bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-time determination of intracellular oxygen in bacteria using a genetically encoded FRET-based biosensor
Authors: Potzkei Janko , Kunze Martin , Drepper Thomas , Gensch Thomas , Jaeger Karl-Erich , Büchs Jochen 
Published: March 2012

Abstract

Background
Molecular oxygen (O2) is one of the key metabolites of all obligate and facultative aerobic pro- and eukaryotes. It plays a fundamental role in energy homeostasis whereas oxygen deprivation, in turn, broadly affects various physiological and pathophysiological processes. Therefore, real-time monitoring of cellular oxygen levels is basically a prerequisite for the analysis of hypoxia-induced processes in living cells and tissues.

Results
We developed a genetically encoded Förster resonance energy transfer (FRET)-based biosensor allowing the observation of changing molecular oxygen concentrations inside living cells. This biosensor named FluBO (fluorescent protein-based biosensor for oxygen) consists of the yellow fluorescent protein (YFP) that is sensitive towards oxygen depletion and the hypoxia-tolerant flavin-binding fluorescent protein (FbFP). Since O2 is essential for the formation of the YFP chromophore, efficient FRET from the FbFP donor domain to the YFP acceptor domain only occurs in the presence but not in the absence of oxygen. The oxygen biosensor was used for continuous real-time monitoring of temporal changes of O2 levels in the cytoplasm of Escherichia coli cells during batch cultivation.

Conclusions
FluBO represents a unique FRET-based oxygen biosensor which allows the non-invasive ratiometric readout of cellular oxygen. Thus, FluBO can serve as a novel and powerful probe for investigating the occurrence of hypoxia and its effects on a variety of (patho)physiological processes in living cells.
Targeting of prion-infected lymphoid cells to the central nervous system accelerates prion infection
Authors: Friedman-Levi Yael , Hoftberger Romana , Budka Herbert , Mayer-Sonnenfeld Tehila , Abramsky Oded , Ovadia Haim , Gabizon Ruth 
Published: March 2012

Abstract

Background
Prions, composed of a misfolded protein designated PrPSc, are infectious agents causing fatal neurodegenerative diseases. We have shown previously that, following induction of experimental autoimmune encephalomyelitis, prion-infected mice succumb to disease significantly earlier than controls, concomitant with the deposition of PrPSc aggregates in inflamed white matter areas. In the present work, we asked whether prion disease acceleration by experimental autoimmune encephalomyelitis results from infiltration of viable prion-infected immune cells into the central nervous system.

Methods
C57Bl/6 J mice underwent intraperitoneal inoculation with scrapie brain homogenates and were later induced with experimental autoimmune encephalomyelitis by inoculation of MOG35-55 in complete Freund's adjuvant supplemented with pertussis toxin. Spleen and lymph node cells from the co-induced animals were reactivated and subsequently injected into naïve mice as viable cells or as cell homogenates. Control groups were infected with viable and homogenized scrapie immune cells only with complete Freund's adjuvant. Prion disease incubation times as well as levels and sites of PrPSc deposition were next evaluated.

Results
We first show that acceleration of prion disease by experimental autoimmune encephalomyelitis requires the presence of high levels of spleen PrPSc. Next, we present evidence that mice infected with activated prion-experimental autoimmune encephalomyelitis viable cells succumb to prion disease considerably faster than do mice infected with equivalent cell extracts or other controls, concomitant with the deposition of PrPSc aggregates in white matter areas in brains and spinal cords.

Conclusions
Our results indicate that inflammatory targeting of viable prion-infected immune cells to the central nervous system accelerates prion disease propagation. We also show that in the absence of such targeting it is the load of PrPSc in the inoculum that determines the infectivity titers for subsequent transmissions. Both of these conclusions have important clinical implications as related to the risk of prion disease contamination of blood products.
Reduction of Voltage Gated Sodium Channel Protein in DRG by Vector Mediated miRNA Reduces Pain in Rats with Painful Diabetic Neuropathy
Authors: Chattopadhyay Munmun , Zhou Zhigang , Hao Shuanglin , Mata Marina , Fink David J 
Published: March 2012

Background: Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms NaV1.7 and NaV1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer-mediated release of the inhibitory neurotransmitters enkephalin or gamma amino butyric acid (GABA) from DRG neurons in diabetic animals reduced pain-related behaviors coincident with a reduction in NaV1.7 protein levels in DRG in vivo. To further evaluate the role of NaVα subunit levels in DRG in the pathogenesis of pain in diabetic neuropathy, we constructed a nonreplicating herpes simplex virus (HSV)-based vector expressing a microRNA (miRNA) against NaVα subunits. Results: Subcutaneous inoculation of the miRNA-expressing HSV vector into the feet of diabetic rats to transduce DRG resulted in a reduction in NaVα subunit levels in DRG neurons, coincident with a reduction in cold allodynia, thermal hyperalgesia and mechanical hyperalgesia. Conclusions: These data support the role of increased NaVα protein in DRG in the pathogenesis of pain in diabetic neuropathy, and provide a proof-of-principle demonstration for the development of a novel therapy that could be used to treat intractable pain in patients with diabetic neuropathy.
Comparison of intensity modulated radiotherapy (IMRT) with intensity modulated particle therapy (IMPT) using fixed beams or an ion gantry for the treatment of patients with skull base meningiomas
Authors: Kosaki Katsura , Ecker Swantje , Habermehl Daniel , Rieken Stefan , Jäkel Oliver , Herfarth Klaus , Debus Jürgen , Combs Stephanie E 
Published: March 2012

Abstract

Background
To examine the potential improvement in treatment planning for patients with skull base meningioma using IMRT compared to carbon ion or proton beams with and without a gantry.

Methods
Five patients originally treated with photon IMRT were selected for the study. Ion beams were chosen using a horizontal beam or an ion gantry. Intensity controlled raster scanning and the intensity modulated particle therapy mode were used for plan optimization. The evaluation included analysis of dose-volume histograms of the target volumes and organs at risk.

Results
In comparison with carbon and proton beams only with horizontal beams, carbon ion treatment plans could spare the OARs more and concentrated on the target volumes more than proton and photon IMRT treatment plans. Using only a horizontal fixed beam, satisfactory plans could be achieved for skull base tumors.

Conclusion
The results of the case studies showed that using IMPT has the potential to overcome the lack of a gantry for skull base tumors. Carbon ion plans offered slightly better dose distributions than proton plans, but the differences were not clinically significant with established dose prescription concepts.
Optimization of a synthetic mixture composed of major Trichoderma reesei enzymes for the hydrolysis of steam-exploded wheat straw
Authors: Billard Hélène , Faraj Abdelaziz , Lopes Ferreira Nicolas , Menir Sandra , Heiss-Blanquet Senta 
Published: March 2012

Abstract

Background
An efficient hydrolysis of lignocellulosic substrates to soluble sugars for biofuel production necessitates the interplay and synergistic interaction of multiple enzymes. An optimized enzyme mixture is crucial for reduced cost of the enzymatic hydrolysis step in a bioethanol production process and its composition will depend on the substrate and type of pretreatment used. In the present study, an experimental design was used to determine the optimal composition of a Trichoderma reesei enzyme mixture, comprising the main cellulase and hemicellulase activities, for the hydrolysis of steam-exploded wheat straw.

Methods
Six enzymes, CBH1 (Cel7a), CBH2 (Cel6a), EG1 (Cel7b), EG2 (Cel5a), as well as the xyloglucanase Cel74a and the xylanase XYN1 (Xyl11a) were purified from a T. reesei culture under lactose/xylose-induced conditions. Sugar release was followed in milliliter-scale hydrolysis assays for 48 hours and the influence of the mixture on initial conversion rates and final yields is assessed.

Results
The developed model could show that both responses were strongly correlated. Model predictions suggest that optimal hydrolysis yields can be obtained over a wide range of CBH1 to CBH2 ratios, but necessitates a high proportion of EG1 (13% to 25%) which cannot be replaced by EG2. Whereas 5% to 10% of the latter enzyme and a xylanase content above 6% are required for highest yields, these enzymes are predicted to be less important in the initial stage of hydrolysis.

Conclusions
The developed model could reliably predict hydrolysis yields of enzyme mixtures in the studied domain and highlighted the importance of the respective enzyme components in both the initial and the final hydrolysis phase of steam-exploded wheat straw.
The value of serum CA125 for the development of virtual follow-up strategies for patients with epithelial ovarian cancer: a retrospective study
Authors: Varughese Elizabeth , Kondalsamy-Chennakesavan Srinivas , Obermair Andreas 
Published: March 2012

Abstract

Background
Serum CA125 is routinely used in the follow up of ovarian cancer. The objective of the present study was to evaluate the usefulness of CA125 in the detection of ovarian cancer recurrence.

Methods
This retrospective case study was carried out at a tertiary gynaecological cancer centre in Australia. Patients with all cell types of epithelial ovarian cancer (EOC) treated between 2003 and2010 were considered eligible. We excluded patients whose aim of treatment was palliative, had no follow-up, had no pre-operative CA125 reading or had pre-operative CA125 levels < 35 U/mL. After primary treatment, patients were followed up as per guidelines suggested by National Comprehensive Cancer Network (NCCN). We recorded if symptoms, findings from physical examination, imaging or serum CA125 levels led to the diagnosis of recurrence. An increase in CA125 levels to twice the postoperative nadir was considered as "doubling" at any time during follow up.

Results
Analysis is based on 56 patients who completed primary treatment and who presented for a total of 274 follow-up episodes. Of those, 29 patients (52%) developed a recurrence within the follow up period. Recurrence was diagnosed by CA125 alone in 14 of 29 patients (48%). CA125 was not elevated in 7 patients (24%) who recurred. Doubling of CA125 from nadir was observed in 27/29 patients. Of those 27 patients the doubling from nadir occurred within the normal range of 35 U/ml in 3 cases and outside the normal range in 24 cases. Multivariate analysis suggests that doubling of serum CA125 (OR 5.10, p 0.036) and nadir CA125 > 10 U/ml (OR 2.86, p 0.01) remained the only independent factors to predict ovarian cancer recurrence.

Conclusions
The present paper proposes the validation of a novel CA125 algorithm aiming to detect recurrent EOC. These data may allow us to investigate novel ways of follow up that do not require a patient's physical attendance at a clinic (virtual follow-up).
The epigenetic effects of butyrate: potential therapeutic implications for clinical practice
Authors: Berni Canani Roberto , Di Costanzo Margherita , Leone Ludovica 
Published: March 2012

Abstract
Butyrate is a short chain fatty acid derived from the microbial fermentation of dietary fibers in the colon. In the last decade, multiple beneficial effects of butyrate at intestinal and extraintestinal level have been demonstrated. The mechanisms of action of butyrate are different and many of these involve an epigenetic regulation of gene expression through the inhibition of histone deacetylase. There is a growing interest in butyrate because its impact on epigenetic mechanisms will lead to more specific and efficacious therapeutic strategies for the prevention and treatment of different diseases ranging from genetic/metabolic conditions to neurological degenerative disorders. This review is focused on recent data regarding the epigenetic effects of butyrate with potential clinical implications in human medicine.
Repeated allergen exposure reduce early phase airway response and leukotriene release despite upregulation of 5‐lipoxygenase pathways
Authors: Cui Zhi‐Hua , Rådinger Madeleine , Sjöstrand Margareta , Lötvall Jan 
Published: March 2012

AbstractBackgroundAllergen induced early phase airway response and airway plasma exudation are predominantly mediated by inflammatory mast cell mediators including histamine, cysteinyl leukotrienes (cysLTs) and thromboxane A2 (TXA2). The aim of the present study was to evaluate whether repeated allergen exposure affects early phase airway response to allergen challenge.MethodsA trimellitic anhydride (TMA) sensitized guinea pig model was used to investigate the effects of low dose repeated allergen exposure on cholinergic airway responsiveness, early phase airway response and plasma exudation, as well as local airway production of mast cell derived cysteinyl leukotrienes and thromboxane B2 (TXB2) after allergen challenge.ResultsRepeated low dose allergen exposure increased cholinergic airway responsiveness. In contrast, early phase airway response and plasma exudation in response to a high‐dose allergen challenge were strongly attenuated after repeated low dose allergen exposure. Inhibition of the airway response was unspecific to exposed allergen and independent of histamine receptor blocking. Furthermore, a significant reduction of cysteinyl leukotrienes and TXB2 was found in the airways of animals repeatedly exposed to a low dose allergen. However, in vitro stimulation of airway tissue from animals repeatedly exposed to a low dose allergen with arachidonic acid and calcium ionophore (A23187) induced production of cysteinyl leukotrienes and TXB2, suggesting enhanced activity of 5‐lipoxygenase and cyclooxygenase pathways.ConclusionsThe inhibition of the early phase airway response, cysteinyl leukotriene and TXB2 production after repeated allergen exposure may result from unresponsive effector cells.
Metis: a profiling toolkit based on the virtualization of hardware performance counters
Authors: Xie Xia , Jiang Haiou , Jin Hai , Cao Wenzhi , Yuan Pingpeng , Yang Laurence Tianruo 
Published: March 2012

Abstract
Background
With wide application of virtualization technology, the demand is increasing for performance analysis and system diagnosis in virtualization environment. There are some profiling toolkits based on hardware events, such as OProfile in native Linux and Xenoprof in Xen virtual machine environment. However, sometimes users in different domains need monitor different hardware events individually at the same time. For programming and profiling in environment for virtual machine, it may become popular in the coming future. In this paper, we present Metis, a system-wide profiling toolkit for Xen virtual machine environment based on the virtualization of hardware performance counters.

Methods
Virtualization of hardware performance counters is used to enable profiling of processes and routines running in the domain or Xen virtual machine monitor.

Results
This toolkit allows multiple users in different domains to monitor different hardware events simultaneously in Xen virtual machine environment, obtaining the distribution of hardware events such as clock cycles, instruction execution and cache misses, etc. Our experiments with a real-world benchmark demonstrate the good performance of Metis.

Conclusion
Comparing to all the existing profiling toolkits, Metis is different which enables multiple users in different virtual machines to monitor different CPU events simultaneously, and users in different domains can use this toolkit individually without affecting each other. We apply a popular benchmark to verify the correctness of Metis and its cool features.
All Your Base: a fast and accurate probabilistic approach to base calling
Authors: Massingham Tim , Goldman Nick 
Published: March 2012

AbstractThe accuracy of base calls produced by Illumina sequencers is adversely affected by several processes, with laser cross-talk and cluster phasing being prominent. We introduce an explicit statistical model of the sequencing process that generalizes current models of phasing and cross-talk and forms the basis of a base calling method which improves on the best existing base callers, especially when comparing the number of error-free reads. The novel algorithms implemented in All Your Base (AYB) are comparable in speed to other competitive base-calling methods, do not require training data and are designed to be robust to gross errors, producing sensible results where other techniques struggle. AYB is available at http://www.ebi.ac.uk/goldman-srv/AYB/
Chromatin structural changes around satellite repeats on the female sex chromosome in Schistosoma mansoni and their possible role in sex chromosome emergence
Authors: Lepesant Julie MJ , Cosseau Céline , Boissier Jérome , Freitag Michael , Portela Julien , Climent Déborah , Perrin Cécile , Zerlotini Adhemar , Grunau Christoph 
Published: March 2012

Abstract
Background
In the leuphotrochozoan parasitic platyhelminth Schistosoma mansoni, male individuals are homogametic (ZZ) whereas females are heterogametic (ZW). To elucidate the mechanisms that led to the emergence of sex chromosomes, we compared the genomic sequence and the chromatin structure of male and female individuals. As for many eukaryotes, the lower estimate for the repeat content is 40%, with an unknown proportion of domesticated repeats. We used massive sequencing to de novo assemble all repeats, and identify unambiguously Z-specific, W-specific and pseudoautosomal regions of the S. mansoni sex chromosomes.

Results
We show that 70 to 90% of S. mansoni W and Z are pseudoautosomal. No female-specific gene could be identified. Instead, the W-specific region is composed almost entirely of 36 satellite repeat families, of which 33 were previously unknown. Transcription and chromatin status of female-specific repeats are stage-specific: for those repeats that are transcribed, transcription is restricted to the larval stages lacking sexual dimorphism. In contrast, in the sexually dimorphic adult stage of the life cycle, no transcription occurs. In addition, the euchromatic character of histone modifications around the W-specific repeats decreases during the life cycle. Recombination repression occurs in this region even if homologous sequences are present on both the Z and W chromosomes.

Conclusion
Our study provides for the first time evidence for the hypothesis that, at least in organisms with a ZW type of sex chromosomes, repeat-induced chromatin structure changes could indeed be the initial event in sex chromosome emergence.
Characterizing linkage disequilibrium and evaluating imputation power of human genomic insertion-deletion polymorphisms
Authors: Lu James T , Wang Yi , Gibbs Richard A , Yu Fuli 
Published: March 2012

Abstract
Background
Indels are an important cause of human variation and central to the study of human disease. The 1000 Genomes Project Low-Coverage Pilot identified over 1.3 million indels shorter than 50 bp, of which over 890 were identified as potentially disruptive variants. Yet, despite their ubiquity, the local genomic characteristics of indels remain unexplored.

Results
Herein we describe population- and minor allele frequency-based differences in linkage disequilibrium and imputation characteristics for indels included in the 1000 Genomes Project Low-Coverage Pilot for the CEU, YRI and CHB+JPT populations. Common indels were well tagged by nearby SNPs in all studied populations, and were also tagged at a similar rate to common SNPs. Both neutral and functionally deleterious common indels were imputed with greater than 95% concordance from HapMap Phase 3 and OMNI SNP sites. Further, 38 to 56% of low frequency indels were tagged by low frequency SNPs. We were able to impute heterozygous low frequency indels with over 50% concordance. Lastly, our analysis also revealed evidence of ascertainment bias. This bias prevents us from extending the applicability of our results to highly polymorphic indels that could not be identified in the Low-Coverage Pilot.

Conclusions
Although further scope exists to improve the imputation of low frequency indels, our study demonstrates that there are already ample opportunities to retrospectively impute indels for prior genome-wide association studies and to incorporate indel imputation into future case/control studies.
Etudes in computational rock physics: Alterations and benchmarking
Authors: Dvorkin Jack , Fang Qian , Derzhi Naum 
Published: March 2012

We tested computational benchmarking data for the absolute permeability, electrical formation factor, and elastic moduli based on the Finney pack, a physical dense random pack of identical spheres digitally rendered into a 3D rectangular coordinate system, as the starting digital object. It is altered by (a) changing the radius of each sphere and (b) geometrically inverting these new packs by swapping grains and pores. Porosity, the absolute permeability, electrical formation factor, and elastic moduli are computed for all these alterations. The direct (grain-based) objects are relevant to clastic rock, and the inverse objects are proxies for carbonates with moldic pores. To corroborate these computational results, we matched the permeability versus porosity, formation factor versus porosity, and elastic moduli versus porosity trends they form by established theoretical rock physics models. These trends persisted when we reduced the scale of investigation by subsampling some of the digital objects under examination.
Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population-based study
Authors: Chen Shaw-Ji , Chao Yu-Lin , Chen Chuan-Yu , Chang Chia-Ming , Wu Erin Chia-Hsuan , Wu Chi-Shin , Yeh Hsueh-Han , Chen Chia-Hsiang , Tsai Hui-Ju 
Published: March 2012

BackgroundThe association between autoimmune diseases and schizophrenia has rarely been systematically investigated.AimsTo investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association.MethodTaiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing.ResultsWhen compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04–1.67), psoriasis (OR = 1.48, 95% CI 1.07–2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04–2.80), celiac disease (OR = 2.43, 95% CI 1.12–5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64–15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35–0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis.ConclusionsSchizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases.