bluuebunny/crossref_metadata_2025 huggingface dataset:
The rno‐miR‐34 family is upregulated and targets ACSL1 in dimethylnitrosamine‐induced hepatic fibrosis in rats
Authors: Li Wei‐Qing , Chen Chao , Xu Mi‐Die , Guo Jia , Li Yi‐Ming , Xia Qing‐Mei , Liu Hui‐Min , He Jin , Yu Hong‐Yu , Zhu Liang
Published: March 2011

The mechanisms whereby hepatic fibrosis develops in chronic liver diseases remain incompletely defined. Here, we sought to examine whether microRNA (miRNA) became dysregulated in dimethylnitrosamine‐induced hepatic fibrosis in rats. Our microarray analysis revealed that the miR‐34 family was upregulated along with other miRNAs in liver fibrotic tissues. Six miRNAs, such as rno‐miR‐878, were downregulated. The findings were confirmed by RT‐PCR assays. Gene ontology analysis further showed that many of these dysregulated miRNAs were involved in lipid/fatty acid metabolism. The acyl‐CoA synthetase long‐chain family member 1 (ACSL1) gene contained specific binding sites for miR‐34a/miR‐34c. Additional enhanced green fluorescence protein reporter activity assays indicated that the miR‐34 family targeted ACSL1. Our RT‐PCR and immunoblotting assays further demonstrated that both the mRNA and protein levels of ACSL1 were markedly reduced in fibrotic liver tissues. Our findings suggest that miRNA becomes dysregulated during hepatic fibrosis, and that the miR‐34 family may be involved in the process by targeting ACSL1.
Parental Communication Style's Impact on Children's Attitudes Toward Obesity and Food Advertising
Authors: YU HYUNJAE (JAY)
Published: March 2011

There have been numerous discussions about what factors influence children's obesity level and their attitudes toward advertising. Among many possible factors, parental influence cannot be ignored, because children (7–12 years old) generally spend more time with their parents than with anybody else. This study investigates the possible influences of parental communication styles/patterns while watching TV with their children on their children's obesity level (body mass index) as well as parental influence's effect on children's attitudes toward TV snack/fast‐food ads. The results reveal that parental communication styles/patterns significantly influence children's obesity level and their attitude toward TV snack/fast‐food ads.
How Adolescents' Perceived Media Influence on Peers Affects Smoking Decisions
Authors: PAEK HYE‐JIN , GUNTHER ALBERT C. , McLEOD DOUGLAS M. , HOVE THOMAS
Published: March 2011

Guided by the influence of presumed influence model, this study focuses on the direct and mediating roles of adolescent perceived media influence on peers—i.e., perceptions about how much peers are influenced by antismoking messages—in predicting adolescent smoking attitudes and behavior. Analysis of two‐wave panel data indicates that adolescents' perceived media influence on peers at Time 2 directly influenced their smoking attitudes and behavior at Time 2 and appeared to serve as a causal bridge for the variable at Time 1. The exposure to antismoking campaigns seems to achieve the desired outcome indirectly through perceived media influence on peers.
Comparing isotopic groundwater age measurements with simulated groundwater ages: example of the Abbotsford–Sumas Aquifer (USA and Canada) and application
Authors: Chesnaux R. , Allen D. M. , Simpson M. W. M.
Published: March 2011

Elevated nitrate concentrations have been documented since the 1970s within the trans‐national Abbotsford–Sumas aquifer, situated in the central Fraser Valley of southern British Columbia, Canada, and northern Washington State, United States. Nitrate concentrations in excess of 10 mg/L NO3–N are commonly observed in the monitoring wells. A groundwater model is used in this study to conduct a particle tracking analysis to estimate groundwater travel times and compare these with groundwater ages determined from 3H/3He concentrations measured in several monitoring wells. Groundwater ages estimated from particle tracking show excellent agreement with measured ages (slope=1), although there is scatter (R2=0.76), reflecting the complexity of the travel pathways and ambiguities in groundwater ages because of mixing. An assessment of the efficacy of recommended nutrient management practices, which were implemented in 1992 to reduce nitrogen loading, suggests that wells shallower than about 20 m should be monitoring a decrease in nitrate concentration. However, persistent elevated nitrate concentrations even at shallow depths point to the lingering effects of a remnant manure–nitrate signature in combination with continued high loading.
Intestinal anion exchange in marine teleosts is involved in osmoregulation and contributes to the oceanic inorganic carbon cycle
Authors: Grosell M.
Published: March 2011

Marine teleost fish osmoregulation involves seawater ingestion and intestinal fluid absorption. Solute coupled fluid absorption by the marine teleost fish intestine has long been believed to be the product of Na+ and Cl− absorption via the Na+:K+:2Cl− co‐transporter (NKCC2). However, the past decade has revealed that intestinal anion exchange contributes significantly to Cl− absorption, in exchange for HCO3− secretion, and that this process is important for intestinal water absorption. In addition to contributing to solute coupled water absorption intestinal anion exchange results in luminal precipitation of CaCO3 which acts to reduce luminal osmotic pressure and thus assist water absorption. Most recently, activity of apical H+‐pumps, especially in distal segments of the intestine have been suggested to not only promote anion exchange, but also to reduce luminal osmotic pressure by preventing excess HCO3− concentrations from accumulating in intestinal fluids, thereby aiding water absorption. The present review summarizes and synthesizes the most recent advances in our view of marine teleosts osmoregulation, including our emerging understanding of epithelial transport of acid–base equivalents in the intestine, the consequences for whole organism acid–base balance and finally the impact of piscine CaCO3 formation on the global oceanic carbon cycle.
Technological Optimization of Manufacture of Probiotic Whey Cheese Matrices
Authors: Madureira Ana R. , Brandão Teresa , Gomes Ana M. , Pintado Manuela E. , Malcata F. Xavier
Published: March 2011

Abstract:  In attempts to optimize their manufacture, whey cheese matrices obtained via thermal processing of whey (leading to protein precipitation) and inoculated with probiotic cultures were tested. A central composite, face‐centered design was followed, so a total of 16 experiments were run using fractional addition of bovine milk to feedstock whey, homogenization time, and storage time of whey cheese as processing parameters. Probiotic whey cheese matrices were inoculated with Lactobacillus casei LAFTI®L26 at 10% (v/v), whereas control whey cheese matrices were added with skim milk previously acidified with lactic acid to the same level. All whey cheeses were stored at 7 °C up to 14 d. Chemical and sensory analyses were carried out for all samples, as well as rheological characterization by oscillatory viscometry and textural profiling. As expected, differences were found between control and probiotic matrices: fractional addition of milk and storage time were the factors accounting for the most important effects. Estimation of the best operating parameters was via response surface analysis: milk addition at a rate of 10% to 15% (v/v), and homogenization for 5 min led to the best probiotic whey cheeses in terms of texture and organoleptic properties, whereas the best time for consumption was found to be by 9 d of storage following manufacture.
Volatile Compounds in Light, Medium, and Dark Black Walnut and Their Influence on the Sensory Aromatic Profile
Authors: Lee Jeehyun , Vázquez‐Araújo Laura , Adhikari Koushik , Warmund Michele , Elmore Janelle
Published: March 2011

Abstract:  Light, medium, and dark colored kernels from 3 different cultivars (Emma K, Kwik Krop, and Sparks 127) and one wild species of black walnut were studied for their aroma volatiles. Solid‐phase microextraction‐gas chromatography‐mass spectrometry was used to determine the aromatic compounds present in the headspace of these samples. Partial least square regression was used to correlate the instrumental aromatic data with the sensory responses, obtained in a previous study, for the same samples. Thirty‐four aromatic compounds were found in the black walnut cultivars, highlighting among them the presence of 14 esters. Although more than 50% of the total concentration of volatile compounds, esters were not important compounds in determining the differences in the sensory aromatic profiles of the 3 colors of the nuts. As a general trend, the concentration of total volatile compounds was always significantly higher in light black walnuts than in the medium colored samples; medium colored samples had higher volatile content than the dark black walnuts. The presence of hexanal was related to rancid and acrid aromas and was determined to differentiate the dark black walnuts from the medium and light colored samples.

Practical Application:  The data presented in this article will help understand the aromatic differences between light, medium, and dark colored kernels of domestic and wild black walnut. The aromatic profile of these nuts, not studied until this moment, can be used as a model to develop flavorings and new products by the food industries.
The Biomimetic Immunoassay Based on Molecularly Imprinted Polymer: A Comprehensive Review of Recent Progress and Future Prospects
Authors: Xu Z.X. , Gao H.J. , Zhang L.M. , Chen X.Q. , Qiao X.G.
Published: March 2011

Abstract:  Immunoassay, based on a selective affinity of the biological antibody for its antigen, is one of the most usual analytical methods in food safety and environmental chemistry. However, it presents several drawbacks because of the nature of the antibody. Molecular imprinting technique, due to its high selectivity and stability, ease of preparation and low cost, has shown great potential in producing artificial antibodies in biomimetic immunoassays. This article focuses on the recent states, advantages, current problems and outlooks of molecularly imprinted radio, fluoro, enzyme‐linked and chemiluminescent immunoassays, and biomimetic immunosensor, with special emphasis on the challenges in developing biomimetic enzyme‐linked immunosorbent assays (BELISAs). The biomimetic immunoassay method will provide an important new analysis platform in food safety, although the sensitivity and specificity is relatively low.

Practical Application:  As a new simple analysis method, the biomimetic immunoassay has attractive prospect, although some limitations were existed in real‐sample assay. In this critical review, some promising solutions for overcoming its drawbacks were put forward, which may promote the more quick development and extensive application of this method in food safety.
Antibrowning and Antimicrobial Activities of the Water‐Soluble Extract from Pine Needles of Cedrus deodara
Authors: Zeng Wei‐Cai , Jia Li‐Rong , Zhang Yan , Cen Jia‐Qi , Chen Xi , Gao Hong , Feng Su , Huang Yi‐Na
Published: March 2011

Abstract:  The antibrowning and antimicrobial activities of the water‐soluble extract from pine needles of Cedrus deodara (CDE), a traditional Chinese medicine and raw materials of pine needle tea, was investigated. Total phenols of CDE were 31.4 ± 0.53 mg gallic acid equivalent/g, and total flavonoids were 23.1 ± 0.79 mg rutin equivalent/g. CDE showed a strong antioxidant activity against ABTS free radicals with IC50 (the half‐inhibitory concentration) of 25.5 ± 0.64 μg/mL. In mushroom tyrosinase inhibitory assay, IC50 values were 2.1 ± 0.98 and 2.27 ± 0.93 mg/mL for monophenolase and diphenolase, respectively. Evaluated by detecting changes of L* (indicated the darkness of sample), a* (indicated the redness of sample), and b* (indicated the yellowness of sample) values in fresh‐cut apple slices model, CDE showed a significant antibrowning effect when compared with ascorbic acid. In addition, it was discovered that CDE in combination with 0.5% ascorbic acid exhibited a synergistic antibrowning effect. Meanwhile, CDE was observed to show a potent antimicrobial effect on all of the tested Gram‐positive and Gram‐negative bacteria. In conclusion, the results of the present research suggested that pine needles of C. deodara could be used as a natural resource of antibrowning and antimicrobial agents in food preservation.

Practical Application:  The present study provides a theoretical basis for the potential application of pine needles of C. deodara to be used as a natural resource of antibrowning and antimicrobial agents in food industry.
Production of L‐Arabinose from Corn Hull Arabinoxylan by Arthrobacter aurescens MK5 α‐L‐Arabinofuranosidase
Authors: Kurakake Masahiro , Takao Jyunpei , Asano Osamu , Tanimoto Hiroko , Komaki Toshiaki
Published: March 2011

Abstract:  Arabinoxylans, which are comprised of a xylan backbone to which are attached glycosyl units that are primarily L‐arabinofuranosyl units, are ubiquitous among plant species where it is a constituent of the cell wall. Arabinoxylan has attracted much attention as a potential biomass resource and L‐arabinose has recently been reported to possess functional properties that are effective in the treatment of diabetes. Here, we report an α‐L‐arabinofuranohydrolase, isolated from the soil microbe Arthrobacter aurescens strain MK5, effective in releasing L‐arabinose from corn hull arabinoxylan. When A. aurescens strain MK5 was grown in a liquid medium, corn hull arabinoxylan, which has a higher arabinose content (Ara/Xyl = 0.6) than oat spelts xylan (Ara/Xyl = 0.12), induced more efficient arabinoxylan hydrolase production. Analysis of enzyme activity in the culture broth revealed that arabinoxylan hydrolase activity was high, and α‐L‐arabinofuranosidase and β‐xylosidase activities were low. The optimum pH of the MK5 arabinoxylan hydrolase at 40 °C was around 7 and enzyme activity was relatively stable at an alkaline pH up to 9.5. The optimum temperature at pH 7 was around 50 °C and enzyme activity was stable under 50 °C. During the hydrolysis of corn hull arabinoxylan, only L‐arabinose was released and 45.1% maximum sugar recovery was achieved. The A. aurescens MK5 enzyme was a typical arabinoxylan α‐L‐arabinofuranohydrolase and was most effective at releasing L‐arabinose from corn hull arabinoxylan, which has a high arabinose content. This enzyme may have important industrial applications.
Risk and benefit assessment of alien fish species of the aquaculture and aquarium trade into India
Authors: Singh Atul K. , Lakra Wazir S.
Published: March 2011

There has been an increasing demand for alien fish species in India. However, environmental, socioeconomic and biodiversity issues are important considerations when regulating the unauthorized culture and spread of alien species. Information collected in the present review revealed the presence of over 300 alien species imported intentionally or illegally; 291 ornamental species, 31 aquaculture species and two larvicidal fishes. Field data demonstrated the widespread occurrence of some of the world’s worst invasive species, for example, Cyprinus carpio, Oreochromis niloticus, Aristichthys nobilis, Pygocentrus nattereri and Pterygoplichthys spp., in inland waters; other species are emerging as a threat to aquatic biodiversity. The benefits and risks of alien species were analysed and the impact was quantified using a simple developed ‘Fish Invasiveness Screening Test’ (FIST). Our information suggests that alien species, despite possessing some attractive culture characteristics, generally reduce the availability of local species and establish in natural water bodies becoming invasive and consequently adversely affecting fish biodiversity and aquatic ecosystems. In light of the adverse ecological impacts of alien species, we developed strategic regulations and quarantine procedures and advised aquaculturists to strictly follow them to contain potential and plausible menaces.
Genetic improvement of Nile tilapia (Oreochromis niloticus) with special reference to the work conducted by the WorldFish Center with the GIFT strain
Authors: Ponzoni Raul W. , Nguyen Nguyen Hong , Khaw Hooi Ling , Hamzah Azhar , Bakar Khairul Rizal Abu , Yee Hoong Yip
Published: March 2011

We mainly (but not exclusively) draw on research and development work carried out by The WorldFish Center (WorldFish). We review in detail the current state of development of a selection program that has had a main focus on growth rate and body traits. We also present some new, unpublished, information. There is evidence of sustained gains of 10–15% per generation over more than six generations. To date, these gains have not been accompanied by any undesirable correlated response. However, the prospects of altering sexual dimorphism and the shape of the fish appear to be very limited. We also examine the issue of an appropriate environment for selection. Not surprisingly, experimental evidence on genotype by environment interactions suggests that this is more likely to be of importance when the environments in question are markedly dissimilar. We argue that no universal guidelines can be prescribed with regard to the need for more than one selection program to cope with different production environments, but rather, each case should be examined in its own right. Finally, we discuss traits likely to be candidates for inclusion in future, more elaborate, breeding objectives for Nile tilapia (Oreochromis niloticus), comment on selection methods that may be implemented in the future and conclude by stressing the need to maintain an effective population size in selection lines to ensure their sustainability over time.
AMaCAID: a useful tool for Accurate Marker Choice for Accession Identification and Discrimination
Authors: CAROLI S. , SANTONI S. , RONFORT J.
Published: March 2011

AMaCAID is an R program designed to analyse multilocus genotypic patterns in large samples. It allows (i) the computation of the number and frequency of the different multilocus patterns available in a molecular data set and (ii) the analysis of discriminatory power of each combination of k markers among n available. It thus enables the identification of the minimum number of markers required to distinguish all the observed genotypes and the subset of markers that maximize the number of distinct genotypes. AMaCAID can be used with any kind of molecular markers, on data sets mixing different kinds of markers, but also on qualitative characters like morphological or taxonomic traits. AMaCAID has been built primarily to select subsets of markers for identifying accessions and monitoring their genetic stability during regeneration cycles in an ex situ genebank. It can, however, also be used to screen any kind of data set that characterizes a set of individuals or species (e.g. taxonomic or phylogenetic studies) for discrimination purposes. The size of the assayed sample has no limitation, but the program only performs computations on all combinations of markers when there are less than 25 markers. For larger number of markers/characters, it is possible to ask AMaCAID to screen a large but limited number of combinations of markers. We apply AMaCAID to three data sets involving either molecular or taxonomic data and give some results on the computing time of the program with respect to the size of the data set.
Sunbeds and sunlamps: who used them and their risk for melanoma
Authors: Fears Thomas R. , Sagebiel Richard W. , Halpern Allan , Elder David E. , Holly Elizabeth A. , Guerry DuPont , Tucker Margaret A.
Published: March 2011

Sunbed/sunlamp use was recently classified as carcinogenic. This report considers characteristics of those who use sunbeds/sunlamps and the effect of sunbed/sunlamp use on their risk for melanoma within a large case–control study carried out in 1991–1992. Females were more likely than males to have used sunbeds/sunlamps. Use by females increased strongly and significantly with younger ages and with the perceived ability to tan. For females, the individual risk for melanoma increased with typical session time and frequency of sessions. Use before age 20, current use and years of use were not significant. The use patterns of occasional and frequent users were very different. We estimate that typical 5‐min sessions would increase the risk for melanoma by 19% for frequent users (10+ sessions) and by 3% for occasional users (1–9 sessions). Body sites that are not generally exposed to sunlight were more common sites of primary melanomas for frequent sunbed/sunlamp users. For males, measures of sunbed/sunlamp use were not significantly associated with melanoma risk.
Melt in the impact breccias from the Eyreville drill cores, Chesapeake Bay impact structure, USA
Authors: BARTOSOVA Katerina , HECHT Lutz , KOEBERL Christian , LIBOWITZKY Eugen , REIMOLD Wolf Uwe
Published: March 2011

Abstract–

The center of the 35.3 Ma Chesapeake Bay impact structure (85 km diameter) was drilled during 2005/2006 in an ICDP–USGS drilling project. The Eyreville drill cores include polymict impact breccias and associated rocks (1397–1551 m depth). Tens of melt particles from these impactites were studied by optical and electron microscopy, electron microprobe, and microRaman spectroscopy, and classified into six groups: m1—clear or brownish melt, m2—brownish melt altered to phyllosilicates, m3—colorless silica melt, m4—melt with pyroxene and plagioclase crystallites, m5—dark brown melt, and m6—melt with globular texture. These melt types have partly overlapping major element abundances, and large compositional variations due to the presence of schlieren, poorly mixed melt phases, partly digested clasts, and variable crystallization and alteration. The different melt types also vary in their abundance with depth in the drill core. Based on the chemical data, mixing calculations were performed to determine possible precursors of these melt particles. The calculations suggest that most melt types formed mainly from the thick sedimentary section of the target sequence (mainly the Potomac Formation), but an additional crystalline basement (schist/gneiss) precursor is likely for the most abundant melt types m2 and m5. Sedimentary rocks with compositions similar to those of the melt particles are present among the Eyreville core samples. Therefore, sedimentary target rocks were the main precursor of the Eyreville melt particles. However, the composition of the melt particles is not only the result of the precursor composition but also the result of changes during melting and solidification, as well as postimpact alteration, which must also be considered. The variability of the melt particle compositions reflects the variety of target rocks and indicates that there was no uniform melt source. Original heterogeneities, resulting from melting of different target rocks, may be preserved in impactites of some large impact structures that formed in volatile‐rich targets, because no large melt body exists, in which homogenization would have taken place.
Mitochondrial production of reactive oxygen species contributes to the β‐adrenergic stimulation of mouse cardiomycytes
Authors: Andersson Daniel C. , Fauconnier Jérémy , Yamada Takashi , Lacampagne Alain , Zhang Shi‐Jin , Katz Abram , Westerblad Håkan
Published: March 2011

Non‐technical summary  When under stress, the heart beat becomes stronger, in part due to enhanced fluxes of Ca2+ at the level of the cardiac cell. It is known that this effect is mediated by activation of β‐receptors on the cardiac cell surface. This leads to modifications of intracellular proteins that in turn increase the flux of Ca2+ within the cell. In this study we show that activation of β‐receptors increases the production of reactive oxygen species (ROS) in the heart cell. These ROS generate enhanced Ca2+ fluxes and more vigorous contraction. This finding shows a new cellular signalling route for regulating the power of the heart beat and might contribute to our understanding of diseases with defective cardiac contraction, such as heart failure.
The Cav3.2 T‐type calcium channel regulates temporal coding in mouse mechanoreceptors
Authors: Wang Rui , Lewin Gary R.
Published: March 2011

Non‐technical summary  Highly sensitive mechanoreceptors in the skin are responsible for our ability to discriminate fine textures. One feature of skin mechanoreceptors in mammals is their high sensitivity and speed. We show here that an ion channel that passes calcium ions following very small membrane depolarization caused by tactile stimuli acts as an amplifier increasing mechanoreceptor sensitivity. We also show that this calcium ion channel, called Cav3.2, only amplifies mechanosensory signals in a subset of touch receptors which happen to be several‐fold more sensitive than other specialized mechanoreceptors. Thus, the expression of one specific calcium channel serves especially to increase the speed of tactile encoding. The special sensitivity and high speed of these touch receptors may enable animals and humans to react very rapidly to tactile stimuli that guide movement.
Brainstem serotonin deficiency in the neonatal period: autonomic dysregulation during mild cold stress
Authors: Cummings Kevin J. , Li Aihua , Nattie Eugene E.
Published: March 2011

Non‐technical summary  In adult animals serotonergic neurones contribute to heat production (thermogenesis) in response to severe cold stress, as well as the respiratory response to increasing carbon dioxide. We show that in neonatal life, serotonin in the brainstem is absolutely essential for the thermogenic and heart rate responses to very mild (5°C) environmental cooling, probably by aiding the response of the sympathetic nervous system. In contrast, the respiratory response to increasing carbon dioxide is unaffected by a 90% loss of serotonin. Human infants with brainstem serotonin deficiency may be prone to a variety of homeostatic deficits owing to a reduced sympathetic response to mild cold stress.
Growth of epitaxial NiTi shape memory alloy films on GaAs(001) and evidence of martensitic transformation
Authors: Buschbeck J. , Kawasaki J. , Buehl T. E. , Gossard A. C. , Palmstrøm C. J.
Published: March 2011

The molecular beam epitaxy growth of epitaxial NiTi shape memory alloy films on GaAs(001) semiconductor substrates is demonstrated. An ErAs interlayer was used as a template to promote the epitaxial growth and as a diffusion barrier to effectively suppress intermixing between NiTi film and GaAs substrate. Though the films are constrained by the substrate, temperature dependent x-ray diffraction and resistivity measurements reveal reversible martensitic transformations upon heating and cooling near room temperature.
Photonic crystal structures with ultrahigh aspect ratio in lithium niobate fabricated by focused ion beam milling
Authors: Si Guangyuan , Danner Aaron J. , Teo Siew Lang , Teo Ee Jin , Teng Jinghua , Bettiol Andrew A.
Published: March 2011

Lithium niobate (LiNbO3, LN) is an important material which is widely applied in fabricating photonic and acoustic devices. However, it is difficult to either wet etch or dry etch LN due to the material’s properties. Here, the authors report novel pattern fabrication based on LN using focused ion beam (FIB) milling. When an array of small holes is etched, a severe tapering problem is observed as is common, but by replacing the nanocylindrical hole array with a nanoring structure, the authors obtain photonic crystals with an aspect ratio of up to 50:1 (2 μm total etching depth and 40 nm gap aperture). Dense nanorod arrays with sub-30-nm ultrasmall gaps and more than 2.5 μm etching depth are also achieved with FIB milling.
Electrical properties of Er-doped In0.53Ga0.47As
Authors: Burke Peter G. , Lu Hong , Rudawski Nicholas G. , Stemmer Susanne , Gossard Arthur C. , Bahk Je-Hyeong , Bowers John E.
Published: March 2011

The electrical properties of In0.53Ga0.47As thin films Er-doped to concentrations of 1.5×1017–7.2×1020 cm−3 grown by molecular beam epitaxy at 490 °C on (001) InP substrates were studied. Electrical conductivity, carrier density, and carrier mobility as a function of Er doping were measured by Hall effect at temperatures of 20–750 K. Additionally, high-angle annular dark-field scanning transmission electron microscopy and infrared absorption spectroscopy confirmed the presence of epitaxially embedded ErAs nanoparticles at Er concentrations ≥8×1019 cm−3. The observed electrical properties are discussed in terms of the dependence of ErAs nanoparticle formation with Er doping.
Impact of Ciprofloxacin Exposure on Staphylococcus aureus Genomic Alterations Linked with Emergence of Rifampin Resistance
Authors: Didier Jean-Philippe , Villet Régis , Huggler Elzbieta , Lew Daniel P. , Hooper David C. , Kelley William L. , Vaudaux Pierre
Published: March 2011

Intensive use of antimicrobial agents in health care settings not only leads to the selection of multiresistant nosocomial isolates of
Staphylococcus aureus
but may also promote endogenous, resistance-conferring mutations in bacterial genes that encode drug targets. We evaluated the spectrum of rifampin resistance-conferring mutations in cultures of methicillin-susceptible
S. aureus
(MSSA) or methicillin-resistant
S. aureus
(MRSA) strains exposed
in vitro
to sub-MICs of ciprofloxacin. Growth of ciprofloxacin-susceptible MRSA strain MRGR3 and ciprofloxacin-resistant MSSA strain RA1 (a NCTC 8325 derivative) in the presence of 1/2× or 1/4× MIC of ciprofloxacin led to higher frequencies of rifampin-resistant mutants on agar supplemented with rifampin (0.25 mg/liter) than under ciprofloxacin-free conditions. While rifampin-resistant mutants from ciprofloxacin-free cultures essentially showed single-amino-acid substitutions, a significant proportion of rifampin-resistant mutants from ciprofloxacin-exposed cultures displayed in-frame deletions or insertions in the
rpoB
gene at several positions of the rifampin resistance cluster I. In-frame deletions or insertions were also recorded in
rpoB
cluster I of rifampin-resistant mutants from ciprofloxacin-exposed cultures of
mutS
and
mutL
DNA repair mutants of ciprofloxacin-resistant
S. aureus
strain RA1. Frequencies of rifampin-resistant mutants grown under ciprofloxacin-free medium were higher for mutant strains RA1
mutS2
and RA1
mutL
, but not RA1
recA
, than for their parent RA1. In conclusion, ciprofloxacin-mediated DNA damage in
S. aureus
, as exemplified by the wide diversity of deletions or insertions in
rpoB
, suggests the occurrence of major, quinolone-mediated disturbances in DNA fork progression and replication repair. Besides promoting antibiotic resistance, accumulation of unrepaired DNA replication errors, including insertions and deletions, may also contribute to potentially lethal mutations.
Attributable Hospital Cost and Antifungal Treatment of Invasive Fungal Diseases in High-Risk Hematology Patients: an Economic Modeling Approach
Authors: Ananda-Rajah Michelle R. , Cheng Allen , Morrissey C. Orla , Spelman Tim , Dooley Michael , Neville A. Munro , Slavin Monica
Published: March 2011

Studies using patient-level data to determine the attributable cost of invasive fungal diseases (IFDs) are few. Using a case-control study with activity-based costing of patients admitted to a quaternary hospital from 2002 to 2007, we determined attributable hospitalization cost (and 12 weeks thereafter), length of stay (LOS), and costly antifungal treatment (C-AT; liposomal amphotericin B, voriconazole, posaconazole, caspofungin), expressed as defined daily doses (DDDs) per IFD episode, in patients with hematological malignancies and hematopoietic stem cell recipients. Matching criteria and median regression modeling controlled for confounding variables, including LOS prior to IFD onset. Multiple mycoses were identified in 43 matched case-control pairs (
n
= 86). A separate sensitivity analysis included 22 unmatched patients. IFD status was associated with a median excess cost of AU$30,957 (95% confidence interval [CI] = AU$2,368 to AU$59,546;
P
= 0.034), approximating at purchasing power parity US$21,203 (95% CI = US$1,622 to US$40,784) and €15,788 (95% CI = €1,208 to €30,368), increasing to AU$80,291 (95% CI = AU$33,636 to AU$126,946;
P
= 0.001), i.e., US$54,993 (95% CI = US$23,038 to US$86,948) and €40,948 (95% CI = €17,154 to €64,742), with intensive care unit (ICU) requirement. Cost determinants were pharmacy costs (64%;
P
< 0.001) inclusive of antifungal treatment (27%;
P
< 0.001) and ward costs (27%;
P
= 0.091), with proportions persisting through 12 weeks for 25 surviving matched pairs (pharmacy, 60% [
P
= 0.12]; ward, 31% [
P
= 0.21]). Median LOS was not significantly increased unless unmatched patients were included (8 days, 95% CI = 1.8 to 14 days;
P
= 0.012). Excess C-ATs were 17 DDDs (95% CI = 15 to 19 DDDs;
P
< 0.001) per case patient and 19 DDDs (95% CI = 16 to 22 DDDs;
P
< 0.001) per ICU patient. The sensitivity analysis was confirmatory (for median cost, AU$29,441, 95% CI = AU$5,571 to AU$53,310,
P
= 0.016; for C-AT, 17 DDDs, 95% CI = 16 to 18 DDDs,
P
< 0.001). IFD results in increased hospital and ICU costs, with pharmacy costs, including antifungal treatment, being major determinants. Consumption of costly antifungal drugs may be a novel resource metric with wider generalizability than cost alone.
Emergence of Linezolid-Resistant Mutants in a Susceptible-Cell Population of Methicillin-Resistant Staphylococcus aureus
Authors: Ikeda-Dantsuji Yurika , Hanaki Hideaki , Nakae Taiji , Takesue Yoshio , Tomono Kazunori , Honda Junichi , Yanagihara Katsunori , Mikamo Hiroshige , Fukuchi Kunihiko , Kaku Mitsuo , Kohno Shigeru , Niki Yoshihito
Published: March 2011

Methicillin-resistant
Staphylococcus aureus
with a MIC of linezolid of 4 μg/ml, isolated from a patient who had undergone unsuccessful linezolid therapy, yielded linezolid-resistant mutants in blood agar at 48 h of incubation. The resistant clones showed a MIC of linezolid ranging from 8 to 64 μg/ml and accumulated the T2500A mutation(s) of the rRNA genes. Emergence of these resistant clones appears to be facilitated by a cryptic mutation or mutations associated with chloramphenicol resistance.
Selection and Characterization of HIV-1 with a Novel S68 Deletion in Reverse Transcriptase
Authors: Schinazi Raymond F. , Massud Ivana , Rapp Kimberly L. , Cristiano Meta , Detorio Mervi A. , Stanton Richard A. , Bennett Matthew A. , Kierlin-Duncan Monique , Lennerstrand Johan , Nettles James H.
Published: March 2011

Resistance to human immunodeficiency virus type 1 (HIV-1) represents a significant problem in the design of novel therapeutics and the management of treatment regimens in infected persons. Resistance profiles can be elucidated by defining modifications to the viral genome conferred upon exposure to novel nucleoside reverse transcriptase (RT) inhibitors (NRTI).In vitrotesting of HIV-1LAI-infected primary human lymphocytes treated with β-d-2′,3′-dideoxy-2′,3′-didehydro-5-fluorocytidine (DFC; Dexelvucitabine; Reverset) produced a novel deletion of AGT at codon 68 (S68Δ) alone and in combination with K65R that differentially affects drug response. Dual-approach clone techniques utilizing TOPO cloning and pyrosequencing confirmed the novel S68Δ in the HIV-1 genome. The S68Δ HIV-1 RT was phenotyped against various antiviral agents in a heteropolymeric DNA polymerase assay and in human lymphocytes. Drug susceptibility results indicate that the S68Δ displayed a 10- to 30-fold increase in resistance to DFC, lamivudine, emtricitabine, tenofovir, abacavir, and amdoxovir and modest resistance to stavudine, β-d-2′,3′-oxa-5-fluorocytidine, or 9-(β-d-1,3-dioxolan-4-yl)guanine and remained susceptible to 3′-azido-3′-deoxythymidine, 2′,3′-dideoxyinosine (ddI), 1-(β-d-dioxolane)thymine (DOT) and lopinavir. Modeling revealed a central role for S68 in affecting conformation of the β3-β4 finger region and provides a rational for the selective resistance. These data indicate that the novel S68Δ is a previously unrecognized deletion that may represent an important factor in NRTI multidrug resistance treatment strategies.
Activity of NXL104 in Combination with β-Lactams against Genetically Characterized Escherichia coli and Klebsiella pneumoniae Isolates Producing Class A Extended-Spectrum β-Lactamases and Class C β-Lactamases
Authors: Lagacé-Wiens P. R. S. , Tailor F. , Simner P. , DeCorby M. , Karlowsky J. A. , Walkty A. , Hoban D. J. , Zhanel G. G.
Published: March 2011

The novel non-β-lactam β-lactamase inhibitor NXL104, in combination with cefepime, ceftazidime, ceftriaxone, amdinocillin, and meropenem, was tested against 190 extended-spectrum β-lactamase (ESBL)-producing
Escherichia coli
and
Klebsiella pneumoniae
isolates, 94 AmpC-hyperproducing
E. coli
isolates, and 8 AmpC/ESBL-coexpressing
E. coli
isolates. NXL104 restored 100% susceptibility to the partner cephalosporins for all isolates tested. Amdinocillin and meropenem MICs were modestly improved (2 to 32 times lower) by NXL104. These results suggest that NXL104 may be useful in combination with β-lactams for the treatment of infections caused by ESBL- and AmpC-producing
Enterobacteriaceae
.
Antigen-Specific CD8
+
T Cells Fail To Respond to Shigella flexneri
Authors: Jehl Stephanie P. , Doling Amy M. , Giddings Kara S. , Phalipon Armelle , Sansonetti Philippe J. , Goldberg Marcia B. , Starnbach Michael N.
Published: March 2011

CD8
+
T lymphocytes often play a primary role in adaptive immunity to cytosolic microbial pathogens. Surprisingly, CD8
+
T cells are not required for protective immunity to the enteric pathogen
Shigella flexneri
, despite the ability of
Shigella
to actively secrete proteins into the host cytoplasm, a location from which antigenic peptides are processed for presentation to CD8
+
T cells. To determine why CD8
+
T cells fail to play a role in adaptive immunity to
S. flexneri
, we investigated whether antigen-specific CD8
+
T cells are primed during infection but are unable to confer protection or, alternatively, whether T cells fail to be primed. To test whether
Shigella
is capable of stimulating an antigen-specific CD8
+
T-cell response, we created an
S. flexneri
strain that constitutively secretes a viral CD8
+
T-cell epitope via the
Shigella
type III secretion system and characterized the CD8
+
T-cell response to this strain both in mice and in cultured cells. Surprisingly, no T cells specific for the viral epitope were stimulated in mice infected with this strain, and cells infected with the recombinant strain were not targeted by epitope-specific T cells. Additionally, we found that the usually robust T-cell response to antigens artificially introduced into the cytoplasm of cultured cells was significantly reduced when the antigen-presenting cell was infected with
Shigella
. Collectively, these results suggest that antigen-specific CD8
+
T cells are not primed during
S. flexneri
infection and, as a result, afford little protection to the host during primary or subsequent infection.
Identification of Cytokeratin 18 as a Biomarker of Mouse and Human Hepatosplenic Schistosomiasis
Authors: Manivannan Bhagyashree , Rawson Pisana , Jordan T. William , Karanja Diana M. S. , Mwinzi Pauline N. M. , Secor William Evan , La Flamme Anne Camille
Published: March 2011

Previously, we demonstrated unique protein expression patterns in 20-week-Schistosoma mansoni-infected CBA/J mice with moderate splenomegaly syndrome (MSS) or hypersplemomegaly syndrome (HSS). To better understand the development of severe pathology, we compared the two-dimensional differential in-gel electrophoresis (2D-DIGE) proteomic signatures of livers from uninfected mice and mice infected for 6, 8, 12, or 20 weeks and found significant changes in collagen isoforms, interleukin-2 (IL-2), cytokeratin 18, hydroxyproline,S. mansoniphosphoenolpyruvate carboxykinase, major urinary protein isoforms, and peroxiredoxin 6. Cytokeratin 18, hydroxyproline, and connective tissue growth factor (CTGF) were chosen for analysis in mouse and human sera using targeted biochemical assays. Consistent with the liver analysis, cytokeratin 18, CTGF, and hydroxyproline were significantly elevated in sera from mice with HSS compared to those from uninfected mice or mice with MSS. Moreover, cytokeratin 18 and CTGF were found to be markers for subjects with hepatosplenic and intestinal schistosomiasis, respectively, while serum hydroxyproline was a strong indicator of fibrosis for severe HS. These findings indicate that schistosome-associated changes to the liver can be detected in the serum and reveal the potential for cytokeratin 18 to be used as a diagnostic marker for early detection of hepatosplenic schistosomiasis.
Transcriptome Analysis of Avian Pathogenic Escherichia coli O1 in Chicken Serum Reveals Adaptive Responses to Systemic Infection
Authors: Li Ganwu , Tivendale Kelly A. , Liu Peng , Feng Yaping , Wannemuehler Yvonne , Cai Wentong , Mangiamele Paul , Johnson Timothy J. , Constantinidou Chrystala , Penn Charles W. , Nolan Lisa K.
Published: March 2011

Infections of avian pathogenic
Escherichia coli
(APEC) result in annual multimillion-dollar losses to the poultry industry. Despite this, little is known about the mechanisms by which APEC survives and grows in the bloodstream. Thus, the aim of this study was to identify molecular mechanisms enabling APEC to survive and grow in this critical host environment. To do so, we compared the transcriptome of APEC O1 during growth in Luria-Bertani broth and chicken serum. Several categories of genes, predicted to contribute to adaptation and growth in the avian host, were identified. These included several known virulence genes and genes involved in adaptive metabolism, protein transport, biosynthesis pathways, stress resistance, and virulence regulation. Several genes with unknown function, which were localized to pathogenicity islands or APEC O1's large virulence plasmid, pAPEC-O1-ColBM, were also identified, suggesting that they too contribute to survival in serum. The significantly upregulated genes
dnaK
,
dnaJ
,
phoP
, and
ybtA
were subsequently subjected to mutational analysis to confirm their role in conferring a competitive advantage during infection. This genome-wide analysis provides novel insight into processes that are important to the pathogenesis of APEC O1.
Discriminating Lyme Neuroborreliosis from Other Neuroinflammatory Diseases by Levels of CXCL13 in Cerebrospinal Fluid
Authors: van Burgel N. D. , Bakels F. , Kroes A. C. M. , van Dam A. P.
Published: March 2011

CXCL13 in cerebrospinal fluid (CSF) could be an important component for diagnosing Lyme neuroborreliosis (LNB). Levels of intrathecal CXCL13 were determined for 58 LNB patients and 210 controls; sensitivity was 88% and specificity was 89% (cutoff, 250 pg of CXCL13/ml of CSF). Elevated levels of CXCL13 can aid in the diagnosis of LNB, but levels should be interpreted with care.
“Candidatus Neoehrlichia mikurensis” Infection in a Dog from Germany
Authors: Diniz Pedro Paulo V. P. , Schulz Bianka S. , Hartmann Katrin , Breitschwerdt Edward B.
Published: March 2011

“
Candidatus
Neoehrlichia mikurensis” is a new intracellular pathogen associated with human infection and death. “
Candidatus
Neoehrlichia mikurensis” infection in a chronically neutropenic dog from Germany was confirmed by DNA sequencing. The same organism was previously described from ticks and two sick human beings from Germany.
Monte Carlo simulation of fluorescence correlation spectroscopy data
Authors: Košovan Peter , Uhlík Filip , Kuldová Jitka , Štěpánek Miroslav , Limpouchová Zuzana , Procházka Karel , Benda Aleš , Humpolíčková Jana , Hof Martin
Published: March 2011

We employed the Monte Carlo simulation methodology to emulate the diffusion of fluorescently labeled particles and understand the source of differences between values of diffusion coefficients (and consequently hydrodynamic radii) of fluorescently labeled nanoparticles measured by fluorescence correlation spectroscopy (FCS) and dynamic light scattering (DLS). We used the simulation program developed in our laboratory and studied the diffusion of spherical particles of different sizes, which are labeled on their surface. In this study, we focused on two complicating effects: (i) multiple labeling and (ii) rotational diffusion which affect the fluorescence signal from large particles and hinder the analysis of autocorrelation functions according to simple analytical models. We have shown that the fluorescence fluctuations can be well fitted using the analytical model for small point-like particles, but the obtained parameters deviate in some cases significantly from the real ones. It means that the current data treatment yields apparent values of diffusion coefficients and other parameters only and the interpretation of experimental results for systems of particles with sizes comparable to the size of the active illuminated volume requires great care and precaution.
CeCl3·7H2O as mild and efficient catalyst for the one-pot multicomponent synthesis of 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-ones
Authors: Wu Li-Qiang , Li Wei-Lin , Yan Fu-Lin
Published: March 2011

A series of new 8-aryl-7,8-dihydro[1,3]dioxolo[4,5-g]chromen-6-ones were synthesized via a three-component reaction of 3,4-methylenedioxyphenol, aromatic aldehydes and Meldrum’s acid in the presence of CeCl3·7H2O under solvent-free conditions. The method provided several advantages such as easy work-up, high yields and environmentally benign procedure.
Rounded intraplacental haematomas due to decidual vasculopathy have a distinctive morphology
Authors: Fitzgerald Brendan , Shannon Patrick , Kingdom John , Keating Sarah
Published: March 2011

Within the placenta, most centrally placed intervillous thrombi are thought to form at sites of foetomaternal haemorrhage, while parabasally located intervillous thombi have been linked to maternal vascular disease. To determine whether parabasally located haemorrhagic lesions were morphologically heterogeneous, the authors performed a retrospective review of 25 placentas with thrombohaematomas occurring in the vicinity of the basal plate. Using morphological criteria, two lesions were distinguished: (1) the parabasally located intervillous thrombus, which had all the morphological features of more centrally located intervillous thrombi; and (2) the rounded intraplacental haematoma. Rounded intraplacental haematomas form as a result of disruption of vasculopathic decidual arterioles in a setting of maternal vascular underperfusion and are thus aetiologically distinct from classically described intervillous thrombi.
Demonstration of the metaphylactic use of gamithromycin against bacterial pathogens associated with bovine respiratory disease in a multicentre farm trial
Authors: Baggott D. , Casartelli A. , Fraisse F. , Manavella C. , Marteau R. , Rehbein S. , Wiedemann M. , Yoon S.
Published: March 2011

On five commercial cattle rearing sites across Europe, a total of 802 young cattle at high risk of developing bovine respiratory disease (BRD) associated with the bacterial pathogens Mannheimia haemolytica or Pasteurella multocida and/or Mycoplasma bovis were enrolled into a multicentre, controlled field trial. Half were treated with a single dose of gamithromycin at 6 mg/kg bodyweight by subcutaneous injection and half received an injection of a saline placebo as the control. All animals were observed daily for 14 days for signs of BRD as defined by set criteria. The proportion of metaphylactic preventive treatment successes, defined as animals surviving to day 14 without signs of BRD, in the gamithromycin‐treated group (86 per cent) was significantly (P=0.0012) higher than in the saline‐treated controls (61 per cent). Morbidity among the treated animals was reduced by 64 per cent compared with the controls.