bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationale and Design of the PRegnancy and Infant DEvelopment (PRIDE) Study
Authors: van Gelder Marleen M. H. J. , Bretveld Reini W. , Roukema Jolt , Steenhoek Morac , van Drongelen Joris , Spaanderman Marc E. A. , van Rumpt Dick , Zielhuis Gerhard A. , Verhaak Chris M. , Roeleveld Nel
Published: December 2012

Background

To optimise the health of pregnant women and their children by evidence‐based primary and secondary prevention, more scientific knowledge is needed. To overcome the methodological limitations of many studies on pregnancy and child health, which often use a retrospective design, we established the PRIDE (PRegnancy and Infant DEvelopment) Study.

Methods and Results

The PRIDE Study is a large prospective cohort study that aims at including 150 000–200 000 women in early pregnancy to study a broad range of research questions pertaining to pregnancy complications, maternal and child health, and adverse developmental effects in offspring. Women are invited to participate by their prenatal care provider before or at their first prenatal care visit and are asked to fill out web‐based questionnaires in gestational weeks 8–10, 17, and 34, as well as biannually throughout childhood. In addition, a food frequency questionnaire and a paternal questionnaire are administered and medical records are consulted. Multiple validation studies will be conducted and paper‐and‐pencil questionnaires are available for women who cannot or do not want to participate through the Internet. For subgroups of participants, blood and saliva samples for genetic and biochemical analyses are being collected. The pilot phase, which started in July 2011, showed a response rate of 47%. Recruitment will eventually cover all of the Netherlands.

Conclusions

We expect that this study, which will be the largest birth cohort in the world so far, will provide new insights in the aetiology of disorders and diseases that originate in pregnancy. The PRIDE Study is open for collaboration.
A novel HLA‐B*54 allele, B*54:16
Authors: Gong Z. , Zhang Z. X. , Shan X. , Li D. , Li W.
Published: December 2012

The HLA‐B*54:16 allele differs from the B*54:01 by one nucleotide substitution in exon 3 at NT412.
Characterization of the novel HLA‐B*18:79 allele
Authors: Endres R.O. , Hoffman A.D. , Palmer P. , Scott I. , Souza S.
Published: December 2012

Characterization of the novel HLA B*18:79 allele is described.
On the role of HLA antibodies in hematopoietic stem cell transplantation
Authors: Brand A. , Doxiadis I. N. , Roelen D. L.
Published: December 2012

While the role of donor‐specific antibodies (DSA) in solid organ transplantation is well established, their importance in hematopoietic stem cell transplantation (HSCT) is only now becoming clear. A review of the literature reporting on HLA immunization in HSCT provides ample circumstantial evidence that donor‐specific HLA antibodies (DSA) are associated with a 2‐ to 10‐fold increase of graft failure of HLA mismatched HSCT, irrespective the type of the graft, or the patient conditioning. Nevertheless, this is not a condition ‘sine qua non’, and engraftment has been documented despite the presence of DSA. However, prediction of graft failure based on serology is cumbersome. Although sensitivity and specificity of current solid‐phase assays (SPAs) for HLA antibody detection are high, correlation with graft failure remains elusive. When lacking an alternative donor, reduction of strong reacting DSA must be attempted. Unfortunately, results of DSA reduction treatments in HSCT are scarcely reported. Case reports show that persisting DSA after plasma‐exchange and immunosuppressive treatment can become negative after a ‘last rescue’ in vivo absorption with antigen‐bearing platelets or donor lymphocyte transfusions. The destruction of engrafting hematopoietic cells by antibodies appears to be an immediate event. Blocking antibody mediated effector functions, e.g. with intravenous immunoglobulin (IvIg), may have additional value, despite IvIg often not reducing the antibody titre. An even less explored aspect of HLA‐immunization is the presence of non‐DSA antibodies in the host or HLA antibodies emerging post‐transplantation. Such antibodies, either causally or as confounders, may be associated with negative transplant outcome. We conclude that HLA antibody assessment should be at the forefront in the treatment handbook of HSCT.
A review of subspecies recognition in polydesmidan millipedes (Diplopoda) with a revision of the subspecies of Euryuridae (Xystodesmoidea)
Authors: Jorgensen Michael C. , Sierwald Petra , Mason‐Gamer Roberta J.
Published: December 2012

Jorgensen, M. C., Sierwald, P. & Mason‐Gamer, R. J. (2012). A review of subspecies recognition in polydesmidan millipedes (Diplopoda) with a revision of the subspecies of Euryuridae (Xystodesmoidea). —Zoologica Scripta, 42, 317–326.

Taxonomic subspecies recognition is controversial due to the lack of an objective definition of the concept and inconsistent use of the category. The practice of designating subspecies is assessed here through a thorough review of 244 subspecies designations of polydesmidan millipedes over a 50‐year period. The survey focuses on the justification given for subspecies recognition, the amount of data available for the designation, the handling of nominate subspecies and the criteria used for diagnosis. We address several problematic issues and provide suggestions to enhance future work. Three examples of subdivided species from the Euryuridae (Polydesmida) are presented in detail with some taxonomic revision. Euryurus leachii leachii and E. leachii fraternus are synonymized, and the subspecific epithets are discarded. Auturus erythropygos erythropygos and A. erythropygos becki are returned to full species rank.
Acute upper airway muscle and inspiratory flow responses to transcranial magnetic stimulation during sleep in apnoeic patients
Authors: Melo‐Silva César Augusto , Borel Jean‐Christian , Gakwaya Simon , Sériès Frédéric
Published: December 2012

New Findings

What is the central question of this study?

Peripheral hypoglossal nerve stimulation is a novel therapeutic approach aimed at recruiting lingual muscles electrically and thus relieving pharyngeal airflow obstruction during sleep but the effects of corticomotor stimulation of upper airway muscles during sleep are unknown.

What is the main finding and its importance?

Using transcranial magnetic stimulation, we show that corticobulbar excitability of the submental muscles is decreased during sleep in apnoeic patients. Furthermore, we demonstrate that transcranial magnetic stimulation briefly recruits submental muscles and increases maximal inspiratory flow as well as the inspiratory volume of flow‐limited respiratory cycles without arousing patients from sleep. We suggest that this central neurostimulation approach is capable of improving upper airway mechanics in sleep apnoea patients.

Transcranial magnetic stimulation (TMS) can activate the corticobulbar system and briefly recruit upper airway dilator muscles, improving the inspiratory airflow dynamics of flow‐limited respiratory cycles during sleep. The purpose of this investigation was to quantify the effects of TMS‐induced twitches applied during sleep on flow‐limited respiratory cycles in 14 obstructive sleep apnoea patients. Submental muscle motor threshold (SUBMT) and motor‐evoked potential (SUBMEP) were examined during wakefulness and sleep. The TMS‐induced twitches were applied during stable non‐rapid eye movement (NREM) sleep, during non‐consecutive flow‐limited respiratory cycles at the beginning of inspiration, with intensities varying from sleep SUBMT up to maximal stimulation without arousal. Maximal inspiratory flow, inspiratory volume, shifts of electroencephalogram frequency and pulse rate variability were assessed. Cortical and/or autonomic arousal after TMS was observed in only 13.8% of all twitches applied. The SUBMT increased during NREM sleep (wakefulness, 24.8 ± 9.3%; and NREM sleep, 28.3 ± 9.5%; P= 0.003). Augmenting stimulator output from SUBMT to maximal stimulation before arousal enhanced SUBMEP peak‐to‐peak amplitude (from 0.09 ± 0.05 to 0.4 ± 0.3 mV; P= 0.005) with a concomitant rise in maximal inspiratory flow (from 376.2 ± 107.9 to 411.9 ± 109.3 ml s−1; P= 0.008) and inspiratory volume (from 594.8 ± 189.2 to 663.7 ± 203.1 ml; P= 0.001) in all but one patient. Corticobulbar excitability of submental muscles decreases during NREM sleep. Brief recruitment of submental muscles with TMS during sleep improves upper airway mechanics without arousing patients from sleep.
A Numerical Study of Aortic Flow Stability and Comparison With In Vivo Flow Measurements
Authors: Kousera C. A. , Wood N. B. , Seed W. A. , Torii R. , O'Regan D. , Xu X. Y.
Published: December 2012

The development of an engineering transitional turbulence model and its subsequent evaluation and validation for some diseased cardiovascular flows have been suggestive of its likely utility in normal aortas. The existence of experimental data from human aortas, acquired in the early 1970s with catheter-mounted hot film velocimeters, provided the opportunity to compare the performance of the model on such flows. A generic human aorta, derived from magnetic resonance anatomical and velocity images of a young volunteer, was used as the basis for varying both Reynolds number (Re) and Womersley parameter (α) to match four experimental data points from human ascending aortas, comprising two with disturbed flow and two with apparently undisturbed flow. Trials were made with three different levels of inflow turbulence intensity (Tu) to find if a single level could represent the four different cases with 4000 < Re < 10,000 and 17 < α < 26. A necessary boundary condition includes the inflow “turbulence” level, and convincing results were obtained for all four cases with inflow Tu = 1.0%, providing additional confidence in the application of the transitional model in flows in larger arteries. The Reynolds-averaged Navier–Stokes (RANS)-based shear stress transport (SST) transitional model is capable of capturing the correct flow state in the human aorta when low inflow turbulence intensity (1.0%) is specified.
A Coupled Fiber-Matrix Model Demonstrates Highly Inhomogeneous Microstructural Interactions in Soft Tissues Under Tensile Load
Authors: Zhang Lijuan , Lake Spencer P. , Lai Victor K. , Picu Catalin R. , Barocas Victor H. , Shephard Mark S.
Published: December 2012

A soft tissue's macroscopic behavior is largely determined by its microstructural components (often a collagen fiber network surrounded by a nonfibrillar matrix (NFM)). In the present study, a coupled fiber-matrix model was developed to fully quantify the internal stress field within such a tissue and to explore interactions between the collagen fiber network and nonfibrillar matrix (NFM). Voronoi tessellations (representing collagen networks) were embedded in a continuous three-dimensional NFM. Fibers were represented as one-dimensional nonlinear springs and the NFM, meshed via tetrahedra, was modeled as a compressible neo-Hookean solid. Multidimensional finite element modeling was employed in order to couple the two tissue components and uniaxial tension was applied to the composite representative volume element (RVE). In terms of the overall RVE response (average stress, fiber orientation, and Poisson's ratio), the coupled fiber-matrix model yielded results consistent with those obtained using a previously developed parallel model based upon superposition. The detailed stress field in the composite RVE demonstrated the high degree of inhomogeneity in NFM mechanics, which cannot be addressed by a parallel model. Distributions of maximum/minimum principal stresses in the NFM showed a transition from fiber-dominated to matrix-dominated behavior as the matrix shear modulus increased. The matrix-dominated behavior also included a shift in the fiber kinematics toward the affine limit. We conclude that if only gross averaged parameters are of interest, parallel-type models are suitable. If, however, one is concerned with phenomena, such as individual cell-fiber interactions or tissue failure that could be altered by local variations in the stress field, then the detailed model is necessary in spite of its higher computational cost.
Characterization of atomic layer deposition HfO2, Al2O3, and plasma-enhanced chemical vapor deposition Si3N4 as metal–insulator–metal capacitor dielectric for GaAs HBT technology
Authors: Yota Jiro , Shen Hong , Ramanathan Ravi
Published: December 2012

Characterization was performed on the application of atomic layer deposition (ALD) of hafnium dioxide (HfO2) and aluminum oxide (Al2O3), and plasma-enhanced chemical vapor deposition (PECVD) of silicon nitride (Si3N4) as metal–insulator–metal (MIM) capacitor dielectric for GaAs heterojunction bipolar transistor (HBT) technology. The results show that the MIM capacitor with 62 nm of ALD HfO2 resulted in the highest capacitance density (2.67 fF/μm2), followed by capacitor with 59 nm of ALD Al2O3 (1.55 fF/μm2) and 63 nm of PECVD Si3N4 (0.92 fF/μm2). The breakdown voltage of the PECVD Si3N4 was measured to be 73 V, as compared to 34 V for ALD HfO2 and 41 V for Al2O3. The capacitor with Si3N4 dielectric was observed to have lower leakage current than both with Al2O3 and HfO2. As the temperature was increased from 25 to 150 °C, the breakdown voltage decreased and the leakage current increased for all three films, while the capacitance increased for the Al2O3 and HfO2. Additionally, the capacitance of the ALD Al2O3 and HfO2 films was observed to change, when the applied voltage was varied from −5 to +5 V, while no significant change was observed on the capacitance of the PECVD Si3N4. Furhermore, no significant change in capacitance was seen for these silicon nitride, aluminum oxide, and hafnium dioxide films, as the frequency was increased from 1 kHz to 1 MHz. These results show that the ALD films of Al2O3 and HfO2 have good electrical characteristics and can be used to fabricate high density capacitor. As a result, these ALD Al2O3 and HfO2 films, in addition to PECVD Si3N4, are suitable as MIM capacitor dielectric for GaAs HBT technology, depending on the specific electrical characteristics requirements and application of the GaAs devices.
Atomic layer deposition of Al2O3 and AlxTi1−xOy thin films on N2O plasma pretreated carbon materials
Authors: Markeev Andrey M. , Chernikova Anna G. , Chouprik Anastasya A. , Zaitsev Sergey A. , Ovchinnikov Dmitry V. , Althues Holger , Dörfler Susanne
Published: December 2012

A mild N2O plasma treatment technique (low power and low substrate temperature) for carbon materials' (including graphite and carbon nanotubes) functionalization followed by subsequent high-k dielectric atomic layer deposition (ALD) was developed. It was shown that N2O plasma carbon functionalization leads to the formation of epoxide and carboxylic groups on the carbon surface which act as active centers for ALD and, as a result, conformal and uniform Al2O3 and TixAl1−xOy films' growth occurred on the carbon surfaces. It was shown that the electrical properties of multinary TixAl1−xOy oxides are more promising in comparison to single Al2O3 oxide. Some electrical properties of the TixAl1−xOy films observed were a high dielectric constant ∼19, low leakage current density (<3 × 10−5 A/cm2 at 1 MV/cm), and high breakdown field (∼5.5 MV/cm).
Nanoporous gold—Application to extraordinary optical transmission of light
Authors: Garoli Denis , Ruffato Gianluca , Cattarin Sandro , Barison Simona , Perino Mauro , Ongarello Tommaso , Romanato Filippo
Published: December 2012

The authors present their work in the preparation of nanoporous gold layers and their patterning with an original procedure preserving the porosity, to obtain the phenomenon of extraordinary transmission of light with a porous material. The design, fabrication, and characterization of nanoslit arrays made with bulk gold and nanoporous gold films are presented and their sensing performances are compared after coating with thiolated organic molecules. Thanks to a greatly enhanced surface-to-volume ratio, nanoporous gold reveals benefits for better reaction efficiency and detection sensitivity. Moreover, plasmonic properties in the near-IR range assure employment in plasmonic devices.
Absorbed doses behind bones with MR image‐based dose calculations for radiotherapy treatment planning
Authors: Korhonen Juha , Kapanen Mika , Keyriläinen Jani , Seppälä Tiina , Tuomikoski Laura , Tenhunen Mikko
Published: December 2012

Purpose:

Magnetic resonance (MR) images are used increasingly in external radiotherapy target delineation because of their superior soft tissue contrast compared to computed tomography (CT) images. Nevertheless, radiotherapy treatment planning has traditionally been based on the use of CT images, due to the restrictive features of MR images such as lack of electron density information. This research aimed to measure absorbed radiation doses in material behind different bone parts, and to evaluate dose calculation errors in two pseudo‐CT images; first, by assuming a single electron density value for the bones, and second, by converting the electron density values inside bones from T1/T2*‐weighted MR image intensity values.

Methods:

A dedicated phantom was constructed using fresh deer bones and gelatine. The effect of different bone parts to the absorbed dose behind them was investigated with a single open field at 6 and 15 MV, and measuring clinically detectable dose deviations by an ionization chamber matrix. Dose calculation deviations in a conversion‐based pseudo‐CT image and in a bulk density pseudo‐CT image, where the relative electron density to water for the bones was set as 1.3, were quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms.

Results:

The calculations revealed that the applied bulk density pseudo‐CT image causes deviations up to 2.7% (6 MV) and 2.0% (15 MV) to the dose behind the examined bones. The corresponding values in the conversion‐based pseudo‐CT image were 1.3% (6 MV) and 1.0% (15 MV). The examinations illustrated that the representation of the heterogeneous femoral bone (cortex denser compared to core) by using a bulk density for the whole bone causes dose deviations up to 2% both behind the bone edge and the middle part of the bone (diameter <2.5 cm), but in the opposite directions. The measured doses and the calculated ones in the standard CT image were within 0.4% (through gelatine only) and 0.9% (behind bones).

Conclusions:

This study indicates that the decrease in absorbed dose is not dependent on the bone diameter with all types of bones. Thus, performing dose calculation in a pseudo‐CT image by assuming a single electron density value for the bones can lead to a substantial misrepresentation of the dose distribution profile. This work showed that dose calculation accuracy can be improved by using a pseudo‐CT image in which the electron density values have been converted from the MR image intensity values inside bones.
U.S. Regulation of Stem Cells as Medical Products
Authors: Sipp Douglas , Turner Leigh
Published: December 2012

Premarketing approval by the federal government should ensure not only safety, but efficacy as well.
Platelets Kill the Parasite Within
Authors: Engwerda Christian R. , Good Michael F.
Published: December 2012

Platelets destroy
P. falciparum
by secreting a factor that enters infected blood cells and destroys the parasite.
Failure of Skin-Deep Learning
Authors: Alberts Bruce
Published: December 2012

There is a disconnect at the heart of the U.S. education system that is having a devastating effect on how and what children learn. Research shows that the most meaningful learning takes place when students are challenged to address an issue in depth, which can only be done for a relatively small number of topics in any school year.
*
But the traditional process of setting standards tends to promote a superficial “comprehensive coverage” of a field, whether it be biology or history, leaving little room for in-depth learning. The curricula and textbooks that result are skin-deep and severely flawed.
White House Panel Urges Agencies to Take More Risks
Authors: Mervis Jeffrey
Published: December 2012

A new report by a presidential advisory panel urges U.S. research agencies to make a bigger commitment to supporting high-risk, interdisciplinary research by investigators with a strong track record.
Normal Operating Range of Bacterial Communities in Soil Used for Potato Cropping
Authors: İnceoğlu Özgül , van Overbeek Leo Simon , Falcão Salles Joana , van Elsas Jan Dirk
Published: December 2012

In this study, the impacts of six potato (
Solanum tuberosum
) cultivars with different tuber starch allocations (including one genetically modified [GM] line) on the bacterial communities in field soil were investigated across two growth seasons interspersed with 1 year of barley cultivation, using quantitative PCR, clone library, and PCR-denaturing gradient gel electrophoresis (DGGE) analyses. It was hypothesized that the modifications in the tuber starch contents of these plants, yielding changed root growth rates and exudation patterns, might have elicited altered bacterial communities in the soil. The data showed that bacterial abundances in the bulk soil varied over about 2 orders of magnitude across the 3 years. As expected, across all cultivars, positive potato rhizosphere effects on bacterial abundances were noted in the two potato years. The bulk soil bacterial community structures revealed progressive shifts across time, and moving-window analysis revealed a 60% change over the total experiment. Consistent with previous findings, the community structures in the potato rhizosphere compartments were mainly affected by the growth stage of the plants and, to a lesser extent, by plant cultivar type. The data from the soil under the non-GM potato lines were then taken to define the normal operating range (NOR) of the microbiota under potatoes. Interestingly, the bacterial communities under the GM potato line remained within this NOR. In regard to the bacterial community compositions, particular bacterial species in the soil appeared to be specific to (i) the plant species under investigation (barley versus potato) or, with respect to potatoes, (ii) the plant growth stage. Members of the genera
Arthrobacter
,
Streptomyces
,
Rhodanobacter
, and
Dokdonella
were consistently found only at the flowering potato plants in both seasons, whereas
Rhodoplanes
and
Sporosarcina
were observed only in the soil planted to barley.
Intercontinental Dispersal of Bacteria and Archaea by Transpacific Winds
Authors: Smith David J. , Timonen Hilkka J. , Jaffe Daniel A. , Griffin Dale W. , Birmele Michele N. , Perry Kevin D. , Ward Peter D. , Roberts Michael S.
Published: December 2012

Microorganisms are abundant in the upper atmosphere, particularly downwind of arid regions, where winds can mobilize large amounts of topsoil and dust. However, the challenge of collecting samples from the upper atmosphere and reliance upon culture-based characterization methods have prevented a comprehensive understanding of globally dispersed airborne microbes. In spring 2011 at the Mt. Bachelor Observatory in North America (2.8 km above sea level), we captured enough microbial biomass in two transpacific air plumes to permit a microarray analysis using 16S rRNA genes. Thousands of distinct bacterial taxa spanning a wide range of phyla and surface environments were detected before, during, and after each Asian long-range transport event. Interestingly, the transpacific plumes delivered higher concentrations of taxa already in the background air (particularly
Proteobacteria
,
Actinobacteria
, and
Firmicutes
). While some bacterial families and a few marine archaea appeared for the first and only time during the plumes, the microbial community compositions were similar, despite the unique transport histories of the air masses. It seems plausible, when coupled with atmospheric modeling and chemical analysis, that microbial biogeography can be used to pinpoint the source of intercontinental dust plumes. Given the degree of richness measured in our study, the overall contribution of Asian aerosols to microbial species in North American air warrants additional investigation.
S-Layer Protein Mediates the Stimulatory Effect of Lactobacillus helveticus MIMLh5 on Innate Immunity
Authors: Taverniti Valentina , Stuknyte Milda , Minuzzo Mario , Arioli Stefania , De Noni Ivano , Scabiosi Christian , Cordova Zuzet Martinez , Junttila Ilkka , Hämäläinen Sanna , Turpeinen Hannu , Mora Diego , Karp Matti , Pesu Marko , Guglielmetti Simone
Published: December 2012

The ability to positively affect host health through the modulation of the immune response is a feature of increasing importance in measuring the probiotic potential of a bacterial strain. However, the identities of the bacterial cell components involved in cross talk with immune cells remain elusive. In this study, we characterized the dairy strainLactobacillus helveticusMIMLh5 and its surface-layer protein (SlpA) usingin vitroandex vivoanalyses. We found that MIMLh5 and SlpA exert anti-inflammatory effects by reducing the activation of NF-κB on the intestinal epithelial Caco-2 cell line. On the contrary, MIMLh5 and SlpA act as stimulators of the innate immune system by triggering the expression of proinflammatory factors tumor necrosis factor alpha and COX-2 in the human macrophage cell line U937 via recognition through Toll-like receptor 2. In the same experiments, SlpA protein did not affect the expression of the anti-inflammatory cytokine interleukin-10. A similar response was observed following stimulation of macrophages isolated from mouse bone marrow or the peritoneal cavity. These results suggest that SlpA plays a major role in mediating bacterial immune-stimulating activity, which could help to induce the host's defenses against and responses toward infections. This study supports the concept that the viability of bacterial cells is not always essential to exert immunomodulatory effects, thus permitting the development of safer therapies for the treatment of specific diseases according to a paraprobiotic intervention.
Specific Properties of Enteropathogenic Escherichia coli Isolates from Diarrheal Patients and Comparison to Strains from Foods and Fecal Specimens from Cattle, Swine, and Healthy Carriers in Osaka City, Japan
Authors: Wang Lili , Wakushima Mitsuko , Aota Tetsu , Yoshida Yuka , Kita Toshimasa , Maehara Tomofumi , Ogasawara Jun , Choi Changsun , Kamata Yoichi , Hara-Kudo Yukiko , Nishikawa Yoshikazu
Published: December 2012

For exhaustive detection of diarrheagenicEscherichia coli, we previously developed a colony-hybridization method using hydrophobic grid-membrane filters in combination with multiplex real-time PCR. To assess the role of domestic animals as the source of atypical enteropathogenicE. coli(aEPEC), a total of 679 samples (333 from foods, fecal samples from 227 domestic animals, and 119 from healthy people) were examined. Combining 48 strains previously isolated from patients and carriers, 159 aEPEC strains were classified by phylogroup, virulence profile, and intimin typing. Phylogroup B1 was significantly more prevalent among aEPEC from patients (50%) and bovine samples (79%) than from healthy carriers (16%) and swine strains (23%), respectively. Intimin type β1 was predominant in phylogroup B1; B1-β1 strains comprised 26% of bovine strains and 25% of patient strains. The virulence profile groups Ia and Ib were also observed more frequently among bovine strains than among porcine strains. Similarly, virulence group Ia was detected more frequently among patient strains than strains of healthy carriers. A total of 85 strains belonged to virulence group I, and 63 of these strains (74%) belonged to phylogroup B1. The present study suggests that the etiologically important aEPEC in diarrheal patients could be distinguished from aEPEC strains indigenous to humans based on type, such as B1, Ia, and β1/γ1, which are shared with bovine strains, while the aEPEC strains in healthy humans are different, and some of these were also present in porcine samples.
Lucilia sericata Chymotrypsin Disrupts Protein Adhesin-Mediated Staphylococcal Biofilm Formation
Authors: Harris Llinos G. , Nigam Yamni , Sawyer James , Mack Dietrich , Pritchard David I.
Published: December 2012

Staphylococcus aureus
and
Staphylococcus epidermidis
biofilms cause chronic infections due to their ability to form biofilms. The excretions/secretions of
Lucilia sericata
larvae (maggots) have effective activity for debridement and disruption of bacterial biofilms. In this paper, we demonstrate how chymotrypsin derived from maggot excretions/secretions disrupts protein-dependent bacterial biofilm formation mechanisms.
Isoprenoid Biosynthesis Inhibition Disrupts Rab5 Localization and Food Vacuolar Integrity in Plasmodium falciparum
Authors: Howe Ruth , Kelly Megan , Jimah John , Hodge Dana , Odom Audrey R.
Published: December 2012

The antimalarial agent fosmidomycin is a validated inhibitor of the nonmevalonate isoprenoid biosynthesis (methylerythritol 4-phosphate [MEP]) pathway in the malaria parasite,
Plasmodium falciparum
. Since multiple classes of prenyltransferase inhibitors kill
P. falciparum
, we hypothesized that protein prenylation was one of the essential functions of this pathway. We found that MEP pathway inhibition with fosmidomycin reduces protein prenylation, confirming that
de novo
isoprenoid biosynthesis produces the isoprenyl substrates for protein prenylation. One important group of prenylated proteins is small GTPases, such as Rab family members, which mediate cellular vesicular trafficking. We have found that Rab5 proteins dramatically mislocalize upon fosmidomycin treatment, consistent with a loss of protein prenylation. Fosmidomycin treatment caused marked defects in food vacuolar morphology and integrity, consistent with a defect in Rab-mediated vesicular trafficking. These results provide insights to the biological functions of isoprenoids in malaria parasites and may assist the rational selection of secondary agents that will be useful in combination therapy with new isoprenoid biosynthesis inhibitors.
Orthologous Gene Clusters and Taxon Signature Genes for Viruses of Prokaryotes
Authors: Kristensen David M. , Waller Alison S. , Yamada Takuji , Bork Peer , Mushegian Arcady R. , Koonin Eugene V.
Published: December 2012

Viruses are the most abundant biological entities on earth and encompass a vast amount of genetic diversity. The recent rapid increase in the number of sequenced viral genomes has created unprecedented opportunities for gaining new insight into the structure and evolution of the virosphere. Here, we present an update of the phage orthologous groups (POGs), a collection of 4,542 clusters of orthologous genes from bacteriophages that now also includes viruses infecting archaea and encompasses more than 1,000 distinct virus genomes. Analysis of this expanded data set shows that the number of POGs keeps growing without saturation and that a substantial majority of the POGs remain specific to viruses, lacking homologues in prokaryotic cells, outside known proviruses. Thus, the great majority of virus genes apparently remains to be discovered. A complementary observation is that numerous viral genomes remain poorly, if at all, covered by POGs. The genome coverage by POGs is expected to increase as more genomes are sequenced. Taxon-specific, single-copy signature genes that are not observed in prokaryotic genomes outside detected proviruses were identified for two-thirds of the 57 taxa (those with genomes available from at least 3 distinct viruses), with half of these present in all members of the respective taxon. These signatures can be used to specifically identify the presence and quantify the abundance of viruses from particular taxa in metagenomic samples and thus gain new insights into the ecology and evolution of viruses in relation to their hosts.
Genotypic Prediction of HIV-1 CRF01-AE Tropism
Authors: Raymond Stéphanie , Delobel Pierre , Rogez Sylvie , Encinas Stéphanie , Bruel Patrick , Pasquier Christophe , Sandres-Sauné Karine , Marchou Bruno , Massip Patrice , Izopet Jacques
Published: December 2012

HIV-1 subtype CRF01-AE predominates in south Asia and has spread throughout the world. The virus tropism must be determined before using CCR5 antagonists. Genotypic methods could be used, but the prediction algorithms may be inaccurate for non-B subtypes like CRF01-AE and the correlation with the phenotypic approach has not been assessed. We analyzed 61 CRF01-AE V3 clonal sequences of known phenotype from the GenBank database. The sensitivity of the Geno2pheno10 genotypic algorithm was 91%, but its specificity was poor (54%). In contrast, the combined 11/25 and net charge rule was highly specific (98%) but rather insensitive (64%). We thus identified subtype CRF01-AE determinants in the V3 region that are associated with CXCR4 use and developed a new simple rule for optimizing the genotypic prediction of CRF01-AE tropism. The concordance between the predicted CRF01-AE genotype and the phenotype was 95% for the clonal data set. We then validated this algorithm by analyzing the data from 44 patients infected with subtype CRF01-AE, whose tropism was determined using a recombinant phenotypic entry assay and V3-loop bulk sequencing. The CRF01-AE genotypic tool was 70% sensitive and 96% specific for predicting CXCR4 use, and the concordance between genotype and phenotype was 84%, approaching the concordance obtained for predicting the tropism of HIV-1 subtype B. Genotypic predictions that use a subtype CRF01-AE-specific algorithm appear to be preferable for characterizing coreceptor usage both in pathophysiological studies and for ensuring the appropriate use of CCR5 antagonists.
Multiple-Locus Variable-Number Tandem-Repeat Analysis of 201 Mycoplasma pneumoniae Isolates from Beijing, China, from 2008 to 2011
Authors: Zhao Fei , Liu Gang , Cao Bin , Wu Jiang , Gu Yixin , He Lihua , Meng Fanliang , Zhu Liang , Yin Yudong , Lv Min , Zhang Jianzhong
Published: December 2012

A total of 201
Mycoplasma pneumoniae
clinical isolates from Beijing, China, isolated from 2008 to 2011, were clustered into 16 multiple-locus variable-number tandem-repeat analysis (MLVA) types, of which 6 new MLVA types have never been reported previously. Type 1 isolates based on p1 gene genotyping were mainly MLVA types E, J, P, U, and X. There was no correlation between macrolide-resistant
Mycoplasma pneumoniae
and their MLVA type.
Explore the Causes of Health-Care-Acquired Infections: Who Is at Fault?Review of:
Partnering to Heal
(video simulation); US Department of Health and Human Services Healthcare-Associated Infections Initiative. www.hhs.gov/ash/initiatives/hai/training/partneringtoheal.html, and www.hhs.gov/ash/initiatives/hai/training/ (home page).
Authors: Sigmon Janie
Published: December 2012

Review of:
Partnering to Heal
video simulation from the U. S. Department of Health and Human Services Healthcare-Associated Infections Initiative
Two Thumbs-Up for Holistic Approach to Understanding VirusesReview of:	Understanding Viruses,	2nd ed.;	ShorsTeri; (	2013).	Jones and Bartlett Learning,	Burlington, MA.	704 pages.
Authors: Marintcheva Boriana
Published: December 2012

Review of:
Understanding Viruses, 2nd ed.;
Teri Shors (2013). Jones and Bartlett Learning, Burlington, MA. 704 pages.
Understanding How the Brain Learns Should Inform Our Teaching PracticesComparative review of:	The Brain-Targeted Teaching Model for 21st-Century Schools;	HardimanMariale; (	2012).	Corwin,	Thousand Oaks, CA.	223 pages; and	How the Brain Learns,	4th ed.;	SousaDavid A.; (	2011).	Corwin,	Thousand Oaks, CA.	321 pages.
Authors: Darden Alix
Published: December 2012

Comparative review of:
The Brain-Targeted Teaching Model for 21st-Century Schools;
Mariale Hardiman; (2012). Corwin, Thousand Oaks, CA. 223 pages; and How the Brain Learns, 4th ed.; David A. Sousa; (2011). Corwin, Thousand Oaks, CA. 321 pages.
Helping Students Help ThemselvesReview of three resources: How to Get the Most Out of Studying: A Video Series; ChewS. L.; ( 2011). http://www.samford.edu/how-to-study/default.aspx?id=45097158404 (accessed August 10, 2012). Study Smarter, Not Harder: Use the Genius in You, 3rd ed.; PaulKevin; ( 2009). Self-Counsel Press, North Vancouver, BC. 224 pages How to Study Science, 4th ed.; DrewesFrederick W.MilliganKristin L. D.; ( 2002). McGraw Hill, New York, NY. 128 pages.
Authors: Marshall Pamela A.
Published: December 2012

Review of:Three tools that aim to teach students more effective study habits:How to Get the Most Out of Studying: A Video Seriesby S.L. Chew,Study Smarter, Not Harder: Use the Genius in You, 3rd Editionby Kevin Paul, andHow to Study Science 4th Editionby Frederick W. Drewes and Kristin L.D. Milligan.
Towards a Mastery Understanding of Critical Reading in Biology: The Use of Highlighting by Students to Assess Their Value Judgment of the Importance of Primary Literature
Authors: Gallo Mark , Rinaldo Vince
Published: December 2012

An analysis of critical reading styles of freshmen and senior biology students was compared to that of biology faculty members through the use of highlighting a primary research article. Sentence-by-sentence comparisons were made within each group and the data were analyzed; the composite picture from each group was then compared to the other groups. There appears to be a close agreement of what is deemed important content as judged by faculty but less agreement by seniors and even less agreement by freshmen regarding the value of each line of the text. The results imply that experts in a field appear able to discriminate what is important and valuable in the primary literature and that the novice appears to develop some degree of scientific literacy during his or her undergraduate career.
Impaired Virion Secretion by Hepatitis B Virus Immune Escape Mutants and Its Rescue by Wild-Type Envelope Proteins or a Second-Site Mutation
Authors: Kwei Karen , Tang Xiaoli , Lok Anna S. , Sureau Camille , Garcia Tamako , Li Jisu , Wands Jack , Tong Shuping
Published: December 2012

Hepatitis B virus immune escape mutants have been associated with vaccine failure and reinfection of grafted liver despite immune prophylaxis, but their biological properties remain largely unknown. Transfection of 20 such mutants in a human hepatoma cell line identified many with severe impairment in virion secretion, which can be rescued to various extents by coexpression of wild-type envelope proteins or introduction of a novel glycosylation site. Consistent with their role in maintaining intra- or intermolecular disulfide bonds, cysteine residues within the “a” determinant are critical for virion secretion.
Hirayama disease: a frequently undiagnosed condition with simple inexpensive treatment
Authors: Verma Rajesh , Lalla Rakesh , Patil Tushar B , Gupta Arvind
Published: December 2012

Hirayama disease is a non-progressive asymmetric juvenile muscular atrophy involving C7-T1 myotomes leading to weakness and atrophy of intrinsic muscles of hand and forearm with relative sparing of the brachioradialis muscle. This benign focal cervical poliopathy is believed to be caused by forward displacement of the posterior cervical dural sac. In this case report we highlight the importance of dynamic MRI of cervical spine for diagnosis of the above condition and the use of hard cervical collar to prevent further flexion injury.
Accounting for recent trends in the prevalence of diarrhoea in the Democratic Republic of Congo (DRC): results from consecutive cross-sectional surveys
Authors: Emina Jacques B O , Kandala Ngianga-Bakwin
Published: December 2012

Objectives

To analyse trends in diarrhoea prevalence by maternal education, access to clean water and improved sanitation, household wealth index; to identify the sources of variation and assess contribution of changes in socioeconomic characteristics in the Democratic Republic of Congo (DRC).

Design

Consecutive cross-sectional surveys.

Setting

DRC.

Participants

The databases contain information on 9748 children from the 2001 Multiple Indicators Cluster Survey and 7987 children from the 2007 Demographic and Health Survey.

Interventions

N/A.

Primary and secondary outcome measures

Whether the child had diarrhoea 14 days preceding the survey.

Results

The overall prevalence of diarrhoea decreased by 26 percent (from 22.1% in 2001 to 16.4% in 2007). Findings from the three complementary statistical methods are consistent and confirm a significant decrease in diarrhoea regardless of socioeconomic characteristics. Changes in behaviour and/or in public health policy seem to be the likely main source of the change. There were no significant changes in diarrhoea prevalence associated with variation of the population structure. It is worth mentioning that the decrease in diarrhoea prevalence is in contrast to the generalised poor living conditions of the population. Therefore, it is difficult to ascertain whether the decline in diarrhoea prevalence was due to real improvement in public-health policy or to data quality issues.

Conclusions

The decline of diarrhoea prevalence in our study need to be further investigated by conducting district-based or provincial-based studies to validate findings from household surveys such as Demographic and Health Surveys and Multiple Indicators Cluster Survey taking into account the current context of the country: ongoing conflict, poor socioeconomic and poor health infrastructure. However, improvement in living conditions such as access to clean water and improved sanitation will contribute to accelerate the reduction of diarrhoea prevalence as well as reduction of child mortality.
AFFINE ACTIONS ON NON-ARCHIMEDEAN TREES
Authors: ROURKE SHANE O.
Published: December 2012

We initiate the study of affine actions of groups on Λ-trees for a general ordered abelian group Λ; these are actions by dilations rather than isometries. This gives a common generalization of isometric action on a Λ-tree, and affine action on an ℝ-tree as studied by Liousse. The duality between based length functions and actions on Λ-trees is generalized to this setting. We are led to consider a new class of groups: those that admit a free affine action on a Λ-tree for some Λ. Examples of such groups are presented, including soluble Baumslag–Solitar groups and the discrete Heisenberg group.
Stimulation of human TRPA1 channels by clinical concentrations of the antirheumatic drug auranofin
Authors: Hatano Noriyuki , Suzuki Hiroka , Muraki Yukiko , Muraki Katsuhiko
Published: December 2012

Gold compounds, which were widely used to treat rheumatoid arthritis, have been recently used as experimental agents for tumor treatment. Transient receptor potential (TRP) ankyrin repeat 1 (TRPA1) is a Ca2+-permeable ion channel that senses acute and inflammatory pain signals. Electrophilic compounds such as mustard oil and cinnamaldehyde activate TRPA1 by interacting with TRPA1 cysteine residues. Here we investigate the effects of the gold compound auranofin (AUR) on TRPA1 channels. Intracellular Ca2+ and whole cell patch-clamp recordings were performed on human embryonic kidney cells transiently expressed with TRPA1, TRP melastatin 8 (TRPM8), and vanilloid type TRP (TRPV1–4) channels. AUR stimulated TRPA1 in a concentration-dependent manner with a half-maximum potency of around 1.0 μM. The AUR-induced response was effectively blocked by HC030031, a TRPA1 antagonist. On the other hand, AUR failed to activate TRPM8 and TRPV1–4 channels, which are highly expressed in sensory neurons as nociceptors. The stimulatory effect on TRPA1 channels depended on the C414, C421, C621, and C633 cysteine residues and not on the inhibition of thioredoxin reductase by AUR. Moreover, AUR effectively activated TRPA1 channels expressed in human differentiated neuroblastoma cell lines. The study shows that AUR is a potent stimulator of TRPA1 channels.
A novel in vitro model system for smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells
Authors: Guo Xia , Stice Steven L. , Boyd Nolan L. , Chen Shi-You
Published: December 2012

The objective of this study was to develop a novel in vitro model for smooth muscle cell (SMC) differentiation from human embryonic stem cell-derived mesenchymal cells (hES-MCs). We found that hES-MCs were differentiated to SMCs by transforming growth factor-β (TGF-β) in a dose- and time-dependent manner as demonstrated by the expression of SMC-specific genes smooth muscle α-actin, calponin, and smooth muscle myosin heavy chain. Under normal growth conditions, however, the differentiation capacity of hES-MCs was very limited. hES-MC-derived SMCs had an elongated and spindle-shaped morphology and contracted in response to the induction of carbachol and KCl. KCl-induced calcium transient was also evident in these cells. Compared with the parental cells, TGF-β-treated hES-MCs sustained the endothelial tube formation for a longer time due to the sustained SMC phenotype. Mechanistically, TGF-β-induced differentiation was both Smad- and serum response factor/myocardin dependent. TGF-β regulated myocardin expression via multiple signaling pathways including Smad2/3, p38 MAPK, and PI3K. Importantly, we found that a low level of myocardin was present in mesoderm prior to SMC lineage determination, and a high level of myocardin was not induced until the differentiation process was initiated. Taken together, our study characterized a novel SMC differentiation model that can be used for studying human SMC differentiation from mesoderm during vascular development.
Circulating humanin levels are associated with preserved coronary endothelial function
Authors: Widmer R. J. , Flammer A. J. , Herrmann J. , Rodriguez-Porcel M. , Wan J. , Cohen P. , Lerman L. O. , Lerman A.
Published: December 2012

Humanin is a small endogenous antiapoptotic peptide, originally identified as protective against Alzheimer's disease, but subsequently also found on human endothelium as well as carotid artery plaques. Endothelial dysfunction is a precursor to the development of atherosclerotic plaques, which are characterized by a highly proinflammatory, reactive oxygen species, and apoptotic milieu. Previous animal studies demonstrated that humanin administration may improve endothelial function. Thus the aim of this study was to test the hypothesis that patients with coronary endothelial dysfunction have reduced systemic levels of humanin. Forty patients undergoing coronary angiography and endothelial function testing were included and subsequently divided into two groups based on coronary blood flow (CBF) response to intracoronary acetylcholine (normal ≥ 50% increase from baseline, n = 20 each). Aortic plasma samples were obtained at the time of catheterization for the analysis of humanin levels and traditional biomarkers of atherosclerosis including C-reactive protein, Lp-Pla2, and homocysteine. Baseline characteristics were similar in both groups. Patients with coronary endothelial dysfunction (change in CBF = −33 ± 25%) had significantly lower humanin levels (1.3 ± 1.1 vs. 2.2 ± 1.5 ng/ml, P = 0.03) compared with those with normal coronary endothelial function (change in CBF = 194 ± 157%). There was a significant and positive correlation between improved CBF and humanin levels ( P = 0.0091) not seen with changes in coronary flow reserve ( P = 0.76). C-reactive protein, Lp-Pla2, and homocysteine were not associated with humanin levels. Thus we observed that preserved human coronary endothelial function is uniquely associated with higher systemic humanin levels, introducing a potential diagnostic and/or therapeutic target for patients with coronary endothelial function.