bluuebunny/crossref_metadata_2025 huggingface dataset:
D(NA) Coding the Ethnic: Jeffrey Eugenides'sMiddlesex
Authors: Chu Patricia E.
Published: October 2009

This essay discusses Jeffrey Eugenides's novel Middlesex as a project in the American immigrant tradition, about the (self) making of its protagonist. The project is narrative (Callie/Cal is the narrator, even of things that happened before she/he was born), biological (Cal must negotiate the determinism of the DNA that gives him the condition of hermaphroditism), economic (the family fortunes sit precariously atop Detroit in the 1970s), racial (the immigrants “become white”), and cultural (she/he is Greek American). The novel uses new biological epistemologies to alleviate both anxiety about determinism and, paradoxically, anxiety about lack of clear identities, a tug of war that is of course intrinsic to American ethnic literature. Eugenides could be said to recoup the old American immigrant novel promising self-making within the political context of a city of race riots and a declining manufacturing economy. The new biology allows Cal to imagine his condition and his conditions of narration as those of plenitude (like those of Tiresias). He can narrate through his grandparents' and parents' mouths—literally make himself—as he recounts the night his parents conceived him. The “ancient Greek notion,” the old-world notion of “fate,” is akin to the racial determinism of the nineteenth century. The new genomic biology allows for excessive narrative and free will. Any analysis of the implications of Eugenides's narrative strategies should be as multifaceted and nuanced as the strategies themselves, particularly in light of other post-1990s developments in Asian American and African American literature. The renewal of the white immigrant saga in the era of the genome certainly bears both aesthetic and political analysis.
History, the Twentieth Century, and a Contemporary Novel
Authors: DeKoven Marianne
Published: October 2009

The term history gathers to itself, and disperses, as troubled and complex a nexus of theory, ideology and practice as any term in our critical vocabulary. Yet I argue here that this term is as inevitable and necessary as it is problematic, especially in discussions of the novel. For me there is no question that shifts in novelistic form are enabled by (and constitutive of) specific historical conjunctures, understood within a notion of contemporaneous historical formations. In order to understand what has made possible certain novelistic forms that are either dominant or culturally powerful at any given historical moment, it is necessary to look at the culture surrounding the production of that novel, and to do so in a way that takes into account the historical conditions that produced or made possible that particular cultural configuration. The modernist novel was perfectly ambivalent about the threat or promise of what Perry Anderson has called “the revolutionary horizon” visible at the turn into the twentieth century. In a contemporary, postmodern, historical novel such as Thomas Pynchon's Against the Day, history is what Pynchon calls “time's pathology”—a pathology whose symptoms and pain can perhaps be managed, if not cured.
Remembering Benjamin from South of the Pyrenees: The Two-Gauge Problem
Authors: Valverde Mariana
Published: October 2009

This essay is a personal reflection on the absence of the Spanish civil war refugees from the cultured public's collective memory of the place where Walter Benjamin died.
Complexio Oppositorum: Notes on the Left in Neoliberal Italy
Authors: Muehlebach Andrea
Published: October 2009

The contemporary situation is seldom best characterized as a battlefield with clearly drawn political dividing lines. In fact, neoliberalism is often better understood as a form to contain the oppositional—old leftist solidarity and new rightist utopias—and fold them into a single moral order: a complexio oppositorum, in Carl Schmitt's words.
Secular Populism and the Semiotics of the Crowd in Turkey
Authors: Tambar Kabir
Published: October 2009

In much of the Muslim world, secularization has proceeded through the modernizing mechanisms of the region's various states. By contrast, social movements committed to the (re)introduction of religion into public and political life have frequently functioned through appeals to the popular will. Recent political events in Turkey present a dramatic contrast to this historically established antagonism between secularization and populist politics. In the spring of 2007 a series of mass demonstrations, rallied in the name of secularism and against the elected Islamist regime, were conducted in several of Turkey's major urban centers. The figure of the secularist crowd provides an image of secularism grounded not in the coercive apparatuses of the military and the modernizing bureaucracy but in an assertion of populism. This article explores the tentative formation of a secular populism. I argue that this particular conjuncture not only displays the persistent contradictions that subtend the relationship between secularism and populist politics but also reveals the tensions that sustain the field of democratic politics in Turkey.
Nicotinamidase modulation of NAD+ biosynthesis and nicotinamide levels separately affect reproductive development and cell survival inC. elegans
Authors: Vrablik Tracy L. , Huang Li , Lange Stephanie E. , Hanna-Rose Wendy
Published: October 2009

Nicotinamide adenine dinucleotide (NAD+) is a central molecule in cellular metabolism and an obligate co-substrate for NAD+-consuming enzymes, which regulate key biological processes such as longevity and stress responses. Although NAD+ biosynthesis has been intensely studied, little analysis has been done in developmental models. We have uncovered novel developmental roles for a nicotinamidase(PNC), the first enzyme in the NAD+ salvage pathway of invertebrates. Mutations in the Caenorhabditis elegans nicotinamidase PNC-1 cause developmental and functional defects in the reproductive system;the development of the gonad is delayed, four uterine cells die by necrosis and the mutant animals are egg-laying defective. The temporal delay in gonad development results from depletion of the salvage pathway product NAD+, whereas the uv1 cell necrosis and egg-laying defects result from accumulation of the substrate nicotinamide. Thus, regulation of both substrate and product level is key to the biological activity of PNC-1. We also find that diet probably affects the levels of these metabolites, as it affects phenotypes. Finally, we identified a secreted isoform of PNC-1 and confirmed its extracellular localization and functional activity in vivo. We demonstrate that nicotinamide phosphoribosyltransferase (Nampt), the equivalent enzyme in nicotinamide recycling to NAD+ in vertebrates,can functionally substitute for PNC-1. As Nampt is also secreted, we postulate an evolutionarily conserved extracellular role for NAD+biosynthetic enzymes during development and physiology.
Regulation of podosome dynamics by WASp phosphorylation: implication in matrix degradation and chemotaxis in macrophages
Authors: Dovas Athanassios , Gevrey Jean-Claude , Grossi Alberto , Park Haein , Abou-Kheir Wassim , Cox Dianne
Published: October 2009

Podosomes, adhesion structures capable of matrix degradation, have been linked with the ability of cells to perform chemotaxis and invade tissues. Wiskott-Aldrich Syndrome protein (WASp), an effector of the RhoGTPase Cdc42 and a Src family kinase substrate, regulates macrophage podosome formation. In this study, we demonstrate that WASp is active in podosomes by using TIRF-FRET microscopy. Pharmacological and RNA interference approaches suggested that continuous WASp activity is required for podosome formation and function. Rescue experiments using point mutations demonstrate an absolute requirement for Cdc42 binding to WASp in podosome formation. Although tyrosine phosphorylation was not absolutely required for podosome formation, phosphorylation did regulate the rate of podosome nucleation and actin filament stability. Importantly, WASp tyrosine phosphorylation does not alter WASp activation, instead phosphorylation appears to be important for the restriction of WASp activity to podosomes. In addition, the matrix-degrading ability of cells requires WASp phosphorylation. Chemotactic responses to CSF-1 were also attenuated in the absence of endogenous WASp, which could not be rescued with either tyrosine mutation. These results suggest a more complex role for tyrosine phosphorylation than simply in the regulation of WASp activity, and suggest a link between podosome dynamics and macrophage migration.
Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding
Authors: Goldyn Alexandra M. , Rioja Borja Aragüés , Spatz Joachim P. , Ballestrem Christoph , Kemkemer Ralf
Published: October 2009

Mechanical forces play a crucial role in controlling the integrity and functionality of cells and tissues. External forces are sensed by cells and translated into signals that induce various responses. To increase the detailed understanding of these processes, we investigated cell migration and dynamic cellular reorganisation of focal adhesions and cytoskeleton upon application of cyclic stretching forces. Of particular interest was the role of microtubules and GTPase activation in the course of mechanotransduction. We showed that focal adhesions and the actin cytoskeleton undergo dramatic reorganisation perpendicular to the direction of stretching forces even without microtubules. Rather, we found that microtubule orientation is controlled by the actin cytoskeleton. Using biochemical assays and fluorescence resonance energy transfer (FRET) measurements, we revealed that Rac1 and Cdc42 activities did not change upon stretching, whereas overall RhoA activity increased dramatically, but independently of intact microtubules. In conclusion, we demonstrated that key players in force-induced cellular reorganisation are focal-adhesion sliding, RhoA activation and the actomyosin machinery. In contrast to the importance of microtubules in migration, the force-induced cellular reorganisation, including focal-adhesion sliding, is independent of a dynamic microtubule network. Consequently, the elementary molecular mechanism of cellular reorganisation during migration is different to the one in force-induced cell reorganisation.
Mouse oviduct-specific glycoprotein is an egg-associated ZP3-independent sperm-adhesion ligand
Authors: Lyng Robert , Shur Barry D.
Published: October 2009

Mouse sperm-egg binding requires a multiplicity of receptor-ligand interactions, including an oviduct-derived, high molecular weight, wheat germ agglutinin (WGA)-binding glycoprotein that associates with the egg coat at ovulation. Herein, we report the purification and identification of this sperm-binding ligand. WGA-binding, high molecular weight glycoproteins isolated from hormonally primed mouse oviduct lysates competitively inhibit sperm-egg binding in vitro. Within this heterogeneous glycoprotein preparation, a distinct 220 kDa protein selectively binds to sperm surfaces, and was identified by sequence analysis as oviduct-specific glycoprotein (OGP). The sperm-binding activity of OGP was confirmed by the loss of sperm-binding following immunodepletion of OGP from oviduct lysates, and by the ability of both immunoprecipitated OGP and natively purified OGP to competitively inhibit sperm-egg binding. As expected, OGP is expressed by the secretory cells of the fimbriae and infundibulum; however, in contrast to previous reports, OGP is also associated with both the zona pellucida and the perivitelline space of mouse oocytes. Western blot analysis and lectin affinity chromatography demonstrate that whereas the bulk of OGP remains soluble in the ampullar fluid, distinct glycoforms associate with the cumulus matrix, zona pellucida and perivitelline space. The sperm-binding activity of OGP is carbohydrate-dependent and restricted to a relatively minor peanut agglutinin (PNA)-binding glycoform that preferentially associates with the sperm surface, zona pellucida and perivitelline space, relative to other more abundant glycoforms. Finally, pretreatment of two-cell embryos, which do not normally bind sperm, with PNA-binding OGP stimulates sperm binding.
A new lateral impact warning system with grey prediction
Authors: Huang S-J , Chao S-T
Published: October 2009

Vehicle lateral impact is one of the major traffic collision accidents. Usually, this collision accident is caused when the target vehicle appears in the driver's blind spot during lane change or crowded urban travelling and the driver has not carefully observed the approaching vehicle from the rear and side mirrors. Hence, additional sensors need to be installed to measure the relative distance between two closing vehicles for active collision warning purpose. Generally, the lateral distance between two neighbouring vehicles is small compared with longitudinal distance: for crowded city traffic it is less than 1.5m. It is difficult to estimate accurately or assess the time-to-collision (TTC) based on a single relative distance index between two cars. Here, a novel two-indices TTC decision algorithm is proposed, which can distinguish the safe passing of neighbouring lanes from the essential dangerous lateral collision situation. In addition, the grey prediction theory is introduced to estimate the relative distance of two approaching vehicles one step ahead for TTC estimation to gain additional driver reaction time. The simulation results show that this strategy can create 0.5s extra time for the driver to take collision avoidance action.
In Situ Scanning Tunneling Microscopy Observation of Metal–Cluster Redox Interconversion and CO Dissociation Reactions at a Solution/Au(111) Interface
Authors: Noda Hiroyuki , Uehara Hiromitsu , Abe Masaaki , Michi Takayuki , Osawa Masatoshi , Uosaki Kohei , Sasaki Yoichi
Published: October 2009

We present here an in situ scanning tunneling microscopy (STM) study of potential-induced reactions of oxo-centered acetato-bridged triruthenium clusters on Au(111) under electrochemical conditions, in which (i) reversible interconversion between two different redox states of the cluster and (ii) spontaneous dissociation of CO from the cluster were probed and visualized. It is known that the triruthenium complex [Ru3(μ3-O)(μ-CH3COO)6(CO)(4-methylpyridine){(NC5H4)CH2NHC(O)(CH2)10S}] (1), which is in the mixed-valent {(RuII–CO)RuIIIRuIII} state, on Au(111) is one-electron oxidized to cationic complex 1+ which corresponds to a {(RuIII–CO)RuIIIRuIII} oxidation state. The redox reaction is reversible on a cyclic voltammetry timescale. Complex 1+ undergoes irreversible dissociation of CO in an aqueous phase on a longer timescale (ca. minutes) to form an aqua ligand-coordinated complex, 2+, which is expressed as {(RuIII–OH2)RuIIIRuIII}. The reversible redox reaction (11+) and the irreversible ligand substitution reaction (1+ → 2+) were independently examined with in situ STM in a monolayer level by visualizing molecular-sized spots showing a different extent of brightness in STM images. We show here that the molecular-sized spots corresponding to 1, 1+, and 2+ are resolved by their brightness, which strongly depends on both the oxidation states and the ligand nature of the clusters. By employing multiple fast scans at an applied potential of +0.80 V vs. Ag/AgCl, we obtained STM images that follow the irreversible 1+ → 2+ reaction on the surface, from which a rate constant of the CO release was calculated to be 1.9 (±0.2) × 10−2 s−1 (25 °C; in contact with 0.1 mol dm−3 aqueous HClO4 solution). The difference in brightness of the molecular spots is rationalized in terms of orbital-mediated tunneling by considering the difference in electronic states of the dπ–pπ system in the μ3-O triruthenium cluster.
Pore Structure of Hard Carbon Made from Phenolic Resin Studied by 129Xe NMR
Authors: Gotoh Kazuma , Ueda Takahiro , Eguchi Taro , Kawabata Koji , Yamamoto Kenji , Murakami Yuki , Hayakawa Satoshi , Ishida Hiroyuki
Published: October 2009

The pore structure of hard carbon samples made from two kinds of phenolic resins by heating between 1073 and 1473 K was investigated by 129Xe NMR. The difference of porous structure of hard carbon samples by heat treatment temperature, which was difficult to analyze precisely by general gas adsorption methods, could be evaluated by Xe NMR at an equilibrium state of xenon gas adsorption. Carbon samples produced by heating precursors under a 0.1 MPa xenon atmosphere showed stronger NMR signals than carbon heated at reduced pressure, despite their almost identical powder X-ray diffraction (XRD) patterns. Applying this method, the dependence of NMR spectra on heating temperature between 1073 and 1473 K was examined. A carbon sample consisting of smaller particles showed almost constant shift values at about 102 ppm, while the peak of another sample with larger particles shifted between 118 and 82 ppm depending on the heating temperature. Then, almost all entrances of each sample closed above 1273 K. Using NMR with the improved heat-treatment by xenon gas, we evaluated pores in hard carbon that were hard to access from the outer surface of the hard carbon.
Behavior of Glass and Supercooled Liquid Alkylbenzenes Vapor-Deposited on Cold Substrates: Toward the Understanding of the Curious Light Scattering Observed in Some Supercooled Liquid States
Authors: Ishii Kikujiro , Nakayama Hideyuki , Moriyama Ryo , Yokoyama Yuki
Published: October 2009

Ethylbenzene (EB) films prepared on cold metal substrates by vapor deposition in vacuum show a curious light scattering in the supercooled liquid (SCL) state when the temperature is raised at a constant rate. To investigate the cause of this phenomenon, we examined the behavior of similarly prepared samples of a series of alkylbenzenes. We found that the vapor-deposited glass of propylbenzene (PB) and isopropylbenzene (IPB) showed a deposition-temperature (Td) dependence of the initial molar volume (Vm) on deposition similar to EB glass. Interestingly, the samples of the three compounds, which were formed initially as glasses with Vm much larger than that of SCL at the same temperature, exhibited the curious light scattering when they transformed to SCL states after the temperature elevation to above their glass-transition temperature, while the corresponding samples with initial Vm smaller than that of SCL did not exhibit this light scattering. On the basis of these observations, a hypothesis on the cause of the light scattering in the SCL state is proposed in relation to structural transformation between different SCL states. A microscopic mechanism of the formation of a high-density glass with Vm smaller than that of SCL is briefly discussed by referring to the observations of toluene samples which showed a slightly different Td dependence of Vm and did not show the curious light scattering in the SCL state.
Circular Dichroism of Neutral Zinc Porphyrin–Oligonucleotide Conjugates Modified with Flexible Linker
Authors: Onoda Akira , Igarashi Masahiro , Naganawa Satoshi , Sasaki Kiyomi , Ariyasu Shinya , Yamamura Takeshi
Published: October 2009

Neutral zinc porphyrin containing flexible alkyl linker, 5-[4-(5-hydroxypentyloxy)phenyl]-10,15,20-tri-p-tolylporphyrinatozinc, was attached to the 5′ ends of 20- and 30-bp oligodeoxynucleotides (ODN) by solid-phase synthesis. Zinc porphyrin-modified double-stranded DNA (dsDNAs), which included dsDNAs with porphyrin moieties on one end and on both ends (ZnPor–ds20, ds20–ZnPor, ZnPor–ds20–ZnPor, ZnPor–ds30, ds30–ZnPor, and ZnPor–ds30–ZnPor), were successfully prepared and were analyzed by variable-temperature UV–vis spectroscopy and CD measurements to elucidate the interaction behavior of the porphyrin ring. Detailed investigation revealed that the zinc porphyrin–DNA conjugates exhibited intra-duplex porphyrin–ODN interaction in a low-salt condition and inter-duplex porphyrin–porphyrin interaction in a high-salt condition.
Roles of Chloride Anions in the Shape Evolution of Anisotropic Silver Nanostructures in Poly(vinylpyrrolidone) (PVP)-Assisted Polyol Process
Authors: Tang Xinling , Tsuji Masaharu , Nishio Michiko , Jiang Peng
Published: October 2009

The roles of Cl− ions on the shape evolution of various silver (Ag) nanostructures including cubes, triangular bipyramids, and rods/wires in AgNO3/poly(vinylpyrrolidone) (PVP)/ethylene glycol (EG) solution have been investigated by changing the concentration of added NaCl, the reaction solution temperature, and the temperature of injection of NaCl to the original AgNO3/PVP/EG solution under oil-bath heating. The addition of different amounts of NaCl could tune morphologies and sizes of the final products from spheres via cubes to rods/wires. Reaction temperature decided the reduction power and the yield of bipyramids increased with decreasing the reaction temperature from 198 to 120 °C. Changing the solution temperature at which NaCl was introduced into the solution could effectively influence the yields of different Ag structures by adjusting the ratios of Ag and AgCl seeds formed in the solution. We found that AgCl could be an important precursor for the formation of the Ag cubes and bipyramids. The roles of Cl− anions for the evolution of various Ag nanostructures have been discussed by taking account of the formation of AgCl as seeds, selective adsorption of Cl− on {100} facets of Ag nanoparticles, and oxidative etching of the Ag particles by Cl−/O2.
Structure of Lamellar Polysiloxane Induced by Interaction between Carboxylate (Alkanoate and Alkylsuccinate) and Aminosilane (Aminopropyl- and Aminoethylaminopropylsilanes)
Authors: Nakajima Hitomi , Oumi Yasunori , Sano Tsuneji , Yoshitake Hideaki
Published: October 2009

We demonstrate that the dehydration condensation of 3-aminopropylsilane (APTES) and 3-(2-aminoethyl)aminopropylsilane (AeAPTES) in the presence of alkylsuccinate and alkanoic acid provide layered polysiloxanes where the interlayer is filled with self-assembled carboxylate. Their structure was investigated by XRD, IR, and 29Si NMR. Lamellar solids were successfully obtained by the combination of monocarboxylate–APTES and dicarboxylate–AeAPTES, while the addition of alkanol and TEOS was necessary for the synthesis by cross combinations, dicarboxylate–APTES and monocarboxylate–AeAPTES. The series of lamellar solids with different interlayer distance are formed with alkylsuccinate and AeAPTES. The d-spacing is increased linearly with the number of carbons in the alkyl chain of surfactant. Only T3 species is detected in the 29Si NMR spectrum of hexadecylsuccinic acid–AeAPTES, implying that the structure of polysiloxane is a thin layer with complete condensation of silane molecules. This structural uniqueness is also supported by the IR bands due to Si–O–Si asymmetric vibration at 1132–1140 cm−1, suggesting a large Si–O–Si angle. This is because an angle near 180° is necessary for the structure of a R–SiO1.5 layer solid that has organic groups equally populated on both sides. The amount of Fe3+ sorbed in diaminoalkylpolysiloxanes was smaller than in monoaminoalkylpolysiloxane.
Consumption Responses to In-Kind Transfers: Evidence from the Introduction of the Food Stamp Program
Authors: Hoynes Hilary W , Schanzenbach Diane Whitmore
Published: October 2009

Economists have strong theoretical predictions about how in-kind transfers, such as providing vouchers for food, impact consumption. Despite the prominence of the theory, there is little empirical work on responses to in-kind transfers, and most existing work fails to support the canonical theoretical model. We employ difference-in-difference methods to estimate the impact of program introduction on food spending. Consistent with predictions, we find that food stamps reduce out-of-pocket food spending and increase overall food expenditures. We also find that households are inframarginal and respond similarly to one dollar in cash income and one dollar in food stamps. (JEL D12, H23, I38)
Using Mental Skills to Improve Golfing Performance: A Theory-Based Case Study for Golf Coaches
Authors: Finn Jon
Published: October 2009

The manner in which golfers think on the golf course significantly influences their performance. In 2008, the author provided an overview of golf-specific mental skills with the intention of raising golf coaches' awareness of psychological techniques they could use to help their golfers think more effectively. The aim of this paper is to follow up the author's overview by providing an introduction to mental skills interventions, specifically focusing on how they can be tailored to individual golfer's needs, and how they can be applied, analysed, and evaluated to facilitate the performance of competitive golfers. This five-part paper will: 1) outline the current state of formal mental skills education among golf coaches; 2) introduce selected theories that underpin mental skills interventions; 3) address the role of golf coaches in delivering these interventions; 4) suggest some frameworks which might help to increase the effectiveness of these interventions; and 5) illustrate the practical application of these theories and frameworks by describing a mental skills intervention that was used with a tour-level golfer to improve playing performance.
Gastrointestinal Safety of Nonsteroidal Antiinflammatory Drugs and Selective Cyclooxygenase-2 Inhibitors in Patients on Warfarin
Authors: Cheetham T Craig , Levy Gerald , Niu Fang , Bixler Felicia
Published: October 2009

Background:

The interaction between warfarin and nonsteroidal antiinflammatory drugs (NSAIDs) is well known. However, warfarin and NSAIDs are still commonly prescribed together. Selective cyclooxygenase-2 (COX-2) inhibitors, a newer class of NSAID, offer potential advantages over the nonselective NSAIDs in patients treated with warfarin.

Objective:

To study the rates of hospitalization for gastrointestinal (GI) bleeding events in 3 groups of patients: those taking warfarin only, those taking warfarin plus a nonselective NSAID, and those taking warfarin plus a selective COX-2 inhibitor.

Methods:

This was a retrospective cohort analysis in a large nonprofit health maintenance organization. All warfarin users from January 1, 2000, to December 31, 2005, were eligible for inclusion in the study. Eligible patients were grouped by their exposure time to warfarin only, warfarin plus nonselective NSAIDs, or warfarin plus selective COX-2 inhibitor. The study endpoint was hospitalization for a GI bleed. Patients were matched using a propensity scoring methodology. A multivariate Cox proportional hazards model was used to estimate the hazard ratio for GI bleeding between patient cohorts, controlling for age, sex, baseline medical conditions, prior history of GI bleeding, and prescription drug use.

Results:

The eligible population consisted of 35,548 patients undergoing 46.214 courses of warfarin therapy. The adjusted hazard ratio for hospital-associated GI bleeding in the warfarin plus nonselective NSAID group versus warfarin alone was 3.58 (95% CI 2.31 to 5.55; p < 0.01) and for warfarin plus selective COX-2 inhibitor versus warfarin alone was 1.71 (95% CI 0.60 to 4.84; p = 0.31). For nonselective NSAIDs plus warfarin versus selective COX-2 inhibitor plus warfarin, the adjusted hazard ratio was 3.69 (95% CI 1.42 to 9.60; p = 0.01).

Conclusions:

In general, nonselective NSAIDs and selective COX-2 inhibitors should be avoided in patients taking warfarin. In situations where patients require NSAIDs and cannot be managed using other therapies, our results suggest that selective COX-2 inhibitors are associated with fewer hospitalizations for GI bleeding.
Staphylococcus aureus Strain Typing by Single-Molecule DNA Mapping in Fluidic Microchips with Fluorescent Tags
Authors: White Eric J , Fridrikh Sergey V , Chennagiri Nirupama , Cameron Douglas B , Gauvin Gregory P , Gilmanshin Rudolf
Published: October 2009

Background: Epidemiologic studies require identification or typing of microbial strains. Macrorestriction DNA mapping analyzed by pulsed-field gel electrophoresis (PFGE) is considered the current gold standard of genomic typing. This technique, however, is difficult to implement because it is labor-intensive and difficult to automate, it requires a long time to obtain results, and results often vary between laboratories.

Methods: We used direct linear analysis (DLA), which uses a single reagent set and long fragments of microbial genomic DNA to identify various microbes. In this technique, an automated system extracts fragments exceeding 100 kb from restriction enzyme digests of genomic DNA from microbial isolates and hybridizes them with a sequence-dependent fluorescent tag. These fragments are then stretched in a microfluidics chip, and the patterns of the distribution of the tags are discerned with fluorescence confocal microscopy. The tag pattern on each DNA fragment is compared with a database of known microbial DNA sequences or with measured patterns of other microbial DNAs.

Results: We used DLA to type 71 Staphylococcus aureus strains. Of these, 9 had been sequenced, 10 were representative of the major pulsed-field types present in the US, and 52 were isolated recently in a hospital in Cambridge, MA. Matching DNA fragments were identified in different samples by a clustering algorithm and were used to quantify the similarities of the strains.

Conclusions: DLA-based strain typing is a powerful technique with a resolution comparable to macrorestriction mapping with PFGE, but DLA is faster, more automated, and more reproducible.
Neurons of the Dopaminergic/Calcitonin Gene-Related Peptide A11 Cell Group Modulate Neuronal Firing in the Trigeminocervical Complex: An Electrophysiological and Immunohistochemical Study
Authors: Charbit Annabelle R. , Akerman Simon , Holland Philip R. , Goadsby Peter J.
Published: October 2009

Activation of spinal trigeminal afferents innervating the cranial vasculature is likely to play a role in migraine, although some parts of the clinical presentation may have a dopaminergic basis. The A11 nucleus, located in the posterior hypothalamus, provides the only known source of descending dopaminergic innervation for the spinal gray matter. Extracellular recordings were made in the trigeminocervical complex (TCC) in response to electrical stimulation of the dura mater. Receptive fields were characterized by mechanical noxious and innocuous stimulation of the ipsilateral ophthalmic dermatome. Stimulation of the A11 significantly inhibited peri-middle meningeal artery dural and noxious pinch evoked firing of neurons in the TCC. This inhibition was reversed by the D2receptor antagonist eticlopride. Lesioning of the A11 significantly facilitated dural and noxious pinch and innocuous brush evoked firing from the TCC. In previous work using immunohistofluorescence, it was shown that D1and D2receptors were found in the rat TCC, and here we report, in addition, that D4and D5dopamine receptors are also present, whereas D3receptors are not. No dopamine receptors were present in the A11 nucleus itself. However, the A11 does contain dopamine and calcitonin gene-related peptide (CGRP) and, by this combination, is distinct from the neighboring CGRPergic subparafascicular nucleus. Exploration of dopaminergic influences and mechanisms in migraine may open up an almost untapped opportunity to pursue potential new therapeutic options for the disorder.
Mature BDNF, But Not proBDNF, Reduces Excitability of Fast-Spiking Interneurons in Mouse Dentate Gyrus
Authors: Holm Mai Marie , Nieto-Gonzalez Jose Luis , Vardya Irina , Vaegter Christian Bjerggaard , Nykjaer Anders , Jensen Kimmo
Published: October 2009

Mature BDNF and its precursor proBDNF may both be secreted to exert opposite effects on synaptic plasticity in the hippocampus. However, it is unknown how proBDNF and mature BDNF affect the excitability of GABAergic interneurons and thereby regulate GABAergic inhibition. We made recordings of GABAergic spontaneous IPSCs (sIPSCs) in mouse dentate gyrus granule cells and found that chronic or acute BDNF reductions led to large increases in the sIPSC frequencies, which were TTX (tetrodotoxin) sensitive and therefore action-potential driven. Conversely, addition of mature BDNF, but not proBDNF, within minutes led to a decrease in the sIPSC frequency to 44%. Direct recordings from fast-spiking GABAergic interneurons revealed that mature BDNF reduced their excitability and depressed their action potential firing, whereas proBDNF had no effect. Using the TrkB inhibitor K-252a, or mice deficient for the common neurotrophin receptor p75NTR, the regulation of GABAergic activity was shown specifically to be mediated by BDNF binding to the neurotrophin receptor TrkB. In agreement, immunohistochemistry demonstrated that TrkB, but not p75NTR, was expressed in parvalbumin-positive interneurons. Our results suggest that mature BDNF decreases the excitability of GABAergic interneurons via activation of TrkB, while proBDNF does not impact on GABAergic activity. Thus, by affecting the firing of GABAergic interneurons, mature BDNF may play an important role in regulating network oscillations in the hippocampus.
Chronic Exposure to Anabolic Androgenic Steroids Alters Neuronal Function in the Mammalian Forebrain via Androgen Receptor- and Estrogen Receptor-Mediated Mechanisms
Authors: Penatti Carlos A. A. , Porter Donna M. , Henderson Leslie P.
Published: October 2009

Anabolic androgenic steroids (AAS) can promote detrimental effects on social behaviors for which GABA type A (GABAA) receptor-mediated circuits in the forebrain play a critical role. While all AAS bind to androgen receptors (AR), they may also be aromatized to estrogens and thus potentially impart effects via estrogen receptors (ER). Chronic exposure of wild-type male mice to a combination of chemically distinct AAS increased action potential (AP) frequency, selective GABAAreceptor subunit mRNAs, and GABAergic synaptic current decay in the medial preoptic area (mPOA). Experiments performed with pharmacological agents and in AR-deficientTfmmutant mice suggest that the AAS-dependent enhancement of GABAergic transmission in wild-type mice is AR-mediated. In AR-deficient mice, the AAS elicited dramatically different effects, decreasing AP frequency, spontaneous IPSC amplitude and frequency and the expression of selective GABAAreceptor subunit mRNAs. Surprisingly, in the absence of AR signaling, the data indicate that the AAS do not act as ER agonists, but rather suggest a novelin vivoaction in which the AAS inhibit aromatase and impair endogenous ER signaling. These results show that the AAS have the capacity to alter neuronal function in the forebrain via multiple steroid signaling mechanisms and suggest that effects of these steroids in the brain will depend not only on the balance of AR- versus ER-mediated regulation for different target genes, but also on the ability of these drugs to alter steroid metabolism and thus the endogenous steroid milieu.
Introduction
Authors: Bischof Delaloye Angelika , Conti Peter S. , Gisselbrecht Christian , Gregory Stephanie A.
Published: October 2009

This article introduces this supplement, which summarizes and explores the emerging data and changing protocols for the diagnosis and treatment of non-Hodgkin’s lymphoma discussed at the 6th International Workshop on Nuclear Oncology, held April 17–19, 2008.
Summary
Authors: Bischof Delaloye Angelika , Conti Peter S. , Gisselbrecht Christian , Gregory Stephanie A.
Published: October 2009

This article summarizes the International Workshop on Nuclear Oncology scientific committee’s conclusions.
The Pit-1/Pou1f1 transcription factor regulates and correlates with prolactin expression in human breast cell lines and tumors
Authors: Ben-Batalla I , Seoane S , Macia M , Garcia-Caballero T , Gonzalez L O , Vizoso F , Perez-Fernandez R
Published: October 2009

The transcription factor Pit-1/Pou1f1 regulates GH and prolactin (PRL) secretion in the pituitary gland. Pit-1 expression and GH regulation by Pit-1 have also been demonstrated in mammary gland. However, no data are available on the role of Pit-1 on breast PRL. To evaluate this role, several human breast cancer cell lines were transfected with either the Pit-1 expression vector or a Pit-1 small interference RNA construct, followed by PRL mRNA and protein evaluation. In addition, transient transfection of MCF-7 cells by a reporter construct containing the proximal PRL promoter, and ChIP assays were performed. Our data indicate that Pit-1 regulates mammary PRL at transcriptional level by binding to the proximal PRL promoter. We also found that Pit-1 raises cyclin D1 expression before increasing PRL levels, suggesting a PRL-independent effect of Pit-1 on cell proliferation. By using immunohistochemistry, we found a significant correlation between Pit-1 and PRL expression in 94 human breast invasive ductal carcinomas. Considering the possible role of PRL in breast cancer disorders, the function of Pit-1 in breast should be the focus of further research.
Age, Period, and Cohort Effects on Intimate Partner Violence
Authors: Rivara Frederick P. , Anderson Melissa L. , Fishman Paul , Reid Robert J. , Bonomi Amy E. , Carrell David , Thompson Robert S.
Published: October 2009

This study sought to determine if the recent secular decrease in reported intimate partner violence (IPV) in women was due to cohort or period effects. Women ages 18 to 64 were interviewed about IPV during their adult lifetimes. The lifetime prevalence of any IPV was 42%. Regardless of birth cohort, IPV was most common among women in their mid-20s to early 30s. After adjusting for cohort and period effects, women 26 to 30 had the highest risk of any IPV; risk decreased with age. Younger birth cohorts were at decreased risk for IPV. The estimated risk is lowest for those born between 1966 and 1975, with 31% lower risk of IPV than those born in 1946–1955. There was a substantial drop in IPV for all age-groups beginning in the 1990s.
Mental Health Disparities
Authors: Safran Marc A. , Mays Robert A. , Huang Larke Nahme , McCuan Ron , Pham Phuong Kim , Fisher Sylvia Kay , McDuffie Kathleen Y. , Trachtenberg Alan
Published: October 2009

Mental health disparities have received increased attention in the literature in recent years. After considering 165 different health disparity conditions, the Federal Collaborative for Health Disparities Research chose mental health disparity as one of four topics warranting its immediate national research attention. In this essay, we describe the challenges and opportunities encountered in developing a research agenda to address mental health disparities in the United States. Varying definitions of mental health disparity, the heterogeneity of populations facing such disparity, and the power, complexity, and intertwined nature of contributing factors are among the many challenges. We convey an evolving interagency approach to mental health disparities research and guidance for further work in the field.
Effects of R-Alpha Lipoic Acid on HbA1c, Lipids and Blood Pressure in Type-2 Diabetics: A Preliminary Study
Authors: Lukaszuk Judith M. , Schultz Theresa M. , Prawitz Aimee D. , Hofmann Elisa
Published: October 2009

R-alpha lipoic acid (R-ALA) supplementation improves blood glucose in diabetic animals, but there have been no long-term clinical trials in humans testing its use for glucose control (HbA1c). This double-blind study pre-/post-test control group (PL) design sought to determine the effect of R-ALA on HbA1c. Twenty type-2 diabetics were randomly assigned to 200 mg capsules of R-ALA (n=13; 8M 5F) or PL (n=7; 2M 5F) 3 times daily, 30 minutes before meals (600 mg total) for 91 days. Samples were obtained for HbA1c at baseline and day 91. No significant differences between R-ALA and PL groups were found at baseline or day 91. However, three distinct reactions to the supplement were noted. The first group (n=3) responded to R-ALA with a >25% drop in HbA1c range from 6.1-12.5 to 6.2- 9.0 mg/dL and/or halved their anti-diabetic medication. The second group (n=5) had no change in HbA1c. The third group (n=5) had changes in medication or concurrent chronic adverse events that should have raised HbA1c, but did not beyond that of the placebo. Conclusions: Three months of R-ALA supplementation may lower HbA1c in a small number of individuals. However, to further confirm these findings, larger studies of longer duration are needed.
Zinc Transporter 8 Antibodies Complement GAD and IA-2 Antibodies in the Identification and Characterization of Adult-Onset Autoimmune Diabetes
Authors: Lampasona Vito , Petrone Antonio , Tiberti Claudio , Capizzi Marco , Spoletini Marialuisa , di Pietro Sergio , Songini Marco , Bonicchio Sara , Giorgino Francesco , Bonifacio Ezio , Bosi Emanuele , Buzzetti Raffaella ,   for the Non Insulin Requiring Autoimmune Diabetes (NIRAD) Study Group
Published: October 2009

OBJECTIVE

Zinc transporter 8 (ZnT8) is an islet β-cell secretory granule membrane protein recently identified as an autoantibody antigen in type 1 diabetes. The aim of this study was to determine the prevalence and role of antibodies to ZnT8 (ZnT8As) in adult-onset diabetes.

RESEARCH DESIGN AND METHODS

ZnT8As were measured by a radioimmunoprecipitation assay using recombinant ZnT8 COOH-terminal or NH2-terminal proteins in 193 patients with adult-onset autoimmune diabetes having antibodies to either GAD (GADAs) or IA-2 (IA-2As) and in 1,056 antibody-negative patients with type 2 diabetes from the Non Insulin Requiring Autoimmune Diabetes (NIRAD) study.

RESULTS

ZnT8As-COOH were detected in 18.6% patients with autoimmune diabetes and 1.4% with type 2 diabetes. ZnT8As-NH2 were rare. ZnT8As were associated with younger age and a high GADA titer. The use of GADAs, IA-2As, and ZnT8As in combination allowed a stratification of clinical phenotype, with younger age of onset of diabetes and characteristics of more severe insulin deficiency (higher fasting glucose and A1C, lower BMI, total cholesterol, and triglycerides) in patients with all three markers, with progressive attenuation in patients with two, one, and no antibodies (all Ptrend < 0.001). Autoantibody titers, association with high-risk HLA genotypes, and prevalence of thyroid peroxidase antibodies followed the same trend (all P < 0.001).

CONCLUSIONS

ZnT8As are detectable in a proportion of patients with adult-onset autoimmune diabetes and seem to be a valuable marker to differentiate clinical phenotypes.
Relationship Between CarotidIntima-Media Thickness and Silent Cerebral Infarction in Japanese Subjects With Type 2 Diabetes
Authors: Nomura Kazuhiro , Hamamoto Yoshiyuki , Takahara Shiho , Kikuchi Osamu , Honjo Sachiko , Ikeda Hiroki , Wada Yoshiharu , Nabe Koichro , Okumra Ryosuke , Koshiyama Hiroyuki
Published: October 2009

OBJECTIVE

We examined the relationship between intima-media thickness of common carotid artery (CCA-IMT) and silent cerebral infarction (SCI) with the magnetic resonance imaging (MRI) study in Japanese subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS

The brain MRI study and the carotid ultrasonography were performed in a total of 217 consecutive Japanese subjects with type 2 diabetes. Various risk factors for SCI were examined using multiple logistic analyses.

RESULTS

The SCI was found in 60.4% of the diabetic subjects. In the diabetic subjects, age, systolic blood pressure (SBP), pulse wave velocity, and CCA-IMT were significantly higher in the subjects with SCI than in those without it. Multiple logistic analyses indicated that age, SBP, and CCA-IMT were significant and independent risk factors of SCI in the diabetic subjects.

CONCLUSIONS

CCA-IMT, but not pulse wave velocity, was independently associated with SCI in Japanese subjects with type 2 diabetes.
Patients Diagnosed With Diabetes Are at Increased Risk for Asthma, Chronic Obstructive Pulmonary Disease, Pulmonary Fibrosis, and Pneumonia but Not Lung Cancer
Authors: Ehrlich Samantha F. , Quesenberry Charles P. , Van Den Eeden Stephen K. , Shan Jun , Ferrara Assiamira
Published: October 2009

OBJECTIVE

There are limited data on the risk of pulmonary disease in patients with diabetes. The aim of this study was to evaluate and compare the incidence of asthma, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, pneumonia, and lung cancer in patients with and without a diagnosis of diabetes.

RESEARCH DESIGN AND METHODS

We conducted a retrospective, longitudinal cohort study using the electronic records of a large health plan in northern California. Age and sex data were available for all cohort members (n = 1,811,228). Data on confounders were available for a subcohort that responded to surveys (n = 121,886), among whom Cox proportional hazards regression models were fit.

RESULTS

Age- and sex-adjusted incidence rates and 95% CIs were calculated for members with and without diabetes in the full cohort and the subcohort. No difference was observed for lung cancer, but the incidence of asthma, COPD, fibrosis, and pneumonia was significantly higher in those members with a diagnosis of diabetes. These differences remained significant in regression models adjusted for age, sex, race/ethnicity, smoking, BMI, education, alcohol consumption, and outpatient visits (asthma hazard ratio [HR] 1.08 [95% CI 1.03–1.12], COPD HR 1.22 [1.15–1.28], pulmonary fibrosis HR 1.54 [1.31–1.81], and pneumonia HR 1.92 [1.84–1.99]). The risk of pneumonia and COPD increased significantly with increasing A1C.

CONCLUSIONS

Individuals with diabetes are at increased risk of several pulmonary conditions (asthma, COPD, fibrosis, and pneumonia) but not lung cancer. This increased risk may be a consequence of declining lung function in patients with diabetes.
Utility of Homeostasis Model Assessment of β-Cell Function in Predicting Diabetes in 12,924 Healthy Koreans
Authors: Sung Ki-Chul , Reaven Gerald M. , Kim Sun H.
Published: October 2009

OBJECTIVE

It is unclear how well homeostasis model assessment of β-cell function (HOMA-β) predicts diabetes development beyond its components, especially glucose.

RESEARCH DESIGN AND METHODS

We identified 12,924 nondiabetic Koreans who had fasting plasma glucose and insulin concentrations measured in 2003 and again in 2008. To minimize the impact of differences in baseline glucose concentration, individuals were divided into three glucose categories: normal fasting glucose (NFG, glucose <5.6 mmol/l), impaired fasting glucose (IFG-100) (5.6–6.0 mmol/l), and IFG-110 (6.1–6.9 mmol/l).

RESULTS

Diabetes developed in 29% of individuals in the IFG-110 group, compared with 5% in IFG-100 and 0.3% in NFG groups. Within each glucose category, those who progressed to diabetes had higher baseline glucose concentrations (P ≤ 0.04). Baseline HOMA-β, however, was not lower but higher in individuals who developed diabetes in the NFG group (P = 0.009) and similar in the IFG-100 and IFG-110 groups.

CONCLUSIONS

These data question the utility of using HOMA-β to predict the development of diabetes.