bluuebunny/crossref_metadata_2025 huggingface dataset:
Instability and dynamics of two nonlinearly coupled intense laser beams in a quantum plasma
Authors: Wang Yunliang , Shukla P. K. , Eliasson B.
Published: January 2013

We consider nonlinear interactions between two relativistically strong laser beams and a quantum plasma composed of degenerate electron fluids and immobile ions. The collective behavior of degenerate electrons is modeled by quantum hydrodynamic equations composed of the electron continuity, quantum electron momentum (QEM) equation, as well as the Poisson and Maxwell equations. The QEM equation accounts the quantum statistical electron pressure, the quantum electron recoil due to electron tunneling through the quantum Bohm potential, electron-exchange, and electron-correlation effects caused by electron spin, and relativistic ponderomotive forces (RPFs) of two circularly polarized electromagnetic (CPEM) beams. The dynamics of the latter are governed by nonlinear wave equations that include nonlinear currents arising from the relativistic electron mass increase in the CPEM wave fields, as well as from the beating of the electron quiver velocity and electron density variations reinforced by the RPFs of the two CPEM waves. Furthermore, nonlinear electron density variations associated with the driven (by the RPFs) quantum electron plasma oscillations obey a coupled nonlinear Schrödinger and Poisson equations. The nonlinearly coupled equations for our purposes are then used to obtain a general dispersion relation (GDR) for studying the parametric instabilities and the localization of CPEM wave packets in a quantum plasma. Numerical analyses of the GDR reveal that the growth rate of a fastest growing parametrically unstable mode is in agreement with the result that has been deduced from numerical simulations of the governing nonlinear equations. Explicit numerical results for two-dimensional (2D) localized CPEM wave packets at nanoscales are also presented. Possible applications of our investigation to intense laser-solid density compressed plasma experiments are highlighted.
Micro-/nanofluidics based cell electroporation
Authors: Wang Shengnian , Lee L. James
Published: January 2013

Non-viral gene delivery has been extensively explored as the replacement for viral systems. Among various non-viral approaches, electroporation has gained increasing attention because of its easy operation and no restrictions on probe or cell type. Several effective systems are now available on the market with reasonably good gene delivery performance. To facilitate broader biological and medical applications, micro-/nanofluidics based technologies were introduced in cell electroporation during the past two decades and their advances are summarized in this perspective. Compared to the commercially available bulk electroporation systems, they offer several advantages, namely, (1) sufficiently high pulse strength generated by a very low potential difference, (2) conveniently concentrating, trapping, and regulating the position and concentration of cells and probes, (3) real-time monitoring the intracellular trafficking at single cell level, and (4) flexibility on cells to be transfected (from single cell to large scale cell population). Some of the micro-devices focus on cell lysis or fusion as well as the analysis of cellular properties or intracellular contents, while others are designed for gene transfection. The uptake of small molecules (e.g., dyes), DNA plasmids, interfering RNAs, and nanoparticles has been broadly examined on different types of mammalian cells, yeast, and bacteria. A great deal of progress has been made with a variety of new micro-/nanofluidic designs to address challenges such as electrochemical reactions including water electrolysis, gas bubble formation, waste of expensive reagents, poor cell viability, low transfection efficacy, higher throughput, and control of transfection dosage and uniformity. Future research needs required to advance micro-/nanofluidics based cell electroporation for broad life science and medical applications are discussed.
Rapid isolation of cancer cells using microfluidic deterministic lateral displacement structure
Authors: Liu Zongbin , Huang Fei , Du Jinghui , Shu Weiliang , Feng Hongtao , Xu Xiaoping , Chen Yan
Published: January 2013

This work reports a microfluidic device with deterministic lateral displacement (DLD) arrays allowing rapid and label-free cancer cell separation and enrichment from diluted peripheral whole blood, by exploiting the size-dependent hydrodynamic forces. Experiment data and theoretical simulation are presented to evaluate the isolation efficiency of various types of cancer cells in the microfluidic DLD structure. We also demonstrated the use of both circular and triangular post arrays for cancer cell separation in cell solution and blood samples. The device was able to achieve high cancer cell isolation efficiency and enrichment factor with our optimized design. Therefore, this platform with DLD structure shows great potential on fundamental and clinical studies of circulating tumor cells.
Modified theory of secondary electron emission from spherical particles and its effect on dust charging in complex plasma
Authors: Misra Shikha , Mishra S. K. , Sodha M. S.
Published: January 2013

The authors have modified Chow's theory of secondary electron emission (SEE) to take account of the fact that the path length of a primary electron in a spherical particle varies between zero to the diameter or xm the penetration depth depending on the distance of the path from the centre of the particle. Further by including this modified expression for SEE efficiency, the charging kinetics of spherical grains in a Maxwellian plasma has been developed; it is based on charge balance over dust particles and number balance of electrons and ionic species. It is seen that this effect is more pronounced for smaller particles and higher plasma temperatures. Desirable experimental work has also been discussed.
Controlling voluntary intake of molasses-based supplements in grazing cattle
Authors: Dixon R. M.
Published: January 2013

Molasses-based liquid supplements fed ad libitum are widely used to provide additional metabolisable energy, non-protein N (NPN) and other nutrients to grazing cattle, but it is often difficult to achieve target intakes of supplementary nutrients. Experiments examined the effects of increasing concentrations of phosphoric acid, urea and ammonium sulfate on the voluntary intake (VI) of molasses-based supplements offered ad libitum to heifers grazing tropical pastures. In Experiment 1, the VI of a supplement containing 78 g urea/kg and 26 g phosphoric acid/kg as-fed (M80U+PA) was 3.61 g DM/kg liveweight (LW) per day, and provided 181 mg NPN and 32.4 mg phosphorus (P)/kg LW per day. Increasing the urea content of the supplement to 137 g/kg (M140U+PA) or 195 g/kg (M200U+PA) reduced VI of supplement DM, NPN and P by up to 76%, 44% and 80%, respectively. VI of supplement containing ammonium sulfate (M140+AS+PA) was lower (P < 0.05) than that of M140U+PA supplement, and tended (P > 0.05) to be lower than that of M200U+PA supplement. In experiment 2, the VI by heifers of a supplement containing 200 g urea/kg (M200U) was 1.53 g supplement DM/kg LW per day, which provided 186 mg NPN/kg LW per day. Inclusion of 49 g phosphoric acid/kg as-fed in this supplement (M190U+50PA) reduced (P < 0.05) VI of supplement DM and NPN by 33% and 36%, respectively, while inclusion of 97 g phosphoric acid/kg (M180U+100PA) reduced (P < 0.05) VI of supplement DM and NPN by 43% and 48%, respectively. The M190U+50PA and M180U+100PA supplements provided 16 and 26 mg P/kg LW per day, respectively. Heifers not fed supplements gained 0.07 kg/day, and the M200U supplement increased (P < 0.05) LW gain to 0.18 kg/day. LW gain was further increased (P < 0.05) by the M190U+50PA to 0.28 kg/day, indicating a growth response to supplementary P. No adverse effects of the supplements on animal health were observed in any of the experiments. In conclusion, addition of urea and/or phosphoric acid to molasses supplements effectively reduced VI of supplementary DM, NPN and P, and in the circumstances of Experiment 2, both molasses-urea and P supplements increased heifer LW.
Noncanonical GPCR signaling arising from a PTH receptor–arrestin–Gβγ complex
Authors: Wehbi Vanessa L. , Stevenson Hilary P. , Feinstein Timothy N. , Calero Guillermo , Romero Guillermo , Vilardaga Jean-Pierre
Published: January 2013

G protein-coupled receptors (GPCRs) participate in ubiquitous transmembrane signal transduction processes by activating heterotrimeric G proteins. In the current “canonical” model of GPCR signaling, arrestins terminate receptor signaling by impairing receptor–G-protein coupling and promoting receptor internalization. However, parathyroid hormone receptor type 1 (PTHR), an essential GPCR involved in bone and mineral metabolism, does not follow this conventional desensitization paradigm. β-Arrestins prolong G protein (G
S
)-mediated cAMP generation triggered by PTH, a process that correlates with the persistence of arrestin–PTHR complexes on endosomes and which is thought to be associated with prolonged physiological calcemic and phosphate responses. This presents an inescapable paradox for the current model of arrestin-mediated receptor–G-protein decoupling. Here we show that PTHR forms a ternary complex that includes arrestin and the Gβγ dimer in response to PTH stimulation, which in turn causes an accelerated rate of G
S
activation and increases the steady-state levels of activated G
S
, leading to prolonged generation of cAMP. This work provides the mechanistic basis for an alternative model of GPCR signaling in which arrestins contribute to sustaining the effect of an agonist hormone on the receptor.
Nonmonotonic quantum-to-classical transition in multiparticle interference
Authors: Ra Young-Sik , Tichy Malte C. , Lim Hyang-Tag , Kwon Osung , Mintert Florian , Buchleitner Andreas , Kim Yoon-Ho
Published: January 2013

Quantum-mechanical wave–particle duality implies that probability distributions for granular detection events exhibit wave-like interference. On the single-particle level, this leads to self-interference—e.g., on transit across a double slit—for photons as well as for large, massive particles, provided that no which-way information is available to any observer, even in principle. When more than one particle enters the game, their specific many-particle quantum features are manifested in correlation functions, provided the particles cannot be distinguished. We are used to believe that interference fades away monotonically with increasing distinguishability—in accord with available experimental evidence on the single- and on the many-particle level. Here, we demonstrate experimentally and theoretically that such monotonicity of the quantum-to-classical transition is the exception rather than the rule whenever more than two particles interfere. As the distinguishability of the particles is continuously increased, different numbers of particles effectively interfere, which leads to interference signals that are, in general, nonmonotonic functions of the distinguishability of the particles. This observation opens perspectives for the experimental characterization of many-particle coherence and sheds light on decoherence processes in many-particle systems.
Mars 520-d mission simulation reveals protracted crew hypokinesis and alterations of sleep duration and timing
Authors: Basner Mathias , Dinges David F. , Mollicone Daniel , Ecker Adrian , Jones Christopher W. , Hyder Eric C. , Di Antonio Adrian , Savelev Igor , Kan Kevin , Goel Namni , Morukov Boris V. , Sutton Jeffrey P.
Published: January 2013

The success of interplanetary human spaceflight will depend on many factors, including the behavioral activity levels, sleep, and circadian timing of crews exposed to prolonged microgravity and confinement. To address the effects of the latter, we used a high-fidelity ground simulation of a Mars mission to objectively track sleep–wake dynamics in a multinational crew of six during 520 d of confined isolation. Measurements included continuous recordings of wrist actigraphy and light exposure (4.396 million min) and weekly computer-based neurobehavioral assessments (
n
= 888) to identify changes in the crew's activity levels, sleep quantity and quality, sleep–wake periodicity, vigilance performance, and workload throughout the record-long 17 mo of mission confinement. Actigraphy revealed that crew sedentariness increased across the mission as evident in decreased waking movement (i.e., hypokinesis) and increased sleep and rest times. Light exposure decreased during the mission. The majority of crewmembers also experienced one or more disturbances of sleep quality, vigilance deficits, or altered sleep–wake periodicity and timing, suggesting inadequate circadian entrainment. The results point to the need to identify markers of differential vulnerability to hypokinesis and sleep–wake changes during the prolonged isolation of exploration spaceflight and the need to ensure maintenance of circadian entrainment, sleep quantity and quality, and optimal activity levels during exploration missions. Therefore, successful adaptation to such missions will require crew to transit in spacecraft and live in surface habitats that instantiate aspects of Earth's geophysical signals (appropriately timed light exposure, food intake, exercise) required for temporal organization and maintenance of human behavior.
Midlatitude cooling caused by geomagnetic field minimum during polarity reversal
Authors: Kitaba Ikuko , Hyodo Masayuki , Katoh Shigehiro , Dettman David L. , Sato Hiroshi
Published: January 2013

The climatic effects of cloud formation induced by galactic cosmic rays (CRs) has recently become a topic of much discussion. The CR–cloud connection suggests that variations in geomagnetic field intensity could change climate through modulation of CR flux. This hypothesis, however, is not well-tested using robust geological evidence. Here we present paleoclimate and paleoenvironment records of five interglacial periods that include two geomagnetic polarity reversals. Marine oxygen isotope stages 19 and 31 contain both anomalous cooling intervals during the sea-level highstands and the Matuyama–Brunhes and Lower Jaramillo reversals, respectively. This contrasts strongly with the typical interglacial climate that has the temperature maximum at the sea-level peak. The cooling occurred when the field intensity dropped to <40% of its present value, for which we estimate >40% increase in CR flux. The climate warmed rapidly when field intensity recovered. We suggest that geomagnetic field intensity can influence global climate through the modulation of CR flux.
ICAM-1–dependent tuning of memory CD8 T-cell responses following acute infection
Authors: Cox Maureen A. , Barnum Scott R. , Bullard Daniel C. , Zajac Allan J.
Published: January 2013

CD8 T-cell responses are critical for protection against intracellular pathogens and tumors. The induction and properties of these responses are governed by a series of integrated processes that rely heavily on cell–cell interactions. Intercellular adhesion molecule (ICAM)-1 functions to enhance the strength of antigenic stimulation, extend the duration of contact with antigen-presenting cells, and augment cytokine signals, which are all factors that influence peripheral CD8 T-cell differentiation. Although previous studies suggest that ICAM-1 is essential for establishing memory T-cell populations following peptide immunization, the roles of ICAM-1 in antiviral cellular immunity are less well understood. Here we show that, following a prototypic acute viral infection, the formation and maintenance of memory-phenotype CD127hi, KLRG-1loCD8 T cells does not require ICAM-1. Nevertheless, ICAM-1 expression on nonlymphocytes dictates the phenotypic and functional attributes of the antiviral CD8 T-cell populations that develop and promotes the gradual attrition of residual effector-like CD127lo, KLRG-1hiCD8 T cells during the memory phase of the response. Although memory T cells do emerge and are maintained if ICAM-1 expression is abolished, the secondary proliferative capacity of these T cells is severely curtailed. Collectively, these studies reveal potential dual roles for ICAM-1 in both promoting the decay of effector responses and programming the sensitivity of memory CD8 T cells to secondary stimuli.
Follistatin antagonizes Activin signaling and acts with Notum to direct planarian head regeneration
Authors: Roberts-Galbraith Rachel H. , Newmark Phillip A.
Published: January 2013

Animals establish their body plans in embryogenesis, but only a few animals can recapitulate this signaling milieu for regeneration after injury. In planarians, a pluripotent stem cell population and perpetual signaling of polarity axes collaborate to direct a steady replacement of cells during homeostasis and to power robust regeneration after even severe injuries. Several studies have documented the roles of conserved signaling pathways in maintaining and resetting axial polarity in planarians, but it is unclear how planarians reestablish polarity signaling centers after injury and whether these centers serve to influence identity decisions of stem cell progeny during their differentiation. Here we find that a planarian Follistatin homolog directs regeneration of anterior identity by opposing an Activin/ActR-1/Smad2/3 signaling pathway. Follistatin and Notum, a Wnt inhibitor, are mutually required to reestablish an anterior signaling center that expresses both cues. Furthermore, we show that the direction of cells down particular differentiation paths requires regeneration of this anterior signaling center. Just as its amphibian counterpart in the organizer signals body plan and cell fate during embryogenesis, planarian Follistatin promotes reestablishment of anterior polarity during regeneration and influences specification of cell types in the head and beyond.
Histone methyltransferase MLL3 contributes to genome-scale circadian transcription
Authors: Valekunja Utham K. , Edgar Rachel S. , Oklejewicz Malgorzata , van der Horst Gijsbertus T. J. , O’Neill John S. , Tamanini Filippo , Turner Daniel J. , Reddy Akhilesh B.
Published: January 2013

Daily cyclical expression of thousands of genes in tissues such as the liver is orchestrated by the molecular circadian clock, the disruption of which is implicated in metabolic disorders and cancer. Although we understand much about the circadian transcription factors that can switch gene expression on and off, it is still unclear how global changes in rhythmic transcription are controlled at the genomic level. Here, we demonstrate circadian modification of an activating histone mark at a significant proportion of gene loci that undergo daily transcription, implicating widespread epigenetic modification as a key node regulated by the clockwork. Furthermore, we identify the histone-remodelling enzyme mixed lineage leukemia (MLL)3 as a clock-controlled factor that is able to directly and indirectly modulate over a hundred epigenetically targeted circadian “output” genes in the liver. Importantly, catalytic inactivation of the histone methyltransferase activity of MLL3 also severely compromises the oscillation of “core” clock gene promoters, including
Bmal1
,
mCry1
,
mPer2
, and
Rev-erbα
, suggesting that rhythmic histone methylation is vital for robust transcriptional oscillator function. This highlights a pathway by which the clockwork exerts genome-wide control over transcription, which is critical for sustaining temporal programming of tissue physiology.
Sortase-mediated modification of αDEC205 affords optimization of antigen presentation and immunization against a set of viral epitopes
Authors: Swee Lee Kim , Guimaraes Carla P. , Sehrawat Sharvan , Spooner Eric , Barrasa M. Inmaculada , Ploegh Hidde L.
Published: January 2013

A monoclonal antibody against the C-type lectin DEC205 (αDEC205) is an effective vehicle for delivery of antigens to dendritic cells through creation of covalent αDEC205–antigen adducts. These adducts can induce antigen-specific T-cell immune responses or tolerance. We exploit the transpeptidase activity of sortase to install modified peptides and protein-sized antigens onto the heavy chain of αDEC205, including linkers that contain nonnatural amino acids. We demonstrate stoichiometric site-specific labeling on a scale not easily achievable by genetic fusions (49 distinct fusions in this report). We conjugated a biotinylated version of a class I MHC-restricted epitope to unlabeled αDEC205 and monitored epitope generation upon binding of the adduct to dendritic cells. Our results show transfer of αDEC205 heavy chain to the cytoplasm, followed by proteasomal degradation. Introduction of a labile dipeptide linker at the N terminus of a T-cell epitope improves proteasome-dependent class I MHC-restricted peptide cross-presentation when delivered by αDEC205 in vitro and in vivo. We also conjugated αDEC205 with a linker-optimized peptide library of known CD8 T-cell epitopes from the mouse γ-herpes virus 68. Animals immunized with such conjugates displayed a 10-fold reduction in viral load.
SLC4 family transporters in a marine diatom directly pump bicarbonate from seawater
Authors: Nakajima Kensuke , Tanaka Atsuko , Matsuda Yusuke
Published: January 2013

Photosynthesis in marine diatoms is a vital fraction of global primary production empowered by CO
2
-concentrating mechanisms. Acquisition of HCO
3
−
from seawater is a critical primary step of the CO
2
-concentrating mechanism, allowing marine photoautotrophic eukaryotes to overcome CO
2
limitation in alkaline high-salinity water. However, little is known about molecular mechanisms governing this process. Here, we show the importance of a plasma membrane-type HCO
3
−
transporter for CO
2
acquisition in a marine diatom. Ten putative solute carrier (SLC) family HCO
3
−
transporter genes were found in the genome of the marine pennate diatom
Phaeodactylum tricornutum
. Homologs also exist in marine centric species,
Thalassiosira pseudonana
, suggesting a general occurrence of SLC transporters in marine diatoms. Seven genes were found to encode putative mammalian-type SLC4 family transporters in
P. tricornutum
, and three of seven genes were specifically transcribed under low CO
2
conditions. One of these gene products, PtSLC4-2, was localized at the plasmalemma and significantly stimulated both dissolved inorganic carbon (DIC) uptake and photosynthesis in
P. tricornutum
. DIC uptake by PtSLC4-2 was efficiently inhibited by an anion-exchanger inhibitor, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, in a concentration-dependent manner and highly dependent on Na
+
ions at concentrations over 100 mM. These results show that DIC influx into marine diatoms is directly driven at the plasmalemma by a specific HCO
3
−
transporter with a significant halophilic nature.
Molecular and microscopic evidence of viruses in marine copepods
Authors: Dunlap Darren S. , Ng Terry Fei Fan , Rosario Karyna , Barbosa Jorge G. , Greco Anthony M. , Breitbart Mya , Hewson Ian
Published: January 2013

As dominant members of marine mesozooplankton communities, copepods play critical roles in oceanic food webs and biogeochemical cycling. Despite the ecological significance of copepods, little is known regarding the causes of copepod mortality, and up to 35% of total copepod mortality cannot be accounted for by predation alone. Viruses have been established as ecologically important infectious agents in the oceans; however, viral infection has not been investigated in mesozooplankton communities. Here we used molecular and microscopic techniques to document viral infection in natural populations of the calanoid copepods
Acartia tonsa
(Dana) and
Labidocera aestiva
(Wheeler) in Tampa Bay, FL. Viral metagenomics revealed previously undocumented viruses in each species, named
Acartia tonsa
copepod circo-like virus (AtCopCV) and
Labidocera aestiva
copepod circo-like virus (LaCopCV). LaCopCV was found to be extremely prevalent and abundant in
L. aestiva
populations, with up to 100% prevalence in some samples and average viral loads of 1.13 × 10
5
copies per individual. LaCopCV transcription was also detected in the majority of
L. aestiva
individuals, indicating viral activity. AtCopCV was sporadically detected in
A. tonsa
populations year-round, suggesting temporal variability in viral infection dynamics. Finally, virus-like particles of unknown identity were observed in the connective tissues of
A. tonsa
and
L. aestiva
by transmission electron microscopy, demonstrating that viruses were actively proliferating in copepod connective tissue as opposed to infecting gut contents, parasites, or symbionts. Taken together, these results provide strong independent lines of evidence for active viral infection in dominant copepod species, indicating that viruses may significantly influence mesozooplankton ecology.
Neuronal correlates of visual time perception at brief timescales
Authors: Mayo J. Patrick , Sommer Marc A.
Published: January 2013

Successful interaction with the world depends on accurate perception of the timing of external events. Neurons at early stages of the primate visual system represent time-varying stimuli with high precision. However, it is unknown whether this temporal fidelity is maintained in the prefrontal cortex, where changes in neuronal activity generally correlate with changes in perception. One reason to suspect that it is not maintained is that humans experience surprisingly large fluctuations in the perception of time. To investigate the neuronal correlates of time perception, we recorded from neurons in the prefrontal cortex and midbrain of monkeys performing a temporal-discrimination task. Visual time intervals were presented at a timescale relevant to natural behavior (<500 ms). At this brief timescale, neuronal adaptation—time-dependent changes in the size of successive responses—occurs. We found that visual activity fluctuated with timing judgments in the prefrontal cortex but not in comparable midbrain areas. Surprisingly, only response strength, not timing, predicted task performance. Intervals perceived as longer were associated with larger visual responses and shorter intervals with smaller responses, matching the dynamics of adaptation. These results suggest that the magnitude of prefrontal activity may be read out to provide temporal information that contributes to judging the passage of time.
Nuclear export inhibition through covalent conjugation and hydrolysis of Leptomycin B by CRM1
Authors: Sun Qingxiang , Carrasco Yazmin P. , Hu Youcai , Guo Xiaofeng , Mirzaei Hamid , MacMillan John , Chook Yuh Min
Published: January 2013

The polyketide natural product Leptomycin B inhibits nuclear export mediated by the karyopherin protein chromosomal region maintenance 1 (CRM1). Here, we present 1.8- to 2.0-Å-resolution crystal structures of CRM1 bound to Leptomycin B and related inhibitors Anguinomycin A and Ratjadone A. Structural and complementary chemical analyses reveal an unexpected mechanism of inhibition involving covalent conjugation and CRM1-mediated hydrolysis of the natural products’ lactone rings. Furthermore, mutagenesis reveals the mechanism of hydrolysis by CRM1. The nuclear export signal (NES)-binding groove of CRM1 is able to drive a chemical reaction in addition to binding protein cargos for transport through the nuclear pore complex.
Energy systems transformation
Authors: Dangerman A. T. C. Jérôme , Schellnhuber Hans Joachim
Published: January 2013

Significance

Energy systems based on fossil fuels and uranium have brought about modernity and its specific agro-industrial metabolism. Although this achievement creates a deep lock-in effect, collateral damages such as climate change and large-scale contamination cast doubts on the sustainability of the current mode of global socioeconomic operation. This article analyzes why the incumbent energy systems are so rigid and still outcompete their more sustainable rivals. We elucidate the role of contemporary corporate law in this context and argue that the stiffness of current energy systems could be overcome by assigning unlimited responsibilities to shareholders.
Increased neuronal activity fragments the Golgi complex
Authors: Thayer Desiree A. , Jan Yuh Nung , Jan Lily Yeh
Published: January 2013

The Golgi complex is essential for many aspects of cellular function, including trafficking and sorting of membrane and secretory proteins and posttranslational modification by glycosylation. We observed reversible fragmentation of the Golgi complex in cultured hippocampal neurons cultured in hyperexcitable conditions. In addition, Golgi fragmentation was found in cultured neurons with hyperactivity due to prolonged blockade of GABAA-mediated inhibition or withdrawal of NMDA receptor antagonism. The interplay between neuronal hyperactivity and Golgi structure established in this study thus reveals a previously uncharacterized impact of neuronal activity on organelle structure. This finding may have important roles in protein processing and trafficking in the Golgi as well as effects on neuronal signaling.
Solvent fluctuations in hydrophobic cavity–ligand binding kinetics
Authors: Setny Piotr , Baron Riccardo , Michael Kekenes-Huskey Peter , McCammon J. Andrew , Dzubiella Joachim
Published: January 2013

Water plays a crucial part in virtually all protein–ligand binding processes in and out of equilibrium. Here, we investigate the role of water in the binding kinetics of a ligand to a prototypical hydrophobic pocket by explicit-water molecular dynamics (MD) simulations and implicit diffusional approaches. The concave pocket in the unbound state exhibits wet/dry hydration oscillations whose magnitude and time scale are significantly amplified by the approaching ligand. In turn, the ligand’s stochastic motion intimately couples to the slow hydration fluctuations, leading to a sixfold-enhanced friction in the vicinity of the pocket entrance. The increased friction considerably decelerates association in the otherwise barrierless system, indicating the importance of molecular-scale hydrodynamic effects in cavity–ligand binding arising due to capillary fluctuations. We derive and analyze the diffusivity profile and show that the mean first passage time distribution from the MD simulation can be accurately reproduced by a standard Brownian dynamics simulation if the appropriate position-dependent friction profile is included. However, long-time decays in the water–ligand (random) force autocorrelation demonstrate violation of the Markovian assumption, challenging standard diffusive approaches for rate prediction. Remarkably, the static friction profile derived from the force correlations strongly resembles the profile derived on the Markovian assumption apart from a simple shift in space, which can be rationalized by a time–space retardation in the ligand’s downhill dynamics toward the pocket. The observed spatiotemporal hydrodynamic coupling may be of biological importance providing the time needed for conformational receptor–ligand adjustments, typical of the induced-fit paradigm.
Ethnic party competition beyond the segmented market
Authors: Zuber Christina Isabel
Published: January 2013

The outbidding model of ethnic politics focuses on party competition in an ethnically perfectly segmented electoral market where no party appeals to voters across the ethnic divide. The power sharing model retains this assumption, yet tries to prevent outbidding through moderation-inducing institutional design. Empirically, imperfectly segmented electoral markets and variance of ethnic party strategies beyond radical outbidding have been observed. To provide a stepping stone towards a more complete theory of ethnic party competition, this article introduces the notion ofnested competition, defined as party competition in an imperfectly segmented market where some — but not all — parties make offers across ethnic divides and where competition in intra-ethnic arenas is nested within an inter-ethnic arena of party competition. The notion of nested competition helps explain why ethnic outbidding is not omnipresent in contemporary multi-ethnic democracies. A moderate position on the ethnic dimension that appears inauspicious from the perspective of intra-ethnic competition can turn into the strategically superior choice once ethnic parties take the whole system of competitive interactions within intra- and inter-ethnic arenas into account. A case study of nested competition for Hungarian votes in the Vojvodina region of Northern Serbia illustrates the conceptual innovations.
RamiGO: an R/Bioconductor package providing an AmiGO Visualize interface
Authors: Schröder Markus S. , Gusenleitner Daniel , Quackenbush John , Culhane Aedín C. , Haibe-Kains Benjamin
Published: January 2013

Summary: The R/Bioconductor package RamiGO is an R interface to AmiGO that enables visualization of Gene Ontology (GO) trees. Given a list of GO terms, RamiGO uses the AmiGO visualize API to import Graphviz-DOT format files into R, and export these either as images (SVG, PNG) or into Cytoscape for extended network analyses. RamiGO provides easy customization of annotation, highlighting of specific GO terms, colouring of terms by P-value or export of a simplified summary GO tree. We illustrate RamiGO functionalities in a genome-wide gene set analysis of prognostic genes in breast cancer.

Availability and implementation: RamiGO is provided in R/Bioconductor, is open source under the Artistic-2.0 License and is available with a user manual containing installation, operating instructions and tutorials. It requires R version 2.15.0 or higher. URL: http://bioconductor.org/packages/release/bioc/html/RamiGO.html

Contact:  markus.schroeder@ucdconnect.ie

Supplementary information:  Supplementary data are available at Bioinformatics online.
Assessing identity, redundancy and confounds in Gene Ontology annotations over time
Authors: Gillis Jesse , Pavlidis Paul
Published: January 2013

Motivation: The Gene Ontology (GO) is heavily used in systems biology, but the potential for redundancy, confounds with other data sources and problems with stability over time have been little explored.

Results: We report that GO annotations are stable over short periods, with 3% of genes not being most semantically similar to themselves between monthly GO editions. However, we find that genes can alter their ‘functional identity’ over time, with 20% of genes not matching to themselves (by semantic similarity) after 2 years. We further find that annotation bias in GO, in which some genes are more characterized than others, has declined in yeast, but generally increased in humans. Finally, we discovered that many entries in protein interaction databases are owing to the same published reports that are used for GO annotations, with 66% of assessed GO groups exhibiting this confound. We provide a case study to illustrate how this information can be used in analyses of gene sets and networks.

Availability: Data available at http://chibi.ubc.ca/assessGO.

Contact:  paul@chibi.ubc.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
A Plant Stem Inoculation Assay for Assessing Transmission of Phytophthora infestans from Potato Seed Tubers to Emerged Shoots
Authors: Johnson Dennis A. , Cummings Thomas F.
Published: January 2013

A stem inoculation assay was developed to assess transmission of Phytophthora infestans from the base of belowground potato stems to emerged aboveground shoots. Sporangia of P. infestans subsequently developed on aboveground stems after belowground stems were inoculated with isolates BF05 (US 8 genotype), WA10.1 (US 24), and 110B (US 11) by (i) placing a filter paper square saturated with a spore suspension onto nonwounded belowground stem tissue, (ii) placing a filter paper square saturated with a spore suspension onto wounded belowground stem tissue, and (iii) dipping the base of the cut belowground stem into a spore suspension. Plant stems were then incubated in a humidity chamber at 10 to 21.5°C for 7 to 28 days. Incidence of aboveground stems with sporulation was significantly less when stems were inoculated with isolate 110B than with isolates BF05 and WA10.1 but length of latent period did not differ among the three isolates. Incidence of aboveground stems with sporangia was significantly (P < 0.05) greater for ‘Russet Norkotah’ than for ‘Umatilla Russet’ when inoculated near the point of seed piece attachment. Incidence of aboveground stems with sporulation did not differ among incubation temperatures of 10, 15, and 21.5°C. Latent period significantly increased as temperature decreased. Age of stem did not appear to affect incidence of transmission. Incidence of transmission of P. infestans to aboveground stems from the base of belowground stems was significantly lowered when aboveground stems were treated with selected fungicides 1 h before inoculation.
Genetic Structure ofColletotrichum gloeosporioidessensu lato Isolates Infecting Papaya Inferred by Multilocus ISSR Markers
Authors: Rampersad Sephra N.
Published: January 2013

Colletotrichum gloeosporioides sensu lato is widely distributed throughout temperate and tropical regions and causes anthracnose disease in numerous plant species. Development of effective disease management strategies is dependent on, among other factors, an understanding of pathogen genetic diversity and population stratification at the intraspecific level. For 132 isolates of C. gloeosporioides sensu lato collected from papaya in Trinidad, inter-simple-sequence repeat-polymerase chain reaction (ISSR-PCR) generated 121 polymorphic loci from five ISSR primers selected from an initial screen of 22 ISSR primers. The mean percentage of polymorphic loci was 99.18%. Bayesian cluster analysis inferred three genetic subpopulations, where group 1 consisted exclusively of isolates collected in the southern part of Trinidad whereas groups 2 and 3, although genetically distinct, were mixtures of isolates collected from both the northern and southern parts of Trinidad. Principal coordinates analysis and unweighted pair-group method with arithmetic mean phylogeny were concordant with Bayesian cluster analysis and supported subdivision into the three subpopulations. Overall, the total mean gene diversity was 0.279, the mean within-population gene diversity was 0.2161, and genetic differentiation for the Trinidad population was 0.225. Regionally, northern isolates had a lower gene diversity compared with southern isolates. Nei's gene diversity was highest for group 1 (h = 0.231), followed by group 2 (h = 0.215) and group 3 (h = 0.202). Genotypic diversity was at or near maximum for all three subpopulations after clone correction. Pairwise estimates of differentiation indicated high and significant genetic differentiation among the inferred subpopulations (Weir's θ of 0.212 to 0.325). Pairwise comparisons among subpopulations suggested restricted gene flow between groups 1 and 2 and groups 1 and 3 but not between groups 2 and 3. The null hypothesis of random mating was rejected for all three inferred subpopulations. These results suggest that pathogen biology and epidemiology as well as certain evolutionary factors may play an important role in population substructuring of C. gloeosporioides sensu lato isolates infecting papaya in Trinidad.
Isolation and Characterization of Nucleotide-Binding Site Resistance Gene Homologues in Common Bean (Phaseolus vulgaris)
Authors: Garzón Luz N. , Oliveros Oscar A. , Rosen Benjamin , Ligarreto Gustavo A. , Cook Douglas R. , Blair Matthew W.
Published: January 2013

Common bean production is constrained by many fungal, viral, and bacterial pathogens. Thus, the identification of resistance (R) genes is an important focal point of common bean research. The main goal of our study was to identify resistance gene homologues (RGH) in the crop, using degenerate primers designed from conserved sequences in the nucleotide-binding site (NBS) domains of R-genes from the model legume Medicago truncatula. Total DNA of the Andean common bean genotype G19833 was used for amplification of over 500 primer combinations. Sequencing of amplicons showed that 403 cloned fragments had uninterrupted open reading frames and were considered representative of functional RGH genes. The sequences were grouped at two levels of nucleotide identity (90 and 80%) and representative sequences of each group were used for phylogenetic analyses. The RGH sequence diversity of common bean was divided into TIR and non-TIR families, each with different clusters. The TIR sequences grouped into 14 clades while non-TIR sequences grouped into seven clades. Pairwise comparisons showed purifying selection, although some sequences may have been the result of diversifying selection. Knowledge about RGH genes in common bean can allow the design of molecular markers for pyramiding of resistance genes against various pathogens.
Flower colour and cytochromes P450
Authors: Tanaka Yoshikazu , Brugliera Filippa
Published: January 2013

Cytochromes P450 play important roles in biosynthesis of flavonoids and their coloured class of compounds, anthocyanins, both of which are major floral pigments. The number of hydroxyl groups on the B-ring of anthocyanidins (the chromophores and precursors of anthocyanins) impact the anthocyanin colour, the more the bluer. The hydroxylation pattern is determined by two cytochromes P450, flavonoid 3′-hydroxylase (F3′H) and flavonoid 3′,5′-hydroxylase (F3′5′H) and thus they play a crucial role in the determination of flower colour. F3′H and F3′5′H mostly belong to CYP75B and CYP75A, respectively, except for the F3′5′Hs in Compositae that were derived from gene duplication of CYP75B and neofunctionalization. Roses and carnations lack blue/violet flower colours owing to the deficiency of F3′5′H and therefore lack the B-ring-trihydroxylated anthocyanins based upon delphinidin. Successful redirection of the anthocyanin biosynthesis pathway to delphinidin was achieved by expressing
F3′5′H
coding regions resulting in carnations and roses with novel blue hues that have been commercialized. Suppression of F3′5′H and F3′H in delphinidin-producing plants reduced the number of hydroxyl groups on the anthocyanidin B-ring resulting in the production of monohydroxylated anthocyanins based on pelargonidin with a shift in flower colour to orange/red. Pelargonidin biosynthesis is enhanced by additional expression of a dihydroflavonol 4-reductase that can use the monohydroxylated dihydrokaempferol (the pelargonidin precursor). Flavone synthase II (FNSII)-catalysing flavone biosynthesis from flavanones is also a P450 (CYP93B) and contributes to flower colour, because flavones act as co-pigments to anthocyanins and can cause blueing and darkening of colour. However, transgenic plants expression of a
FNSII
gene yielded paler flowers owing to a reduction of anthocyanins because flavanones are precursors of anthocyanins and flavones.
Di-μ-chlorido-bis{[2-(di-tert-butylphosphanyl)biphenyl-3-yl-κ2C3,P]palladium(II)} dichloromethane disolvate
Authors: Holzapfel Cedric W. , Omondi Bernard
Published: January 2013

The asymmetric unit of the title compound, [Pd2Cl2(C20H26P)2]·2CH2Cl2, contains one half-molecule of the palladium complex and a dichloromethane solvent molecule. In the complex, two PdIIatoms are bridged by two Cl atoms, with the other two coordination sites occupied by a C atom of the biphenyl system and a P atom, resulting in a distorted square-planar coordination geometry of the PdIIatom and a cyclometallated four-membered ring. The Pd2Cl2unit is located about an inversion center. The planes of the rings of the biphenyl system make a dihedral angle of 66.36 (11)°.
Tetrabromido[4-(triphenylphosphanyloxy)butyl]tellurium acetonitrile monosolvate
Authors: Närhi Sari M. , Oilunkaniemi Raija , Laitinen Risto S.
Published: January 2013

In the title compound, [TeBr4(C22H23OP)]·CH3CN, the Te atom exhibits a square-pyramidal coordination with an apical Te—C bond and four basal Te—Br bonds. The conformation of the aliphatic C—C—C—C chain isgauche[torsion angle = −67.7 (8)°]. A weak C—H...Br interaction helps to establish the conformation. In the crystal, there is a weak secondary bonding interaction [Te...N = 3.456 (11) Å] between the Te atom and the N atom of the solvent molecule, which completes a distorted TeNCBr4octahedron. Inversion dimers linked by pairs of C—H...Br interactions are also observed.
endo,endo-Tetracyclo[6.2.1.13,6.02,7]dodeca-9-en-anti-11-yl 4-bromobenzoate
Authors: Lloyd Barry A. , Arif Atta M. , Coots Robert J.
Published: January 2013

The title compound 1-OPBB, C19H19BrO2, contains a dechlorinated and hydrogenated isodrin backbone with ananti-4-bromobenzoate substituent at one of the methano bridges. The dihedral angle between the CO2ester plane and the benzene ring plane is 8.5 (2)°. In the crystal, the ester groups stack over benzene rings: the molecules pack as conformational enantiomers, with nearest parallel benzene ring planes separated by a perpendicular distance of 3.339 (1) Å. The nearest benzene-ring centroids are 5.266 (1) Å apart. Possible structural correlation with enhanced solvolytic reactivity is investigated.
[2,7-Dihydroxy-8-(4-phenoxybenzoyl)naphthalen-1-yl](4-phenoxyphenyl)methanone
Authors: Hijikata Daichi , Sasagawa Kosuke , Yoshiwaka Sayaka , Okamoto Akiko , Yonezawa Noriyuki
Published: January 2013

In the title compound, C36H24O6, the benzoyl groups at the 1- and 8-positions of the naphthalene system are in anantiorientation. Both carbonyl groups form intramolecular O—H...O hydrogen bonds with hydroxy groups affording six-membered rings. The benzene rings of the benzoyl groups make dihedral angles of 59.26 (13) and 59.09 (13)° with the naphthalene ring system. Zigzag C—H...O chains and ladder C—H...O chains between the phenoxybenzoyl groups along theabdiagonals form an undulating checkered sheet. The molecules are further connected into a three-dimensional network by C—H...π interactions.
Endoscopic resection for gastric epithelial neoplasia: How to solve pathological discrepancy and achieve curative resection?
Authors: Zhu Ling Yin , Dai Jun , Zhao Yun Jia , Xue Han Bin , Ge Zhi Zheng , Li Xiao Bo
Published: January 2013

Objective

Endoscopic resection (ER) was introduced to China from Japan, while most pathologists are influenced by Western criteria. Japanese and Western pathologists have debated for decades how best to distinguish between gastric intraepithelial neoplasia (GIEN) and early gastric cancer (EGC). In this study we aimed to find out how to solve this pathological discrepancy and improve the curative resection of lesions based on our experiences.

Methods

In total, 143 patients with GIEN or EGC were treated by ER in our hospital from April 2008 to April 2012. The risk factors related to the degree of malignancy of the lesions and the non‐curability of ER were analyzed. Pathological discrepancy between forceps biopsies and ER specimens was also compared.

Results

According to the histological types of the ER specimens, there were 67 patients with low‐grade intraepithelial neoplasia (LGIN), 35 with high‐grade intraepithelial neoplasia (HGIN) and 41 with EGC. The ER histological type was significantly correlated with gender, ER method, macroscopic type, tumor size, ulcer and histological type of the forceps biopsy (P < 0.05). The discrepancy between forceps biopsy and ER specimens was 41.3% (59/143). Furthermore, the depth of tumor invasion and ER histological type were associated with the curative resection of HGIN and EGC (P < 0.05).

Conclusions

The pathological discrepancy shows that patients with HGIN in forceps biopsy should be considered candidates for ER. The risk factors of lesion malignancy and ER curability indicate the great importance of pretreatment evaluation for ER.