bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-healing characteristics of bituminous mastics using a modified direct tension test
Authors: Qiu Jian , van de Ven Martin , Wu Shaopeng , Molenaar André , Yu Jianying
Published: December 2012

Cracking is one of the main distresses responsible for the service life reduction of asphalt pavement. On the contrary, self-healing is a process that reverses to cracking and increases the service life. Understanding of the cracking and healing behavior of bituminous materials is very important for service life predictions. Instead of a complex and time-consuming fatigue test, a modified direct tension test with a loading–healing–reloading procedure was developed in this article to characterize the cracking and healing behavior of bituminous mastics. A displacement-controlled loading was applied to obtain damaged specimens with different crack sizes at various postpeak elongations. After unloading and healing, the reloading was applied to quantify the healing behavior under different conditions. The healing behavior is very dependent on rest periods, crack phases, and material types. A clear difference in self-healing property between a polymer-modified bituminous mastic and a conventional penetration grade bituminous mastic was observed for different phases of crack. As a result, the modified direct tension test is believed to be an effective tool for characterizing the self-healing capability of bituminous mastics.
The Rise of Party/Leader Identification in Western Europe
Authors: Garzia Diego
Published: December 2012

This article investigates the attitudinal drivers of partisanship in Western Europe, focusing in particular on the role exerted by voters’ evaluation of party leaders. The cross-sectional analysis is performed on pooled national election study data from three established parliamentary democracies (Britain, Germany, and the Netherlands). Results highlight the growing statistical association between leader evaluations and voters’ feelings of partisan attachment throughout the last three decades. Further analyses of selected panel data provide evidence for a causal interpretation in which voters’ evaluation of party leaders plays a crucial role in shaping their feelings of attachment to parties.
Media Coverage of Minority Congresswomen and Voter Evaluations
Authors: Gershon Sarah Allen
Published: December 2012

Scholars of gender and race politics have long drawn links between the media’s less than favorable treatment of women and minorities, and these candidates’ struggles to curry favor with voters. However, few have examined minority women’s coverage. This multimethodological study examines the nature and implications of the media’s treatment of Anglo, Latina, and African American congresswomen. The results indicate significant differences in the content of these women’s media coverage and its influence on voters’ attitudes. The implications of these findings for Anglo and minority women campaigning for and holding elective office are discussed.
A Hybrid Recursive Model for Teaching and Learning Business Writing
Authors: Schultz Heidi
Published: December 2012

To replicate the need for communication speed and effectiveness in the workplace, I have designed a successful business writing course based on a hybrid recursive model that combines prescriptive rhetorical patterns with a perceptive application of those patterns. The model draws inspiration from (a) current-traditional rhetoric, modified for a business context, to address the need to write quickly, which I label the “prescriptive phase,” and from (b) cognitive rhetoric, again modified for a business context, to address the need to write effectively, which I label the “perceptive phase.”
Using Problem-Based Scenarios to Teach Writing
Authors: Smart Karl L. , Hicks Nancy , Melton James
Published: December 2012

The ability to communicate effectively remains a critical skill for obtaining a job and achieving success in the workplace; however, many still lack these skills. In particular, graduates lack adequate writing skills. This article advocates the use of problem-based scenarios to teach writing, which focuses on authentic rhetorical framing similar to writing done in the workplace. A sample scenario is provided along with three responses, showing the type of issues involved in helping students develop writing skills appropriate to an organizational context.
Evaluation of the Toxicity of Intravenous Delivery of Auroshell Particles (Gold–Silica Nanoshells)
Authors: Gad Shayne C. , Sharp Kelly L. , Montgomery Charles , Payne J. Donald , Goodrich Glenn P.
Published: December 2012

Gold nanoshells (155 nm in diameter with a coating of polyethylene glycol 5000) were evaluated for preclinical biocompatibility, toxicity, and biodistribution as part of a program to develop an injectable device for use in the photothermal ablation of tumors. The evaluation started with a complete good laboratory practice (GLP) compliant International Organization for Standardization (ISO)-10993 biocompatibility program, including cytotoxicity, pyrogenicity (US Pharmacopeia [USP] method in the rabbit), genotoxicity (bacterial mutagenicity, chromosomal aberration assay in Chinese hamster ovary cells, and in vivo mouse micronucleus), in vitro hemolysis, intracutaneous reactivity in the rabbit, sensitization (in the guinea pig maximization assay), and USP/ISO acute systemic toxicity in the mouse. There was no indication of toxicity in any of the studies. Subsequently, nanoshells were evaluated in vivo by intravenous (iv) infusion using a trehalose/water solution in a series of studies in mice, Sprague-Dawley rats, and Beagle dogs to assess toxicity for time durations of up to 404 days. Over the course of 14 GLP studies, the gold nanoshells were well tolerated and, when injected iv, no toxicities or bioincompatibilities were identified.
Pre-service student-teachers’ conceptions of creativity in the primary music classroom
Authors: Kokotsaki Dimitra
Published: December 2012

This study explores pre-service teachers’ (referred to as student-teachers) notions of creativity in music, particularly in relation to the classroom. Seventeen student-teachers wishing to pursue a career in primary education were interviewed and completed questionnaires. In general terms, all participants talked about the high value of creative musical activities for primary age pupils as they recognized a wide range of benefits. However, the analysis revealed that some student-teachers held richer conceptions than others. Student-teachers holding richer conceptions: (a) provided more articulate and detailed answers, and were able to describe the creative process more accurately and comfortably; (b) had taught the lesson that they described and were more enthusiastic and keen to talk about it; and (c) tended to emphasize the learning that would take place during the creative process. These findings are discussed in terms of their practical educational implications in the primary music classroom and beyond.
Necrobiotic Xanthogranuloma as an Unusual Cause of Refractive Chronic Bilateral Leg Ulceration
Authors: Ghiasi Nazli , Alavi Afsaneh , Coutts Patricia M. , Ghazarian Danny , Sibbald R. Gary
Published: December 2012

Necrobiotic xanthogranuloma is a progressive histiocytic granulomatous disease with frequent extracutaneous involvement. We have documented an unusual case of necrobiotic xanthogranuloma in a 58-year-old man with a history of recalcitrant and chronic arm and leg ulcerations in the absence of characteristic periorbital involvement. Our patient demonstrates a therapeutic challenge and may display a new necrobiotic inflammatory disorder not previously characterized.
Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project
Authors: Loh Mignon L. , Zhang Jinghui , Harvey Richard C. , Roberts Kathryn , Payne-Turner Debbie , Kang Huining , Wu Gang , Chen Xiang , Becksfort Jared , Edmonson Michael , Buetow Kenneth H. , Carroll William L. , Chen I-Ming , Wood Brent , Borowitz Michael J. , Devidas Meenakshi , Gerhard Daniela S. , Bowman Paul , Larsen Eric , Winick Naomi , Raetz Elizabeth , Smith Malcolm , Downing James R. , Willman Cheryl L. , Mullighan Charles G. , Hunger Stephen P.
Published: December 2012

One recently identified subtype of pediatric B-precursor acute lymphoblastic leukemia (ALL) has been termed BCR-ABL1–like or Ph-like because of similarity of the gene expression profile to BCR-ABL1 positive ALL suggesting the presence of lesions activating tyrosine kinases, frequent alteration of IKZF1, and poor outcome. Prior studies demonstrated that approximately half of these patients had genomic lesions leading to CRLF2 overexpression, with half of such cases harboring somatic mutations in the Janus kinases JAK1 and JAK2. To determine whether mutations in other tyrosine kinases might also occur in ALL, we sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with either a Ph-like gene expression profile or other alterations suggestive of activated kinase signaling. Aside from JAK mutations and 1 FLT3 mutation, no somatic mutations were found in any other tyrosine kinases, suggesting that alternative mechanisms are responsible for activated kinase signaling in high-risk ALL.
Human plasmacytoid dendritic cells efficiently cross-present exogenous Ags to CD8+ T cells despite lower Ag uptake than myeloid dendritic cell subsets
Authors: Tel Jurjen , Schreibelt Gerty , Sittig Simone P. , Mathan Till S. M. , Buschow Sonja I. , Cruz Luis J. , Lambeck Annechien J. A. , Figdor Carl G. , de Vries I. Jolanda M.
Published: December 2012

In human peripheral blood, 4 populations of dendritic cells (DCs) can be distinguished, plasmacytoid dendritic cells (pDCs) and CD16+, CD1c+, and BDCA-3+ myeloid DCs (mDCs), each with distinct functional characteristics. DCs have the unique capacity to cross-present exogenously encountered antigens (Ags) to CD8+ T cells. Here we studied the ability of all 4 blood DC subsets to take up, process, and present tumor Ags to T cells. Although pDCs take up less Ags than CD1c+ and BDCA3+ mDCs, pDCs induce potent Ag-specific CD4+ and CD8+ T-cell responses. We show that pDCs can preserve Ags for prolonged periods of time and on stimulation show strong induction of both MHC class I and II, which explains their efficient activation of both CD4+ and CD8+ T cells. Furthermore, pDCs cross-present soluble and cell-associated tumor Ags to cytotoxic T lymphocytes equally well as BDCA3+ mDCs. These findings, and the fact that pDCs outnumber BDCA3+ mDCs, both in peripheral blood and lymph nodes, together with their potent IFN-I production, known to activate both components of the innate and adaptive immune system, put human pDCs forward as potent activators of CD8+ T cells in antitumor responses. Our findings may therefore have important consequences for the development of antitumor immunotherapy.
Mononuclear phagocyte miRNome analysis identifies miR-142 as critical regulator of murine dendritic cell homeostasis
Authors: Mildner Alexander , Chapnik Elik , Manor Ohad , Yona Simon , Kim Ki-Wook , Aychek Tegest , Varol Diana , Beck Gilad , Itzhaki Zohar Barnett , Feldmesser Ester , Amit Ido , Hornstein Eran , Jung Steffen
Published: December 2012

Key Points

Ex vivo isolated myeloid populations of the mononuclear phagocyte network display specific microRNA expression signatures. miR-142–deficient mice display a reduction of splenic CD4+ dendritic cells resulting in impaired priming of CD4 T-cell responses.
Flexible and efficient genome tiling design with penalized uniqueness score
Authors: Du Yang , Murani Eduard , Ponsuksili Siriluck , Wimmers Klaus
Published: December 2012

Background

As a powerful tool in whole genome analysis, tiling array has been widely used in the answering of many genomic questions. Now it could also serve as a capture device for the library preparation in the popular high throughput sequencing experiments. Thus, a flexible and efficient tiling array design approach is still needed and could assist in various types and scales of transcriptomic experiment.

Results

In this paper, we address issues and challenges in designing probes suitable for tiling array applications and targeted sequencing. In particular, we define the penalized uniqueness score, which serves as a controlling criterion to eliminate potential cross-hybridization, and a flexible tiling array design pipeline. Unlike BLAST or simple suffix array based methods, computing and using our uniqueness measurement can be more efficient for large scale design and require less memory. The parameters provided could assist in various types of genomic tiling task. In addition, using both commercial array data and experiment data we show, unlike previously claimed, that palindromic sequence exhibiting relatively lower uniqueness.

Conclusions

Our proposed penalized uniqueness score could serve as a better indicator for cross hybridization with higher sensitivity and specificity, giving more control of expected array quality. The flexible tiling design algorithm incorporating the penalized uniqueness score was shown to give higher coverage and resolution. The package to calculate the penalized uniqueness score and the described probe selection algorithm are implemented as a Perl program, which is freely available at http://www1.fbn-dummerstorf.de/en/forschung/fbs/fb3/paper/2012-yang-1/OTAD.v1.1.tar.gz.
DTome: a web-based tool for drug-target interactome construction
Authors: Sun Jingchun , Wu Yonghui , Xu Hua , Zhao Zhongming
Published: December 2012

Background

Understanding drug bioactivities is crucial for early-stage drug discovery, toxicology studies and clinical trials. Network pharmacology is a promising approach to better understand the molecular mechanisms of drug bioactivities. With a dramatic increase of rich data sources that document drugs' structural, chemical, and biological activities, it is necessary to develop an automated tool to construct a drug-target network for candidate drugs, thus facilitating the drug discovery process.

Results

We designed a computational workflow to construct drug-target networks from different knowledge bases including DrugBank, PharmGKB, and the PINA database. To automatically implement the workflow, we created a web-based tool called DTome (Drug-Target interactome tool), which is comprised of a database schema and a user-friendly web interface. The DTome tool utilizes web-based queries to search candidate drugs and then construct a DTome network by extracting and integrating four types of interactions. The four types are adverse drug interactions, drug-target interactions, drug-gene associations, and target-/gene-protein interactions. Additionally, we provided a detailed network analysis and visualization process to illustrate how to analyze and interpret the DTome network. The DTome tool is publicly available athttp://bioinfo.mc.vanderbilt.edu/DTome.

Conclusions

As demonstrated with the antipsychotic drug clozapine, the DTome tool was effective and promising for the investigation of relationships among drugs, adverse interaction drugs, drug primary targets, drug-associated genes, and proteins directly interacting with targets or genes. The resultant DTome network provides researchers with direct insights into their interest drug(s), such as the molecular mechanisms of drug actions. We believe such a tool can facilitate identification of drug targets and drug adverse interactions.
Directional selection on cold tolerance does not constrain plastic capacity in a butterfly
Authors: Franke Kristin , Dierks Anneke , Fischer Klaus
Published: December 2012

Background

Organisms may respond to environmental change by means of genetic adaptation, phenotypic plasticity or both, which may result in genotype-environment interactions (G x E) if genotypes differ in their phenotypic response. We here specifically target the latter source of variation (i.e. G x E) by comparing plastic responses among lines of the tropical butterflyBicyclus anynanathat had been selected for increased cold tolerance and according controls. Our main aim here was to test the hypothesis that directional selection on cold tolerance will interfere with plastic capacities.

Results

Plastic responses to temperature and feeding treatments were strong, with e.g. higher compared to lower temperatures reducing cold tolerance, longevity, pupal mass, and development time. We report a number of statistically significant genotype-environment interactions (i.e. interactions between selection regime and environmental variables), but most of these were not consistent across treatment groups. We found some evidence though for larger plastic responses to different rearing temperatures in the selection compared to the control lines, while plastic responses to different adult temperatures and feeding treatments were overall very similar across selection regimes.

Conclusion

Our results indicate that plastic capacities are not always constrained by directional selection (on cold tolerance) and therefore genetic changes in trait means, but may operate independently.
Development of coronary artery stenosis in a patient with metastatic renal cell carcinoma treated with sorafenib
Authors: Pantaleo Maria Abbondanza , Mandrioli Anna , Saponara Maristella , Nannini Margherita , Erente Giovanna , Lolli Cristian , Biasco Guido
Published: December 2012

Background

Tyrosine kinase inhibitors (TKIs) are currently approved for the treatment of metastatic renal cell carcinoma (mRCC). The cardiotoxic effects of sorafenib and sunitinib may cause hypertension, left ventricular ejection fraction (LVEF) dysfunction and/or congestive heart failure (CHF), and arterial thrombo-embolic events (ATE). Only three cases of coronary artery disease related to sorafenib therapy have been described in the literature, and all were due to arterial vasospasm without evidence of coronary artery stenosis on angiography. Cardiotoxicity is commonly associated with the presence of cardiovascular risk factors, such as a history of hypertension or coronary artery disease.

Case presentation

We describe a patient who experienced an unusual cardiac event after 2 years of sorafenib treatment. A 58-year-old man with mRCC developed acute coronary syndrome (ischemia/infarction) associated with critical sub-occlusion of the common trunk of the left coronary artery and some of its branches, which was documented on coronary angiography. The patient underwent triple coronary artery bypass surgery, and sorafenib treatment was discontinued. He did not have any cardiovascular risk factors, and his cardiac function and morphology were normal prior to sorafenib treatment.

Conclusions

Further investigation of a larger patient population is needed to better understand cardiac damage due to TKI treatment. Understanding the usefulness of careful cardiovascular monitoring might be important for the prevention of fatal cardiovascular events, and to avoid discontinuation of therapy for the underlying cancer.
The impact of physical activity on fatigue and quality of life in lung cancer patients: a randomised controlled trial protocol
Authors: Dhillon Haryana M , van der Ploeg Hidde P , Bell Melanie L , Boyer Michael , Clarke Stephen , Vardy Janette
Published: December 2012

Background

People with lung cancer have substantial symptom burden and more unmet needs than the general cancer population. Physical activity (PA) has been shown to positively influence quality of life (QOL), fatigue and daily functioning in the curative treatment of people with breast and colorectal cancers and lung diseases, as well as in palliative settings. A randomised controlled trial (RCT) is needed to determine if lung cancer patients benefit from structured PA intervention. The Physical Activity in Lung Cancer (PAL) trial is designed to evaluate the impact of a 2-month PA intervention on fatigue and QOL in patients with non-resectable lung cancer. Biological mechanisms will also be studied.

Methods/design

A multi-centre RCT with patients randomised to usual care or a 2-month PA programme, involving supervised PA sessions including a behavioural change component and home-based PA. QOL questionnaires, disease and functional status and body composition will be assessed at baseline, 2, 4 and 6 months follow-up. The primary endpoint is comparative levels of fatigue between the 2 arms. Secondary endpoints include: QOL, functional abilities and physical function. Exploratory endpoints include: anxiety, depression, distress, dyspnoea, PA behaviour, fitness, hospitalisations, survival, cytokines and insulin-like growth factor levels.

Discussion

This study will provide high-level evidence of the effect of PA programmes on cancer-related fatigue and QOL in patients with advanced lung cancer. If positive, the study has the potential to change care for people with cancer using a simple, inexpensive intervention to improve their QOL and help them maintain independent function for as long as possible.

Trial registration

Australian New Zealand Clinical Trials Registry No. ACTRN12609000971235
Individual development of preschool children-prevalences and determinants of delays in Germany: a cross-sectional study in Southern Bavaria
Authors: Stich Heribert L , Baune Bernhard Th , Caniato Riccardo N , Mikolajczyk Rafael T , Krämer Alexander
Published: December 2012

Background

Even minor abnormalities of early child development may have dramatic long term consequences. Accurate prevalence rates for a range of developmental impairments have been difficult to establish. Since related studies have used different methodological approaches, direct comparisons of the prevalence of developmental delays are difficult. The understanding of the key factors affecting child development, especially in preschool aged children remains limited. We used data from school entry examinations in Bavaria to measure the prevalence of developmental impairments in pre-school children beginning primary school in 1997–2009.

Methods

The developmental impairments of all school beginners in the district of Dingolfing- Landau, Bavaria were assessed using modified “Bavarian School Entry Model” examination from 1997 to 2009 (N=13,182). The children were assessed for motor, cognitive, language and psychosocial impairments using a standardised medical protocol. Prevalence rates of impairments in twelve domains of development were estimated. Using uni- and multivariable logistic regression models, association between selected factors and development delays were assessed.

Results

The highest prevalence existed for impairments of pronunciation (13.8%) followed by fine motor impairments (12.2%), and impairments of memory and concentration (11.3%) and the lowest for impairments of rhythm of speech (3.1%). Younger children displayed more developmental delays. Male gender was strongly associated with all developmental impairments (highest risk for fine motor impairments = OR 3.22, 95% confidence interval 2.86-3.63). Preschool children with siblings (vs. children without any siblings) were at higher risk of having impairments in pronunciation (OR 1.31, 1.14-1.50). The influence of the non-German nationality was strong, with a maximum risk increase for the subareas of grammar and psychosocial development. Although children with non-German nationality had a reduced risk of disorders for the rhythm of speech and pronunciation, in all other 10 subareas their risk was increased.

Conclusions

In preschool children, most common were delays of pronunciation, memory and concentration. Age effects suggest that delays can spontaneously resolve, but providing support at school entry might be helpful. Boys and migrant children appear at high risk of developmental problems, which may warrant tailored intervention strategies.
Prevalence and predictors of giving birth in health facilities in Bugesera District, Rwanda
Authors: Joharifard Shahrzad , Rulisa Stephen , Niyonkuru Francine , Weinhold Andrew , Sayinzoga Felix , Wilkinson Jeffrey , Ostermann Jan , Thielman Nathan M
Published: December 2012

Background

The proportion of births attended by skilled health personnel is one of two indicators used to measure progress towards Millennium Development Goal 5, which aims for a 75% reduction in global maternal mortality ratios by 2015. Rwanda has one of the highest maternal mortality ratios in the world, estimated between 249–584 maternal deaths per 100,000 live births. The objectives of this study were to quantify secular trends in health facility delivery and to identify factors that affect the uptake of intrapartum healthcare services among women living in rural villages in Bugesera District, Eastern Province, Rwanda.

Methods

Using census data and probability proportional to size cluster sampling methodology, 30 villages were selected for community-based, cross-sectional surveys of women aged 18–50 who had given birth in the previous three years. Complete obstetric histories and detailed demographic data were elicited from respondents using iPad technology. Geospatial coordinates were used to calculate the path distances between each village and its designated health center and district hospital. Bivariate and multivariate logistic regressions were used to identify factors associated with delivery in health facilities.

Results

Analysis of 3106 lifetime deliveries from 859 respondents shows a sharp increase in the percentage of health facility deliveries in recent years. Delivering a penultimate baby at a health facility (OR = 4.681 [3.204 - 6.839]), possessing health insurance (OR = 3.812 [1.795 - 8.097]), managing household finances (OR = 1.897 [1.046 - 3.439]), attending more antenatal care visits (OR = 1.567 [1.163 - 2.112]), delivering more recently (OR = 1.438 [1.120 - 1.847] annually), and living closer to a health center (OR = 0.909 [0.846 - 0.976] per km) were independently associated with facility delivery.

Conclusions

The strongest correlates of facility-based delivery in Bugesera District include previous delivery at a health facility, possession of health insurance, greater financial autonomy, more recent interactions with the health system, and proximity to a health center. Recent structural interventions in Rwanda, including the rapid scale-up of community-financed health insurance, likely contributed to the dramatic improvement in the health facility delivery rate observed in our study.
Protein Nano-Object Integrator (ProNOI) for generating atomic style objects for molecular modeling
Authors: Smith Nicholas , Campbell Brandon , Li Lin , Li Chuan , Alexov Emil
Published: December 2012

Background

With the progress of nanotechnology, one frequently has to model biological macromolecules simultaneously with nano-objects. However, the atomic structures of the nano objects are typically not available or they are solid state entities. Because of that, the researchers have to investigate such nano systems by generating models of the nano objects in a manner that the existing software be able to carry the simulations. In addition, it should allow generating composite objects with complex shape by combining basic geometrical figures and embedding biological macromolecules within the system.

Results

Here we report the Protein Nano-Object Integrator (ProNOI) which allows for generating atomic-style geometrical objects with user desired shape and dimensions. Unlimited number of objects can be created and combined with biological macromolecules in Protein Data Bank (PDB) format file. Once the objects are generated, the users can use sliders to manipulate their shape, dimension and absolute position. In addition, the software offers the option to charge the objects with either specified surface or volumetric charge density and to model them with user-desired dielectric constants. According to the user preference, the biological macromolecule atoms can be assigned charges and radii according to four different force fields: Amber, Charmm, OPLS and PARSE. The biological macromolecules and the atomic-style objects are exported as a position, charge and radius (PQR) file, or if a default dielectric constant distribution is not selected, it is exported as a position, charge, radius and epsilon (PQRE) file. As illustration of the capabilities of the ProNOI, we created a composite object in a shape of a robot, aptly named the Clemson Robot, whose parts are charged with various volumetric charge densities and holds the barnase-barstar protein complex in its hand.

Conclusions

The Protein Nano-Object Integrator (ProNOI) is a convenient tool for generating atomic-style nano shapes in conjunction with biological macromolecule(s). Charges and radii on the macromolecule atoms and the atoms in the shapes are assigned according to the user’s preferences allowing various scenarios of modeling. The default output file is in PQR (PQRE) format which is readable by almost any software available in biophysical field. It can be downloaded from: http://compbio.clemson.edu/downloadDir/ProNO_integrator.tar.gz
Investigating the effects of perturbations to pgi and eno gene expression on central carbon metabolism in Escherichia coli using 13 C metabolic flux analysis
Authors: Usui Yuki , Hirasawa Takashi , Furusawa Chikara , Shirai Tomokazu , Yamamoto Natsuko , Mori Hirotada , Shimizu Hiroshi
Published: December 2012

Background

It has long been recognized that analyzing the behaviour of the complex intracellular biological networks is important for breeding industrially useful microorganisms. However, because of the complexity of these biological networks, it is currently not possible to obtain all the desired microorganisms. In this study, we constructed a system for analyzing the effect of gene expression perturbations on the behavior of biological networks inEscherichia coli. Specifically, we utilized13C metabolic flux analysis (13C-MFA) to analyze the effect of perturbations to the expression levels ofpgiandenogenes encoding phosphoglucose isomerase and enolase, respectively on metabolic fluxes.

Results

We constructed gene expression-controllableE. colistrains using a single-copy mini F plasmid. Using thepgiexpression-controllable strain, we found that the specific growth rate correlated with thepgiexpression level.13C-MFA of this strain revealed that the fluxes for the pentose phosphate pathway and Entner-Doudoroff pathway decreased, as thepgiexpression lelvel increased. In addition, the glyoxylate shunt became active when thepgiexpression level was almost zero. Moreover, the flux for the glyoxylate shunt increased when thepgiexpression level decreased, but was significantly reduced in thepgi-knockout cells. Comparatively,enoexpression could not be decreased compared to the parent strain, but we found that increasedenoexpression resulted in a decreased specific growth rate.13C-MFA revealed that the metabolic flux distribution was not altered by an increasedenoexpression level, but the overall metabolic activity of the central metabolism decreased. Furthermore, to evaluate the impact of perturbed expression ofpgiandenogenes on changes in metabolic fluxes inE. coliquantitatively, metabolic sensitivity analysis was performed. As a result, the perturbed expression ofpgigene had a great impact to the metabolic flux changes in the branch point between the glycolysis and pentose phosphate pathway, isocitrate dehydrogenase reaction, anaplerotic pathways and Entner-Doudoroff pathway. In contrast, the impact of perturbedenoexpression to the flux changes inE. colimetabolic network was small.

Conclusions

Our results indicate that the response of metabolic fluxes to perturbation topgiexpression was different from that toenoexpression; perturbations topgiexpression affect the reaction related to the Pgi protein function, the isocitrate dehydrogenase reaction, anaplerotic reactions and Entner-Doudoroff pathway. Meanwhile,enoexpression seems to affect the overall metabolic activity, and the impact of perturbedenoexpression on metabolic flux change is small. Using the gene expression control system reported here, it is expected that we can analyze the response and adaptation process of complex biological networks to gene expression perturbations.
Activation of nuclear factor kappa B in peripheral blood mononuclear cells from malaria patients
Authors: Punsawad Chuchard , Krudsood Srivicha , Maneerat Yaowapa , Chaisri Urai , Tangpukdee Noppadon , Pongponratn Emsri , Nantavisai Kwannan , Udomsangpetch Rachanee , Viriyavejakul Parnpen
Published: December 2012

Background

Malaria parasites and their products can activate a specific immune response by stimulating cytokine production in the host’s immune cells. Transcription nuclear factor kappa B (NF-κB) is an important regulator for the control of many pro-inflammatory genes, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). The activation and expression of NF-κB p65 in peripheral blood mononuclear cells (PBMCs) of malaria patients were investigated and correlated with the levels of IL-10 and TNF to study the nature of NF-κB p65 and its linkage to inflammatory cytokines.

Methods

The sample group comprised 33 patients admitted with malaria caused byPlasmodium vivax(n = 11), uncomplicatedPlasmodium falciparum(n = 11), and complicatedPlasmodium falciparum(n = 11). Peripheral blood was collected at admission and on day 7 for PBMC isolation. Healthy subjects were used as a control group. The expressions of NF-κB p65 in the PBMCs from malaria patients and the plasma levels of IL-10 and TNF were measured by using enzyme-linked immunosorbent assay (ELISA). The immunofluorescence technique was used to determine NF-κB nuclear translocation.

Results

At admission, patients withP. vivaxand uncomplicatedP. falciparumhad significantly elevated phospho-NF-κB p65 levels in the PBMCs compared with those of healthy controls. However, patients with complicatedP. falciparummalaria had decreased levels of phospho-NF-κB p65. On day 7 post-treatment, significantly increased phospho-NF-κB p65 was found in the PBMCs of patients with complicatedP. falciparum, compared with healthy controls. The plasma level of IL-10 was elevated in day 0 in patients with complicatedP. falciparummalaria and was found to be negatively correlated with phospho-NF-κB p65 level (rs = −0.630,p = 0.038). However, there was no correlation between phospho-NF-κB p65 expression and TNF level in patients with complicatedP. falciparummalaria.

Conclusions

This is the first report demonstrating alterations in NF-κB p65 activity in the PBMCs of malaria patients. The altered lower features of NF-κB p65 in the PBMCs of patients with complicatedP. falciparumat admission could be due to a suppressive effect of high IL-10 associated with complicatedP. falciparummalaria.
Comparison of the absolute and relative efficiencies of electroporation-based transfection protocols for Plasmodium falciparum
Authors: Hasenkamp Sandra , Russell Karen T , Horrocks Paul
Published: December 2012

Background

Several electroporation protocols exist to transfect exogenous DNA into Plasmodium falciparum. To date, however, only a subjective analysis of their relative efficiencies has been reported.

Methods

A time-course of luciferase reporter expression is used to provide an objective quantitative analysis of the absolute efficiency of three electroporation techniques; direct electroporation of ring stage infected erythrocytes, preloading of erythrocytes and a novel “double-tap” protocol that combines both approaches.

Results

Preloading of erythrocytes shows a mean efficiency of 9.59x10-6, some 5–180 fold more efficient than matched experiments utilizing the “double-tap” and direct electroporation of ring stage infected erythrocytes alone, respectively.

Conclusion

Evidence presented here provides the first quantitative assessment of both the absolute and relative efficiencies of a key molecular tool used to study the biology and pathogenesis of this important human pathogen.
Dihydrotestosterone regulating apolipoprotein M expression mediates via protein kinase C in HepG2 cells
Authors: Yi-zhou Ye , Bing Cao , Ming-qiu Li , Wei Wang , Ru-xing Wang , Jun Rui , Liu-yan Wei , Zhao-hui Jing , Yong Ji , Guo qing Jiao , Jian Zou
Published: December 2012

Background

Administration of androgens decreases plasma concentrations of high-density lipid cholesterol (HDL-C). However, the mechanisms by which androgens mediate lipid metabolism remain unknown. This present study used HepG2 cell cultures and ovariectomized C57BL/6 J mice to determine whether apolipoprotein M (ApoM), a constituent of HDL, was affected by dihydrotestosterone (DHT).

Methods

HepG2 cells were cultured in the presence of either DHT, agonist of protein kinase C (PKC), phorbol-12-myristate-13-acetate (PMA), blocker of androgen receptor flutamide together with different concentrations of DHT, or DHT together with staurosporine at different concentrations for 24 hrs. Ovariectomized C57BL/6 J mice were treated with DHT or vehicle for 7d or 14d and the levels of plasma ApoM and livers ApoM mRNA were measured. The mRNA levels of ApoM, ApoAI were determined by real-time RT-PCR. ApoM and ApoAI were determined by western blotting analysis.

Results

Addition of DHT to cell culture medium selectively down-regulated ApoM mRNA expression and ApoM secretion in a dose-dependent manner. At 10 nM DHT, the ApoM mRNA levels were about 20% lower than in untreated cells and about 40% lower at 1000 nM DHT than in the control cells. The secretion of ApoM into the medium was reduced to a similar extent. The inhibitory effect of DHT on ApoM secretion was not blocked by the classical androgen receptor blocker flutamide but by an antagonist of PKC, Staurosporine. Agonist of PKC, PMA, also reduced ApoM. At 0.5 μM PMA, the ApoM mRNA levels and the secretion of ApoM into the medium were about 30% lower than in the control cells. The mRNA expression levels and secretion of another HDL-associated apolipoprotein AI (ApoAI) were not affected by DHT. The levels of plasma ApoM and liver ApoM mRNA of DHT-treated C57BL/6 J mice were lower than those of vehicle-treated mice.

Conclusions

DHT directly and selectively down-regulated the level of ApoM mRNA and the secretion of ApoM by protein kinase C but independently of the classical androgen receptor.
Local bifurcation of limit cycles and integrability of a class of nilpotent systems
Authors: Li Hongwei , Wu Yusen , Jin Yinlai
Published: December 2012

In this article, center conditions and bifurcation of limit cycles at the nilpotent critical point in a class of seventh-degree systems are investigated. With the help of computer algebra system MATHEMATICA, the first 13 quasi-Lyapunov constants are deduced. As a result, sufficient and necessary conditions in order to have a center are obtained. The result that there exist 13 small amplitude limit cycles created from the three-order nilpotent critical point is also proved. Henceforth, we give a lower bound of cyclicity of three-order nilpotent critical point for seventh-degree nilpotent systems.

MSC: 34C05; 34C07.
A comparative review of cell culture systems for the study of microglial biology in Alzheimer’s disease
Authors: Stansley Branden , Post Jan , Hensley Kenneth
Published: December 2012

Over the past two decades, it has become increasingly apparent that Alzheimer’s disease neuropathology is characterized by activated microglia (brain resident macrophages) as well as the classic features of amyloid plaques and neurofibrillary tangles. The intricacy of microglial biology has also become apparent, leading to a heightened research interest in this particular cell type. Over the years a number of different microglial cell culturing techniques have been developed to study either primary mammalian microglia, or immortalized cell lines. Each microglial system has advantages and disadvantages and should be selected for its appropriateness in a particular research context. This review summarizes several of the most common microglial cell culture systems currently being employed in Alzheimer’s research including primary microglia; BV2 and N9 retroviral immortalized microglia; human immortalized microglia (HMO6); and spontaneously immortalized rodent microglial lines (EOC lines and HAPI cells). Particularities of cell culture requirements and characteristics of microglial behavior, especially in response to applied inflammogen stimuli, are compared and discussed across these cell types.
DHEA administration and exercise training improves insulin resistance in obese rats
Authors: Sato Koji , Iemitsu Motoyuki , Aizawa Katsuji , Mesaki Noboru , Ajisaka Ryuichi , Fujita Satoshi
Published: December 2012

Background

Dehydroepiandrosterone (DHEA) is precursor of sex steroid hormone. We demonstrated that acute DHEA injection to type 1 diabetes model rats induced improvement of hyperglycemia. However, the effect of the combination of DHEA administration and exercise training on insulin resistance is still unclear. This study was undertaken to determine whether 6-weeks of DHEA administration and/or exercise training improve insulin resistance in obese male rats.

Methods

After 14 weeks of a high-sucrose diet, obese male Wistar rats were assigned randomly to one of four groups: control, DHEA administration, exercise training, and a combination of DHEA administration and exercise training (n = 10 each group).

Results

After 6-weeks of DHEA administration and/or exercise training, rats in the combination group weighed significantly less and had lower serum insulin levels than rats in the other groups. Moreover, the rats treated with DHEA alone or DHEA and exercise had significantly lower fasting glucose levels (combination, 84 ± 6.5 mg/dL; DHEA, 102 ± 9.5 mg/dL; control, 148 ± 10.5 mg/dL). In addition, insulin sensitivity check index showed significant improvements in the combination group (combination, 0.347 ± 0.11; exercise, 0.337 ± 0.16%; DHEA, 0.331 ± 0.14; control, 0.308 ± 0.12). Muscular DHEA and 5α-dihydrotestosterone (DHT) concentrations were significantly higher in the combination group, and closely correlated with the quantitative insulin-sensitivity check index (DHEA: r = 0.71, p < 0.01; DHT: r = 0.69, p < 0.01).

Conclusion

These results showed that a combination of DHEA administration and exercise training effectively improved fasting blood glucose and insulin levels, and insulin sensitivity, which may reflect increased muscular DHEA and DHT concentrations.
Mucinous adenocarcinoma of the intestinal type arising from mature cystic teratoma of the ovary: a rare case report and review of the literature
Authors: Takai Masaaki , Kanemura Masanori , Kawaguchi Hiroshi , Fujiwara Satoe , Yoo Saha , Tanaka Yoshimichi , Tsunetoh Satoshi , Terai Yoshito , Yamada Takashi , Ohmichi Masahide
Published: December 2012

Background

Mature cystic teratomas (MCTs) are the most common germ cell tumors of the ovary. Malignant tranformation occurs in 1-2% of these neoplasms. Although most of the malignancies arising from MCTs are squamous cell carcinomas, adenocarcinoma of the gastrointestinal type is extremery rare. We herein present a case of adenocarcinoma of the intestinal type arising from a MCT.

Case

A 49-year-old female underwent surgery for a left ovarian tumor. The histology of the cyst walls revealed a MCT with a few hair shafts and a squamous layer, while another part of the tumor showed adenocarcinoma of the intestinal type. Five years after surgery, she is alive without disease.
Phytochemical screening and evaluation of cardioprotective activity of ethanolic extract of Ocimum basilicum L. (basil) against isoproterenol induced myocardial infarction in rats
Authors: Fathiazad Fatemeh , Matlobi Amin , Khorrami Arash , Hamedeyazdan Sanaz , Soraya Hamid , Hammami Mojtaba , Maleki-Dizaji Nasrin , Garjani Alireza
Published: December 2012

Background and the purpose of the study

The objectives of the present study were phytochemical screening and study of the effects of ethanolic extract of aerial parts of Ocimum basilicum (basil) on cardiac functions and histopathological changes in isoproterenol-induced myocardial infarction (MI).

Methods

The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent CAMAG's TLC scanning were performed to quantify rosmarinic acid content. Wistar rats were assigned to 6 groups of normal control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg of the extract two times per day concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used to induce MI.

Results

Phytochemical screening indicated the presence of phenolic compounds (5.36%) and flavonoids (1.86%). Rosmarinic acid was the principal phenolic compound with a 15.74% existence. The ST-segment elevation induced by isoproterenol was significantly suppressed by all doses of the extract. A severe myocardial necrosis and fibrosis with a sharp reduction in left ventricular contractility and a marked increase in left ventricular end-diastolic pressure were seen in the isoproterenol group, all of which were significantly improved by the extract treatment. In addition to in-vitro antioxidant activity, the extract significantly suppressed the elevation of malondialdehyde levels both in the serum and the myocardium.

Conclusion

The results of the study demonstrate that Ocimum basilicum strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidative activities.
Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia
Authors: Padberg Jan-Sören , Van Meurs Matijs , Kielstein Jan T , Martens-Lobenhoffer Jens , Bode-Böger Stefanie M , Zijlstra Jan G , Kovesdy Csaba P , Kümpers Philipp
Published: December 2012

Background

Excessive tryptophan metabolism to kynurenine by the rate-limiting enzyme endothelial indoleamine 2,3-dioxygenase 1 (IDO) controls arterial vessel relaxation and causes hypotension in murine endotoxemia. However, its relevance in human endotoxemia has not been investigated so far. We thus aimed to study changes in blood pressure in parallel with tryptophan and kynurenine levels during experimental endotoxemia in humans.

Findings

Six healthy male volunteers were given E. coli lipopolysaccharide (LPS; 4 ng/kg) as a 1-min intravenous infusion. They had levels of soluble E-Selectin and soluble vascular cell adhesion molecule-1 as well as IDO activity assessed as the kynurenine-to-tryptophan plasma ratio by liquid chromatography-tandem mass spectrometry at various time points during a 24 h time course. During endotoxemia, IDO activity significantly increased, reaching peak levels at 8 h after LPS infusion (44.0 ± 15.2 vs. 29.4 ± 6.8 at baseline, P<0.0001). IDO activity correlated inversely with the development of hypotension as shown by random effects linear regression models. Finally, IDO activity exhibited a kinetic profile similar to that of soluble endothelial-specific adhesion molecules.

Conclusions

LPS is a triggering factor for the induction of IDO in men. Our findings strongly support the concept that the induction of IDO in the vascular endothelium contributes to hypotension in human sepsis.
Persistent complete molecular remission after nilotinib and graft-versus-leukemia effect in an acute lymphoblastic leukemia patient with cytogenetic relapse after allogeneic stem cell transplantation
Authors: Farnsworth Paul , Ward David , Reddy Vijay
Published: December 2012

We report the successful treatment and sustained molecular remission using single agent nilotinib in a relapsed Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia patient after allogeneic hematopoietic stem cell transplantation. Compared to previously published studies, this is the first report where a patient did not receive additional chemotherapy after relapse, nor did she receive donor lymphocyte infusions. With nilotinib, the patient reverted back to normal blood counts and 100% donor reconstitution by single tandem repeat (STR) chimerism analysis in the bone marrow and in peripheral blood, granulocytes, T and B-lymphocytes. This report also highlights the use of nilotinib in combination with extracorporeal photopheresis (ECP) for concomitant graft-versus-host disease. Our data suggests that ECP, together with nilotinib, did not adversely affect the overall Graft-versus-leukemia (GVL) effect.