bluuebunny/crossref_metadata_2025 huggingface dataset:
A simulation study integrated with analytic hierarchy process (AHP) in an automotive manufacturing system
Authors: Xu Te , Moon Dug Hee , Baek Seung Geun
Published: May 2011

A variety of circumstances, such as developing a new product, changing the design of an existing product, changing the production volume, or changing the product mix, can drive the need for a manufacturing system redesign. Simulation technology has been widely used for evaluating manufacturing system design alternatives. Various performance measures including throughput, utilization of resources, lead-time, and work in process are obtained from simulation studies. However, the dimensions of performance measures are different, and it requires that the trade-offs between them should be considered. In addition, personal preferences in the selection of performance measures vary from person to person. Thus, the multi-criteria decision-making (MCDM) system is required to complement the simulation technology. This paper presents a case study that integrates a simulation study with analytic hierarchy process (AHP), applied to the design of a transmission case line in a Korean automotive factory. The simulation model is developed with QUEST®. Four performance measures (criteria) and seven design alternatives are considered utilizing AHP.
Community Dissemination of the Early Start Denver Model
Authors: Vismara Laurie A. , Young Gregory S. , Rogers Sally J.
Published: May 2011

The growing number of Autism Spectrum Disorder cases exceeds the services available for these children. This increase challenges both researchers and service providers to develop systematic, effective dissemination strategies for transporting university research models to community early intervention (EI) programs. The current study developed an abbreviated training workshop to teach the Early Start Denver Model (ESDM) to 24 community EI practitioners and examined their fidelity of implementation posttraining and 4 months later. Practitioners successfully implemented and self-assessed their delivery of the ESDM teaching strategies compared with fidelity ratings by expert trainers by the end of the workshop. Those who submitted follow-up materials met fidelity in their direct delivery, whereas their self-assessment of skill delivery appeared lower compared with trainers’ fidelity ratings. Findings are discussed about the immediate gains and challenges of community-based dissemination of the ESDM, and the priority for continued research in implementation science to support and sustain intervention delivery.
Macro-Systems Role of Marketing
Authors: Kadirov Djavlonbek
Published: May 2011

The purpose of this research is to advance understanding of the macro-systems role of marketing. The author augments the equivocal principle of marketing (EPM) with the hypothesis that marketing has a negative indirect impact on societal welfare. The estimation of a structural error correction model in the context of the U.S. marketing system confirms that there exists a negative long-run relationship between environmental entropy and sustainable welfare with marketing positively associated with environmental entropy. This fact invalidates the assumptions behind the trade-off conjecture, which could only be supported if one is willing to accept the economic welfare myth.
Coupled system simulator for air screw compressors and their drive systems
Authors: Kameya H , Yamasaki M , Ajima T , Senoh M , Tanaka H , Suzuki N
Published: May 2011

An electric and mechanical coupled system simulator has been developed for designing screw compressors. The simulator contains both electric and mechanical models and analysed them simultaneously. The simulator covers the input of electric power to output of air supply including an inverter, motor, torque transmission, screw air-end, capacity controller, and air receiver tank. It momentarily indicates all parameters, for example, electric voltage, current, magnetic flux density, torque, acceleration, air flowrate, and pressure anywhere in those models. Therefore, even in unsteady or extraordinary conditions, any weak points or over-specifications can be found easily. The simulator can be used in model-based developments for screw compressors to improve their efficiency and reliability in a short term.
Children's Reading Comprehension Difficulties
Authors: Hulme Charles , Snowling Margaret J.
Published: May 2011

The goal of reading is to extract meaning from text, and this depends upon both decoding and language-comprehension skills. Recently there has been growing interest in children who can read accurately but have poor comprehension. Reading-comprehension impairment is relatively common, although it often goes unrecognized in the classroom. Children with reading-comprehension impairment have a range of oral-language weaknesses, which impede their comprehension of both written and spoken language. Recent studies indicate that these underlying oral-language difficulties can be ameliorated by school-based interventions, which can, in turn, improve both reading- and listening-comprehension skills. Early interventions to reduce such language-learning weaknesses potentially have very important educational, social, and economic implications.
Sudden Sensorineural Hearing Loss
Authors: Kuhn Maggie , Heman-Ackah Selena E. , Shaikh Jamil A. , Roehm Pamela C.
Published: May 2011

Sudden sensorineural hearing loss (SSNHL) is commonly encountered in audiologic and otolaryngologic practice. SSNHL is most commonly defined as sensorineural hearing loss of 30dB or greater over at least three contiguous audiometric frequencies occurring within a 72-hr period. Although the differential for SSNHL is vast, for the majority of patients an etiologic factor is not identified. Treatment for SSNHL of known etiology is directed toward that agent, with poor hearing outcomes characteristic for discoverable etiologies that cause inner ear hair cell loss. Steroid therapy is the current mainstay of treatment of idiopathic SSNHL in the United States. The prognosis for hearing recovery for idiopathic SSNHL is dependent on a number of factors including the severity of hearing loss, age, presence of vertigo, and shape of the audiogram.
Withdrawal of life sustaining therapy after traumatic injury
Authors: Weiser Thomas G , Cooper Zara
Published: May 2011

Background: Each year, traumatic injury accounts for large number of patient admissions and deaths in the US. Injuries have tremendous public health implications, and controlling and treating traumatised patients is an essential part of any health delivery system. Nonetheless, traumatised patients whose terminal hospitalisation ends in the intensive care unit (ICU) are a particular demographic group that has not been well studied.

Methods: Here, we review demographic trends, critical care unit utilisation and outcomes for trauma patients. Based on the available data, we discuss issues related to specific patient groups (such as the elderly), management of end-of-life patients in the ICU, views of medical professionals relative to end-of-life care and costs associated and with care of terminally ill patients. In this context, we also review and discuss recent data on withdrawal of life-sustaining therapies for trauma patients.

Conclusions: We conclude that it is difficult for physicians, patients and their families to recognise when care should focus on comfort rather than aggressive interventions that prolong dying. This is particularly difficult in situations of trauma, where unexpected injury causes profound disability. Nonetheless, the challenges pertain to trauma patients as they do to all critically ill patients, where providing an ethical and dignified death can be as heroic as aggressive measures to save life. More studies are needed to determine how we can best meet the needs of terminally ill trauma patients and their families.
Self-Naming Practices on the Internet: Identity, Authenticity, and Community
Authors: Gatson Sarah N.
Published: May 2011

The author was a member and participant observer of a community that was initially exclusively based in online interactions. Over time, the community developed several regular offline interactions as well as a rich and extensive set of online interactive communication spaces. Herein, the author explores the symbolic meanings of members’ practices on choosing names for their initial and ongoing self-presentations to the community. These practices are discussed with regard to the matching of online to offline (so-called virtual vs. so-called real life ) symbolic identities or statuses such as age, gender, race, geography, and occupation. The idea that meanings emerging from everyday interaction are discovered through close observation and intimate familiarity with participants’ cultural settings are explored in an Internet setting. The author concludes that a rendition of the online persona as inherently less truthful—or at least less dense/rich/full—than offline presentations is problematic at best.
Should Certification of Meteorologists Serve as a Model for Broadcast Journalists?
Authors: Owens Lynn C. , Tuggle C. A. , Holman Lynette
Published: May 2011

This study explores the idea of establishing a certification process for broadcast journalists in order to distinguish themselves from the growing number of internet users posting news online. Certified broadcast meteorologists were surveyed about certification, its effect on First Amendment rights of press freedom, and whether a certification of all broadcast journalists could work to distinguish the profession as credible, competent, and professional. A vast majority of respondents felt they could be credible and professional without certification, but at the same time felt they should be certified. Most respondents said certification helped in both getting a job in the profession and in stations' promotions efforts.
“Remain Calm. Be Kind.” Effects of Relaxing Video Games on Aggressive and Prosocial Behavior
Authors: Whitaker Jodi L. , Bushman Brad J.
Published: May 2011

Research shows that violent video games increase aggressive behavior and decrease prosocial behavior, but could relaxing video games have the opposite effects? In two experiments, participants were randomly assigned to play a relaxing, neutral, or prosocial video game for 20 min. In Experiment 1, participants competed with an ostensible partner on a competitive reaction time task in which they could behave in an aggressive manner (by blasting their partner with loud noise), or in a prosocial manner (by giving their partner money). In Experiment 2, participants reported their mood after playing the video game. After the study was over, they could help the experimenter by sharpening pencils. Compared to those who played violent or neutral video games, those who played relaxing video games were less aggressive and more helpful. Playing a relaxing video game put people in a good mood, and those in a good mood were more helpful.
GPCR-SSFE: A comprehensive database of G-protein-coupled receptor template predictions and homology models
Authors: Worth Catherine L , Kreuchwig Annika , Kleinau Gunnar , Krause Gerd
Published: May 2011

Background

G protein-coupled receptors (GPCRs) transduce a wide variety of extracellular signals to within the cell and therefore have a key role in regulating cell activity and physiological function. GPCR malfunction is responsible for a wide range of diseases including cancer, diabetes and hyperthyroidism and a large proportion of drugs on the market target these receptors. The three dimensional structure of GPCRs is important for elucidating the molecular mechanisms underlying these diseases and for performing structure-based drug design. Although structural data are restricted to only a handful of GPCRs, homology models can be used as a proxy for those receptors not having crystal structures. However, many researchers working on GPCRs are not experienced homology modellers and are therefore unable to benefit from the information that can be gleaned from such three-dimensional models. Here, we present a comprehensive database called the GPCR-SSFE, which provides initial homology models of the transmembrane helices for a large variety of family A GPCRs.

Description

Extending on our previous theoretical work, we have developed an automated pipeline for GPCR homology modelling and applied it to a large set of family A GPCR sequences. Our pipeline is a fragment-based approach that exploits available family A crystal structures. The GPCR-SSFE database stores the template predictions, sequence alignments, identified sequence and structure motifs and homology models for 5025 family A GPCRs. Users are able to browse the GPCR dataset according to their pharmacological classification or search for results using a UniProt entry name. It is also possible for a user to submit a GPCR sequence that is not contained in the database for analysis and homology model building. The models can be viewed using a Jmol applet and are also available for download along with the alignments.

Conclusions

The data provided by GPCR-SSFE are useful for investigating general and detailed sequence-structure-function relationships of GPCRs, performing structure-based drug design and for better understanding the molecular mechanisms underlying disease-associated mutations in GPCRs. The effectiveness of our multiple template and fragment approach is demonstrated by the accuracy of our predicted homology models compared to recently published crystal structures.
Stereochemical errors and their implications for molecular dynamics simulations
Authors: Schreiner Eduard , Trabuco Leonardo G , Freddolino Peter L , Schulten Klaus
Published: May 2011

Background

Biological molecules are often asymmetric with respect to stereochemistry, and correct stereochemistry is essential to their function. Molecular dynamics simulations of biomolecules have increasingly become an integral part of biophysical research. However, stereochemical errors in biomolecular structures can have a dramatic impact on the results of simulations.

Results

Here we illustrate the effects that chirality and peptide bond configuration flips may have on the secondary structure of proteins throughout a simulation. We also analyze the most common sources of stereochemical errors in biomolecular structures and present software tools to identify, correct, and prevent stereochemical errors in molecular dynamics simulations of biomolecules.

Conclusions

Use of the tools presented here should become a standard step in the preparation of biomolecular simulations and in the generation of predicted structural models for proteins and nucleic acids.
Novel molecular markers of Chlamydia pecorum genetic diversity in the koala (Phascolarctos cinereus)
Authors: Marsh James , Kollipara Avinash , Timms Peter , Polkinghorne Adam
Published: May 2011

Background

Chlamydia pecorum is an obligate intracellular bacterium and the causative agent of reproductive and ocular disease in several animal hosts including koalas, sheep, cattle and goats. C. pecorum strains detected in koalas are genetically diverse, raising interesting questions about the origin and transmission of this species within koala hosts. While the ompA gene remains the most widely-used target in C. pecorum typing studies, it is generally recognised that surface protein encoding genes are not suited for phylogenetic analysis and it is becoming increasingly apparent that the ompA gene locus is not congruent with the phylogeny of the C. pecorum genome. Using the recently sequenced C. pecorum genome sequence (E58), we analysed 10 genes, including ompA, to evaluate the use of ompA as a molecular marker in the study of koala C. pecorum genetic diversity.

Results

Three genes (incA, ORF663, tarP) were found to contain sufficient nucleotide diversity and discriminatory power for detailed analysis and were used, with ompA, to genotype 24 C. pecorum PCR-positive koala samples from four populations. The most robust representation of the phylogeny of these samples was achieved through concatenation of all four gene sequences, enabling the recreation of a "true" phylogenetic signal. OmpA and incA were of limited value as fine-detailed genetic markers as they were unable to confer accurate phylogenetic distinctions between samples. On the other hand, the tarP and ORF663 genes were identified as useful "neutral" and "contingency" markers respectively, to represent the broad evolutionary history and intra-species genetic diversity of koala C. pecorum. Furthermore, the concatenation of ompA, incA and ORF663 sequences highlighted the monophyletic nature of koala C. pecorum infections by demonstrating a single evolutionary trajectory for koala hosts that is distinct from that seen in non-koala hosts.

Conclusions

While the continued use of ompA as a fine-detailed molecular marker for epidemiological analysis appears justified, the tarP and ORF663 genes also appear to be valuable markers of phylogenetic or biogeographic divisions at the C. pecorum intra-species level. This research has significant implications for future typing studies to understand the phylogeny, genetic diversity, and epidemiology of C. pecorum infections in the koala and other animal species.
An adjuvant free mouse model of oral allergenic sensitization to rice seeds protein
Authors: Chen Xiao-Wei , Lau Ken Wan-Keung , Yang Fan , Sun Samuel Sai-Ming , Fung Ming-Chiu
Published: May 2011

Background

Rice is commonly known as a staple crop consumed worldwide, though with several rice proteins being reported for allergic properties in clinical studies. Thus, there is a growing need for the development of an animal model to better understand the allergenicity of rice proteins and the immunological and pathophysiological mechanisms underlying the development of food allergy.

Methods

Groups of BALB/c mice were sensitized daily with freshly homogenized rice flour (30 mg or 80 mg) without adjuvant by intragastric gavage. In addition, the mice were challenged with extracted rice flour proteins at several time points intragastrically. Hypersensitivity symptoms in mice were evaluated according to a scoring system. Vascular leakage, ELISA of rice protein-specific IgE, histopathology of small intestine, and passive cutaneous anaphylaxis were conducted on challenged mice.

Results

An adjuvant free mouse model of rice allergy was established with sensitized mice showing increased scratching behaviors and increased vascular permeability. Rice protein-specific IgE was detected after eighteen days of sensitization and from the fifth challenge onwards. Inflammatory damage to the epithelium in the small intestine of mice was observed beyond one month of sensitization. Passive cutaneous anaphylaxis results confirmed the positive rice allergy in the mouse model.

Conclusions

We introduced a BALB/c mouse model of rice allergy with simple oral sensitization without the use of adjuvant. This model would serve as a useful tool for further analysis on the immunopathogenic mechanisms of the various rice allergens, for the evaluation of the hypersensitivity of rice or other cereal grains, and to serve as a platform for the development of immunotherapies against rice allergens.
Mitochondrial targeted catalase suppresses invasive breast cancer in mice
Authors: Goh Jorming , Enns Linda , Fatemie Soroosh , Hopkins Heather , Morton John , Pettan-Brewer Christina , Ladiges Warren
Published: May 2011

Background

Treatment of invasive breast cancer has an alarmingly high rate of failure because effective targets have not been identified. One potential target is mitochondrial generated reactive oxygen species (ROS) because ROS production has been associated with changes in substrate metabolism and lower concentration of anti-oxidant enzymes in tumor and stromal cells and increased metastatic potential.

Methods

Transgenic mice expressing a human catalase gene (mCAT) were crossed with MMTV-PyMT transgenic mice that develop metastatic breast cancer. All mice (33 mCAT positive and 23 mCAT negative) were terminated at 110 days of age, when tumors were well advanced. Tumors were histologically assessed for invasiveness, proliferation and metastatic foci in the lungs. ROS levels and activation status of p38 MAPK were determined.

Results

PyMT mice expressing mCAT had a 12.5 per cent incidence of high histological grade primary tumor invasiveness compared to a 62.5 per cent incidence in PyMT mice without mCAT. The histological grade correlated with incidence of metastasis with 56 per cent of PyMT mice positive for mCAT showing evidence of pulmonary metastasis compared to 85.4 per cent of PyMT mice negative for mCAT with pulmonary metastasis (p ≤ 0.05). PyMT tumor cells expressing mCAT had lower ROS levels and were more resistant to hydrogen peroxide-induced oxidative stress than wild type tumor cells, suggesting that mCAT has the potential of quenching intracellular ROS and subsequent invasive behavior. The metastatic tumor burden in PyMT mice expressing mCAT was 0.1 mm2/cm2 of lung tissue compared with 1.3 mm2/cm2 of lung tissue in PyMT mice expressing the wild type allele (p ≤ 0.01), indicating that mCAT could play a role in mitigating metastatic tumor progression at a distant organ site. Expression of mCAT in the lungs increased resistance to hydrogen peroxide-induced oxidative stress that was associated with decreased activation of p38MAPK suggesting ROS signaling is dependent on p38MAPK for at least some of its downstream effects.

Conclusion

Targeting catalase within mitochondria of tumor cells and tumor stromal cells suppresses ROS-driven tumor progression and metastasis. Therefore, increasing the antioxidant capacity of the mitochondrial compartment could be a rational therapeutic approach for invasive breast cancer.

Please see related commentary article: http://www.biomedcentral.com/1741-7015/9/62
Pharmacologic disruption of Polycomb Repressive Complex 2 inhibits tumorigenicity and tumor progression in prostate cancer
Authors: Crea Francesco , Hurt Elaine M , Mathews Lesley A , Cabarcas Stephanie M , Sun Lei , Marquez Victor E , Danesi Romano , Farrar William L
Published: May 2011

Background

Polycomb repressive complex 2 (PRC2) mediates gene silencing through histone H3K27 methylation. PRC2 components are over-expressed in metastatic prostate cancer (PC), and are required for cancer stem cell (CSC) self-renewal. 3-Dezaneplanocin-A (DZNeP) is an inhibitor of PRC2 with broad anticancer activity.

Method

we investigated the effects of DZNeP on cell proliferation, tumorigenicity and invasive potential of PC cell lines (LNCaP and DU145).

Results

Exploring GEO and Oncomine databases, we found that specific PRC2 genes (EED, EZH2, SUZ12) predict poor prognosis in PC. Non-toxic DZNeP concentrations completely eradicated LNCaP and DU145 prostatosphere formation, and significantly reduced the expression of CSC markers. At comparable doses, other epigenetic drugs were not able to eradicate CSCs. DZNeP was also able to reduce PC cell invasion. Cells pre-treated with DZNeP were significantly less tumorigenic (LNCaP) and formed smaller tumors (DU145) in immunocompromised mice.

Conclusion

DZNeP is effective both in vitro and in vivo against PC cells. DZNeP antitumor activity is in part mediated by inhibition of CSC tumorigenic potential.
Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations
Authors: Niehr Franziska , von Euw Erika , Attar Narsis , Guo Deliang , Matsunaga Doug , Sazegar Hooman , Ng Charles , Glaspy John A , Recio Juan A , Lo Roger S , Mischel Paul S , Comin-Anduix Begonya , Ribas Antoni
Published: May 2011

Background

A molecular linkage between the MAPK and the LKB1-AMPK energy sensor pathways suggests that combined MAPK oncogene inhibition and metabolic modulation of AMPK would be more effective than either manipulation alone in melanoma cell lines.

Materials and methods

The combination of the BRAF inhibitor vemurafenib (formerly PLX4032) and metformin were tested against a panel of human melanoma cell lines with defined BRAF and NRAS mutations for effects on viability, cell cycle and apoptosis. Signaling molecules in the MAPK, PI3K-AKT and LKB1-AMPK pathways were studied by Western blot.

Results

Single agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status, but in one NRASQ61K mutant cell line it powerfully stimulated cell growth. Synergistic anti-proliferative effects of the combination of metformin with vemurafenib were observed in 6 out of 11 BRAFV600E mutants, including highly synergistic effects in two BRAFV600E mutant melanoma cell lines. Antagonistic effects were noted in some cell lines, in particular in BRAFV600E mutant cell lines resistant to single agent vemurafenib. Seven out of 8 BRAF wild type cell lines showed marginally synergistic anti-proliferative effects with the combination, and one cell line had highly antagonistic effects with the combination. The differential effects were not dependent on the sensitivity to each drug alone, effects on cell cycle or signaling pathways.

Conclusions

The combination of vemurafenib and metformin tended to have stronger anti-proliferative effects on BRAFV600E mutant cell lines. However, determinants of vemurafenib and metformin synergism or antagonism need to be understood with greater detail before any potential clinical utility of this combination.
Biomechanical analysis and modeling of different vertebral growth patterns in adolescent idiopathic scoliosis and healthy subjects
Authors: Shi Lin , Wang Defeng , Driscoll Mark , Villemure Isabelle , Chu Winnie CW , Cheng Jack CY , Aubin Carl-Eric
Published: May 2011

Background

The etiology of AIS remains unclear, thus various hypotheses concerning its pathomechanism have been proposed. To date, biomechanical modeling has not been used to thoroughly study the influence of the abnormal growth profile (i.e., the growth rate of the vertebral body during the growth period) on the pathomechanism of curve progression in AIS. This study investigated the hypothesis that AIS progression is associated with the abnormal growth profiles of the anterior column of the spine.

Methods

A finite element model of the spinal column including growth dynamics was utilized. The initial geometric models were constructed from the bi-planar radiographs of a normal subject. Based on this model, five other geometric models were generated to emulate different coronal and sagittal curves. The detailed modeling integrated vertebral body growth plates and growth modulation spinal biomechanics. Ten years of spinal growth was simulated using AIS and normal growth profiles. Sequential measures of spinal alignments were compared.

Results

(1) Given the initial lateral deformity, the AIS growth profile induced a significant Cobb angle increase, which was roughly between three to five times larger compared to measures utilizing a normal growth profile. (2) Lateral deformities were absent in the models containing no initial coronal curvature. (3) The presence of a smaller kyphosis did not produce an increase lateral deformity on its own. (4) Significant reduction of the kyphosis was found in simulation results of AIS but not when using the growth profile of normal subjects.

Conclusion

Results from this analysis suggest that accelerated growth profiles may encourage supplementary scoliotic progression and, thus, may pose as a progressive risk factor.
The Bowge of Courte and the Afterlives of Allegory
Authors: Crawford J. M.
Published: May 2011

John Skelton is a transitional poet. He is perhaps the last practitioner in the visionary forms of the English fifteenth century, and he is an early practitioner in the secularized poetry to which those old forms give way. Many scholars regard Skelton's allegorical poems, especially, as experiments in secularity, as adaptations of allegory's visionary energies to the social and institutional secularization of early modern England. But in one poem, The Bowge of Courte, Skelton remakes allegory not just as an idiom of social and institutional analysis but also, much more powerfully, as an idiom of reflexive consciousness. He explores the moment at which social secularity emerges in private neurosis. And he discovers, in the structures of medieval allegory, the germ of a new sort of allegorical poetry, a poetry marked by solitude, paranoia, melancholy, and hallucinatory self-regard.
DrosophilaMon2 couples Oskar-induced endocytosis with actin remodeling for cortical anchorage of the germ plasm
Authors: Tanaka Tsubasa , Kato Yasuko , Matsuda Kazuki , Hanyu-Nakamura Kazuko , Nakamura Akira
Published: May 2011

Drosophila pole (germ) plasm contains germline and abdominal determinants. Its assembly begins with the localization and translation of oskar (osk) RNA at the oocyte posterior, to which the pole plasm must be restricted for proper embryonic development. Osk stimulates endocytosis, which in turn promotes actin remodeling to form long F-actin projections at the oocyte posterior pole. Although the endocytosis-coupled actin remodeling appears to be crucial for the pole plasm anchoring, the mechanism linking Osk-induced endocytic activity and actin remodeling is unknown. Here, we report that a Golgi-endosomal protein, Mon2, acts downstream of Osk to remodel cortical actin and to anchor the pole plasm. Mon2 interacts with two actin nucleators known to be involved in osk RNA localization in the oocyte, Cappuccino (Capu) and Spire (Spir), and promotes the accumulation of the small GTPase Rho1 at the oocyte posterior. We also found that these actin regulators are required for Osk-dependent formation of long F-actin projections and cortical anchoring of pole plasm components. We propose that, in response to the Osk-mediated endocytic activation, vesicle-localized Mon2 acts as a scaffold that instructs the actin-remodeling complex to form long F-actin projections. This Mon2-mediated coupling event is crucial to restrict the pole plasm to the oocyte posterior cortex.
Regulative deployment of the skeletogenic gene regulatory network during sea urchin development
Authors: Sharma Tara , Ettensohn Charles A.
Published: May 2011

The well-known regulative properties of the sea urchin embryo, coupled with the recent elucidation of gene regulatory networks (GRNs) that underlie cell specification, make this a valuable experimental model for analyzing developmental plasticity. In the sea urchin, the primary mesenchyme cell (PMC) GRN controls the development of the embryonic skeleton. Remarkably, experimental manipulations reveal that this GRN can be activated in almost any cell of the embryo. Here, we focus on the activation of the PMC GRN during gastrulation by non-skeletogenic mesoderm (NSM) cells and by endoderm cells. We show that most transfating NSM cells are prospective blastocoelar cells, not prospective pigment cells, as was previously believed. Earlier work showed that the regulative deployment of the GRN, unlike its deployment in the micromere-PMC lineage, is independent of the transcriptional repressor Pmar1. In this work, we identify several additional differences in the upstream regulation of the GRN during normal and regulative development. We provide evidence that, despite these changes in the upstream regulation of the network, downstream regulatory genes and key morphoregulatory genes are deployed in transfating NSM cells in a fashion that recapitulates the normal deployment of the GRN, and which can account for the striking changes in migratory behavior that accompany NSM transfating. Finally, we report that mitotic cell division is not required for genomic reprogramming in this system, either within a germ layer (NSM transfating) or across a germ layer boundary (endoderm transfating).
A versatile strategy for gene trapping and trap conversion in emerging model organisms
Authors: Kontarakis Zacharias , Pavlopoulos Anastasios , Kiupakis Alexandros , Konstantinides Nikolaos , Douris Vassilis , Averof Michalis
Published: May 2011

Genetic model organisms such as Drosophila, C. elegans and the mouse provide formidable tools for studying mechanisms of development, physiology and behaviour. Established models alone, however, allow us to survey only a tiny fraction of the morphological and functional diversity present in the animal kingdom. Here, we present iTRAC, a versatile gene-trapping approach that combines the implementation of unbiased genetic screens with the generation of sophisticated genetic tools both in established and emerging model organisms. The approach utilises an exon-trapping transposon vector that carries an integrase docking site, allowing the targeted integration of new constructs into trapped loci. We provide proof of principle for iTRAC in the emerging model crustacean Parhyale hawaiensis: we generate traps that allow specific developmental and physiological processes to be visualised in unparalleled detail, we show that trapped genes can be easily cloned from an unsequenced genome, and we demonstrate targeting of new constructs into a trapped locus. Using this approach, gene traps can serve as platforms for generating diverse reporters, drivers for tissue-specific expression, gene knockdown and other genetic tools not yet imagined.
Development of a high-dynamic range, GFP-based FRET probe sensitive to oxidative microenvironments
Authors: Kolossov Vladimir L , Spring Bryan Q , Clegg Robert M , Henry Jennifer J , Sokolowski Anna , Kenis Paul J A , Gaskins H Rex
Published: May 2011

We report the optimization of a novel redox-sensitive probe with enhanced dynamic range and an exceptionally well-positioned oxidative midpoint redox potential. The present work characterizes factors that contribute to the improved Förster resonance energy transfer (FRET) performance of this green fluorescent protein (GFP)-based redox sensor. The α-helical linker, which separates the FRET donor and acceptor, has been extended in the new probe and leads to a decreased FRET efficiency in the linker's reduced, ‘FRET-off’ state. Unexpectedly, the FRET efficiency is increased in the new linker's oxidized, ‘FRET-on’ state compared with the parent probe, in spite of the longer linker sequence. The combination of a lowered baseline ‘FRET-off’ and an increased ‘FRET-on’ signal significantly improves the dynamic range of the probe for a more robust discrimination of its reduced and oxidized linker states. Mutagenesis of the cysteine residues within the α-helix linker reveals the importance of the fourth, C-terminal cysteine and the relative insignificance of the second cysteine in forming the disulfide bridge to clamp the linker into the high-FRET, oxidized state. To further optimize the performance of the redox probe, various cyan fluorescent protein (CFP)/yellow fluorescent protein (YFP) FRET pairs, placed at opposite ends of the improved redox linker (RL7), were quantitatively compared and exchanged. We found that the CyPet/YPet and ECFP/YPet FRET pairs when attached to RL7 do not function well as sensitive redox probes due to a strong tendency to form heterodimers, which disrupt the α-helix. However, monomeric versions of CyPet and YPet (mCyPet and mYPet) eliminate dimerization and restore redox sensitivity of the probe. The best performing probe, ECFP-RL7-EYFP, exhibits an approximately six-fold increase in FRET efficiency in vitro when passing from the oxidized to the reduced state. We determined the midpoint redox potential of the probe to be −143 ± 6 mV, which is ideal for measuring glutathione (GSH/GSSG) redox potentials in oxidative compartments of mammalian cells (e.g. the endoplasmic reticulum).
Effect of stem cells seeded onto biomaterial on the progression of experimental chronic kidney disease
Authors: Caldas Heloisa C , Fernandes Ida M M , Kawasaki-Oyama Rosa S , Baptista Maria Alice S F , Plepis Ana Maria G , Martins Virginia A , Coimbra Terezila M , Goloni-Bertollo Eny M , Braile Domingo M , Abbud-Filho Mario
Published: May 2011

Different routes for the administration of bone marrow-derived cells (BMDC) have been proposed to treat the progression of chronic renal failure (CRF). We investigated whether (1) the use of bovine pericardium (BP) as a scaffold for cell therapy would retard the progression of CRF and (2) the efficacy of cell therapy differently impacts distinct degrees of CRF. We used 2/3 and 5/6 models of renal mass reduction to simulate different stages of chronicity. Treatments consisted of BP seeded with either mesenchymal or mononuclear cells implanted in the parenchyma of remnant kidney. Renal function and proteinuria were measured at days 45 and 90 after cell implantation. BMDC treatment reduced glomerulosclerosis, interstitial fibrosis and lymphocytic infiltration. Immunohistochemistry showed decreased macrophage accumulation, proliferative activity and the expression of fibronectin and α-smooth muscle-actin. Our results demonstrate: (1) biomaterial combined with BMDC did retard the progression of experimental CRF; (2) cellular therapy stabilized serum creatinine (sCr), improved creatinine clearance and 1/sCr slope when administered during the less severe stages of CRF; (3) treatment with combined therapy decreased glomerulosclerosis, fibrosis and the expression of fibrogenic molecules; and (4) biomaterials seeded with BMDC can be an alternative route of cellular therapy.
Ken Burns Gone Wild: Naturalizing the Nation in The National Parks: America's Best Idea
Authors: Jacoby Karl
Published: May 2011

The release of Ken Burns's documentary on the national parks is to be celebrated for bringing national attention to the field of environmental history. Yet for all the movie's strengths, Burns only partially engaged two concepts central to contemporary environmental history: social difference and the cultural construction of nature. As a result, the series devoted less attention than it might have to such important issues as the removal of Native Americans from the national parks and to the ways nature in the parks has changed over time.
Hypoparathyroidism and autoimmunity in the 22q11.2 deletion syndrome
Authors: Lima Kari , Abrahamsen Tore G , Wolff Anette Bøe , Husebye Eystein , Alimohammadi Mohammad , Kämpe Olle , Følling Ivar
Published: May 2011

Objective

To characterize the endocrine and autoimmune disturbances with emphasis on parathyroid dysfunction in patients with 22q11.2 deletion syndrome (22q11.2 DS).

Design

In this nationwide survey; 59 patients (age 1–54 years) out of 86 invited with a 22q11.2 DS were recruited through all the genetic institutes in Norway.

Methods

Data was collected from blood tests, medical records, a physical examination and a semi-structured interview. We registered autoimmune diseases and measured autoantibodies, hormone levels and HLA types.

Results

Twenty-eight (47%) patients had hypoparathyroidism or a history of neonatal or transient hypocalcemia. Fifteen patients had neonatal hypocalcemia. Fourteen patients had permanent hypoparathyroidism including seven (54%) of those above age 15 years. A history of neonatal hypocalcemia did not predict later occurring hypoparathyroidism. Parathyroid hormone levels were generally low indicating a low reserve capacity. Twenty-eight patients were positive for autoantibodies. Six (10%) persons had developed an autoimmune disease, and all were females (P<0.02). Hypoparathyroidism correlated with autoimmune diseases (P<0.05), however, no antibodies were detected against the parathyroid glands.

Conclusions

Hypoparathyroidism and autoimmunity occur frequently in the 22q11.2 DS. Neonatal hypocalcemia is not associated with later development of permanent hypoparathyroidism. Hypoparathyroidism may present at any age, also in adults, and warrants regular measurement of calcium levels. Hypoparathyroidism and autoimmunity occur frequently together. Our findings of autoimmune diseases in 10% of the patients highlight the importance of stringent screening and follow-up routines.
Insulin receptor and cancer
Authors: Belfiore Antonino , Malaguarnera Roberta
Published: May 2011

The widespread epidemic of obesity and type 2 diabetes has raised concern for the impact of these disorders as risk factors for cancer and has renewed the interest for studies regarding the involvement of hyperinsulinemia and insulin receptor (IR) in cancer progression. Overexpression of IR in cancer cells may explain their increased sensitivity to hyperinsulinemia. Moreover, IR isoform A (IR-A) together with autocrine production of its ligand IGF2 is emerging as an important mechanism of normal and cancer stem cell expansion and is a feature of several malignancies.De novoactivation of the IR-A/IGF2 autocrine loop also represents a mechanism of resistance to anticancer therapies. Increasing knowledge of the IR role in cancer has important implications for cancer prevention, which should include control of insulin resistance and hyperinsulinemia in the population and meticulous evaluation of new antidiabetic drugs for their metabolic:mitogenic ratio. We are now aware that several anticancer treatments may induce or worsen insulin resistance that may limit therapy efficacy. Future anticancer therapies need to target the IR-A pathway in order to inhibit the tumor promoting effect of IR without impairing the metabolic effect of insulin.
Fermented Milk Containing Bifidobacterium lactis DN-173 010 in Childhood Constipation: A Randomized, Double-Blind, Controlled Trial
Authors: Tabbers Merit M. , Chmielewska Ania , Roseboom Maaike G. , Crastes Nolwenn , Perrin Catherine , Reitsma Johannes B. , Norbruis Obbe , Szajewska Hania , Benninga Marc A.
Published: May 2011

BACKGROUND:

Constipation is a frustrating symptom affecting 3% of children worldwide. A fermented dairy product containing Bifidobacterium lactis strain DN-173 010 was effective in increasing stool frequency in constipated women. Our aim was to assess the effects of this product in constipated children.

METHODS:

In this prospective randomized, double-blind, controlled trial, 159 constipated children (defecation frequency < 3 times per week) were randomly allocated to receive either a fermented dairy product that contains B lactis DN-173 010 (n = 79) or a control product (n = 80) twice a day for 3 weeks. The primary endpoint was the change in stool frequency from baseline to after 3 weeks of product consumption. Analyses were by intention to treat.

RESULTS:

Eleven children did not return to any follow-up visit (5 in the probiotic group, 6 in the control group) and were therefore excluded from the final analysis. Thus, 74 children in each group were analyzed. The change in stool frequency from baseline to after 3 weeks of product consumption increased in both groups, but the difference was not statistically significant (2.9 ± 3.2 in probiotic group versus 2.6 ± 2.6 in control group, P = .35). There were no serious adverse events.

CONCLUSIONS:

In constipated children, the fermented dairy product containing B lactis strain DN-173 010 did increase stool frequency, but this increase was comparable in the control group. There is currently not sufficient evidence to recommend fermented dairy products containing B lactis strain DN-173 010 in this category of patients. Future studies should focus on whether a longer period of probiotic products is more effective in children who have a short history of constipation.
Antibiotic Prescribing During Pediatric Ambulatory Care Visits for Asthma
Authors: Paul Ian M. , Maselli Judith H. , Hersh Adam L. , Boushey Homer A. , Nielson Dennis W. , Cabana Michael D.
Published: May 2011

OBJECTIVE:

National guidelines do not recommend antibiotics as an asthma therapy. We sought to examine the frequency of inappropriate antibiotic prescribing during US ambulatory care pediatric asthma visits as well as the patient, provider, and systemic variables associated with such practice.

PATIENTS AND METHODS:

Data from the National Ambulatory Medical Care Surveys and National Hospital Ambulatory Medical Care Survey were examined to assess office and emergency-department asthma visits made by children (aged <18 years) for frequencies of antibiotic prescription. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to assess the presence of coexisting conditions warranting antibiotics. Multivariable logistic regression models assessed associations with the prescription of antibiotics.

RESULTS:

From 1998 to 2007, an estimated 60.4 million visits occurred for asthma without another ICD-9 code justifying antibiotic prescription. Antibiotics were prescribed during 16% of these visits, most commonly macrolides (48.8%). In multivariate analysis, controlling for patient age, gender, race, insurance type, region, and controller medication use, systemic corticosteroid prescription (odds ratio [OR]: 2.69 [95% confidence interval (CI): 1.68–4.30]) and treatment during the winter (OR: 1.92 [95% CI: 1.05–3.52]) were associated with an increased likelihood of antibiotic prescription, whereas treatment in an emergency department was associated with decreased likelihood (OR: 0.48 [95% CI: 0.26–0.89]). A second multivariate analysis of only office-based visits demonstrated that asthma education during the visits was associated with reduced antibiotic prescriptions (OR: 0.46 [95% CI: 0.24–0.86]).

CONCLUSIONS:

Antibiotics are prescribed during nearly 1 in 6 US pediatric ambulatory care visits for asthma, ∼1 million prescriptions annually, when antibiotic need is undocumented. Additional education and interventions are needed to prevent unnecessary antibiotic prescribing for asthma.
A intersubjetividade no cuidado à Saúde Mental: narrativas de técnicos e auxiliares de enfermagem de um Centro de Atenção Psicossocial
Authors: Campos Rosana Onocko , Baccari Ivana Preto
Published: May 2011

Diante da demanda por atenção em Saúde Mental e na tentativa de se renovar o tratamento psiquiátrico destinado a portadores de transtornos mentais severos, surgiram os Centros de Atenção Psicossocial (Caps). Este artigo visa à análise de repercussões subjetivas do trabalho nos Caps nos profissionais de nível médio, buscandose contribuir para o planejamento em saúde. Realizaram-se dois grupos focais com trabalhadores de um Caps III. A metodologia utilizada para análise alicerça-se na abordagem hermenêutico-crítica proposta por Ricoeur e na filosofia gadameriana. Revelou-se como principal desencadeante de sofrimento a desvalorização do trabalho. Destacaram-se temas como dificuldade de cooperação com familiares de usuários, a fraca interligação do Caps com a rede de saúde, a responsabilização pelo plantão noturno, controvérsias sobre a liberação de pacientes em leito-noite e excesso de carga horária. Propõe-se adequado planejamento de estrutura e de organização institucional quando da abertura de novos Caps, visando diminuir impacto de trabalho nos técnicos e melhorar o desempenho clínico da equipe.