bluuebunny/crossref_metadata_2025 huggingface dataset:
Signaling pathway of inflammatory responses in the mouse liver caused by TiO2 nanoparticles
Authors: Cui Yaling , Liu Huiting , Zhou Min , Duan Yanmei , Li Na , Gong Xiaolan , Hu Renping , Hong Mengmeng , Hong Fashui
Published: November 2010

In an effort to examine signaling pathway of inflammation of the mouse liver caused by intragastric administration of titanium dioxide nanoparticles (NPs), we assessed Toll‐like receptor‐2 (TLR2), TLR‐4, IκB kinase (IKK‐α, IKK‐β), IκB nucleic factor‐κB (NF‐κB), NF‐κBP52, NF‐κBP65, tumor necrosis factor‐α (TNF‐α), NF‐κB‐inducible kinase (NIK), interleukin‐2 (IL‐2), biochemical parameters of liver functions, and histopathological changes and liver ultrastructure in the TiO2 NPs‐treated mice. The results showed the titanium accumulation in liver, histopathological changes and hepatocytes apoptosis of mice liver, and the liver function damaged by TiO2 NPs. The real‐time quantitative reverse transcriptase polymerase chain reaction and enzyme‐linked immunosorbent assay analyses showed that TiO2 NPs can significantly increase the mRNA and protein expression of TLR2 and TLR4 and several inflammatory cytokines, including IKK1, IKK2, NF‐κB, NF‐κBP52, NF‐κBP65, TNF‐α, and NIK, and TiO2 NPs can significantly decrease the mRNA and protein expression of IκB and IL‐2. The results of this study added to our understanding of TiO2 NPs‐induced liver toxicity. It implied that the signaling pathway of liver injury in the TiO2 NPs‐stimulated mouse liver sequentially might occur via activation of TLRs→NIK→IκB kinase→NF‐κB→TNF‐α→inflammation→apoptosis→liver injury. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Fibronectin fragment activation of ERK increasing integrin α5 and β1 subunit expression to degenerate nucleus pulposus cells
Authors: Xia Maosheng , Zhu Yue
Published: November 2010

Fibronectin fragments (Fn‐f), which are the breakdown products of fibronectin, accumulate in the disc during degeneration and are proved to induce the degeneration of intervertebral disc. The goal of this investigation was to determine the functional role of integrin α5β1, extracellular signal‐regulated kinase (ERK), and protein kinase C (PKC) in the process of Fn‐f degeneration nucleus pulposus (NP) cells. We found that Fn‐f (100 nM, 30 kDa) exposure led to degeneration of NP cells, up‐regulation of integrin α5β1 expression and phosphorylation of the ERK1/2. After the expression of integrin α5β1 was silenced in NP cells, the phosphorylation of ERK1/2 and the expression of MMP9, MMP13, and collagen II had no difference with control under the treatment of Fn‐f. Finally, when the inhibitor of ERK1/2 and the inhibitor of PKC were added into the medium of NP cells; we found these two inhibitors could eliminate the effect of Fn‐f on NP cells. It is concluded that Fn‐f had the potential to enhance the NP cell degeneration in a vicious circle. And the integrin α5β1 subunit, ERK, and PKC were all included in this loop. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:556–561, 2011
Relative arithmetic
Authors: Sanders Sam
Published: November 2010

In nonstandard mathematics, the predicate ‘x is standard’ is fundamental. Recently, ‘relative’ or ‘stratified’ nonstandard theories have been developed in which this predicate is replaced with ‘x is y ‐standard’. Thus, objects are not (non)standard in an absolute sense, but (non)standard relative to other objects and there is a whole stratified universe of ‘levels’ or ‘degrees’ of standardness. Here, we study stratified nonstandard arithmetic and the related transfer principle. Using the latter, we obtain the ‘reduction theorem’ which states that arithmetical formulas can be reduced to equivalent bounded formulas. Surprisingly, the reduction theorem is also equivalent to the transfer principle. As applications, we obtain a truth definition for arithmetical sentences and we formalize Nelson's notion of impredicativity (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Refinement is equivalent to Fullness
Authors: Ziegler Albert
Published: November 2010

In the article [4], a new constructive set theoretic principle called Refinement was introduced and analysed. While it seemed to be significantly weaker than its alternative, the more established axiom of Fullness (a constructive version of the Powerset axiom from classical set theory), it was shown to suffice to imply many of the mathematically important consequences. In this article, we will define for each set A a set of truth values which measures the complexity of the equality relation on A. Using these sets we will show that Refinement is actually equivalent to Fullness on the basis of the other axioms of constructive Zermelo‐Fraenkel set theory (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Is advanced cancer associated with demoralization and lower global meaning? The role of tumor stage and physical problems in explaining existential distress in cancer patients
Authors: Vehling Sigrun , Lehmann Claudia , Oechsle Karin , Bokemeyer Carsten , Krüll Andreas , Koch Uwe , Mehnert Anja
Published: November 2010

Objective: This longitudinal study examines the extent to which global meaning, existential distress in terms of demoralization, and depression are predicted by tumor stage (UICC stages 0–II vs III/IV), palliative treatment, and physical problems in cancer patients.

 Methods: N = 270 cancer patients were studied at baseline (T1, response rate: 41%) and after 3 months (T2) (N = 178, 72%). The following standardized self‐report measures were used: Demoralization Scale, Life Attitude Profile—Revised, Hospital Anxiety and Depression Scale, NCCN DT (physical problems list).

 Results: Multivariate regression analyses controlling for sociodemographic variables showed the number of physical problems significantly predicting higher demoralization (β = 0.42, p<0.001) and depression (β = 0.34, p<0.001), but not global meaning. While palliative treatment intention was related to higher depression (β = 0.21, p = 0.03) and higher demoralization (ns), there was no effect of tumor stage on dependent variables. The hypothesized moderating effect of global meaning on the relation between physical problems and depression or demoralization, respectively, was not found.

 Conclusions: Results indicate a risk of existential distress in cancer patients across all disease stages, possibly due to confrontation with, albeit different, existential stressors throughout the illness. The general protective effect of global meaning against distress, independent of the number of physical problems, underscores the notion of existential concerns being relevant to cancer patients more generally, rather than just to a subgroup. However, physical problems might play a central role in the process of becoming demoralized through impairing the sense of mastery and competence. Findings finally strengthen the difference between the concepts of demoralization and global meaning. Copyright © 2010 John Wiley & Sons, Ltd.
Human thymidylate synthase with loop 181–197 stabilized in an inactive conformation: Ligand interactions, phosphorylation, and inhibition profiles
Authors: Luo BeiBei , Repalli Jayanthi , Yousef Al‐Motassem , Johnson Saphronia R. , Lebioda Lukasz , Berger Sondra H.
Published: November 2010

Thymidylate synthase (TS) is a well‐validated cancer target that undergoes conformational switching between active and inactive states. Two mutant human TS (hTS) proteins are predicted from crystal structures to be stabilized in an inactive conformation to differing extents, with M190K populating the inactive conformation to a greater extent than A191K. Studies of intrinsic fluorescence and circular dichroism revealed that the structures of the mutants differ from those of hTS. Inclusion of the substrate dUMP was without effect on M190K but induced structural changes in A191K that are unique, relative to hTS. The effect of strong stabilization in an inactive conformation on protein phosphorylation by casein kinase 2 (CK2) was investigated. M190K was highly phosphorylated by CK2 relative to an active‐stabilized mutant, R163K hTS. dUMP had no detectable effect on phosphorylation of M190K; however, dUMP inhibited phosphorylation of hTS and R163K. Studies of temperature dependence of catalysis revealed that the Eact and temperature optimum are higher for A191K than hTS. The potency of the active‐site inhibitor, raltitrexed, was lower for A191K than hTS. The response of A191K to the allosteric inhibitor, propylene diphosphonate (PDPA) was concentration dependent. Mixed inhibition was observed at low concentrations; at higher concentrations, A191K exhibited nonhyperbolic behavior with respect to dUMP and inhibition of catalysis was reversed by substrate saturation. In summary, inactive‐stabilized mutants differ from hTS in thermal stability and response to substrates and PDPA. Importantly, phosphorylation of hTS by CK2 is selective for the inactive conformation, providing the first indication of physiological relevance for conformational switching.
Prediction of ligand‐binding sites of proteins by molecular docking calculation for a random ligand library
Authors: Fukunishi Yoshifumi , Nakamura Haruki
Published: November 2010

A new approach to predicting the ligand‐binding sites of proteins was developed, using protein‐ligand docking computation. In this method, many compounds in a random library are docked onto the whole protein surface. We assumed that the true ligand‐binding site would exhibit stronger affinity to the compounds in the random library than the other sites, even if the random library did not include the ligand corresponding to the true binding site. We also assumed that the affinity of the true ligand‐binding site would be correlated to the docking scores of the compounds in the random library, if the ligand‐binding site was correctly predicted. We call this method the molecular‐docking binding‐site finding (MolSite) method. The MolSite method was applied to 89 known protein‐ligand complex structures extracted from the Protein Data Bank, and it predicted the correct binding sites with about 80–99% accuracy, when only the single top‐ranked site was adopted. In addition, the average docking score was weakly correlated to the experimental protein‐ligand binding free energy, with a correlation coefficient of 0.44.
Effect of lattice deformation on photoinduced phase transition process in RbMn[Fe(CN)6]
Authors: Fukaya R. , Nakajima M. , Tokoro H. , Ohkoshi S. , Suemoto T.
Published: November 2010

Structural transformation effect on a photoinduced (PI) charge‐transfer process leading to a phase transition in RbMn[Fe(CN)6], which exhibits a magnetic phase transition with a hysteresis loop between 230 and 300 K, has been investigated by Raman spectroscopy. The valence states of the transition metal ions and the lattice symmetry are reflected in the vibrational frequency of the adjacent CN ions. The charge‐transfer phase transition from the high‐temperature (HT) phase to low‐temperature (LT) phase can be induced by the photo‐excitation with 395 nm light in resonance with the ligand‐to‐metal charge transfer (LMCT) band. The conversion efficiency is lowered with decreasing temperature within the hysteresis loop. However, upon further lowering the temperature, the photo‐conversion restarts in the residual HT configuration units and domains around 50 K. The behavior is ascribed to the change of the potential curves in the excited electronic state due to the lattice deformation caused by the cubic‐to‐tetragonal phase transition in the surrounding lattice.
VAMAS interlaboratory study on organic depth profiling
Authors: Shard A. G. , Ray S. , Seah M. P. , Yang L.
Published: November 2010

We present the results of a VAMAS (Versailles project on Advanced Materials and Standards) interlaboratory study on organic depth profiling, in which twenty laboratories submitted data from a multilayer organic reference material. Individual layers were identified using a range of different sputtering species (C60n+, Cs+, SF5+ and Xe+), but in this study only the C60n+ ions were able to provide truly ‘molecular’ depth profiles from the reference samples. The repeatability of profiles carried out on three separate days by participants was shown to be excellent, with a number of laboratories obtaining better than 5% RSD (relative standard deviation) in depth resolution and sputtering yield, and better than 10% RSD in relative secondary ion intensities. Comparability between laboratories was also good in terms of depth resolution and sputtering yield, allowing useful relationships to be found between ion energy, sputtering yield and depth resolution. The study has shown that organic depth profiling results can, with care, be compared on a day‐to‐day basis and between laboratories. The study has also validated three approaches that significantly improve the quality of organic depth profiling: sample cooling, sample rotation and grazing angles of ion incidence. © Crown copyright 2010.
Small Upconverting Fluorescent Nanoparticles for Biomedical Applications
Authors: Chatterjee Dev K. , Gnanasammandhan Muthu Kumara , Zhang Yong
Published: November 2010

Fluorescent labels have been widely used for biological applications, primarily in imaging and assays. Traditional fluorophores such as fluorescent dyes are mainly based on downconversion fluorescence, which have several drawbacks such as photobleaching, high background noise from autofluorescence, and considerable photodamage to biological materials. Upconverting fluorescent nanoparticles emit detectable photons of higher energy in the near‐infrared (NIR) or visible range upon irradiation with an NIR light in a process termed ‘upconversion.’ They overcome some of the disadvantages faced by conventional downconversion labels, thus making them an ideal fluorescent label for biological applications. This review looks at the development of these particles, critically examines the reported applications, and discusses their future in biomedicine.
Estimating daily walking distance of captive African elephants using an accelerometer
Authors: Rothwell Emily S. , Bercovitch Fred B. , Andrews Jeff R.M. , Anderson Matthew J.
Published: November 2010

Two central concerns for elephant husbandry and management are whether zoological enclosures are appropriately sized and the degree to which naturalistic exercise and activity are observed in such enclosures. In order to address these issues, accurate data on the daily walking distance of elephants both in situ and ex situ are necessary. We used an accelerometer, a pedometer that measures step count and activity level, to estimate walking distance in African elephants (Loxodonta africana) at the San Diego Zoo's Wild Animal Park. The accelerometer was worn simultaneously with a GPS unit that recorded actual walking distance. Estimates of walking distance were extrapolated from the accelerometer and compared with actual distances determined by GPS data. The accelerometer was found to overestimate step count, and subsequently walking distance, by including false counts of steps. Extrapolating walking distance based upon stride length measurements did not match actual GPS walking distance. However, activity level output from the accelerometer significantly correlated with actual GPS walking distance. In addition, we report that the rate of movement is comparable to that reported in other zoological settings. We provide a linear regression equation that can be utilized by other institutions to estimate daily walking distance of elephants in their collection who are outfitted with accelerometers. Zoo Biol 30:579–591, 2011. © 2010 Wiley Periodicals, Inc.
Defining optimal treatment with cholinesterase inhibitors in Alzheimer's disease
Authors: Small Gary , Bullock Roger
Published: November 2010

Despite growing recognition that Alzheimer's disease (AD) represents a global public health and social care crisis, diagnosis is frequently slow and many patients still receive no treatment at all. Of those who do receive treatment, many remain on lower than recommended doses. The Alzheimer's disease International Global Charter promotes awareness and understanding of AD, stressing the importance of optimal treatment. However, the definition of “optimal treatment” is unclear. Since cholinesterase inhibitors became available nearly 20 years ago, clinicians have developed a variety of protocols on the basis of clinical experiences. This review considers what is optimal for several aspects of cholinesterase inhibitor therapy, taking into account initiation strategies, dosages, modes of drug delivery (e.g., oral vs. transdermal), and treatment durations. Regardless of management approach, individuals with AD, their families, and caregivers have a right to a timely diagnosis and access to best available treatment.
Boston (r): Neighbo(r)s nea(r) and fa(r)
Authors: Nagy Naomi , Irwin Patricia
Published: November 2010

The influence of linguistic and social factors on (r) in Boston and two New Hampshire towns is described. The preceding vowel and geographic, ethnic, and age-related differences were found to have strong effects. In comparison to Bostonians, New Hampshire speakers exhibit a higher rate of rhoticity, and fewer factors constrain their variability. Younger speakers are more rhotic than older speakers, as are more educated speakers and those in higher linguistic marketplace positions. This study demonstrates that these patterns fit the transmission (within Boston) and diffusion (to New Hampshire) framework (Labov, 2007) only with the addition of accommodation theory (Niedzielski & Giles, 1996), which connects our linguistic findings to evidence that many New Hampshire residents do not identify with Boston. The effects on (r) in other studies are compared to determine which effects are particular to individual communities (nonuniversal) and which occur across all communities examined. The nonuniversal effects are therefore available as measures of contact-induced change. This study introduces a method for quantitatively comparing the amount of change between communities.
Is Standard Dutch with a regional accent standard or not? Evidence from native speakers' attitudes
Authors: Grondelaers Stefan , van Hout Roeland
Published: November 2010

This paper reports a speaker evaluation experiment that investigated the competition between three regional accents of Standard Dutch and references to the speaker's profession as determinants of attitude formation. A stratified sample of listener-judges rated speech stimuli that were presented in two guises, a neutral guise and a teacher guise (the latter containing multiple references that revealed the speaker to be a high school teacher of Dutch). The experimental findings corroborate our earlier claim that regional flavoring is embedded in lay conceptualizations of Standard Dutch. Although teachers of Dutch may be the last “gatekeepers” of the standard in the Low Countries, they are not automatically downgraded when they have a regional accent: What matters is, clearly,whichaccent they have. Analysis of the ratings further suggests a hierarchical relation between accent and occupation as perception triggers: Even though regional accent clearly is the stronger attitude determinant, it does not suppress occupational information but interacts with it to generate richer social meaning.
A Reassessment of the Chronology and Function of Gordon's Cave #3, Copan, Honduras
Authors: Brady James E.
Published: November 2010

Recent excavations in the first chamber of Gordon's Cave #3 encountered a use floor with a substantial quantity of sherds and artifacts. Middle Preclassic, Gordon subphase sherds were recovered, but overall the ceramics suggest that Preclassic use of the cave was minor with the most intensive use occurring during the Classic period. The artifact assemblage provides a fuller picture of cave rituals which appear to be similar in many respects to those practiced by modern groups in the Guatemalan highlands.
Naïve blood monocytes suppress T‐cell function. A possible mechanism for protection from autoimmunity
Authors: Slaney Clare Y , Toker Aras , La Flamme Anne , Bäckström B Thomas , Harper Jacquie L
Published: November 2010

In certain disease context, cells of the monocyte/macrophage lineage are known to exhibit T‐cell suppressor function. However, whether naïve monocytes are also able to suppress T‐cell responses has not been previously investigated. In this study, we have discovered that CD11b+Ly6G− mononuclear cells in the blood of naïve mice are potent suppressors of T‐cell proliferation in vitro. The suppression of T‐cell proliferation requires cell‐cell contact and is partially dependent on nitric oxide production. Following the induction of experimental autoimmune encephalomyelitis in mice, the suppressor function of this blood CD11b+Ly6G− cell population is impaired. Therefore, blood CD11b+Ly6G− cells appear to be intrinsically suppressive and may have a key role in maintaining immune homoeostasis. Loss of this suppressive function may contribute to development of autoimmunity.
Shaping the T‐cell repertoire: a matter of life and death
Authors: Wiegers G Jan , Kaufmann Manuel , Tischner Denise , Villunger Andreas
Published: November 2010

Thymocyte selection aims to shape a T‐cell repertoire that, on the one hand, is able to recognize and respond to foreign peptides and, on the other hand, tolerizes the presence of self‐peptides in the periphery. Deletion of T cells or their precursors that fail to fulfill these criteria is mainly mediated by the Bcl‐2‐regulated apoptosis pathway. Absence of T‐cell receptor (TCR)‐mediated signals or hyperactivation of the TCR by high‐affinity self‐peptide‐major histocompatibility complexes can both trigger apoptotic cell death in developing thymocytes. Notably, TCR‐signaling strength also defines survival and outgrowth of the fittest antigen‐specific T‐cell clones in the periphery. TCR threshold activity leading to such drastically opposing signaling outcomes (life or death) is modulated in part by cytokines and other factors, such as glucocorticoids, that fine‐tune the Bcl‐2 rheostat, thereby impacting on cell survival. This review aims to highlight the role of Bcl‐2‐regulated cell death for clonal T‐cell selection.
Toward spectroscopic accuracy for open-shell systems: Molecular structure and hyperfine coupling constants of H2CN, H2CP, NH2, and PH2 as test cases
Authors: Puzzarini Cristina , Barone Vincenzo
Published: November 2010

In the present paper, we investigate the molecular structure and hyperfine couplings of a series of σ radicals containing first- and second-row atoms (H2CN,H2CP,NH2,PH2) for which accurate gas-phase microwave results are available. The presence of α- and, especially, β-hydrogen atoms makes the evaluation of magnetic properties of these radicals particularly challenging. Geometrical parameters have been computed by the coupled-cluster ansatz in conjunction with hierarchical series of basis sets, thus accounting for extrapolation to the complete basis-set limit. Core correlation as well as higher excitations in the electronic-correlation treatment have also been taken into account. An analogous approach has been employed for evaluating hyperfine coupling constants with particular emphasis given to basis-set, correlation, and geometrical effects. The corresponding vibrational corrections, required for a meaningful comparison to experimental data, have also been investigated. The remarkable agreement with experiment confirms the reliability of the present computational approach, already validated for π radicals, thus establishing the way for setting up a benchmark database for magnetic properties.
Numerical simulations of nonlinear thermally stratified spin-up in a circular cylinder
Authors: Smirnov Sergey A. , Pacheco J. Rafael , Verzicco Roberto
Published: November 2010

We present a numerical study of incremental spin-up of a thermally stratified fluid enclosed within a right circular cylinder with rigid bottom and side walls and stress-free upper surface. This investigation reveals a feasibility for transition from an axisymmetric initial circulation to nonaxisymmetric flow patterns, and it is motivated by the desire to compare the spin-up for Dirichlet and Neumann thermal boundary conditions. The numerical simulations demonstrate that the destabilizing mechanism is not purely baroclinic but that vertical and horizontal shears may contribute to the instability. By characterizing the azimuthal instabilities without introducing any simplification, we were able to assess to what extent an insulating boundary condition changes the time-dependent emergence of the instability. Our results agree with previous experimental data and provide a framework for understanding the role played by the baroclinic vorticity in the development of instabilities in thermally stratified incremental spin-up flows.
HIV super-infection beliefs and sexual practices of people living with HIV/AIDS
Authors: Kalichman Seth C. , Eaton Lisa , Cherry Chauncey , Kalichman Moira O. , Pope Howard , White Denise , Amaral Christina M. , Swetzes Connie , Macy Rene
Published: November 2010

Background: People living with HIV can be reinfected with a new viral strain resulting in potential treatment resistant recombinant virus known as HIV super-infection. Individual’s beliefs about the risks for HIV super-infection may have significant effects on the sexual behaviours of people living with HIV/AIDS. HIV super-infection beliefs and sexual behaviours among people living with HIV/AIDS were examined in the present study. Methods: Three hundred and twenty men, 137 women, and 33 transgender persons completed confidential surveys in a community research setting. Results: A majority of participants were aware of HIV super-infection and most believed it was harmful to their health. Hierarchical multiple regressions predicting protected anal/vaginal intercourse with same HIV status (seroconcordant) partners showed that older age and less alcohol use were associated with greater protected sex. In addition, HIV super-infection beliefs predicted protected sexual behaviour over and above participant age and alcohol use. Conclusions: Beliefs about HIV super-infection exert significant influence on sexual behaviours of people living with HIV/AIDS and should be targeted in HIV prevention messages for HIV infected persons.
Pleasurable behaviors reduce stress via brain reward pathways
Authors: Ulrich-Lai Yvonne M. , Christiansen Anne M. , Ostrander Michelle M. , Jones Amanda A. , Jones Kenneth R. , Choi Dennis C. , Krause Eric G. , Evanson Nathan K. , Furay Amy R. , Davis Jon F. , Solomon Matia B. , de Kloet Annette D. , Tamashiro Kellie L. , Sakai Randall R. , Seeley Randy J. , Woods Stephen C. , Herman James P.
Published: November 2010

Individuals often eat calorically dense, highly palatable “comfort” foods during stress for stress relief. This article demonstrates that palatable food intake (limited intake of sucrose drink) reduces neuroendocrine, cardiovascular, and behavioral responses to stress in rats. Artificially sweetened (saccharin) drink reproduces the stress dampening, whereas oral intragastric gavage of sucrose is without effect. Together, these results suggest that the palatable/rewarding properties of sucrose are necessary and sufficient for stress dampening. In support of this finding, another type of natural reward (sexual activity) similarly reduces stress responses. Ibotenate lesions of the basolateral amygdala (BLA) prevent stress dampening by sucrose, suggesting that neural activity in the BLA is necessary for the effect. Moreover, sucrose intake increases mRNA and protein expression in the BLA for numerous genes linked with functional and/or structural plasticity. Lastly, stress dampening by sucrose is persistent, which is consistent with long-term changes in neural activity after synaptic remodeling. Thus, natural rewards, such as palatable foods, provide a general means of stress reduction, likely via structural and/or functional plasticity in the BLA. These findings provide a clearer understanding of the motivation for consuming palatable foods during times of stress and influence therapeutic strategies for the prevention and/or treatment of obesity and other stress-related disorders.
tRNA
His
guanylyltransferase (THG1), a unique 3′-5′ nucleotidyl transferase, shares unexpected structural homology with canonical 5′-3′ DNA polymerases
Authors: Hyde Samantha J. , Eckenroth Brian E. , Smith Brian A. , Eberley William A. , Heintz Nicholas H. , Jackman Jane E. , Doublié Sylvie
Published: November 2010

All known DNA and RNA polymerases catalyze the formation of phosphodiester bonds in a 5′ to 3′ direction, suggesting this property is a fundamental feature of maintaining and dispersing genetic information. The tRNA
His
guanylyltransferase (Thg1) is a member of a unique enzyme family whose members catalyze an unprecedented reaction in biology: 3′-5′ addition of nucleotides to nucleic acid substrates. The 2.3-Å crystal structure of human THG1 (hTHG1) reported here shows that, despite the lack of sequence similarity, hTHG1 shares unexpected structural homology with canonical 5′-3′ DNA polymerases and adenylyl/guanylyl cyclases, two enzyme families known to use a two-metal-ion mechanism for catalysis. The ability of the same structural architecture to catalyze both 5′-3′ and 3′-5′ reactions raises important questions concerning selection of the 5′-3′ mechanism during the evolution of nucleotide polymerases.
Postdetonation nuclear debris for attribution
Authors: Fahey A. J. , Zeissler C. J. , Newbury D. E. , Davis J. , Lindstrom R. M.
Published: November 2010

On the morning of July 16, 1945, the first atomic bomb was exploded in New Mexico on the White Sands Proving Ground. The device was a plutonium implosion device similar to the device that destroyed Nagasaki, Japan, on August 9 of that same year. Recently, with the enactment of US public law 111-140, the “Nuclear Forensics and Attribution Act,” scientists in the government and academia have been able, in earnest, to consider what type of forensic-style information may be obtained after a nuclear detonation. To conduct a robust attribution process for an exploded device placed by a nonstate actor, forensic analysis must yield information about not only the nuclear material in the device but about other materials that went into its construction. We have performed an investigation of glassed ground debris from the first nuclear test showing correlations among multiple analytical techniques. Surprisingly, there is strong evidence, obtainable only through microanalysis, that secondary materials used in the device can be identified and positively associated with the nuclear material.
Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth
Authors: Rogan Mark P. , Reznikov Leah R. , Pezzulo Alejandro A. , Gansemer Nicholas D. , Samuel Melissa , Prather Randall S. , Zabner Joseph , Fredericks Douglas C. , McCray Paul B. , Welsh Michael J. , Stoltz David A.
Published: November 2010

People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation. We found that, like humans, CF pigs were smaller than non-CF littermates and had lower IGF1 levels. To better understand the basis of IGF1 reduction, we studied newborn pigs and found low IGF1 levels within 12 h of birth. Moreover, humerus length and bone mineral content were decreased, consistent with less IGF1 activity in utero. These findings led us to test newborn humans with CF, and we found that they also had reduced IGF1 levels. Discovering lower IGF1 levels in newborn pigs and humans indicates that the decrease is not solely a consequence of malnutrition or pulmonary inflammation and that loss of cystic fibrosis transmembrane conductance regulator function has a more direct effect. Consistent with this hypothesis, we discovered reduced growth hormone release in organotypic pituitary slice cultures of newborn CF pigs. These findings may explain the long-standing observation that CF newborns are smaller than non-CF babies and why some patients with good clinical status fail to reach their growth potential. The results also suggest that measuring IGF1 levels might be of value as a biomarker to predict disease severity or the response to therapeutics. Finally, they raise the possibility that IGF1 supplementation beginning in infancy might be beneficial in CF.
microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus
Authors: Magill Stephen T. , Cambronne Xiaolu A. , Luikart Bryan W. , Lioy Daniel T. , Leighton Barbara H. , Westbrook Gary L. , Mandel Gail , Goodman Richard H.
Published: November 2010

Newborn neurons in the dentate gyrus of the adult hippocampus rely upon cAMP response element binding protein (CREB) signaling for their differentiation into mature granule cells and their integration into the dentate network. Among its many targets, the transcription factor CREB activates expression of a gene locus that produces two microRNAs, miR-132 and miR-212. In cultured cortical and hippocampal neurons, miR-132 functions downstream from CREB to mediate activity-dependent dendritic growth and spine formation in response to a variety of signaling pathways. To investigate whether miR-132 and/or miR-212 contribute to the maturation of dendrites in newborn neurons in the adult hippocampus, we inserted LoxP sites surrounding the miR-212/132 locus and specifically targeted its deletion by stereotactically injecting a retrovirus expressing Cre recombinase. Deletion of the miR-212/132 locus caused a dramatic decrease in dendrite length, arborization, and spine density. The miR-212/132 locus may express up to four distinct microRNAs, miR-132 and -212 and their reverse strands miR-132* and -212*. Using ratiometric microRNA sensors, we determined that miR-132 is the predominantly active product in hippocampal neurons. We conclude that miR-132 is required for normal dendrite maturation in newborn neurons in the adult hippocampus and suggest that this microRNA also may participate in other examples of CREB-mediated signaling.
Society, polity, and language community
Authors: Silverstein Michael
Published: November 2010

How do the social institutional agglomerations we call societies interact with levels of political groupness up to and including states and beyond? In the modern First World and more widely, the post-Lockean Enlightenment has brought denotational language itself to the fore as the salient vehicle of mediation — presumed upon by theorists as well as by politicians — by which stable polities have depended upon the existence of social institutions of various sorts. Reciprocally, such mediation has underlain ideological consciousness of what a language community should normatively be like, to wit, a polity-in-potentia able to assert “language rights” in a politics of recognition in a wider social order. This political culture has shaped some of the more salient forces on language communities within the social institutional order of complex, plurilingual speech communities in which people actually live.
Hsp70 gene association with nuclear speckles is Hsp70 promoter specific
Authors: Hu Yan , Plutz Matt , Belmont Andrew S.
Published: November 2010

Many mammalian genes localize near nuclear speckles, nuclear bodies enriched in ribonucleic acid–processing factors. In this paper, we dissect cis-elements required for nuclear speckle association of the heat shock protein 70 (Hsp70) locus. We show that speckle association is a general property of Hsp70 bacterial artificial chromosome transgenes, independent of the chromosome integration site, and can be recapitulated using a 2.8-kilobase HSPA1A gene fragment. Association of Hsp70 transgenes and their transcripts with nuclear speckles is transcription dependent, independent of the transcribed sequence identity, but dependent on the Hsp70 promoter sequence. Transgene speckle association does not correlate with the amount of transcript accumulation, with large transgene arrays driven by different promoters showing no speckle association, but smaller Hsp70 transgene arrays with lower transcript accumulation showing high speckle association. Moreover, despite similar levels of transcript accumulation, Hsp70 transgene speckle association is observed after heat shock but not cadmium treatment. We suggest that certain promoters may direct specific chromatin and/or transcript ribonucleoprotein modifications, leading to nuclear speckle association.
Flotillin microdomains interact with the cortical cytoskeleton to control uropod formation and neutrophil recruitment
Authors: Ludwig Alexander , Otto Grant P. , Riento Kirsi , Hams Emily , Fallon Padraic G. , Nichols Ben J.
Published: November 2010

We studied the function of plasma membrane microdomains defined by the proteins flotillin 1 and flotillin 2 in uropod formation and neutrophil chemotaxis. Flotillins become concentrated in the uropod of neutrophils after exposure to chemoattractants such as N-formyl-Met-Leu-Phe (fMLP). Here, we show that mice lacking flotillin 1 do not have flotillin microdomains, and that recruitment of neutrophils toward fMLP in vivo is reduced in these mice. Ex vivo, migration of neutrophils through a resistive matrix is reduced in the absence of flotillin microdomains, but the machinery required for sensing chemoattractant functions normally. Flotillin microdomains specifically associate with myosin IIa, and spectrins. Both uropod formation and myosin IIa activity are compromised in flotillin 1 knockout neutrophils. We conclude that the association between flotillin microdomains and cortical cytoskeleton has important functions during neutrophil migration, in uropod formation, and in the regulation of myosin IIa.
The class IA phosphatidylinositol 3-kinase p110-β subunit is a positive regulator of autophagy
Authors: Dou Zhixun , Chattopadhyay Mohar , Pan Ji-An , Guerriero Jennifer L. , Jiang Ya-Ping , Ballou Lisa M. , Yue Zhenyu , Lin Richard Z. , Zong Wei-Xing
Published: November 2010

Autophagy is an evolutionarily conserved cell renewal process that depends on phosphatidylinositol 3-phosphate (PtdIns(3)P). In metazoans, autophagy is inhibited by PtdIns(3,4,5)P3, the product of class IA PI3Ks, which mediates the activation of the Akt–TOR kinase cascade. However, the precise function of class IA PI3Ks in autophagy remains undetermined. Class IA PI3Ks are heterodimeric proteins consisting of an 85-kD regulatory subunit and a 110-kD catalytic subunit. Here we show that the class IA p110-β catalytic subunit is a positive regulator of autophagy. Genetic deletion of p110-β results in impaired autophagy in mouse embryonic fibroblasts, liver, and heart. p110-β does not promote autophagy by affecting the Akt–TOR pathway. Rather, it associates with the autophagy-promoting Vps34–Vps15–Beclin 1–Atg14L complex and facilitates the generation of cellular PtdIns(3)P. Our results unveil a previously unknown function for p110-β as a positive regulator of autophagy in multicellular organisms.
Lack of the purinergic receptor P2X7 results in resistance to contact hypersensitivity
Authors: Weber Felix C. , Esser Philipp R. , Müller Tobias , Ganesan Jayanthi , Pellegatti Patrizia , Simon Markus M. , Zeiser Robert , Idzko Marco , Jakob Thilo , Martin Stefan F.
Published: November 2010

Sensitization to contact allergens requires activation of the innate immune system by endogenous danger signals. However, the mechanisms through which contact allergens activate innate signaling pathways are incompletely understood. In this study, we demonstrate that mice lacking the adenosine triphosphate (ATP) receptor P2X7 are resistant to contact hypersensitivity (CHS). P2X7-deficient dendritic cells fail to induce sensitization to contact allergens and do not release IL-1β in response to lipopolysaccharide (LPS) and ATP. These defects are restored by pretreatment with LPS and alum in an NLRP3- and ASC-dependent manner. Whereas pretreatment of wild-type mice with P2X7 antagonists, the ATP-degrading enzyme apyrase or IL-1 receptor antagonist, prevents CHS, IL-1β injection restores CHS in P2X7-deficient mice. Thus, P2X7 is a crucial receptor for extracellular ATP released in skin in response to contact allergens. The lack of P2X7 triggering prevents IL-1β release, which is an essential step in the sensitization process. Interference with P2X7 signaling may be a promising strategy for the prevention of allergic contact dermatitis.
Silencing of Host Basal Defense Response-Related Gene Expression Increases Susceptibility of Nicotiana benthamiana to Clavibacter michiganensis subsp. michiganensis
Authors: Balaji Vasudevan , Sessa Guido , Smart Christine D.
Published: November 2010

Clavibacter michiganensis subsp. michiganensis is an actinomycete, causing bacterial wilt and canker disease of tomato (Solanum lycopersicum). We used virus-induced gene silencing (VIGS) to identify genes playing a role in host basal defense response to C. michiganensis subsp. michiganensis infection using Nicotiana benthamiana as a model plant. A preliminary VIGS screen comprising 160 genes from tomato known to be involved in defense-related signaling identified a set of 14 genes whose suppression led to altered host–pathogen interactions. Expression of each of these genes and three additional targets was then suppressed in larger-scale VIGS experiments and the effect of silencing on development of wilt disease symptoms and bacterial growth during an N. benthamiana–C. michiganensis subsp. michiganensis compatible interaction was determined. Disease susceptibility and in planta bacterial population size were enhanced by silencing genes encoding N. benthamiana homologs of ubiquitin activating enzyme, snakin-2, extensin-like protein, divinyl ether synthase, 3-hydroxy-3-methylglutaryl-coenzyme A reductase 2, and Pto-like kinase. The identification of genes having a role in the host basal defense-response to C. michiganensis subsp. michiganensis advances our understanding of the plant responses activated by C. michiganensis subsp. michiganensis and raises possibilities for devising novel and effective molecular strategies to control bacterial canker and wilt in tomato.
Menthol and non‐menthol smoking: the impact of prices and smoke‐free air laws
Authors: Tauras John A. , Levy David , Chaloupka Frank J. , Villanti Andrea , Niaura Raymond S. , Vallone Donna , Abrams David B.
Published: November 2010

Aims  To examine the relationship between menthol and non‐menthol prices and smoke‐free air laws and the choice between menthol and non‐menthol cigarettes among current smokers.

Design, setting and participants  Data were extracted from the nationally representative (USA) 2003 and 2006/07 Tobacco Use Supplements to the Current Population Survey. A total of 57 383 adult smokers (aged 18+) were examined.

Measurements  A regression model was used to estimate the probability of being a menthol smoker conditional on being a current smoker who had a distinct preference for either non‐menthol or menthol cigarettes. Cigarette prices, smoke‐free air laws and socio‐economic and demographic characteristics were examined as covariates.

Findings  The prices of menthol and non‐menthol cigarettes were associated with the choice between menthol and non‐menthol cigarettes. However, smokers did not find menthol and non‐menthol cigarettes to be close substitutes for one another. Non‐menthol cigarettes were found to be less of a substitute for menthol cigarettes than vice versa. Young adults and African Americans were less responsive to prices with respect to switching between menthol and non‐menthol cigarettes than were older adults and non‐African Americans, respectively.

Conclusions  The US Food and Drug Administration (FDA) is grappling with the issue of whether or not to ban menthol cigarettes. The findings from this study suggest that smokers do not find menthol and non‐menthol cigarettes to be close substitutes. The strong preference for mentholated cigarettes may serve as a lever to reduce smoking prevalence when combined with increased access to effective cessation treatments.
Trends in eczema in the first 18 years of life: results from the Isle of Wight 1989 birth cohort study
Authors: Ziyab A. H. , Raza A. , Karmaus W. , Tongue N. , Zhang H. , Matthews S. , Arshad S. H. , Roberts G.
Published: November 2010

Background
Trends in the prevalence of eczema in the course of childhood and adolescence are not clear although often a net remission during childhood is assumed.

Objectives
To investigate the dynamics of change in eczema from 1 to 18 years in a prospective study and to understand the influence of gender and atopy.

Methods
Detailed information regarding eczema were collected at ages 1, 2, 4, 10 and 18 years from the 1989 Isle of Wight birth cohort (n=1456). Skin prick testing was performed at 4, 10 and 18 years of age. The 12‐month period prevalence, positive and negative transitions (defined as change in disease status in two consecutive study assessments) were stratified by gender and atopic status.

Results
The period prevalence of eczema from birth to 18 years of age remained relatively constant (11.9–14.2%) with minimal remission. Up to 10 years of age, gender did not influence prevalence. From 10 to 18 years, eczema became more prevalent among girls (16.3% for girls vs. 8.3% for boys, P<0.001) as a result of a greater positive transition in girls (9.4% for girls vs. 4.3% for boys, P=0.001) and greater negative transition in boys (65.4% for boys vs. 50% for girls, P=0.04). The higher positive transition of eczema in girls was most pronounced for non‐atopic eczema (5.9% for girls vs. 1.5% for boys, P=0.002).

Conclusions
We found only a minimal reduction in the prevalence of eczema during childhood and adolescence. During adolescence, more girls develop eczema and more boys outgrow it suggesting a role for gender‐specific pubertal factors.

Cite this as: A. H. Ziyab, A. Raza, W. Karmaus, N. Tongue, H. Zhang, S. Matthews, S. H. Arshad and G. Roberts, Clinical & Experimental Allergy, 2010 (40) 1776–1784.
Evening circadian oscillator as the primary determinant of rhythmic motivation for Drosophila courtship behavior
Authors: Hamasaka Yasutaka , Suzuki Takahiro , Hanai Shuji , Ishida Norio
Published: November 2010

Circadian clocks of Drosophila melanogaster motivate males to court females at a specific time of day. However, clock neurons involved in courtship rhythms in the brain of Drosophila remain totally unknown. The circadian locomotor behavior of Drosophila is controlled by morning (M cells) and evening (E cells) cells in the brain, which regulate morning and evening activities, respectively. Here, we identified the brain clock neurons that are responsible for the circadian rhythms of the close‐proximity (CP) behavior that reflects male courtship motivation. Interestingly, the ablation or functional molecular clock disruption of E cells caused arrhythmic CP behavior, but that of M cells resulted in sustained CP rhythms even in constant darkness. In addition, the ablation of some dorsal lateral neurons (LNd) of E cells using neuropeptide‐F (NPF)‐GAL4 did not impair CP rhythms. These findings suggested that the NPF‐negative LNds and DN1s of E cells include cells essential for circadian CP behavior in Drosophila.