bluuebunny/crossref_metadata_2025 huggingface dataset:
Polarity-dependent resistance switching in GeSbTe phase-change thin films: The importance of excess Sb in filament formation
Authors: Pandian Ramanathaswamy , Kooi Bart J. , Oosthoek Jasper L. M. , van den Dool Pim , Palasantzas George , Pauza Andrew
Published: December 2009

We show that polarity-dependent resistance switching in GeSbTe thin films depends strongly on Sb composition by comparing current-voltage characteristics in Sb-excess Ge2Sb2+xTe5 and stoichiometric Ge2Sb2Te5 samples. This type of switching in Ge2Sb2+xTe5 films is reversible with both continuous and pulsed dc voltages less than 1.5 V. Low and high resistance states of this switching can be attributed to formation and rupture, respectively, of electrically conductive Sb-bridges between the Ge2Sb2Te5 crystals and electrodes through the resistive amorphous phase. The coexistence of polarity-dependent resistance switching with amorphous-crystalline phase-changes renders great opportunities to expand the applicability of GeSbTe films for data storage applications.
Theory of damped quantum rotation in nuclear magnetic resonance spectra. III. Nuclear permutation symmetry of the line shape equation
Authors: Szymański S.
Published: December 2009

The damped quantum rotation (DQR) theory describes manifestations in nuclear magnetic resonance spectra of the coherent and stochastic dynamics of N-fold molecular rotors composed of indistinguishable particles. The standard jump model is only a limiting case of the DQR approach; outside this limit, the stochastic motions of such rotors have no kinematic description. In this paper, completing the previous two of this series, consequences of nuclear permutation symmetry for the properties of the DQR line shape equation are considered. The systems addressed are planar rotors, such as aromatic hydrocarbons’ rings, occurring inside of molecular crystals oriented in the magnetic field. Under such conditions, oddfold rotors can have nontrivial permutation symmetries only for peculiar orientations while evenfold ones always retain their intrinsic symmetry element, which is rotation by 180° about the N-fold axis; in specific orientations the latter can gain two additional symmetry elements. It is shown that the symmetry selection rules applicable to the classical rate processes in fluids, once recognized as having two diverse aspects, macroscopic and microscopic, are also rigorously valid for the DQR processes in the solid state. However, formal justification of these rules is different because the DQR equation is based on the Pauli principle, which is ignored in the jump model. For objects like the benzene ring, exploitation of these rules in simulations of spectra using the DQR equation can be of critical significance for the feasibility of the calculations. Examples of such calculations for the proton system of the benzene ring in a general orientation are provided. It is also shown that, because of the intrinsic symmetries of the evenfold rotors, many of the DQR processes, which such rotors can undergo, are unobservable in NMR spectra.
An energetic stability predictor of hydrogen-terminated Si nanostructures
Authors: Xu Hu , Yang X. B. , Guo C. S. , Zhang R. Q.
Published: December 2009

We present a linear relationship between the cohesive energies and the H/Si ratio for hydrogen-terminated Si semiconductor nanostructures based on our model analysis and first-principles calculations. The H/Si ratio is shown to be a universal predictor of the nanostructure’s energetic stability and allows easily searching of magic numbers in Si quantum dots. Our findings substantially improve the understanding of nanostructure stability and make practical the prediction of structural properties.
DNA-psoralen: Single-molecule experiments and first principles calculations
Authors: Rocha M. S. , Lúcio A. D. , Alexandre S. S. , Nunes R. W. , Mesquita O. N.
Published: December 2009

The authors measure the persistence and contour lengths of DNA-psoralen complexes, as a function of psoralen concentration, for intercalated and crosslinked complexes. In both cases, the persistence length monotonically increases until a certain critical concentration is reached, above which it abruptly decreases and remains approximately constant. The contour length of the complexes exhibits no such discontinuous behavior. By fitting the relative increase of the contour length to the neighbor exclusion model, we obtain the exclusion number and the intrinsic intercalating constant of the interaction. Ab initio calculations are employed in order to provide an atomistic picture of these experimental findings.
Quasiclassical trajectory calculations of correlated product distributions for the F+CHD3(v1=,1) reactions using an ab initio potential energy surface
Authors: Czakó Gábor , Bowman Joel M.
Published: December 2009

We report quasiclassical trajectory (QCT) calculations of the correlated product distributions and branching ratios of the reactions F+CHD3(v1=0,1)→HF(v)+CD3(v) and DF(v)+CHD2(v) using a recently published ab initio-based full-dimensional global potential energy surface [G. Czakó et al., J. Chem. Phys. 130, 084301 (2009)]. Harmonic normal mode analysis is done for the methyl products to determine the classical actions of each normal mode and then standard histogram binning and Gaussian binning (GB) methods are employed to obtain quantum state-resolved probabilities of the products. QCT calculations have been performed for both the vibrationally ground state and the CH stretching excited F+CHD3(v1=0,1) reactions at eight different collision energies in the 0.5–7.0 kcal/mol range. HF and DF vibrationally state-resolved rotational and angular distributions, CD3 and CHD2 mode-specific vibrational distributions, and correlated vibrationally state-specific distributions for the product pairs have been obtained and the correlated results were compared to the experiment. We find that the use of GB can be advantageous especially in the threshold regions. The CH stretching excitation in the reactant does not change the CD3 vibrational distributions significantly, whereas the HF molecules become vibrationally and rotationally hotter. On the other hand in the case of the DF+CHD2 channel the initially excited CH stretch appears mainly “intact” in the CHD2 product and the DF distributions are virtually the same as formed from the ground state CHD3 reaction. The computed results qualitatively agree with recent crossed molecular beam experiment [W. Zhang et al., Science 325, 303 (2009)] that (a) CHD2(v1=1) is the most populated product state of the F+CHD3(v1=1) reaction and this reaction produces much less CHD2(v=0) compared to the reaction F+CHD3(v=0); (b) the cross section ratio of CHD2(v1=1):CHD2(v=0) formed from the reactions F+CHD3(v1=1):F+CHD3(v=0) is less than 1 and shows little collision energy dependency; (c) the reactant CH stretch excitation increases the DF:HF ratio at low collision energies; (d) the correlated vibrational and angular distributions for DF(v)+CHD2(v1=0,1) from the ground state and stretch-excited reactions, respectively, are almost identical.
Close packing density of polydisperse hard spheres
Authors: Farr Robert S. , Groot Robert D.
Published: December 2009

The most efficient way to pack equally sized spheres isotropically in three dimensions is known as the random close packed state, which provides a starting point for many approximations in physics and engineering. However, the particle size distribution of a real granular material is never monodisperse. Here we present a simple but accurate approximation for the random close packing density of hard spheres of any size distribution based upon a mapping onto a one-dimensional problem. To test this theory we performed extensive simulations for mixtures of elastic spheres with hydrodynamic friction. The simulations show a general (but weak) dependence of the final (essentially hard sphere) packing density on fluid viscosity and on particle size but this can be eliminated by choosing a specific relation between mass and particle size, making the random close packed volume fraction well defined. Our theory agrees well with the simulations for bidisperse, tridisperse, and log-normal distributions and correctly reproduces the exact limits for large size ratios.
Precipitation extreme changes exceeding moisture content increases in MIROC and IPCC climate models
Authors: Sugiyama Masahiro , Shiogama Hideo , Emori Seita
Published: December 2009

Precipitation extreme changes are often assumed to scale with, or are constrained by, the change in atmospheric moisture content. Studies have generally confirmed the scaling based on moisture content for the midlatitudes but identified deviations for the tropics. In fact half of the twelve selected Intergovernmental Panel on Climate Change (IPCC) models exhibit increases faster than the climatological-mean precipitable water change for high percentiles of tropical daily precipitation, albeit with significant intermodel scatter. Decomposition of the precipitation extreme changes reveals that the variations among models can be attributed primarily to the differences in the upward velocity. Both the amplitude and vertical profile of vertical motion are found to affect precipitation extremes. A recently proposed scaling that incorporates these dynamical effects can capture the basic features of precipitation changes in both the tropics and midlatitudes. In particular, the increases in tropical precipitation extremes significantly exceed the precipitable water change in Model for Interdisciplinary Research on Climate (MIROC), a coupled general circulation model with the highest resolution among IPCC climate models whose precipitation characteristics have been shown to reasonably match those of observations. The expected intensification of tropical disturbances points to the possibility of precipitation extreme increases beyond the moisture content increase as is found in MIROC and some of IPCC models.
Activation of articulatory information in speech perception
Authors: Yuen Ivan , Davis Matthew H. , Brysbaert Marc , Rastle Kathleen
Published: December 2009

Emerging neurophysiologic evidence indicates that motor systems are activated during the perception of speech, but whether this activity reflects basic processes underlying speech perception remains a matter of considerable debate. Our contribution to this debate is to report direct behavioral evidence that specific articulatory commands are activated
automatically
and
involuntarily
during speech perception. We used electropalatography to measure whether motor information activated from spoken distractors would yield specific distortions on the articulation of printed target syllables. Participants produced target syllables beginning with /k/ or /s/ while listening to the same syllables or to incongruent rhyming syllables beginning with /t/. Tongue–palate contact for target productions was measured during the articulatory closure of /k/ and during the frication of /s/. Results revealed “traces” of the incongruent distractors on target productions, with the incongruent /t/-initial distractors inducing greater alveolar contact in the articulation of /k/ and /s/ than the congruent distractors. Two further experiments established that (
i
) the nature of this interference effect is dependent specifically on the articulatory properties of the spoken distractors; and (
ii
) this interference effect is unique to spoken distractors and does not arise when distractors are presented in printed form. Results are discussed in terms of a broader emerging framework concerning the relationship between perception and action, whereby the perception of action entails activation of the motor system.
Ocean acidification and marine trace gas emissions
Authors: Hopkins Frances E. , Turner Suzanne M. , Nightingale Philip D. , Steinke Michael , Bakker Dorothee , Liss Peter S.
Published: December 2009

The oceanic uptake of man-made CO
2
emissions is resulting in a measureable decrease in the pH of the surface oceans, a process which is predicted to have severe consequences for marine biological and biogeochemical processes [Caldeira K, Wickett ME (2003)
Nature
425:365; The Royal Society (2005)
Policy Document 12/05
(Royal Society, London)]. Here, we describe results showing how a doubling of current atmospheric CO
2
affects the production of a suite of atmospherically important marine trace gases. Two CO
2
treatments were used during a mesocosm CO
2
perturbation experiment in a Norwegian fjord (present day: ∼380 ppmv and year 2100: ∼750 ppmv), and phytoplankton blooms were stimulated by the addition of nutrients. Seawater trace gas concentrations were monitored over the growth and decline of the blooms, revealing that concentrations of methyl iodide and dimethylsulfide were significantly reduced under high CO
2.
Additionally, large reductions in concentrations of other iodocarbons were observed. The response of bromocarbons to high CO
2
was less clear cut. Further research is now required to understand how ocean acidification might impact on global marine trace gas fluxes and how these impacts might feed through to changes in the earth's future climate and atmospheric chemistry.
Ecological indicators display reduced variation in North American catch share fisheries
Authors: Essington Timothy E.
Published: December 2009

A growing push to implement catch share fishery programs is based partly on the recognition that they may provide stronger incentives for ecological stewardship than conventional fisheries management. Using data on population status, quota compliance, discard rates, use of habitat-damaging gear, and landings for 15 catch share programs in North America, I tested the hypothesis that catch share systems lead to improved ecological stewardship and status of exploited populations. Impacts of catch share programs were measured through comparisons of fisheries with catch shares to fisheries without catch shares or by comparing fisheries before and after catch shares were implemented. The average levels of most indicators were unaffected by catch share implementation: only discard rate, which declined significantly in catch share fisheries, showed a significant response. However, catch share fisheries were distinguished by markedly reduced interannual variability in all indicators, being statistically significant for exploitation rate, landings, discard rate, and the ratio of catch to catch quotas. These impacts of catch shares were common between nations and ocean basins and were independent of the number of years that catch share programs had been in place. These findings suggest that for the indicators examined, the primary effect of catch shares was greater consistency over time. This enhanced consistency could be beneficial to fishery systems and might also be an indication of more effective management.
WDR5 is essential for assembly of the VISA-associated signaling complex and virus-triggered IRF3 and NF-κB activation
Authors: Wang Yan-Yi , Liu Li-Juan , Zhong Bo , Liu Tian-Tian , Li Ying , Yang Yan , Ran Yong , Li Shu , Tien Po , Shu Hong-Bing
Published: December 2009

Viral infection causes activation of the transcription factors NF-κB and IRF3, which collaborate to induce type I interferons (IFNs) and cellular antiviral response. The mitochondrial outer membrane protein VISA acts as a critical adapter for assembling a virus-induced complex that signals NF-κB and IRF3 activation. Using a biochemical purification approach, we identified the WD repeat protein WDR5 as a VISA-associated protein. WDR5 was recruited to VISA in a viral infection dependent manner. Viral infection also caused translocation of WDR5 from the nucleus to mitochondria. Knockdown of WDR5 impaired the formation of virus-induced VISA-associated complex. Consistently, knockdown of WDR5 inhibited virus-triggered activation of IRF3 and NF-κB as well as transcription of the
IFNB1
gene. These findings suggest that WDR5 is essential in assembling a virus-induced VISA-associated complex and plays an important role in virus-triggered induction of type I IFNs.
Structural basis for cofactor-independent dioxygenation of
N
-heteroaromatic compounds at the α/β-hydrolase fold
Authors: Steiner Roberto A. , Janssen Helge J. , Roversi Pietro , Oakley Aaron J. , Fetzner Susanne
Published: December 2009

Enzymatic catalysis of oxygenation reactions in the absence of metal or organic cofactors is a considerable biochemical challenge. The CO-forming 1-
H
-3-hydroxy-4-oxoquinaldine 2,4-dioxygenase (HOD) from
Arthrobacter nitroguajacolicus
Rü61a and 1-
H
-3-hydroxy-4-oxoquinoline 2,4-dioxygenase (QDO) from
Pseudomonas putida
33/1 are homologous cofactor-independent dioxygenases involved in the breakdown of
N
-heteroaromatic compounds. To date, they are the only dioxygenases suggested to belong to the α/β-hydrolase fold superfamily. Members of this family typically catalyze hydrolytic processes rather than oxygenation reactions. We present here the crystal structures of both HOD and QDO in their native state as well as the structure of HOD in complex with its natural 1-
H
-3-hydroxy-4-oxoquinaldine substrate, its
N
-acetylanthranilate reaction product, and chloride as dioxygen mimic. HOD and QDO are structurally very similar. They possess a classical α/β-hydrolase fold core domain additionally equipped with a cap domain. Organic substrates bind in a preorganized active site with an orientation ideally suited for selective deprotonation of their hydroxyl group by a His/Asp charge-relay system affording the generation of electron-donating species. The “oxyanion hole” of the α/β-hydrolase fold, typically employed to stabilize the tetrahedral intermediate in ester hydrolysis reactions, is utilized here to host and control oxygen chemistry, which is proposed to involve a peroxide anion intermediate. Product release by proton back transfer from the catalytic histidine is driven by minimization of intramolecular charge repulsion. Structural and kinetic data suggest a nonnucleophilic general-base mechanism. Our analysis provides a framework to explain cofactor-independent dioxygenation within a protein architecture generally employed to catalyze hydrolytic reactions.
IL-4-induced transcription factor NFIL3/E4BP4 controls IgE class switching
Authors: Kashiwada Masaki , Levy Deborah M. , McKeag Lisa , Murray Keri , Schröder Andreas J. , Canfield Stephen M. , Traver Geri , Rothman Paul B.
Published: December 2009

IL-4 signaling promotes IgE class switching through STAT6 activation and the induction of Ig germ-line ε (GLε) transcription. Previously, we and others identified a transcription factor,Nfil3, as a gene induced by IL-4 stimulation in B cells. However, the precise roles of nuclear factor, IL-3-regulated (NFIL3) in IL-4 signaling are unknown. Here, we report that NFIL3 is important for IgE class switching. NFIL3-deficient mice show impaired IgE class switching, and this defect is B-cell intrinsic. The induction of GLε transcripts after LPS and IL-4 stimulation is significantly reduced in NFIL3-deficient B cells. Expression of NFIL3 in NFIL3-deficient B cells restores the impairment of IgE production, and overexpression of NFIL3 in the presence of cycloheximide induces GLε transcripts. Moreover, NFIL3 binds to Iε promoter in vivo. Together, these results identify NFIL3 as a key regulator of IL-4-induced GLε transcription in response to IL-4 and subsequent IgE class switching.
Genome-wide patterns of population structure and admixture in West Africans and African Americans
Authors: Bryc Katarzyna , Auton Adam , Nelson Matthew R. , Oksenberg Jorge R. , Hauser Stephen L. , Williams Scott , Froment Alain , Bodo Jean-Marie , Wambebe Charles , Tishkoff Sarah A. , Bustamante Carlos D.
Published: December 2009

Quantifying patterns of population structure in Africans and African Americans illuminates the history of human populations and is critical for undertaking medical genomic studies on a global scale. To obtain a fine-scale genome-wide perspective of ancestry, we analyze Affymetrix GeneChip 500K genotype data from African Americans (
n
= 365) and individuals with ancestry from West Africa (
n
= 203 from 12 populations) and Europe (
n
= 400 from 42 countries). We find that population structure within the West African sample reflects primarily language and secondarily geographical distance, echoing the Bantu expansion. Among African Americans, analysis of genomic admixture by a principal component-based approach indicates that the median proportion of European ancestry is 18.5% (25th–75th percentiles: 11.6–27.7%), with very large variation among individuals. In the African-American sample as a whole, few autosomal regions showed exceptionally high or low mean African ancestry, but the X chromosome showed elevated levels of African ancestry, consistent with a sex-biased pattern of gene flow with an excess of European male and African female ancestry. We also find that genomic profiles of individual African Americans afford personalized ancestry reconstructions differentiating ancient vs. recent European and African ancestry. Finally, patterns of genetic similarity among inferred African segments of African-American genomes and genomes of contemporary African populations included in this study suggest African ancestry is most similar to non-Bantu Niger-Kordofanian-speaking populations, consistent with historical documents of the African Diaspora and trans-Atlantic slave trade.
DNA aptamer–micelle as an efficient detection/delivery vehicle toward cancer cells
Authors: Wu Yanrong , Sefah Kwame , Liu Haipeng , Wang Ruowen , Tan Weihong
Published: December 2009

We report the design of a self-assembled aptamer–micelle nanostructure that achieves selective and strong binding of otherwise low-affinity aptamers at physiological conditions. Specific recognition ability is directly built into the nanostructures. The attachment of a lipid tail onto the end of nucleic acid aptamers provides these unique nanostructures with an internalization pathway. Other merits include: extremely low off rate once bound with target cells, rapid recognition ability with enhanced sensitivity, low critical micelle concentration values, and dual-drug delivery pathways. To prove the potential detection/delivery application of this aptamer–micelle in biological living systems, we mimicked a tumor site in the blood stream by immobilizing tumor cells onto the surface of a flow channel device. Flushing the aptamer–micelles through the channel demonstrated their selective recognition ability under flow circulation in human whole-blood sample. The aptamer–micelles show great dynamic specificity in flow channel systems that mimic drug delivery in the blood system. Therefore, our DNA aptamer–micelle assembly has shown high potential for cancer cell recognition and for in vivo drug delivery applications.
Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation
Authors: Heller Aaron S. , Johnstone Tom , Shackman Alexander J. , Light Sharee N. , Peterson Michael J. , Kolden Gregory G. , Kalin Ned H. , Davidson Richard J.
Published: December 2009

Anhedonia, the loss of pleasure or interest in previously rewarding stimuli, is a core feature of major depression. While theorists have argued that anhedonia reflects a reduced capacity to experience pleasure, evidence is mixed as to whether anhedonia is caused by a reduction in hedonic capacity. An alternative explanation is that anhedonia is due to the inability to sustain positive affect across time. Using positive images, we used an emotion regulation task to test whether individuals with depression are unable to sustain activation in neural circuits underlying positive affect and reward. While up-regulating positive affect, depressed individuals failed to sustain nucleus accumbens activity over time compared with controls. This decreased capacity was related to individual differences in self-reported positive affect. Connectivity analyses further implicated the fronto-striatal network in anhedonia. These findings support the hypothesis that anhedonia in depressed patients reflects the inability to sustain engagement of structures involved in positive affect and reward.
How telomeric protein POT1 avoids RNA to achieve specificity for single-stranded DNA
Authors: Nandakumar Jayakrishnan , Podell Elaine R. , Cech Thomas R.
Published: December 2009

The POT1-TPP1 heterodimer, the major telomere-specific single-stranded DNA-binding protein in mammalian cells, protects chromosome ends and contributes to the regulation of telomerase. The recent discovery of telomeric RNA raises the question of how POT1 faithfully binds telomeric ssDNA and avoids illicit RNA binding that could result in its depletion from telomeres. Here we show through binding studies that a single deoxythymidine in a telomeric repeat dictates the DNA versus RNA discrimination by human POT1 and mouse POT1A. We solve the crystal structure of hPOT1 bound to DNA with a ribouridine in lieu of the critical deoxythymidine and show that this substitution results in burying the 2
′
-hydroxyl group in a hydrophobic region (Phe62) of POT1 in addition to eliminating favorable hydrogen-bonding interactions at the POT1–nucleic acid interface. At amino acid 62, Phe discriminates against RNA binding and Tyr allows RNA binding. We further show that TPP1 greatly augments POT1’s discrimination against RNA.
Endocannabinoids selectively enhance sweet taste
Authors: Yoshida Ryusuke , Ohkuri Tadahiro , Jyotaki Masafumi , Yasuo Toshiaki , Horio Nao , Yasumatsu Keiko , Sanematsu Keisuke , Shigemura Noriatsu , Yamamoto Tsuneyuki , Margolskee Robert F. , Ninomiya Yuzo
Published: December 2009

Endocannabinoids such as anandamide [N-arachidonoylethanolamine (AEA)] and 2-arachidonoyl glycerol (2-AG) are known orexigenic mediators that act via CB
1
receptors in hypothalamus and limbic forebrain to induce appetite and stimulate food intake. Circulating endocannabinoid levels inversely correlate with plasma levels of leptin, an anorexigenic mediator that reduces food intake by acting on hypothalamic receptors. Recently, taste has been found to be a peripheral target of leptin. Leptin selectively suppresses sweet taste responses in wild-type mice but not in leptin receptor-deficient
db/db
mice. Here, we show that endocannabinoids oppose the action of leptin to act as enhancers of sweet taste. We found that administration of AEA or 2-AG increases gustatory nerve responses to sweeteners in a concentration-dependent manner without affecting responses to salty, sour, bitter, and umami compounds. The cannabinoids increase behavioral responses to sweet-bitter mixtures and electrophysiological responses of taste receptor cells to sweet compounds. Mice genetically lacking CB
1
receptors show no enhancement by endocannnabinoids of sweet taste responses at cellular, nerve, or behavioral levels. In addition, the effects of endocannabinoids on sweet taste responses of taste cells are diminished by AM251, a CB
1
receptor antagonist, but not by AM630, a CB
2
receptor antagonist. Immunohistochemistry shows that CB
1
receptors are expressed in type II taste cells that also express the T1r3 sweet taste receptor component. Taken together, these observations suggest that the taste organ is a peripheral target of endocannabinoids. Reciprocal regulation of peripheral sweet taste reception by endocannabinoids and leptin may contribute to their opposing actions on food intake and play an important role in regulating energy homeostasis.
Direct control of mitochondrial function by mTOR
Authors: Ramanathan Arvind , Schreiber Stuart L.
Published: December 2009

mTOR is a central regulator of cellular growth and metabolism. Using metabolic profiling and numerous small-molecule probes, we investigated whether mTOR affects immediate control over cellular metabolism by posttranslational mechanisms. Inhibiting the FKBP12/rapamycin-sensitive subset of mTOR functions in leukemic cells enhanced aerobic glycolysis and decreased uncoupled mitochondrial respiration within 25 min. mTOR is in a complex with the mitochondrial outer-membrane protein Bcl-xl and VDAC1. Bcl-xl, but not VDAC1, is a kinase substrate for mTOR in vitro, and mTOR regulates the association of Bcl-xl with mTOR. Inhibition of mTOR not only enhances aerobic glycolysis, but also induces a state of increased dependence on aerobic glycolysis in leukemic cells, as shown by the synergy between the glycolytic inhibitor 2-deoxyglucose and rapamycin in decreasing cell viability.
A conserved MutS homolog connector domain interface interacts with MutL homologs
Authors: Mendillo Marc L. , Hargreaves Victoria V. , Jamison Jonathan W. , Mo Ashley O. , Li Sheng , Putnam Christopher D. , Woods Virgil L. , Kolodner Richard D.
Published: December 2009

Escherichia coli
MutS forms a mispair-dependent ternary complex with MutL that is essential for initiating mismatch repair (MMR) but is structurally uncharacterized, in part owing to its dynamic nature. Here, we used hydrogen/deuterium exchange mass spectrometry and other methods to identify a region in the connector domain (domain II) of MutS that binds MutL and is required for mispair-dependent ternary complex formation and MMR. A structurally conserved region in Msh2, the eukaryotic homolog, was required for formation of a mispair-dependent Msh2–Msh6–Mlh1–Pms1 ternary complex. These data indicate that the connector domain of MutS and Msh2 contains the interface for binding MutL and Mlh1–Pms1, respectively, and support a mechanism whereby mispair and ATP binding induces a conformational change that allows the MutS and Msh2 interfaces to interact with their partners.
The birdlike raptor
Sinornithosaurus
was venomous
Authors: Gong Enpu , Martin Larry D. , Burnham David A. , Falk Amanda R.
Published: December 2009

We suggest that some of the most avian dromaeosaurs, such as
Sinornithosaurus
, were venomous, and propose an ecological model for that taxon based on its unusual dentition and other cranial features including grooved teeth, a possible pocket for venom glands, and a groove leading from that pocket to the exposed bases of the teeth. These features are all analogous to the venomous morphology of lizards.
Sinornithosaurus
and related dromaeosaurs probably fed on the abundant birds of the Jehol forests during the Early Cretaceous in northeastern China.
A neuroeconomic theory of the decision process
Authors: Dickhaut John , Rustichini Aldo , Smith Vernon
Published: December 2009

We develop a neuronal theory of the choice process (NTCP), which takes a subject from the moment in which two options are presented to the selection of one of the two. The theory is based on an optimal signal detection, which generalizes the signal detection theory by adding the choice of effort as optimal choice for a given informational value of the signal for every effort level and a cost of effort. NTCP predicts the choice made as a stochastic choice: That is, as a probability distribution over two options in a set, the level of effort provided, the error rate, and the time to respond. The theory provides a unified account of behavioral evidence (choices made, error rate, time to respond) as well as neural evidence (represented by the effort rate measured for example by the level of brain activation). The theory also provides a unified explanation of several facts discovered and interpreted in the last decades of experimental economic analysis of choices, which we review.
The neural bases of key competencies of emotional intelligence
Authors: Krueger Frank , Barbey Aron K. , McCabe Kevin , Strenziok Maren , Zamboni Giovanna , Solomon Jeffrey , Raymont Vanessa , Grafman Jordan
Published: December 2009

Emotional intelligence (EI) refers to a set of competencies that are essential features of human social life. Although the neural substrates of EI are virtually unknown, it is well established that the prefrontal cortex (PFC) plays a crucial role in human social-emotional behavior. We studied a unique sample of combat veterans from the Vietnam Head Injury Study, which is a prospective, long-term follow-up study of veterans with focal penetrating head injuries. We administered the Mayer-Salovey-Caruso Emotional Intelligence Test as a valid standardized psychometric measure of EI behavior to examine two key competencies of EI: (
i
) Strategic EI as the competency to understand emotional information and to apply it for the management of the self and of others and (
ii
) Experiential EI as the competency to perceive emotional information and to apply it for the integration into thinking. The results revealed that key competencies underlying EI depend on distinct neural PFC substrates. First, ventromedial PFC damage diminishes Strategic EI, and therefore, hinders the understanding and managing of emotional information. Second, dorsolateral PFC damage diminishes Experiential EI, and therefore, hinders the perception and integration of emotional information. In conclusion, EI should be viewed as complementary to cognitive intelligence and, when considered together, provide a more complete understanding of human intelligence.
High skill in low-frequency climate response through fluctuation dissipation theorems despite structural instability
Authors: Majda Andrew J. , Abramov Rafail , Gershgorin Boris
Published: December 2009

Climate change science focuses on predicting the coarse-grained, planetary-scale, longtime changes in the climate system due to either changes in external forcing or internal variability, such as the impact of increased carbon dioxide. The predictions of climate change science are carried out through comprehensive, computational atmospheric, and oceanic simulation models, which necessarily parameterize physical features such as clouds, sea ice cover, etc. Recently, it has been suggested that there is irreducible imprecision in such climate models that manifests itself as structural instability in climate statistics and which can significantly hamper the skill of computer models for climate change. A systematic approach to deal with this irreducible imprecision is advocated through algorithms based on the Fluctuation Dissipation Theorem (FDT). There are important practical and computational advantages for climate change science when a skillful FDT algorithm is established. The FDT response operator can be utilized directly for multiple climate change scenarios, multiple changes in forcing, and other parameters, such as damping and inverse modelling directly without the need of running the complex climate model in each individual case. The high skill of FDT in predicting climate change, despite structural instability, is developed in an unambiguous fashion using mathematical theory as guidelines in three different test models: a generic class of analytical models mimicking the dynamical core of the computer climate models, reduced stochastic models for low-frequency variability, and models with a significant new type of irreducible imprecision involving many fast, unstable modes.
CRFR1 is expressed on pancreatic β cells, promotes β cell proliferation, and potentiates insulin secretion in a glucose-dependent manner
Authors: Huising Mark O. , van der Meulen Talitha , Vaughan Joan M. , Matsumoto Masahito , Donaldson Cynthia J. , Park Hannah , Billestrup Nils , Vale Wylie W.
Published: December 2009

Corticotropin-releasing factor (CRF), originally characterized as the principal neuroregulator of the hypothalamus-pituitary-adrenal axis, has broad central and peripheral distribution and actions. We demonstrate the presence of CRF receptor type 1 (CRFR1) on primary β cells and show that activation of pancreatic CRFR1 promotes insulin secretion, thus contributing to the restoration of normoglycemic equilibrium. Stimulation of pancreatic CRFR1 initiates a cAMP response that promotes insulin secretion in vitro and in vivo and leads to the phosphorylation of cAMP response element binding and the induction of the expression of several immediate-early genes. Thus, the insulinotropic actions of pancreatic CRFR1 oppose the activation of CRFR1 on anterior pituitary corticotropes, leading to the release of glucocorticoids that functionally antagonize the actions of insulin. Stimulation of the MIN6 insulinoma line and primary rat islets with CRF also activates the MAPK signaling cascade leading to rapid phosphorylation of Erk1/2 in response to CRFR1-selective ligands, which induce proliferation in primary rat neonatal β cells. Importantly, CRFR1 stimulates insulin secretion only during conditions of intermediate to high ambient glucose, and the CRFR1-dependent phosphorylation of Erk1/2 is greater with elevated glucose concentrations. This response is reminiscent of the actions of the incretins, which potentiate insulin secretion only during elevated glucose conditions. The presence of CRFR1 on β cells adds another layer of complexity to the intricate network of paracrine and autocrine factors and their cognate receptors whose coordinated efforts can dictate islet hormone output and regulate β cell proliferation.
Hypoxia-inducible Factor-dependent Regulation of Platelet-activating Factor Receptor as a Route for Gram-Positive Bacterial Translocation across Epithelia
Authors: Keely Simon , Glover Louise E. , Weissmueller Thomas , MacManus Christopher F. , Fillon Sophie , Fennimore Blair , Colgan Sean P.
Published: December 2009

Mucosal surfaces, such as the lung and intestine, are lined by a monolayer of epithelia that provides tissue barrier and transport function. It is recently appreciated that a common feature of inflammatory processes within the mucosa is hypoxia (so-called inflammatory hypoxia). Given the strong association between bacterial translocation and mucosal inflammatory disease, we hypothesized that intestinal epithelial hypoxia influences bacterial translocation. Initial studies revealed that exposure of cultured intestinal epithelia to hypoxia (pO2, 20 torr; 24–48 h) resulted in a increase of up to 40-fold in the translocation of some strains of Gram-positive bacteria, independently of epithelial barrier function. A screen of relevant pathway inhibitors identified a prominent role for the platelet-activating factor receptor (PAFr) in hypoxia-associated bacterial translocation, wherein pharmacologic antagonists of PAFr blocked bacterial translocation by as much as 80 ± 6%. Extensions of these studies revealed that hypoxia prominently induces PAFr through a hypoxia-inducible factor (HIF)-dependent mechanism. Indeed, HIF and PAFr loss of function studies (short hairpin RNA) revealed that apically expressed PAFr is central to the induction of translocation for the Gram-positive bacteria Enterococcus faecalis . Together, these findings reveal that some strains of Gram-positive bacteria exploit HIF-regulated PAFr as a means for translocation through intestinal epithelial cells.
Analyzing Cytotoxic and Apoptogenic Properties of Scutellaria litwinowii Root Extract on Cancer Cell Lines
Authors: Tayarani-Najaran Zahra , Emami Seyed Ahmad , Asili Javad , Mirzaei Alireza , Mousavi Seyed Hadi
Published: December 2009

The Scutellaria species (Lamiaceae) is used as a source of flavonoids to treat a variety of diseases in traditional medicine. In spite of many reports about the cytotoxic and antitumor effects of some species of this genus, anticancer researches on one of the Iranian species S. litwinowii have not yet been conducted. The cytotoxic properties of total methanol extract of S. litwinowii and its fractions were investigated on different cancer cell lines including AGS, HeLa, MCF‐7, PC12 and NIH 3T3. Meanwhile, the role of apoptosis in this toxicity was explored. The cells were cultured in DMEM medium and incubated with different concentrations of herb plant extracts. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub‐G1 peak). Scutellaria litwinowii inhibited the growth of malignant cells in a dose‐dependent manner. Among solvent fractions of S. litwinowii, the methylene chloride fraction was found to be more toxic compared to other fractions. The IC50 values of this fraction against AGS, HeLa, MCF‐7 and PC12 cell lines after 24 h were determined, 121.2 ± 3.1, 40.9 ± 2.5, 115.9 ± 3.5 and 64.5 ± 3.4 μg/ml, respectively. Scutellaria litwinowii induced a sub‐G1 peak in the flow cytometry histogram of treated cells compared to control cells indicating that apoptotic cell death is involved in S. litwinowii toxicity. Scutellaria litwinowii exerts cytotoxic and proapototic effects in a variety of malignant cell lines and could be considered as a potential chemotherapeutic agent in cancer treatment.
The Efficacy of Ultramolecular Aqueous Dilutions on a Wheat Germination Model as a Function of Heat and Aging‐Time
Authors: Brizzi Maurizio , Elia Vittorio , Trebbi Grazia , Nani Daniele , Peruzzi Maurizio , Betti Lucietta
Published: December 2009

This study evaluates the effects of temperature and aging on the efficacy of As2O3 at the 45th decimal potency in a wheat germination model, compared against a control and potentized H2O 45×. Each treatment‐temperature combination was tested on seeds (Triticum aestivum L.) of Pandas variety, using six Petri dishes (33 seeds/dish) per trial, performing eight trials. Seeds were pre‐treated by poisoning with 0.1% As2O3 solution to reduce germination, to allow a better evaluation of homeopathic treatment effects. The outcome variable was the number of non‐germinated seeds after 96 h. Temperature effect was investigated by heating each treatment in a water bath for 30 min (at 20, 40 or 70°C), or for 5 min (at 100°C), and that of aging by dividing experimental data, collected over a period of nearly five months, into two groups: early and late experiments. Results seem to show that the efficacy of As2O3 45× is unaltered at 20 and 40°C, increases at 70°C and decreases at 100°C. As regards aging, a notable difference was found between early trials, with no significant efficacy, and late trials, where As2O3 45× exhibits a repeated significant effect versus control, except at 100°C. A reduction in variability was observed for As2O3 45× at 20°C versus control, confirming the findings of previous work. The main conclusion suggested by this experiment is that the efficacy of As2O3 45× on wheat germination may be influenced by heating degree and seems to have an increasing trend as a function of aging.
Left bundle branch block and mortality in patients with acute heart failure syndrome: a substudy of the EFICA cohort
Authors: Huvelle Etienne , Fay Renaud , Alla François , Cohen Solal Alain , Mebazaa Alexandre , Zannad Faiez
Published: December 2009

Aims

In patients with chronic heart failure (CHF), left bundle branch block (LBBB) is associated with an increased risk of cardiovascular mortality. We aimed to investigate the association of LBBB with short‐ and long‐term outcome in patients discharged after a de novo episode of acute heart failure (AHF) or AHF complicating a mild CHF.

Methods and results

Patients with no history of New York Heart Association class III and IV CHF, who were admitted for a severe AHF episode and enrolled in the prospective observational EFICA study (n = 403), were included. Left bundle branch block prevalence was 16%. Patients with LBBB had a higher prevalence of dilated cardiomyopathy (23 vs. 10%, P < 0.005), a higher percentage of AHF episodes without identified precipitating factor (15 vs. 2%, P < 0.001), and were less likely to present increased markers of cardiac injury (41 vs. 56%, P = 0.04). The 4‐week mortality was 24.8% with no difference between LBBB and no LBBB patients. Left bundle branch block was however an independent predictor of 1‐year mortality in the 4‐week survivors [hazards ratio (95% confidence interval) = 2.01 (1.12–3.64), P = 0.02].

Conclusion

Long‐term outcome of patients surviving a severe episode of de novo AHF or AHF complicating a mild CHF is worsened by LBBB. These patients may constitute a subgroup at high risk in whom specific therapeutic solutions should be investigated.
Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus
Authors: Javierre Biola M. , Fernandez Agustin F. , Richter Julia , Al-Shahrour Fatima , Martin-Subero J. Ignacio , Rodriguez-Ubreva Javier , Berdasco Maria , Fraga Mario F. , O'Hanlon Terrance P. , Rider Lisa G. , Jacinto Filipe V. , Lopez-Longo F. Javier , Dopazo Joaquin , Forn Marta , Peinado Miguel A. , Carreño Luis , Sawalha Amr H. , Harley John B. , Siebert Reiner , Esteller Manel , Miller Frederick W. , Ballestar Esteban
Published: December 2009

Monozygotic (MZ) twins are partially concordant for most complex diseases, including autoimmune disorders. Whereas phenotypic concordance can be used to study heritability, discordance suggests the role of non-genetic factors. In autoimmune diseases, environmentally driven epigenetic changes are thought to contribute to their etiology. Here we report the first high-throughput and candidate sequence analyses of DNA methylation to investigate discordance for autoimmune disease in twins. We used a cohort of MZ twins discordant for three diseases whose clinical signs often overlap: systemic lupus erythematosus (SLE), rheumatoid arthritis, and dermatomyositis. Only MZ twins discordant for SLE featured widespread changes in the DNA methylation status of a significant number of genes. Gene ontology analysis revealed enrichment in categories associated with immune function. Individual analysis confirmed the existence of DNA methylation and expression changes in genes relevant to SLE pathogenesis. These changes occurred in parallel with a global decrease in the 5-methylcytosine content that was concomitantly accompanied with changes in DNA methylation and expression levels of ribosomal RNA genes, although no changes in repetitive sequences were found. Our findings not only identify potentially relevant DNA methylation markers for the clinical characterization of SLE patients but also support the notion that epigenetic changes may be critical in the clinical manifestations of autoimmune disease.
Stress impairs optimal behavior in a water foraging choice task in rats
Authors: Graham Lauren K. , Yoon Taejib , Kim Jeansok J.
Published: December 2009

Stress is a biologically significant social–environmental factor that plays a pervasive role in influencing human and animal behaviors. While stress effects on various types of memory are well characterized, its effects on other cognitive functions are relatively unknown. Here, we investigated the effects of acute, uncontrollable stress on subsequent decision-making performance in rats, using a computer vision-based water foraging choice task. Experiencing stress significantly impaired the animals' ability to progressively bias (but not maintain) their responses toward the larger reward when transitioning from equal to unequal reward quantities. Temporary inactivation of the amygdala during stress, however, blocked impairing effects on decision making.
Object recognition memory and the rodent hippocampus
Authors: Broadbent Nicola J. , Gaskin Stephane , Squire Larry R. , Clark Robert E.
Published: December 2009

In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR task. Rats received 12 5-min exposures to two identical objects and then received either bilateral lesions of the hippocampus or sham surgery 1 d, 4 wk, or 8 wk after the final exposure. On a retention test 2 wk after surgery, the 1-d and 4-wk hippocampal lesion groups exhibited impaired object recognition memory. In contrast, the 8-wk hippocampal lesion group performed similarly to controls, and both groups exhibited a preference for the novel object. These same rats were then given four postoperative tests using unique object pairs and a 3-h delay between the exposure phase and the test phase. Hippocampal lesions produced moderate and reliable memory impairment. The results suggest that the hippocampus is important for object recognition memory.