bluuebunny/crossref_metadata_2025 huggingface dataset:
The nNOS inhibitor, AR‐R17477AR, prevents the loss of NF68 immunoreactivity induced by methamphetamine in the mouse striatum
Authors: Sanchez Veronica , Zeini Miriam , Camarero Jorge , O'Shea Esther , Bosca Lisardo , Green A. Richard , Colado M. Isabel
Published: February 2008

The present study examined the time‐course and regionally‐selective changes in the levels of the neurofilament protein NF68 in the mouse brain induced by methamphetamine (METH). The ability of low ambient temperature, or of the specific neuronal nitric oxide synthase (nNOS) inhibitor AR‐R17477AR, to protect against both long‐term striatal NF68 and dopamine loss induced by METH (3 mg/kg, i.p.) was also studied. Seven days after METH administration (3, 6 and 9 mg/kg, i.p., three times at 3 h intervals), mice showed a reduction of about 40% in immunoreactivity for NF68 in the striatum. This effect was not produced in cortex after METH administration at the dose of 3 mg/kg. No difference from controls was observed when measurements were carried out 1 h and 24 h after the last METH injection at the dose of 3 mg/kg. The loss of NF68 immunoreactivity seems to be associated with the long‐term dopamine depletion induced by METH, since no change in serotonin concentration is observed in either the striatum or cortex 7 days after dosing. Animals kept at a room temperature of 4°C showed a loss of NF68 similar to those treated at 22°C but an attenuation of dopamine depletion in the striatum. Pre‐treatment with AR‐R17477AR (5 mg/kg, s.c.) 30 min before each of the three METH (3 mg/kg, i.p.) injections provided complete protection against METH‐induced loss of NF68 immunoreactivity and attenuated the decrease in striatal dopamine and HVA concentrations by about 50%. These data indicate that both the reduction of NF68 immunoreactivity and the loss of dopamine concentration are due to an oxidative stress process mediated by reactive nitrogen species, and are not due to changes in body temperature.
Calculation of extracted ion beam particle distribution including within-extractor collisions from H-alpha Doppler shift measurements
Authors: Kim Tae-Seong , Kim Jinchoon , In Sang Ryul , Jeong Seung Ho
Published: February 2008

Prototype long pulse ion sources are being developed and tested toward the goal of a deuterium beam extraction of 120keV∕65A. The latest prototype source consists of a magnetic bucket plasma generator and a four-grid copper accelerator system with multicircular apertures of 568 holes. To measure the angular divergence and the ion species of the ion beam, an optical multichannel analyzer (OMA) system for a Doppler-shifted H-alpha lights was set up at the end of a gas-cell neutralizer. But the OMA data are very difficult to analyze due to a large background level on the top of the three energy peaks (coming from H+, H2+, and H3+). These background spectra in the OMA signals seem to result from partially accelerated ion beams in the accelerator. Extracted ions could undergo a premature charge exchange as the accelerator column tends to have a high hydrogen partial pressure from the unused gas from the plasma generator, resulting in a continuous background of partially accelerated beam particles at the accelerator exit. This effect is calculated by accounting for all the possible atomic collision processes and numerically summing up three ion species across the accelerator column. The collection of all the atomic reaction cross sections and the numerical summing up will be presented. The result considerably depends on the background pressure and the ion beam species ratio (H+, H2+, and H3+). This effect constitutes more than 20% of the whole particle distribution. And the energy distribution of those suffering from collisions is broad and shows a broad maximum in the vicinity of the half and the third energy region.
Biocompatible core-shell magnetic nanoparticles for cancer treatment
Authors: Sharma Amit , Qiang You , Meyer Daniel , Souza Ryan , Mcconnaughoy Alan , Muldoon Leslie , Baer Donald
Published: February 2008

Nontoxic magnetic nanoparticles (MNPs) have expanded treatment delivery options in the medical world. With a size range from 2to200nm, MNPs can be compiled with most of the small cells and tissues in the living body. Monodispersive iron-iron oxide core-shell nanoparticles were prepared by our novel cluster deposition system. This unique method of preparing core-shell MNPs gives the nanoparticles a very high magnetic moment. We tested the nontoxicity and uptake of MNPs coated with/without dextrin by incubating them with rat LX-1 small cell lung cancer cells. Since core iron enhances the heating effect [L. Baker, Q. Zeing, W. Li, and S. Sullivan, J. Appl. Phys. 99, 08H106 (2006)], the rate of oxidation of iron nanoparticles was also tested in de-ionized water at a certain time interval. Both coated and noncoated MNPs were successfully uptaken by the cells, indicating that the nanoparticles were not toxic. The stability of MNPs was verified by x-ray diffraction scan after 0, 24, 48, 96, and 204h. Due to the high magnetic moment offered by MNPs produced in our laboratory, we predict that even at low applied external alternating field, the desired temperature could be reached in cancer cells in comparison to the commercially available nanoparticles. Moreover our MNPs do not require additional transfection agent, providing a cost effective means of treatment with significantly lower dosage in the body in comparison to commercially available nanoparticles.
Linear-scaling multipole-accelerated Gaussian and finite-element Coulomb method
Authors: Watson Mark A. , Kurashige Yuki , Nakajima Takahito , Hirao Kimihiko
Published: February 2008

A linear-scaling implementation of the Gaussian and finite-element Coulomb (GFC) method is presented for the rapid computation of the electronic Coulomb potential. The current work utilizes the fast multipole method (FMM) for the evaluation of the Poisson equation boundary condition. The FMM affords significant savings for small- and medium-sized systems and overcomes the bottleneck in the GFC method for very large systems. Compared to an exact analytical treatment of the boundary, more than 100-fold speedups are observed for systems with more than 1000 basis functions without any significant loss of accuracy. We present CPU times to demonstrate the effectiveness of the linear-scaling GFC method for both one-dimensional polyalanine chains and the challenging case of three-dimensional diamond fragments.
Stochastic-parametric amplification of narrow-band signals in a single-junction SQUID interferometer
Authors: Turutanov O. G. , Shnyrkov V. I. , Glukhov A. M.
Published: February 2008

The features of the response of a single-junction superconducting quantum interferometer to a low-frequency harmonic signal in the presence of noise and a high-frequency electromagnetic field are investigated through numerical solution of the equations of motion. It is shown that in this situation a system described by a double-well potential will display stochastic-parametric amplification of weak harmonic signals owing to the cooperative effects of noise and the high-frequency field. The gain is a nonmonotonic function of the amplitude of the high-frequency field and the variance of the noise flux and passes through a maximum. A detailed numerical analysis of the dependence of the gain on the noise intensity and on the frequency and amplitude of the high-frequency field is carried out in the stochastic, parametric, and stochastic-parametric amplification regimes. It is shown that at optimal amplitude of the high-frequency field the gain for a weak harmonic signal reaches rather high values (10–30). The specific properties of stochastic-parametric amplification are discussed, and the possible applications of this effect for constructing input circuits of detectors based on SQUIDs with registration of weak narrow-band information signals are considered.
Peculiarities of EPR spectra of methyl radicals in quench-condensed krypton films
Authors: Dmitriev Yu. A.
Published: February 2008

Methyl radicals are trapped in the solid Kr film by simultaneous condensation of gaseous Kr and the products of a gas discharge in CH4-doped Kr on a low-temperature (4.2K) substrate located at the center of the microwave cavity. The observed EPR spectrum is a superposition of broad-line and narrow-line series. At a low resonance microwave power, the latter series consists of four hyperfine components with nearly equal intensities and shows small axial anisotropy of both the g and A tensors. At a sufficiently high power the two central narrow lines split, so that the narrow-line series takes on the appearance recorded elsewhere for CH3 in Ar at higher temperatures above 12K. Simultaneously, the intensity of the two central broad lines increases dramatically, while the outer components become saturated. A possible explanation is discussed.
Structure, magnetic properties, and exchange coupling in thermally processed NdDyFeCoB∕α-Fe nanoscale multilayer magnets
Authors: Liu W. , Li X. Z. , Sui Y. C. , Zhou J. , Ren W. J. , Zhang Z. D. , Sellmyer D. J.
Published: February 2008

The structure and magnetic properties of multilayer magnets with a hard phase (HP1=Nd13.5Dy1.5Fe68Co10B7 or HP2=Nd14Dy1Fe68Co10B7) and soft phase Fe, prepared by sputtering and subsequent heat treatment, have been investigated. For Si∕Ti(20nm)∕[HP1(2.0nm)∕Fe(0.5nm)]×200∕Ti(10nm) multilayer film, transmission electron microscopy results show that Fe disperses in amorphous NdDyFeCoB alloy. After annealing at 575°C for 5min, the hard Nd2Fe14B phase typically with grains of about 50nm and some amount of α-Fe coexist in the film. The grain size of the hard and soft phases can be controlled by the proper thickness of the layer and the period. A coercivity of 7.7kOe and a ratio Mr∕Ms of 0.74 are achieved in the multilayer Si∕Ti(20nm)∕[HP2(2nm)∕Fe(0.5nm)]×200∕Ti(10nm). A good squareness of the hysteresis loop (measured even at 200K) is observed, due to the effective exchange coupling between the magnetically soft and hard nanograins in the film. A pinning-type mechanism dominates the magnetization reversal process. In addition, the effect of the effective anisotropy, the grain size, and interfaces between the magnetically hard and soft phases on the exchange coupling is discussed.
Magnetophoresis of flexible DNA-based dumbbell structures
Authors: Babić B. , Ghai R. , Dimitrov K.
Published: February 2008

Controlled movement and manipulation of magnetic micro- and nanostructures using magnetic forces can give rise to important applications in biomedecine, diagnostics, and immunology. We report controlled magnetophoresis and stretching, in aqueous solution, of a DNA-based dumbbell structure containing magnetic and diamagnetic microspheres. The velocity and stretching of the dumbbell were experimentally measured and correlated with a theoretical model based on the forces acting on individual magnetic beads or the entire dumbbell structures. The results show that precise and predictable manipulation of dumbbell structures is achievable and can potentially be applied to immunomagnetic cell separators.
In situ spectroscopic ellipsometry growth studies on the Al-doped ZnO films deposited by remote plasma-enhanced metalorganic chemical vapor deposition
Authors: Volintiru I. , Creatore M. , van de Sanden M. C. M.
Published: February 2008

In situ spectroscopic ellipsometry (SE) was applied to study the pyramidlike and pillarlike growth of Al doped ZnO (AZO) films deposited by means of remote plasma-enhanced metalorganic chemical vapor deposition for transparent conductive oxide applications. Real time SE studies in the visible region allowed discerning between the two growth modes by addressing the time evolution of the bulk and surface roughness layer thickness. While the pillarlike mode is characterized by a constant growth rate, a slower rate in the initial stage (up to 150–200 nm film thickness), compared to the bulk, is observed for the growth of pyramidlike AZO films. The two modes differ also in terms of surface roughness development: a saturation behavior is observed for film thickness above 150–200 nm in the case of the pyramidlike films, while a slow linear increase with film thickness characterizes the pillarlike mode. By extending the SE analysis of the AZO films to the near infrared region, valuable information about the in grain properties could be extracted: excellent in grain mobility values, i.e., larger than 100 and 50 cm2/V s, are determined for the pyramidlike and pillarlike AZO layers, respectively. The comparison between the outcome of the in situ real time SE studies and the ex situ electrical and chemical characterization highlights the limitations in the electron transport occurring in both types of films and allows one to address routes toward further improvement in AZO conductivity.
Inverse spin-Hall effect and spin pumping in metallic films (invited)
Authors: Harii K. , Ando K. , Inoue H. Y. , Sasage K. , Saitoh E.
Published: February 2008

Inverse spin-Hall effect (ISHE) was investigated in Ni81Fe19∕Pt and Ni81Fe19∕Cu films. By applying a microwave and a magnetic field to the films, a spin current is injected into the paramagnetic layer from the ferromagnetic Ni81Fe19 layer due to the spin-pumping effect operated by the ferromagnetic resonance. In the Ni81Fe19∕Pt film, this spin-current injection gives rise to electromotive force, which is attributed to ISHE in the Pt layer. In the Ni81Fe19∕Cu film, in contrast, this electromotive force disappears, indicating an important role of strong spin-orbit interaction in ISHE.
Reactivity and morphology of vapor-deposited Al/polymer interfaces for organic semiconductor devices
Authors: Demirkan K. , Mathew A. , Weiland C. , Reid M. , Opila R. L.
Published: February 2008

The chemistry and the morphology of metal-deposited organic semiconductor interfaces play a significant role in determining the performance and reliability of organic semiconductor devices. We investigated the aluminum metallization of poly(2-methoxy-5,2′-ethyl-hexyloxy-phenylene vinylene) (MEH-PPV), polystyrene, and ozone-treated polystyrene surfaces by chemical (x-ray and ultraviolet photoelectron spectroscopy) and microscopic [atomic force microscopy, scanning electron microscopy (SEM), focused ion beam (FIB)] analyses. Photoelectron spectroscopy showed the degree of chemical interaction between Al and each polymer; for MEH-PPV, the chemical interactions were mainly through the C–O present in the side chain of the polymer structure. The chemical interaction of aluminum with polystyrene was less significant, but it showed a dramatic increase after ozone treatment of the polystyrene surface (due to the formation of exposed oxygen sites). Results showed a strong relationship between the surface reactivity and the condensation/sticking of the aluminum atoms on the surface. SEM analysis showed that, during the initial stages of the metallization, a significant clustering of aluminum takes place. FIB analysis showed that such clustering yields a notably porous structure. The chemical and the morphological properties of the vapor-deposited Al on organic semiconductor surfaces makes such electrical contacts more complicated. The possible effects of surface chemistry and interface morphology on the electrical properties and reliability of organic semiconductor devices are discussed in light of the experimental findings.
Colloid probes with increased tip height for higher sensitivity in friction force microscopy and less cantilever damping in dynamic force microscopy
Authors: Schmutz Jan-Erik , Schäfer Marcus M. , Hölscher Hendrik
Published: February 2008

We present a method how to glue small spheres to atomic force microscope cantilevers. In difference to an often used approach where the sphere is glued to a tipless cantilever, we suggest to mount small spheres to a conventional cantilever with integrated tips modified by a focused ion beam. In this way it is possible to manufacture a spherical probe with increased tip height which enhances the sensitivity in friction force microscopy and reduces the cantilever damping in dynamic force microscopy. By milling cavities for the spheres at the tip apex the colloid particles can be attached at defined positions and contamination with glue can be prevented.
The development of habitat selection by subadult koalas
Authors: Tucker G. , Melzer A. , Ellis W.
Published: February 2008

Dispersal by subadults is the principal source of gene flow between groups of koalas in Queensland, so understanding the behaviour of these immature animals is a priority for understanding the ecology of the species. Recent reports postulate that dispersing young koalas may inherit maternal tree selection, but avoid competing with adults. We compared the tree use and diet of adult female koalas with that of their offspring on St Bees Island, Queensland, using radio-tracking and faecal cuticle analysis, to examine this prediction. Koalas at St Bees Island used both fodder and non-fodder species during daytime, moving into fodder species at night. Koala diets were dominated by Eucalyptus tereticornis with E. platyphylla and Corymbia intermedia also represented. Utilisation of daytime tree species was diverse, but at night koalas were found almost exclusively in those species present in their diet. Use of trees during daytime by natal young and young adult koalas were similar to that of maternal adults, but tree use by intermediate stages (independent and dispersing young) during daytime varied from that of the mothers. This resource separation indicates that if tree utilisation for resting is learned from the mother, young animals are excluded from preferred trees while dispersing.
Zero-field remote detection of NMR with a microfabricated atomic magnetometer
Authors: Ledbetter M. P. , Savukov I. M. , Budker D. , Shah V. , Knappe S. , Kitching J. , Michalak D. J. , Xu S. , Pines A.
Published: February 2008

We demonstrate remote detection of nuclear magnetic resonance (NMR) with a microchip sensor consisting of a microfluidic channel and a microfabricated vapor cell (the heart of an atomic magnetometer). Detection occurs at zero magnetic field, which allows operation of the magnetometer in the spin-exchange relaxation-free (SERF) regime and increases the proximity of sensor and sample by eliminating the need for a solenoid to create a leading field. We achieve pulsed NMR linewidths of 26 Hz, limited, we believe, by the residence time and flow dispersion in the encoding region. In a fully optimized system, we estimate that for 1 s of integration, 7 × 10
13
protons in a volume of 1 mm
3
, prepolarized in a 10-kG field, can be detected with a signal-to-noise ratio of ≈3. This level of sensitivity is competitive with that demonstrated by microcoils in 100-kG magnetic fields, without requiring superconducting magnets.
Distribution of cytotoxic and DNA ADP-ribosylating activity in crude extracts from butterflies among the family Pieridae
Authors: Matsumoto Yasuko , Nakano Tsuyoshi , Yamamoto Masafumi , Matsushima-Hibiya Yuko , Odagiri Ken-Ichi , Yata Osamu , Koyama Kotaro , Sugimura Takashi , Wakabayashi Keiji
Published: February 2008

Cabbage butterflies,
Pieris rapae
and
Pieris brassicae
, contain strong cytotoxic proteins, designated as pierisin-1 and -2, against cancer cell lines. These proteins exhibit DNA ADP-ribosylating activity. To determine the distribution of substances with cytotoxicity and DNA ADP-ribosylating activity among other species, crude extracts from 20 species of the family Pieridae were examined for cytotoxicity in HeLa cells and DNA ADP-ribosylating activity. Both activities were detected in extracts from 13 species: subtribes Pierina (
Pieris rapae
,
Pieris canidia
,
Pieris napi
,
Pieris melete
,
Pieris brassicae
,
Pontia daplidice
, and
Talbotia naganum
), Aporiina (
Aporia gigantea
,
Aporia crataegi
,
Aporia hippia
, and
Delias pasithoe
), and Appiadina (
Appias nero
and
Appias paulina
). All of these extracts contained substances recognized by anti-pierisin-1 antibodies, with a molecular mass of ≈100 kDa established earlier for pierisin-1. Moreover, sequences containing NAD-binding sites, conserved in ADP-ribosyltransferases, were amplified from genomic DNA from 13 species of butterflies with cytotoxicity and DNA ADP-ribosylating activity by PCR. Extracts from seven species,
Appias lyncida
,
Leptosia nina
,
Anthocharis scolymus
,
Eurema hecabe
,
Catopsilia pomona
,
Catopsilia scylla
, and
Colias erate
, showed neither cytotoxicity nor DNA ADP-ribosylating activity, and did not contain substances recognized by anti-pierisin-1 antibodies. Sequences containing NAD-binding sites were not amplified from genomic DNA from these seven species. Thus, pierisin-like proteins, showing cytotoxicity and DNA ADP-ribosylating activity, are suggested to be present in the extracts from butterflies not only among the subtribe Pierina, but also among the subtribes Aporiina and Appiadina. These findings offer insight to understanding the nature of DNA ADP-ribosylating activity in the butterfly.
Benefits of Electronic Audience Response Systems on Student Participation, Learning, and Emotion
Authors: Stowell Jeffrey R. , Nelson Jason M.
Published: February 2008

We compared an electronic audience response system (clickers) to standard lecture, hand-raising, and response card methods of student feedback in simulated introductory psychology classes. After hearing the same 30-min psychology lecture, participants in the clicker group had the highest classroom participation, followed by the response card group, both of which were significantly higher than the hand-raising group. Participants in the clicker group also reported greater positive emotion during the lecture and were more likely to respond honestly to in-class review questions.
Rates of Surgical Site Infection After Hip Replacement as a Hospital Performance Indicator: Analysis of Data From the English Mandatory Surveillance System
Authors: Wilson J. , Charlett A. , Leong G. , McDougall C. , Duckworth G.
Published: February 2008

Objective.

To describe rates of surgical site infection (SSI) after hip replacement and to use these data to provide a simple mechanism for identifying poorly performing hospitals that takes into account variations in sample size.

Design.

Prospective surveillance study.

Setting.

A total of 125 acute care hospitals in England that participated in mandatory SSI surveillance from April 1, 2004 through March 31, 2005.

Patients.

Patients who underwent total hip replacement (THR) or hip hemiarthroplasty (HH).

Methods.

A standard data set was collected for all eligible operations at participating hospitals for a minimum of 3 months annually. Defined methods were used to identify SSIs that occurred during the inpatient stay. Data were checked for quality and accuracy, and funnel plots were constructed by plotting the incidence of SSI against the number of operations.

Results.

Data were collected on 16,765 THRs and 5,395 HHs. The cumulative SSI incidence rates were 1.26% for THR and 4.06% for HH; the incidence densities were 1.38 SSIs per 1,000 postoperative inpatient days for THR and 2.3 SSIs per 1,000 postoperative inpatient days for HH. The risk of infection associated with revision surgery was significantly higher than that associated with primary surgery (2.7% [95% confidence interval, 2.0%-3.5%] vs. 1.1% [95% confidence interval, 1.0%-1.2%];P = .003). Rates varied considerably among hospitals. Nineteen hospitals had rates above the 90th percentile. However, the use of funnel plots to adjust for the precision of estimated SSI rates identified 7 hospitals that warranted further investigation, including 2 with crude rates below the 90th percentile.

Conclusions.

Funnel plots of rates of SSI after hip replacement provide a valuable method of presenting hospital performance data, clearly identifying hospitals with unusually high or low rates while adjusting for the precision of the estimated rate. This information can be used to target and support local interventions to reduce the risk of infection.
Immortalization of Neural Precursors When Telomerase Is Overexpressed in Embryonal Carcinomas and Stem Cells
Authors: Schwob Anneke E. , Nguyen Lilly J. , Meiri Karina F.
Published: February 2008

The DNA repair enzyme telomerase maintains chromosome stability by ensuring that telomeres regenerate each time the cell divides, protecting chromosome ends. During onset of neuroectodermal differentiation in P19 embryonal carcinoma (EC) cells three independent techniques (Southern blotting, Q-FISH, and Q-PCR) revealed a catastrophic reduction in telomere length in nestin-expressing neuronal precursors even though telomerase activity remained high. Overexpressing telomerase protein (mTERT) prevented telomere collapse and the neuroepithelial precursors produced continued to divide, but deaggregated and died. Addition of FGF-2 prevented deaggregation, protected the precursors from the apoptotic event that normally accompanies onset of terminal neuronal differentiation, allowed them to evade senescence, and enabled completion of morphological differentiation. Similarly, primary embryonic stem (ES) cells overexpressing mTERT also initiated neuroectodermal differentiation efficiently, acquiring markers of neuronal precursors and mature neurons. ES precursors are normally cultured with FGF-2, and overexpression of mTERT alone was sufficient to allow them to evade senescence. However, when FGF-2 was removed in order for differentiation to be completed most neural precursors underwent apoptosis indicating that in ES cells mTERT is not sufficient allow terminal differentiation of ES neural precursors in vitro. The results demonstrate that telomerase can potentiate the transition between pluripotent stem cell and committed neuron in both EC and ES cells.
Schizosaccharomyces pombePxl1 Is a Paxillin Homologue That Modulates Rho1 Activity and Participates in Cytokinesis
Authors: Pinar Mario , Coll Pedro M. , Rincón Sergio A. , Pérez Pilar
Published: February 2008

Schizosaccharomyces pombe Rho GTPases regulate actin cytoskeleton organization and cell integrity. We studied the fission yeast gene SPBC4F6.12 based on its ability to suppress the thermosensitivity of cdc42-1625 mutant strain. This gene, named pxl1+, encodes a protein with three LIM domains that is similar to paxillin. Pxl1 does not interact with Cdc42 but it interacts with Rho1, and it negatively regulates this GTPase. Fission yeast Pxl1 forms a contractile ring in the cell division region and deletion of pxl1+causes a delay in cell–cell separation, suggesting that it has a function in cytokinesis. Pxl1 N-terminal region is required and sufficient for its localization to the medial ring, whereas the LIM domains are necessary for its function. Pxl1 localization requires actin polymerization and the actomyosin ring, but it is independent of the septation initiation network (SIN) function. Moreover, Pxl1 colocalizes and interacts with Myo2, and Cdc15, suggesting that it is part of the actomyosin ring. Here, we show that in cells lacking Pxl1, the myosin ring is not correctly assembled and that actomyosin ring contraction is delayed. Together, these data suggest that Pxl1 modulates Rho1 GTPase signaling and plays a role in the formation and contraction of the actomyosin ring during cytokinesis.
Phosphatidylinositol-4-Kinase Type II Alpha Contains an AP-3–sorting Motif and a Kinase Domain That Are Both Required for Endosome Traffic
Authors: Craige Branch , Salazar Gloria , Faundez Victor
Published: February 2008

The adaptor complex 3 (AP-3) targets membrane proteins from endosomes to lysosomes, lysosome-related organelles and synaptic vesicles. Phosphatidylinositol-4-kinase type II α (PI4KIIα) is one of several proteins possessing catalytic domains that regulate AP-3–dependent sorting. Here we present evidence that PI4KIIα uniquely behaves both as a membrane protein cargo as well as an enzymatic regulator of adaptor function. In fact, AP-3 and PI4KIIα form a complex that requires a dileucine-sorting motif present in PI4KIIα. Mutagenesis of either the PI4KIIα-sorting motif or its kinase-active site indicates that both are necessary to interact with AP-3 and properly localize PI4KIIα to LAMP-1–positive endosomes. Similarly, both the kinase activity and the sorting signal present in PI4KIIα are necessary to rescue endosomal PI4KIIα siRNA-induced mutant phenotypes. We propose a mechanism whereby adaptors use canonical sorting motifs to selectively recruit a regulatory enzymatic activity to restricted membrane domains.
Natural variability in δ18O values of otoliths of young Pacific sardine captured in Mexican waters indicates subpopulation mixing within the first year of life
Authors: Valle Sonia R. , Herzka Sharon Z.
Published: February 2008

Valle, S. R., and Herzka, S. Z. 2008. Natural variability in δ18O values of otoliths of young Pacific sardine captured in Mexican waters indicates subpopulation mixing within the first year of life. – ICES Journal of Marine Science, 65: 174–190. Oxygen stable isotopes were measured in whole sagittae of young Pacific sardine (δ18Ooto) collected throughout their range in the Mexican Pacific to quantify natural variability, to reconstruct temperature histories, and to infer whether fish mix at a population or subpopulation level. Isotopic values and derived temperature estimates (Toto) of sardine captured simultaneously showed high variability (up to 2.0‰ and 10°C at a given location). Given limited variations in salinity, this implies differences in thermal history and the prevalence of subpopulation-level mixing processes. We tested the null hypothesis of local residence by comparing δ18Ooto values with predicted isotopic values on a location-specific basis, and age- and location-specific average sea surface temperatures (SSTs) with derived Toto. Some fish exhibited values outside the local range of predicted oxygen isotope values and SSTs, suggesting that they were not permanent residents. Using an otolith growth model, we show that otolith growth and age differences cannot fully account for the variability in δ18Ooto values. The absence of significant differences in δ18Ooto values between the Pacific and Gulf indicates that oxygen isotope ratios cannot be used to examine population structure or migration among these regions. However, they can be used to infer mixing within and among subpopulations.
OsRAR1 and OsSGT1 Physically Interact and Function in Rice Basal Disease Resistance
Authors: Wang Yaling , Gao Mingjun , Li Qun , Wang Linyou , Wang Jianjun , Jeon Jong-Seong , Qu Na , Zhang Yuelin , He Zuhua
Published: February 2008

The RAR1 and SGT1 proteins function synergistically or antagonistically in plant innate immune responses. Here, we show that the rice orthologs OsRAR1 and OsSGT1 physically interact in vivo and in yeast. They displayed conserved roles in Arabidopsis disease resistance through ectopic expression in the Arabidopsis rar1 and sgt1 mutants. Overexpression of OsRar1 and OsSGT1 in rice significantly increased basal resistance to a virulent bacterial blight Xanthomonas oryzae pv. oryzae PXO99 but not to another virulent strain DY89031, suggesting race-specific-like basal resistance conferred by OsRar1 and OsSGT1. OsRar1-OE and OsSGT1-OE plants also enhanced resistance to all four virulent blast fungal Magnaporthe oryzae races. Overexpression of the OsSGT1-green fluorescent protein (GFP) fusion most likely caused a dominant negative phenotype which led to race-specific-like basal resistance. Transgenic plants overexpressing OsSGT1-GFP show enhanced resistance to DY89031 but decreased resistance to PXO99, implying that OsSGT1 might be the target of a component required for DY89031 virulence or OsSGT1-GFP might stabilize weak resistance proteins against DY89031. Consistent with the hypothesis of the dominant negative regulation, we observed the reduced sensitivity to auxin of OsSGT1-GFP plants compared with the wild-type ones, and the curling-root phenotype in OsSGT1-OE plants. These results collectively suggest that OsRar1 and OsSGT1 might be differentially required for rice basal disease resistance. Our current study also provides new insight into the roles of OsSGT1 in basal disease resistance.
The Arg-Gly-Asp–Containing, Solvent-Exposed Loop of Ptr ToxA Is Required for Internalization
Authors: Manning Viola A. , Hamilton Sara M. , Karplus P. Andrew , Ciuffetti Lynda M.
Published: February 2008

Internalization of the proteinaceous host-selective toxin, Ptr ToxA (ToxA), into sensitive wheat mesophyll cells is correlated with toxin activity. The solvent-exposed, Arg-Gly-Asp (RGD)-containing loop of ToxA is a candidate for interaction with the plasma membrane, which is a likely prerequisite to toxin internalization. Based on the percentage of cells affected by a given number of ToxA molecules in a treatment zone, the number of ToxA molecules bound to high-affinity sites was estimated at 3 × 106 per cell and the Kd for binding was estimated to be near 1 nM. An improved heterologous expression method of proteins that contain mutations in ToxA, coupled with a newly developed semiquantitative bioassay, revealed that some amino acids in the RGD-containing loop contribute more to toxin activity than others. Protease protection assays that detect internalized protein and inhibition of toxin uptake indicated that, for each ToxA variant tested, the extent of toxin activity correlates with the amount of internalized protein. RGD-containing peptide inhibition of both activity and internalization supported these findings. These data support the hypothesis that ToxA interacts with a high-affinity binding site on wheat mesophyll cells through the RGD-containing, solvent-exposed loop, resulting in toxin internalization and eventual cell death. The inability to detect phosphorylation of ToxA in vitro and in vivo suggests that a putative CKII phosphorylation site in the RGD-containing loop is required for internalization, not phosphorylation.
Tobacco mosaic virus (TMV) Replicase and Movement Protein Function Synergistically in Facilitating TMV Spread by Lateral Diffusion in the Plasmodesmal Desmotubule of Nicotiana benthamiana
Authors: Guenoune-Gelbart Dana , Elbaum Michael , Sagi Guy , Levy Amit , Epel Bernard L.
Published: February 2008

Virus spread through plasmodesmata (Pd) is mediated by virus-encoded movement proteins (MPs) that modify Pd structure and function. The MP of Tobacco mosaic virus (TMVMP) is an endoplasmic reticulum (ER) integral membrane protein that binds viral RNA (vRNA), forming a vRNA:MP:ER complex. It has been hypothesized that TMVMP causes Pd to dilate, thus potentiating a cytoskeletal mediated sliding of the vRNA:MP:ER complex through Pd; in the absence of MP, by contrast, the ER cannot move through Pd. An alternate model proposes that cell-to-cell spread takes place by diffusion of the MP:vRNA complex in the ER membranes which traverse Pd. To test these models, we measured the effect of TMVMP and replicase expression on cell-to-cell spread of several green fluorescent protein-fused probes: a soluble cytoplasmic protein, two ER lumen proteins, and two ER membrane-bound proteins. Our data support the diffusion model in which a complex that includes ER-embedded MP, vRNA, and other components diffuses in the ER membrane within the Pd driven by the concentration gradient between an infected cell and adjacent noninfected cells. The data also suggest that the virus replicase and MP function together in altering Pd conductivity.
Use of Pyrosequencing to Quantify Incidence of a SpecificAspergillus flavusStrain Within Complex Fungal Communities Associated with Commercial Cotton Crops
Authors: Das Modan K. , Ehrlich Kenneth C. , Cotty Peter J.
Published: February 2008

Atoxigenic strains of Aspergillus flavus have been used as aflatoxin management tools on over 50,000 hectares of commercial crops since 2000. To assess treatment efficacy, atoxigenic strain incidence is routinely monitored by vegetative compatibility analyses (VCA) that require culturing, generation of auxotrophs, and complementation with tester mutants. Two pyrosequencing assays (PA) that require no culturing were developed for monitoring incidences of atoxigenic strains on ginned cottonseed. The assays, which quantify frequencies of characteristic single nucleotide polymorphisms (SNPs) in the aflR and pksA genes, were validated against standard VCA on cottonseed collected from commercial gins in South Texas, Arizona, and Southern California where the atoxigenic strain AF36 is used to manage aflatoxin contamination. Cottonseed washings were subjected to both VCA and PA. PA was performed directly on DNA isolated from particulates pelleted from the wash water by centrifugation. Addition of CaCl2and diatomaceous earth prior to pelleting increased the amount of DNA isolated. Accuracy and reproducibility of the PA were contrasted with those for the VCA that has been used for over a decade. Correlation coefficients between VCA and PA indicated good correspondence between the results from the two assays (r = 0.91 for aflR assay and r = 0.80 for pksA assay). PAs were highly variable for samples with low incidences of A. flavus due to variability in the initial polymerase chain reaction step. This held for both DNA isolated from cottonseed washes and for mixtures of purified DNA. For samples yielding low quantities of A. flavus DNA, averaging of results from 4 to 5 replicates was required to achieve acceptable correlations with VCA. Pyrosequencing has the potential to become a powerful tool for monitoring atoxigenic strains within complex A. flavus communities without limitations imposed by traditional culturing methods.
A Set of Novel RNAs Transcribed from the Chloroplast Genome Accumulates in Date Palm Leaflets Affected by Brittle Leaf Disease
Authors: Marqués J. , Fadda Z. G. N. , Duran-Vila N. , Flores R. , Bové J. M. , Daròs J. A.
Published: February 2008

Brittle leaf disease or maladie des feuilles cassantes (MFC) is a lethal disorder of date palms that has assumed epidemic proportions in the oases of southern Tunisia. After a prolonged period during which palms are declining, the disease ends with the death of the palms. Whereas no pathogen could ever be associated with the disease, leaflets of affected palms have been previously shown to be deficient in manganese. Analysis of RNA preparations from leaflets of MFC-affected palms revealed the presence of a set of novel RNAs (MFC-RNAs) of sense and antisense polarities, which are homologous to various regions of the date palm chloroplast genome, such as the regions containing genes rrn5S-trnR(ACG) and trnM(CAU)-atpE. In the RNA preparations obtained from leaflets of affected palms, some of these RNAs are present as double-stranded species (MFC-dsRNAs), as witnessed by results from cellulose chromatography, end labeling, RNase digestion, and northern hybridization with strand specific probes. These MFC-RNAs represent a novel type of host-derived RNAs, and their presence in MFC-affected date palms is of diagnostic value.
Genome-wide mapping and characterization of hypomethylated sites in human tissues and breast cancer cell lines
Authors: Shann Yih-Jyh , Cheng Ching , Chiao Chun-Hui , Chen Dow-Tien , Li Pei-Hsin , Hsu Ming-Ta
Published: February 2008

We have developed a method for mapping unmethylated sites in the human genome based on the resistance of TspRI-digested ends to ExoIII nuclease degradation. Digestion with TspRI and methylation-sensitive restriction endonuclease HpaII, followed by ExoIII and single-strand DNA nuclease allowed removal of DNA fragments containing unmethylated HpaII sites. We then used array comparative genomic hybridization (CGH) to map the sequences depleted by these procedures in human genomes derived from five human tissues, a primary breast tumor, and two breast tumor cell lines. Analysis of methylation patterns of the normal tissue genomes indicates that the hypomethylated sites are enriched in the 5′ end of widely expressed genes, including promoter, first exon, and first intron. In contrast, genomes of the MCF-7 and MDA-MB-231 cell lines show extensive hypomethylation in the intragenic and intergenic regions whereas the primary tumor exhibits a pattern between those of the normal tissue and the cell lines. A striking characteristic of tumor cell lines is the presence of megabase-sized hypomethylated zones. These hypomethylated zones are associated with large genes, fragile sites, evolutionary breakpoints, chromosomal rearrangement breakpoints, tumor suppressor genes, and with regions containing tissue-specific gene clusters or with gene-poor regions containing novel tissue-specific genes. Correlation with microarray analysis shows that genes with a hypomethylated sequence 2 kb up- or downstream of the transcription start site are highly expressed, whereas genes with extensive intragenic and 3′ untranslated region (UTR) hypomethylation are silenced. The method described herein can be used for large-scale screening of changes in the methylation pattern in the genome of interest.
Systematic functional characterization ofcis-regulatory motifs in human core promoters
Authors: Sinha Saurabh , Adler Adam S. , Field Yair , Chang Howard Y. , Segal Eran
Published: February 2008

A large number ofcis-regulatory motifs involved in transcriptional control have been identified, but the regulatory context and biological processes in which many of them function are unknown. Here, we computationally identify the sets of human core promoters targeted by motifs, and systematically characterize their function by using a robust gene-set-based approach and diverse sources of biological data. We find that the target sets of most motifs contain both genes with similar function and genes that are coregulated in vivo, thereby suggesting both the biological process regulated by the motifs and the conditions in which this regulation may occur. Our analysis also identifies many motifs whose target sets are predicted to be regulated by a common microRNA, suggesting a connection between transcriptional and post-transcriptional control processes. Finally, we predict novel roles for uncharacterized motifs in the regulation of specific biological processes and certain types of human cancer, and experimentally validate four such predictions, suggesting regulatory roles for four uncharacterized motifs in cell cycle progression. Our analysis thus provides a concrete framework for uncovering the biological function ofcis-regulatory motifs genome wide.
The Effect of Attitudes in the Therapy of the Alcoholic*
Authors: KENDIS JOSEPH B.
Published: February 2008

Résumé Le type d'alcoolisme discuté dans ce rapport est celui décrit par Jellinek comme alcoolisme gamma, la forme prédominante de cette maladie aux Etats Unis.

Les attitudes décrites comprennent celles du médecin de famille, du psychiatre, du personnel de l'hôpital, de la famille elle‐même, des agences communautaires, de l'industrie et de tous ceux qui pourraient être en contact et avoir quelque influence dans la vie de l'alcoolique.

Des suggestions sont faites, pour améliorer les attitudes afin que l'alcoolique reçoive plus de compréhension et d'aide.

Finalement, il est précisé que de justes attitudes pourraient assister et être d'une très grande valeur, non seulement pour l'alcoolique mais également à sa famille et à son entourage de même qu'à la communauté entière.

Die in dieser Abhandlung beschriebene Art von Alkoholismus wird von Jellenek als “Gamma Alkoholismus” bezeichnet und stellt die vorherrschende Form dieses Übels in den Vereinigten Staaten dar.

Die beschriebenen Einstellungen umfassen die des Hausarztes, des Psychiaters, des Krankenhauspersonals, der Familie selbst, der öffentlichen Gemeinschaftsstellen, der Industrie und aller jener, welche mit Alkoholikern in Kontakt kommen können und einigen Einfluss auf deren Lebensweise haben.

Es werden Vorschläge zur Verbesserung der Einstellungen gemacht, um grösseres Verständnis und mehr Hilfe für Alkoholiker zu erzielen.

Abschliessend wird darauf hingewiesen, dass richtige Einstellungen nicht nur für den Alkoholiker sondern auch für seine Familie und seine Umgebung sowie das gesamte Gemeinwesen von Hilfe und grossem Wert sein können.
Klinische Untersuchungsergebnisse an Alkoholkranken
Authors: SCHMIDT L.
Published: February 2008

Abstract— Examination at a clinical department for internal medicine of 84 alcoholics, who had primarily been admitted on account of alcoholism, revealed that these patients had also organic defects. Nearly all alcoholics showed changes in the region of the gastrointestinal tract; 33.3% had a roentgenologically detectable gastritis and 80% a “SAB” or anacidity.

In addition to palpation and liver blank punctures, a series of functional liver tests were carried out and their diagnostic value for the alcohol‐damaged liver evaluated. It appeared necessary that liver puctures and liver examinations should be carried out as soon as possible after the last alcoholic excess. The Menghini blank puncture, which is usually made 4 days after alcohol deprivation, showed in 38˙2% of the cases a diffuse adipohepatic liver, in 26˙9% a fatty liver with fibroplasia and in 13˙3% a fatty liver with lobuli umbones in the sense of a cirrhosis. During commencement of the treatment it could frequently be established that, apart from upper‐abdominal pressure and hepatomegaly, the following symptoms were present: a contracted Weltmann's coagulation band, a slight cooling of the sero‐cholesterol and bilirubin concentration levels, a slight reduction in the prothrombin content, a positive two‐stain test, increased S6OT and S6PT activities, a slight increase in the blood sedimentation rate and a decrease in the serum with increased globulin.

Multiplex haemosiderosis of the liver could not be detected; 19˙6% of the patients showed increased sero‐diastatic values. It is to be hoped that pancreas diagnosis will profit from Weber's lipase evaluation.

Alcoholism affects the circulatory and myocardial metabolism. An increase of the eosinophil cells could be observed in the blood count. As a slight transitory proteinuria sets in after alcoholic excess, it may be assumed that alcohol affects the kidneys. Hence, alcoholism causes multiplex functional disorders, organic damage respectively.
Nutmeg as a Psychoactive Agent
Authors: BEATTIE R. T.
Published: February 2008

Résumé— La muscade n'a pas d'effet psychologique dans le domaine du comportement, quand elle est administrée dans cette quantité. Il paraît très improbable qu'elle ait quelque effet quand elle est donné dans des quantités plus grandes; donc, il paraît très probable que les rapports publiés concernant son efficacité sont basés sur des expériences subjectives causées par la signification des conditions dans lesquelles elle a été prise.

Zusammenfassung— Muskatnuss, wenn in diesen Mengen verabreicht, hat keinerlei psychologischen Effekt im Bereiche der Verhaltens‐Erhebungsauswahl. Auch scheint es höchst unwahrscheinlich, dass bei Verabreichung grösserer Mengen eine Wirkung erzielt wird, weshalb es sehr wahrscheinlich ist, dass sich Berichte über die Wirksamkeit dieses Mittlcs vollständig auf subjektive Erfahrungen stützen, welche durch Beziehungsandeu‐tungen der Bedingungen, unter welchen es eingenommen wurde, ausgelöst wurden.