bluuebunny/crossref_metadata_2025 huggingface dataset:
Carl Kisslinger (1926–2008)
Authors: Engdahl E. Robert , Sheehan Anne , Kisslinger Jerry
Published: July 2009

Carl Kisslinger, a geophysicist who furthered scientific and international understanding through tireless devotion to his field, died on 31 December 2008 at his home in Boulder, Colo. He was 82.

Studying geophysics under J. B. Macelwane at Saint Louis University, in Missouri, Carl earned his bachelor's degree in 1947 after an interruption due to World War II; he had been drafted into the U.S. Navy and taught radar, the then new technology, on Treasure Island in San Francisco Bay. Carl earned his master's degree in 1949 and his Ph.D. in 1952.
Expression of the Arabidopsis jasmonate signalling repressor JAZ1/TIFY10A is stimulated by auxin
Authors: Grunewald Wim , Vanholme Bartel , Pauwels Laurens , Plovie Eva , Inzé Dirk , Gheysen Godelieve , Goossens Alain
Published: July 2009

Plant hormones have pivotal roles in almost every aspect of plant development. Over the past decades, physiological and genetic studies have revealed that hormone action in plants is determined by complex interactions between hormonal signalling pathways. Evidence is accumulating for the existence of crosstalk between the auxin and jasmonate (JA) signalling pathways. Recently, the JASMONATE ZIM‐domain (JAZ) proteins have been identified as the long‐sought repressors of JA signalling. Here, we show that expression of JAZ1/TIFY10A is not solely inducible by JA, but that it is also an early auxin‐responsive gene. Furthermore, we could show that the auxin‐inducible expression of JAZ1/TIFY10A is independent of the JA signalling pathway but is controlled by the auxin/indole‐3‐acetic acid‐auxin response transcription factor signalling pathway. Our results provide evidence for the existence of at least two different input signals regarding JAZ1/TIFY10A expression and thus support the idea of an intimate molecular interplay between auxin and JA signalling.
CDK9 directs H2B monoubiquitination and controls replication‐dependent histone mRNA 3′‐end processing
Authors: Pirngruber Judith , Shchebet Andrei , Schreiber Lisa , Shema Efrat , Minsky Neri , Chapman Rob D , Eick Dirk , Aylon Yael , Oren Moshe , Johnsen Steven A
Published: July 2009

Post‐translational histone modifications have essential roles in controlling nuclear processes; however, the specific mechanisms regulating these modifications and their combinatorial activities remain elusive. Cyclin‐dependent kinase 9 (CDK9) regulates gene expression by phosphorylating transcriptional regulatory proteins, including the RNA polymerase II carboxy‐terminal domain. Here, we show that CDK9 activity is essential for maintaining global and gene‐associated levels of histone H2B monoubiquitination (H2Bub1). Furthermore, CDK9 activity and H2Bub1 help to maintain correct replication‐dependent histone messenger RNA (mRNA) 3′‐end processing. CDK9 knockdown consistently resulted in inefficient recognition of the correct mRNA 3′‐end cleavage site and led to increased read‐through of RNA polymerase II to an alternative downstream polyadenylation signal. Thus, CDK9 acts to integrate phosphorylation during transcription with chromatin modifications to control co‐transcriptional histone mRNA processing.
The NALCN ion channel is activated by M3 muscarinic receptors in a pancreatic β‐cell line
Authors: Swayne Leigh Anne , Mezghrani Alexandre , Varrault Annie , Chemin Jean , Bertrand Gyslaine , Dalle Stephane , Bourinet Emmanuel , Lory Philippe , Miller Richard J , Nargeot Joel , Monteil Arnaud
Published: July 2009

A previously uncharacterized putative ion channel, NALCN (sodium leak channel, non‐selective), has been recently shown to be responsible for the tetrodotoxin (TTX)‐resistant sodium leak current implicated in the regulation of neuronal excitability. Here, we show that NALCN encodes a current that is activated by M3 muscarinic receptors (M3R) in a pancreatic β‐cell line. This current is primarily permeant to sodium ions, independent of intracellular calcium stores and G proteins but dependent on Src activation, and resistant to TTX. The current is recapitulated by co‐expression of NALCN and M3R in human embryonic kidney‐293 cells and inXenopusoocytes. We also show that NALCN and M3R belong to the same protein complex, involving the intracellular I–II loop of NALCN and the intracellular i3 loop of M3R. Taken together, our data show the molecular basis of a muscarinic‐activated inward sodium current that is independent of G‐protein activation, and provide new insights into the properties of NALCN channels.
Detection of Sugarcane Yellow Leaf Luteovirus of India
Authors: Gaur Rajarshi , Rao G.P , Lehrer Axel
Published: July 2009

A luteovirus was found associated with midrib yellowing symptoms of sugarcane in India. The virus was earlier identified as sugarcane yellow leaf virus (SCYLV) on the basis of particle morphology and serological relationships. In this study, we attempted molecular characterization of an Indian isolate of SCYLV through reverse trascriptase-polymerase chain reaction (RT-PCR). Comparison showed that the deduced amino acid sequence share 98% homology with an isolate from Texas (cultivar CC85-964) and 100% homology with corresponding sequences of an Australian isolate of SCYLV (found in cultivar CP 65-357). Phylogenetic analysis also suggests that the coat protein of the SCYLV genome possesses different taxonomic affinities with other members of the family Luteoviridae.
Electrospinning route for the fabrication of p-n junction using nanofiber yarns
Authors: Lotus A. F. , Bhargava S. , Bender E. T. , Evans E. A. , Ramsier R. D. , Reneker D. H. , Chase G. G.
Published: July 2009

Electrospinning is a simple, versatile, and cost effective method for generating nanoscale fibers, wires, and tubes. Nanowires and nanotubes could be important building blocks for nanoscale electronics, optoelectronics, and sensors as they can function as miniaturized devices as well as electrical interconnects. We report on a simple method to fabricate free standing ceramic nanofiber heterostructures, which exhibit rectifying behavior of a p-n junction.
Thermal stability of Cu and Fe nitrides and their applications for writing locally spin valves
Authors: Navío C. , Alvarez J. , Capitan M. J. , Camarero J. , Miranda R.
Published: July 2009

We have studied the thermal stability of the Cu and Fe nitrides. These results show that a nanometer-thick Cu nitride film decomposes at the Fe4N growth temperature. Considering this, we propose for their use in spintronics, the room temperature growth of a nonmagnetic (FeN)/semiconducting (Cu3N) epitaxial nitride bilayer that transforms into a ferromagnetic (Fe4N)/metallic (Cu) one by mild thermal annealing at 700 K. This process can be employed to locally decompose by laser (or ion) irradiation FeN/Cu3N/Fe4N) trilayers, giving rise to an array of lithographically defined Fe4N/Cu/Fe4N spin valves surrounded by metal/semiconductor spacers.
Electric detection of spin wave resonance using inverse spin-Hall effect
Authors: Ando K. , Ieda J. , Sasage K. , Takahashi S. , Maekawa S. , Saitoh E.
Published: July 2009

Spin wave resonance in Ni81Fe19/Pt thin wire arrays has been investigated using the inverse spin-Hall effect (ISHE). The spin wave in the Ni81Fe19 layer drives spin pumping, generation of spin currents from magnetization precession, and the pumped spin current is converted into a charge current by ISHE in the Pt layer. We found an electromotive force transverse to the spatial and the spin-polarization directions of the spin current. The experimental results indicate that the amplitude of the electromotive force is proportional to the spin wave resonance absorption intensity, enabling the electric measurement of spin wave resonance in nanostructured magnetic systems.
Efficient computation of optimal actions
Authors: Todorov Emanuel
Published: July 2009

Optimal choice of actions is a fundamental problem relevant to fields as diverse as neuroscience, psychology, economics, computer science, and control engineering. Despite this broad relevance the abstract setting is similar: we have an agent choosing actions over time, an uncertain dynamical system whose state is affected by those actions, and a performance criterion that the agent seeks to optimize. Solving problems of this kind remains hard, in part, because of overly generic formulations. Here, we propose a more structured formulation that greatly simplifies the construction of optimal control laws in both discrete and continuous domains. An exhaustive search over actions is avoided and the problem becomes linear. This yields algorithms that outperform Dynamic Programming and Reinforcement Learning, and thereby solve traditional problems more efficiently. Our framework also enables computations that were not possible before: composing optimal control laws by mixing primitives, applying deterministic methods to stochastic systems, quantifying the benefits of error tolerance, and inferring goals from behavioral data via convex optimization. Development of a general class of easily solvable problems tends to accelerate progress—as linear systems theory has done, for example. Our framework may have similar impact in fields where optimal choice of actions is relevant.
Control of heart rate by cAMP sensitivity of HCN channels
Authors: Alig Jacqueline , Marger Laurine , Mesirca Pietro , Ehmke Heimo , Mangoni Matteo E. , Isbrandt Dirk
Published: July 2009

“Pacemaker” f-channels mediating the hyperpolarization-activated nonselective cation current
I
f
are directly regulated by cAMP. Accordingly, the activity of f-channels increases when cellular cAMP levels are elevated (e.g., during sympathetic stimulation) and decreases when they are reduced (e.g., during vagal stimulation). Although these biophysical properties seem to make f-channels ideal molecular targets for heart rate regulation by the autonomic nervous system, the exact contribution of the major
I
f
-mediating cardiac isoforms HCN2 and HCN4 to sinoatrial node (SAN) function remains highly controversial. To directly investigate the role of cAMP-dependent regulation of hyperpolarization activated cyclic nucleotide activated (HCN) channels in SAN activity, we generated mice with heart-specific and inducible expression of a human
HCN4
mutation (573X) that abolishes the cAMP-dependent regulation of HCN channels. We found that hHCN4–573X expression causes elimination of the cAMP sensitivity of
I
f
and decreases the maximum firing rates of SAN pacemaker cells. In conscious mice, hHCN4–573X expression leads to a marked reduction in heart rate at rest and during exercise. Despite the complete loss of cAMP sensitivity of
I
f
, the relative extent of SAN cell frequency and heart rate regulation are preserved. Our data demonstrate that cAMP-mediated regulation of
I
f
determines basal and maximal heart rates but does not play an indispensable role in heart rate adaptation during physical activity. Our data also reveal the pathophysiologic mechanism of hHCN4–573X–linked SAN dysfunction in humans.
miR-23a functions downstream of NFATc3 to regulate cardiac hypertrophy
Authors: Lin Zhiqiang , Murtaza Iram , Wang Kun , Jiao Jianqin , Gao Jie , Li Pei-Feng
Published: July 2009

Cardiac hypertrophy is accompanied by maladaptive cardiac remodeling, which leads to heart failure or sudden death. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that mediate posttranscriptional gene silencing. Recent studies show that miRNAs are involved in the pathogenesis of hypertrophy, but their signaling regulations remain to be understood. Here, we report that miR-23a is a pro-hypertrophic miRNA, and its expression is regulated by the transcription factor, nuclear factor of activated T cells (NFATc3). The results showed that miR-23a expression was up-regulated upon treatment with the hypertrophic stimuli including isoproterenol and aldosterone. Knockdown of miR-23a could attenuate hypertrophy, suggesting that miR-23a is able to convey the hypertrophic signal. In exploring the molecular mechanism by which miR-23a is up-regulated, we identified that NFATc3 could directly activate miR-23a expression through the transcriptional machinery. The muscle specific ring finger protein 1, an anti-hypertrophic protein, was identified to be a target of miR-23a. Its translation could be suppressed by miR-23a. Our data provide a model in which the miRNA expression is regulated by the hypertrophic transcriptional factor.
Processing and phosphorylation of the Fat receptor
Authors: Feng Yongqiang , Irvine Kenneth D.
Published: July 2009

The
Drosophila
tumor suppressors
fat
and
discs overgrown
(
dco
) function within an intercellular signaling pathway that controls growth and polarity.
fat
encodes a transmembrane receptor, but post-translational regulation of Fat has not been described. We show here that Fat is subject to a constitutive proteolytic processing, such that most or all cell surface Fat comprises a heterodimer of stably associated N- and C-terminal fragments. The cytoplasmic domain of Fat is phosphorylated, and this phosphorylation is promoted by the Fat ligand Dachsous.
dco
encodes a kinase that influences Fat signaling, and Dco is able to promote the phosphorylation of the Fat intracellular domain in cultured cells and in vivo. Evaluation of
dco
mutants indicates that they affect Fat's influence on growth and gene expression but not its influence on planar cell polarity. Our observations identify processing and phosphorylation as post-translational modifications of Fat, correlate the phosphorylation of Fat with its activation by Dachsous in the Fat-Warts pathway, and enhance our understanding of the requirement for Dco in Fat signaling.
5′-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I
Authors: Schmidt Andreas , Schwerd Tobias , Hamm Wolfgang , Hellmuth Johannes C. , Cui Sheng , Wenzel Michael , Hoffmann Franziska S. , Michallet Marie-Cecile , Besch Robert , Hopfner Karl-Peter , Endres Stefan , Rothenfusser Simon
Published: July 2009

The ATPase retinoid acid-inducible gene (RIG)-I senses viral RNA in the cytoplasm of infected cells and subsequently activates cellular antiviral defense mechanisms. RIG-I recognizes molecular structures that discriminate viral from host RNA. Here, we show that RIG-I ligands require base-paired structures in conjunction with a free 5′-triphosphate to trigger antiviral signaling. Hitherto unavailable chemically synthesized 5′-triphosphate RNA ligands do not trigger RIG-I-dependent IFN production in cells, and they are unable to trigger the ATPase activity of RIG-I without a base-paired stretch. Consistently, immunostimulatory RNA from cells infected with a virus recognized by RIG-I is sensitive to double-strand, but not single-strand, specific RNases. In vitro, base-paired stretches and the 5′-triphosphate bind to distinct sites of RIG-I and synergize to trigger the induction of signaling competent RIG-I multimers. Strengthening our model of a bipartite molecular pattern for RIG-I activation, we show that the activity of supposedly “single-stranded” 5′-triphosphate RNAs generated by in vitro transcription depends on extended and base-paired by-products inadvertently, but commonly, produced by this method. Together, our findings accurately define a minimal molecular pattern sufficient to activate RIG-I that can be found in viral genomes or transcripts.
Virtual taphonomy using synchrotron tomographic microscopy reveals cryptic features and internal structure of modern and fossil plants
Authors: Smith Selena Y. , Collinson Margaret E. , Rudall Paula J. , Simpson David A. , Marone Federica , Stampanoni Marco
Published: July 2009

While more commonly applied in zoology, synchrotron radiation X-ray tomographic microscopy (SRXTM) is well-suited to nondestructive study of the morphology and anatomy of both fossil and modern plants. SRXTM uses hard X-rays and a monochromatic light source to provide high-resolution data with little beam-hardening, resulting in slice data with clear boundaries between materials. Anatomy is readily visualized, including various planes of section from a single specimen, as clear as in traditional histological sectioning at low magnifications. Thus, digital sectioning of rare or difficult material is possible. Differential X-ray attenuation allows visualization of different layers or chemistries to enable virtual 3-dimensional (3D) dissections of material. Virtual potential fossils can be visualized and digital tissue removal reveals cryptic underlying morphology. This is essential for fossil identification and for comparisons between assemblages where fossils are preserved by different means. SRXTM is a powerful approach for botanical studies using morphology and anatomy. The ability to gain search images in both 2D and 3D for potential fossils gives paleobotanists a tool—virtual taphonomy—to improve our understanding of plant evolution and paleobiogeography.
Surviving mass extinction by bridging the benthic/planktic divide
Authors: Darling Kate F. , Thomas Ellen , Kasemann Simone A. , Seears Heidi A. , Smart Christopher W. , Wade Christopher M.
Published: July 2009

Evolution of planktic organisms from benthic ancestors is commonly thought to represent unidirectional expansion into new ecological domains, possibly only once per clade. For foraminifera, this evolutionary expansion occurred in the Early–Middle Jurassic, and all living and extinct planktic foraminifera have been placed within 1 clade, the Suborder Globigerinina. The subsequent radiation of planktic foraminifera in the Jurassic and Cretaceous resulted in highly diverse assemblages, which suffered mass extinction at the end of the Cretaceous, leaving an impoverished assemblage dominated by microperforate triserial and biserial forms. The few survivor species radiated to form diverse assemblages once again in the Cenozoic. There have, however, long been doubts regarding the monophyletic origin of planktic foraminifera. We present surprising but conclusive genetic evidence that the Recent biserial planktic
Streptochilus globigerus
belongs to the same biological species as the benthic
Bolivina variabilis
, and geochemical evidence that this ecologically flexible species actively grows within the open-ocean surface waters, thus occupying both planktic and benthic domains. Such a lifestyle (tychopelagic) had not been recognized as adapted by foraminifera. Tychopelagic are endowed with great ecological advantage, enabling rapid recolonization of the extinction-susceptible pelagic domain from the benthos. We argue that the existence of such forms must be considered in resolving foraminiferal phylogeny.
Development of GFP-based biosensors possessing the binding properties of antibodies
Authors: Pavoor Tej V. , Cho Yong Ku , Shusta Eric V.
Published: July 2009

Proteins that can bind specifically to targets that also have an intrinsic property allowing for easy detection could facilitate a multitude of applications. While the widely used green fluorescent protein (GFP) allows for easy detection, attempts to insert multiple binding loops into GFP to impart affinity for a specific target have been met with limited success because of the structural sensitivity of the GFP chromophore. In this study, directed evolution using a surrogate loop approach and yeast surface display yielded a family of GFP scaffolds capable of accommodating 2 proximal, randomized binding loops. The library of potential GFP-based binders or ″GFAbs″ was subsequently mined for GFAbs capable of binding to protein targets. Identified GFAbs bound with nanomolar affinity and required binding contributions from both loops indicating the advantage of a dual loop GFAb platform. Finally, GFAbs were solubly produced and used as fluorescence detection reagents to demonstrate their utility.
Protein dynamics-induced variation of excitation energy transfer pathways
Authors: Brecht M. , Radics V. , Nieder J. B. , Bittl R.
Published: July 2009

Strong anticorrelation between the fluorescence emission of different emitters is observed by employing single-molecule fluorescence spectroscopy on photosystem I at cryogenic temperatures. This anticorrelation demonstrates a time-dependent interaction between pigments participating in the exciton transfer chain, implying that uniquely defined energy transfer pathways within the complex do not exist. Fluctuations of the chromophores themselves or their immediate protein surroundings induce changes in their site energy, and, as a consequence, these fluctuations change the coupling within the excitation transfer pathways. The time scales of the site energy fluctuations of the individual emitters do not meet the time scales of the observed correlated emission behavior. Therefore, the emitters must be fed individually by energetically higher lying states, causing the observed intensity variations. This phenomenon is shown for photosystem I pigment–protein complexes from 2 different cyanobacteria (
Thermosynechococcus elongatus
and
Synechocystis
sp. PCC 6803) with strongly different spectral properties underlining the general character of the findings. The variability of energy transfer pathways might play a key role in the extreme robustness of light-harvesting systems in general.
Endosomal TLR signaling is required for anti-nucleic acid and rheumatoid factor autoantibodies in lupus
Authors: Kono Dwight H. , Haraldsson M. Katarina , Lawson Brian R. , Pollard K. Michael , Koh Yi Ting , Du Xin , Arnold Carrie N. , Baccala Roberto , Silverman Gregg J. , Beutler Bruce A. , Theofilopoulos Argyrios N.
Published: July 2009

Using the
Unc93b1 3d
mutation that selectively abolishes nucleic acid-binding Toll-like receptor (TLR) (TLR3, -7, -9) signaling, we show these endosomal TLRs are required for optimal production of IgG autoAbs, IgM rheumatoid factor, and other clinical parameters of disease in 2 lupus strains, B6-

Fas
lpr

and BXSB. Strikingly, treatment with lipid A, an autoAb-inducing TLR4 agonist, could not overcome this requirement. The
3d
mutation slightly reduced complete Freund's adjuvant (CFA)-mediated antigen presentation, but did not affect T-independent type 1 or alum-mediated T-dependent humoral responses or TLR-independent IFN production induced by cytoplasmic nucleic acids. These findings suggest that nucleic acid-sensing TLRs might act as an Achilles' heel in susceptible individuals by providing a critical pathway by which relative tolerance for nucleic acid-containing antigens is breached and systemic autoimmunity ensues. Importantly, this helps provide an explanation for the high frequency of anti-nucleic acid Abs in lupus-like systemic autoimmunity.
Cervical length measurement and cervical phosphorylated insulin‐like growth factor binding protein‐1 testing in prediction of preterm birth in patients reporting uterine contractions
Authors: RAHKONEN LEENA , UNKILA‐KALLIO LEILA , NUUTILA MIKA , SAINIO SUSANNA , SAISTO TERHI , RUTANEN EEVA‐MARJA , PAAVONEN JORMA
Published: July 2009

Objectives. To evaluate the performance of cervical phosphorylated insulin‐like growth factor binding protein‐1 (phIGFBP‐1) testing and cervical length measurement separately and in combination with physician's clinical judgment in prediction of preterm birth among patients with self‐reported uterine contractions and intact membranes. Design. We enrolled a total of 246 women between 22 and 34 weeks of gestation. Methods. The initial evaluation included cervical length measurement using transvaginal ultrasonography. Short cervix was defined as <25 mm. A swab sample was obtained from the cervix for phIGFBP‐1. Admission was used as a clinical marker of an increased risk of preterm delivery ≤34 weeks. The diagnostic performances of the tests and clinician's judgment, as well as likelihood ratios (LRs) were calculated. Main outcome measures. Delivery ≤34 weeks and within 14 days. Results. The overall rate of spontaneous preterm delivery ≤34 weeks was 4.1% (10/246). Short cervix, positive phIGFBP‐1 test, combination of both, and clinician's judgment were all associated with preterm delivery ≤34 weeks or within 14 days (p<0.01). The negative predictive values for delivery ≤34 weeks were 97.4, 97.6, 97.1, and 98.7%, respectively, and within 14 days 98.7, 99.0, 98.3, and 99.6%, respectively. The corresponding positive LRs for delivery ≤34 weeks were 6.8, 3.8, 75.0, 14.9, and within 14 days 9.7, 5.5, 107.3, 17.1. The negative LRs were 0.6, 0.6, 0.7, 0.3 and 0.5, 0.3, 0.6, 0.2. Conclusion. The rapid phIGFBP‐1‐test has a high negative predictive value for preterm delivery, comparable to that of ultrasonographic cervical length measurement.
Factor Demand and Price Sensitivity of Forest-Based Biomass in the European Energy and Forest Sectors
Authors: Lundmark Robert
Published: July 2009

An increasing utilization of biomass is, in the short-term, one of the most realistic alternatives to meet the energy and the environmental goals established by the European Union. As a result, the demand for forest-based products from European forests will increase. However, glaringly little research effort has been made towards analyzing the price effect resulting from the increasing demand for forest-based biomass and how the relevant industry sectors adjust their input demands due to these price changes. The purpose of this paper is thus to provide a disaggregated and detailed empirical estimation and analysis of the various input demand elasticities, as well as of the relevant substitution elasticities. The model is estimated using a panel of 23 European countries for the period between 1999 and 2005, thus allowing for specific country effects. The results indicate that the energy sector is relatively more price sensitive in its input demand for fossil fuels compared to the fibrous fuel categories. Thus, higher fibrous input prices will have a relatively small effect on the quantity of fibrous inputs that the energy sector demands. The forest industry is comparatively more price sensitive in its procurement of fibrous inputs than the energy sector, and will therefore reduce its input demand relatively more as a consequence from a fibrous input price increase. Furthermore, the cross-price elasticities reveal some interesting findings. In general, the energy sector will increase its utilization of fossil fuels as a result of increasing fibrous input price. Conversely, the energy sector will increase the utilization of fibrous input relatively less as a consequence of increasing fossil fuel prices.
Multicriteria Analysis for Disaster Risk Reduction in Virginia, USA: A Policy-Focused Approach to Oil and Gas Drilling in the Outer Continental Shelf
Authors: Levy Jason K. , Gopalakrishnan Chennat
Published: July 2009

Multiple Criteria Analysis (MCA) is a collection of methodologies to compare, select, or rank multiple alternatives that typically involve incommensurate attributes. MCA is well-suited for eliciting and modeling the disaster management preferences of stakeholders and for improving the coordination among emergency response agencies, organizations and affected citizens. Many Americans favour new drilling for oil and gas in the Outer Continental Shelf, and a Congressional moratorium on new offshore oil and gas drilling was lifted last year for the first time in three decades. The Facilitator Decision Support System for Multiple Criteria Analysis is used to explore whether it is in the interest of Virginia and the United States to maintain the current offshore exploration schedule. The issue is timely and important, as legislation (H.R. 1696) has been introduced in the 111th US Congress to place regions in the North Atlantic and Mid-Atlantic permanently off-limits to oil and gas leasing and development.
Unite and conquer: univariate and multivariate approaches for finding differentially expressed gene sets
Authors: Glazko Galina V. , Emmert-Streib Frank
Published: July 2009

Motivation: Recently, many univariate and several multivariate approaches have been suggested for testing differential expression of gene sets between different phenotypes. However, despite a wealth of literature studying their performance on simulated and real biological data, still there is a need to quantify their relative performance when they are testing different null hypotheses.

Results: In this article, we compare the performance of univariate and multivariate tests on both simulated and biological data. In the simulation study we demonstrate that high correlations equally affect the power of both, univariate as well as multivariate tests. In addition, for most of them the power is similarly affected by the dimensionality of the gene set and by the percentage of genes in the set, for which expression is changing between two phenotypes. The application of different test statistics to biological data reveals that three statistics (sum of squared t-tests, Hotelling's T2, N-statistic), testing different null hypotheses, find some common but also some complementing differentially expressed gene sets under specific settings. This demonstrates that due to complementing null hypotheses each test projects on different aspects of the data and for the analysis of biological data it is beneficial to use all three tests simultaneously instead of focusing exclusively on just one.

Contact:  Galina_Glazko@urmc.rochester.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
‘My friends love to tan’: examining sensation seeking and the mediating role of association with friends who use tanning beds on tanning bed use intentions
Authors: Banerjee Smita C. , Greene Kathryn , Bagdasarov Zhanna , Campo Shelly
Published: July 2009

This paper explored how sensation seeking contributes to the likelihood of tanning bed use intentions both directly and indirectly through the way it shapes interaction with peers who use tanning beds and attitudes toward tanning bed. Eight hundred and ninety six (n = 896) male and female college students were recruited for the study. Measured variables included sensation seeking, association with friends who use tanning beds, attitudes toward tanning and tanning bed use intentions. Structural equation modeling was performed to test the hypotheses. In general, results supported the proposed hypotheses and documented that sensation seeking is indirectly associated with tanning bed use intentions through the mediation of association with peers who use tanning beds and attitudes toward tanning. The article discusses theoretical and methodological implications of the findings demonstrating the pathways of influence of sensation seeking on tanning bed use intentions.
Two components of Northeast Atlantic herring within the same school during spawning: support for the existence of a metapopulation?
Authors: Johannessen Arne , Nøttestad Leif , Fernö Anders , Langård Lise , Skaret Georg
Published: July 2009

Johannessen, A., Nøttestad, L., Fernö, A., Langård, L., and Skaret, G. 2009. Two components of Northeast Atlantic herring within the same school during spawning: support for the existence of a metapopulation? – ICES Journal of Marine Science, 66: 1740–1748. It has been hypothesized that some stocks of Atlantic herring are subject to genetic exchange and therefore should fit the definition of a metapopulation with subunits. Genetic exchange requires spatial overlap of individuals from different populations during spawning. We investigated a local herring population that is assumed to feed and spawn within the semi-enclosed marine ecosystem of Lindåspollene in west Norway, which is connected with the outer fjord only by a narrow sill. Acoustic recordings and gillnet samples demonstrated the mixed presence of two components within a single school throughout the spawning period 2005–2007. Members of the two components were of about the same size and in a similar stage of gonad development at all times, but the age composition was completely different. These observations represent the first documented case of different components being present in a spawning school and provide strong indications of regular interbreeding. Our data suggest that the two components represent autochthonous Lindås herring and allochthonous herring of coastal/oceanic origin, thereby supporting the metapopulation concept. Two alternative explanations, based on one migratory and one resident component of a single Lindås stock, are also discussed.
The conditional economics of sexual conflict
Authors: Fricke Claudia , Perry Jen , Chapman Tracey , Rowe Locke
Published: July 2009

Sexual conflict is a fundamentally important aspect of male–female interactions. In this opinion piece, we emphasize two approaches that warrant significantly greater attention. First, we review the importance of understanding the ‘economics’ (costs and benefits) of sexual interactions and note surprisingly large, unrecognized gaps in our knowledge. Second, we highlight the novel obstacles and opportunities afforded by the dependence of sexually antagonistic (SA) selection on both the local environment and condition of the interacting individuals. We conclude that more research in these two areas is essential to fully understand the evolution of SA interactions and will provide significant new insights into the extent to which coevolution of the sexes is shaped by conflict. We argue that these approaches, although not new to the field, are undervalued and under-represented.
On hybrid objects and their trajectories: Beddoes, Davy and the Battery
Authors: Pancaldi Giuliano
Published: July 2009

In this article I follow the voltaic battery as it was appropriated by the network of people centred on Thomas Beddoes and the Pneumatic Institution in Bristol. I use the case to explore the vicissitudes of a quite special ‘hybrid object’: I consider what we can learn from the trajectories that objects such as the battery describe when they travel across expert communities.
The axial element protein HTP-3 promotes cohesin loading and meiotic axis assembly in C. elegans to implement the meiotic program of chromosome segregation
Authors: Severson Aaron F. , Ling Lorraine , van Zuylen Vanessa , Meyer Barbara J.
Published: July 2009

Faithful transmission of the genome through sexual reproduction requires reduction of genome copy number during meiosis to produce haploid sperm and eggs. Meiosis entails steps absent from mitosis to achieve this goal. When meiosis begins, sisters are held together by sister chromatid cohesion (SCC), mediated by the cohesin complex. Homologs then become linked through crossover recombination. SCC subsequently holds both sisters and homologs together. Separation of homologs and then sisters requires two successive rounds of chromosome segregation and the stepwise removal of Rec8, a meiosis-specific cohesin subunit. We show that HTP-3, a known component of the C. elegans axial element (AE), molecularly links these meiotic innovations. We identified HTP-3 in a genetic screen for factors necessary to maintain SCC until meiosis II. Our data show that interdependent loading of HTP-3 and cohesin is a principal step in assembling the meiotic chromosomal axis and in establishing SCC. HTP-3 recruits all known AE components to meiotic chromosomes and promotes cohesin loading, the first known involvement of an AE protein in this process. Furthermore, REC-8 and two paralogs, called COH-3 and COH-4, together mediate meiotic SCC, but they perform specialized functions. REC-8 alone is necessary and sufficient for the persistence of SCC after meiosis I. In htp-3 and rec-8 mutants, sister chromatids segregate away from one another in meiosis I (equational division), rather than segregating randomly, as expected if SCC were completely eliminated. AE assembly fails only when REC-8, COH-3, and COH-4 are simultaneously disrupted. Premature equational sister separation in rec8 mutants of other organisms suggests the involvement of multiple REC-8 paralogs, which may have masked a conserved requirement for cohesin in AE assembly.
HuR recruits let-7/RISC to repress c-Myc expression
Authors: Kim Hyeon Ho , Kuwano Yuki , Srikantan Subramanya , Lee Eun Kyung , Martindale Jennifer L. , Gorospe Myriam
Published: July 2009

RNA-binding proteins (RBPs) and microRNAs (miRNAs) are potent post-transcriptional regulators of gene expression. Here, we show that the RBP HuR reduced c-Myc expression by associating with the c-Myc 3′ untranslated region (UTR) next to a miRNA let-7-binding site. Lowering HuR or let-7 levels relieved the translational repression of c-Myc. Unexpectedly, HuR and let-7 repressed c-Myc through an interdependent mechanism, as let-7 required HuR to reduce c-Myc expression and HuR required let-7 to inhibit c-Myc expression. Our findings suggest a regulatory paradigm wherein HuR inhibits c-Myc expression by recruiting let-7-loaded RISC (RNA miRNA-induced silencing complex) to the c-Myc 3′UTR.
Identification of rare cancer driver mutations by network reconstruction
Authors: Torkamani Ali , Schork Nicholas J.
Published: July 2009

Recent large-scale tumor resequencing studies have identified a number of mutations that might be involved in tumorigenesis. Analysis of the frequency of specific mutations across different tumors has been able to identify some, but not all of the mutated genes that contribute to tumor initiation and progression. One reason for this is that other functionally important genes are likely to be mutated more rarely and only in specific contexts. Thus, for example, mutation in one member of a collection of functionally related genes may result in the same net effect, and/or mutations in certain genes may be observed less frequently if they play functional roles in later stages of tumor development, such as metastasis. We modified and applied a network reconstruction and coexpression module identification-based approach to identify functionally related gene modules targeted by somatic mutations in cancer. This method was applied to available breast cancer, colorectal cancer, and glioblastoma sequence data, and identified Wnt/TGF-beta cross-talk, Wnt/VEGF signaling, and MAPK/focal adhesion kinase pathways as targets of rare driver mutations in breast, colorectal cancer, and glioblastoma, respectively. These mutations do not appear to alter genes that play a central role in these pathways, but rather contribute to a more refined shaping or “tuning” of the functioning of these pathways in such a way as to result in the inhibition of their tumor-suppressive signaling arms, and thereby conserve or enhance tumor-promoting processes.
Mechanism of REP27 Protein Action in the D1 Protein Turnover and Photosystem II Repair from Photodamage
Authors: Dewez David , Park Sungsoon , García-Cerdán Jose Gines , Lindberg Pia , Melis Anastasios
Published: July 2009

The function of the REP27 protein (GenBank accession no. EF127650) in the photosystem II (PSII) repair process was elucidated. REP27 is a nucleus-encoded and chloroplast-targeted protein containing two tetratricopeptide repeat (TPR) motifs, two putative transmembrane domains, and an extended carboxyl (C)-terminal region. Cell fractionation and western-blot analysis localized the REP27 protein in the Chlamydomonas reinhardtii chloroplast thylakoids. A folding model for REP27 suggested chloroplast stroma localization for amino- and C-terminal regions as well as the two TPRs. A REP27 gene knockout strain of Chlamydomonas, termed the rep27 mutant, was employed for complementation studies. The rep27 mutant was aberrant in the PSII-repair process and had substantially lower than wild-type levels of D1 protein. Truncated REP27 cDNA constructs were made for complementation of rep27, whereby TPR1, TPR2, TPR1+TPR2, or the C-terminal domains were deleted. rep27-complemented strains minus the TPR motifs showed elevated levels of D1 in thylakoids, comparable to those in the wild type, but the PSII photochemical efficiency of these strains was not restored, suggesting that the functionality of the PSII reaction center could not be recovered in the absence of the TPR motifs. It is suggested that TPR motifs play a role in the functional activation of the newly integrated D1 protein in the PSII reaction center. rep27-complemented strains missing the C-terminal domain showed low levels of D1 protein in thylakoids as well as low PSII photochemical efficiency, comparable to those in the rep27 mutant. Therefore, the C-terminal domain is needed for a de novo biosynthesis and/or assembly of D1 in the photodamaged PSII template. We conclude that REP27 plays a dual role in the regulation of D1 protein turnover by facilitating cotranslational biosynthesis insertion (C-terminal domain) and activation (TPR motifs) of the nascent D1 during the PSII repair process.
Posttranslational Elevation of Cell Wall Invertase Activity by Silencing Its Inhibitor in Tomato Delays Leaf Senescence and Increases Seed Weight and Fruit Hexose Level
Authors: Jin Ye , Ni Di-An , Ruan Yong-Ling
Published: July 2009

Invertase plays multiple pivotal roles in plant development. Thus, its activity must be tightly regulated in vivo. Emerging evidence suggests that a group of small proteins that inhibit invertase activity in vitro appears to exist in a wide variety of plants. However, little is known regarding their roles in planta. Here, we examined the function of INVINH1, a putative invertase inhibitor, in tomato (Solanum lycopersicum). Expression of a INVINH1:green fluorescent protein fusion revealed its apoplasmic localization. Ectopic overexpression of INVINH1 in Arabidopsis thaliana specifically reduced cell wall invertase activity. By contrast, silencing its expression in tomato significantly increased the activity of cell wall invertase without altering activities of cytoplasmic and vacuolar invertases. Elevation of cell wall invertase activity in RNA interference transgenic tomato led to (1) a prolonged leaf life span involving in a blockage of abscisic acid–induced senescence and (2) an increase in seed weight and fruit hexose level, which is likely achieved through enhanced sucrose hydrolysis in the apoplasm of the fruit vasculature. This assertion is based on (1) coexpression of INVINH1 and a fruit-specific cell wall invertase Lin5 in phloem parenchyma cells of young fruit, including the placenta regions connecting developing seeds; (2) a physical interaction between INVINH1 and Lin5 in vivo; and (3) a symplasmic discontinuity at the interface between placenta and seeds. Together, the results demonstrate that INVINH1 encodes a protein that specifically inhibits the activity of cell wall invertase and regulates leaf senescence and seed and fruit development in tomato by limiting the invertase activity in planta.
The Maize Transcription Factor Myb-Related Protein-1 Is a Key Regulator of the Differentiation of Transfer Cells
Authors: Gómez Elisa , Royo Joaquín , Muñiz Luis M. , Sellam Olivier , Paul Wyatt , Gerentes Denise , Barrero Cristina , López Maribel , Perez Pascual , Hueros Gregorio
Published: July 2009

Transfer cells are highly modified plant cells specialized in the transport of solutes. They differentiate at many plant exchange surfaces, including phloem loading and unloading zones such as those present in the sink organs and seeds. In maize (Zea mays) seeds, transfer cells are located at the base of the endosperm. It is currently unknown how apical-basal polarity is established or why the peripheral cells at the base of the endosperm differentiate into transfer instead of aleurone cells. Here, we show that in epidermal cells committed to develop into aleurone cells, the ectopic expression of the transfer cell-specific transcriptional activator Myb-Related Protein-1 (MRP-1) is sufficient to temporarily transform them into transfer cells. These transformed cells acquire distinct transfer cell features, such as cell wall ingrowths and an elongated shape. In addition, they express a number of MRP-1 target genes presumably involved in defense. We also show that the expression of MRP-1 is needed to maintain the transfer cell phenotype. Later in development, an observed reduction in the ectopic expression of MRP-1 was followed by the reversion of the transformed cells, which then acquire aleurone cell features.
Review article: cellular and molecular mechanisms of NSAID‐induced peptic ulcers
Authors: MUSUMBA C. , PRITCHARD D. M. , PIRMOHAMED M.
Published: July 2009

Background Nonsteroidal anti‐inflammatory drugs (NSAIDs) are some of the most prescribed drugs worldwide and have now probably overtakenHelicobacter pylorias the most common cause of gastrointestinal injury in Western countries. Further understanding of the pathogenesis of NSAID‐induced ulcers is important to enable the development of novel and effective preventive strategies.

Aims To provide an update on recent advances in our understanding of the cellular and molecular mechanisms involved in the development of NSAID‐induced ulcers.

Methods A Medline search was performed to identify relevant literature using search terms including ‘nonsteroidal anti‐inflammatory drugs, aspirin, gastric ulcer, duodenal ulcer, pathogenesis, pharmacogenetics’.

Results The mechanisms of NSAID‐induced ulcers can be divided into topical and systemic effects and the latter may be prostaglandin‐dependent (through COX inhibition) or prostaglandin‐independent. Genetic factors may play an important role in determining individual predisposition.

Conclusions The pathogenesis of NSAID‐induced peptic ulcers is complex and multifactorial. Recent advances in cellular and molecular biology have highlighted the importance of various prostaglandin‐independent mechanisms. Pharmacogenetic studies may provide further insights into the pathogenetic mechanisms of NSAID‐induced ulcers and help identify patients at increased risk.
Systematic review: accuracy of symptom‐based criteria for diagnosis of irritable bowel syndrome in primary care
Authors: JELLEMA P. , VAN DER WINDT D. A. W. M. , SCHELLEVIS F. G. , VAN DER HORST H. E.
Published: July 2009

Background  Despite the trend towards making a positive diagnosis of irritable bowel syndrome (IBS), many health care providers approach IBS as a diagnosis of exclusion.

Aim  To summarize available evidence on the diagnostic performance of symptom‐based IBS criteria in excluding organic diseases, and of individual signs and symptoms in diagnosing IBS and to additionally assess the influence of sources of heterogeneity on diagnostic performance.

Methods  We searched PubMed and EMBASE and screened references. Studies were selected if the design was a primary diagnostic study; the patients were adults consulting because of non‐acute abdominal symptoms; the diagnostic test included an externally validated set of IBS criteria, signs, or symptoms. Data extraction and quality assessment were performed by two reviewers independently. The review adhered to the most recent guidelines as described in the Cochrane Diagnostic Reviewers’ Handbook.

Results  A total of 25 primary diagnostic studies were included in the review. The performance of symptom‐based criteria in the exclusion of organic disease was highly variable. Patients fulfilling IBS criteria had, however, a lower risk of organic diseases than those not fulfilling the criteria.

Conclusions  With none of the criteria showing sufficiently homogeneous and favourable results, organic disease cannot be accurately excluded by symptom‐based IBS criteria alone. However, the low pre‐test probability of organic disease especially among patients who meet symptom‐based criteria in primary care argues against exhaustive diagnostic evaluation. We advise validation of the new Rome III criteria in primary care populations.