bluuebunny/crossref_metadata_2025_split huggingface dataset:
G-quadruplex recognition activities of E. Coli MutS
Authors: Ehrat Edward A , Johnson Bradley R , Williams Jonathan D , Borchert Glen M , Larson Erik D 
Published: July 2012

Abstract

Background
Guanine quadruplex (G4 DNA) is a four-stranded structure that contributes to genome instability and site-specific recombination. G4 DNA folds from sequences containing tandemly repetitive guanines, sequence motifs that are found throughout prokaryote and eukaryote genomes. While some cellular activities have been identified with binding or processing G4 DNA, the factors and pathways governing G4 DNA metabolism are largely undefined. Highly conserved mismatch repair factors have emerged as potential G4-responding complexes because, in addition to initiating heteroduplex correction, the human homologs bind non-B form DNA with high affinity. Moreover, the MutS homologs across species have the capacity to recognize a diverse range of DNA pairing variations and damage, suggesting a conserved ability to bind non-B form DNA.

Results
Here, we asked if E. coli MutS and a heteroduplex recognition mutant, MutS F36A, were capable of recognizing and responding to G4 DNA structures. We find by mobility shift assay that E. coli MutS binds to G4 DNA with high affinity better than binding to G-T heteroduplexes. In the same assay, MutS F36A failed to recognize G-T mismatched oligonucleotides, as expected, but retained an ability to bind to G4 DNA. Association with G4 DNA by MutS is not likely to activate the mismatch repair pathway because nucleotide binding did not promote release of MutS or MutS F36A from G4 DNA as it does for heteroduplexes. G4 recognition activities occur under physiological conditions, and we find that M13 phage harboring G4-capable DNA poorly infected a MutS deficient strain of E. coli compared to M13mp18, suggesting functional roles for mismatch repair factors in the cellular response to unstable genomic elements.

Conclusions
Taken together, our findings demonstrate that E. coli MutS has a binding activity specific for non-B form G4 DNA, but such binding appears independent of canonical heteroduplex repair activation.
The functional and structural characterization of a novel oncogene GIG47 involved in the breast tumorigenesis
Authors: Han Kyou-Hoon , Lee Si-Hyung , Ha Seon-Ah , Kim Hyun Kee , Lee CheWook , Kim Do-Hyoung , Gong Kee Hwan , Yoo JinAh , Kim Sanghee , Kim Jin Woo 
Published: July 2012

Abstract

Background
A candidate oncogene GIG47, previously known as a neudesin with a neurotrophic activity, was identified by applying the differential expression analysis method.

Methods
As a first step to understand the molecular role of GIG47, we analyzed the expression profile of GIG47 in multiple human cancers including the breast cancer and characterized its function related to human carcinogenesis. Based on this oncogenic role of GIG47, we then embarked on determining the high-resolution structure of GIG47. We have applied multidimensional heteronuclear NMR methods to GIG47.

Results
GIG47 was over-expressed in primary breast tumors as well as other human tumors including carcinomas of the uterine cervix, malignant lymphoma, colon, lung, skin, and leukemia. To establish its role in the pathogenesis of breast cancer in humans, we generated stable transfectants of MCF7 cells. The ectopic expression of GIG47 in MCF7 cells promoted the invasiveness in the presence of 50% serum. In addition, it also resulted in the increased tumorigenicity in in vivo tumor formation assay. The tumorigenesis mechanism involving GIG47 might be mediated by the activation of MAPK and PI3K pathways. These results indicate that GIG47 plays a role in the breast tumorigenesis, thus representing a novel target for the treatment of breast cancer. To facilitate the development of GIG47-targeted therapeutics, we determined the structural configuration of GIG47. The high-resolution structure of GIG47 was obtained by combination of NMR and homology modeling. The overall structure of GIG47 has four α-helices and 6 β-strands, arranged in a β1-α1-β2-β3-α2-β4-α3-α4-β5-β6 topology. There is a potential heme/steroid binding pocket formed between two helices α2 and α3.

Conclusion
The determined three-dimensional structure of GIG47 may facilitate the development of potential anti-cancer agents.
Anti-plasmodial and insecticidal activities of the essential oils of aromatic plants growing in the Mediterranean area
Authors: Dell’Agli Mario , Sanna Cinzia , Rubiolo Patrizia , Basilico Nicoletta , Colombo Elisa , Scaltrito Maria M , Ndiath Mamadou Ousmane , Maccarone Luca , Taramelli Donatella , Bicchi Carlo , Ballero Mauro , Bosisio Enrica 
Published: July 2012

Abstract

Background
Sardinia is a Mediterranean area endemic for malaria up to the last century. During a screening study to evaluate the anti-plasmodial activity of some aromatic plants traditionally used in Sardinia, Myrtus communis (myrtle, Myrtaceae), Satureja thymbra (savory, Lamiaceae), and Thymus herba-barona (caraway thyme, Lamiaceae) were collected in three vegetative periods: before, during and after flowering.

Methods
The essential oils were obtained by steam distillation, fractionated by silica gel column chromatography and analysed by GC-FID-MS. Total oil and three main fractions were tested on D10 and W2 strains of Plasmodium falciparum in vitro. Larvicidal and adulticidal activities were tested on Anopheles gambiae susceptible strains.

Results
The essential oil of savory, rich in thymol, was the most effective against P. falciparum with an inhibitory activity independent from the time of collection (IC50 17–26 μg/ml on D10 and 9–11 μg/ml on W2). Upon fractionation, fraction 1 was enriched in mono-sesquiterpenoid hydrocarbons; fraction 2 in thymol (73-83%); and fraction 3 contained thymol, carvacrol and terpinen-4-ol, with a different composition depending on the time of collection. Thymol-enriched fractions were the most active on both strains (IC50 20–22 μg/ml on D10 and 8–10 μg/ml on W2) and thymol was confirmed as mainly responsible for this activity (IC50 19.7± 3.0 and 10.6 ± 2.0 μg/ml on D10 and W2, respectively). The essential oil of S. thymbra L. showed also larvicidal and adulticidal activities. The larvicidal activity, expressed as LC50, was 0.15 ± 0.002; 0.21 ± 0.13; and 0.15 ± 0.09 μg/ml (mean ± sd) depending on the time of collection: before, during and after flowering, respectively.

Conclusions
This study provides evidence for the use of essential oils for treating malaria and fighting the vector at both the larval and adult stages. These findings open the possibility for further investigation aimed at the isolation of natural products with anti-parasitic properties.
Clinically uncomplicated Plasmodium falciparum malaria with high schizontaemia: A case report
Authors: Lwin Khin Maung , Ashley Elizabeth A , Proux Stephane , Silamut Kamolrat , Nosten François , McGready Rose 
Published: July 2012

Abstract

Background
The treatment options for acute Plasmodium falciparum malaria are based on the clinician classifying the patient as uncomplicated or severe according to the clinical and parasitological findings. This process is not always straightforward.

Case presentation
An adult male presented to a clinic on the western border of Thailand with a physical examination and P. falciparum trophozoite count (1.2% of infected red blood cells, IRBC) from malaria blood smear, consistent with a diagnosis of uncomplicated P. falciparum infection. However, the physician on duty treated the patient for severe malaria based on the reported P. falciparum schizont count, which was very high (0.3% IRBC), noticeably in relation to the trophozoite count and schizont:trophozoite ratio 0.25:1. On intravenous artesunate, the patient deteriorated clinically in the first 24 hours. The trophozoite count increased from 1.2% IRBC at baseline to 20.5% IRBC 18 hours following the start of treatment. By day three, the patient recovered and was discharged on day seven having completed a seven-day treatment with artesunate and mefloquine.

Conclusion
The malaria blood smear provides only a guide to the overall parasite biomass in the body, due to the ability of P. falciparum to sequester in the microvasculature. In severe malaria, high schizont counts are associated with worse prognosis. In low transmission areas or in non-immune travelers the presence of schizonts in the peripheral circulation is an indication for close patient supervision. In this case, an unusually high schizont count in a clinically uncomplicated patient was indicative of potential deterioration. Prompt treatment with intravenous artesunate is likely to have been responsible for the good clinical outcome in this case.
Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cγ at the centrosome
Authors: Lelièvre Hélène , Chevrier Véronique , Tassin Anne-Marie , Birnbaum Daniel 
Published: July 2012

Abstract

Background
The t(6;8) translocation found in rare and agressive myeloproliferative disorders results in a chimeric gene encoding the FOP-FGFR1 fusion protein. This protein comprises the N-terminal region of the centrosomal protein FOP and the tyrosine kinase of the FGFR1 receptor. FOP-FGFR1 is localized at the centrosome where it exerts a constitutive kinase activity.

Results
We show that FOP-FGFR1 interacts with the large centrosomal protein CAP350 and that CAP350 is necessary for FOP-FGFR1 localisation at centrosome. FOP-FGFR1 activates the phosphoinositide-3 kinase (PI3K) pathway. We show that p85 interacts with tyrosine 475 of FOP-FGFR1, which is located in a YXXM consensus binding sequence for an SH2 domain of p85. This interaction is in part responsible for PI3K activation. Ba/F3 cells that express FOP-FGFR1 mutated at tyrosine 475 have reduced proliferative ability. Treatment with PI3K pathway inhibitors induces death of FOP-FGFR1 expressing cells. FOP-FGFR1 also recruits phospholipase Cγ1 (PLCγ1) at the centrosome. We show that this enzyme is recruited by FOP-FGFR1 at the centrosome during interphase.

Conclusion
These results delineate a particular type of oncogenic mechanism by which an ectopic kinase recruits its substrates at the centrosome whence unappropriate signaling induces continuous cell growth and MPD.
Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1
Authors: Zall Henry , Weber Arnim , Besch Robert , Zantl Niko , Häcker Georg 
Published: July 2012

Abstract

Background
Human renal cell carcinoma (RCC) is very resistant to chemotherapy. ABT-737 is a novel inhibitor of anti-apoptotic proteins of the Bcl-2 family that has shown promise in various preclinical tumour models.

Results
We here report a strong over-additive pro-apoptotic effect of ABT-737 and etoposide, vinblastine or paclitaxel but not 5-fluorouracil in cell lines from human RCC. ABT-737 showed very little activity as a single agent but killed RCC cells potently when anti-apoptotic Mcl-1 or, unexpectedly, A1 was targeted by RNAi. This potent augmentation required endogenous Noxa protein since RNAi directed against Noxa but not against Bim or Puma reduced apoptosis induction by the combination of ABT-737 and etoposide or vinblastine. At the level of mitochondria, etoposide-treatment had a similar sensitizing activity and allowed for ABT-737-induced release of cytochrome c.

Conclusions
Chemotherapeutic drugs can overcome protection afforded by Mcl-1 and A1 through endogenous Noxa protein in RCC cells, and the combination of such drugs with ABT-737 may be a promising strategy in RCC. Strikingly, A1 emerged in RCC cell lines as a protein of similar importance as the well-established Mcl-1 in protection against apoptosis in these cells.
Dasatinib reverses Cancer-associated Fibroblasts (CAFs) from primary Lung Carcinomas to a Phenotype comparable to that of normal Fibroblasts
Authors: Haubeiss Silke , Schmid Jens O , Mürdter Thomas E , Sonnenberg Maike , Friedel Godehard , van der Kuip Heiko , Aulitzky Walter E 
Published: July 2012

Abstract
Cancer associated fibroblasts (CAFs) play a critical role for growth, invasion, and metastasis of cancer. Therefore, targeting CAFs with small molecule inhibitors may be an attractive anti-tumor strategy. The current study aims to identify small molecule kinase inhibitors affecting CAF's growth and to characterize the biological effects of active compounds on primary CAFs from lung cancer. We screened two individual CAF strains for their sensitivity to a panel of 160 kinase inhibitors. Five kinase inhibitors were identified inhibiting more than 50% of the growth of both cell lines. Three of them were inhibitors of PDGFR at nanomolar concentrations. Therefore, we further tested the FDA approved PDGFR inhibitors Dasatinib, Nilotinib, Sorafenib, and Imatinib. All 37 CAF strains investigated were highly sensitive to Dasatinib at clinically relevant concentrations. Imatinib was slightly less effective, whereas the inhibitory effects of Nilotinib and Sorafenib were significantly less pronounced.
We investigated the effect of Dasatinib on the CAF transcriptome by microarray analysis of 9 individual CAF strains. 492 genes were identified whose expression was changed at least twofold. 104 of these encoded cell cycle related proteins with 97 of them being downregulated by Dasatinib. The majority of regulated genes, however, were of diverse biological functions not directly related to proliferation. We compared this Dasatinib expression signature to previously described differential signatures of normal tissue associated fibroblasts (NAFs) and CAFs and to a signature of fibroblast serum response. There was a significant overlap between genes regulated by Dasatinib and serum repression genes. More importantly, of the 313 genes downregulated by Dasatinib 64 were also reduced in NAFs compared to CAFs. Furthermore, 26 of 179 genes identified as upregulated by Dasatinib were also found to be elevated in NAFs compared to CAFs. These data demonstrate that Dasatinib partially reverses the phenotype of CAFs to a normal fibroblast like phenotype. This is further supported by the finding that incubation of tumor cells with conditioned medium from CAFs pre-incubated with Dasatinib significantly reduced tumor cell proliferation, suggesting that Dasatinib partially reverses the CAF mediated tumor promoting effect. Therefore, targeting CAFs with Dasatinib represents a promising therapeutic principle.
Diversity of the gut microbiota and eczema in early life
Authors: Forno Erick , Onderdonk Andrew B , McCracken John , Litonjua Augusto A , Laskey Daniel , Delaney Mary L , DuBois Andrea M , Gold Diane R , Ryan Louise M , Weiss Scott T , Celedón Juan C 
Published: July 2012

AbstractBackgroundA modest number of prospective studies of the composition of the intestinal microbiota and eczema in early life have yielded conflicting results.ObjectiveTo examine the relationship between the bacterial diversity of the gut and the development of eczema in early life by methods other than stool culture.MethodsFecal samples were collected from 21 infants at 1 and 4 months of life. Nine infants were diagnosed with eczema by the age of 6 months (cases) and 12 infants were not (controls). After conducting denaturating gradient gel electrophoresis (DGGE) of stool samples, we compared the microbial diversity of cases and controls using the number of electrophoretic bands and the Shannon index of diversity (H') as indicators.ResultsControl subjects had significantly greater fecal microbial diversity than children with eczema at ages 1 (meanH'for controls = 0.75 vs. 0.53 for cases, P = 0.01) and 4 months (meanH'for controls = 0.92 vs. 0.59 for cases, P = 0.02). The increase in diversity from 1 to 4 months of age was significant in controls (P = 0.04) but not in children who developed eczema by 6 months of age (P = 0.32).ConclusionOur findings suggest that reduced microbial diversity is associated with the development of eczema in early life.
Obesity suppresses circulating level and function of endothelial progenitor cells and heart function
Authors: Tsai Tzu-Hsien , Chai Han-Tan , Sun Cheuk-Kwan , Yen Chia-Hung , Leu Steve , Chen Yung-Lung , Chung Sheng-Ying , Ko Sheung-Fat , Chang Hsueh-Wen , Wu Chiung-Jen , Yip Hon-Kan 
Published: July 2012

Abstract

Background and aim
This study tested the hypothesis that obesity suppresses circulating number as well as the function of endothelial progenitor cells (EPCs) and left ventricular ejection fraction (LVEF).

Methods
High fat diet (45 Kcal% fat) was given to 8-week-old C57BL/6 J mice (n = 8) for 20 weeks to induce obesity (group 1). Another age-matched group (n = 8) were fed with control diet for 20 weeks as controls (group 2). The animals were sacrificed at the end of 20 weeks after obesity induction.

Results
By the end of study period, the heart weight, body weight, abdominal fat weight, serum levels of total cholesterol and fasting blood sugar were remarkably higher in group 1 than in group 2 (all p<0.01). The circulating level of EPCs (C-kit/CD31, Sca-1/KDR, CXCR4/CD34) was significantly lower in group 1 than in group 2 (p<0.03) at 18 h after critical limb ischemia induction. The angiogenesis and migratory ability of bone marrow-derived EPCs was remarkably impaired in group 1 compared to that in group 2 (all p<0.01). The repair ability of aortic endothelium damage by lipopolysaccharide was notably attenuated in group 1 compared with that in group 2 (p<0.01). Collagen deposition (Sirius red staining) and fibrotic area (Masson's Trichrome staining) in LV myocardium were notably increased in group 1 compared with group 2 (p<0.001). LVEF was notably lower, whereas LV end-diastolic and end-systolic dimensions were remarkably higher in group 1 than in group 2 (all p<0.001).

Conclusions
Obesity diminished circulating EPC level, impaired the recovery of damaged endothelium, suppressed EPC angiogenesis ability and LVEF, and increased LV remodeling.
Preparation and optimization of matrix metalloproteinase-1-loaded poly(lactide-co-glycolide-co-caprolactone) nanoparticles with rotatable central composite design and response surface methodology
Authors: Sun Ping , Song Hua , Cui Daxiang , Qi Jun , Xu Mousheng , Geng Hongquan 
Published: July 2012

Abstract
Matrix metalloproteases are key regulatory molecules in the breakdown of extracellular matrix and in inflammatory processes. Matrix metalloproteinase-1 (MMP-1) can significantly enhance muscle regeneration by promoting the formation of myofibers and degenerating the fibrous tissue. Herein, we prepared novel MMP-1-loaded poly(lactide-co-glycolide-co-caprolactone) (PLGA-PCL) nanoparticles (NPs) capable of sustained release of MMP-1. We established quadratic equations as mathematical models and employed rotatable central composite design and response surface methodology to optimize the preparation procedure of the NPs. Then, characterization of the optimized NPs with respect to particle size distribution, particle morphology, drug encapsulation efficiency, MMP-1 activity assay and in vitro release of MMP-1 from NPs was carried out. The results of mathematical modeling show that the optimal conditions for the preparation of MMP-1-loaded NPs were as follows: 7 min for the duration time of homogenization, 4.5 krpm for the agitation speed of homogenization and 0.4 for the volume ratio of organic solvent phase to external aqueous phase. The entrapment efficiency and the average particle size of the NPs were 38.75 ± 4.74% and 322.7 ± 18.1 nm, respectively. Further scanning electron microscopy image shows that the NPs have a smooth and spherical surface, with mean particle size around 300 nm. The MMP-1 activity assay and in vitro drug release profile of NPs indicated that the bioactivity of the enzyme can be reserved where the encapsulation allows prolonged release of MMP-1 over 60 days. Taken together, we reported here novel PLGA-PCL NPs for sustained release of MMP-1, which may provide an ideal MMP-1 delivery approach for tissue reconstruction therapy.
The effect of ambient humidity on the electrical properties of graphene oxide films
Authors: Yao Yao , Chen Xiangdong , Zhu Jinfeng , Zeng Baoqing , Wu Zuquan , Li Xiaoyu 
Published: July 2012

Abstract
We investigate the effect of water adsorption on the electrical properties of graphene oxide (GO) films using the direct current (DC) measurement and alternating current (AC) complex impedance spectroscopy. GO suspension synthesized by a modified Hummer's method is deposited on Au interdigitated electrodes. The strong electrical interaction of water molecules with GO films was observed through electrical characterizations. The DC measurement results show that the electrical properties of GO films are humidity- and applied voltage amplitude-dependent. The AC complex impedance spectroscopy method is used to analyze the mechanism of electrical interaction between water molecules and GO films in detail. At low humidity, GO films exhibit poor conductivity and can be seen as an insulator. However, at high humidity, the conductivity of GO films increases due to the enhancement of ion conduction. Our systematic research on this effect provides the fundamental supports for the development of graphene devices originating from solution-processed graphene oxide.
Removal of muscle artifact from EEG data: comparison between stochastic (ICA and CCA) and deterministic (EMD and wavelet-based) approaches
Authors: Safieddine Doha , Kachenoura Amar , Albera Laurent , Birot Gwénaël , Karfoul Ahmad , Pasnicu Anca , Biraben Arnaud , Wendling Fabrice , Senhadji Lotfi , Merlet Isabelle 
Published: July 2012

Abstract
Electroencephalographic (EEG) recordings are often contaminated with muscle artifacts. This disturbing myogenic activity not only strongly affects the visual analysis of EEG, but also most surely impairs the results of EEG signal processing tools such as source localization. This article focuses on the particular context of the contamination epileptic signals (interictal spikes) by muscle artifact, as EEG is a key diagnosis tool for this pathology. In this context, our aim was to compare the ability of two stochastic approaches of blind source separation, namely independent component analysis (ICA) and canonical correlation analysis (CCA), and of two deterministic approaches namely empirical mode decomposition (EMD) and wavelet transform (WT) to remove muscle artifacts from EEG signals. To quantitatively compare the performance of these four algorithms, epileptic spike-like EEG signals were simulated from two different source configurations and artificially contaminated with different levels of real EEG-recorded myogenic activity. The efficiency of CCA, ICA, EMD, and WT to correct the muscular artifact was evaluated both by calculating the normalized mean-squared error between denoised and original signals and by comparing the results of source localization obtained from artifact-free as well as noisy signals, before and after artifact correction. Tests on real data recorded in an epileptic patient are also presented. The results obtained in the context of simulations and real data show that EMD outperformed the three other algorithms for the denoising of data highly contaminated by muscular activity. For less noisy data, and when spikes arose from a single cortical source, the myogenic artifact was best corrected with CCA and ICA. Otherwise when spikes originated from two distinct sources, either EMD or ICA offered the most reliable denoising result for highly noisy data, while WT offered the better denoising result for less noisy data. These results suggest that the performance of muscle artifact correction methods strongly depend on the level of data contamination, and of the source configuration underlying EEG signals. Eventually, some insights into the numerical complexity of these four algorithms are given.