bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smoking decreases the response of human lung macrophages to double-stranded RNA by reducing TLR3 expression
Authors: Todt Jill C , Freeman Christine M , Brown Jeanette P , Sonstein Joanne , Ames Theresa M , McCubbrey Alexandra L , Martinez Fernando J , Chensue Stephen W , Beck James M , Curtis Jeffrey L 
Published: March 2013

Abstract

Background
Cigarette smoking is associated with increased frequency and duration of viral respiratory infections, but the underlying mechanisms are incompletely defined. We investigated whether smoking reduces expression by human lung macrophages (Mø) of receptors for viral nucleic acids and, if so, the effect on CXCL10 production.

Methods
We collected alveolar macrophages (AMø) by bronchoalveolar lavage of radiographically-normal lungs of subjects undergoing bronchoscopies for solitary nodules (n = 16) and of volunteers who were current or former smokers (n = 7) or never-smokers (n = 13). We measured expression of mRNA transcripts for viral nucleic acid receptors by real-time PCR in those AMø and in the human Mø cell line THP-1 following phorbol myristate acetate/vitamin D3 differentiation and exposure to cigarette smoke extract, and determined TLR3 protein expression using flow cytometry and immunohistochemistry. We also used flow cytometry to examine TLR3 expression in total lung Mø from subjects undergoing clinically-indicated lung resections (n = 25). Of these, seven had normal FEV1 and FEV1/FVC ratio (three former smokers, four current smokers); the remaining 18 subjects (14 former smokers; four current smokers) had COPD of GOLD stages I-IV. We measured AMø production of CXCL10 in response to stimulation with the dsRNA analogue poly(I:C) using Luminex assay.

Results
Relative to AMø of never-smokers, AMø of smokers demonstrated reduced protein expression of TLR3 and decreased mRNA for TLR3 but not TLR7, TLR8, TLR9, RIG-I, MDA-5 or PKR. Identical changes in TLR3 gene expression were induced in differentiated THP-1 cells exposed to cigarette smoke-extract in vitro for 4 hours. Among total lung Mø, the percentage of TLR3-positive cells correlated inversely with active smoking but not with COPD diagnosis, FEV1% predicted, sex, age or pack-years. Compared to AMø of never-smokers, poly(I:C)-stimulated production of CXCL10 was significantly reduced in AMø of smokers.

Conclusions
Active smoking, independent of COPD stage or smoking duration, reduces both the percent of human lung Mø expressing TLR3, and dsRNA-induced CXCL10 production, without altering other endosomal or cytoplasmic receptors for microbial nucleic acids. This effect provides one possible mechanism for increased frequency and duration of viral lower respiratory tract infections in smokers.

Trial registration
ClinicalTrials.gov NCT00281190, NCT00281203 and NCT00281229.
An improved sequence based prediction protocol for DNA-binding proteins using SVM and comprehensive feature analysis
Authors: Zou Chuanxin , Gong Jiayu , Li Honglin 
Published: March 2013

Abstract

Background
DNA-binding proteins (DNA-BPs) play a pivotal role in both eukaryotic and prokaryotic proteomes. There have been several computational methods proposed in the literature to deal with the DNA-BPs, many informative features and properties were used and proved to have significant impact on this problem. However the ultimate goal of Bioinformatics is to be able to predict the DNA-BPs directly from primary sequence.

Results
In this work, the focus is how to transform these informative features into uniform numeric representation appropriately and improve the prediction accuracy of our SVM-based classifier for DNA-BPs. A systematic representation of some selected features known to perform well is investigated here. Firstly, four kinds of protein properties are obtained and used to describe the protein sequence. Secondly, three different feature transformation methods (OCTD, AC and SAA) are adopted to obtain numeric feature vectors from three main levels: Global, Nonlocal and Local of protein sequence and their performances are exhaustively investigated. At last, the mRMR-IFS feature selection method and ensemble learning approach are utilized to determine the best prediction model. Besides, the optimal features selected by mRMR-IFS are illustrated based on the observed results which may provide useful insights for revealing the mechanisms of protein-DNA interactions. For five-fold cross-validation over the DNAdset and DNAaset, we obtained an overall accuracy of 0.940 and 0.811, MCC of 0.881 and 0.614 respectively.

Conclusions
The good results suggest that it can efficiently develop an entirely sequence-based protocol that transforms and integrates informative features from different scales used by SVM to predict DNA-BPs accurately. Moreover, a novel systematic framework for sequence descriptor-based protein function prediction is proposed here.
EGFR inhibition prevents in vitro tumor growth of salivary adenoid cystic carcinoma
Authors: Huang Yi , Yu Tao , Fu Xiaoyue , Chen Jiao , Liu Ying , Li Chunjie , Xia Yichao , Zhang Zhuoyuan , Li Longjiang 
Published: March 2013

Abstract

Background
Epidermal growth factor receptor (EGFR) is involved in the development of many human malignant tumors and plays an important role in tumor growth and metastasis. Antagonists of EGFR can suppress the growth of several malignancies; however, their therapeutic effect in adenoid cystic carcinoma (ACC) is controversial.

Results
The increased proliferation of two ACC cell lines induced by EGF-treatment was reversed by nimotuzumab. Regardless of EGF stimulation, nimotuzumab-treated ACC cells were arrested in G1 phase and showed decreased expression of Ki67. In addition, EGF activated the MAPK-dependent pathway and up-regulated the expression of matrix metalloproteinase-9 and Snail, enhancing the invasive potential of an ACC cell line (ACC-M). The effects of EGF were down-regulated by nimotuzumab treatment.

Conclusions
These results suggest that nimotuzumab can inhibit the growth and invasion of ACC cells induced by EGF, probably through inactivation of ERK phosphorylation. Thus, nimotuzumab should be considered as a promising novel agent for the treatment of ACC.
Pearl millet [Pennisetum glaucum(L.) R. Br.] consensus linkage map constructed using four RIL mapping populations and newly developed EST-SSRs
Authors: Rajaram Vengaldas , Nepolean Thirunavukkarasu , Senthilvel Senapathy , Varshney Rajeev K , Vadez Vincent , Srivastava Rakesh K , Shah Trushar M , Supriya Ambawat , Kumar Sushil , Ramana Kumari Basava , Bhanuprakash Amindala , Lakshmi Narasu Mangamoori , Riera-Lizarazu Oscar , Hash Charles Thomas 
Published: March 2013

Abstract

Background
Pearl millet [Pennisetum glaucum (L.) R. Br.] is a widely cultivated drought- and high-temperature tolerant C4 cereal grown under dryland, rainfed and irrigated conditions in drought-prone regions of the tropics and sub-tropics of Africa, South Asia and the Americas. It is considered an orphan crop with relatively few genomic and genetic resources. This study was undertaken to increase the EST-based microsatellite marker and genetic resources for this crop to facilitate marker-assisted breeding.

Results
Newly developed EST-SSR markers (99), along with previously mapped EST-SSR (17), genomic SSR (53) and STS (2) markers, were used to construct linkage maps of four F7 recombinant inbred populations (RIP) based on crosses ICMB 841-P3 × 863B-P2 (RIP A), H 77/833-2 × PRLT 2/89-33 (RIP B), 81B-P6 × ICMP 451-P8 (RIP C) and PT 732B-P2 × P1449-2-P1 (RIP D). Mapped loci numbers were greatest for RIP A (104), followed by RIP B (78), RIP C (64) and RIP D (59). Total map lengths (Haldane) were 615 cM, 690 cM, 428 cM and 276 cM, respectively. A total of 176 loci detected by 171 primer pairs were mapped among the four crosses. A consensus map of 174 loci (899 cM) detected by 169 primer pairs was constructed using MergeMap to integrate the individual linkage maps. Locus order in the consensus map was well conserved for nearly all linkage groups. Eighty-nine EST-SSR marker loci from this consensus map had significant BLAST hits (top hits with e-value ≤ 1E-10) on the genome sequences of rice, foxtail millet, sorghum, maize and Brachypodium with 35, 88, 58, 48 and 38 loci, respectively.

Conclusion
The consensus map developed in the present study contains the largest set of mapped SSRs reported to date for pearl millet, and represents a major consolidation of existing pearl millet genetic mapping information. This study increased numbers of mapped pearl millet SSR markers by >50%, filling important gaps in previously published SSR-based linkage maps for this species and will greatly facilitate SSR-based QTL mapping and applied marker-assisted selection programs.
The genome- and transcriptome-wide analysis of innate immunity in the brown planthopper, Nilaparvata lugens
Authors: Bao Yan-Yuan , Qu Lv-Yu , Zhao Dong , Chen Li-Bo , Jin Hong-Yuan , Xu Liang-Min , Cheng Jia-An , Zhang Chuan-Xi 
Published: March 2013

Abstract

Background
The brown planthopper (Nilaparvata lugens) is one of the most serious rice plant pests in Asia. N. lugens causes extensive rice damage by sucking rice phloem sap, which results in stunted plant growth and the transmission of plant viruses. Despite the importance of this insect pest, little is known about the immunological mechanisms occurring in this hemimetabolous insect species.

Results
In this study, we performed a genome- and transcriptome-wide analysis aiming at the immune-related genes. The transcriptome datasets include the N. lugens intestine, the developmental stage, wing formation, and sex-specific expression information that provided useful gene expression sequence data for the genome-wide analysis. As a result, we identified a large number of genes encoding N. lugens pattern recognition proteins, modulation proteins in the prophenoloxidase (proPO) activating cascade, immune effectors, and the signal transduction molecules involved in the immune pathways, including the Toll, Immune deficiency (Imd) and Janus kinase signal transducers and activators of transcription (JAK-STAT) pathways. The genome scale analysis revealed detailed information of the gene structure, distribution and transcription orientations in scaffolds. A comparison of the genome-available hemimetabolous and metabolous insect species indicate the differences in the immune-related gene constitution. We investigated the gene expression profiles with regards to how they responded to bacterial infections and tissue, as well as development and sex expression specificity.

Conclusions
The genome- and transcriptome-wide analysis of immune-related genes including pattern recognition and modulation molecules, immune effectors, and the signal transduction molecules involved in the immune pathways is an important step in determining the overall architecture and functional network of the immune components in N. lugens. Our findings provide the comprehensive gene sequence resource and expression profiles of the immune-related genes of N. lugens, which could facilitate the understanding of the innate immune mechanisms in the hemimetabolous insect species. These data give insight into clarifying the potential functional roles of the immune-related genes involved in the biological processes of development, reproduction, and virus transmission in N. lugens.
Auditory-motor adaptation to frequency-altered auditory feedback occurs when participants ignore feedback
Authors: Keough Dwayne , Hawco Colin , Jones Jeffery A 
Published: March 2013

Abstract

Background
Auditory feedback is important for accurate control of voice fundamental frequency (F
0). The purpose of this study was to address whether task instructions could influence the compensatory responding and sensorimotor adaptation that has been previously found when participants are presented with a series of frequency-altered feedback (FAF) trials. Trained singers and musically untrained participants (nonsingers) were informed that their auditory feedback would be manipulated in pitch while they sang the target vowel [/ɑ /]. Participants were instructed to either ‘compensate’ for, or ‘ignore’ the changes in auditory feedback. Whole utterance auditory feedback manipulations were either gradually presented (‘ramp’) in -2 cent increments down to -100 cents (1 semitone) or were suddenly (’constant‘) shifted down by 1 semitone.

Results
Results indicated that singers and nonsingers could not suppress their compensatory responses to FAF, nor could they reduce the sensorimotor adaptation observed during both the ramp and constant FAF trials.

Conclusions
Compared to previous research, these data suggest that musical training is effective in suppressing compensatory responses only when FAF occurs after vocal onset (500-2500 ms). Moreover, our data suggest that compensation and adaptation are automatic and are influenced little by conscious control.
Expression profiling of tomato pre-abscission pedicels provides insights into abscission zone properties including competence to respond to abscission signals
Authors: Nakano Toshitsugu , Fujisawa Masaki , Shima Yoko , Ito Yasuhiro 
Published: March 2013

Abstract

Background
Detachment of plant organs occurs in abscission zones (AZs). During plant growth, the AZ forms, but does not develop further until the cells perceive abscission-promoting signals and initiate detachment. Upon signal perception, abscission initiates immediately; if there is no signal, abscission is not induced and the organ remains attached to the plant. However, little attention has been paid to the genes that maintain competence to respond to the abscission signal in the pre-abscission AZ. Recently, we found that the tomato (Solanum lycopersicum) transcription factors BLIND (Bl), GOBLET (GOB), Lateral suppressor (Ls) and a tomato WUSCHEL homologue (LeWUS) are expressed specifically in pre-abscission tissue, the anthesis pedicel AZs. To advance our understanding of abscission, here we profiled genome-wide gene expression in tomato flower pedicels at the pre-abscission stage.

Results
We examined the transcriptomes of three tomato flower pedicel regions, the AZ and flanking proximal- (Prox) and distal- (Dis) regions, and identified 89 genes that were preferentially expressed in the AZ compared to both Prox and Dis. These genes included several transcription factors that regulate apical or axillary shoot meristem activity. Also, genes associated with auxin activity were regulated in a Prox-Dis region-specific manner, suggesting that a gradient of auxin exists in the pedicel. A MADS-box gene affecting floral transition was preferentially expressed in the Prox region and other MADS-box genes for floral organ identification were preferentially expressed in Dis, implying that the morphologically similar Prox and Dis regions have distinct identities. We also analyzed the expression of known regulators; in anthesis pedicels, Bl, GOB, Ls and LeWUS were expressed in the vascular cells of the AZ region. However, after an abscission signal, Bl was up-regulated, but GOB, Ls and LeWUS were down-regulated, suggesting that Bl may be a positive regulator of abscission, but the others may be negative regulators.

Conclusions
This study reveals region-specific gene expression in tomato flower pedicels at anthesis and identifies factors that may determine the physiological properties of the pre-abscission pedicel. The region-specific transcriptional regulators and genes for auxin activity identified here may prevent flower abscission in the absence of signal or establish competence to respond to the abscission signal.
Trial Protocol: A randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study)
Authors: Tullett Jayne , Murray Ellen , Nichols Linda , Holder Roger , Lester Will , Rose Peter , Hobbs FD Richard , Fitzmaurice David 
Published: March 2013

AbstractBackgroundVenous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot. However, the recurrence rate following a deep vein thrombosis remains approximately 10% per annum following treatment cessation irrespective of the duration of anticoagulation therapy. Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence.Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration. It has a cumulative incidence after 2 years of around 25% and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure.Methods/designPatients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and randomly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis. At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device. In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study. Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life questionnaires.DiscussionThe primary aim of the study is to investigate whether extending oral anticoagulation treatment (prior to discontinuing treatment) beyond 3–6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence. The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and identify the potential of D-dimer point of care testing for identification of high risk patients within a primary care setting.Trial registrationISRCTN73819751
Schizophrenia susceptibility and NMDA-receptor mediated signalling: an association study involving 32 tagSNPs of DAO, DAOA, PPP3CC, and DTNBP1genes
Authors: Sacchetti Emilio , Scassellati Catia , Minelli Alessandra , Valsecchi Paolo , Bonvicini Cristian , Pasqualetti Patrizio , Galluzzo Alessandro , Pioli Rosaria , Gennarelli Massimo 
Published: March 2013

Abstract

Background
Recent studies supported associations between four NMDA-receptor-mediated signalling genes (D-amino acid oxidase, DAO; D-amino acid oxidase activator, DAOA; protein phosphatase 3 catalytic subunit gamma isoform, PPP3CC; dystrobrevin-binding protein 1, DTNBP1) and schizophrenia susceptibility, even though with contrasting results.

Methods
In an attempt to replicate these findings for the first time in an Italian population, a panel of 32 tagSNPs was analysed in a representative case-control sample involving 879 subjects.

Results
An association in the allele frequency was observed for the estimated PPP3CC CAG triplotype in the SNP window rs4872499 T/C-rs11780915 A/G-rs13271367 G/A (pcorrect = 0.001). Similarly, the clustered genotype frequencies of the estimated/phased CAG triplotype differed between cases and controls (p = 0.004), with the carriers having a higher frequency in the control population (p = 0.002, odd ratio OR = 0.59, 95% confident interval CI: 0.43-0.82).
Following the phenotypic dissection strategy, the analysis of single SNPs evidenced a protective effect in males of rs11780915 and rs13271367 in PPP3CC gene (pcorrect = 0.02, pcorrect = 0.04 respectively). Moreover the estimated/phased GT diplotype (rs2070586A/G-rs3741775G/T) carriers of the DAO gene were more highly represented in female controls (p = 0.017, OR = 0.58, 95% CI: 0.37-0.90), as were the estimated/phased CAG triplotype carriers of the PPP3CC gene in females (p = 0.01, OR = 0.53, 95% CI: 0.32-0.87). In addition, we performed an interaction analysis, and a 66% (p = 0.003, OR = 0.34, 95% CI: 0.17-0.70) lower risk of developing schizophrenia for female (CAG + GT) carriers versus non-CAG or -GT carriers was observed. For DTNBP1, we found a protective effect in males for the rs6459409 (pcorrect = 0.02) and the estimated/phased CT diplotype (rs6459409-rs9476886) carriers (p = 3x10-4
, OR = 0.46, 95% CI: 0.30-0.70).
In relation to diagnostic subtypes, the estimated/phased DAO GT diplotype and PPP3CC CAG triplotype female carriers were found to show relative risk ratio (RRR) values of 0.52 and 0.54 lower risk for a paranoid phenotype respectively.

Conclusions
Although the results are preliminary and needed replication in a larger sample, this study suggests that NMDA receptor-mediated signalling genes (DAO, PPP3CC, DTNBP1) might be involved in schizophrenia pathogenic mechanisms related to gender.
Preeclampsia and long-term risk of cardiovascular disease: what do obstetrician-gynecologists know?
Authors: Heidrich May-Britt , Wenzel Daniela , von Kaisenberg Constantin S , Schippert Cordula , von Versen-Höynck Frauke M 
Published: March 2013

Abstract

Background
Preeclampsia (PE), a hypertensive disorder of pregnancy affects 2-8% of women and is associated with increased cardiovascular disease (CVD) risk later in life. There is little information about the knowledge of obstetrician-gynecologists in German outpatient care setting regarding the future health risk of PE and knowledge of the current guidelines on treatment and counseling patients post PE. This study aimed to assess whether obstetrician-gynecologists are aware of PE’s association with maternal long-term adverse outcomes and providing appropriate counseling.

Methods
A random sample of 500 obstetrician-gynecologists in the federal state of Lower Saxony was mailed a survey and a reminder with a second copy of the survey. The questionnaire elicited both personal information, and knowledge on future disease risks, e.g. cardiovascular disease (CVD) and current guidelines as well as on counseling practice. Descriptive analysis was used to analyze the responses.

Results
A total of 212 obstetrician-gynecologists (42.4%) responded to the questionnaire. A large proportion of physicians stated that PE was associated with a higher risk for the development for hypertension (86.6%), stroke (78.5%) and kidney disease (78.0%). Of the participants 75.8% reported that women after PE have a shorter life expectancy. Respondents with knowledge of the current guidelines of the German Association of Obstetrics and Gynecology concerning follow up and risk management of PE (45.2%) were more often aware of the development of CVD and stroke and counseled patients on self -blood-pressure measurement, meaning and long-term-risks of PE and attached importance to family history of PE compared to physicians with no knowledge of the guidelines.

Conclusion
Although the majority of obstetrician-gynecologists were aware of higher CVD risk after PE, weaknesses exist in the follow up care and counseling of these patients. These deficiencies would be amendable to directed educational activities to improve the implementation of current guidelines.