteins, a wider group of gene elements is needed. It is also surprising that despite an investigator bias for IgG- rather than IgM-secreting immortal B cells (because of their high affinity and neutralizing abilities), 26% of light chains and 13% of heavy chains showed a very low level of somatic mutation, equivalent to an IgM molecule that has not undergone affinity maturation. Although some highly mutated IgG molecules are present in the anti-pathogen response, most of the monoclonal antibodies specific for viruses or bacteria have a level of somatic hypermutation similar to that of the adult IgM repertoire. A number of studies have shown that there are similarities in the antibody responses to pathogens and to self (autoantibodies).(ABSTRACT TRUNCATED AT 250 WORDS)

  16. The ethics of gene therapy.

    Science.gov (United States)

    Chan, Sarah; Harris, John

    2006-10-01

    Recent developments have progressed in areas of science that pertain to gene therapy and its ethical implications. This review discusses the current state of therapeutic gene technologies, including stem cell therapies and genetic modification, and identifies ethical issues of concern in relation to the science of gene therapy and its application, including the ethics of embryonic stem cell research and therapeutic cloning, the risks associated with gene therapy, and the ethics of clinical research in developing new therapeutic technologies. Additionally, ethical issues relating to genetic modification itself are considered: the significance of the human genome, the distinction between therapy and enhancement, and concerns regarding gene therapy as a eugenic practice.

  17. Radiopharmaceuticals to monitor gene transfer

    International Nuclear Information System (INIS)

    Wiebe, L. I.; Morin, K. W.; Knaus, E. E.

    1997-01-01

    Advances in genetic engineering and molecular biology have opened the door to disease treatment by transferring genes to cells that are responsible for the pathological condition being addressed. These genes can serve to supplement or introduce the function of indigenous genes that are either inadequately expressed or that are congenitally absent in the patient. They can introduce new functions such as drug sensitization to provide a unique therapeutic target. Gene transfer is readily monitored in vitro using a range of histochemical and biochemical tests that are ''built in'' to the therapeutic gene cassette. In vivo, in situ monitoring of the gene transfer and gene expression processes can be achieved with these tests only if biopsy is possible. Scintigraphic imaging can offer unique information on both the extent and location of gene expression, provided that an appropriate reporter gene is included in the therapeutic cassette. This overview includes a brief orientation to gene transfer therapy and is followed by a review of current approaches to gene therapy imaging. The concluding section deals with imaging based on radiolabelled nucleoside substrates for herpes simplex type-1 thymidine kinase, with emphasis on IVFRU, a stable potent and selective HSV-1 TK substrate developed in their laboratories

  18. 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.

  19. Gene Circuit Analysis of the Terminal Gap Gene huckebein

    Science.gov (United States)

    Ashyraliyev, Maksat; Siggens, Ken; Janssens, Hilde; Blom, Joke; Akam, Michael; Jaeger, Johannes

    2009-01-01

    The early embryo of Drosophila melanogaster provides a powerful model system to study the role of genes in pattern formation. The gap gene network constitutes the first zygotic regulatory tier in the hierarchy of the segmentation genes involved in specifying the position of body segments. Here, we use an integrative, systems-level approach to investigate the regulatory effect of the terminal gap gene huckebein (hkb) on gap gene expression. We present quantitative expression data for the Hkb protein, which enable us to include hkb in gap gene circuit models. Gap gene circuits are mathematical models of gene networks used as computational tools to extract regulatory information from spatial expression data. This is achieved by fitting the model to gap gene expression patterns, in order to obtain estimates for regulatory parameters which predict a specific network topology. We show how considering variability in the data combined with analysis of parameter determinability significantly improves the biological relevance and consistency of the approach. Our models are in agreement with earlier results, which they extend in two important respects: First, we show that Hkb is involved in the regulation of the posterior hunchback (hb) domain, but does not have any other essential function. Specifically, Hkb is required for the anterior shift in the posterior border of this domain, which is now reproduced correctly in our models. Second, gap gene circuits presented here are able to reproduce mutants of terminal gap genes, while previously published models were unable to reproduce any null mutants correctly. As a consequence, our models now capture the expression dynamics of all posterior gap genes and some variational properties of the system correctly. This is an important step towards a better, quantitative understanding of the developmental and evolutionary dynamics of the gap gene network. PMID:19876378

  20. The Caenorhabditis chemoreceptor gene families

    Directory of Open Access Journals (Sweden)

    Robertson Hugh M

    2008-10-01

    Full Text Available Abstract Background Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Results Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Conclusion Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  1. The Caenorhabditis chemoreceptor gene families.

    Science.gov (United States)

    Thomas, James H; Robertson, Hugh M

    2008-10-06

    Chemoreceptor proteins mediate the first step in the transduction of environmental chemical stimuli, defining the breadth of detection and conferring stimulus specificity. Animal genomes contain families of genes encoding chemoreceptors that mediate taste, olfaction, and pheromone responses. The size and diversity of these families reflect the biology of chemoperception in specific species. Based on manual curation and sequence comparisons among putative G-protein-coupled chemoreceptor genes in the nematode Caenorhabditis elegans, we identified approximately 1300 genes and 400 pseudogenes in the 19 largest gene families, most of which fall into larger superfamilies. In the related species C. briggsae and C. remanei, we identified most or all genes in each of the 19 families. For most families, C. elegans has the largest number of genes and C. briggsae the smallest number, suggesting changes in the importance of chemoperception among the species. Protein trees reveal family-specific and species-specific patterns of gene duplication and gene loss. The frequency of strict orthologs varies among the families, from just over 50% in two families to less than 5% in three families. Several families include large species-specific expansions, mostly in C. elegans and C. remanei. Chemoreceptor gene families in Caenorhabditis species are large and evolutionarily dynamic as a result of gene duplication and gene loss. These dynamics shape the chemoreceptor gene complements in Caenorhabditis species and define the receptor space available for chemosensory responses. To explain these patterns, we propose the gray pawn hypothesis: individual genes are of little significance, but the aggregate of a large number of diverse genes is required to cover a large phenotype space.

  2. Maximum Gene-Support Tree

    Directory of Open Access Journals (Sweden)

    Yunfeng Shan

    2008-01-01

    Full Text Available Genomes and genes diversify during evolution; however, it is unclear to what extent genes still retain the relationship among species. Model species for molecular phylogenetic studies include yeasts and viruses whose genomes were sequenced as well as plants that have the fossil-supported true phylogenetic trees available. In this study, we generated single gene trees of seven yeast species as well as single gene trees of nine baculovirus species using all the orthologous genes among the species compared. Homologous genes among seven known plants were used for validation of the finding. Four algorithms—maximum parsimony (MP, minimum evolution (ME, maximum likelihood (ML, and neighbor-joining (NJ—were used. Trees were reconstructed before and after weighting the DNA and protein sequence lengths among genes. Rarely a gene can always generate the “true tree” by all the four algorithms. However, the most frequent gene tree, termed “maximum gene-support tree” (MGS tree, or WMGS tree for the weighted one, in yeasts, baculoviruses, or plants was consistently found to be the “true tree” among the species. The results provide insights into the overall degree of divergence of orthologous genes of the genomes analyzed and suggest the following: 1 The true tree relationship among the species studied is still maintained by the largest group of orthologous genes; 2 There are usually more orthologous genes with higher similarities between genetically closer species than between genetically more distant ones; and 3 The maximum gene-support tree reflects the phylogenetic relationship among species in comparison.

  3. Gene and MicroRNA transcriptome analysis of Parkinson's related LRRK2 mouse models.

    Directory of Open Access Journals (Sweden)

    Véronique Dorval

    Full Text Available Mutations in leucine-rich repeat kinase 2 (LRRK2 are the most frequent cause of genetic Parkinson's disease (PD. The biological function of LRRK2 and how mutations lead to disease remain poorly defined. It has been proposed that LRRK2 could function in gene transcription regulation; however, this issue remains controversial. Here, we investigated in parallel gene and microRNA (miRNA transcriptome profiles of three different LRRK2 mouse models. Striatal tissue was isolated from adult LRRK2 knockout (KO mice, as well as mice expressing human LRRK2 wildtype (hLRRK2-WT or the PD-associated R1441G mutation (hLRRK2-R1441G. We identified a total of 761 genes and 24 miRNAs that were misregulated in the absence of LRRK2 when a false discovery rate of 0.2 was applied. Notably, most changes in gene expression were modest (i.e., <2 fold. By real-time quantitative RT-PCR, we confirmed the variations of selected genes (e.g., adra2, syt2, opalin and miRNAs (e.g., miR-16, miR-25. Surprisingly, little or no changes in gene expression were observed in mice expressing hLRRK2-WT or hLRRK2-R1441G when compared to non-transgenic controls. Nevertheless, a number of miRNAs were misexpressed in these models. Bioinformatics analysis identified several miRNA-dependent and independent networks dysregulated in LRRK2-deficient mice, including PD-related pathways. These results suggest that brain LRRK2 plays an overall modest role in gene transcription regulation in mammals; however, these effects seem context and RNA type-dependent. Our data thus set the stage for future investigations regarding LRRK2 function in PD development.

  4. Identification of genes associated with resilience/vulnerability to sleep deprivation and starvation in Drosophila.

    Science.gov (United States)

    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.

  5. Dissecting a hidden gene duplication: the Arabidopsis thaliana SEC10 locus.

    Directory of Open Access Journals (Sweden)

    Nemanja Vukašinović

    Full Text Available Repetitive sequences present a challenge for genome sequence assembly, and highly similar segmental duplications may disappear from assembled genome sequences. Having found a surprising lack of observable phenotypic deviations and non-Mendelian segregation in Arabidopsis thaliana mutants in SEC10, a gene encoding a core subunit of the exocyst tethering complex, we examined whether this could be explained by a hidden gene duplication. Re-sequencing and manual assembly of the Arabidopsis thaliana SEC10 (At5g12370 locus revealed that this locus, comprising a single gene in the reference genome assembly, indeed contains two paralogous genes in tandem, SEC10a and SEC10b, and that a sequence segment of 7 kb in length is missing from the reference genome sequence. Differences between the two paralogs are concentrated in non-coding regions, while the predicted protein sequences exhibit 99% identity, differing only by substitution of five amino acid residues and an indel of four residues. Both SEC10 genes are expressed, although varying transcript levels suggest differential regulation. Homozygous T-DNA insertion mutants in either paralog exhibit a wild-type phenotype, consistent with proposed extensive functional redundancy of the two genes. By these observations we demonstrate that recently duplicated genes may remain hidden even in well-characterized genomes, such as that of A. thaliana. Moreover, we show that the use of the existing A. thaliana reference genome sequence as a guide for sequence assembly of new Arabidopsis accessions or related species has at least in some cases led to error propagation.

  6. Expression of Root Genes in Arabidopsis Seedlings Grown by Standard and Improved Growing Methods.

    Science.gov (United States)

    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.

  7. Expanded functional diversity of shaker K(+ channels in cnidarians is driven by gene expansion.

    Directory of Open Access Journals (Sweden)

    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.

  8. MUTATIONS IN CALMODULIN GENES

    DEFF Research Database (Denmark)

    2013-01-01

    The present invention relates to an isolated polynucleotide encoding at least a part of calmodulin and an isolated polypeptide comprising at least a part of a calmodulin protein, wherein the polynucleotide and the polypeptide comprise at least one mutation associated with a cardiac disorder. The ...... the binding of calmodulin to ryanodine receptor 2 and use of such compound in a treatment of an individual having a cardiac disorder. The invention further provides a kit that can be used to detect specific mutations in calmodulin encoding genes....

  9. Genes and Disease: Prader-Willi Syndrome

    Science.gov (United States)

    ... MD): National Center for Biotechnology Information (US); 1998-. Genes and Disease [Internet]. Show details National Center for ... 45K) PDF version of this title (3.8M) Gene sequence Genome view see gene locations Entrez Gene ...

  10. Gene Therapy and Children (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Gene Therapy and Children KidsHealth / For Parents / Gene Therapy ... that don't respond to conventional therapies. About Genes Our genes help make us unique. Inherited from ...

  11. T4 genes in the marine ecosystem: studies of the T4-like cyanophages and their role in marine ecology

    Directory of Open Access Journals (Sweden)

    Millard Andrew D

    2010-10-01

    Full Text Available Abstract From genomic sequencing it has become apparent that the marine cyanomyoviruses capable of infecting strains of unicellular cyanobacteria assigned to the genera Synechococcus and Prochlorococcus are not only morphologically similar to T4, but are also genetically related, typically sharing some 40-48 genes. The large majority of these common genes are the same in all marine cyanomyoviruses so far characterized. Given the fundamental physiological differences between marine unicellular cyanobacteria and heterotrophic hosts of T4-like phages it is not surprising that the study of cyanomyoviruses has revealed novel and fascinating facets of the phage-host relationship. One of the most interesting features of the marine cyanomyoviruses is their possession of a number of genes that are clearly of host origin such as those involved in photosynthesis, like the psbA gene that encodes a core component of the photosystem II reaction centre. Other host-derived genes encode enzymes involved in carbon metabolism, phosphate acquisition and ppGpp metabolism. The impact of these host-derived genes on phage fitness has still largely to be assessed and represents one of the most important topics in the study of this group of T4-like phages in the laboratory. However, these phages are also of considerable environmental significance by virtue of their impact on key contributors to oceanic primary production and the true extent and nature of this impact has still to be accurately assessed.

  12. Genome-wide evolutionary characterization and expression analyses of major latex protein (MLP) family genes in Vitis vinifera.

    Science.gov (United States)

    Zhang, Ningbo; Li, Ruimin; Shen, Wei; Jiao, Shuzhen; Zhang, Junxiang; Xu, Weirong

    2018-04-27

    The major latex protein/ripening-related protein (MLP/RRP) subfamily is known to be involved in a wide range of biological processes of plant development and various stress responses. However, the biological function of MLP/RRP proteins is still far from being clear and identification of them may provide important clues for understanding their roles. Here, we report a genome-wide evolutionary characterization and gene expression analysis of the MLP family in European Vitis species. A total of 14 members, was found in the grape genome, all of which are located on chromosome 1, where are predominantly arranged in tandem clusters. We have noticed, most surprisingly, promoter-sharing by several non-identical but highly similar gene members to a greater extent than expected by chance. Synteny analysis between the grape and Arabidopsis thaliana genomes suggested that 3 grape MLP genes arose before the divergence of the two species. Phylogenetic analysis provided further insights into the evolutionary relationship between the genes, as well as their putative functions, and tissue-specific expression analysis suggested distinct biological roles for different members. Our expression data suggested a couple of candidate genes involved in abiotic stresses and phytohormone responses. The present work provides new insight into the evolution and regulation of Vitis MLP genes, which represent targets for future studies and inclusion in tolerance-related molecular breeding programs.

  13. Stress tolerances of nullmutants of function-unknown genes encoding menadione stress-responsive proteins in Aspergillus nidulans.

    Science.gov (United States)

    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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen.

    Directory of Open Access Journals (Sweden)

    Malene Hansen

    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.

  15. New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen.

    Directory of Open Access Journals (Sweden)

    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.

  16. Speciation with gene flow in whiptail lizards from a Neotropical xeric biome.

    Science.gov (United States)

    Oliveira, Eliana F; Gehara, Marcelo; São-Pedro, Vinícius A; Chen, Xin; Myers, Edward A; Burbrink, Frank T; Mesquita, Daniel O; Garda, Adrian A; Colli, Guarino R; Rodrigues, Miguel T; Arias, Federico J; Zaher, Hussam; Santos, Rodrigo M L; Costa, Gabriel C

    2015-12-01

    Two main hypotheses have been proposed to explain the diversification of the Caatinga biota. The riverine barrier hypothesis (RBH) claims that the São Francisco River (SFR) is a major biogeographic barrier to gene flow. The Pleistocene climatic fluctuation hypothesis (PCH) states that gene flow, geographic genetic structure and demographic signatures on endemic Caatinga taxa were influenced by Quaternary climate fluctuation cycles. Herein, we analyse genetic diversity and structure, phylogeographic history, and diversification of a widespread Caatinga lizard (Cnemidophorus ocellifer) based on large geographical sampling for multiple loci to test the predictions derived from the RBH and PCH. We inferred two well-delimited lineages (Northeast and Southwest) that have diverged along the Cerrado-Caatinga border during the Mid-Late Miocene (6-14 Ma) despite the presence of gene flow. We reject both major hypotheses proposed to explain diversification in the Caatinga. Surprisingly, our results revealed a striking complex diversification pattern where the Northeast lineage originated as a founder effect from a few individuals located along the edge of the Southwest lineage that eventually expanded throughout the Caatinga. The Southwest lineage is more diverse, older and associated with the Cerrado-Caatinga boundaries. Finally, we suggest that C. ocellifer from the Caatinga is composed of two distinct species. Our data support speciation in the presence of gene flow and highlight the role of environmental gradients in the diversification process. © 2015 John Wiley & Sons Ltd.

  17. The human cytochrome P450 3A locus. Gene evolution by capture of downstream exons.

    Science.gov (United States)

    Finta, C; Zaphiropoulos, P G

    2000-12-30

    Using a bacterial artificial chromosome (BAC) clone, we have mapped the human cytochrome P450 3A (CYP3A) locus containing the genes encoding for CYP3A4, CYP3A5 and CYP3A7. The genes lie in a head-to-tail orientation in the order of 3A4, 3A7 and 3A5. In both intergenic regions (3A4-3A7 and 3A7-3A5), we have detected several additional cytochrome P450 3A exons, forming two CYP3A pseudogenes. These pseudogenes have the same orientation as the CYP3A genes. To our surprise, a 3A7 mRNA species has been detected in which the exons 2 and 13 of one of the pseudogenes (the one that is downstream of 3A7) are spliced after the 3A7 terminal exon. This results in an mRNA molecule that consists of the 13 3A7 exons and two additional exons at the 3' end. The additional two exons originating from the pseudogene are in an altered reading frame and consequently have the capability to code a completely different amino acid sequence than the canonical CYP3A exons 2 and 13. These findings may represent a generalized evolutionary process with genes having the potential to capture neighboring sequences and use them as functional exons.

  18. Primary structure and mapping of the hupA gene of Salmonella typhimurium.

    Science.gov (United States)

    Higgins, N P; Hillyard, D

    1988-01-01

    In bacteria, the complex nucleoid structure is folded and maintained by negative superhelical tension and a set of type II DNA-binding proteins, also called histonelike proteins. The most abundant type II DNA-binding protein is HU. Southern blot analysis showed that Salmonella typhimurium contained two HU genes that corresponded to Escherichia coli genes hupA (encoding HU-2 protein) and hupB (encoding HU-1). Salmonella hupA was cloned, and the nucleotide sequence of the gene was determined. Comparison of hupA of E. coli and S. typhimurium revealed that the HU-2 proteins were identical and that there was high conservation of nucleotide sequences outside the coding frames of the genes. A 300-member genomic library of S. typhimurium was constructed by using random transposition of MudP, a specialized chimeric P22-Mu phage that packages chromosomal DNA unidirectionally from its insertion point. Oligonucleotide hybridization against the library identified one MudP insertion that lies within 28 kilobases of hupA; the MudP was 12% linked to purH at 90.5 min on the standard map. Plasmids expressing HU-2 had a surprising phenotype; they caused growth arrest when they were introduced into E. coli strains bearing a himA or hip mutation. These results suggest that IHF and HU have interactive roles in bacteria. Images PMID:3056912

  19. Genetic homogeneity of Clostridium botulinum type A1 strains with unique toxin gene clusters.

    Science.gov (United States)

    Raphael, Brian H; Luquez, Carolina; McCroskey, Loretta M; Joseph, Lavin A; Jacobson, Mark J; Johnson, Eric A; Maslanka, Susan E; Andreadis, Joanne D

    2008-07-01

    A group of five clonally related Clostridium botulinum type A strains isolated from different sources over a period of nearly 40 years harbored several conserved genetic properties. These strains contained a variant bont/A1 with five nucleotide polymorphisms compared to the gene in C. botulinum strain ATCC 3502. The strains also had a common toxin gene cluster composition (ha-/orfX+) similar to that associated with bont/A in type A strains containing an unexpressed bont/B [termed A(B) strains]. However, bont/B was not identified in the strains examined. Comparative genomic hybridization demonstrated identical genomic content among the strains relative to C. botulinum strain ATCC 3502. In addition, microarray data demonstrated the absence of several genes flanking the toxin gene cluster among the ha-/orfX+ A1 strains, suggesting the presence of genomic rearrangements with respect to this region compared to the C. botulinum ATCC 3502 strain. All five strains were shown to have identical flaA variable region nucleotide sequences. The pulsed-field gel electrophoresis patterns of the strains were indistinguishable when digested with SmaI, and a shift in the size of at least one band was observed in a single strain when digested with XhoI. These results demonstrate surprising genomic homogeneity among a cluster of unique C. botulinum type A strains of diverse origin.

  20. Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis

    Directory of Open Access Journals (Sweden)

    Alexandre A.S.F. Raposo

    2015-03-01

    Full Text Available The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.

  1. Mapping of repair genes

    International Nuclear Information System (INIS)

    Hori, Tadaaki

    1985-01-01

    Chromosome mapping of repair genes involved in U.V. sensitivity is reported. Twenty-three of 25 hybrid cells were resistant to U.V. light. Survival curves of 2 U.V.-resistant cell strains, which possessed mouse chromosomes and human chromosome No.7 - 16, were similar to those of wild strain (L5178Y). On the other hand, survival curves of U.V.-sensitive hybrid cells was analogous to those of Q31. There was a definitive difference in the frequency of inducible chromosome aberrations between U.V. resistant and sensitive mouse-human hybrid cells. U.V.-resistant cell strains possessed the ability of excision repair. Analysis of karyotype in hybrid cells showed that the difference in U.V. sensitivity is dependent upon whether or not human chromosome No.13 is present. Synteny test on esterase D-determining locus confirmed that there is an agreement between the presence of chromosome No.13 and the presence of human esterase D activity. These results led to a conclusion that human genes which compensate recessive character of U.V.-sensitive mutant strain, Q31, with mouse-human hybrid cells are located on the locus of chromosome No.13. (Namekawa, K.)

  2. Gene therapy for ocular diseases.

    Science.gov (United States)

    Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

    2011-05-01

    The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

  3. Evolving chromosomes and gene regulatory networks

    Indian Academy of Sciences (India)

    Aswin

    Genes under H NS control can be. (a) regulated by H NS. (b) regulated by H NS and StpA. Because backup by StpA is partial. Page 19. Gene expression level. H NS regulated xenogenes. Other genes. Page 20 ... recollect: H&NS silences highl transcribable genes. Gene expression level unilateral. Other genes epistatic ...

  4. Bayesian assignment of gene ontology terms to gene expression experiments.

    Science.gov (United States)

    Sykacek, P

    2012-09-15

    Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Source code under GPL license is available from the author. peter.sykacek@boku.ac.at.

  5. Bayesian assignment of gene ontology terms to gene expression experiments

    Science.gov (United States)

    Sykacek, P.

    2012-01-01

    Motivation: Gene expression assays allow for genome scale analyses of molecular biological mechanisms. State-of-the-art data analysis provides lists of involved genes, either by calculating significance levels of mRNA abundance or by Bayesian assessments of gene activity. A common problem of such approaches is the difficulty of interpreting the biological implication of the resulting gene lists. This lead to an increased interest in methods for inferring high-level biological information. A common approach for representing high level information is by inferring gene ontology (GO) terms which may be attributed to the expression data experiment. Results: This article proposes a probabilistic model for GO term inference. Modelling assumes that gene annotations to GO terms are available and gene involvement in an experiment is represented by a posterior probabilities over gene-specific indicator variables. Such probability measures result from many Bayesian approaches for expression data analysis. The proposed model combines these indicator probabilities in a probabilistic fashion and provides a probabilistic GO term assignment as a result. Experiments on synthetic and microarray data suggest that advantages of the proposed probabilistic GO term inference over statistical test-based approaches are in particular evident for sparsely annotated GO terms and in situations of large uncertainty about gene activity. Provided that appropriate annotations exist, the proposed approach is easily applied to inferring other high level assignments like pathways. Availability: Source code under GPL license is available from the author. Contact: peter.sykacek@boku.ac.at PMID:22962488

  6. Close linkage of the mouse and human CD3 γ- and δ-chain genes suggests that their transcription is controlled by common regulatory elements

    International Nuclear Information System (INIS)

    Saito, H.; Koyama, T.; Georgopoulos, K.; Clevers, H.; Haser, W.G.; LeBien, T.; Tonegawa, S.; Terhorst, C.

    1987-01-01

    Antigen receptors on the T-cell surface are noncovalently associated with at least four invariant polypeptide chains, CD3-γ, -δ, -epsilon, and -zeta. The mouse CD3-γ gene, consisting of seven exons, was found to be highly homologous to the CD3-γ described earlier. Both the high level of sequence homology and the exon/intron organization indicate that the CD3-γ and -δ genes arose by gene duplication. Surprisingly, murine and human genomic DNA clones could be isolated that contained elements of both the CD3-γ and CD3-δ genes. In fact, the putative transcription start site of the mouse CD3-γ gene is less than 1.4 kilobases from the transcription initiation site of the mouse CD3-δ gene. Common elements that regulate the divergent transcription of the two genes are therefore proposed to be located in the intervening 1.4-kilobase DNA segment. This might contribute to the coordinate expression of the CD3-γ and -δ genes during intrathymic maturation of T lymphocytes

  7. Based on Molecular Profiling of Gene Expression, Palmoplantar Pustulosis and Palmoplantar Pustular Psoriasis Are Highly Related Diseases that Appear to Be Distinct from Psoriasis Vulgaris.

    Directory of Open Access Journals (Sweden)

    Robert Bissonnette

    Full Text Available There is a controversy surrounding the existence of palmoplantar pustulosis (PPP and palmoplantar pustular psoriasis (PPPP as separate clinical entities or as variants of the same clinical entity. We used gene expression microarray to compare gene expression in PPP and PPPP.Skin biopsies from subjects with PPP (3, PPPP (6, psoriasis vulgaris (10 and acral skin from normal subjects (7 were analyzed using gene expression microarray. Principal component analysis showed that PPP and PPPP were different from psoriasis vulgaris and normal acral skin. However gene expression of PPP and PPPP clustered together and could not be used to differentiate PPP from PPPP. Gene-wise comparison between PPP and PPPP found no gene to be differentially expressed at a false discovery rate lower than 0.05. Surprisingly we found a higher expression of several genes involved in neural pathways (e.g. GPRIN and ADAM23 in PPP/PPPP as compared to psoriasis vulgaris and normal acral skin. Immunohistochemistry confirmed those findings and showed a keratinocyte localization for those proteins.PPP and PPPP could not be differentiated using gene expression microarray suggesting that they are not distinct clinical entities. Increased expression of GPRIN1, and ADAM23 in keratinocytes suggests that these proteins could be new therapeutic targets for PPP/PPPP.

  8. Rare MDM4 gene amplification in colorectal cancer: The principle of a mutually exclusive relationship between MDM alteration and TP53 inactivation is not applicable.

    Science.gov (United States)

    Suda, Tetsuji; Yoshihara, Mitsuyo; Nakamura, Yoshiyasu; Sekiguchi, Hironobu; Godai, Ten-I; Sugano, Nobuhiro; Tsuchida, Kazuhito; Shiozawa, Manabu; Sakuma, Yuji; Tsuchiya, Eiju; Kameda, Yoichi; Akaike, Makoto; Matsukuma, Shoichi; Miyagi, Yohei

    2011-07-01

    MDM4, a homolog of MDM2, is considered a key negative regulator of p53. Gene amplification of MDM4 has been identified in a variety of tumors. MDM2 or MDM4 gene amplification is only associated with the wild-type TP53 gene in retinoblastomas, thus the amplification of the two genes is mutually exclusive. Previously, we demonstrated that MDM2 amplification and TP53 alteration were not mutually exclusive in colorectal cancer, and we identified a subset of colorectal cancer patients without alterations in either the TP53 or the MDM2 gene. In this study, we investigated the gene amplification status of MDM4 in the same set of colorectal cancer cases. Unexpectedly, MDM4 amplification was rare, detected in only 1.4% (3 out of 211) of colorectal cancer cases. All the three gene-amplified tumors also harbored TP53-inactivating mutations. This contradicts the simple mutually exclusive relationship observed in retinoblastomas. Surprisingly, two of the three MDM4-amplified tumors also demonstrated MDM2 amplification. Paradoxically, the MDM4 protein levels were decreased in the tumor tissue of the gene-amplified cases compared with levels in the matched normal mucosa. We speculate that MDM4 might play a role in colorectal carcinogenesis that is not limited to negative regulation of p53 in combination with MDM2. The functional significance of MDM4 is still unclear and further studies are needed.

  9. Differential Gene Expression and Aging

    Directory of Open Access Journals (Sweden)

    Laurent Seroude

    2002-01-01

    Full Text Available It has been established that an intricate program of gene expression controls progression through the different stages in development. The equally complex biological phenomenon known as aging is genetically determined and environmentally modulated. This review focuses on the genetic component of aging, with a special emphasis on differential gene expression. At least two genetic pathways regulating organism longevity act by modifying gene expression. Many genes are also subjected to age-dependent transcriptional regulation. Some age-related gene expression changes are prevented by caloric restriction, the most robust intervention that slows down the aging process. Manipulating the expression of some age-regulated genes can extend an organism's life span. Remarkably, the activity of many transcription regulatory elements is linked to physiological age as opposed to chronological age, indicating that orderly and tightly controlled regulatory pathways are active during aging.

  10. Generalist genes and learning disabilities.

    Science.gov (United States)

    Plomin, Robert; Kovas, Yulia

    2005-07-01

    The authors reviewed recent quantitative genetic research on learning disabilities that led to the conclusion that genetic diagnoses differ from traditional diagnoses in that the effects of relevant genes are largely general rather than specific. This research suggests that most genes associated with common learning disabilities--language impairment, reading disability, and mathematics disability--are generalists in 3 ways. First, genes that affect common learning disabilities are largely the same genes responsible for normal variation in learning abilities. Second, genes that affect any aspect of a learning disability affect other aspects of the disability. Third, genes that affect one learning disability are also likely to affect other learning disabilities. These quantitative genetic findings have far-reaching implications for molecular genetics and neuroscience as well as psychology. Copyright 2005 APA, all rights reserved.

  11. Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data

    International Nuclear Information System (INIS)

    Lenburg, Marc E; Liou, Louis S; Gerry, Norman P; Frampton, Garrett M; Cohen, Herbert T; Christman, Michael F

    2003-01-01

    Renal cell carcinoma is a common malignancy that often presents as a metastatic-disease for which there are no effective treatments. To gain insights into the mechanism of renal cell carcinogenesis, a number of genome-wide expression profiling studies have been performed. Surprisingly, there is very poor agreement among these studies as to which genes are differentially regulated. To better understand this lack of agreement we profiled renal cell tumor gene expression using genome-wide microarrays (45,000 probe sets) and compare our analysis to previous microarray studies. We hybridized total RNA isolated from renal cell tumors and adjacent normal tissue to Affymetrix U133A and U133B arrays. We removed samples with technical defects and removed probesets that failed to exhibit sequence-specific hybridization in any of the samples. We detected differential gene expression in the resulting dataset with parametric methods and identified keywords that are overrepresented in the differentially expressed genes with the Fisher-exact test. We identify 1,234 genes that are more than three-fold changed in renal tumors by t-test, 800 of which have not been previously reported to be altered in renal cell tumors. Of the only 37 genes that have been identified as being differentially expressed in three or more of five previous microarray studies of renal tumor gene expression, our analysis finds 33 of these genes (89%). A key to the sensitivity and power of our analysis is filtering out defective samples and genes that are not reliably detected. The widespread use of sample-wise voting schemes for detecting differential expression that do not control for false positives likely account for the poor overlap among previous studies. Among the many genes we identified using parametric methods that were not previously reported as being differentially expressed in renal cell tumors are several oncogenes and tumor suppressor genes that likely play important roles in renal cell

  12. Gene-gene interactions and gene polymorphisms of VEGFA and EG-VEGF gene systems in recurrent pregnancy loss.

    Science.gov (United States)

    Su, Mei-Tsz; Lin, Sheng-Hsiang; Chen, Yi-Chi; Kuo, Pao-Lin

    2014-06-01

    Both vascular endothelial growth factor A (VEGFA) and endocrine gland-derived vascular endothelial growth factor (EG-VEGF) systems play major roles in angiogenesis. A body of evidence suggests VEGFs regulate critical processes during pregnancy and have been associated with recurrent pregnancy loss (RPL). However, little information is available regarding the interaction of these two major major angiogenesis-related systems in early human pregnancy. This study was conducted to investigate the association of gene polymorphisms and gene-gene interaction among genes in VEGFA and EG-VEGF systems and idiopathic RPL. A total of 98 women with history of idiopathic RPL and 142 controls were included, and 5 functional SNPs selected from VEGFA, KDR, EG-VEGF (PROK1), PROKR1 and PROKR2 were genotyped. We used multifactor dimensionality reduction (MDR) analysis to choose a best model and evaluate gene-gene interactions. Ingenuity pathways analysis (IPA) was introduced to explore possible complex interactions. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL (P<0.01). The MDR test revealed that the KDR (Q472H) polymorphism was the best loci to be associated with RPL (P=0.02). IPA revealed EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3 signaling pathways. Two receptor gene polymorphisms [KDR (Q472H) and PROKR2 (V331M)] were significantly associated with idiopathic RPL. EG-VEGF and VEGFA systems shared several canonical signaling pathways that may contribute to gene-gene interactions, including the Akt, IL-8, EGFR, MAPK, SRC, VHL, HIF-1A and STAT3.

  13. A genetic ensemble approach for gene-gene interaction identification

    Directory of Open Access Journals (Sweden)

    Ho Joshua WK

    2010-10-01

    Full Text Available Abstract Background It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging. Methods In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA and an ensemble of classifiers (called genetic ensemble. Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise double fault is designed to quantify the degree of complementarity. Conclusions Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR and is slightly better than Polymorphism Interaction Analysis (PIA, which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of

  14. IS30-related transposon mediated insertional inactivation of bile salt hydrolase (bsh1) gene of Lactobacillus plantarum strain Lp20.

    Science.gov (United States)

    Kumar, Rajesh; Grover, Sunita; Kaushik, Jai K; Batish, Virender Kumar

    2014-01-01

    Lactobacillus plantarum is a flexible and versatile microorganism that inhabits a variety of niches, and its genome may express up to four bsh genes to maximize its survival in the mammalian gut. However, the ecological significance of multiple bsh genes in L. plantarum is still not clearly understood. Hence, this study demonstrated the disruption of bile salt hydrolase (bsh1) gene due to the insertion of a transposable element in L. plantarum Lp20 - a wild strain of human fecal origin. Surprisingly, L. plantarum strain Lp20 produced a ∼2.0 kb bsh1 amplicon against the normal size (∼1.0 kb) bsh1 amplicon of Bsh(+)L. plantarum Lp21. Strain Lp20 exhibited minimal Bsh activity in spite of having intact bsh2, bsh3 and bsh4 genes in its genome and hence had a Bsh(-) phenotype. Cloning and sequence characterization of Lp20 bsh1 gene predicted four individual open reading frames (ORFs) within this region. BLAST analysis of ORF1 and ORF2 revealed significant sequence similarity to the L. plantarum bsh1 gene while ORF3 and ORF4 showed high sequence homology to IS30-family transposases. Since, IS30-related transposon element was inserted within Lp20 bsh1 gene in reverse orientation (3'-5'), it introduced several stop codons and disrupted the protein reading frames of both Bsh1 and transposase. Inverted terminal repeats (GGCAGATTG) of transposon, mediated its insertion at 255-263 nt and 1301-1309 nt positions of Lp20 bsh1 gene. In conclusion, insertion of IS30 related-transposon within the bsh1 gene sequence of L. plantarum strain Lp20 demolished the integrity and functionality of Bsh1 enzyme. Additionally, this transposon DNA sequence remains active among various Lactobacillus spp. and hence harbors the potential to be explored in the development of efficient insertion mutagenesis system. Copyright © 2013 Elsevier GmbH. All rights reserved.

  15. SVM classifier to predict genes important for self-renewal and pluripotency of mouse embryonic stem cells

    Directory of Open Access Journals (Sweden)

    Xu Huilei

    2010-12-01

    Full Text Available Abstract Background Mouse embryonic stem cells (mESCs are derived from the inner cell mass of a developing blastocyst and can be cultured indefinitely in-vitro. Their distinct features are their ability to self-renew and to differentiate to all adult cell types. Genes that maintain mESCs self-renewal and pluripotency identity are of interest to stem cell biologists. Although significant steps have been made toward the identification and characterization of such genes, the list is still incomplete and controversial. For example, the overlap among candidate self-renewal and pluripotency genes across different RNAi screens is surprisingly small. Meanwhile, machine learning approaches have been used to analyze multi-dimensional experimental data and integrate results from many studies, yet they have not been applied to specifically tackle the task of predicting and classifying self-renewal and pluripotency gene membership. Results For this study we developed a classifier, a supervised machine learning framework for predicting self-renewal and pluripotency mESCs stemness membership genes (MSMG using support vector machines (SVM. The data used to train the classifier was derived from mESCs-related studies using mRNA microarrays, measuring gene expression in various stages of early differentiation, as well as ChIP-seq studies applied to mESCs profiling genome-wide binding of key transcription factors, such as Nanog, Oct4, and Sox2, to the regulatory regions of other genes. Comparison to other classification methods using the leave-one-out cross-validation method was employed to evaluate the accuracy and generality of the classification. Finally, two sets of candidate genes from genome-wide RNA interference screens are used to test the generality and potential application of the classifier. Conclusions Our results reveal that an SVM approach can be useful for prioritizing genes for functional validation experiments and complement the analyses of high

  16. Introduction: Cancer Gene Networks.

    Science.gov (United States)

    Clarke, Robert

    2017-01-01

    Constructing, evaluating, and interpreting gene networks generally sits within the broader field of systems biology, which continues to emerge rapidly, particular with respect to its application to understanding the complexity of signaling in the context of cancer biology. For the purposes of this volume, we take a broad definition of systems biology. Considering an organism or disease within an organism as a system, systems biology is the study of the integrated and coordinated interactions of the network(s) of genes, their variants both natural and mutated (e.g., polymorphisms, rearrangements, alternate splicing, mutations), their proteins and isoforms, and the organic and inorganic molecules with which they interact, to execute the biochemical reactions (e.g., as enzymes, substrates, products) that reflect the function of that system. Central to systems biology, and perhaps the only approach that can effectively manage the complexity of such systems, is the building of quantitative multiscale predictive models. The predictions of the models can vary substantially depending on the nature of the model and its inputoutput relationships. For example, a model may predict the outcome of a specific molecular reaction(s), a cellular phenotype (e.g., alive, dead, growth arrest, proliferation, and motility), a change in the respective prevalence of cell or subpopulations, a patient or patient subgroup outcome(s). Such models necessarily require computers. Computational modeling can be thought of as using machine learning and related tools to integrate the very high dimensional data generated from modern, high throughput omics technologies including genomics (next generation sequencing), transcriptomics (gene expression microarrays; RNAseq), metabolomics and proteomics (ultra high performance liquid chromatography, mass spectrometry), and "subomic" technologies to study the kinome, methylome, and others. Mathematical modeling can be thought of as the use of ordinary

  17. Gene therapy for hemophilia

    Science.gov (United States)

    Rogers, Geoffrey L.; Herzog, Roland W.

    2015-01-01

    Hemophilia is an X-linked inherited bleeding disorder consisting of two classifications, hemophilia A and hemophilia B, depending on the underlying mutation. Although the disease is currently treatable with intravenous delivery of replacement recombinant clotting factor, this approach represents a significant cost both monetarily and in terms of quality of life. Gene therapy is an attractive alternative approach to the treatment of hemophilia that would ideally provide life-long correction of clotting activity with a single injection. In this review, we will discuss the multitude of approaches that have been explored for the treatment of both hemophilia A and B, including both in vivo and ex vivo approaches with viral and nonviral delivery vectors. PMID:25553466

  18. Gene therapy and reproductive medicine.

    Science.gov (United States)

    Stribley, John M; Rehman, Khurram S; Niu, Hairong; Christman, Gregory M

    2002-04-01

    To review the literature on the principles of gene therapy and its potential application in reproductive medicine. Literature review. Gene therapy involves transfer of genetic material to target cells using a delivery system, or vector. Attention has primarily focused on viral vectors. Significant problems remain to be overcome including low efficacy of gene transfer, the transient expression of some vectors, safety issues with modified adenoviruses and retroviruses, and ethical concerns. If these issues can be resolved, gene therapy will be applicable to an increasing spectrum of single and multiple gene disorders, as the Human Genome Project data are analyzed, and the genetic component of human disease becomes better understood. Gynecologic gene therapy has advanced to human clinical trials for ovarian carcinoma, and shows potential for the treatment of uterine leiomyomata. Obstetric applications of gene therapy, including fetal gene therapy, remain more distant goals. Concerns about the safety of human gene therapy research are being actively addressed, and remarkable progress in improving DNA transfer has been made. The first treatment success for a genetic disease (severe combined immunodeficiency disease) has been achieved, and ongoing research efforts will eventually yield clinical applications in many spheres of reproductive medicine.

  19. Synthetic sustained gene delivery systems.

    Science.gov (United States)

    Agarwal, Ankit; Mallapragada, Surya K

    2008-01-01

    Gene therapy today is hampered by the need of a safe and efficient gene delivery system that can provide a sustained therapeutic effect without cytotoxicity or unwanted immune responses. Bolus gene delivery in solution results in the loss of delivered factors via lymphatic system and may cause undesired effects by the escape of bioactive molecules to distant sites. Controlled gene delivery systems, acting as localized depot of genes, provide an extended sustained release of genes, giving prolonged maintenance of the therapeutic level of encoded proteins. They also limit the DNA degradation in the nuclease rich extra-cellular environment. While attempts have been made to adapt existing controlled drug delivery technologies, more novel approaches are being investigated for controlled gene delivery. DNA encapsulated in nano/micro spheres of polymers have been administered systemically/orally to be taken up by the targeted tissues and provide sustained release once internalized. Alternatively, DNA entrapped in hydrogels or scaffolds have been injected/implanted in tissues/cavities as platforms for gene delivery. The present review examines these different modalities for sustained delivery of viral and non-viral gene-delivery vectors. Design parameters and release mechanisms of different systems made with synthetic or natural polymers are presented along with their prospective applications and opportunities for continuous development.

  20. The ambiguous ripening nature of the fig (Ficus carica L.) fruit: a gene-expression study of potential ripening regulators and ethylene-related genes

    Science.gov (United States)

    Freiman, Zohar E.; Rosianskey, Yogev; Dasmohapatra, Rajeswari; Kamara, Itzhak; Flaishman, Moshe A.

    2015-01-01

    The traditional definition of climacteric and non-climacteric fruits has been put into question. A significant example of this paradox is the climacteric fig fruit. Surprisingly, ripening-related ethylene production increases following pre- or postharvest 1-methylcyclopropene (1-MCP) application in an unexpected auto-inhibitory manner. In this study, ethylene production and the expression of potential ripening-regulator, ethylene-synthesis, and signal-transduction genes are characterized in figs ripening on the tree and following preharvest 1-MCP application. Fig ripening-related gene expression was similar to that in tomato and apple during ripening on the tree, but only in the fig inflorescence–drupelet section. Because the pattern in the receptacle is different for most of the genes, the fig drupelets developed inside the syconium are proposed to function as parthenocarpic true fruit, regulating ripening processes for the whole accessory fruit. Transcription of a potential ripening regulator, FcMADS8, increased during ripening on the tree and was inhibited following 1-MCP treatment. Expression patterns of the ethylene-synthesis genes FcACS2, FcACS4, and FcACO3 could be related to the auto-inhibition reaction of ethylene production in 1-MCP-treated fruit. Along with FcMADS8 suppression, gene expression analysis revealed upregulation of FcEBF1, and downregulation of FcEIL3 and several FcERFs by 1-MCP treatment. This corresponded with the high storability of the treated fruit. One FcERF was overexpressed in the 1-MCP-treated fruit, and did not share the increasing pattern of most FcERFs in the tree-ripened fig. This demonstrates the potential of this downstream ethylene-signal-transduction component as an ethylene-synthesis regulator, responsible for the non-climacteric auto-inhibition of ethylene production in fig. PMID:25956879

  1. Evaluation of suitable reference genes for gene expression studies ...

    Indian Academy of Sciences (India)

    2011-12-14

    Dec 14, 2011 ... MADS family of TFs control floral organ identity within each whorl of the flower by activating downstream genes. Measuring gene expression in different tissue types and developmental stages is of fundamental importance in TFs functional research. In last few years, quantitative real-time. PCR (qRT-PCR) ...

  2. Are TMEM genes potential candidate genes for panic disorder?

    DEFF Research Database (Denmark)

    NO, Gregersen; Buttenschøn, Henriette Nørmølle; Hedemand, Anne

    2014-01-01

    We analysed single nucleotide polymorphisms in two transmembrane genes (TMEM98 and TMEM132E) in panic disorder (PD) patients and control individuals from the Faroe Islands, Denmark and Germany. The genes encode single-pass membrane proteins and are located within chromosome 17q11.2-q12...

  3. Functional Analysis of the FZF1 Genes of Saccharomyces uvarum

    Directory of Open Access Journals (Sweden)

    Xiaozhen Liu

    2018-02-01

    Full Text Available Being a sister species of Saccharomyces cerevisiae, Saccharomyces uvarum shows great potential regarding the future of the wine industry. The sulfite tolerance of most S. uvarum strains is poor, however. This is a major flaw that limits its utility in the wine industry. In S. cerevisiae, FZF1 plays a positive role in the transcription of SSU1, which encodes a sulfite efflux transport protein that is critical for sulfite tolerance. Although FZF1 has previously been shown to play a role in sulfite tolerance in S. uvarum, there is little information about its action mechanism. To assess the function of FZF1, two over-expression vectors that contained different FZF1 genes, and one FZF1 silencing vector, were constructed and introduced into a sulfite-tolerant S. uvarum strain using electroporation. In addition, an FZF1-deletion strain was constructed. Both of the FZF1-over-expressing strains showed an elevated tolerance to sulfite, and the FZF1-deletion strain showed the opposite effect. Repression of FZF1 transcription failed, however, presumably due to the lack of alleles of DCR1 and AGO. The qRT-PCR analysis was used to examine changes in transcription in the strains. Surprisingly, neither over-expressing strain promoted SSU1 transcription, although MET4 and HAL4 transcripts significantly increased in both sulfite-tolerance increased strains. We conclude that FZF1 plays a different role in the sulfite tolerance of S. uvarum compared to its role in S. cerevisiae.

  4. Classifying genes to the correct Gene Ontology Slim term in Saccharomyces cerevisiae using neighbouring genes with classification learning

    Directory of Open Access Journals (Sweden)

    Tsatsoulis Costas

    2010-05-01

    Full Text Available Abstract Background There is increasing evidence that gene location and surrounding genes influence the functionality of genes in the eukaryotic genome. Knowing the Gene Ontology Slim terms associated with a gene gives us insight into a gene's functionality by informing us how its gene product behaves in a cellular context using three different ontologies: molecular function, biological process, and cellular component. In this study, we analyzed if we could classify a gene in Saccharomyces cerevisiae to its correct Gene Ontology Slim term using information about its location in the genome and information from its nearest-neighbouring genes using classification learning. Results We performed experiments to establish that the MultiBoostAB algorithm using the J48 classifier could correctly classify Gene Ontology Slim terms of a gene given information regarding the gene's location and information from its nearest-neighbouring genes for training. Different neighbourhood sizes were examined to determine how many nearest neighbours should be included around each gene to provide better classification rules. Our results show that by just incorporating neighbour information from each gene's two-nearest neighbours, the percentage of correctly classified genes to their correct Gene Ontology Slim term for each ontology reaches over 80% with high accuracy (reflected in F-measures over 0.80 of the classification rules produced. Conclusions We confirmed that in classifying genes to their correct Gene Ontology Slim term, the inclusion of neighbour information from those genes is beneficial. Knowing the location of a gene and the Gene Ontology Slim information from neighbouring genes gives us insight into that gene's functionality. This benefit is seen by just including information from a gene's two-nearest neighbouring genes.

  5. Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

    Directory of Open Access Journals (Sweden)

    Abhay Sharma

    Full Text Available Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1 adults after treating F(0 adult males with PTZ and of F(2 adults resulting from a cross between F(1 males and normal females. Surprisingly, microarray clustering showed F(1 male profile as closest to F(1 female and F(0 male profile closest to F(2 male. Differentially expressed genes in F(1 males, F(1 females and F(2 males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2 males. Next, we generated microarray expression profiles of adult testis from F(0 and F(1 males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying

  6. Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

    Science.gov (United States)

    Sharma, Abhay; Singh, Priyanka

    2009-06-02

    Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ) induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1) adults after treating F(0) adult males with PTZ and of F(2) adults resulting from a cross between F(1) males and normal females. Surprisingly, microarray clustering showed F(1) male profile as closest to F(1) female and F(0) male profile closest to F(2) male. Differentially expressed genes in F(1) males, F(1) females and F(2) males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2) males. Next, we generated microarray expression profiles of adult testis from F(0) and F(1) males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying the

  7. Gene expression analysis in human breast cancer associated blood vessels.

    Directory of Open Access Journals (Sweden)

    Dylan T Jones

    Full Text Available Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of

  8. Gene doping: possibilities and practicalities.

    Science.gov (United States)

    Wells, Dominic J

    2009-01-01

    Our ever-increasing understanding of the genetic control of cardiovascular and musculoskeletal function together with recent technical improvements in genetic manipulation generates mounting concern over the possibility of such technology being abused by athletes in their quest for improved performance. Genetic manipulation in the context of athletic performance is commonly referred to as gene doping. A review of the literature was performed to identify the genes and methodologies most likely to be used for gene doping and the technologies that might be used to identify such doping. A large number of candidate performance-enhancing genes have been identified from animal studies, many of them using transgenic mice. Only a limited number have been shown to be effective following gene transfer into adults. Those that seem most likely to be abused are genes that exert their effects locally and leave little, if any, trace in blood or urine. There is currently no evidence that gene doping has yet been undertaken in competitive athletes but the anti-doping authorities will need to remain vigilant in reviewing this rapidly emerging technology. The detection of gene doping involves some different challenges from other agents and a number of promising approaches are currently being explored. 2009 S. Karger AG, Basel

  9. Determining Semantically Related Significant Genes.

    Science.gov (United States)

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  10. Gene set analysis for GWAS

    DEFF Research Database (Denmark)

    Debrabant, Birgit; Soerensen, Mette

    2014-01-01

    Abstract We discuss the use of modified Kolmogorov-Smirnov (KS) statistics in the context of gene set analysis and review corresponding null and alternative hypotheses. Especially, we show that, when enhancing the impact of highly significant genes in the calculation of the test statistic, the co...

  11. On meme--gene coevolution.

    Science.gov (United States)

    Bull, L; Holland, O; Blackmore, S

    2000-01-01

    In this article we examine the effects of the emergence of a new replicator, memes, on the evolution of a pre-existing replicator, genes. Using a version of the NKCS model we examine the effects of increasing the rate of meme evolution in relation to the rate of gene evolution, for various degrees of interdependence between the two replicators. That is, the effects of memes' (suggested) more rapid rate of evolution in comparison to that of genes is investigated using a tunable model of coevolution. It is found that, for almost any degree of interdependence between the two replicators, as the rate of meme evolution increases, a phase transition-like dynamic occurs under which memes have a significantly detrimental effect on the evolution of genes, quickly resulting in the cessation of effective gene evolution. Conversely, the memes experience a sharp increase in benefit from increasing their rate of evolution. We then examine the effects of enabling genes to reduce the percentage of gene-detrimental evolutionary steps taken by memes. Here a critical region emerges as the comparative rate of meme evolution increases, such that if genes cannot effectively select memes a high percentage of the time, they suffer from meme evolution as if they had almost no selective capability.

  12. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  13. Gene polymorphisms in chronic periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Loos, B.G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or

  14. High prevalence of human polyomavirus JC VP1 gene sequences in pediatric malignancies.

    Science.gov (United States)

    Shiramizu, B; Hu, N; Frisque, R J; Nerurkar, V R

    2007-05-15

    The oncogenic potential of human polyomavirus JC (JCV), a ubiquitous virus that establishes infection during early childhood in approximately 70% of the human population, is unclear. As a neurotropic virus, JCV has been implicated in pediatric central nervous system tumors and has been suggested to be a pathogenic agent in pediatric acute lymphoblastic leukemia. Recent studies have demonstrated JCV gene sequences in pediatric medulloblastomas and among patients with colorectal cancer. JCV early protein T-antigen (TAg) can form complexes with cellular regulatory proteins and thus may play a role in tumorigenesis. Since JCV is detected in B-lymphocytes, a retrospective analysis of pediatric B-cell and non-B-cell malignancies as well as other HIV-associated pediatric malignancies was conducted for the presence of JCV gene sequences. DNA was extracted from 49 pediatric malignancies, including Hodgkin disease, non-Hodgkin lymphoma, large cell lymphoma and sarcoma. Polymerase chain reaction (PCR) was conducted using JCV specific nested primer sets for the transcriptional control region (TCR), TAg, and viral capsid protein 1 (VP1) genes. Southern blot analysis and DNA sequencing were used to confirm specificity of the amplicons. A 215-bp region of the JCV VP1 gene was amplified from 26 (53%) pediatric tumor tissues. The JCV TCR and two JCV gene regions were amplified from a leiomyosarcoma specimen from an HIV-infected patient. The leiomyosarcoma specimen from the cecum harbored the archetype strain of JCV. Including the leiomyosarcoma specimen, three of five specimens sequenced were typed as JCV genotype 2. The failure to amplify JCV TCR, and TAg gene sequences in the presence of JCV VP1 gene sequence is surprising. Even though JCV TAg gene, which is similar to the SV40 TAg gene, is oncogenic in animal models, the presence of JCV gene sequences in pediatric malignancies does not prove causality. In light of the available data on the presence of JCV in normal and cancerous

  15. Presence of pathogenicity island genes in Enterococcus faecalis isolates from pigs in Denmark

    DEFF Research Database (Denmark)

    Shankar, Nathan; Baghdayan, Arto S.; Willems, Rob

    2006-01-01

    Enterococcus faecalis isolates of porcine origin were screened for the presence of a previously identified pathogenicity island (PAI). By using the esp gene as a genetic marker for the presence of this PAI, 9 esp-positive and 10 esp-negative isolates of porcine origin were investigated by use...... of a designed oligonucleotide array. The results indicated the clustering of esp-positive strains by multilocus sequence typing (MLST), but surprisingly, all strains investigated contained parts of the PAL None of the strains of animal origin investigated belonged to previously identified MLST complex 2, where...... most isolates from patients cluster. Five of the nine esp-positive E. faecalis isolates of animal origin belonged to the same PAI complex as human isolate MMH594 but differed in their sequence types, which strongly indicates the horizontal transfer of the PAI between enterococci of porcine and human...

  16. A false single nucleotide polymorphism generated by gene duplication compromises meat traceability.

    Science.gov (United States)

    Sanz, Arianne; Ordovás, Laura; Zaragoza, Pilar; Sanz, Albina; de Blas, Ignacio; Rodellar, Clementina

    2012-07-01

    Controlling meat traceability using SNPs is an effective method of ensuring food safety. We have analyzed several SNPs to create a panel for bovine genetic identification and traceability studies. One of these was the transversion g.329C>T (Genbank accession no. AJ496781) on the cytochrome P450 17A1 gene, which has been included in previously published panels. Using minisequencing reactions, we have tested 701 samples belonging to eight Spanish cattle breeds. Surprisingly, an excess of heterozygotes was detected, implying an extreme departure from Hardy-Weinberg equilibrium (PT SNP is a false positive polymorphism, which allows us to explain the inflated heterozygotic value. We recommend that this ambiguous SNP, as well as other polymorphisms located in this region, should not be used in identification, traceability or disease association studies. Annotation of these false SNPs should improve association studies and avoid misinterpretations. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Imaging after vascular gene therapy

    International Nuclear Information System (INIS)

    Manninen, Hannu I.; Yang, Xiaoming

    2005-01-01

    Targets for cardiovascular gene therapy currently include limiting restenosis after balloon angioplasty and stent placement, inhibiting vein bypass graft intimal hyperplasia/stenosis, therapeutic angiogenesis for cardiac and lower-limb ischemia, and prevention of thrombus formation. While catheter angiography is still standard method to follow-up vascular gene transfer, other modern imaging techniques, especially intravascular ultrasound (IVUS), magnetic resonance (MR), and positron emission tomography (PET) imaging provide complementary information about the therapeutic effect of vascular gene transfer in humans. Although molecular imaging of therapeutic gene expression in the vasculatures is still in its technical development phase, it has already offered basic medical science an extremely useful in vivo evaluation tool for non- or minimally invasive imaging of vascular gene therapy

  18. Function analysis of unknown genes

    DEFF Research Database (Denmark)

    Rogowska-Wrzesinska, A.

    2002-01-01

      This thesis entitled "Function analysis of unknown genes" presents the use of proteome analysis for the characterisation of yeast (Saccharomyces cerevisiae) genes and their products (proteins especially those of unknown function). This study illustrates that proteome analysis can be used...... to describe different aspects of molecular biology of the cell, to study changes that occur in the cell due to overexpression or deletion of a gene and to identify various protein modifications. The biological questions and the results of the described studies show the diversity of the information that can...... genes and proteins. It reports the first global proteome database collecting 36 yeast single gene deletion mutants and selecting over 650 differences between analysed mutants and the wild type strain. The obtained results show that two-dimensional gel electrophoresis and mass spectrometry based proteome...

  19. The polyketide synthase gene pks4 is essential for sexual development and regulates fruiting body morphology in Sordaria macrospora.

    Science.gov (United States)

    Schindler, Daniel; Nowrousian, Minou

    2014-07-01

    Filamentous ascomycetes have long been known as producers of a variety of secondary metabolites, many of which have toxic effects on other organisms. However, the role of these metabolites in the biology of the fungi that produce them remains in most cases enigmatic. A major group of fungal secondary metabolites are polyketides. They are chemically diverse, but have in common that their chemical scaffolds are synthesized by polyketide synthases (PKSs). In a previous study, we analyzed development-dependent expression of pks genes in the filamentous ascomycete Sordaria macrospora. Here, we show that a deletion mutant of the pks4 gene is sterile, producing only protoperithecia but no mature perithecia, whereas overexpression of pks4 leads to enlarged, malformed fruiting bodies. Thus, correct expression levels of pks4 are essential for wild type-like perithecia formation. The predicted PKS4 protein has a domain structure that is similar to homologs in other fungi, but conserved residues of a methyl transferase domain present in other fungi are mutated in PKS4. Expression of several developmental genes is misregulated in the pks4 mutant. Surprisingly, the development-associated app gene is not downregulated in the mutant, in contrast to all other previously studied mutants with a block at the protoperithecial stage. Our data show that the polyketide synthase gene pks4 is essential for sexual development and plays a role in regulating fruiting body morphology. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Gene Set Analyses of Genome-Wide Association Studies on 49 Quantitative Traits Measured in a Single Genetic Epidemiology Dataset

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    Jihye Kim

    2013-09-01

    Full Text Available Gene set analysis is a powerful tool for interpreting a genome-wide association study result and is gaining popularity these days. Comparison of the gene sets obtained for a variety of traits measured from a single genetic epidemiology dataset may give insights into the biological mechanisms underlying these traits. Based on the previously published single nucleotide polymorphism (SNP genotype data on 8,842 individuals enrolled in the Korea Association Resource project, we performed a series of systematic genome-wide association analyses for 49 quantitative traits of basic epidemiological, anthropometric, or blood chemistry parameters. Each analysis result was subjected to subsequent gene set analyses based on Gene Ontology (GO terms using gene set analysis software, GSA-SNP, identifying a set of GO terms significantly associated to each trait (pcorr < 0.05. Pairwise comparison of the traits in terms of the semantic similarity in their GO sets revealed surprising cases where phenotypically uncorrelated traits showed high similarity in terms of biological pathways. For example, the pH level was related to 7 other traits that showed low phenotypic correlations with it. A literature survey implies that these traits may be regulated partly by common pathways that involve neuronal or nerve systems.

  1. Shifts in Selective Pressures on Snake Phototransduction Genes Associated with Photoreceptor Transmutation and Dim-Light Ancestry.

    Science.gov (United States)

    Schott, Ryan K; Van Nynatten, Alexander; Card, Daren C; Castoe, Todd A; S W Chang, Belinda

    2018-06-01

    The visual systems of snakes are heavily modified relative to other squamates, a condition often thought to reflect their fossorial origins. Further modifications are seen in caenophidian snakes, where evolutionary transitions between rod and cone photoreceptors, termed photoreceptor transmutations, have occurred in many lineages. Little previous work, however, has focused on the molecular evolutionary underpinnings of these morphological changes. To address this, we sequenced seven snake eye transcriptomes and utilized new whole-genome and targeted capture sequencing data. We used these data to analyze gene loss and shifts in selection pressures in phototransduction genes that may be associated with snake evolutionary origins and photoreceptor transmutation. We identified the surprising loss of rhodopsin kinase (GRK1), despite a low degree of gene loss overall and a lack of relaxed selection early during snake evolution. These results provide some of the first evolutionary genomic corroboration for a dim-light ancestor that lacks strong fossorial adaptations. Our results also indicate that snakes with photoreceptor transmutation experienced significantly different selection pressures from other reptiles. Significant positive selection was found primarily in cone-specific genes, but not rod-specific genes, contrary to our expectations. These results reveal potential molecular adaptations associated with photoreceptor transmutation and also highlight unappreciated functional differences between rod- and cone-specific phototransduction proteins. This intriguing example of snake visual system evolution illustrates how the underlying molecular components of a complex system can be reshaped in response to changing selection pressures.

  2. Spicing Up the N Gene: F. O. Holmes and Tobacco mosaic virus Resistance in Capsicum and Nicotiana Plants.

    Science.gov (United States)

    Scholthof, Karen-Beth G

    2017-02-01

    One of the seminal events in plant pathology was the discovery by Francis O. Holmes that necrotic local lesions induced on certain species of Nicotiana following rub-inoculation of Tobacco mosaic virus (TMV) was due to a specific interaction involving a dominant host gene (N). From this, Holmes had an idea that if the N gene from N. glutinosa was introgressed into susceptible tobacco, the greatly reduced titer of TMV would, by extension, prevent subsequent infection of tomato and pepper plants by field workers whose hands were contaminated with TMV from their use of chewing and smoking tobacco. The ultimate outcome has many surprising twists and turns, including Holmes' failure to obtain fertile crosses of N. glutinosa × N. tabacum after 3 years of intensive work. Progress was made with N. digluta, a rare amphidiploid that was readily crossed with N. tabacum. And, importantly, the first demonstration by Holmes of the utility of interspecies hybridization for virus resistance was made with Capsicum (pepper) species with the identification of the L gene in Tabasco pepper, that he introgressed into commercial bell pepper varieties. Holmes' findings are important as they predate Flor's gene-for-gene hypothesis, show the use of interspecies hybridization for control of plant pathogens, and the use of the local lesion as a bioassay to monitor resistance events in crop plants.

  3. Reference Gene Screening for Analyzing Gene Expression Across Goat Tissue

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    Yu Zhang

    2013-12-01

    Full Text Available Real-time quantitative PCR (qRT-PCR is one of the important methods for investigating the changes in mRNA expression levels in cells and tissues. Selection of the proper reference genes is very important when calibrating the results of real-time quantitative PCR. Studies on the selection of reference genes in goat tissues are limited, despite the economic importance of their meat and dairy products. We used real-time quantitative PCR to detect the expression levels of eight reference gene candidates (18S, TBP, HMBS, YWHAZ, ACTB, HPRT1, GAPDH and EEF1A2 in ten tissues types sourced from Boer goats. The optimal reference gene combination was selected according to the results determined by geNorm, NormFinder and Bestkeeper software packages. The analyses showed that tissue is an important variability factor in genes expression stability. When all tissues were considered, 18S, TBP and HMBS is the optimal reference combination for calibrating quantitative PCR analysis of gene expression from goat tissues. Dividing data set by tissues, ACTB was the most stable in stomach, small intestine and ovary, 18S in heart and spleen, HMBS in uterus and lung, TBP in liver, HPRT1 in kidney and GAPDH in muscle. Overall, this study provided valuable information about the goat reference genes that can be used in order to perform a proper normalisation when relative quantification by qRT-PCR studies is undertaken.

  4. Therapeutic genes for anti-HIV/AIDS gene therapy.

    Science.gov (United States)

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  5. Contradiction between plastid gene transcription and function due to complex posttranscriptional splicing: an exemplary study of ycf15 function and evolution in angiosperms.

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    Chao Shi

    Full Text Available Plant chloroplast genes are usually co-transcribed while its posttranscriptional splicing is fairly complex and remains largely unsolved. On basis of sequencing the three complete Camellia (Theaceae chloroplast genomes for the first time, we comprehensively analyzed the evolutionary patterns of ycf15, a plastid gene quite paradoxical in terms of its function and evolution, along the inferred angiosperm phylogeny. Although many species in separate lineages including the three species reported here contained an intact ycf15 gene in their chloroplast genomes, the phylogenetic mixture of both intact and obviously disabled ycf15 genes imply that they are all non-functional. Both intracellular gene transfer (IGT and horizontal gene transfer (HGT failed to explain such distributional anomalies. While, transcriptome analyses revealed that ycf15 was transcribed as precursor polycistronic transcript which contained ycf2, ycf15 and antisense trnL-CAA. The transcriptome assembly was surprisingly found to cover near the complete Camellia chloroplast genome. Many non-coding regions including pseudogenes were mapped by multiple transcripts, indicating the generality of pseudogene transcriptions. Our results suggest that plastid DNA posttranscriptional splicing may involve complex cleavage of non-functional genes.

  6. Global analysis of gene expression in response to L-Cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica

    Science.gov (United States)

    2011-01-01

    Background Entamoeba histolytica, an enteric protozoan parasite, causes amebic colitis and extra intestinal abscesses in millions of inhabitants of endemic areas. E. histolytica completely lacks glutathione metabolism but possesses L-cysteine as the principle low molecular weight thiol. L-Cysteine is essential for the structure, stability, and various protein functions, including catalysis, electron transfer, redox regulation, nitrogen fixation, and sensing for regulatory processes. Recently, we demonstrated that in E. histolytica, L-cysteine regulates various metabolic pathways including energy, amino acid, and phospholipid metabolism. Results In this study, employing custom-made Affymetrix microarrays, we performed time course (3, 6, 12, 24, and 48 h) gene expression analysis upon L-cysteine deprivation. We identified that out of 9,327 genes represented on the array, 290 genes encoding proteins with functions in metabolism, signalling, DNA/RNA regulation, electron transport, stress response, membrane transport, vesicular trafficking/secretion, and cytoskeleton were differentially expressed (≥3 fold) at one or more time points upon L-cysteine deprivation. Approximately 60% of these modulated genes encoded proteins of no known function and annotated as hypothetical proteins. We also attempted further functional analysis of some of the most highly modulated genes by L-cysteine depletion. Conclusions To our surprise, L-cysteine depletion caused only limited changes in the expression of genes involved in sulfur-containing amino acid metabolism and oxidative stress defense. In contrast, we observed significant changes in the expression of several genes encoding iron sulfur flavoproteins, a major facilitator super-family transporter, regulator of nonsense transcripts, NADPH-dependent oxido-reductase, short chain dehydrogenase, acetyltransferases, and various other genes involved in diverse cellular functions. This study represents the first genome-wide analysis of

  7. Global analysis of gene expression in response to L-Cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica

    Directory of Open Access Journals (Sweden)

    Jeelani Ghulam

    2011-05-01

    Full Text Available Abstract Background Entamoeba histolytica, an enteric protozoan parasite, causes amebic colitis and extra intestinal abscesses in millions of inhabitants of endemic areas. E. histolytica completely lacks glutathione metabolism but possesses L-cysteine as the principle low molecular weight thiol. L-Cysteine is essential for the structure, stability, and various protein functions, including catalysis, electron transfer, redox regulation, nitrogen fixation, and sensing for regulatory processes. Recently, we demonstrated that in E. histolytica, L-cysteine regulates various metabolic pathways including energy, amino acid, and phospholipid metabolism. Results In this study, employing custom-made Affymetrix microarrays, we performed time course (3, 6, 12, 24, and 48 h gene expression analysis upon L-cysteine deprivation. We identified that out of 9,327 genes represented on the array, 290 genes encoding proteins with functions in metabolism, signalling, DNA/RNA regulation, electron transport, stress response, membrane transport, vesicular trafficking/secretion, and cytoskeleton were differentially expressed (≥3 fold at one or more time points upon L-cysteine deprivation. Approximately 60% of these modulated genes encoded proteins of no known function and annotated as hypothetical proteins. We also attempted further functional analysis of some of the most highly modulated genes by L-cysteine depletion. Conclusions To our surprise, L-cysteine depletion caused only limited changes in the expression of genes involved in sulfur-containing amino acid metabolism and oxidative stress defense. In contrast, we observed significant changes in the expression of several genes encoding iron sulfur flavoproteins, a major facilitator super-family transporter, regulator of nonsense transcripts, NADPH-dependent oxido-reductase, short chain dehydrogenase, acetyltransferases, and various other genes involved in diverse cellular functions. This study represents the first

  8. Removal of unwanted variation reveals novel patterns of gene expression linked to sleep homeostasis in murine cortex

    Directory of Open Access Journals (Sweden)

    Jason R. Gerstner

    2016-10-01

    Full Text Available Abstract Background Why we sleep is still one of the most perplexing mysteries in biology. Strong evidence indicates that sleep is necessary for normal brain function and that sleep need is a tightly regulated process. Surprisingly, molecular mechanisms that determine sleep need are incompletely described. Moreover, very little is known about transcriptional changes that specifically accompany the accumulation and discharge of sleep need. Several studies have characterized differential gene expression changes following sleep deprivation. Much less is known, however, about changes in gene expression during the compensatory response to sleep deprivation (i.e. recovery sleep. Results In this study we present a comprehensive analysis of the effects of sleep deprivation and subsequent recovery sleep on gene expression in the mouse cortex. We used a non-traditional analytical method for normalization of genome-wide gene expression data, Removal of Unwanted Variation (RUV. RUV improves detection of differential gene expression following sleep deprivation. We also show that RUV normalization is crucial to the discovery of differentially expressed genes associated with recovery sleep. Our analysis indicates that the majority of transcripts upregulated by sleep deprivation require 6 h of recovery sleep to return to baseline levels, while the majority of downregulated transcripts return to baseline levels within 1–3 h. We also find that transcripts that change rapidly during recovery (i.e. within 3 h do so on average with a time constant that is similar to the time constant for the discharge of sleep need. Conclusions We demonstrate that proper data normalization is essential to identify changes in gene expression that are specifically linked to sleep deprivation and recovery sleep. Our results provide the first evidence that recovery sleep is comprised of two waves of transcriptional regulation that occur at different times and affect functionally

  9. Extreme Mutation Tolerance: Nearly Half of the Archaeal Fusellovirus Sulfolobus Spindle-Shaped Virus 1 Genes Are Not Required for Virus Function, Including the Minor Capsid Protein Gene vp3.

    Science.gov (United States)

    Iverson, Eric A; Goodman, David A; Gorchels, Madeline E; Stedman, Kenneth M

    2017-05-15

    Viruses infecting the Archaea harbor a tremendous amount of genetic diversity. This is especially true for the spindle-shaped viruses of the family Fuselloviridae , where >90% of the viral genes do not have detectable homologs in public databases. This significantly limits our ability to elucidate the role of viral proteins in the infection cycle. To address this, we have developed genetic techniques to study the well-characterized fusellovirus Sulfolobus spindle-shaped virus 1 (SSV1), which infects Sulfolobus solfataricus in volcanic hot springs at 80°C and pH 3. Here, we present a new comparative genome analysis and a thorough genetic analysis of SSV1 using both specific and random mutagenesis and thereby generate mutations in all open reading frames. We demonstrate that almost half of the SSV1 genes are not essential for infectivity, and the requirement for a particular gene correlates well with its degree of conservation within the Fuselloviridae The major capsid gene vp1 is essential for SSV1 infectivity. However, the universally conserved minor capsid gene vp3 could be deleted without a loss in infectivity and results in virions with abnormal morphology. IMPORTANCE Most of the putative genes in the spindle-shaped archaeal hyperthermophile fuselloviruses have no sequences that are clearly similar to characterized genes. In order to determine which of these SSV genes are important for function, we disrupted all of the putative genes in the prototypical fusellovirus, SSV1. Surprisingly, about half of the genes could be disrupted without destroying virus function. Even deletions of one of the known structural protein genes that is present in all known fuselloviruses, vp3 , allows the production of infectious viruses. However, viruses lacking vp3 have abnormal shapes, indicating that the vp3 gene is important for virus structure. Identification of essential genes will allow focused research on minimal SSV genomes and further understanding of the structure of

  10. RNomics and Modomics in the halophilic archaea Haloferax volcanii: identification of RNA modification genes

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    Decatur Wayne A

    2008-10-01

    Full Text Available Abstract Background Naturally occurring RNAs contain numerous enzymatically altered nucleosides. Differences in RNA populations (RNomics and pattern of RNA modifications (Modomics depends on the organism analyzed and are two of the criteria that distinguish the three kingdoms of life. If the genomic sequences of the RNA molecules can be derived from whole genome sequence information, the modification profile cannot and requires or direct sequencing of the RNAs or predictive methods base on the presence or absence of the modifications genes. Results By employing a comparative genomics approach, we predicted almost all of the genes coding for the t+rRNA modification enzymes in the mesophilic moderate halophile Haloferax volcanii. These encode both guide RNAs and enzymes. Some are orthologous to previously identified genes in Archaea, Bacteria or in Saccharomyces cerevisiae, but several are original predictions. Conclusion The number of modifications in t+rRNAs in the halophilic archaeon is surprisingly low when compared with other Archaea or Bacteria, particularly the hyperthermophilic organisms. This may result from the specific lifestyle of halophiles that require high intracellular salt concentration for survival. This salt content could allow RNA to maintain its functional structural integrity with fewer modifications. We predict that the few modifications present must be particularly important for decoding, accuracy of translation or are modifications that cannot be functionally replaced by the electrostatic interactions provided by the surrounding salt-ions. This analysis also guides future experimental validation work aiming to complete the understanding of the function of RNA modifications in Archaeal translation.

  11. Detection and characterization of Pasteuria 16S rRNA gene sequences from nematodes and soils.

    Science.gov (United States)

    Duan, Y P; Castro, H F; Hewlett, T E; White, J H; Ogram, A V

    2003-01-01

    Various bacterial species in the genus Pasteuria have great potential as biocontrol agents against plant-parasitic nematodes, although study of this important genus is hampered by the current inability to cultivate Pasteuria species outside their host. To aid in the study of this genus, an extensive 16S rRNA gene sequence phylogeny was constructed and this information was used to develop cultivation-independent methods for detection of Pasteuria in soils and nematodes. Thirty new clones of Pasteuria 16S rRNA genes were obtained directly from nematodes and soil samples. These were sequenced and used to construct an extensive phylogeny of this genus. These sequences were divided into two deeply branching clades within the low-G + C, Gram-positive division; some sequences appear to represent novel species within the genus Pasteuria. In addition, a surprising degree of 16S rRNA gene sequence diversity was observed within what had previously been designated a single strain of Pasteuria penetrans (P-20). PCR primers specific to Pasteuria 16S rRNA for detection of Pasteuria in soils were also designed and evaluated. Detection limits for soil DNA were 100-10,000 Pasteuria endospores (g soil)(-1).

  12. Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum.

    Science.gov (United States)

    Kidwell, Chelsea U; Su, Chen-Ying; Hibi, Masahiko; Moens, Cecilia B

    2018-06-01

    A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons. Surprisingly, the two genes are expressed in non-overlapping granule cell progenitor populations, indicating that fish use duplicate atoh1 genes to generate granule cell diversity that is not detected in mammals. Finally, live imaging of granule cell migration in wildtype and atoh1c mutant embryos reveals that while atoh1c is not required for granule cell specification per se, it is required for granule cells to delaminate and migrate away from the rhombic lip. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Variability of Pasteurella multocida isolated from Icelandic sheep and detection of the toxA gene.

    Science.gov (United States)

    Einarsdottir, Thorbjorg; Gunnarsson, Eggert; Sigurdardottir, Olof G; Jorundsson, Einar; Fridriksdottir, Vala; Thorarinsdottir, Gudridur E; Hjartardottir, Sigridur

    2016-09-01

    Pasteurella multocida can be part of the upper respiratory flora of animals, but under conditions of stress or immunocompromisation, the bacteria can cause severe respiratory symptoms. In this study, we compared 10 P. multocida isolates from Icelandic sheep with respiratory symptoms and 19 isolates from apparently healthy abattoir sheep. We examined capsule type, genetic variability and the presence of the toxA gene in the two groups. Surprisingly, we found that all ovine P. multocida isolates examined in this study carried the toxA gene, which markedly differs from what has been published from other studies. Interestingly, all isolates from abattoir animals were capsule type D, whilst bacteria isolated from animals with clinical respiratory symptoms had capsule type A, D or F. Examination of seven housekeeping genes indicated that the clinical respiratory isolates were significantly more heterogeneous than the abattoir isolates (P<0.05, two-tailed Mann-Whitney U test). The results suggest that there may be at least two groups of P. multocida in sheep - a genetically homogeneous group that resides in the respiratory tract and a genetically heterogeneous group that is the predominant cause of disease.

  14. A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila

    Science.gov (United States)

    Verd, Berta; Clark, Erik; Wotton, Karl R.; Janssens, Hilde; Jiménez-Guri, Eva; Crombach, Anton

    2018-01-01

    Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene regulation. Gap genes constitute the first layer of the Drosophila segmentation gene hierarchy, downstream of maternal gradients such as that of Caudal (Cad). We use data-driven mathematical modelling and phase space analysis to show that shifting gap domains in the posterior half of the Drosophila embryo are an emergent property of a robust damped oscillator mechanism, suggesting that the regulatory dynamics underlying long- and short-germband segmentation are much more similar than previously thought. In Tribolium, Cad has been proposed to modulate the frequency of the segmentation oscillator. Surprisingly, our simulations and experiments show that the shift rate of posterior gap domains is independent of maternal Cad levels in Drosophila. Our results suggest a novel evolutionary scenario for the short- to long-germband transition and help explain why this transition occurred convergently multiple times during the radiation of the holometabolan insects. PMID:29451884

  15. With a pinch of extra salt-Did predatory protists steal genes from their food?

    Science.gov (United States)

    Czech, Laura; Bremer, Erhard

    2018-02-01

    The cellular adjustment of Bacteria and Archaea to high-salinity habitats is well studied and has generally been classified into one of two strategies. These are to accumulate high levels either of ions (the "salt-in" strategy) or of physiologically compliant organic osmolytes, the compatible solutes (the "salt-out" strategy). Halophilic protists are ecophysiological important inhabitants of salt-stressed ecosystems because they are not only very abundant but also represent the majority of eukaryotic lineages in nature. However, their cellular osmostress responses have been largely neglected. Recent reports have now shed new light on this issue using the geographically widely distributed halophilic heterotrophic protists Halocafeteria seosinensis, Pharyngomonas kirbyi, and Schmidingerothrix salinarum as model systems. Different approaches led to the joint conclusion that these unicellular Eukarya use the salt-out strategy to cope successfully with the persistent high salinity in their habitat. They accumulate various compatible solutes, e.g., glycine betaine, myo-inositol, and ectoines. The finding of intron-containing biosynthetic genes for ectoine and hydroxyectoine, their salt stress-responsive transcription in H. seosinensis, and the production of ectoine and its import by S. salinarum come as a considerable surprise because ectoines have thus far been considered exclusive prokaryotic compatible solutes. Phylogenetic considerations of the ectoine/hydroxyectoine biosynthetic genes of H. seosinensis suggest that they have been acquired via lateral gene transfer by these bacterivorous Eukarya from ectoine/hydroxyectoine-producing food bacteria that populate the same habitat.

  16. With a pinch of extra salt—Did predatory protists steal genes from their food?

    Science.gov (United States)

    Czech, Laura

    2018-01-01

    The cellular adjustment of Bacteria and Archaea to high-salinity habitats is well studied and has generally been classified into one of two strategies. These are to accumulate high levels either of ions (the “salt-in” strategy) or of physiologically compliant organic osmolytes, the compatible solutes (the “salt-out” strategy). Halophilic protists are ecophysiological important inhabitants of salt-stressed ecosystems because they are not only very abundant but also represent the majority of eukaryotic lineages in nature. However, their cellular osmostress responses have been largely neglected. Recent reports have now shed new light on this issue using the geographically widely distributed halophilic heterotrophic protists Halocafeteria seosinensis, Pharyngomonas kirbyi, and Schmidingerothrix salinarum as model systems. Different approaches led to the joint conclusion that these unicellular Eukarya use the salt-out strategy to cope successfully with the persistent high salinity in their habitat. They accumulate various compatible solutes, e.g., glycine betaine, myo-inositol, and ectoines. The finding of intron-containing biosynthetic genes for ectoine and hydroxyectoine, their salt stress–responsive transcription in H. seosinensis, and the production of ectoine and its import by S. salinarum come as a considerable surprise because ectoines have thus far been considered exclusive prokaryotic compatible solutes. Phylogenetic considerations of the ectoine/hydroxyectoine biosynthetic genes of H. seosinensis suggest that they have been acquired via lateral gene transfer by these bacterivorous Eukarya from ectoine/hydroxyectoine-producing food bacteria that populate the same habitat. PMID:29394244

  17. GENES IN SPORT AND DOPING

    Directory of Open Access Journals (Sweden)

    Andrzej Pokrywka

    2013-06-01

    Full Text Available Genes control biological processes such as muscle production of energy, mitochondria biogenesis, bone formation erythropoiesis, angiogenesis, vasodilation, neurogenesis, etc. DNA profiling for athletes reveals genetic variations that may be associated with endurance ability, muscle performance and power exercise, tendon susceptibility to injuries and psychological aptitude. Already, over 200 genes relating to physical performance have been identified by several research groups. Athletes’ genotyping is developing as a tool for the formulation of personalized training and nutritional programmes to optimize sport training as well as for the prediction of exercise-related injuries. On the other hand, development of molecular technology and gene therapy creates a risk of non-therapeutic use of cells, genes and genetic elements to improve athletic performance. Therefore, the World Anti-Doping Agency decided to include prohibition of gene doping within their World Anti-Doping Code in 2003. In this review article, we will provide a current overview of genes for use in athletes’ genotyping and gene doping possibilities, including their development and detection techniques.

  18. [Gene doping: gene transfer and possible molecular detection].

    Science.gov (United States)

    Argüelles, Carlos Francisco; Hernández-Zamora, Edgar

    2007-01-01

    The use of illegal substances in sports to enhance athletic performance during competition has caused international sports organizations such as the COI and WADA to take anti doping measures. A new doping method know as gene doping is defined as "the non-therapeutic use of genes, genetic elements and/or cells that have the capacity to enhance athletic performance". However, gene doping in sports is not easily identified and can cause serious consequences. Molecular biology techniques are needed in order to distinguish the difference between a "normal" and an "altered" genome. Further, we need to develop new analytic methods and biological molecular techniques in anti-doping laboratories, and design programs that avoid the non therapeutic use of genes.

  19. Delimiting Coalescence Genes (C-Genes) in Phylogenomic Data Sets.

    Science.gov (United States)

    Springer, Mark S; Gatesy, John

    2018-02-26

    coalescence methods have emerged as a popular alternative for inferring species trees with large genomic datasets, because these methods explicitly account for incomplete lineage sorting. However, statistical consistency of summary coalescence methods is not guaranteed unless several model assumptions are true, including the critical assumption that recombination occurs freely among but not within coalescence genes (c-genes), which are the fundamental units of analysis for these methods. Each c-gene has a single branching history, and large sets of these independent gene histories should be the input for genome-scale coalescence estimates of phylogeny. By contrast, numerous studies have reported the results of coalescence analyses in which complete protein-coding sequences are treated as c-genes even though exons for these loci can span more than a megabase of DNA. Empirical estimates of recombination breakpoints suggest that c-genes may be much shorter, especially when large clades with many species are the focus of analysis. Although this idea has been challenged recently in the literature, the inverse relationship between c-gene size and increased taxon sampling in a dataset-the 'recombination ratchet'-is a fundamental property of c-genes. For taxonomic groups characterized by genes with long intron sequences, complete protein-coding sequences are likely not valid c-genes and are inappropriate units of analysis for summary coalescence methods unless they occur in recombination deserts that are devoid of incomplete lineage sorting (ILS). Finally, it has been argued that coalescence methods are robust when the no-recombination within loci assumption is violated, but recombination must matter at some scale because ILS, a by-product of recombination, is the raison d'etre for coalescence methods. That is, extensive recombination is required to yield the large number of independently segregating c-genes used to infer a species tree. If coalescent methods are powerful

  20. Gene therapy of cancer by vaccines carrying inserted immunostimulatory genes

    Czech Academy of Sciences Publication Activity Database

    Bubeník, Jan

    2007-01-01

    Roč. 53, č. 3 (2007), s. 71-73 ISSN 0015-5500 Grant - others:EU-FP6 NoE Clinigene(XE) 018933; Liga proti rakovině, Praha(CZ) XX Institutional research plan: CEZ:AV0Z50520514 Keywords : gene therapy * immunostimulatory genes * vaccine Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.596, year: 2007

  1. Cloning and selection of reference genes for gene expression ...

    African Journals Online (AJOL)

    Full length mRNA sequences of Ac-β-actin and Ac-gapdh, and partial mRNA sequences of Ac-18SrRNA and Ac-ubiquitin were cloned from pineapple in this study. The four genes were tested as housekeeping genes in three experimental sets. GeNorm and NormFinder analysis revealed that β-actin was the most ...

  2. The hunt for gene dopers.

    Science.gov (United States)

    Mansour, Mai M H; Azzazy, Hassan M E

    2009-07-01

    Gene doping, the abuse of gene therapy for illicit athletic enhancement, is perceived as a coming threat and is a prime concern to the anti-doping community. This doping technique represents a significant ethical challenge and there are concerns regarding its safety for athletes. This article presents the basics of gene doping, potential strategies for its detection and the role of promising new technologies in aiding detection efforts. These include the use of lab-on-a-chip techniques as well as nanoparticles to enhance the performance of current analytical methods and to develop new doping detection strategies.

  3. Gene Therapy Approaches to Hemoglobinopathies.

    Science.gov (United States)

    Ferrari, Giuliana; Cavazzana, Marina; Mavilio, Fulvio

    2017-10-01

    Gene therapy for hemoglobinopathies is currently based on transplantation of autologous hematopoietic stem cells genetically modified with a lentiviral vector expressing a globin gene under the control of globin transcriptional regulatory elements. Preclinical and early clinical studies showed the safety and potential efficacy of this therapeutic approach as well as the hurdles still limiting its general application. In addition, for both beta-thalassemia and sickle cell disease, an altered bone marrow microenvironment reduces the efficiency of stem cell harvesting as well as engraftment. These hurdles need be addressed for gene therapy for hemoglobinopathies to become a clinical reality. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Gene expression in colorectal cancer

    DEFF Research Database (Denmark)

    Birkenkamp-Demtroder, Karin; Christensen, Lise Lotte; Olesen, Sanne Harder

    2002-01-01

    Understanding molecular alterations in colorectal cancer (CRC) is needed to define new biomarkers and treatment targets. We used oligonucleotide microarrays to monitor gene expression of about 6,800 known genes and 35,000 expressed sequence tags (ESTs) on five pools (four to six samples in each...... pool) of total RNA from left-sided sporadic colorectal carcinomas. We compared normal tissue to carcinoma tissue from Dukes' stages A-D (noninvasive to distant metastasis) and identified 908 known genes and 4,155 ESTs that changed remarkably from normal to tumor tissue. Based on intensive filtering 226...

  5. Correction of gene expression data

    DEFF Research Database (Denmark)

    Darbani Shirvanehdeh, Behrooz; Stewart, C. Neal, Jr.; Noeparvar, Shahin

    2014-01-01

    This report investigates for the first time the potential inter-treatment bias source of cell number for gene expression studies. Cell-number bias can affect gene expression analysis when comparing samples with unequal total cellular RNA content or with different RNA extraction efficiencies....... For maximal reliability of analysis, therefore, comparisons should be performed at the cellular level. This could be accomplished using an appropriate correction method that can detect and remove the inter-treatment bias for cell-number. Based on inter-treatment variations of reference genes, we introduce...

  6. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Gene & Cell Therapy Defined Gene therapy and cell therapy are overlapping fields of biomedical research that aim to repair the direct cause of genetic diseases. Read More Gene & Cell Therapy FAQ's Read the most common questions raised by ...

  7. Basics on Genes and Genetic Disorders

    Science.gov (United States)

    ... for Educators Search English Español The Basics on Genes and Genetic Disorders KidsHealth / For Teens / The Basics ... such as treating health problems. What Is a Gene? To understand how genes work, let's review some ...

  8. Norrie disease gene is distinct from the monoamine oxidase genes.

    Science.gov (United States)

    Sims, K B; Ozelius, L; Corey, T; Rinehart, W B; Liberfarb, R; Haines, J; Chen, W J; Norio, R; Sankila, E; de la Chapelle, A

    1989-09-01

    The genes for MAO-A and MAO-B appear to be very close to the Norrie disease gene, on the basis of loss and/or disruption of the MAO genes and activities in atypical Norrie disease patients deleted for the DXS7 locus; linkage among the MAO genes, the Norrie disease gene, and the DXS7 locus; and mapping of all these loci to the chromosomal region Xp11. The present study provides evidence that the MAO genes are not disrupted in "classic" Norrie disease patients. Genomic DNA from these "nondeletion" Norrie disease patients did not show rearrangements at the MAOA or DXS7 loci. Normal levels of MAO-A activities, as well as normal amounts and size of the MAO-A mRNA, were observed in cultured skin fibroblasts from these patients, and MAO-B activity in their platelets was normal. Catecholamine metabolites evaluated in plasma and urine were in the control range. Thus, although some atypical Norrie disease patients lack both MAO-A and MAO-B activities, MAO does not appear to be an etiologic factor in classic Norrie disease.

  9. Mutational studies of putative biosynthetic genes for the cyanobacterial sunscreen scytonemin in Nostoc punctiforme ATCC 29133

    Directory of Open Access Journals (Sweden)

    Daniela eFerreira

    2016-05-01

    Full Text Available The heterocyclic indole-alkaloid scytonemin is a sunscreen found exclusively among cyanobacteria. An 18-gene cluster is responsible for scytonemin production in Nostoc punctiforme ATCC 29133. The upstream genes scyABCDEF in the cluster are proposed to be responsible for scytonemin biosynthesis from aromatic amino acid substrates. In vitro studies of ScyA, ScyB and ScyC proved that these enzymes indeed catalyze initial pathway reactions. Here we characterize the role of ScyD, ScyE and ScyF, which were logically predicted to be responsible for late biosynthetic steps, in the biological context of N. punctiforme. In-frame deletion mutants of each were constructed (∆scyD, ∆scyE and ∆scyF and their phenotypes studied. Expectedly, ∆scyE presents a scytoneminless phenotype, but no accumulation of the predicted intermediaries. Surprisingly, ∆scyD retains scytonemin production, implying that it is not required for biosynthesis. Indeed, scyD presents an interesting evolutionary paradox: it likely originated in a duplication event from scyE, and unlike other genes in the operon, it has not been subjected to purifying selection. This would suggest that it is a pseudogene, and yet scyD is highly conserved in the scytonemin operon of cyanobacteria. ∆scyF also retains scytonemin production, albeit exhibiting a reduction of the production yield compared with the wild-type. This indicates that ScyF is not essential but may play an adjuvant role for scytonemin synthesis. Altogether, our findings suggest that these downstream genes are not responsible, as expected, for the late steps of scytonemin synthesis and we must look for those functions elsewhere. These findings are particularly important for biotechnological production of this sunscreen through heterologous expression of its genes in more tractable organisms.

  10. Domain movement within a gene: a novel evolutionary mechanism for protein diversification.

    Directory of Open Access Journals (Sweden)

    Yoshikazu Furuta

    Full Text Available A protein function is carried out by a specific domain localized at a specific position. In the present study, we report that, within a gene, a specific amino acid sequence can move between a certain position and another position. This was discovered when the sequences of restriction-modification systems within the bacterial species Helicobacter pylori were compared. In the specificity subunit of Type I restriction-modification systems, DNA sequence recognition is mediated by target recognition domain 1 (TRD1 and TRD2. To our surprise, several sequences are shared by TRD1 and TRD2 of genes (alleles at the same locus (chromosomal location; these domains appear to have moved between the two positions. The gene/protein organization can be represented as x-(TRD1-y-x-(TRD2-y, where x and y represent repeat sequences. Movement probably occurs by recombination at these flanking DNA repeats. In accordance with this hypothesis, recombination at these repeats also appears to decrease two TRDs into one TRD or increase these two TRDs to three TRDs (TRD1-TRD2-TRD2 and to allow TRD movement between genes even at different loci. Similar movement of domains between TRD1 and TRD2 was observed for the specificity subunit of a Type IIG restriction enzyme. Similar movement of domain between TRD1 and TRD2 was observed for Type I restriction-modification enzyme specificity genes in two more eubacterial species, Streptococcus pyogenes and Mycoplasma agalactiae. Lateral domain movements within a protein, which we have designated DOMO (domain movement, represent novel routes for the diversification of proteins.

  11. Using The Corngrass1 Gene To Enhance The Biofuel Properties Of Crop Plants

    Energy Technology Data Exchange (ETDEWEB)

    Hake, Sarah [USDA Agricultural Research Service, Washington DC (United States); Chuck, George [USDA Agricultural Research Service, Washington DC (United States)

    2015-10-29

    The development of novel plant germplasm is vital to addressing our increasing bioenergy demands. The major hurdle to digesting plant biomass is the complex structure of the cell walls, the substrate of fermentation. Plant cell walls are inaccessible matrices of macromolecules that are polymerized with lignin, making fermentation difficult. Overcoming this hurdle is a major goal toward developing usable bioenergy crop plants. Our project seeks to enhance the biofuel properties of perennial grass species using the Corngrass1 (Cg1) gene and its targets. Dominant maize Cg1 mutants produce increased biomass by continuously initiating extra axillary meristems and leaves. We cloned Cg1 and showed that its phenotype is caused by over expression of a unique miR156 microRNA gene that negatively regulates SPL transcription factors. We transferred the Cg1 phenotype to other plants by expressing the gene behind constitutive promoters in four different species, including the monocots, Brachypodium and switchgrass, and dicots, Arabidopsis and poplar. All transformants displayed a similar range of phenotypes, including increased biomass from extended leaf production, and increased vegetative branching. Field grown switchgrass transformants showed that overall lignin content was reduced, the ratio of glucans to xylans was increased, and surprisingly, that starch levels were greatly increased. The goals of this project are to control the tissue and temporal expression of Cg1 by using different promoters to drive its expression, elucidate the function of the SPL targets of Cg1 by generating gain and loss of function alleles, and isolate downstream targets of select SPL genes using deep sequencing and chromatin immunoprecipitation. We believe it is possible to control biomass accumulation, cell wall properties, and sugar levels through manipulation of either the Cg1 gene and/or its SPL targets.

  12. Information-processing genes

    International Nuclear Information System (INIS)

    Tahir Shah, K.

    1995-01-01

    There are an estimated 100,000 genes in the human genome of which 97% is non-coding. On the other hand, bacteria have little or no non-coding DNA. Non-coding region includes introns, ALU sequences, satellite DNA, and other segments not expressed as proteins. Why it exists? Why nature has kept non-coding during the long evolutionary period if it has no role in the development of complex life forms? Does complexity of a species somehow correlated to the existence of apparently useless sequences? What kind of capability is encoded within such nucleotide sequences that is a necessary, but not a sufficient condition for the evolution of complex life forms, keeping in mind the C-value paradox and the omnipresence of non-coding segments in higher eurkaryotes and also in many archea and prokaryotes. The physico-chemical description of biological processes is hardware oriented and does not highlight algorithmic or information processing aspect. However, an algorithm without its hardware implementation is useless as much as hardware without its capability to run an algorithm. The nature and type of computation an information-processing hardware can perform depends only on its algorithm and the architecture that reflects the algorithm. Given that enormously difficult tasks such as high fidelity replication, transcription, editing and regulation are all achieved within a long linear sequence, it is natural to think that some parts of a genome are involved is these tasks. If some complex algorithms are encoded with these parts, then it is natural to think that non-coding regions contain processing-information algorithms. A comparison between well-known automatic sequences and sequences constructed out of motifs is found in all species proves the point: noncoding regions are a sort of ''hardwired'' programs, i.e., they are linear representations of information-processing machines. Thus in our model, a noncoding region, e.g., an intron contains a program (or equivalently, it is

  13. Gene Therapy for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Rachel Denyer

    2012-01-01

    Full Text Available Current pharmacological and surgical treatments for Parkinson's disease offer symptomatic improvements to those suffering from this incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel approaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used to provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects. More radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of Parkinson's disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective approach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy agents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the theoretical approaches to gene therapy for Parkinson's disease and the findings of clinical trials in this rapidly changing field.

  14. [Obesity studies in candidate genes].

    Science.gov (United States)

    Ochoa, María del Carmen; Martí, Amelia; Martínez, J Alfredo

    2004-04-17

    There are more than 430 chromosomic regions with gene variants involved in body weight regulation and obesity development. Polymorphisms in genes related to energy expenditure--uncoupling proteins (UCPs), related to adipogenesis and insulin resistance--hormone-sensitive lipase (HLS), peroxisome proliferator-activated receptor gamma (PPAR gamma), beta adrenergic receptors (ADRB2,3), and alfa tumor necrosis factor (TNF-alpha), and related to food intake--ghrelin (GHRL)--appear to be associated with obesity phenotypes. Obesity risk depends on two factors: a) genetic variants in candidate genes, and b) biographical exposure to environmental risk factors. It is necessary to perform new studies, with appropriate control groups and designs, in order to reach relevant conclusions with regard to gene/environmental (diet, lifestyle) interactions.

  15. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  16. Gene discovery in Triatoma infestans

    Directory of Open Access Journals (Sweden)

    de Burgos Nelia

    2011-03-01

    Full Text Available Abstract Background Triatoma infestans is the most relevant vector of Chagas disease in the southern cone of South America. Since its genome has not yet been studied, sequencing of Expressed Sequence Tags (ESTs is one of the most powerful tools for efficiently identifying large numbers of expressed genes in this insect vector. Results In this work, we generated 826 ESTs, resulting in an increase of 47% in the number of ESTs available for T. infestans. These ESTs were assembled in 471 unique sequences, 151 of which represent 136 new genes for the Reduviidae family. Conclusions Among the putative new genes for the Reduviidae family, we identified and described an interesting subset of genes involved in development and reproduction, which constitute potential targets for insecticide development.

  17. Gene therapy of thyroid carcinoma

    International Nuclear Information System (INIS)

    Zheng Wei; Tan Jian

    2007-01-01

    Normally, differentiated thyroid carcinoma(DTC) is a disease of good prognosis, but about 30% of the tumors are dedifferentiate, which are inaccessible to standard therapeutic procedures such as 'operation, 131 I therapy and thyroid hormone'. Both internal and abroad experts are researching a new therapy of dedifferentiated thyroid carcinoma--gene therapy. Many of them utilize methods of it, but follow different strategies: (1) transduction of the thyroid sodium/iodide transporter gene to make tissues that do not accumulate iodide treatable by 131 I therapy; (2) strengthening of the anti-tumor immune response; (3) suicide gene therapy; (4) depression the generation of tumor cells; (5) gene therapy of anti- vascularization. (authors)

  18. Tubulin evolution in insects: gene duplication and subfunctionalization provide specialized isoforms in a functionally constrained gene family

    Directory of Open Access Journals (Sweden)

    Gadagkar Sudhindra R

    2010-04-01

    with microtubule-associated proteins. CTT residues overwhelming comprise the co-evolving residues between Drosophila alpha 2 and beta 3 tubulin proteins, indicating CTT specializations can be mediated at the level of the tubulin dimer. Gene duplications post-dating separation of the insect orders are unevenly distributed, most often appearing in major alpha 1 and minor beta 2 clades. More than 40 introns are found in tubulins. Their distribution among tubulins reveals that insertion and deletion events are common, surprising given their potential for disrupting tubulin coding sequence. Compensatory evolution is found in Drosophila beta 2 tubulin cis-regulation, and reveals selective pressures acting to maintain testis expression without the use of previously identified testis cis-regulatory elements. Conclusion Tubulins have stringent structure/function relationships, indicated by strong purifying selection, the loss of many gene duplication products, alpha-beta co-evolution in the tubulin dimer, and compensatory evolution in beta 2 tubulin cis-regulation. They evolve through gene duplication, subfunctionalization in expression domain and divergence of duplication products, largely in CTT residues that mediate interactions with other proteins. This has resulted in the tissue-specific minor insect isoforms, and in particular the highly diverse α3, α4, and β2 reproductive tissue-specific tubulin isoforms, illustrating that even a highly conserved protein family can participate in the adaptive process and respond to sexual selection.

  19. MADS-box gene evolution - structure and transcription patterns

    DEFF Research Database (Denmark)

    Johansen, Bo; Pedersen, Louise Buchholt; Skipper, Martin

    2002-01-01

    Mads-box genes, ABC model, Evolution, Phylogeny, Transcription patterns, Gene structure, Conserved motifs......Mads-box genes, ABC model, Evolution, Phylogeny, Transcription patterns, Gene structure, Conserved motifs...

  20. Endocrine aspects of cancer gene therapy.

    Science.gov (United States)

    Barzon, Luisa; Boscaro, Marco; Palù, Giorgio

    2004-02-01

    The field of cancer gene therapy is in continuous expansion, and technology is quickly moving ahead as far as gene targeting and regulation of gene expression are concerned. This review focuses on the endocrine aspects of gene therapy, including the possibility to exploit hormone and hormone receptor functions for regulating therapeutic gene expression, the use of endocrine-specific genes as new therapeutic tools, the effects of viral vector delivery and transgene expression on the endocrine system, and the endocrine response to viral vector delivery. Present ethical concerns of gene therapy and the risk of germ cell transduction are also discussed, along with potential lines of innovation to improve cell and gene targeting.