bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel chemogenomics analysis of G protein-coupled receptors (GPCRs) and their ligands: a potential strategy for receptor de-orphanization
Authors: van der Horst Eelke , Peironcely Julio E , IJzerman Adriaan P , Beukers Margot W , Lane Jonathan R , van Vlijmen Herman WT , Emmerich Michael TM , Okuno Yasushi , Bender Andreas 
Published: June 2010

Abstract

Background
G protein-coupled receptors (GPCRs) represent a family of well-characterized drug targets with significant therapeutic value. Phylogenetic classifications may help to understand the characteristics of individual GPCRs and their subtypes. Previous phylogenetic classifications were all based on the sequences of receptors, adding only minor information about the ligand binding properties of the receptors. In this work, we compare a sequence-based classification of receptors to a ligand-based classification of the same group of receptors, and evaluate the potential to use sequence relatedness as a predictor for ligand interactions thus aiding the quest for ligands of orphan receptors.

Results
We present a classification of GPCRs that is purely based on their ligands, complementing sequence-based phylogenetic classifications of these receptors. Targets were hierarchically classified into phylogenetic trees, for both sequence space and ligand (substructure) space. The overall organization of the sequence-based tree and substructure-based tree was similar; in particular, the adenosine receptors cluster together as well as most peptide receptor subtypes (e.g. opioid, somatostatin) and adrenoceptor subtypes. In ligand space, the prostanoid and cannabinoid receptors are more distant from the other targets, whereas the tachykinin receptors, the oxytocin receptor, and serotonin receptors are closer to the other targets, which is indicative for ligand promiscuity. In 93% of the receptors studied, de-orphanization of a simulated orphan receptor using the ligands of related receptors performed better than random (AUC > 0.5) and for 35% of receptors de-orphanization performance was good (AUC > 0.7).

Conclusions
We constructed a phylogenetic classification of GPCRs that is solely based on the ligands of these receptors. The similarities and differences with traditional sequence-based classifications were investigated: our ligand-based classification uncovers relationships among GPCRs that are not apparent from the sequence-based classification. This will shed light on potential cross-reactivity of GPCR ligands and will aid the design of new ligands with the desired activity profiles. In addition, we linked the ligand-based classification with a ligand-focused sequence-based classification described in literature and proved the potential of this method for de-orphanization of GPCRs.
Identification of four novel small non-coding RNAs from Xanthomonas campestris pathovar campestris
Authors: Jiang Rui-Ping , Tang Dong-Jie , Chen Xiao-Lin , He Yong-Qiang , Feng Jia-Xun , Jiang Bo-Le , Lu Guang-Tao , Lin Min , Tang Ji-Liang 
Published: June 2010

Abstract

Background
In bacteria, small non-coding RNAs (sRNAs) have been recognized as important regulators of various cellular processes. Approximately 200 bacterial sRNAs in total have been reported. However, very few sRNAs have been identified from phytopathogenic bacteria.

Results

Xanthomons campestris pathovar campestris (Xcc) is the causal agent of black rot disease of cruciferous crops. In this study, a cDNA library was constructed from the low-molecular weight RNA isolated from the Xcc strain 8004 grown to exponential phase in the minimal medium XVM2. Seven sRNA candidates were obtained by sequencing screen of 2,500 clones from the library and four of them were confirmed to be sRNAs by Northern hybridization, which were named sRNA-Xcc 1, sRNA-Xcc 2, sRNA-Xcc 3, and sRNA-Xcc 4. The transcription start and stop sites of these sRNAs were further determined. BLAST analysis revealed that the four sRNAs are novel. Bioinformatics prediction showed that a large number of genes with various known or unknown functions in Xcc 8004 are potential targets of sRNA-Xcc 1, sRNA-Xcc 3 and sRNA-Xcc 4. In contrast, only a few genes were predicted to be potential targets of sRNA-Xcc 2.

Conclusion
We have identified four novel sRNAs from Xcc by a large-scale screen. Bioinformatics analysis suggests that they may perform various functions. This work provides the first step toward understanding the role of sRNAs in the molecular mechanisms of Xanthomonas campestris pathogenesis.
Epigallocatechin-3-gallate suppresses the expression of HSP70 and HSP90 and exhibits anti-tumor activity in vitro and in vivo
Authors: Tran Phan LCHB , Kim Soo-A , Choi Hong Seok , Yoon Jung-Hoon , Ahn Sang-Gun 
Published: June 2010

Abstract

Background
Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression.

Methods
Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. In vivo effect of EGCG on tumor growth was examined in a xenograft model.

Results
Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44°C for 1 h) or oxidative stress (H2O2, 500 μM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression.

Conclusions
Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer.
Associations of ECP (eosinophil cationic protein)-gene polymorphisms to allergy, asthma, smoke habits and lung function in two Estonian and Swedish sub cohorts of the ECRHS II study
Authors: Jönsson Ulla-Britt , Håkansson Lena Douhan , Jõgi Rain , Janson Christer , Venge Per 
Published: June 2010

Abstract

Background
The Eosinophil Cationic Protein (ECP) is a potent multifunctional protein. Three common polymorphisms are present in the ECP gene, which determine the function and production of the protein. The aim was to study the relationship of these ECP gene polymorphisms to signs and symptoms of allergy and asthma in a community based cohort (The European Community Respiratory Health Survey (ECRHS)).

Methods
Swedish and Estonian subjects (n = 757) were selected from the larger cohort of the ECRHS II study cohort. The prevalence of the gene polymorphisms ECP434(G>C) (rs2073342), ECP562(G>C) (rs2233860) and ECP c.-38(A>C) (rs2233859) were analysed by DNA sequencing and/or real-time PCR and related to questionnaire-based information of allergy, asthma, smoking habits and to lung functions.

Results
Genotype prevalence showed both ethnic and gender differences. Close associations were found between the ECP434(G>C) and ECP562(G>C) genotypes and smoking habits, lung function and expression of allergic symptoms. Non-allergic asthma was associated with an increased prevalence of the ECP434GG genotype. The ECP c.-38(A>C) genotypes were independently associated to the subject being atopic.

Conclusion
Our results show associations of symptoms of allergy and asthma to ECP-genotypes, but also to smoking habits. ECP may be involved in impairment of lung functions in disease. Gender, ethnicity and smoking habits are major confounders in the evaluations of genetic associations to allergy and asthma.
The chemopreventive retinoid 4HPR impairs prostate cancer cell migration and invasion by interfering with FAK/AKT/GSK3β pathway and β-catenin stability
Authors: Benelli Roberto , Monteghirfo Stefano , Venè Roberta , Tosetti Francesca , Ferrari Nicoletta 
Published: June 2010

AbstractBackgroundProstate cancer shows an extremely slow progression, appearing in its metastatic, hormone refractory phenotype mostly in elderly men. The chemopreventive targeting of this tumor could accordingly delay its malignancy over life expectancy. The cancer chemopreventive retinoidN-(4 hydroxyphenyl)retinamide (4HPR) has already been shown to restrain prostate cancer growth in vitro and in vivo, though its mechanisms of action are only partially explained.ResultsWe found that 4HPR impairs DU145 and PC3 prostate cancer cells migration and invasion by down-regulating FAK and AKT activation and by enhancing β-catenin degradation, causing the downregulation of target genes like cyclin D1, survivin and VEGF. This non-migratory phenotype was similarly produced in both cell lines by stable silencing of β-catenin. 4HPR was able to decrease AKT phosphorylation also when powerfully upregulated by IGF-1 and, consequently, to impair IGF-1-stimulated cell motility. Conversely, the expression of constitutively active AKT (myr-AKT) overcame the effects of 4HPR and β-catenin-silencing on cell migration. In addition, we found that BMP-2, a 4HPR target with antiangiogenic activity, decreased prostate cancer cell proliferation, migration and invasion by down-regulating the pathway described involving AKT phosphorylation, β-catenin stability and cyclin D1 expression.ConclusionThese data point to 4HPR as a negative regulator of AKT phosphorylation, effectively targeting the β-catenin pathway and inducing a relatively benign phenotype in prostate cancer cells, limiting neoangiogenesis and cell invasion.
Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitroeffects on cartilage metabolism and intra-articular levels after injection
Authors: Rutgers Marijn , Saris Daniël BF , Dhert Wouter JA , Creemers Laura B 
Published: June 2010

Abstract
Introduction
Intraarticular administration of autologous conditioned serum (ACS) recently demonstrated some clinical effectiveness in treatment of osteoarthritis (OA). The current study aims to evaluate the in vitro effects of ACS on cartilage proteoglycan (PG) metabolism, its composition and the effects on synovial fluid (SF) cytokine levels following intraarticular ACS administration.

Methods
The effect of conditioned serum on PG metabolism of cultured OA cartilage explants was compared to unconditioned serum. The effect of serum conditioning on levels of interleukin-1beta (IL-1β), IL-4, IL-6, IL-10, IL-13, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), osteoprotegerin (OPG), oncostatin M (OSM), interleukin-1 receptor (IL-1ra) and transforming growth factor beta (TGF-β) were measured by multiplex ELISA. As TNF-α levels were found to be increased in conditioned serum, the effect of TNF-α inhibition by etanercept on PG metabolism was studied in cartilage explants cultured in the presence of conditioned serum. Furthermore, cytokine levels in SF were measured three days after intraarticular ACS injection in OA patients to verify their retention time in the joint space.

Results
PG metabolism was not different in the presence of conditioned serum compared to unconditioned serum. Levels of the anti-inflammatory cytokines IL-1ra, TGF-β, IL-10 as well as of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and OSM were increased. IL-4, IL-13 and IFN-γ levels remained similar, while OPG levels decreased. TNF-α inhibition did not influence PG metabolism in cartilage explant culture in the presence of condtioned serum. Although OPG levels were higher and TGF-β levels were clearly lower in ACS than in SF, intraarticular ACS injection in OA patients did not result in significant changes in these cytokine levels.

Conclusions
ACS for treatment of osteoarthritis contains increased levels of anti-inflammatory as well as pro-inflammatory cytokines, in particular TNF-α, but conditioned serum does not seem to have a net direct effect on cartilage metabolism, even upon inhibition of TNF-α. The fast intraarticular clearance of cytokines in the injected ACS may explain the limited effects found previously in vivo.
Technical Advance: Autofluorescence as a tool for myeloid cell analysis
Authors: Mitchell Andrew J , Pradel Lydie C , Chasson Lionel , Van Rooijen Nico , Grau Georges E , Hunt Nicholas H , Chimini Giovanna 
Published: June 2010

Abstract
The autofluorescence of myeloid cell populations is heterogeneous and can be used as a tool for identification and phenotyping of myeloid subsets.
Cellular AF is usually considered a hindrance to flow cytometric analysis. Here, we incorporate AF into analysis of complex mixtures of leukocytes. Using a mouse model, we examined cellular AF at multiple excitation and emission wavelengths, and populations with discrete patterns were gated and examined for surface marker expression. In the spleen, all major myeloid populations were identified. In particular, the approach allowed simultaneous characterization of RPM and resident monocytes. When monocytes and RPM were compared, RPM exhibited a phenotype that was consistent with involvement in physiological processes, including expression of genes involved in lipid and iron metabolism. The presence of large amounts of stored ferric iron within RPM enabled purification of these cells using a magnetic-based approach. When adapted for use on leukocytes isolated from a range of other organs, incorporation of AF into analysis allowed identification and isolation of biologically important myeloid populations, including subsets that were not readily identifiable by conventional cytometric analysis.
A Large Study of Androgen Receptor Germline Variants and Their Relation to Sex Hormone Levels and Prostate Cancer Risk. Results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium
Authors: Lindström Sara , Ma Jing , Altshuler David , Giovannucci Edward , Riboli Elio , Albanes Demetrius , Allen Naomi E. , Berndt Sonja I. , Boeing Heiner , Bueno-de-Mesquita H. Bas , Chanock Stephen J. , Dunning Alison M. , Feigelson Heather Spencer , Gaziano J. Michael , Haiman Christopher A. , Hayes Richard B. , Henderson Brian E. , Hunter David J. , Kaaks Rudolf , Kolonel Laurence N. , Le Marchand Loic , Martínez Carmen , Overvad Kim , Siddiq Afshan , Stampfer Meir , Stattin Pär , Stram Daniel O. , Thun Michael J. , Trichopoulos Dimitrios , Tumino Rosario , Virtamo Jarmo , Weinstein Stephanie J. , Yeager Meredith , Kraft Peter , Freedman Matthew L. 
Published: June 2010

Background: Androgens are key regulators of prostate gland maintenance and prostate cancer growth, and androgen deprivation therapy has been the mainstay of treatment for advanced prostate cancer for many years. A long-standing hypothesis has been that inherited variation in the androgen receptor (AR) gene plays a role in prostate cancer initiation. However, studies to date have been inconclusive and often suffered from small sample sizes.Objective and Methods: We investigated the association of AR sequence variants with circulating sex hormone levels and prostate cancer risk in 6058 prostate cancer cases and 6725 controls of Caucasian origin within the Breast and Prostate Cancer Cohort Consortium. We genotyped a highly polymorphic CAG microsatellite in exon 1 and six haplotype tagging single nucleotide polymorphisms and tested each genetic variant for association with prostate cancer risk and with sex steroid levels.Results: We observed no association between AR genetic variants and prostate cancer risk. However, there was a strong association between longer CAG repeats and higher levels of testosterone (P = 4.73 × 10−5) and estradiol (P = 0.0002), although the amount of variance explained was small (0.4 and 0.7%, respectively).Conclusions: This study is the largest to date investigating AR sequence variants, sex steroid levels, and prostate cancer risk. Although we observed no association between AR sequence variants and prostate cancer risk, our results support earlier findings of a relation between the number of CAG repeats and circulating levels of testosterone and estradiol.
Zirconia Removable Telescopic Dentures Retained on Teeth or Implants for Maxilla Rehabilitation. Three-Year Observation of Three Cases
Authors: Zafiropoulos Gregory-George , Rebbe Jochen , Thielen Ulrich , Deli Giorgio , Beaumont Christian , Hoffmann Oliver 
Published: June 2010

AbstractThis report addresses maxillary restoration with removable telescopic crown-retained palatal free dentures. One patient with 7 natural teeth (PERIO), a second patient with 6 dental implants (IMPL), and a third patient with 2 natural teeth and 4 dental implants (IMPL-PERIO) were treated. Zirconia copings for natural teeth and individual zirconia implant abutments were fabricated in CAD/CAM and used as primary crowns. Electroformed gold copings were used as secondary telescopes. All maxilla supraconstructions were fabricated with zirconia and CAD/CAM. Patients were monitored during a 3-year period; all teeth and implants survived, and no biological or mechanical complications occurred. The peri-implant and periodontal conditions were healthy. While recognizing the limitations of this report, results showed that fabricating removable zirconia structures by means of CAD/CAM can yield highly functional and esthetic results. Galvanoforming technology is the preferable means of fabricating secondary crowns. The combination of these techniques and materials results in a prosthetic reconstruction of high quality, good fit, and biocompatibility. Long-term studies of large populations are necessary to investigate the clinical properties of the material utilized in this type of construction.
Biomechanical and Microscopic Response of Bone to Titanium Implants in the Presence of Inorganic Grafts
Authors: Munhoz Etiene Andrade , Bodanezi Augusto , Cestari Tania Mary , Taga Rumio , Ferreira Junior Osny , de Carvalho Paulo Sergio Perri 
Published: June 2010

Abstract
This study evaluated the biomechanical and microscopic response of previously grafted bone to titanium implants. The lower incisors of 16 rabbits were surgically extracted, and bilateral perforations communicating with the remaining sockets were created distally. A socket/perforation defect on each mandible was chosen at random to be immediately filled with a xenogenic graft, whereas the contralateral perforation was left to heal naturally and served as a paired control. After 60 days, titanium implants were installed in the previously operated areas. After periods of 2 and 6 months, the animals were killed, and the force necessary to retrieve implants as well as the bone-implant contact (BIC) and bone mass (BM) were quantified and statistically compared by 2-way analysis of variance and Tukey's test (α  =  .05). No significant differences in removal torque were observed, either by time or by treatment condition. Differences in BIC and BM between experimental and control groups were not statistically significant through the intervals studied (P &lt; .05). The presence of a xenogenic graft did not influence the microscopic tissue response to titanium implants or fixation into newly formed or mature bone.
Extraordinary Implant Failure
Authors: Winkler Sheldon 
Published: June 2010

AbstractEvery attempt must be made to keep implant failures to a minimum. Dental implant failure can roughly be divided into 3 broad categories: bacterial factors, occlusal (mechanical factors), and systemic and psychologic factors. All failures should be carefully analyzed and evaluated to identify their causes in order to prevent future reoccurrence. Failures should be documented and used to advantage when treatment planning future implant cases. A panoramic radiograph, mounted diagnostic casts, medical and dental histories, and surgical guides are accepted standards of care prior to beginning oral implant procedures. The identification and management of nutritional deficiencies is a useful adjunct to successful implant treatment.
Temporal Characteristics of Nasalization in Speakers with and without Cleft Palate
Authors: Ha Seunghee , Kuehn David P. 
Published: June 2010

Objective The purposes of the study were to compare the temporal characteristics of nasalization between speakers with cleft palate with or without cleft lip and normal adult speakers and to investigate the relationship between acoustic temporal measures and perceived nasality. Methods Fifteen speakers with cleft palate with or without cleft lip and 15 speakers without cleft palate aged 13 to 45 years participated in this study. Two listeners judged the degree of nasality in speakers with cleft palate with or without cleft lip. Two distinct acoustic energies derived from the mouth and nose were recorded simultaneously while speakers were producing the speech tasks /pimip/, /pamap/, and /pumup/. Absolute and proportional measures related to nasalization duration were obtained. Results Speakers with cleft palate with or without cleft lip exhibited more extensive acoustic nasalization in the time domain than did speakers without cleft palate with or without cleft lip. Speakers without cleft palate with or without cleft lip showed larger nasalization-duration ratios in the high vowel contexts than in the low vowel context. Speakers with cleft palate with or without cleft lip did not exhibit distinct differences in nasalization-duration ratios among the vowel contexts. The acoustic measurements reflecting temporal patterns of oral-nasal acoustic impedance were related to the perception of hypernasality. Conclusions These results suggest that the speakers with cleft palate with or without cleft lip showed longer duration of acoustic nasalization than speakers without cleft palate with or without cleft lip. Temporal characteristics of acoustic nasalization grew longer as the degree of perceived hypernasality increased. The positive correlation between temporal measures of acoustic nasalization and degree of perceived nasality suggests that temporal measures of nasalization would provide supplementary diagnostic information in relation to the degree of hypernasality.
Maxillary Distraction Osteogenesis in the Adolescent Cleft Patient: Three-Dimensional Computed Tomography Analysis of Linear and Volumetric Changes over Five Years
Authors: Kuo-Ting Chen Philip , Por Yong-Chen , Jein-Wein Liou Eric , Chun-Shin Chang Frank 
Published: June 2010

Objective To assess the results of maxillary distraction osteogenesis with the Rigid External Distraction System using three-dimensional computed tomography scan volume-rendered images with respect to stability and facial growth at three time frames: preoperative (T0), 1-year postoperative (T1), and 5-years postoperative (T2). Design Retrospective analysis. Setting Tertiary. Patients A total of 12 patients with severe cleft maxillary hypoplasia were treated between June 30, 1997, and July 15, 1998. The mean age at surgery was 11 years 1 month. Interventions Le Fort I maxillary distraction osteogenesis. Distraction was started 2 to 5 days postsurgery at a rate of 1 mm per day. The consolidation period was 3 months. No face mask was used. A paired t test was used for statistical analysis. Main Outcome Measures Overjet, ANB, and SNA and maxillary, pterygoid, and mandibular volumes. Results From T0 to T1, there were statistically significant increments of overjet, ANB, and SNA and maxillary, pterygoid, and mandibular volumes. The T1 to T2 period demonstrated a reduction of overjet (30.07%) and ANB (54.42%). The maxilla showed a stable SNA and a small but statistically significant advancement of the ANS point. There was a significant increase in the mandibular volume. However, there was no significant change in the maxillary and pterygoid volumes. Conclusions Maxillary distraction osteogenesis demonstrated linear and volumetric maxillary growth during the distraction phase without clinically significant continued growth thereafter. Overcorrection is required to take into account recurrence of midface retrusion over the long term.