bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs) influences their oxidative and pro-inflammatory potential in vitro
Authors: Gasser Michael , Wick Peter , Clift Martin JD , Blank Fabian , Diener Liliane , Yan Bing , Gehr Peter , Krug Harald F , Rothen-Rutishauser Barbara 
Published: June 2012

Abstract

Background
Increasing concern has been expressed regarding the potential adverse health effects that may be associated with human exposure to inhaled multi-walled carbon nanotubes (MWCNTs). Thus it is imperative that an understanding as to the underlying mechanisms and the identification of the key factors involved in adverse effects are gained. In the alveoli, MWCNTs first interact with the pulmonary surfactant. At this interface, proteins and lipids of the pulmonary surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the present study was to investigate if the pre-coating of MWCNTs with pulmonary surfactant has an influence on potential adverse effects, upon both (i) human monocyte derived macrophages (MDM) monocultures, and (ii) a sophisticated in vitro model of the human epithelial airway barrier. Both in vitro systems were exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant (Curosurf) or not. The effect of MWCNTs surface charge was also investigated in terms of amino (−NH2) and carboxyl (−COOH) surface modifications.

Results
Pre-coating of MWCNTs with Curosurf affects their oxidative potential by increasing the reactive oxygen species levels and decreasing intracellular glutathione depletion in MDM as well as decreases the release of Tumour necrosis factor alpha (TNF-α). In addition, an induction of apoptosis was observed after exposure to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of Interleukin-8 (IL-8) was increased after exposure to Curosurf pre-coated MWCNTs. Effects of the MWCNTs functionalizations were minor in both MDM and triple cell co-cultures.

Conclusions
The present study clearly indicates that the pre-coating of MWCNTs with pulmonary surfactant more than the functionalization of the tubes is a key factor in determining their ability to cause oxidative stress, cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with pulmonary surfactant should be considered for future lung in vitro risk assessment studies.
Regulation of mitochondrial permeability transition pore by PINK1
Authors: Gautier Clement A , Giaime Emilie , Caballero Erica , Núñez Lucía , Song Zhiyin , Chan David , Villalobos Carlos , Shen Jie 
Published: June 2012

Abstract

Background
Loss-of-function mutations in PTEN-induced kinase 1 (PINK1) have been linked to familial Parkinson’s disease, but the underlying pathogenic mechanism remains unclear. We previously reported that loss of PINK1 impairs mitochondrial respiratory activity in mouse brains.

Results
In this study, we investigate how loss of PINK1 impairs mitochondrial respiration using cultured primary fibroblasts and neurons. We found that intact mitochondria in PINK1−/− cells recapitulate the respiratory defect in isolated mitochondria from PINK1−/− mouse brains, suggesting that these PINK1−/− cells are a valid experimental system to study the underlying mechanisms. Enzymatic activities of the electron transport system complexes are normal in PINK1−/− cells, but mitochondrial transmembrane potential is reduced. Interestingly, the opening of the mitochondrial permeability transition pore (mPTP) is increased in PINK1−/− cells, and this genotypic difference between PINK1−/− and control cells is eliminated by agonists or inhibitors of the mPTP. Furthermore, inhibition of mPTP opening rescues the defects in transmembrane potential and respiration in PINK1−/− cells. Consistent with our earlier findings in mouse brains, mitochondrial morphology is similar between PINK1−/− and wild-type cells, indicating that the observed mitochondrial functional defects are not due to morphological changes. Following FCCP treatment, calcium increases in the cytosol are higher in PINK1−/− compared to wild-type cells, suggesting that intra-mitochondrial calcium concentration is higher in the absence of PINK1.

Conclusions
Our findings show that loss of PINK1 causes selective increases in mPTP opening and mitochondrial calcium, and that the excessive mPTP opening may underlie the mitochondrial functional defects observed in PINK1−/− cells.
Genome-scale metabolic model of the fission yeast Schizosaccharomyces pombe and the reconciliation of in silico/in vivo mutant growth
Authors: Sohn Seung Bum , Kim Tae Yong , Lee Jay H , Lee Sang Yup 
Published: June 2012

Abstract

Background
Over the last decade, the genome-scale metabolic models have been playing increasingly important roles in elucidating metabolic characteristics of biological systems for a wide range of applications including, but not limited to, system-wide identification of drug targets and production of high value biochemical compounds. However, these genome-scale metabolic models must be able to first predict known in vivo phenotypes before it is applied towards these applications with high confidence. One benchmark for measuring the in silico capability in predicting in vivo phenotypes is the use of single-gene mutant libraries to measure the accuracy of knockout simulations in predicting mutant growth phenotypes.

Results
Here we employed a systematic and iterative process, designated as Reconciling In silico/in vivo mutaNt Growth (RING), to settle discrepancies between in silico prediction and in vivo observations to a newly reconstructed genome-scale metabolic model of the fission yeast, Schizosaccharomyces pombe, SpoMBEL1693. The predictive capabilities of the genome-scale metabolic model in predicting single-gene mutant growth phenotypes were measured against the single-gene mutant library of S. pombe. The use of RING resulted in improving the overall predictive capability of SpoMBEL1693 by 21.5%, from 61.2% to 82.7% (92.5% of the negative predictions matched the observed growth phenotype and 79.7% the positive predictions matched the observed growth phenotype).

Conclusion
This study presents validation and refinement of a newly reconstructed metabolic model of the yeast S. pombe, through improving the metabolic model’s predictive capabilities by reconciling the in silico predicted growth phenotypes of single-gene knockout mutants, with experimental in vivo growth data.
Late somatic sequelae after treatment of childhood cancer in Slovenia
Authors: Erman Nuša , Todorovski Ljupčo , Jereb Berta 
Published: June 2012

Abstract

Background
This is a long-term follow-up clinical study of adolescents and adults, survivors of childhood cancer. We evaluate and analyze the late somatic sequelae of childhood cancer treatment. Many such studies are susceptible to a strong selection bias, i.e., they employ a limited non-systematic sample of patients, based on a clinical hospital that provided the cancer treatment or performed the follow-up. To address the issue of selection bias, we perform here an analysis of late sequelae on a systematic database of the entire population of the children treated for cancer in Slovenia. Due to the specifics of cancer treatment procedures in Slovenia, they have all been treated and followed-up in the same clinic.

Methods
The data are based on the centralized registry of cancer patients in Slovenia and present a controlled and homogeneous collection. Late sequelae are evaluated following a modified CTCAE, i.e., the National Cancer Institute’s Common Terminology Criteria for Adverse Events version 3.0. We use survival analysis method to estimate the incidence of and risk for late sequelae, where the time variable is measured in years from the diagnosis date, while we follow the event of incidence of late sequelae scored other than none. Survival analysis is performed using KaplanMeier estimator and Cox regression model.

Results
The incidence of mild, moderate, or severe late sequelae of childhood cancer treatment significantly decreased from 75% in the group of patients diagnosed before 1975 to 55% for those diagnosed after 1995. The Cox regression analysis of the risk factors for the incidence of late sequelae identifies three significant factors: treatment modalities, age at diagnosis, and primary diagnosis.

Conclusions
The change of treatment modalities in terms of replacement of surgery and radiotherapy with chemotherapy is the main reason for the decrease of the incidence and the risk for late sequelae of childhood cancer treatment; treatment modalities including surgery significantly increase the risk ratio of late sequelae, while those based on chemotherapy only significantly decreases the risk. Risk of late sequelae increases with the diagnosis age: younger children are more susceptible to late effects of treatment. Finally, primary diagnosis significantly influences the risk for late sequelae, but mostly due to the dependency of the treatment modality on the primary diagnosis.
A systems biology analysis of long and short-term memories of osmotic stress adaptation in fungi
Authors: You Tao , Ingram Piers , Jacobsen Mette D , Cook Emily , McDonagh Andrew , Thorne Thomas , Lenardon Megan D , de Moura Alessandro PS , Romano M Carmen , Thiel Marco , Stumpf Michael , Gow Neil AR , Haynes Ken , Grebogi Celso , Stark Jaroslav , Brown Alistair JP 
Published: June 2012

Abstract

Background

Saccharomyces cerevisiae senses hyperosmotic conditions via the HOG signaling network that activates the stress-activated protein kinase, Hog1, and modulates metabolic fluxes and gene expression to generate appropriate adaptive responses. The integral control mechanism by which Hog1 modulates glycerol production remains uncharacterized. An additional Hog1-independent mechanism retains intracellular glycerol for adaptation. Candida albicans also adapts to hyperosmolarity via a HOG signaling network. However, it remains unknown whether Hog1 exerts integral or proportional control over glycerol production in C. albicans.

Results
We combined modeling and experimental approaches to study osmotic stress responses in S. cerevisiae and C. albicans. We propose a simple ordinary differential equation (ODE) model that highlights the integral control that Hog1 exerts over glycerol biosynthesis in these species. If integral control arises from a separation of time scales (i.e. rapid HOG activation of glycerol production capacity which decays slowly under hyperosmotic conditions), then the model predicts that glycerol production rates elevate upon adaptation to a first stress and this makes the cell adapts faster to a second hyperosmotic stress. It appears as if the cell is able to remember the stress history that is longer than the timescale of signal transduction. This is termed the long-term stress memory. Our experimental data verify this. Like S. cerevisiae, C. albicans mimimizes glycerol efflux during adaptation to hyperosmolarity. Also, transient activation of intermediate kinases in the HOG pathway results in a short-term memory in the signaling pathway. This determines the amplitude of Hog1 phosphorylation under a periodic sequence of stress and non-stressed intervals. Our model suggests that the long-term memory also affects the way a cell responds to periodic stress conditions. Hence, during osmohomeostasis, short-term memory is dependent upon long-term memory. This is relevant in the context of fungal responses to dynamic and changing environments.

Conclusions
Our experiments and modeling have provided an example of identifying integral control that arises from time-scale separation in different processes, which is an important functional module in various contexts.
Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes
Authors: Acedo Alberto , Sanz David J , Durán Mercedes , Infante Mar , Pérez-Cabornero Lucía , Miner Cristina , Velasco Eladio A 
Published: June 2012

Abstract
Introduction
The underlying pathogenic mechanism of a large fraction of DNA variants of disease-causing genes is the disruption of the splicing process. We aimed to investigate the effect on splicing of the BRCA2 variants c.8488-1G > A (exon 20) and c.9026_9030del (exon 23), as well as 41 BRCA2 variants reported in the Breast Cancer Information Core (BIC) mutation database.

Methods
DNA variants were analyzed with the splicing prediction programs NNSPLICE and Human Splicing Finder. Functional analyses of candidate variants were performed by lymphocyte RT-PCR and/or hybrid minigene assays. Forty-one BIC variants of exons 19, 20, 23 and 24 were bioinformatically selected and generated by PCR-mutagenesis of the wild type minigenes.

Results
Lymphocyte RT-PCR of c.8488-1G > A showed intron 19 retention and a 12-nucleotide deletion in exon 20, whereas c.9026_9030del did not show any splicing anomaly. Minigene analysis of c.8488-1G > A displayed the aforementioned aberrant isoforms but also exon 20 skipping. We further evaluated the splicing outcomes of 41 variants of four BRCA2 exons by minigene analysis. Eighteen variants presented splicing aberrations. Most variants (78.9%) disrupted the natural splice sites, whereas four altered putative enhancers/silencers and had a weak effect. Fluorescent RT-PCR of minigenes accurately detected 14 RNA isoforms generated by cryptic site usage, exon skipping and intron retention events. Fourteen variants showed total splicing disruptions and were predicted to truncate or eliminate essential domains of BRCA2.

Conclusions
A relevant proportion of BRCA2 variants are correlated with splicing disruptions, indicating that RNA analysis is a valuable tool to assess the pathogenicity of a particular DNA change. The minigene system is a straightforward and robust approach to detect variants with an impact on splicing and contributes to a better knowledge of this gene expression step.
Mammalian tissues defective in nonsense-mediated mRNA decay display highly aberrant splicing patterns
Authors: Weischenfeldt Joachim , Waage Johannes , Tian Geng , Zhao Jing , Damgaard Inge , Jakobsen Janus Schou , Kristiansen Karsten , Krogh Anders , Wang Jun , Porse Bo T 
Published: June 2012

Abstract
Background
Nonsense-mediated mRNA decay (NMD) affects the outcome of alternative splicing by degrading mRNA isoforms with premature termination codons. Splicing regulators constitute important NMD targets; however, the extent to which loss of NMD causes extensive deregulation of alternative splicing has not previously been assayed in a global, unbiased manner. Here, we combine mouse genetics and RNA-seq to provide the first in vivo analysis of the global impact of NMD on splicing patterns in two primary mouse tissues ablated for the NMD factor UPF2.

Results
We developed a bioinformatic pipeline that maps RNA-seq data to a combinatorial exon database, predicts NMD-susceptibility for mRNA isoforms and calculates the distribution of major splice isoform classes. We present a catalog of NMD-regulated alternative splicing events, showing that isoforms of 30% of all expressed genes are upregulated in NMD-deficient cells and that NMD targets all major splicing classes. Importantly, NMD-dependent effects are not restricted to premature termination codon+ isoforms but also involve an abundance of splicing events that do not generate premature termination codons. Supporting their functional importance, the latter events are associated with high intronic conservation.

Conclusions
Our data demonstrate that NMD regulates alternative splicing outcomes through an intricate web of splicing regulators and that its loss leads to the deregulation of a panoply of splicing events, providing novel insights into its role in core- and tissue-specific regulation of gene expression. Thus, our study extends the importance of NMD from an mRNA quality pathway to a regulator of several layers of gene expression.
The genome of the polar eukaryotic microalga Coccomyxa subellipsoidea reveals traits of cold adaptation
Authors: Blanc Guillaume , Agarkova Irina , Grimwood Jane , Kuo Alan , Brueggeman Andrew , Dunigan David D , Gurnon James , Ladunga Istvan , Lindquist Erika , Lucas Susan , Pangilinan Jasmyn , Pröschold Thomas , Salamov Asaf , Schmutz Jeremy , Weeks Donald , Yamada Takashi , Lomsadze Alexandre , Borodovsky Mark , Claverie Jean-Michel , Grigoriev Igor V , Van Etten James L 
Published: June 2012

Abstract
Background
Little is known about the mechanisms of adaptation of life to the extreme environmental conditions encountered in polar regions. Here we present the genome sequence of a unicellular green alga from the division chlorophyta, Coccomyxa subellipsoidea C-169, which we will hereafter refer to as C-169. This is the first eukaryotic microorganism from a polar environment to have its genome sequenced.

Results
The 48.8 Mb genome contained in 20 chromosomes exhibits significant synteny conservation with the chromosomes of its relatives Chlorella variabilis and Chlamydomonas reinhardtii. The order of the genes is highly reshuffled within synteny blocks, suggesting that intra-chromosomal rearrangements were more prevalent than inter-chromosomal rearrangements. Remarkably, Zepp retrotransposons occur in clusters of nested elements with strictly one cluster per chromosome probably residing at the centromere. Several protein families overrepresented in C. subellipsoidae include proteins involved in lipid metabolism, transporters, cellulose synthases and short alcohol dehydrogenases. Conversely, C-169 lacks proteins that exist in all other sequenced chlorophytes, including components of the glycosyl phosphatidyl inositol anchoring system, pyruvate phosphate dikinase and the photosystem 1 reaction center subunit N (PsaN).

Conclusions
We suggest that some of these gene losses and gains could have contributed to adaptation to low temperatures. Comparison of these genomic features with the adaptive strategies of psychrophilic microbes suggests that prokaryotes and eukaryotes followed comparable evolutionary routes to adapt to cold environments.
Growth and Morphology of Graphene on Silicon Carbide Nanoparticles
Authors: Gruen Dieter M. , Mendelsohn Marshall H. , Kirk Marquis 
Published: June 2012

ABSTRACTCatalytic synthesis of graphene occurs when methane reacts with cubic SiC nanopowder at 1000-1200K. The composite, created under relatively mild experimental conditions, consists primarily of 30-40 nm diameter cylinders with aspect ratios near unity whose walls are composed of 10-20 layers of graphene surrounding nano-SiC particles. Sputtering by electron irradiation sequentially removes the graphene shells thus exposing the SiC cores. Electron as well as X-ray diffraction studies reveal the highly crystalline nature of the graphene shells which constitute 90 mol% of the composites. Raman data support a model involving growth of graphene on carbon rather than on silicon terminated SiC.
Optical and Electrical Effect of Texture Morphology on the Performance of Thin-Film Solar Cells
Authors: Kanematsu Daiji , Matsumoto Mitsuhiro , Yata Shigeo , Aya Yoichiro , Terakawa Akira , Iseki Masahiro 
Published: June 2012

ABSTRACTWe correlated the texture morphology and the solar cell properties by measuring the distribution in the texture morphology. As a result, the short-circuit current ISC was approximated across various types of substrates by the standard texture height. Furthermore, we investigated the texture morphology from the point of view of the electrical effects. With regard to this point, the open-circuit voltage VOC was correlated to the steepest texture angle. Therefore, we consider that the both of the ISC and the VOC can be improved by controlling the distribution in the texture morphology.
Optimizing Reservoir Monitoring: Improving PNL Logs in Changing Borehole Environments
Authors: Ariwodo Izu , Kanfar Majed F. , Qatari Ammar M. , Saldungaray Pablo , Rose David Alan 
Published: June 2012

Abstract
The growing demand for oil has emboldened producing companies to reenter old wells to further improve productivity and recovery. This requires monitoring the water saturation. Successes in reservoir saturation monitoring petrophysical analysis have increased the confidence to drill sidetracks in watered wells that have bypassed oil potential. Several techniques can be used to perform the analysis.
The Pulsed Neutron Capture (PNC) log is one of the most popular slim cased hole formation evaluation logging tools, which allow running the surveys without having to pull out the production string. Under the right conditions, the PNC logs can be run periodically in the time-lapse mode to monitor changes in water saturation and movements in the oil-water contact and gas-oil contact.
The wellbore environment may change between runs and this can complicate the analysis. For example, the borehole fluids may be different: gas, oil or brines of varying salinities. Also, changes in the downhole completion hardware can require running the logs through different tubular configurations. One has to be cognizant of all these environmental effects and appropriately correct for them to obtain the true formation properties, and to make comparisons between runs in the time-lapse analysis.
Different vendors use different correction schemes. In this paper we will discuss case studies with a methodology from one Service Company that uses a weighted database approach, which relies on characterizing the tool response in known environments. The paper shows some of the advantages and disadvantages of this technique, and in particular, when the downhole conditions deviate from the characterized environment. Alternative methodologies will be proposed to get the best possible results, based on this study. Finally, examples from Saudi Arabian wells will be shown where the computed capture cross section and neutron porosity were successfully corrected in challenging borehole conditions.
A Comprehensive EOR Study of a Highly Fractured Matured Field-Case Study
Authors: Kharrat R. , Mahdavi S. , Ghorbani Davood 
Published: June 2012

Abstract
Some of the Middle East fields are approaching their final stage of primary production. Most of these fields are highly fractured and carbonate in nature. One major problem is the creation of gas and water invaded zones during the history of production form such fields. Hence, the implementation of proper EOR process requires an extensive laboratory work and simulation studies.
A mature field with more than six decades of production has been considered in this study to explore all possible EOR methods. Several EOR processes such as continuous gas injection (GI), WAG (water alternative gas flooding), SWAG (simultaneous WAG), FAWAG (Foam Assisted WAG), and GAGD (Gas Assisted Gravity Drainage) process were studied in laboratory scale and simulation work. The Gas injection and GAGD were found to be unfeasible due the high fracture frequency and early gas breakthrough even with low rate of injection. However, the WAG, SWAG and FWAG were found to be more feasible. This is possibly due to mobility modification by water phase. During SWAG method all pores displaced at the same time, so that a higher ultimate recovery factor achieved sooner in comparison with WAG process. In order to have better recovery for the residual oil, FAWAG method was applied to control the injectivity of injected gas and reduce the interfacial tension (IFT) between residual oil and rock. Surfactant was chosen in different concentration of 5000, 2000, 1000, and 500 ppm. All experiments were carried out under reservoir condition. The FAWAG process was found to be more suitable process for such reservoirs due to its high recovery.
Finally the simulation study was conducted with different patterns of injection and production for all the mentioned EOR scenarios. It was found that the fractures density had an important role in the selection of the optimum pattern.