bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic identification of type I and type II interferon-induced antiviral factors
Authors: Liu Su-Yang , Sanchez David Jesse , Aliyari Roghiyh , Lu Sun , Cheng Genhong
Published: February 2012

Type I and type II interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type I and II IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type I and type II ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type I and type II IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses.
Strong relationship between elemental stoichiometry and metabolome in plants
Authors: Rivas-Ubach Albert , Sardans Jordi , Pérez-Trujillo Miriam , Estiarte Marc , Peñuelas Josep
Published: February 2012

Shifts in the elemental stoichiometry of organisms in response to their ontogeny and to changing environmental conditions should be related to metabolomic changes because elements operate mostly as parts of molecular compounds. Here we show this relationship in leaves of
Erica multiflora
throughout their seasonal development and in response to moderate experimental field conditions of drought and warming. The N/P ratio in leaves decreased in the metabolically active growing seasons, coinciding with an increase in the content of primary metabolites. These results support the growth-rate hypothesis that states that rapidly growing organisms present low N/P ratios because of the increase in allocation of P to RNA. The foliar N/K and P/K ratios were lower in summer and in the drought treatment, in accordance with the role of K in osmotic protection, and coincided with the increase of compounds related to the avoidance of water stress. These results provide strong evidence of the relationship between the changes in foliar C/N/P/K stoichiometry and the changes in the leaf's metabolome during plant growth and environmental stress. Thus these results represent a step in understanding the relationships between stoichiometry and an organism's lifestyle.
Space environment of an asteroid preserved on micrograins returned by the Hayabusa spacecraft
Authors: Nakamura Eizo , Makishima Akio , Moriguti Takuya , Kobayashi Katsura , Tanaka Ryoji , Kunihiro Tak , Tsujimori Tatsuki , Sakaguchi Chie , Kitagawa Hiroshi , Ota Tsutomu , Yachi Yusuke , Yada Toru , Abe Masanao , Fujimura Akio , Ueno Munetaka , Mukai Toshifumi , Yoshikawa Makoto , Kawaguchi Jun’ichiro
Published: February 2012

Records of micrometeorite collisions at down to submicron scales were discovered on dust grains recovered from near-Earth asteroid 25143 (Itokawa). Because the grains were sampled from very near the surface of the asteroid, by the Hayabusa spacecraft, their surfaces reflect the low-gravity space environment influencing the physical nature of the asteroid exterior. The space environment was examined by description of grain surfaces and asteroidal scenes were reconstructed. Chemical and O isotope compositions of five lithic grains, with diameters near 50 μm, indicate that the uppermost layer of the rubble-pile-textured Itokawa is largely composed of equilibrated LL-ordinary-chondrite-like material with superimposed effects of collisions. The surfaces of the grains are dominated by fractures, and the fracture planes contain not only sub-μm-sized craters but also a large number of sub-μm- to several-μm-sized adhered particles, some of the latter composed of glass. The size distribution and chemical compositions of the adhered particles, together with the occurrences of the sub-μm-sized craters, suggest formation by hypervelocity collisions of micrometeorites at down to nm scales, a process expected in the physically hostile environment at an asteroid’s surface. We describe impact-related phenomena, ranging in scale from 10
-9
to 10
4
meters, demonstrating the central role played by impact processes in the long-term evolution of planetary bodies. Impact appears to be an important process shaping the exteriors of not only large planetary bodies, such as the moon, but also low-gravity bodies such as asteroids.
Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking
Authors: Strochlic Todd I. , Concilio Susanna , Viaud Julien , Eberwine Ryan A. , Wong Lisa Epstein , Minden Audrey , Turk Benjamin E. , Plomann Markus , Peterson Jeffrey R.
Published: February 2012

Synaptic transmission is mediated by a complex set of molecular events that must be coordinated in time and space. While many proteins that function at the synapse have been identified, the signaling pathways regulating these molecules are poorly understood. Pak5 (p21-activated kinase 5) is a brain-specific isoform of the group II Pak kinases whose substrates and roles within the central nervous system are largely unknown. To gain insight into the physiological roles of Pak5, we engineered a Pak5 mutant to selectively radiolabel its substrates in murine brain extract. Using this approach, we identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. These results implicate Pak5 in Pacsin1- and Synaptojanin1-mediated synaptic vesicle trafficking and may partially account for the cognitive and behavioral deficits observed in group II Pak-deficient mice.
RNase H-mediated degradation of toxic RNA in myotonic dystrophy type 1
Authors: Lee Johanna E. , Bennett C. Frank , Cooper Thomas A.
Published: February 2012

Myotonic dystrophy type 1 (DM1) is an RNA-dominant disease caused by abnormal transcripts containing expanded CUG repeats. The CUG transcripts aggregate in the nucleus to form RNA foci and lead to nuclear depletion of Muscleblind-like 1 (MBNL1) and stabilized expression of CUGBP Elav like family 1 (CELF1), both of which are splicing regulatory proteins. The imbalance of these proteins results in misregulation of alternative splicing and neuromuscular abnormalities. Here, we report the use of antisense oligonucleotides (ASOs) as a therapeutic approach to target the pathogenic RNA in DM1. We designed chimeric ASOs, termed gapmers, containing modified nucleic acid residues to induce RNase H-mediated degradation of CUG-repeat transcripts. The gapmers selectively knockdown expanded CUG transcripts and are sufficient to disrupt RNA foci both in cell culture and mouse models for DM1. Furthermore, combination of gapmers with morpholino ASOs that help release binding of MBNL1 to the toxic RNA can potentially enhance the knockdown effect. Additional optimization will be required for systemic delivery; however, our study provides an alternative strategy for the use of ASOs in DM1 therapy.
Honesty mediates the relationship between serotonin and reaction to unfairness
Authors: Takahashi Hidehiko , Takano Harumasa , Camerer Colin F. , Ideno Takashi , Okubo Shigetaka , Matsui Hiroshi , Tamari Yuki , Takemura Kazuhisa , Arakawa Ryosuke , Kodaka Fumitoshi , Yamada Makiko , Eguchi Yoko , Murai Toshiya , Okubo Yoshiro , Kato Motoichiro , Ito Hiroshi , Suhara Tetsuya
Published: February 2012

How does one deal with unfair behaviors? This subject has long been investigated by various disciplines including philosophy, psychology, economics, and biology. However, our reactions to unfairness differ from one individual to another. Experimental economics studies using the ultimatum game (UG), in which players must decide whether to accept or reject fair or unfair offers, have also shown that there are substantial individual differences in reaction to unfairness. However, little is known about psychological as well as neurobiological mechanisms of this observation. We combined a molecular imaging technique, an economics game, and a personality inventory to elucidate the neurobiological mechanism of heterogeneous reactions to unfairness. Contrary to the common belief that aggressive personalities (impulsivity or hostility) are related to the high rejection rate of unfair offers in UG, we found that individuals with apparently peaceful personalities (straightforwardness and trust) rejected more often and were engaged in personally costly forms of retaliation. Furthermore, individuals with a low level of serotonin transporters in the dorsal raphe nucleus (DRN) are honest and trustful, and thus cannot tolerate unfairness, being candid in expressing their frustrations. In other words, higher central serotonin transmission might allow us to behave adroitly and opportunistically, being good at playing games while pursuing self-interest. We provide unique neurobiological evidence to account for individual differences of reaction to unfairness.
Neuronal activity in the primate dorsomedial prefrontal cortex contributes to strategic selection of response tactics
Authors: Matsuzaka Yoshiya , Akiyama Tetsuya , Tanji Jun , Mushiake Hajime
Published: February 2012

The functional roles of the primate posterior medial prefrontal cortex have remained largely unknown. Here, we show that this region participates in the regulation of actions in the presence of multiple response tactics. Monkeys performed a forelimb task in which a visual cue required prompt decision of reaching to a left or a right target. The location of the cue was either ipsilateral (concordant) or contralateral (discordant) to the target. As a result of extensive training, the reaction times for the concordant and discordant trials were indistinguishable, indicating that the monkeys developed tactics to overcome the cue-response conflict. Prefrontal neurons exhibited prominent activity when the concordant and discordant trials were randomly presented, requiring rapid selection of a response tactic (reach toward or away from the cue). The following findings indicate that these neurons are involved in the selection of tactics, rather than the selection of action or monitoring of response conflict: (
i
) The response period activity of neurons in this region disappeared when the monkeys performed the task under the behavioral condition that required a single tactic alone, whereas the action varied across trials. (
ii
) The neuronal activity was found in the dorsomedial prefrontal cortex but not in the anterior cingulate cortex that has been implicated for the response conflict monitoring. These results suggest that the medial prefrontal cortex participates in the selection of a response tactic that determines an appropriate action. Furthermore, the observation of dynamic, task-dependent neuronal activity necessitates reconsideration of the conventional concept of cortical motor representation.
Structural dissection of Ebola virus and its assembly determinants using cryo-electron tomography
Authors: Bharat Tanmay A. M. , Noda Takeshi , Riches James D. , Kraehling Verena , Kolesnikova Larissa , Becker Stephan , Kawaoka Yoshihiro , Briggs John A. G.
Published: February 2012

Ebola virus is a highly pathogenic filovirus causing severe hemorrhagic fever with high mortality rates. It assembles heterogenous, filamentous, enveloped virus particles containing a negative-sense, single-stranded RNA genome packaged within a helical nucleocapsid (NC). We have used cryo-electron microscopy and tomography to visualize Ebola virus particles, as well as Ebola virus-like particles, in three dimensions in a near-native state. The NC within the virion forms a left-handed helix with an inner nucleoprotein layer decorated with protruding arms composed of VP24 and VP35. A comparison with the closely related Marburg virus shows that the N-terminal region of nucleoprotein defines the inner diameter of the Ebola virus NC, whereas the RNA genome defines its length. Binding of the nucleoprotein to RNA can assemble a loosely coiled NC-like structure; the loose coil can be condensed by binding of the viral matrix protein VP40 to the C terminus of the nucleoprotein, and rigidified by binding of VP24 and VP35 to alternate copies of the nucleoprotein. Four proteins (NP, VP24, VP35, and VP40) are necessary and sufficient to mediate assembly of an NC with structure, symmetry, variability, and flexibility indistinguishable from that in Ebola virus particles released from infected cells. Together these data provide a structural and architectural description of Ebola virus and define the roles of viral proteins in its structure and assembly.
Development of GABAergic inputs controls the contribution of maturing neurons to the adult hippocampal network
Authors: Li Yan , Aimone James B. , Xu Xiangming , Callaway Edward M. , Gage Fred H.
Published: February 2012

New neurons are continuously generated in the dentate gyrus (DG) in the adult hippocampus, and new granule cells (GCs) have been shown to be necessary for several aspects of learning and memory. Nonetheless, the limited information available regarding the anatomical and physiological development of synaptic inputs onto maturing neurons has restricted our understanding of how new GCs affect cognition. Here, we use photostimulation to demonstrate the time course by which anatomically isolated inhibitory inputs develop onto maturing GCs. We then show that the gradual development of inhibition is sufficient in a computational model to drive learning of novel information in young neurons. Finally, we validate this model observation by using slice physiology to show how inhibition regulates firing probability and plasticity in young GCs. Combined, these data demonstrate that the unique connectivity of immature GCs affords them a functional role that is different from mature neurons in the DG circuit, a distinction that potentially underlies many of the proposed functions of new neurons in the hippocampal network.
Adaptive horizontal transfer of a bacterial gene to an invasive insect pest of coffee
Authors: Acuña Ricardo , Padilla Beatriz E. , Flórez-Ramos Claudia P. , Rubio José D. , Herrera Juan C. , Benavides Pablo , Lee Sang-Jik , Yeats Trevor H. , Egan Ashley N. , Doyle Jeffrey J. , Rose Jocelyn K. C.
Published: February 2012

Horizontal gene transfer (HGT) involves the nonsexual transmission of genetic material across species boundaries. Although often detected in prokaryotes, examples of HGT involving animals are relatively rare, and any evolutionary advantage conferred to the recipient is typically obscure. We identified a gene (
HhMAN1
) from the coffee berry borer beetle,
Hypothenemus hampei
, a devastating pest of coffee, which shows clear evidence of HGT from bacteria.
HhMAN1
encodes a mannanase, representing a class of glycosyl hydrolases that has not previously been reported in insects. Recombinant HhMAN1 protein hydrolyzes coffee berry galactomannan, the major storage polysaccharide in this species and the presumed food of
H. hampei
.
HhMAN1
was found to be widespread in a broad biogeographic survey of
H. hampei
accessions, indicating that the HGT event occurred before radiation of the insect from West Africa to Asia and South America. However, the gene was not detected in the closely related species
H. obscurus
(the tropical nut borer or “false berry borer”), which does not colonize coffee beans. Thus, HGT of
HhMAN1
from bacteria represents a likely adaptation to a specific ecological niche and may have been promoted by intensive agricultural practices.
Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death
Authors: Noh Kyung-Min , Hwang Jee-Yeon , Follenzi Antonia , Athanasiadou Rodoniki , Miyawaki Takahiro , Greally John M. , Bennett Michael V. L. , Zukin R. Suzanne
Published: February 2012

Dysregulation of the transcriptional repressor element-1 silencing transcription factor (REST)/neuron-restrictive silencer factor is important in a broad range of diseases, including cancer, diabetes, and heart disease. The role of REST-dependent epigenetic modifications in neurodegeneration is less clear. Here, we show that neuronal insults trigger activation of REST and CoREST in a clinically relevant model of ischemic stroke and that REST binds a subset of “transcriptionally responsive” genes (
gria2
,
grin1,
c
hrnb2, nefh, nf
κ
b2, trpv1
,
chrm4
, and
syt6
), of which the AMPA receptor subunit GluA2 is a top hit. Genes with enriched REST exhibited decreased mRNA and protein. We further show that REST assembles with CoREST, mSin3A, histone deacetylases 1 and 2, histone methyl-transferase G9a, and methyl CpG binding protein 2 at the promoters of target genes, where it orchestrates epigenetic remodeling and gene silencing. RNAi-mediated depletion of REST or administration of dominant-negative REST delivered directly into the hippocampus in vivo prevents epigenetic modifications, restores gene expression, and rescues hippocampal neurons. These findings document a causal role for REST-dependent epigenetic remodeling in the neurodegeneration associated with ischemic stroke and identify unique therapeutic targets for the amelioration of hippocampal injury and cognitive deficits.
Suppression of EGFR endocytosis by dynamin depletion reveals that EGFR signaling occurs primarily at the plasma membrane
Authors: Sousa Leiliane P. , Lax Irit , Shen Hongying , Ferguson Shawn M. , Camilli Pietro De , Schlessinger Joseph
Published: February 2012

The role of endocytosis in the control of EGF receptor (EGFR) activation and cell signaling was explored by using mouse fibroblasts in which dynamin was conditionally depleted. Dynamin is a GTPase shown to play an important role in the control clathrin mediated endocytosis of EGFR and other cell surface receptors. In this report, we demonstrate that EGF binding activity and the display of high and low affinity EGFRs on the cell surface are not affected by dynamin depletion. By contrast, dynamin depletion leads to a strong inhibition of EGFR endocytosis, robust enhancement of EGFR autophosphorylation and ubiquitination, and slower kinetics of EGFR degradation. Surprisingly, MAPK stimulation induced by either low or high EGF concentrations is not affected by dynamin depletion. While a similar initial Akt response is detected in control or dynamin depleted fibroblasts, a somewhat more sustained Akt stimulation is detected in the dynamin depleted cells. These experiments demonstrate that dynamin-mediated endocytosis leads to attenuation of EGFR activation and degradation and that stimulation of the MAPK response and Akt activation are primarily mediated by activated EGFR located in the plasma membrane.
Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis
Authors: Marinković Petar , Reuter Miriam S. , Brill Monika S. , Godinho Leanne , Kerschensteiner Martin , Misgeld Thomas
Published: February 2012

Axonal transport deficits have been reported in many neurodegenerative conditions and are widely assumed to be an immediate causative step of axon and synapse loss. By imaging changes in axonal morphology and organelle transport over time in several animal models of amyotrophic lateral sclerosis (ALS), we now find that deficits in axonal transport of organelles (mitochondria, endosomes) and axon degeneration can evolve independently. This conclusion rests on the following results: (
i
) Axons can survive despite long-lasting transport deficits: In the

SOD
G93A

model of ALS, transport deficits are detected soon after birth, months before the onset of axon degeneration. (
ii
) Transport deficits are not necessary for axon degeneration: In the

SOD
G85R

model of ALS, motor axons degenerate, but transport is unaffected. (
iii
) Axon transport deficits are not sufficient to cause immediate degeneration: In mice that overexpress wild-type superoxide dismutase-1 (

SOD
WT

), axons show chronic transport deficits, but survive. These data suggest that disturbances of organelle transport are not a necessary step in the emergence of motor neuron degeneration.
Transformations of the Indo-Iranian Snake-man: Myth, Language, Ethnoarcheology, and Iranian Identity
Authors: Schwartz Martin
Published: February 2012

This article sets forth a history (with literary-textual focus) of the Iranian mythological Snake-man, from the earliest Vedic and Avestan evidence, down to Ferdowsi. The continuous development of the myth in Iran is accompanied by changes in the monster's name, which show linguistic reassociations, while a constant in all of this is the figure's representation as an inimical outsider. The Vedic name of the brute's fortification, the background of which in etymology and realia will be shown to be the pre-Aryan Bactria-Margiana Archeological Complex, finds a clear but hitherto unobserved correlation in Pahlavi. This illuminates the Indo-Iranian antiquity of the myth in terms of prehistoric inter-ethnic rivalries.
Poppy Politics: American Agents, Iranian Addicts and Afghan Opium, 1945–80
Authors: Gingeras Ryan
Published: February 2012

This paper surveys the history of American support for Iranian counter-narcotics policy between 1945 and 1989. In particular, it explores the general failings of Tehran's attempt to ban the domestic production and consumption of opium. The significance of this period is two-fold. First, this essay argues that American-backed efforts to combat the opium trade in Iran highlighted the detrimental effects narcotics had upon both state and society in Iran. Second, it suggests that the Iranian ban upon narcotics helped to stimulate a rise in Afghan opium production before the Soviet invasion of 1979.
Cognitive Load Hypothesis of Item-Method Directed Forgetting
Authors: Lee Yuh-Shiow
Published: February 2012

This study examined the effect of the processing demands of to-be-remembered (TBR) words on item-method directed forgetting. Experiment 1 found that a standard memory group remembered fewer to-be-forgotten (TBF) words than a naming group, in which participants simply named the TBR words during the study phase, even though both groups were equally instructed to forget the TBF words. Experiment 2 manipulated the number of TBR words in the study list, keeping the number of TBF words constant, and found that TBF word forgetting was more difficult in the few TBR words condition than the more TBR words condition. The same pattern was found in the result of Experiment 3 when a cued recall test, instead of a free recall test, was used. In all the experiments, participants were asked to recall the TBF words before the TBR words. These findings are consistent with the cognitive load hypothesis that it is easier to forget when there are fewer cognitive resources available during encoding.
The rate of change in Ca2+ concentration controls sperm chemotaxis
Authors: Alvarez Luis , Dai Luru , Friedrich Benjamin M. , Kashikar Nachiket D. , Gregor Ingo , Pascal René , Kaupp U. Benjamin
Published: February 2012

During chemotaxis and phototaxis, sperm, algae, marine zooplankton, and other microswimmers move on helical paths or drifting circles by rhythmically bending cell protrusions called motile cilia or flagella. Sperm of marine invertebrates navigate in a chemoattractant gradient by adjusting the flagellar waveform and, thereby, the swimming path. The waveform is periodically modulated by Ca2+ oscillations. How Ca2+ signals elicit steering responses and shape the path is unknown. We unveil the signal transfer between the changes in intracellular Ca2+ concentration ([Ca2+]i) and path curvature (κ). We show that κ is modulated by the time derivative d[Ca2+]i/dt rather than the absolute [Ca2+]i. Furthermore, simulation of swimming paths using various Ca2+ waveforms reproduces the wealth of swimming paths observed for sperm of marine invertebrates. We propose a cellular mechanism for a chemical differentiator that computes a time derivative. The cytoskeleton of cilia, the axoneme, is highly conserved. Thus, motile ciliated cells in general might use a similar cellular computation to translate changes of [Ca2+]i into motion.
Dual regulation of IRF4 function in T and B cells is required for the coordination of T–B cell interactions and the prevention of autoimmunity
Authors: Biswas Partha S. , Gupta Sanjay , Stirzaker Roslynn A. , Kumar Varsha , Jessberger Rolf , Lu Theresa T. , Bhagat Govind , Pernis Alessandra B.
Published: February 2012

Effective humoral responses to protein antigens require the precise execution of carefully timed differentiation programs in both T and B cell compartments. Disturbances in this process underlie the pathogenesis of many autoimmune disorders, including systemic lupus erythematosus (SLE). Interferon regulatory factor 4 (IRF4) is induced upon the activation of T and B cells and serves critical functions. In CD4+ T helper cells, IRF4 plays an essential role in the regulation of IL-21 production, whereas in B cells it controls class switch recombination and plasma cell differentiation. IRF4 function in T helper cells can be modulated by its interaction with regulatory protein DEF6, a molecule that shares a high degree of homology with only one other protein, SWAP-70. Here, we demonstrate that on a C57BL/6 background the absence of both DEF6 and SWAP-70 leads to the development of a lupus-like disease in female mice, marked by simultaneous deregulation of CD4+ T cell IL-21 production and increased IL-21 B cell responsiveness. We furthermore show that DEF6 and SWAP-70 are differentially used at distinct stages of B cell differentiation to selectively control the ability of IRF4 to regulate IL-21 responsiveness in a stage-specific manner. Collectively, these data provide novel insights into the mechanisms that normally couple and coordinately regulate T and B cell responses to ensure tight control of productive T–B cell interactions.
An extra allele of Chk1 limits oncogene-induced replicative stress and promotes transformation
Authors: López-Contreras Andres J. , Gutierrez-Martinez Paula , Specks Julia , Rodrigo-Perez Sara , Fernandez-Capetillo Oscar
Published: February 2012

Replicative stress (RS) is a type of endogenous DNA damage that cells suffer every time they duplicate their genomes, and which is further boosted by oncogenes. In mammals, the RS response (RSR) is coordinated by ATR and Chk1 kinases. We sought to develop a mammalian organism that is selectively protected from RS. To this end, mice carrying an extra copy of the Chk1 gene were generated. In vitro, Chk1 transgenic cells are protected from RS-inducing agents. Moreover, an extra Chk1 allele prolongs the survival of ATR-Seckel mice, which suffer from high levels of RS, but not that of ATM-deficient mice, which accumulate DNA breaks. Surprisingly, increased Chk1 levels favor transformation, which we show is associated with a reduction in the levels of RS induced by oncogenes. Our study provides the first example where supra-physiological levels of a tumor suppressor can promote malignant transformation, which is a result of the protection from the RS found in cancer cells.
Water mass transport variability to the North Icelandic shelf, 1994–2010
Authors: Jónsson Steingrímur , Valdimarsson Héðinn
Published: February 2012

Jónsson, S., and Valdimarsson, H. 2012. Water mass transport variability to the North Icelandic shelf, 1994–2010. – ICES Journal of Marine Science, 69: 809–815. In the Denmark Strait between Greenland and Iceland, the north-flowing warm, saline Atlantic Water (AW) of the Irminger Current meets the south-flowing cold, relatively fresh Polar Water (PW) of the East Greenland Current. A mixture of these two surface water masses then flows along the shelf north of Iceland. The mixture can vary from being almost pure AW to consisting, to a large extent, of PW. The relative quantities of each water mass to some extent determine the productivity and the living conditions on the shelf north of Iceland. The flow has been monitored with current meters on a section north of Iceland since 1994, and these measurements, together with hydrographic data, are used to study its structure and variability. The amount of AW carried by the flow is calculated along with the associated heat transport. In the period 1994–2010, the flow consisted on average of 68% of AW with a transport of 0.88 Sv and an associated heat transport of 24 TW. There is notable seasonal variation in the flow and strong interannual variability.
21st century fisheries management: a spatio-temporally explicit tariff-based approach combining multiple drivers and incentivising responsible fishing
Authors: Kraak Sarah B. M. , Reid Dave G. , Gerritsen Hans D. , Kelly Ciarán J. , Fitzpatrick Mike , Codling Edward A. , Rogan Emer
Published: February 2012

Kraak, S. B. M., Reid, D. G., Gerritsen, H. D., Kelly, C. J., Fitzpatrick, M., Codling, E. A., and Rogan, E. 2012. 21st century fisheries management: a spatio-temporally explicit tariff-based approach combining multiple drivers and incentivising responsible fishing. – ICES Journal of Marine Science, 69: 590–601. Traditionally fisheries management has focused on biomass and mortality, expressed annually and across large management units. However, because fish abundance varies at much smaller spatio-temporal scales, fishing mortality can potentially be controlled more effectively if managed at finer scale. The ecosystem approach requires more indicators at finer scales as well. Incorporating ecosystem targets would need additional management tools with potentially conflicting results. We present a simple, integrated, management approach that provides incentives for “good behaviour”. Fishers would be given a number of fishing-impact credits, called real-time incentives (RTIs), to spend according to spatio-temporally varying tariffs per fishing day. RTI quotas and tariffs could be based on commercial stocks and ecosystem targets. Fishers could choose how to spend their RTIs, e.g. by limited fishing in high-catch or sensitive areas or by fishing longer in lower-catch or less sensitive areas. The RTI system does not prescribe and forbid, but instead allows fishers to fish wherever and whenever they want; ecosystem costs are internalized and fishers have to take them into account in their business decisions. We envisage no need for traditional landings or catch quotas for the fleets while operating under the scheme. The approach could facilitate further devolution of responsibility to industry.
Analysis of the Saccharomyces cerevisiae pan-genome reveals a pool of copy number variants distributed in diverse yeast strains from differing industrial environments
Authors: Dunn Barbara , Richter Chandra , Kvitek Daniel J. , Pugh Tom , Sherlock Gavin
Published: February 2012

Although the budding yeast Saccharomyces cerevisiae is arguably one of the most well-studied organisms on earth, the genome-wide variation within this species—i.e., its “pan-genome”—has been less explored. We created a multispecies microarray platform containing probes covering the genomes of several Saccharomyces species: S. cerevisiae, including regions not found in the standard laboratory S288c strain, as well as the mitochondrial and 2-μm circle genomes–plus S. paradoxus, S. mikatae, S. kudriavzevii, S. uvarum, S. kluyveri, and S. castellii. We performed array-Comparative Genomic Hybridization (aCGH) on 83 different S. cerevisiae strains collected across a wide range of habitats; of these, 69 were commercial wine strains, while the remaining 14 were from a diverse set of other industrial and natural environments. We observed interspecific hybridization events, introgression events, and pervasive copy number variation (CNV) in all but a few of the strains. These CNVs were distributed throughout the strains such that they did not produce any clear phylogeny, suggesting extensive mating in both industrial and wild strains. To validate our results and to determine whether apparently similar introgressions and CNVs were identical by descent or recurrent, we also performed whole-genome sequencing on nine of these strains. These data may help pinpoint genomic regions involved in adaptation to different industrial milieus, as well as shed light on the course of domestication of S. cerevisiae.
Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals
Authors: Tani Hidenori , Mizutani Rena , Salam Kazi Abdus , Tano Keiko , Ijiri Kenichi , Wakamatsu Ai , Isogai Takao , Suzuki Yutaka , Akimitsu Nobuyoshi
Published: February 2012

Mammalian genomes produce huge numbers of noncoding RNAs (ncRNAs). However, the functions of most ncRNAs are unclear, and novel techniques that can distinguish functional ncRNAs are needed. Studies of mRNAs have revealed that the half-life of each mRNA is closely related to its physiological function, raising the possibility that the RNA stability of an ncRNA reflects its function. In this study, we first determined the half-lives of 11,052 mRNAs and 1418 ncRNAs in HeLa Tet-off (TO) cells by developing a novel genome-wide method, which we named 5′-bromo-uridine immunoprecipitation chase–deep sequencing analysis (BRIC-seq). This method involved pulse-labeling endogenous RNAs with 5′-bromo-uridine and measuring the ongoing decrease in RNA levels over time using multifaceted deep sequencing. By analyzing the relationship between RNA half-lives and functional categories, we found that RNAs with a long half-life (t1/2 ≥ 4 h) contained a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short half-life (t1/2 < 4 h) included known regulatory ncRNAs and regulatory mRNAs. The stabilities of a significant set of short-lived ncRNAs are regulated by external stimuli, such as retinoic acid treatment. In particular, we identified and characterized several novel long ncRNAs involved in cell proliferation from the group of short-lived ncRNAs. We designated this novel class of ncRNAs with a short half-life as Short-Lived noncoding Transcripts (SLiTs). We propose that the strategy of monitoring RNA half-life will provide a powerful tool for investigating hitherto functionally uncharacterized regulatory RNAs.
The Phosphatidylcholine Diacylglycerol Cholinephosphotransferase Is Required for Efficient Hydroxy Fatty Acid Accumulation in Transgenic Arabidopsis
Authors: Hu Zhaohui , Ren Zhonghai , Lu Chaofu
Published: February 2012

We previously identified an enzyme, phosphatidylcholine diacylglycerol cholinephosphotransferase (PDCT), that plays an important role in directing fatty acyl fluxes during triacylglycerol (TAG) biosynthesis. The PDCT mediates a symmetrical interconversion between phosphatidylcholine (PC) and diacylglycerol (DAG), thus enriching PC-modified fatty acids in the DAG pool prior to forming TAG. We show here that PDCT is required for the efficient metabolism of engineered hydroxy fatty acids in Arabidopsis (Arabidopsis thaliana) seeds. When a fatty acid hydroxylase (FAH12) from castor (Ricinus communis) was expressed in Arabidopsis seeds, the PDCT-deficient mutant accumulated only about half the amount of hydroxy fatty acids compared with that in the wild-type seeds. We also isolated a PDCT from castor encoded by the RcROD1 (Reduced Oleate Desaturation1) gene. Seed-specific coexpression of this enzyme significantly increased hydroxy fatty acid accumulation in wild type-FAH12 and in a previously produced transgenic Arabidopsis line coexpressing a castor diacylglycerol acyltransferase 2. Analyzing the TAG molecular species and regiochemistry, along with analysis of fatty acid composition in TAG and PC during seed development, indicate that PDCT acts in planta to enhance the fluxes of fatty acids through PC and enrich the hydroxy fatty acids in DAG, and thus in TAG. In addition, PDCT partially restores the oil content that is decreased in FAH12-expressing seeds. Our results add a new gene in the genetic toolbox for efficiently engineering unusual fatty acids in transgenic oilseeds.
Low Red/Far-Red Ratios Reduce Arabidopsis Resistance toBotrytis cinereaand Jasmonate Responses via a COI1-JAZ10-Dependent, Salicylic Acid-Independent Mechanism
Authors: Cerrudo Ignacio , Keller Mercedes M. , Cargnel Miriam D. , Demkura Patricia V. , de Wit Mieke , Patitucci Micaela S. , Pierik Ronald , Pieterse Corné M.J. , Ballaré Carlos L.
Published: February 2012

Light is an important modulator of plant immune responses. Here, we show that inactivation of the photoreceptor phytochrome B (phyB) by a low red/far-red ratio (R:FR), which is a signal of competition in plant canopies, down-regulates the expression of defense markers induced by the necrotrophic fungus Botrytis cinerea, including the genes that encode the transcription factor ETHYLENE RESPONSE FACTOR1 (ERF1) and the plant defensin PLANT DEFENSIN1.2 (PDF1.2). This effect of low R:FR correlated with a reduced sensitivity to jasmonate (JA), thus resembling the antagonistic effects of salicylic acid (SA) on JA responses. Low R:FR failed to depress PDF1.2 mRNA levels in a transgenic line in which PDF1.2 transcription was up-regulated by constitutive expression of ERF1 in a coronatine insensitive1 (coi1) mutant background (35S::ERF1/coi1). These results suggest that the low R:FR effect, in contrast to the SA effect, requires a functional SCFCOI1-JASMONATE ZIM-DOMAIN (JAZ) JA receptor module. Furthermore, the effect of low R:FR depressing the JA response was conserved in mutants impaired in SA signaling (sid2-1 and npr1-1). Plant exposure to low R:FR ratios and the phyB mutation markedly increased plant susceptibility to B. cinerea; the effect of low R:FR was (1) independent of the activation of the shade-avoidance syndrome, (2) conserved in the sid2-1 and npr1-1 mutants, and (3) absent in two RNA interference lines disrupted for the expression of the JAZ10 gene. Collectively, our results suggest that low R:FR ratios depress Arabidopsis (Arabidopsis thaliana) immune responses against necrotrophic microorganisms via a SA-independent mechanism that requires the JAZ10 transcriptional repressor and that this effect may increase plant susceptibility to fungal infection in dense canopies.
Disruptive behaviour disorders: a systematic review of environmental antenatal and early years risk factors
Authors: Latimer K. , Wilson P. , Kemp J. , Thompson L. , Sim F. , Gillberg C. , Puckering C. , Minnis H.
Published: February 2012

Disruptive behaviour disorders (DBDs), including attention‐deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD) and conduct disorder (CD) are chronic disorders with significant overlap in aetiology and presentation. An integrative examination of environmental risk factors is lacking. Six literature searches of web‐based bibliographic databases were completed to identify literature on DBDs in general and five disorders in particular: CD, ODD, ADHD, deficits of attention, motor control and perception, and reactive attachment disorder. Searches were filtered to focus on studies including diagnostic assessment, focussing on environmental risk and protective factors in the first 4 years of life. The database searches generated 9806 papers of which 47 were reviewed after filters had been applied. The evidence suggests links between a number of early life risk factors and DBDs, including prenatal cigarette smoking and alcohol use, prenatal viral illness, maternal stress and anxiety, low birthweight, peri‐partum and early neonatal complications, parental stress and parenting styles in infancy, early deprivation, adoption and separation. Despite the understanding that there is sharing of risk factors between the DBDs, there has been a disproportionate focus on the role of certain risk factors at the expense of others and the field is weakened by difficulties in controlling for all potential confounding variables.
The association between neurodevelopmental disability and economic outcomes during mid‐childhood
Authors: Petrou S. , Johnson S. , Wolke D. , Marlow N.
Published: February 2012

Background There is a paucity of evidence on the association between childhood disability and economic outcomes. This study estimates the economic costs and health utilities associated with neurodevelopmental impairment or serious neurodevelopmental disability during the 11th year of life.

Methods Standardized tests of cognitive ability and clinical assessments of functional abilities were performed on participants of a whole population study of extremely preterm children and term‐born controls (EPICure). Profiles of children's use of health, social and education services, and descriptions of their health status using the Health Utilities Index Mark 2 and Mark 3 health status classification systems, were extracted from detailed questionnaires completed by the main parent. Descriptive and multiple regression techniques were used to explore the association between neurodevelopmental impairment or serious neurodevelopmental disability and two sets of economic outcomes; economic costs and health utilities.

Results Mean health and social service costs over the 12‐month period were estimated at £577 [standard error (SE): £141] among children without neurodevelopmental impairment, £831 (£112) among children with a mild neurodevelopmental impairment, £1053 (£176) among children with a moderate neurodevelopmental impairment and £1662 (£316) among children with a severe neurodevelopmental impairment. Mean health and social service costs were estimated at £1223 (£157) and £695 (£92) among children with and without serious neurodevelopmental disability, respectively. After controlling for clinical and sociodemographic confounders, mild, moderate and severe neurodevelopment impairment increased health and social service costs by an average of £397 (95% CI: £86, £707;P= 0.012), £655 (95% CI: £167, £1144;P= 0.009) and £1065 (95% CI: −£113, £2243;P= 0.076), respectively. Cost differences were accentuated when broader public sector costs were considered. The mean (SE) Health Utilities Index Mark 3 multi‐attribute utility score for the children with neurodevelopmental disability was 0.652 (0.039), compared with 0.923 (0.009) for children without neurodevelopmental disability, generating a mean difference in utility score of 0.272 (95% CI: 0.220, 0.323) that was statistically significant (P< 0.001).

Conclusions Our data should act as a significant new resource for economic analysts modelling the overall economic impact of childhood neurodevelopment impairment or disability or the cost‐effectiveness of interventions targeted at neurodevelopmentally impaired or disabled children.
The experience of disabled children as inpatients: a structured review and synthesis of qualitative studies reporting the views of children, parents and professionals
Authors: Shilling V. , Edwards V. , Rogers M. , Morris C.
Published: February 2012

Disabled children are a broad group that includes those with complex, special or additional health needs as a result of chronic physical, cognitive, communication or behavioural problems. These children are more frequently admitted to hospital than other children; however, there appears to be relatively little research on their experience as inpatients. The aim of this structured review and synthesis was to integrate findings from qualitative studies reporting the experience of disabled children when they are hospital inpatients. Inclusion criteria were: qualitative studies that focused on the experience of children less than 18 years old, with a chronic health condition or neurodisability, during an inpatient stay. Studies of outpatient episodes or intensive care units were excluded. A systematic search identified relevant abstracts, selected papers were reviewed and data were extracted. The synthesis involved elucidating and integrating common themes. Eight relevant papers were identified; data were gathered from children, parents and staff. Communication between children and staff was a dominant theme and comprised giving the child information about their condition and appropriate involvement of the child/young person in discussions and decision making that affected them. Also important was communication between parents and staff, particularly around the division of care for their child. Other themes included emotions, particularly fears, the ward environment and confidence in staff. The review suggests that disabled children's experience as inpatients is not always optimal. Improving the communication skills of ward staff and providing information to disabled children and their families would improve disabled children's experience when they are inpatients.
Prediction of asthma exacerbations in children: results of a one‐year prospective study
Authors: Robroeks C. M. H. H. T. , van Vliet D. , Jöbsis Q. , Braekers R. , Rijkers G. T. , Wodzig W. K. W. H. , Bast A. , Zimmermann L. J. I. , Dompeling E.
Published: February 2012

Background

Underdiagnosis and low levels of asthma control are frequent occurring problems in patients with asthma.

Objective

The study aim was to evaluate the ability of non‐invasive inflammatory markers in exhaled breath to predict exacerbations of childhood asthma, and to assess the time course of changes in these exhaled markers before, during and after exacerbations.

Methods

The design was a prospective one‐year longitudinal study. Regular two‐month visits at the outpatient clinic were performed. Forty children with asthma (aged 6–16 years) participated. The primary outcome measure was the occurrence of an exacerbation. Assessment was made of the presence and severity of pulmonary symptoms, use of medication, and measurements of forced expiratory volume in 1 s using home monitor. The following independent parameters were assessed during outpatient visits: (1) exhaled nitric oxide, (2) inflammatory markers in exhaled breath condensate: acidity, nitrite, hydrogen peroxide, interleukin‐1α, ‐5, ‐13, interferon‐γ, (3) lung function, (4) asthma control score.

Results

Thirty‐eight of 40 children completed the study. Sixteen children developed exacerbations, of which ten were moderate and six severe. Univariate Cox regression analysis revealed that condensate acidity, interleukin‐5 and asthma control score were significant predictors of an asthma exacerbation (P < 0.05). In the multivariate Cox regression analysis, exacerbations were best predicted by the asthma control score and by the level of interleukin‐5 in exhaled breath condensate (Wald scores of 7.19 and 4.44, P = 0.007 and P = 0.035 respectively). The predicted survival curve of this multivariate model showed a two times reduced risk on exacerbations in the category of children with the 10% most optimal values of IL‐5 and asthma control score.

Conclusions and Clinical Relevance

Both exhaled breath condensate interleukin‐5 level and asthma control score were significant predictors of asthma exacerbations. These findings open up the possibility of assessing the potential of such parameters to titrate asthma treatment in future studies.