bluuebunny/crossref_metadata_2025 huggingface dataset:
Larval migration ofToxocara canisin piglets and transfer of larvae from infected porcine tissue to mice
Authors: Sasmal N.K. , Acharya S. , Laha R.
Published: April 2008

Visceral larva migrans (VLM), caused byToxocara canislarvae in humans, animals and birds, is now well documented throughout the world. Seven piglets were infected orally with 5 × 104embryonated eggs and the migration and distribution ofT. canislarvae in the tissues were evaluated. After artificial gastric juice digestion, larval yields at necropsy from different organs and muscles on days 1, 3, 7, 15 and 30 post-infection (DPI) revealed 3.05, 0.97, 0.21, 0.13, 0.05, 0.14% recovery from liver, lungs, heart, kidneys, skeletal muscles and brain tissues respectively, with a total of 2486 (4.97%) recovery from all tissues together. The highest number of larvae 1527 (3.05%) was recovered from the liver throughout the period (1–30 DPI), indicating a special affinity of larvae for the liver. Subsequently five mice were each infected orally with 5 g of infected pig liver and, after necropsy on 10 DPI, 20 ± 3.62, 17 ± 5.10, 3 ± 1.26, 12 ± 3.92 and 30 ± 5.69 larvae were recovered from liver, lungs, heart, brain and muscles, respectively. Thus, primarily, the migratory potential and adaptation ofT. canislarvae in porcine tissue was examined and, subsequently, their establishment in the second paratenic host, the mouse, has been successful. No influence of host sex on the migratory potential ofT. canislarvae was observed. The related pathology caused by migratory larvae and its zoonotic significance through the consumption of raw or undercooked pork has been emphasized.
Deafness in the developing world: the place of cochlear implantation
Authors: Tarabichi M B , Todd C , Khan Z , Yang X , Shehzad B , Tarabichi M M
Published: April 2008

Introduction:

This paper attempts to review changes in the lives of hearing-impaired patients within the developing world, brought about by globalisation and development. The paper also explores limitations to improved care and addresses the collective moral responsibility of developed nations.

Methods:

Analysis of literature.

Results:

Within developing nations, large populations have emerged with a similar pattern of problems, access to information and aspirations as those living in developed nations. However, marked differences in income have persisted. These trends have resulted in a relative increase in the proportion of the hearing-impaired population in need of cochlear implantation, while at the same time restricting their access to such treatment.

Conclusions:

The emergence of global markets and media and a shared sense of destiny amongst the people of this planet should translate into a concerted, worldwide effort to assist the deaf in developing countries. Much more can be done within existing resources and frameworks to improve the quality of these peoples' lives.
THEMIS observations of modified Hall fields in asymmetric magnetic field reconnection
Authors: Mozer F. S. , Angelopoulos V. , Bonnell J. , Glassmeier K. H. , McFadden J. P.
Published: April 2008

Field and plasma measurements from three THEMIS spacecraft are compared during a back‐and‐forth crossing of an asymmetric, reconnecting, sub‐solar magnetopause to explain the apparent absence of the quadrupolar magnetic field and part of the bipolar electric field that are found during symmetric magnetic field reconnection. The differences in the reconnection magnetic fields in the asymptotic regions (a factor of three) and the plasma densities (a factor of 30) combine to make the Hall MHD term and the resulting Hall electric field in the Generalized Ohm's law significant only on the magnetospheric side of the magnetopause. Qualitative analysis indicates that the single particle and fluid trajectories in such fields are different from those in the case of symmetric boundary conditions.
Fine aeolian quartz records in Cheju Island, Korea, during the last 6500 years and pathway change of the westerlies over east Asia
Authors: Lim Jaesoo , Matsumoto Eiji
Published: April 2008

We investigated the fine component of aeolian dust deposited on a maar of Cheju Island, Korea, during the last 6500 years to specify the variability of fine aeolian dust transported by the westerlies and its main controlling factor from the viewpoint of global atmospheric circulation. As a proxy for the fine aeolian dust, we used the fine component of chemically isolated aeolian quartz from bulk sediments. The fine quartz flux (FQF) varies from 0.1 to 1.4 mg/cm2/a with periodicities of 1620, 810, 400, 325, and 210 years, mainly providing information on the aridity change in the dust source region (the Taklimakan Desert). The median grain size of the fine quartz (MFQ) representing the pathway of the dust‐transporting westerlies fluctuates between 2 and 6 μm with significant cycles of 1030, 390, 280, 220, and 195 years and shows similar variation pattern to the FQF. On the basis of visual and spectral analyses, the high/low FQF and the large/small MFQ correspond to the warm/cold atmospheric temperature record from Greenland ice cores with significant coherent cycles, indicating that the aridity in the dust source areas and the pathway of the westerlies in east Asia were linked to climatic and atmospheric conditions in Greenland through the pathway change of the westerlies. During the middle to late Holocene, the pathway change of the westerlies mainly responsible for the variability of the fine aeolian dust in east Asia was probably controlled by a climatic response to initial solar activity and resulting atmospheric reorganization in polar and high‐latitude regions.
Temporal and spatial characteristics of positive and negative Indian Ocean dipole with and without ENSO
Authors: Hong Chi‐Cherng , Lu Mong‐Ming , Kanamitsu Masao
Published: April 2008

The differences in the temporal evolution and spatial characteristics of the Indian Ocean Dipole (IOD) between positive and negative events with and without ENSO have been investigated using observations for the period 1948–2002. To document such differences is particularly important for climate forecasts over far east Asia, since distinctly different monsoon activities over China, Korea, and Japan for different types of IOD are found in the composite maps of precipitation anomalies. The composite map of SST and wind during various stages of IOD and the ocean mixed layer heat budget showed that the IOD with and without ENSO has a large difference in its temporal evolutions and their triggering mechanisms. In both negative and positive IOD events without ENSO, the wind anomaly in the eastern Indian Ocean seems to be responsible for the formation of sea surface temperature anomalies, while the anomaly in the western Indian Ocean seems to be the oceanic dynamical response to the anomaly in the east. During the ENSO years, the temporal and spatial contrast of the asymmetry of the IOD evolution is smaller, and the SST anomaly is driven by the anomalies in incoming radiation due to changes in cloudiness caused by the ENSO associated anomalous atmospheric circulations and not by the local wind anomalies.
Volatile organic compounds in northern New England marine and continental environments during the ICARTT 2004 campaign
Authors: White M. L. , Russo R. S. , Zhou Y. , Mao H. , Varner R. K. , Ambrose J. , Veres P. , Wingenter O. W. , Haase K. , Stutz J. , Talbot R. , Sive B. C.
Published: April 2008

Volatile organic compound (VOC) measurements were made during the summer 2004 International Consortium for Atmospheric Research on Transport and Transformation (ICARTT) at Thompson Farm (TF), a continental site 25 km from the New Hampshire coast, and Appledore Island (AI), a marine site 10 km off the Maine coast. The 24 h mean total hydroxyl radical (OH) reactivity (±1σ) for the suite of VOCs was 4.15 (±2.64) s−1 at TF and 2.57 (±1.10) s−1 at AI. The larger range of reactivity at TF was dominated by isoprene and the monoterpenes (mean combined reactivity = 2.01 (±2.57) s−1). The impact of local anthropogenic hydrocarbon sources such as liquefied petroleum gas (LPG) leakage and fossil fuel evaporation was evident at both sites. During the campaign, a propane flux of 9 (±2) × 109 molecules cm−2 s−1 was calculated from the linear regression of the mean 0100–0400 local time mixing ratios at TF. This is consistent with fluxes observed in 2003 at sites spread throughout the coastal area of New Hampshire indicating that LPG tank leakage is a major hydrocarbon source throughout the region. Net monoterpene fluxes during ICARTT at TF were 6 (±2), 1.8 (±0.4), 1.2 (±0.6), and 0.4 (±0.5) × 109 molecules cm−2 s−1 for α‐pinene, β‐pinene, camphene, and limonene, respectively. Comparison to estimated NO3 and O3 loss rates indicate that gross monoterpene emission rates were approximately double the observed net fluxes at TF and comparable to current monoterpene nighttime emission inventory estimates for the northeast.
THEMIS observations of penetration of the plasma sheet into the ring current region during a magnetic storm
Authors: Wang Chih‐Ping , Lyons Larry R. , Angelopoulos Vassilis , Larson Davin , McFadden J. P. , Frey Sabine , Auster Hans‐Ulrich , Magnes Werner
Published: April 2008

Observations from the THEMIS spacecraft during a weak magnetic storm clearly show that the inner edge of the ion plasma sheet near dusk moved from r ∼ 6 RE during the pre‐storm quiet time to r ∼ 3.5 RE during the main phase, and then moved outward during the recovery phase. The plasma sheet particles from the tail reached the inner magnetosphere during the main phase through open drift paths, which extended earthward with increasing convection, and were energized to ring current energies, resulting in an increase in ring current population. During the recovery phase, the plasma sheet region retreated to outside the inner magnetosphere as the region of open drift paths moved outward with decreasing convection, leaving the ring current particles within the expended closed drift path region. With no new particles from the plasma sheet, ring current population gradually decreased due to losses as the recovery phase proceeded.
Calcium carbonate as ikaite crystals in Antarctic sea ice
Authors: Dieckmann Gerhard S. , Nehrke Gernot , Papadimitriou Stathys , Göttlicher Jörg , Steininger Ralph , Kennedy Hilary , Wolf‐Gladrow Dieter , Thomas David N.
Published: April 2008

We report on the discovery of the mineral ikaite (CaCO3·6H2O) in sea‐ice from the Southern Ocean. The precipitation of CaCO3 during the freezing of seawater has previously been predicted from thermodynamic modelling, indirect measurements, and has been documented in artificial sea ice during laboratory experiments but has not been reported for natural sea‐ice. It is assumed that CaCO3 formation in sea ice may be important for a sea ice‐driven carbon pump in ice‐covered oceanic waters. Without direct evidence of CaCO3 precipitation in sea ice, its role in this and other processes has remained speculative. The discovery of CaCO3·6H2O crystals in natural sea ice provides the necessary evidence for the evaluation of previous assumptions and lays the foundation for further studies to help elucidate the role of ikaite in the carbon cycle of the seasonally sea ice‐covered regions
Historical trends in the jet streams
Authors: Archer Cristina L. , Caldeira Ken
Published: April 2008

Jet streams, the meandering bands of fast winds located near the tropopause, are driving factors for weather in the midlatitudes. This is the first study to analyze historical trends of jet stream properties based on the ERA‐40 and the NCEP/NCAR reanalysis datasets for the period 1979 to 2001. We defined jet stream properties based on mass and mass‐flux weighted averages. We found that, in general, the jet streams have risen in altitude and moved poleward in both hemispheres. In the northern hemisphere, the jet stream weakened. In the southern hemisphere, the sub‐tropical jet weakened, whereas the polar jet strengthened. Exceptions to this general behavior were found locally and seasonally. Further observations and analysis are needed to confidently attribute the causes of these changes to anthropogenic climate change, natural variability, or some combination of the two.
Tlr‐4 Deficiency Selectively Protects Against Obesity Induced by Diets High in Saturated Fat
Authors: Davis Jeremy E. , Gabler Nicholas K. , Walker‐Daniels Jennifer , Spurlock Michael E.
Published: April 2008

Toll‐like receptor‐4 (Tlr‐4), a key pattern recognition receptor involved in innate immune response, is activated by saturated fatty acids (SFAs). To investigate the involvement of this receptor in obesity caused by consumption of diets high in fat, we utilized male Tlr‐4‐deficient 10ScN mice and 10J controls. Mice were fed either low fat (low‐fat control (LFC)), high unsaturated fat (high‐fat control (HFC)), or high saturated fat + palmitate (HFP) diets ad libitum for 16 weeks. Relative to the LFC diet, the HFC diet resulted in greater epididymal fat pad weights and adipocyte hypertrophy in both Tlr‐4‐deficient and normal mice. However, the 10ScN mice were completely protected against the obesigenic effects of the HFP diet. Moreover, macrophage infiltration and monocyte chemotactic protein‐1 (MCP‐1) transcript abundance were lower in adipose tissue of 10ScN mice fed the HFP diet, and the hyperinsulinemic response was negated. Tlr‐4‐deficient mice also had markedly lower circulating concentrations of MCP‐1 and much less nuclear factor‐κB (NFκB) protein in nuclear extracts prepared from adipose tissue, irrespective of diet. In contrast, Tlr‐4 deficiency did not attenuate the induction of tumor necrosis factor‐α (TNF‐α) or interleukin‐6 (IL‐6) expression in adipose tissue. These data indicate that Tlr‐4 deficiency selectively protects against the obesigenic effects of SFA and alters obesity‐related inflammatory responses in adipose tissue.
Stardust in the Laboratory
Authors: Zinner Ernst
Published: April 2008

Primitive meteorites and interplanetary dust particles contain small grains that originated in stellar outflows and supernova explosions. These μm- and sub-μm-sized presolar grains can be isolated and studied for their isotopic compositions in the laboratory. They are recognised as stardust by their isotopic compositions, which are completely different from those of the Solar System. They provide new information on stellar evolution, nucleosynthesis, mixing processes in asymptotic giant branch (AGB) stars and supernovae, and Galactic chemical evolution. Red giants, AGB stars, Type II supernovae and possibly novae have been identified as stellar sources of the grains. Of the eight nuclear processes proposed by Burbidge et al. (1957), signatures of all except the r-process can be found in presolar dust grains.
Max Mara and the Origins of Italian Ready-to-Wear
Authors: White Nicola
Published: April 2008

This article charts the establishment and expansion of the ready-to-wear Max Mara label before the birth of the Max Mara group in 1967. Until recently, little consideration has been given to the evolution of Italian fashion, and few histories of dress or Italian culture even mention its presence before the 1970s. Still fewer acknowledge the crucial emergence of fashionable ready-to-wear in Italy in the 1960s, in which Max Mara played a key role, and which anticipated the international success of ‘Italian style’ in the 1970s and 1980s.
THE SOUTH, THE STATE AND ECONOMIC DEVELOPMENT: REMARKS ON PIERO BEVILACQUA'S ‘OLD AND NEW IN THE SOUTHERN QUESTION’
Authors: Bull Anna
Published: April 2008

I am taking the opportunity created by the recent introduction of a section entitled ‘Contexts and Debates’ to put forward some considerations regarding Bevilacqua's contribution on the southern question, which appeared in the last number of this journal. By doing so, I hope to promote a stimulating debate on the South of Italy today and on the way forward for reversing the current process of de-industrialization in the region and the widening gap between the South and the rest of the country. Ideally, the debate should encourage different points of view and interpretations without reopening old wounds or leading to entrenched positions.
Decoding ARE-mediated decay: is microRNA part of the equation?
Authors: von Roretz Christopher , Gallouzi Imed-Eddine
Published: April 2008

Messenger ribonucleic acids (mRNAs) containing adenine/uridine-rich elements (AREs) in their 3′ untranslated region are particularly labile, allowing for the regulation of expression for growth factors, oncoproteins, and cytokines. The regulators, effectors, and location of ARE-mediated decay (AMD) have been investigated by many groups in recent years, and several links have been found between AMD and microRNA-mediated decay. We highlight these similarities, along with recent advances in the field of AMD, and also mention how there is still much left unknown surrounding this specialized mode of mRNA decay.
Whistler wave excitation by a loop antenna in a bounded collisional magnetoplasma
Authors: Kudrin A V , Es'kin V A , Krafft C , Zaboronkova T M
Published: April 2008

Excitation of electromagnetic waves by spatially bounded given electric currents in the presence of an axially magnetized cylindrical plasma column surrounded by free space is studied. A rigorous solution for the total field comprising both the discrete and continuous parts of the spatial spectrum of the excited waves is found. Using the obtained field representation, an expression for the impedance of a loop antenna is derived and the contributions of guided and unguided modes of the column to the antenna impedance are determined for the whistler frequency range. Conditions have been revealed under which the real part of the antenna impedance is dominated by the contribution of guided waves. It is shown that when allowance for relatively small collisional losses in the plasma results in division of the guided whistler waves into weakly and strongly damped modes with significantly different field structures, appreciable redistribution of the antenna-launched power among the excited modes takes place. The results obtained are useful for clarification of the power-absorption mechanisms of whistler-range waves in a cylindrical magnetoplasma.
The Subcellular Distribution of Calnexin Is Mediated by PACS-2
Authors: Myhill Nathan , Lynes Emily M. , Nanji Jalal A. , Blagoveshchenskaya Anastassia D. , Fei Hao , Carmine Simmen Katia , Cooper Timothy J. , Thomas Gary , Simmen Thomas
Published: April 2008

Calnexin is an endoplasmic reticulum (ER) lectin that mediates protein folding on the rough ER. Calnexin also interacts with ER calcium pumps that localize to the mitochondria-associated membrane (MAM). Depending on ER homeostasis, varying amounts of calnexin target to the plasma membrane. However, no regulated sorting mechanism is so far known for calnexin. Our results now describe how the interaction of calnexin with the cytosolic sorting protein PACS-2 distributes calnexin between the rough ER, the MAM, and the plasma membrane. Under control conditions, more than 80% of calnexin localizes to the ER, with the majority on the MAM. PACS-2 knockdown disrupts the calnexin distribution within the ER and increases its levels on the cell surface. Phosphorylation by protein kinase CK2 of two calnexin cytosolic serines (Ser554/564) reduces calnexin binding to PACS-2. Consistent with this, a Ser554/564 [Formula: see text] Asp phosphomimic mutation partially reproduces PACS-2 knockdown by increasing the calnexin signal on the cell surface and reducing it on the MAM. PACS-2 knockdown does not reduce retention of other ER markers. Therefore, our results suggest that the phosphorylation state of the calnexin cytosolic domain and its interaction with PACS-2 sort this chaperone between domains of the ER and the plasma membrane.
Redundant Roles of BIG2 and BIG1, Guanine-Nucleotide Exchange Factors for ADP-Ribosylation Factors in Membrane Traffic between thetrans-Golgi Network and Endosomes
Authors: Ishizaki Ray , Shin Hye-Won , Mitsuhashi Hiroko , Nakayama Kazuhisa
Published: April 2008

BIG2 and BIG1 are closely related guanine-nucleotide exchange factors (GEFs) for ADP-ribosylation factors (ARFs) and are involved in the regulation of membrane traffic through activating ARFs and recruiting coat protein complexes, such as the COPI complex and the AP-1 clathrin adaptor complex. Although both ARF-GEFs are associated mainly with the trans-Golgi network (TGN) and BIG2 is also associated with recycling endosomes, it is unclear whether BIG2 and BIG1 share some roles in membrane traffic. We here show that knockdown of both BIG2 and BIG1 by RNAi causes mislocalization of a subset of proteins associated with the TGN and recycling endosomes and blocks retrograde transport of furin from late endosomes to the TGN. Similar mislocalization and protein transport block, including furin, were observed in cells depleted of AP-1. Taken together with previous reports, these observations indicate that BIG2 and BIG1 play redundant roles in trafficking between the TGN and endosomes that involves the AP-1 complex.
Gcn4 Is Required for the Response to Peroxide Stress in the Yeast Saccharomyces cerevisiae
Authors: Mascarenhas Claire , Edwards-Ingram Laura C. , Zeef Leo , Shenton Daniel , Ashe Mark P. , Grant Chris M.
Published: April 2008

An oxidative stress occurs when reactive oxygen species overwhelm the cellular antioxidant defenses. We have examined the regulation of protein synthesis in Saccharomyces cerevisiae in response to oxidative stress induced by exposure to hydroperoxides (hydrogen peroxide, and cumene hydroperoxide), a thiol oxidant (diamide), and a heavy metal (cadmium). Examination of translational activity indicates that these oxidants inhibit translation at the initiation and postinitiation phases. Inhibition of translation initiation in response to hydroperoxides is entirely dependent on phosphorylation of the α subunit of eukaryotic initiation factor (eIF)2 by the Gcn2 kinase. Activation of Gcn2 is mediated by uncharged tRNA because mutation of its HisRS domain abolishes regulation in response to hydroperoxides. Furthermore, Gcn4 is translationally up-regulated in response to H2O2, and it is required for hydroperoxide resistance. We used transcriptional profiling to identify a wide range of genes that mediate this response as part of the Gcn4-dependent H2O2-regulon. In contrast to hydroperoxides, regulation of translation initiation in response to cadmium and diamide depends on both Gcn2 and the eIF4E binding protein Eap1. Thus, the response to oxidative stress is mediated by oxidant-specific regulation of translation initiation, and we suggest that this is an important mechanism underlying the ability of cells to adapt to different oxidants.
Analysis of the Yeast Kinome Reveals a Network of Regulated Protein Localization during Filamentous Growth
Authors: Bharucha Nikë , Ma Jun , Dobry Craig J. , Lawson Sarah K. , Yang Zhifen , Kumar Anuj
Published: April 2008

The subcellular distribution of kinases and other signaling proteins is regulated in response to cellular cues; however, the extent of this regulation has not been investigated for any gene set in any organism. Here, we present a systematic analysis of protein kinases in the budding yeast, screening for differential localization during filamentous growth. Filamentous growth is an important stress response involving mitogen-activated protein kinase and cAMP-dependent protein kinase signaling modules, wherein yeast cells form interconnected and elongated chains. Because standard strains of yeast are nonfilamentous, we constructed a unique set of 125 kinase-yellow fluorescent protein chimeras in the filamentous Σ1278b strain for this study. In total, we identified six cytoplasmic kinases (Bcy1p, Fus3p, Ksp1p, Kss1p, Sks1p, and Tpk2p) that localize predominantly to the nucleus during filamentous growth. These kinases form part of an interdependent, localization-based regulatory network: deletion of each individual kinase, or loss of kinase activity, disrupts the nuclear translocation of at least two other kinases. In particular, this study highlights a previously unknown function for the kinase Ksp1p, indicating the essentiality of its nuclear translocation during yeast filamentous growth. Thus, the localization of Ksp1p and the other kinases identified here is tightly controlled during filamentous growth, representing an overlooked regulatory component of this stress response.
A qualitative biological risk assessment for vase tunicate Ciona intestinalis in Canadian waters: using expert knowledge
Authors: Therriault Thomas W. , Herborg Leif-Matthias
Published: April 2008

Therriault, T. W., and Herborg, L-M. 2008. A qualitative biological risk assessment for vase tunicate Ciona intestinalis in Canadian waters: using expert knowledge. – ICES Journal of Marine Science, 65: 781–787. Non-indigenous species (NIS) can pose a significant level of risk, through potential ecological or genetic consequences, to environments to which they are introduced. One way to characterize the overall risk posed by a NIS is to combine the probability and consequences of its establishment in a risk assessment that can be used to inform managers and policy-makers. The vase tunicate Ciona intestinalis is considered to be a cryptogenic species in eastern Canadian waters, but has not yet been reported from Pacific Canada. Because it is unclear what level of risk it poses for Canadian waters, we conducted a biological risk assessment for C. intestinalis and its potential pathogens, parasites, and fellow travellers. An expert survey was conducted to inform the risk assessment. The ecological risk posed by C. intestinalis was considered high (moderate uncertainty) on the Atlantic coast, and moderate (high uncertainty) on the Pacific coast. The genetic risk posed by C. intestinalis was considered moderate on both coasts, with low uncertainty on the Atlantic coast and high uncertainty on the Pacific coast, where hybridization with Ciona savignyi may be possible. Pathogens, parasites, and fellow travellers were considered to be a moderate ecological risk and a low genetic risk (with high uncertainty) for both coasts.
Experience Is Not Enough
Authors: Friedman Zeev , Siddiqui Naveed , Katznelson Rita , Devito Isabella , Davies Sharon
Published: April 2008

Background

Invasive procedures such as epidural anesthesia carry risks for complications such as erroneous placement arising from inadequate manual skills and infection secondary to breaches in aseptic technique. Although it is assumed that improvement in aseptic technique parallels improved dexterity, this assertion remains unproven. The aim of this study was to determine whether increased proficiency in the manual skills for epidural anesthesia is associated with improved aseptic technique.

Methods

Second-year anesthesia residents were repeatedly videotaped performing epidural anesthesia over 6-month periods. Three independent examiners blinded to the level of training of the residents evaluated the procedures for manual skills and aseptic technique. Each procedure was graded using a manual skills checklist, a global rating scale, and an aseptic technique checklist. The main outcome measures were the scores for these three tools.

Results

Thirty-five sessions were videotaped over 1 yr. Interrater reliability was nearly perfect. A strong positive association was found between increased experience and manual skills, as reflected by the scores achieved on both the manual skills checklist and the global rating scale. In contrast, a nonsignificant or very weak correlation was found between the aseptic technique checklist total scores and the number of epidurals performed.

Conclusion

Manual skills for invasive procedures improved with increasing experience, but aseptic technique did not, despite formal teaching. These findings reflect major gaps in the understanding and teaching of the principles of aseptic technique, most likely due to lack of structured training. Educational initiatives are needed to correct these teaching gaps.
Local Myotoxicity from Sustained Release of Bupivacaine from Microparticles
Authors: Padera Robert , Bellas Evangelia , Tse Julie Y. , Hao Daphne , Kohane Daniel S.
Published: April 2008

Background

Sustained release of local anesthetics is frequently associated with myotoxicity. The authors investigated the role of particulate delivery systems and of the pattern of drug release in causing myotoxicity.

Methods

Rats were given sciatic nerve blocks with bupivacaine solutions, two types of bupivacaine-containing microparticles (polymeric microspheres and lipid-protein-sugar particles), or blank particles with or without bupivacaine in the carrier fluid. Myotoxicity was scored in histologic sections of the injection sites. Bupivacaine release kinetics from the particles were measured. Myotoxicity of a range of bupivacaine concentrations from exposures up to 3 weeks was assessed in C2C12 myotubes, with or without microparticles.

Results

Both types of bupivacaine-loaded microparticles, but not blank particles, were associated with myotoxicity. Whereas 0.5% bupivacaine solution caused little myotoxicity, a concentration of bupivacaine that mimicked the amount of bupivacaine released initially from particles caused myotoxicity. Local anesthetics showed both concentration and time-dependent myotoxicity in C2C12s. Importantly, even very low concentrations that were nontoxic over brief exposures became highly toxic after days or weeks of exposure. The presence of particles did not increase bupivacaine myotoxicity in vitro but did in vivo. Findings applied to both particle types.

Conclusions

Whereas the release vehicles themselves were not myotoxic, both burst and extended release of bupivacaine were. A possible implication of the latter finding is that myotoxicity is an inevitable concomitant of sustained release of local anesthetics. Particles, and perhaps other vehicles, may enhance local toxicity through indirect mechanisms.
Differential Effects of Isoflurane and Propofol on Upper Airway Dilator Muscle Activity and Breathing
Authors: Eikermann Matthias , Malhotra Atul , Fassbender Philipp , Zaremba Sebastian , Jordan Amy S. , Gautam Shiva , White David P. , Chamberlin Nancy L.
Published: April 2008

Background

Anesthesia impairs upper airway integrity, but recent data suggest that low doses of some anesthetics increase upper airway dilator muscle activity, an apparent paradox. The authors sought to understand which anesthetics increase or decrease upper airway dilator muscle activity and to study the mechanisms mediating the effect.

Methods

The authors recorded genioglossus electromyogram, breathing, arterial blood pressure, and expiratory carbon dioxide in 58 spontaneously breathing rats at an estimated ED50 (median effective dose) of isoflurane or propofol. The authors further evaluated the dose-response relations of isoflurane under different study conditions: (1) normalization of mean arterial pressure, or end-expiratory carbon dioxide; (2) bilateral lesion of the Kölliker-Fuse nucleus; and (3) vagotomy. To evaluate whether the markedly lower inspiratory genioglossus activity during propofol could be recovered by increasing flow rate, a measure of respiratory drive, the authors performed an additional set of experiments during hypoxia or hypercapnia.

Results

In vagally intact rats, tonic and phasic genioglossus activity were markedly higher with isoflurane compared with propofol. Both anesthetics abolished the genioglossus negative pressure reflex. Inspiratory flow rate and anesthetic agent predicted independently phasic genioglossus activity. Isoflurane dose-dependently decreased tonic and increased phasic genioglossus activity, and increased flow rate, and its increasing effects were abolished after vagotomy. Impairment of phasic genioglossus activity during propofol anesthesia was reversed during evoked increase in respiratory drive.

Conclusion

Isoflurane compared with propofol anesthesia yields higher tonic and phasic genioglossus muscle activity. The level of respiratory depression rather than the level of effective anesthesia correlates closely with the airway dilator muscle function during anesthesia.
Glycine Transporter Inhibitors as a Potential Therapeutic Strategy for Chronic Pain with Memory Impairment
Authors: Tanabe Mitsuo , Takasu Keiko , Yamaguchi Sachiko , Kodama Daisuke , Ono Hideki
Published: April 2008

Background

Impaired excitatory and inhibitory balance in the spinal dorsal horn has a crucial role in the pathophysiology of chronic pain. The authors addressed the therapeutic impact of increasing spinal glycine applied exogenously or via blockade of glycine transporter 1 using its selective inhibitors sarcosine and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine on neuropathic and inflammatory pain in mice.

Methods

Mice with thermal and mechanical hypersensitivity after partial ligation of the sciatic nerve (Seltzer model) or mice with mechanical hypersensitivity after streptozotocin injection received intrathecal injection of glycine, sarcosine, and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine. These drugs were also intrathecally injected in mice to assess their effects on formalin-evoked nociceptive behaviors. The supraspinal effect of blockade of glycine transporter 1 was studied on tetanus-induced long-term potentiation of the Schaffer-collateral synapses in hippocampal slices prepared from Seltzer model mice.

Results

Glycine, sarcosine, and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine ameliorated thermal and mechanical hypersensitivity in Seltzer model mice, and reduced mechanical hypersensitivity in streptozotocin-injected diabetic mice. Moreover, they selectively inhibited the second phase of formalin-evoked licking/biting behavior. In hippocampal slices prepared from Seltzer model mice, long-term potentiation was maintained at a significantly lower level than that in sham-treated mice. Such impairment of long-term potentiation was never observed when it was induced in the presence of N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine.

Conclusions

An increase in endogenous glycine via glycine transporter 1 blockade not only results in a net inhibitory influence on pain transmission at the spinal level but also supraspinally relieves decreased synaptic efficacy presumably related to cognitive disturbance often described in patients with chronic pain.
Multiple regions in dengue virus capsid protein contribute to nuclear localization during virus infection
Authors: Sangiambut Sutha , Keelapang Poonsook , Aaskov John , Puttikhunt Chunya , Kasinrerk Watchara , Malasit Prida , Sittisombut Nopporn
Published: April 2008

During infection, the capsid (C) protein of many flaviviruses localizes to the nuclei and nucleoli of several infected cell lines; the underlying basis and significance of C protein nuclear localization remain poorly understood. In this study, double alanine-substitution mutations were introduced into three previously proposed nuclear-localization signals (at positions 6–9, 73–76 and 85–100) of dengue virus C protein, and four viable mutants, c(K6A,K7A), c(K73A,K74A), c(R85A,K86A) and c(R97A,R98A), were generated in a mosquito cell line in which C protein nuclear localization was rarely observed. Indirect immunofluorescence analysis revealed that, whilst C protein was present in the nuclei of PS and Vero cells throughout infection with a dengue serotype 2 parent virus, the substitution mutations in c(K73A,K74A) and c(R85A,K86A) resulted in an elimination of nuclear localization in PS cells and marked reduction in Vero cells. Mutants c(K6A,K7A) and c(R97A,R98A) exhibited reduced nuclear localization at the late period of infection in PS cells only. All four mutants displayed reduced replication in PS, Vero and C6/36 cells, but there was a lack of correlation between nuclear localization and viral growth properties. Distinct dibasic residues within dengue virus C protein, many of which were located on the solvent-exposed side of the C protein homodimer, contribute to its ability to localize to nuclei during virus infection.
Polyinosinic acid enhances delivery of adenovirus vectors in vivo by preventing sequestration in liver macrophages
Authors: Haisma Hidde J. , Kamps Jan A. A. M. , Kamps Gera K. , Plantinga Josee A. , Rots Marianne G. , Bellu Anna Rita
Published: April 2008

Adenovirus is among the preferred vectors for gene therapy because of its superior in vivo gene-transfer efficiency. However, upon systemic administration, adenovirus is preferentially sequestered by the liver, resulting in reduced adenovirus-mediated transgene expression in targeted tissues. In the liver, Kupffer cells are responsible for adenovirus degradation and contribute to the inflammatory response. As scavenger receptors present on Kupffer cells are responsible for the elimination of blood-borne pathogens, we investigated the possible implication of these receptors in the clearance of the adenovirus vector. Polyinosinic acid [poly(I)], a scavenger receptor A ligand, was analysed for its capability to inhibit adenovirus uptake specifically in macrophages. In in vitro studies, the addition of poly(I) before virus infection resulted in a specific inhibition of adenovirus-induced gene expression in a J774 macrophage cell line and in primary Kupffer cells. In in vivo experiments, pre-administration of poly(I) caused a 10-fold transient increase in the number of adenovirus particles circulating in the blood. As a consequence, transgene expression levels measured in different tissues were enhanced (by 5- to 15-fold) compared with those in animals that did not receive poly(I). Finally, necrosis of Kupffer cells, which normally occurs as a consequence of systemic adenovirus administration, was prevented by the use of poly(I). No toxicity, as measured by liver-enzyme levels, was observed after poly(I) treatment. From our data, we conclude that poly(I) can prevent adenovirus sequestration by liver macrophages. These results imply that, by inhibiting adenovirus uptake by Kupffer cells, it is possible to reduce the dose of the viral vector to diminish the liver-toxicity effect and to improve the level of transgene expression in target tissues. In systemic gene-therapy applications, this will have great impact on the development of targeted adenoviral vectors.
Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H
Authors: Köck Josef , Blum Hubert E.
Published: April 2008

Hepatitis B virus (HBV) is a DNA virus that causes liver disease and replicates by reverse transcription of an RNA template. Previous studies have reported that HBV genomes bearing G→A hypermutation are present at low frequency in human serum. These mutations are most likely due to the activity of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like (APOBEC) cytosine deaminases, cellular proteins known to confer innate immunity against retroviruses by generating lethal hypermutations in viral genomes. This study assessed APOBEC3G, APOBEC3C and APOBEC3H, three members of this protein family present in human liver, for their ability to edit HBV genomes. Transfection of human HepG2 hepatoma cells with a plasmid encoding the APOBEC3C protein resulted in abundant G→A mutations in the majority of newly formed HBV genomes. By contrast, transfection of APOBEC3G- and APOBEC3H-encoding plasmids only marginally increased hypermutation rates above the level caused by the cytosine deaminases naturally present in HepG2 cells. APOBEC3G- and APOBEC3H-mediated hypermutation, however, was clearly revealed by transfection of chicken LMH hepatoma cells, which lack endogenous cytosine deaminases. These results indicate that APOBEC3G, APOBEC3C and APOBEC3H have the ability to edit HBV DNA and that each protein is likely to contribute to various degrees to the generation of modified genomes in human liver cells.
ORF018R, a highly abundant virion protein from Singapore grouper iridovirus, is involved in serine/threonine phosphorylation and virion assembly
Authors: Wang Fan , Bi Xuezhi , Chen Li Ming , Hew Choy-Leong
Published: April 2008

Iridovirus is an important pathogen causing serious diseases among wild, cultured and ornamental fish. Previous studies have shown that Singapore grouper iridovirus (SGIV) contains 162 open reading frames (ORFs) from which 51 viral proteins have been confirmed by proteomics studies. ORF018R, which is conserved among vertebrate iridoviruses, is an abundant virion protein identified from SGIV. Here, immunofluorescence staining showed that ORF018R occurred at high abundance throughout SGIV-infected cells. The function of ORF018R was explored using antisense morpholino oligonucleotides (asMOs). Knockdown of ORF018R expression resulted in a reduction in the expression of viral late genes, distortion of viral particle assembly and inhibition of SGIV infection in grouper embryonic cells. Western blotting with phosphoserine-specific antibody indicated that serine phosphorylation was significantly enhanced for proteins of molecular masss 17–32 kDa by SDS-PAGE when ORF018R expression was eliminated. These proteins were analysed further by two-dimensional gel electrophoresis, and numerous protein spots were found to shift to a lower pI and higher molecular mass as a result of the loss of ORF018R function. Five proteins with enhanced phosphorylation were identified by matrix-assisted laser desorption/ionization time-of-flight (TOF)-TOF mass spectrometry, including three viral proteins: ORF049L (dUTPase), ORF075R and ORF086R, and two host proteins: subunit 12 of eukaryotic translation factor 3 and natural killer enhancing factor. These findings suggest that ORF018R is involved in serine/threonine phosphorylation in SGIV-infected late-stage cells and plays an important role in expression of viral late genes and virion assembly.
Extravascular papillary endothelial hyperplasia of the palm masquerading as an angiosarcoma
Authors: ARAI Eiichi , SHIMIZU Michio , OGAWA Fumihiro , HIROSE Takanori , OHBAYASHI Hiroto , TAGUCHI Satoshi , TSUCHIDA Tetsuya
Published: April 2008

Cutaneous extravascular papillary endothelial hyperplasia (PEH) is a rare lesion presenting as a cutaneous mass and histologically mimicking angiosarcoma. Herein, we describe a patient who presented with a palm tumor that had developed after trauma. Histologically, the lesion was ulcerated and showed proliferation of atypical epithelioid cells with nuclear enlargement and mitosis. Vascular proliferation was evident, and these were positive for CD31 and CD34, with approximately 20% positivity for MIB‐1. We diagnosed this case as an extravascular papillary endothelial hyperplasia because there was no evidence of invasion into the surrounding tissue and elastica staining proved it did not have a vascular structure. To our knowledge, cutaneous extravascular PEH has not yet been reported in the published work.
A developmental approach to alcohol drinking behaviour in adulthood: a follow‐up study from age 8 to age 42
Authors: Pitkänen Tuuli , Kokko Katja , Lyyra Anna‐Liisa , Pulkkinen Lea
Published: April 2008

Aims  To study the links of family background, child and adolescent social behaviour, and (mal)adaptation with heavy drinking by age 20 and with the frequency of drinking, binge drinking, Cut‐down, Annoyed, Guilt, Eye‐opener (CAGE) questionnaire scores and problems due to drinking at ages 27 and 42 years.

Design  In the Finnish Jyväskylä Longitudinal Study of Personality and Social Development, data have been collected by interviews, inventories and questionnaires. Behavioural data were gathered at ages 8 and 14; data on alcohol consumption were gathered at ages 14, 20, 27, 36 and 42.

Participants  A total of 184 males and 163 females; 94% of the original sample of the 8‐year‐olds.

Findings  Family adversities, externalizing problem behaviours, low school success, truancy and substance use in adolescence were associated in early middle age with problems due to drinking in both genders, and to binge drinking and CAGE scores in females. The antecedents varied, however, across the indicators of drinking and gender. The frequency of drinking was least predictable by the studied antecedents. Childhood and adolescent antecedents and drinking up to age 20 explained 43% of males' and 31% of females' problem drinking at age 42; 31% and 19%, respectively, at age 27.

Conclusions  The early warning signs of drinking problems should be taken seriously in the preventive work for alcohol abuse. Problem drinking in early middle age is preceded by maladjustment to school, early age of onset of drinking and heavy drinking in adolescence even more significantly than problem drinking in early adulthood.
Adolescent pathways to adulthood drinking: sport activity involvement is not necessarily risky or protective
Authors: Peck Stephen C. , Vida Mina , Eccles Jacquelynne S.
Published: April 2008

Aims  Use pattern‐centered methods to examine how adolescents' alcohol use and sports activities are related both to childhood sport and problem behavior and to heavy drinking in early adulthood.

Design  The data used in this study come from four waves of the Michigan Study of Adolescent Life Transitions (MSALT) that began in 1983, when participants were approximately age 12, and continued into early adulthood, when participants were approximately age 28.

Participants  Sixty per cent of the approximately 1000 MSALT youth living in south‐eastern Michigan were females and 97% were European American. Approximately 28% of one or both parents held at least a college degree, and 45% held a high school diploma or lower.

Findings  Pattern‐centered analyses revealed that the relation between adolescent sport activity and age 28 heavy alcohol use obtained primarily for sport participants who were also using more than the average amount of alcohol and other drugs at age 18. Similarly, children who were characterized by relatively high levels of sport participation, aggression and other problem behavior at age 12 were more likely than expected by chance to become sport participants who used more than the average amount of alcohol and other drugs at age 18.

Conclusions  The results indicate that childhood problem behavior and adolescent sport participation can, but do not necessarily, presage heavy drinking in adulthood and that pattern‐centered analytical techniques are useful for revealing such theoretically generated predictions.
Indole‐3‐acetic acid (IAA) biosynthesis in the smut fungus Ustilago maydis and its relevance for increased IAA levels in infected tissue and host tumour formation
Authors: REINEKE GAVIN , HEINZE BERNADETTE , SCHIRAWSKI JAN , BUETTNER HERMANN , KAHMANN REGINE , BASSE CHRISTOPH W.
Published: April 2008

Infection of maize (Zea mays) plants with the smut fungus Ustilago maydis is characterized by excessive host tumour formation. U. maydis is able to produce indole‐3‐acetic acid (IAA) efficiently from tryptophan. To assess a possible connection to the induction of host tumours, we investigated the pathways leading to fungal IAA biosynthesis. Besides the previously identified iad1 gene, we identified a second indole‐3‐acetaldehyde dehydrogenase gene, iad2. Δiad1Δiad2 mutants were blocked in the conversion of both indole‐3‐acetaldehyde and tryptamine to IAA, although the reduction in IAA formation from tryptophan was not significantly different from Δiad1 mutants. To assess an influence of indole‐3‐pyruvic acid on IAA formation, we deleted the aromatic amino acid aminotransferase genes tam1 and tam2 in Δiad1Δiad2 mutants. This revealed a further reduction in IAA levels by five‐ and tenfold in mutant strains harbouring theΔtam1 andΔtam1Δtam2 deletions, respectively. This illustrates that indole‐3‐pyruvic acid serves as an efficient precursor for IAA formation in U. maydis. Interestingly, the rise in host IAA levels upon U. maydis infection was significantly reduced in tissue infected with Δiad1Δiad2Δtam1 orΔiad1Δiad2Δtam1Δtam2 mutants, whereas induction of tumours was not compromised. Together, these results indicate that fungal IAA production critically contributes to IAA levels in infected tissue, but this is apparently not important for triggering host tumour formation.