bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional profiling of Saccharomyces cerevisiae exposed to propolis
Authors: de Castro Patrícia Alves , Savoldi Marcela , Bonatto Diego , Malavazi Iran , Goldman Maria Helena S , Berretta Andresa A , Goldman Gustavo Henrique 
Published: October 2012

AbstractBackgroundPropolis is a natural product of plant resins collected by honeybees (Apis mellifera) from various plant sources. Our previous studies indicated that propolis sensitivity is dependent on the mitochondrial function and that vacuolar acidification and autophagy are important for yeast cell death caused by propolis. Here, we extended our understanding of propolis-mediated cell death in the yeastSaccharomyces cerevisiaeby applying systems biology tools to analyze the transcriptional profiling of cells exposed to propolis.MethodsWe have used transcriptional profiling ofS. cerevisiaeexposed to propolis. We validated our findings by using real-time PCR of selected genes. Systems biology tools (physical protein-protein interaction [PPPI] network) were applied to analyse the propolis-induced transcriptional bevavior, aiming to identify which pathways are modulated by propolis inS. cerevisiaeand potentially influencing cell death.ResultsWe were able to observe 1,339 genes modulated in at least one time point when compared to the reference time (propolis untreated samples) (t-test,p-value 0.01). Enrichment analysis performed by Gene Ontology (GO) Term finder tool showed enrichment for several biological categories among the genes up-regulated in the microarray hybridization such as transport and transmembrane transport and response to stress. Real-time RT-PCR analysis of selected genes showed by our microarray hybridization approach was capable of providing information aboutS. cerevisiaegene expression modulation with a considerably high level of confidence. Finally, a physical protein-protein (PPPI) network design and global topological analysis stressed the importance of these pathways in response ofS. cerevisiaeto propolis and were correlated with the transcriptional data obtained thorough the microarray analysis.ConclusionsIn summary, our data indicate that propolis is largely affecting several pathways in the eukaryotic cell. However, the most prominent pathways are related to oxidative stress, mitochondrial electron transport chain, vacuolar acidification, regulation of macroautophagy associated with protein target to vacuole, cellular response to starvation, and negative regulation of transcription from RNA polymerase II promoter. Our work emphasizes again the importance ofS. cerevisiaeas a model system to understand at molecular level the mechanism whereby propolis causes cell death in this organism at the concentration herein tested. Our study is the first one that investigates systematically by using functional genomics how propolis influences and modulates the mRNA abundance of an organism and may stimulate further work on the propolis-mediated cell death mechanisms in fungi.
Effects of curcumin on stem-like cells in human esophageal squamous carcinoma cell lines
Authors: Almanaa Taghreed N , Geusz Michael E , Jamasbi Roudabeh J 
Published: October 2012

AbstractBackgroundMany cancers contain cell subpopulations that display characteristics of stem cells. Because these cancer stem cells (CSCs) appear to provide resistance to chemo-radiation therapy, development of therapeutic agents that target CSCs is essential. Curcumin is a phytochemical agent that is currently used in clinical trials to test its effectiveness against cancer. However, the effect of curcumin on CSCs is not well established. The current study evaluated curcumin-induced cell death in six cancer cell lines derived from human esophageal squamous cell carcinomas. Moreover, these cell lines and the ones established from cells that survived curcumin treatments were characterized.MethodsCell loss was assayed after TE-1, TE-8, KY-5, KY-10, YES-1, and YES-2 cells were exposed to 20–80 μM curcumin for 30 hrs. Cell lines surviving 40 or 60 μM curcumin were established from these six original lines. The stem cell markers aldehyde dehydrogenase-1A1 (ALDH1A1) and CD44 as well as NF-κB were used to compare CSC-like subpopulations within and among the original lines as well as the curcumin-surviving lines. YES-2 was tested for tumorsphere-forming capabilities. Finally, the surviving lines were treated with 40 and 60 μM curcumin to determine whether their sensitivity was different from the original lines.ResultsThe cell loss after curcumin treatment increased in a dose-dependent manner in all cell lines. The percentage of cells remaining after 60 μM curcumin treatment varied from 10.9% to 36.3% across the six lines. The cell lines were heterogeneous with respect to ALDH1A1, NF-κB and CD44 expression. KY-5 and YES-1 were the least sensitive and had the highest number of stem-like cells whereas TE-1 had the lowest. The curcumin-surviving lines showed a significant loss in the high staining ALDH1A1 and CD44 cell populations. Tumorspheres formed from YES-2 but were small and rare in the YES-2 surviving line. The curcumin-surviving lines showed a small but significant decrease in sensitivity to curcumin when compared with the original lines.ConclusionOur results suggest that curcumin not only eliminates cancer cells but also targets CSCs. Therefore, curcumin may be an effective compound for treating esophageal and possibly other cancers in which CSCs can cause tumor recurrence.
Construction of a two-parameter empirical model of left ventricle wall motion using cardiac tagged magnetic resonance imaging data
Authors: Shi Jack J , Alenezy Mohammed , Smirnova Irina V , Bilgen Mehmet 
Published: October 2012

Abstract

Background
A one-parameter model was previously proposed to characterize the short axis motion of the LV wall at the mid-ventricle level. The single parameter of this model was associated with the radial contraction of myocardium, but more comprehensive model was needed to account for the rotation at the apex and base levels. The current study developed such model and demonstrated its merits and limitations with examples.

Materials and methods
The hearts of five healthy individuals were visualized using cardiac tagged magnetic resonance imaging (tMRI) covering the contraction and relaxation phases. Based on the characteristics of the overall dynamics of the LV wall, its motion was represented by a combination of two components - radial and rotational. Each component was represented by a transformation matrix with a time-dependent variable α or β.
Image preprocessing step and model fitting algorithm were described and applied to estimate the temporal profiles of α and β within a cardiac cycle at the apex, mid-ventricle and base levels. During this process, the tagged lines of the acquired images served as landmark reference for comparing against the model prediction of the motion. Qualitative and quantitative analyses were performed for testing the performance of the model and thus its validation.

Results
The α and β estimates exhibited similarities in values and temporal trends once they were scaled by the radius of the epicardium (r

epi
)and plotted against the time scaled by the period of the cardiac cycle (T

cardiac
) of each heart measured during the data acquisition. α/r

epi
peaked at about Δt/T

cardiac
=0.4 and with values 0.34, 0.4 and 0.3 for the apex, mid-ventricle and base level, respectively. β/r

epi
similarly maximized in amplitude at about Δt/T

cardiac
=0.4, but read 0.2 for the apex and - 0.08 for the base level. The difference indicated that the apex twisted more than the base.

Conclusion
It is feasible to empirically model the spatial and temporal evolution of the LV wall motion using a two-parameter formulation in conjunction with tMRI-based visualization of the LV wall in the transverse planes of the apex, mid-ventricle and base. In healthy hearts, the analytical model will potentially allow deriving biomechanical entities, such as strain, strain rate or torsion, which are typically used as diagnostic, prognostic or predictive markers of cardiovascular diseases including diabetes.
Charge transfer magnetoexciton formation at vertically coupled quantum dots
Authors: Gutiérrez Willian , Marin Jairo H , Mikhailov Ilia D 
Published: October 2012

Abstract
A theoretical investigation is presented on the properties of charge transfer excitons at vertically coupled semiconductor quantum dots in the presence of electric and magnetic fields directed along the growth axis. Such excitons should have two interesting characteristics: an extremely long lifetime and a permanent dipole moment. We show that wave functions and the low-lying energies of charge transfer exciton can be found exactly for a special morphology of quantum dots that provides a parabolic confinement inside the layers. To take into account a difference between confinement potentials of an actual structure and of our exactly solvable model, we use the Galerkin method. The density of energy states is calculated for different InAs/GaAs quantum dots’ dimensions, the separation between layers, and the strength of the electric and magnetic fields. A possibility of a formation of a giant dipolar momentum under external electric field is predicted.
Naturally occurring mutations to HCV protease inhibitors in treatment-naïve patients
Authors: Paolucci Stefania , Fiorina Loretta , Piralla Antonio , Gulminetti Roberto , Novati Stefano , Barbarini Giorgio , Sacchi Paolo , Gatti Marta , Dossena Luca , Baldanti Fausto 
Published: October 2012

AbstractBackgroundProtease inhibitors (PIs) to treat hepatitis C (HCV) virus infection have been approved and others are under development.ResultsThe aims of this study were to illustrate natural polymorphisms in the HCV protease and measure the frequency of PI resistance mutations in different HCV genotypes from PI-naïve patients.Direct sequencing of HCV NS3/4A protease was performed in 156 HCV patients naïve to PIs who were infected with genotype 1a (n = 31), 1b (n = 39), 2 (n = 30), 3 (n = 33) and 4 (n = 23).Amino acid (aa) substitutions associated with HCV PI resistance were found in 17/156 (10.8%) sequences. Mutations V36L, T54S, V55A/I, and Q80K/L were observed in 29% of patients with genotype 1a, and V55F, Q80L/N and M175L in 10% of patients with genotype 1b. The mutation V158M was found in 3% of patients with genotype 2, D168Q was present in 100% of patients with genotype 3 and D168E was observed in 13% of patients with genotype 4. In addition, multiple aa polymorphisms not associated with PI resistance were detected in patients with genotypes 1a, 1b and 4.ConclusionsAlthough major PI resistance mutations were not detected, other resistance mutations conferring low level resistance to PIs together with a number of natural polymorphisms were observed in proteases of PI naïve HCV patients. A more extensive analysis is needed to better evaluate the impact of baseline resistance and compensatory mutations in the efficacy of HCV PI treatment.
RETRACTED ARTICLE: Assessment of the influence of whole body vibration on Cochlear function
Authors: Moussavi-Najarkola Seyyed-Ali , Khavanin Ali , Mirzaei Ramazan , Salehnia Mojdeh , Akbari Mehdi 
Published: October 2012

Abstract

Background
Whole body vibration (WBV) is a potentially harmful consequence resulting from the dissipation of energy by industrial machineries. The result of WBV exposure on the auditory system remains unknown. The objective of the present research was to evaluate the influence of WBV on cochlear function, in particular outer hair cell function. It is hypothesized that WBV impairs cochlear function resulting in decreased Distortion Product Otoacoustic Emission (DPOAE) levels (Ldp) in rabbits subjected to WBV.

Methods
Twelve rabbits were equally divided into vibration and control groups. Animals in vibration group were exposed to 1.0 ms-2 r.m.s vertical WBV at 4–8 Hz for 8 h/day during 5 consecutive days. Outer hair cell function was assessed by comparing repeated-measurements of DPOAE levels (Ldp) across a range of f2 frequencies in rabbits both exposed and unexposed to WBV. DPOAE level shifts (LSdp) were compared across ears, frequencies, groups, and times.

Results
No differences were seen over time in DPOAE levels in the non-exposed rabbits (p = 0.082). Post-exposure Ldp in rabbits exposed to WBV were significantly increased at all test frequencies in both ears compared to baseline measures (p = 0.021). The greatest increase in Ldp following exposure was seen at 5888.5 Hz (mean shift = 13.25 dB). Post-exposure Ldp in rabbits exposed to WBV were not significantly different between the right and left ears (p = 0.083).

Conclusion
WBV impairs cochlear function resulting in increased DPOAE responses in rabbits exposed to WBV. DPOAE level shifts occurred over a wide range of frequencies following prolonged WBV in rabbits.
Endogenous TDP-43, but not FUS, contributes to stress granule assembly via G3BP
Authors: Aulas Anaïs , Stabile Stéphanie , Vande Velde Christine 
Published: October 2012

Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective loss of upper and lower motor neurons, a cell type that is intrinsically more vulnerable than other cell types to exogenous stress. The interplay between genetic susceptibility and environmental exposures to toxins has long been thought to be relevant to ALS. One cellular mechanism to overcome stress is the formation of small dense cytoplasmic domains called stress granules (SG) which contain translationally arrested mRNAs. TDP-43 (encoded by TARDBP) is an ALS-causative gene that we have previously implicated in the regulation of the core stress granule proteins G3BP and TIA-1. TIA-1 and G3BP localize to SG under nearly all stress conditions and are considered essential to SG formation. Here, we report that TDP-43 is required for proper SG dynamics, especially SG assembly as marked by the secondary aggregation of TIA-1. We also show that SG assembly, but not initiation, requires G3BP. Furthermore, G3BP can rescue defective SG assembly in cells depleted of endogenous TDP-43. We also demonstrate that endogenous TDP-43 and FUS do not have overlapping functions in this cellular process as SG initiation and assembly occur normally in the absence of FUS. Lastly, we observe that SG assembly is a contributing factor in the survival of neuronal-like cells responding to acute oxidative stress. These data raise the possibility that disruptions of normal stress granule dynamics by loss of nuclear TDP-43 function may contribute to neuronal vulnerability in ALS.
Directed evolution of bright mutants of an oxygen-independent flavin-binding fluorescent protein from Pseudomonas putida
Authors: Mukherjee Arnab , Weyant Kevin B , Walker Joshua , Schroeder Charles M 
Published: October 2012

Abstract

Background
Fluorescent reporter proteins have revolutionized our understanding of cellular bioprocesses by enabling live cell imaging with exquisite spatio-temporal resolution. Existing fluorescent proteins are predominantly based on the green fluorescent protein (GFP) and related analogs. However, GFP-family proteins strictly require molecular oxygen for maturation of fluorescence, which precludes their application for investigating biological processes in low-oxygen environments. A new class of oxygen-independent fluorescent reporter proteins was recently reported based on flavin-binding photosensors from Bacillus subtilis and Pseudomonas putida. However, flavin-binding fluorescent proteins show very limited brightness, which restricts their utility as biological imaging probes.

Results
In this work, we report the discovery of bright mutants of a flavin-binding fluorescent protein from P. putida using directed evolution by site saturation mutagenesis. We discovered two mutations at a chromophore-proximal amino acid (F37S and F37T) that confer a twofold enhancement in brightness relative to the wild type fluorescent protein through improvements in quantum yield and holoprotein fraction. In addition, we observed that substitution with other aromatic amino acids at this residue (F37Y and F37W) severely diminishes fluorescence emission. Therefore, we identify F37 as a key amino acid residue in determining fluorescence.

Conclusions
To increase the scope and utility of flavin-binding fluorescent proteins as practical fluorescent reporters, there is a strong need for improved variants of the wild type protein. Our work reports on the application of site saturation mutagenesis to isolate brighter variants of a flavin-binding fluorescent protein, which is a first-of-its-kind approach. Overall, we anticipate that the improved variants will find pervasive use as fluorescent reporters for biological studies in low-oxygen environments.
Paradigmatic status of an endo- and exoglucanase and its effect on crystalline cellulose degradation
Authors: Moraïs Sarah , Barak Yoav , Lamed Raphael , Wilson David B , Xu Qi , Himmel Michael E , Bayer Edward A 
Published: October 2012

Abstract

Background
Microorganisms employ a multiplicity of enzymes to efficiently degrade the composite structure of plant cell wall cellulosic polysaccharides. These remarkable enzyme systems include glycoside hydrolases (cellulases, hemicellulases), polysaccharide lyases, and the carbohydrate esterases. To accomplish this challenging task, several strategies are commonly observed either separately or in combination. These include free enzyme systems, multifunctional enzymes, and multi-enzyme self-assembled designer cellulosome complexes.

Results
In order to compare these different paradigms, we employed a synthetic biology approach to convert two different cellulases from the free enzymatic system of the well-studied bacterium, Thermobifida fusca, into bifunctional enzymes with different modular architectures. We then examined their performance compared to those of the combined parental free-enzyme and equivalent designer-cellulosome systems. The results showed that the cellulolytic activity displayed by the different architectures of the bifunctional enzymes was somewhat inferior to that of the wild-type free enzyme system.

Conclusions
The activity exhibited by the designer cellulosome system was equal or superior to that of the free system, presumably reflecting the combined proximity of the enzymes and high flexibility of the designer cellulosome components, thus enabling efficient enzymatic activity of the catalytic modules.
Positive correlation between circulating cathelicidin antimicrobial peptide (hCAP18/LL-37) and 25-hydroxyvitamin D levels in healthy adults
Authors: Dixon Brian M , Barker Tyler , McKinnon Toni , Cuomo John , Frei Balz , Borregaard Niels , Gombart Adrian F 
Published: October 2012

AbstractBackgroundTranscription of the cathelicidin antimicrobial peptide (CAMP) gene is induced by binding of the bioactive form of vitamin D, 1,25-dihydroxyvitamin D, to the vitamin D receptor. Significant levels of the protein hCAP18/LL-37 are found in the blood and may protect against infection and/or sepsis. We hypothesized that serum vitamin D levels may modulate the circulating levels of hCAP18. Only three studies have shown a positive correlation between circulating 25-hydroxyvitamin D and hCAP18 levels. Here we provide additional evidence for such a correlation in healthy, middle-aged adults.FindingsSerum levels of 25-hydroxyvitamin D [25(OH)D] and plasma levels of hCAP18 were determined in 19 healthy middle-aged (mean of 50.1 years) adult men and women. Plasma hCAP18 concentrations correlated with serum 25(OH)D concentrations in subjects with 25(OH)D levels ≤ 32 ng/ml (r = 0.81, p < 0.005) but not in subjects with concentrations > 32 ng/ml (r = 0.19, p = 0.63).ConclusionsWe conclude that plasma hCAP18 levels correlate with serum 25(OH)D levels in subjects with concentrations of 25(OH)D ≤ 32 ng/ml as opposed to those with concentrations > 32 ng/ml and that vitamin D status may regulate systemic levels of hCAP18/LL-37.
ENU-induced phenovariance in mice: inferences from 587 mutations
Authors: Arnold Carrie N , Barnes Michael J , Berger Michael , Blasius Amanda L , Brandl Katharina , Croker Ben , Crozat Karine , Du Xin , Eidenschenk Celine , Georgel Philippe , Hoebe Kasper , Huang Hua , Jiang Zhengfan , Krebs Philippe , La Vine Diantha , Li Xiaohong , Lyon Stephen , Moresco Eva Marie Y , Murray Anne R , Popkin Daniel L , Rutschmann Sophie , Siggs Owen M , Smart Nora G , Sun Lei , Tabeta Koichi , Webster Victoria , Tomisato Wataru , Won Sungyong , Xia Yu , Xiao Nengming , Beutler Bruce 
Published: October 2012

Abstract

Background
We present a compendium of N-ethyl-N-nitrosourea (ENU)-induced mouse mutations, identified in our laboratory over a period of 10 years either on the basis of phenotype or whole genome and/or whole exome sequencing, and archived in the Mutagenetix database. Our purpose is threefold: 1) to formally describe many point mutations, including those that were not previously disclosed in peer-reviewed publications; 2) to assess the characteristics of these mutations; and 3) to estimate the likelihood that a missense mutation induced by ENU will create a detectable phenotype.

Findings
In the context of an ENU mutagenesis program for C57BL/6J mice, a total of 185 phenotypes were tracked to mutations in 129 genes. In addition, 402 incidental mutations were identified and predicted to affect 390 genes. As previously reported, ENU shows strand asymmetry in its induction of mutations, particularly favoring T to A rather than A to T in the sense strand of coding regions and splice junctions. Some amino acid substitutions are far more likely to be damaging than others, and some are far more likely to be observed. Indeed, from among a total of 494 non-synonymous coding mutations, ENU was observed to create only 114 of the 182 possible amino acid substitutions that single base changes can achieve. Based on differences in overt null allele frequencies observed in phenotypic vs. non-phenotypic mutation sets, we infer that ENU-induced missense mutations create detectable phenotype only about 1 in 4.7 times. While the remaining mutations may not be functionally neutral, they are, on average, beneath the limits of detection of the phenotypic assays we applied.

Conclusions
Collectively, these mutations add to our understanding of the chemical specificity of ENU, the types of amino acid substitutions it creates, and its efficiency in causing phenovariance. Our data support the validity of computational algorithms for the prediction of damage caused by amino acid substitutions, and may lead to refined predictions as to whether specific amino acid changes are responsible for observed phenotypes. These data form the basis for closer in silico estimations of the number of genes mutated to a state of phenovariance by ENU within a population of G3 mice.