bluuebunny/crossref_metadata_2025 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

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

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

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

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

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

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

Background

Allergen 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.

Methods

A 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.

Results

Repeated 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.

Conclusions

The 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

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

The 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

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

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.
Massively parallel structured direct solver for equations describing time-harmonic qP-polarized waves in TTI media
Authors: Wang Shen , Xia Jianlin , de Hoop Maarten V. , Li Xiaoye S.
Published: March 2012

We considered the discretization and approximate solutions of equations describing time-harmonic qP-polarized waves in 3D inhomogeneous anisotropic media. The anisotropy comprises general (tilted) transversely isotropic symmetries. We are concerned with solving these equations for a large number of different sources. We considered higher-order partial differential equations and variable-order finite-difference schemes to accommodate anisotropy on the one hand and allow higher-order accuracy — to control sampling rates for relatively high frequencies — on the other hand. We made use of a nested dissection based domain decomposition in a massively parallel multifrontal solver combined with hierarchically semiseparable matrix compression techniques. The higher-order partial differential operators and the variable-order finite-difference schemes require the introduction of separators with variable thickness in the nested dissection; the development of these and their integration with the multifrontal solver is the main focus of our study. The algorithm that we developed is a powerful tool for anisotropic full-waveform inversion.
Predicting subsurface CO2 movement: From laboratory to field scale
Authors: Ghosh Ranjana , Sen Mrinal K.
Published: March 2012

Finding an appropriate model for time-lapse seismic monitoring of [Formula: see text]-sequestered carbonate reservoir poses a great challenge because carbonate-rocks have varying textures and highly reactive rock-fluid system. We introduced a frequency-dependent model based on Eshelby’s inclusion and differential effective medium (DEM) theory that can account for heterogeneity in microstructure of rocks and squirt flow. We showed that the estimated velocities from the modified DEM theory match well with the laboratory measurements (ultrasonic) of velocities of carbonate rocks saturated with [Formula: see text]-rich water. The theory predicts significant decrease in saturated P- and S-wave velocities in the seismic frequency band as a consequence of porosity and permeability enhancement by the process of chemical dissolution of carbonates with the saturating fluid. The study also showed the combined effect of chemical reaction and free [Formula: see text] saturation on the elastic properties of rock. We observed that the velocity dispersion and attenuation increased from complete gas saturation to water saturation. The proposed model can be used to invert geophysical measurements to detect changes in elastic properties of a carbonate reservoir and interpret the extent of [Formula: see text] movement with time. These are the key elements to ensure that sequestration will not damage underground geologic formation and [Formula: see text] storage is secure and environmentally acceptable.
Crosswell electromagnetic response in a fractured medium
Authors: Donadille Jean-Marc , Al-Ofi Salah M.
Published: March 2012

We experimentally verified that material-averaging techniques can be used for numerically modeling the response of the crosswell electromagnetic (crosswell EM) system in a fractured medium. We have designed a scaled model of the crosswell EM system, and verified that the laboratory data are in good agreement with the simulated response for different cases of fractures present in a host medium. Simulations of realistic scenarios in a hydrocarbon-filled reservoir indicate that the presence of fracture clusters can significantly affect the crosswell EM system response. The magnitude of the effect primarily depends on the number of fractures and their dip relative to the transmitter and receiver wells. In particular, small clusters of fractures filled with saline connate water produce large artifacts on the response, provided that the relative dip to the wells is large enough. The presence of a fracture cluster creates a characteristic signature in the full crosswell EM tomographical data set; therefore, crosswell EM data provides information related to the main fractures that are present between the wells. The inclusion of the fracture information as an additional constraint to the inversion of the crosswell EM data is expected to provide an improved interpretation of the reservoir fluids in the interwell space.
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.
Validity of the acoustic approximation in full-waveform seismic crosshole tomography
Authors: Marelli Stefano , Maurer Hansruedi , Manukyan Edgar
Published: March 2012

Acoustic waveform inversions are an increasingly popular tool for extracting subsurface information from seismic data. They are computationally much more efficient than elastic inversions. Naturally, an inherent disadvantage is that any elastic effects present in the recorded data are ignored in acoustic inversions. We investigate the extent to which elastic effects influence seismic crosshole data. Our numerical modeling studies reveal that in the presence of high contrast interfaces, at which P-to-S conversions occur, elastic effects can dominate the seismic sections, even for experiments involving pressure sources and pressure receivers. Comparisons of waveform inversion results using a purely acoustic algorithm on synthetic data that is either acoustic or elastic, show that subsurface models comprising small low-to-medium contrast ([Formula: see text]) structures can be successfully resolved in the acoustic approximation. However, in the presence of extended high-contrast anomalous bodies, P-to-S-conversions may substantially degrade the quality of the tomographic images. In particular, extended low-velocity zones are difficult to image. Likewise, relatively small low-velocity features are unresolved, even when advanced a priori information is included. One option for mitigating elastic effects is data windowing, which suppresses later arriving seismic arrivals, such as shear waves. Our tests of this approach found it to be inappropriate because elastic effects are also included in earlier arriving wavetrains. Furthermore, data windowing removes later arriving P-wave phases that may provide critical constraints on the tomograms. Finally, we investigated the extent to which acoustic inversions of elastic data are useful for time-lapse analyses of high contrast engineered structures, for which accurate reconstruction of the subsurface structure is not as critical as imaging differential changes between sequential experiments. Based on a realistic scenario for monitoring a radioactive waste repository, we demonstrated that acoustic inversions of elastic data yield substantial distortions of the tomograms and also unreliable information on trends in the velocity changes.
Compensation for transmission losses based on one-way propagators in the mixed domain
Authors: Sun Weijia , Fu Li-Yun
Published: March 2012

Most true-amplitude migration algorithms based on one-way wave equations involve corrections of geometric spreading and seismic [Formula: see text] attenuation. However, few papers discuss the compensation of transmission losses (CTL) based on one-way wave equations. Here, we present a method to compensate for transmission losses using one-way wave propagators for a 2D case. The scheme is derived from the Lippmann-Schwinger integral equation. The CTL scheme is composed of a transmission term and a phase-shift term. The transmission term compensates amplitudes while the wave propagates through subsurfaces. The transmission term is a function of the vertical wavenumbers of two adjacent heterogeneous screens. The phase-shift term is a Fourier finite-difference (FFD) propagator implemented in a mixed domain via Fourier transform. The transmission term can be flexibly incorporated into the conventional phase-shift migration algorithm, i.e., FFD, at every depth step. We analyze the effects of frequency, lateral velocity contrast, and vertical velocity ratio on the accuracy of the presented formulae. Numerical examples from a flat model and a fault model with lateral velocity variations are presented to demonstrate the ability of the proposed scheme for compensation of transmission losses.
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

Background

The association between autoimmune diseases and schizophrenia has rarely been systematically investigated.

Aims

To investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association.

Method

Taiwan'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.

Results

When 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.

Conclusions

Schizophrenia 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.
Public recognition of mental disorders and beliefs about treatment: changes in Australia over 16 years
Authors: Reavley Nicola J. , Jorm Anthony F.
Published: March 2012

Background

A 1995 Australian national survey of mental health literacy showed poor recognition of disorders and beliefs about treatment that differed from those of health professionals. A similar survey carried out in 2003/4 showed some improvements over 8 years.

Aims

To investigate whether recognition of mental disorders and beliefs about treatment have changed over a 16-year period.

Method

A national survey of 6019 adults was carried out in 2011 using the same questions as the 1995 and 2003/4 surveys.

Results

Results showed improved recognition of depression and more positive ratings for a range of interventions, including help from mental health professionals and antidepressants.

Conclusions

Although beliefs about effective medications and interventions have moved closer to those of health professionals since the previous surveys, there is still potential for mental health literacy gains in the areas of recognition and treatment beliefs for mental disorders. This is particularly the case for schizophrenia.
Intrahepatic Insulin Exposure, Intrahepatocellular Lipid and Regional Body Fat in Nonalcoholic Fatty Liver Disease
Authors: Mehta Sanjeev R. , Godsland Ian F. , Thomas E. Louise , Pavitt Darrell V. , Morin Stanislas X. , Bell Jimmy D. , Taylor-Robinson Simon D. , Johnston Desmond G.
Published: March 2012

Context:

Insulin is pivotal in regulating hepatic lipid synthesis, metabolism, and export.

Objective:

We tested the hypothesis that intrahepatic insulin exposure is an important determinant of intrahepatocellular lipid (IHCL), taking into account regional adiposity and both glucoregulatory and antilipolytic insulin sensitivity.

Research Design and Methods:

We compared 21 European males with known nonalcoholic fatty liver disease (NAFLD) with 19 healthy male controls. Insulin sensitivity, secretion, and percentage hepatic extraction were derived from iv glucose tolerance test (IVGTT) glucose, insulin, and C-peptide concentrations. Intrahepatic insulin exposure was calculated as percentage hepatic insulin extraction multiplied by basal or IVGTT insulin secretion. IHCL was quantified by proton magnetic resonance spectroscopy. Total and regional adipose tissue was measured using whole body magnetic resonance imaging.

Results:

Percentage hepatic extraction of newly secreted insulin differed between cases with NAFLD and controls at borderline significance (median, 76 vs. 83%; P = 0.07). Cases had higher intrahepatic insulin exposure than controls, both in the basal (34 vs. 18 pmol; P = 0.0002) and glucose-stimulated states (58 vs. 24 pmol; P = 0.01). IHCL was significantly related to both basal (rs = 0.62; P < 0.0001) and IVGTT intrahepatic insulin exposure (rs = 0.47; P = 0.002). As predictors of IHCL, both basal and IVGTT intrahepatic insulin exposure were dependent on the waist-to-hip ratio and homeostasis model assessment insulin resistance, but not on magnetic resonance imaging fat measures or IVGTT insulin sensitivity.

Conclusions:

Men with NAFLD have higher intrahepatic insulin exposure than controls. This correlates with IHCL, but the principal determinants of IHCL were fat distribution and hepatic rather than peripheral insulin resistance.
Functional comparison of protein domains within aPKCs involved in nucleocytoplasmic shuttling
Authors: Seidl Sebastian , Braun Ursula B. , Leitges Michael
Published: March 2012

The atypical protein kinases C (PKC) isoforms ι and ζ play crucial roles in regulation of signaling pathways related to proliferation, differentiation and cell survival. Over the years several interaction partners and phosphorylation targets have been identified. However, little is known about the regulation of atypical aPKC isoforms. To address this question, we performed a comparative analysis of atypical aPKCι/λ and ζ in MDCK cells. By using green fluorescence protein (GFP) fusion proteins containing the full-length or truncated proteins, we were able to recognize differences in subcellular localization and nucleocytoplasmic shuttling of both isoforms. We show, that an earlier described nuclear localization sequence (NLS), plays a role in the regulation of atypical aPKCζ but not in aPKCι, despite the fact that it is present in both isoforms. Leptomycin B treatment induces accumulation of GFP-fusion protein of both isoforms in the nucleus. Regardless, the loss of the NLS only decreases shuttling of aPKCζ, while aPKCι remains unaffected. In addition, we identified the hinge region as a potential regulator of localization of atypical PKCs. With a set of chimeric proteins we show that the hinge region of aPKCι mediates nuclear localization. In contrast, the hinge region of aPKCζ causes exclusion from the nucleus, indicating two different mechanisms leading to isoform specific regulation. Taken together, we show for the first time, that the atypical isoforms aPKCι and ζ underly different mechanisms regarding their regulation of subcellular localization and translocation into the nucleus in MDCK cells.
A TGFβ-Smad4-Fgf6 signaling cascade controls myogenic differentiation and myoblast fusion during tongue development
Authors: Han Dong , Zhao Hu , Parada Carolina , Hacia Joseph G. , Bringas Pablo , Chai Yang
Published: March 2012

The tongue is a muscular organ and plays a crucial role in speech, deglutition and taste. Despite the important physiological functions of the tongue, little is known about the regulatory mechanisms of tongue muscle development. TGFβ family members play important roles in regulating myogenesis, but the functional significance of Smad-dependent TGFβ signaling in regulating tongue skeletal muscle development remains unclear. In this study, we have investigated Smad4-mediated TGFβ signaling in the development of occipital somite-derived myogenic progenitors during tongue morphogenesis through tissue-specific inactivation of Smad4 (using Myf5-Cre;Smad4flox/flox mice). During the initiation of tongue development, cranial neural crest (CNC) cells occupy the tongue buds before myogenic progenitors migrate into the tongue primordium, suggesting that CNC cells play an instructive role in guiding tongue muscle development. Moreover, ablation of Smad4 results in defects in myogenic terminal differentiation and myoblast fusion. Despite compromised muscle differentiation, tendon formation appears unaffected in the tongue of Myf5-Cre;Smad4flox/flox mice, suggesting that the differentiation and maintenance of CNC-derived tendon cells are independent of Smad4-mediated signaling in myogenic cells in the tongue. Furthermore, loss of Smad4 results in a significant reduction in expression of several members of the FGF family, including Fgf6 and Fgfr4. Exogenous Fgf6 partially rescues the tongue myoblast fusion defect of Myf5-Cre;Smad4flox/flox mice. Taken together, our study demonstrates that a TGFβ-Smad4-Fgf6 signaling cascade plays a crucial role in myogenic cell fate determination and lineage progression during tongue myogenesis.
Germ cell pluripotency, premature differentiation and susceptibility to testicular teratomas in mice
Authors: Heaney Jason D. , Anderson Ericka L. , Michelson Megan V. , Zechel Jennifer L. , Conrad Patricia A. , Page David C. , Nadeau Joseph H.
Published: March 2012

Testicular teratomas result from anomalies in germ cell development during embryogenesis. In the 129 family of inbred strains of mice, teratomas initiate around embryonic day (E) 13.5 during the same developmental period in which female germ cells initiate meiosis and male germ cells enter mitotic arrest. Here, we report that three germ cell developmental abnormalities, namely continued proliferation, retention of pluripotency, and premature induction of differentiation, associate with teratoma susceptibility. Using mouse strains with low versus high teratoma incidence (129 versus 129-Chr19MOLF/Ei), and resistant to teratoma formation (FVB), we found that germ cell proliferation and expression of the pluripotency factor Nanog at a specific time point, E15.5, were directly related with increased tumor risk. Additionally, we discovered that genes expressed in pre-meiotic embryonic female and adult male germ cells, including cyclin D1 (Ccnd1) and stimulated by retinoic acid 8 (Stra8), were prematurely expressed in teratoma-susceptible germ cells and, in rare instances, induced entry into meiosis. As with Nanog, expression of differentiation-associated factors at a specific time point, E15.5, increased with tumor risk. Furthermore, Nanog and Ccnd1, genes with known roles in testicular cancer risk and tumorigenesis, respectively, were co-expressed in teratoma-susceptible germ cells and tumor stem cells, suggesting that retention of pluripotency and premature germ cell differentiation both contribute to tumorigenesis. Importantly, Stra8-deficient mice had an 88% decrease in teratoma incidence, providing direct evidence that premature initiation of the meiotic program contributes to tumorigenesis. These results show that deregulation of the mitotic-meiotic switch in XY germ cells contributes to teratoma initiation.
Mei-P26 regulates the maintenance of ovarian germline stem cells by promoting BMP signaling
Authors: Li Yun , Maines Jean Z. , Tastan Ömür Y. , McKearin Dennis M. , Buszczak Michael
Published: March 2012

In the Drosophila ovary, bone morphogenetic protein (BMP) ligands maintain germline stem cells (GSCs) in an undifferentiated state. The activation of the BMP pathway within GSCs results in the transcriptional repression of the differentiation factor bag of marbles (bam). The Nanos-Pumilio translational repressor complex and the miRNA pathway also help to promote GSC self-renewal. How the activities of different transcriptional and translational regulators are coordinated to keep the GSC in an undifferentiated state remains uncertain. Data presented here show that Mei-P26 cell-autonomously regulates GSC maintenance in addition to its previously described role of promoting germline cyst development. Within undifferentiated germ cells, Mei-P26 associates with miRNA pathway components and represses the translation of a shared target mRNA, suggesting that Mei-P26 can enhance miRNA-mediated silencing in specific contexts. In addition, disruption of mei-P26 compromises BMP signaling, resulting in the inappropriate expression of bam in germ cells immediately adjacent to the cap cell niche. Loss of mei-P26 results in premature translation of the BMP antagonist Brat in germline stem cells. These data suggest that Mei-P26 has distinct functions in the ovary and participates in regulating the fates of both GSCs and their differentiating daughters.
Integration of an abdominal Hox complex with Pax2 yields cell-specific EGF secretion from Drosophila sensory precursor cells
Authors: Li-Kroeger David , Cook Tiffany A. , Gebelein Brian
Published: March 2012

Cis-regulatory modules (CRMs) ensure specific developmental outcomes by mediating both proper spatiotemporal gene expression patterns and appropriate transcriptional levels. In Drosophila, the precise transcriptional control of the serine protease rhomboid regulates EGF signaling to specify distinct cell types. Recently, we identified a CRM that activates rhomboid expression and thereby EGF secretion from a subset of abdominal sensory organ precursor cells (SOPs) to induce an appropriate number of lipid-processing cells called oenocytes. Here, we use scanning mutagenesis coupled with reporter assays, biochemistry and genetics to dissect the transcriptional mechanisms regulating SOP-specific rhomboid activation. Our results show that proper spatial activity of the rhomboid CRM is dependent upon direct integration of the abdomen-specific Hox factor Abdominal-A and the SOP-restricted Pax2 factor. In addition, we show that the Extradenticle and Homothorax Hox co-factors are differentially integrated on the rhomboid CRM by abdominal versus thoracic Hox proteins in the presence of Pax2. Last, we show that Abdominal-A uses both Pax2-dependent and Pax2-independent mechanisms to stimulate rhomboid CRM activity to induce proper oenocyte numbers. Thus, these data demonstrate how a CRM integrates Hox and neural transcriptional inputs to regulate the appropriate spatial pattern and levels of EGF secretion to specify an essential cell fate.
VPS13Regulates Membrane Morphogenesis During Sporulation inSaccharomyces cerevisiae
Authors: Park Jae-Sook , Neiman Aaron M.
Published: March 2012

The hereditary disorders chorea acanthocytosis and Cohen syndrome are caused by mutations in different members of a family of genes that are orthologs of yeast VPS13. In vegetatively growing yeast, VPS13 is involved in the delivery of proteins to the vacuole. During sporulation, VPS13 is important for formation of the prospore membrane that encapsulates the daughter nuclei to give rise to spores. We report that VPS13 is required for multiple aspects of prospore membrane morphogenesis. 1) VPS13 promotes expansion of the prospore membrane via regulation of phosphatidylinositol-phosphates, that in turn activate the phospholipase D, Spo14; 2) VPS13 is required for a late step in cytokinesis at the cell division that gives rise to spores; and 3) VPS13 regulates a membrane bending activity that generates intralumenal vesicles. These results demonstrate that Vps13 plays a broader role in membrane biology than previously known, which may have important implications for the functions of VPS13 orthologs in humans.
Neopterin, inflammation-associated product, prolongs erythropoiesis suppression in aged SAMP1 mice due to senescent stromal-cell impairment
Authors: Aisaki Kazuo , Tsuboi Isao , Harada Tomonori , Oshima Hideki , Yamashita Akiko , Hirabayashi Yoko , Kanno Jun , Inoue Tohru , Aizawa Shin
Published: March 2012

Anemia induced by inflammation is well known to be more serious in the elderly than in non-elderly adults; however, the reason why this is so remains unclear. Neopterin produced by monocytes during inflammation promotes myelopoiesis but suppresses B-lymphopoiesis and erythropoiesis, by activating stromal cells in mice. Here, age-related changes in the erythropoietic response to neopterin were determined using senescence accelerated mice (SAMP1) with senescence stromal-cell impairment. Intravenous injection of neopterin into young mice (8–12 weeks old) resulted in a decrease in erythroid progenitor cell number in the bone marrow (BM), concomitant with an increase in myeloid progenitor cell number over one week. Intravenous injection of neopterin into aged mice (30–36 weeks old) resulted in a prolonged decrease in erythroid progenitor cell number in the BM over three weeks and a limited increase in myeloid progenitor cell number over one day. Neopterin treatment induced a decrease in serum erythropoietin concentrations in young mice but not in aged mice. The gene expression of tumor necrosis factor α (TNF- α),  a negative regulator of erythropoiesis, was up-regulated in the BM of both young and aged mice, and the degree of TNF- α up-regulation  was the same in both groups. The gene expression of interleukin (IL)-11, a positive regulator of erythropoiesis, was also up-regulated over one day in both young and aged mice. However, IL-11 gene expression remained up-regulated thereafter in young mice, whereas it was rapidly down-regulated in aged mice. These data suggest that prolonged suppression of erythropoiesis in aged mice may be due to a decrease in the production of positive regulators rather than to an increase in the production of negative regulators. Our combined data suggest that age-related impairment of stromal cells induces serious anemia in the elderly during inflammation.